Today thanks in large part to a law passed in 1993 that mandated that women and minorities be included in medical research funded by the National Institutes of Health women are more systematically included in studies, yet there are still huge knowledge gaps.

For instance, women with heart disease often have different symptoms from men with heart disease, yet doctors are much more familiar with the male symptoms, said Dr. Jennifer Mieres, a cardiologist with Northwell Health in New York. When women show up with symptoms that dont fit into the algorithm were taught in medical school, she said, they get gaslit and ignored.

By the time Michelle Cho, 32, was diagnosed with systemic lupus erythematosus, a disease in which the body slowly attacks its own tissues, she had developed kidney failure, a heart murmur and pneumonia yet the first doctor she went to diagnosed her with allergies, she said, and the second doctor thought she was pregnant.

I left each time feeling disappointed, sad and uneasy, because I knew they had not solved my problem or helped me in any way, and it had been yet another wasted day, said Ms. Cho, a New York City-based medical student. It felt like they were saying, Its all in my head.

When Raimey Gallant, a 42-year-old writer who lives in Winnipeg, began dropping weight, losing her hair and breaking out in a full-body rash in her 20s, she said her male doctor told her she was young, healthy and just lazy, when in fact, later that year she was diagnosed with Graves Disease, an autoimmune disorder in which the body produces too much thyroid hormone.

She also struggled for 20 years with disabling period pain before finally getting diagnosed last year with endometriosis, an inflammatory disease characterized by the presence of endometrial-like tissue outside the uterus. Ill never get back the pieces of life Ive lost to medical neglect, she said.

Its hard to know how to begin to address these systemic problems, experts said, but scientists argue that at the very least, there needs to be more research on womens health conditions.

See the article here:
What Is Medical Gaslighting and How Can You Elevate Health Care - The New York Times

Recommendation and review posted by Bethany Smith

Anyone whos ever tried to conceive knows that there are countless highs and lows during the process. To say you might be a little stressed during this period is a bit of an understatement.

While trying to conceive (TTC) can be an emotional rollercoaster on its own, the experience can become even more emotionally fraught for people relying on fertility treatments, such as in vitro fertilization (IVF).

How do you go on with everyday life while undergoing treatments? In particular, many people going through fertility treatment still work full time. Understanding how to manage that stress and finding positive outlets for encouragement and support can help you manage.

Experiencing fertility concerns can be an isolating experience, but the reality is that theyre incredibly common. According to the American Society for Reproductive Medicine (ASRM), roughly 10 to 15 percent of American couples experience infertility.

Fertility concerns can impact the sperm-giving partner, too. Male and female infertility each contribute to one-third of infertility cases, according to ASRM. The remaining one-third is a combination of both male and female infertility.

If youre going to continue working during fertility treatment, certain factors can make the experience more complicated. Insurance coverage can vary widely by company, and family leave policies can depend on both your employer and the state you live in.

Before you can begin figuring out how to work through fertility treatments, you need to determine your rights, and what benefits if any you have access to.

Depending on your employer and how long youve worked with them, you might qualify for FMLA. While FMLA guarantees only unpaid time off, you could get up to 12 weeks of unpaid leave every year. You could use this leave toward parental leave.

By strict definition, FMLA isnt designed to cover infertility treatments. However, if your healthcare professional can affirm that your fertility treatments are medically necessary for you to become pregnant, you may potentially apply FMLA leave toward treatments or even medically required bed rest during pregnancy.

Many companies that arent governed by FMLA do offer generous parental leave and health policies including covered health expenses. When in doubt, speak with your companys human resources or benefits manager to fully understand what leave if any you can use. They can also tell you whether your insurance will cover any treatments.

In theory, your medical situation is no ones business, and you have a right to privacy. But depending on the type of fertility treatments youre using, it might be unrealistic to keep this process to yourself.

For example, IVF is managed in cycles that usually coincide with your menstrual cycle. This means that a full IVF cycle can last several weeks, and many couples require more than one cycle to achieve success. Youll need to factor in several appointments, including procedures like egg retrieval and embryo transfer.

Beyond that, keep in mind that some treatments require taking fertility medications. These can create unexpected reactions both physically and emotionally. Many fertility specialists recommend taking 1 or 2 days off from work for the egg retrieval procedure, and some doctors recommend taking a few days off after the embryo transfer as well.

Only you know how agreeable your workplace will be to you taking time off periodically throughout the month to manage fertility treatments. At a minimum, be prepared to talk with direct managers or your human resources point of contact because youll need their approval to take time off or coordinate benefits.

But youll also need to consider other factors.

If youre thinking of taking a hybrid work approach, where youre primarily in the office but working remotely during critical points in an IVF cycle, other people might also need to know why youre out of the office. Anyone considered critical to ensuring that your job runs smoothly should realistically be kept in the loop.

Additionally, if you have close work friends who you trust and believe will provide much-needed support, you might want to tell them. We cant stress enough that fertility treatments can be draining both emotionally and physically.

ASRMs Mental Health Professional Group (MHPG) agrees about this psychological impact. So, having a solid support system in all aspects of your life can be very helpful.

Remember that you control the narrative. You can provide general information without sharing all the details. Fertility concerns are a sensitive topic that not everyone is comfortable talking about.

Plus, theres the added reality that while legal protections against workplace gender discrimination exist, some people have reported feeling like their work ethic or capabilities were questioned once disclosing that they were undergoing fertility treatments.

So, if youre only comfortable saying you have to undergo medically necessary procedures, leave it at that and dont feel pressured to share more. If necessary, get documented support from your healthcare professional.

The TTC process is a rigorous one, but even more so when youre also battling infertility. While its important to cover your bases professionally, you also need to be kind to yourself as you navigate treatment.

Between the physical side effects of fertility drugs and the shifting emotions, you might not be up to maintaining your usual schedule. This is especially true if youre juggling a full-time job, multiple fertility appointments and procedures, and remembering to take medications.

Dont feel pressured to maintain your pre-fertility treatment schedule if its going to leave you frazzled and exhausted. Taking care of yourself is priority number one!

No matter how you conceive, anyone whos ever attempted to get pregnant will tell you that having a sympathetic and supportive network can help make the experience more manageable.

You may choose to round up friends and family in your social network who can help you get through this time. Its also good to connect with fertility treatment support groups so you can talk with someone who knows what youre going through.

Youre going through a rough period, so feel free to pamper yourself just a bit more. Whether self-care looks like booking a massage or having a reality show marathon, you deserve to spend a few moments not being preoccupied with your fertility.

If youre undergoing fertility treatments, youre already taking one of the most proactive steps possible to achieve your ultimate goal of getting pregnant.

It can be tempting to spend time online looking up details about fertility treatment success rates, plus what early pregnancy symptoms to expect and how to spot them. But this can encourage rumination and spiraling thoughts, which can make an already stressful situation feel worse.

If you have questions about fertility or fertility treatments, talk with your healthcare professional about them instead. After all, theyre the pro!

Dont underestimate the importance of spending time talking with someone whos not in your social circle and who can serve as a neutral sounding board. Again, fertility concerns and, by extension, fertility treatments can throw you for many emotional loops.

Countless studies have shown that living with infertility can have a serious and long-term impact on your mental health, according to a 2008 research review. Having a safe space to talk through whats bothering you, as well as learning other effective coping methods, is important.

Not everyone can take time off from work to accommodate fertility treatments. If youre able, work with your companys human resources or benefits director to determine what leave or medical coverage can be applied to your treatments.

While you may need to tell key stakeholders at work whats going on, dont feel pressured to share every little detail or tell every single person. Its important to take care of yourself and make sure you have a strong support system around you during treatment.

Excerpt from:
What You Need to Know When You're Working During Fertility Treatment - Healthline

Recommendation and review posted by Bethany Smith

Ovarian cancer is a growth of cells that forms in the ovaries.The cells multiply quickly and can invade and destroy healthy body tissue.The female reproductive system contains two ovaries, one on each side of the uterus.The ovaries each about the size of an Almond produce eggs(ova) as well as the hormones estrogen and progesterone.

Signs & symptoms

When ovarian cancer first develops,it might not cause any noticeable symptoms.When ovarian cancer symptoms happen,they're usually attributed to other,more common conditions.

Signs and symptoms of ovarian cancer may include:

a.Abdominal bloating or swelling.

b.Quickly feeling full when eating.

c.Weight loss.

d.Discomfort in the pelvic area.

e.Fatigue.

f.Back pain.

g.Changes in bowel habits,such as constipation.

h.A frequent need to urinate.

Causes of Ovarian Cancer

It's not clear what causes ovarian cancer, though doctors have identified things that can increase the risk of the disease.

Doctors know that ovarian cancer begins when cells in or near the ovaries develop changes(mutations) in their DNA.A cell's DNA contains the instructions that tell the cell what to do.The changes tell the cells to grow and multiply quickly,creating a mass (tumor)of cancer cells.The cancer cells continue living when healthy cells would die.They can invade nearby tissues and break off from an initial tumor to spread (metastasize) to other parts of the body.

Types of ovarian cancer

The type of cell where the cancer begins determines the type of ovarian cancer you have and helps your doctor determine which treatments are best for you.Ovarian cancer types include:

a.Epithelial ovarian cancer:This type is the most common.It includes several subtypes, including serous carcinoma and mucinous carcinoma.

b.Stromal tumors:These rare tumors are usually diagnosed at an earlier stage than other ovarian cancers.

c.Germ cell tumors:These rare ovarian cancers tend to occur at a younger age.

Risk factors

Factors that can increase your risk of ovarian cancer include:

a.Older age:The risk of ovarian cancer increases as you age. It's most often diagnosed in older adults.

b.Inherited gene changes:A small percentage of ovarian cancers are caused by genes changes you inherit from your parents.The genes that increase the risk of ovarian cancer include BRCA1 and BRCA2. These genes also increase the risk of breast cancer.Several other gene changes are known to increase the risk of ovarian cancer, including gene changes associated with Lynch syndrome and the genes BRIP1, RAD51C and RAD51D.

c.Family history of ovarian cancer:If you have blood relatives who have been diagnosed with ovarian cancer,you may have an increased risk of the disease.

Being overweight or obese.Being overweight or obese increases the risk of ovarian cancer.

d.Postmenopausal hormone replacement therapy:Taking hormone replacement therapy to control menopause signs and symptoms may increase the risk of ovarian cancer.

e.Endometriosis:Endometriosis is an often painful disorder in which tissue similar to the tissue that lines the inside of your uterus grows outside your uterus.

f.Age: Age when menstruation started and ended.Beginning menstruation at an early age or starting menopause at a later age, or both,may increase the risk of ovarian cancer.

g.Never having been pregnant:If you've never been pregnant, you may have an increased risk of ovarian cancer.

Prevention

There's no sure way to prevent ovarian cancer.But there may be ways to reduce your risk:

a.Consider taking birth control pills:Ask your Physician whether birth control pills (oral contraceptives)may be right for you. Taking birth control pills reduces the risk of ovarian cancer.But these medications do have risks,so discuss whether the benefits outweigh those risks based on your situation.

b.Discuss your risk factors with your doctor:If you have a family history of breast and ovarian cancers, bring this up with your doctor.Your doctor can determine what this may mean for your own risk of cancer. You may be referred to a genetic counselor who can help you decide whether genetic testing may be right for you.If you're found to have a gene change that increases your risk of ovarian cancer,you may consider surgery to remove your ovaries to prevent cancer.

Diagnosis

Tests and procedures used to diagnose ovarian cancer include:

a.Pelvic exam:During a pelvic exam,your physician inserts gloved fingers into your vagina and simultaneously presses a hand on your abdomen in order to feel(palpate) your pelvic organs.The doctor also visually examines your external genitalia,vagina and cervix.

b.Imaging tests:Tests,such as ultrasound or CT scans of your abdomen and pelvis, may help determine the size,shape and structure of your ovaries.

c.Blood tests:Blood tests might include organ function tests that can help determine your overall health.

Your doctor might also test your blood for tumor markers that indicate ovarian cancer. For example, a cancer antigen(CA) 125 test can detect a protein that's often found on the surface of ovarian cancer cells.These tests can't tell your doctor whether you have cancer,but they may provide clues about your diagnosis and prognosis.

d.Surgery:Sometimes your doctor can't be certain of your diagnosis until you undergo surgery to remove an ovary and have it tested for signs of cancer.

e.Genetic testing:Your doctor may recommend testing a sample of your blood to look for gene changes that increase the risk of ovarian cancer.Knowing you have an inherited change in your DNA helps your doctor make decisions about your treatment plan.You may wish to share the information with your blood relatives,such as your siblings and your children,since they also may have a risk of having those same gene changes.Once it's confirmed that you have ovarian cancer,your doctor will use information from your tests and procedures to assign your cancer a stage. The stages of ovarian cancer range from 1 to 4, which are often indicated with Roman numerals I to IV.The lowest stage indicates that the cancer is confined to the ovaries. By stage 4,the cancer has spread to distant areas of the body.

Treatment

Treatment of ovarian cancer usually involves a combination of surgery and chemotherapy.Other treatments may be used in certain situations.

a. Surgery to remove one ovary:For early-stage cancer that hasn't spread beyond one ovary, surgery may involve removing the affected ovary and its fallopian tube.This procedure may preserve your ability to have children.

b. Surgery to remove both ovaries:If cancer is present in both your ovaries,but there are no signs of additional cancer,your surgeon may remove both ovaries and both fallopian tubes.This procedure leaves your uterus intact,so you may still be able to become pregnant using your own frozen embryos or eggs or with eggs from a donor.

c.Surgery to remove both ovaries and the uterus:If your cancer is more extensive or if you don't wish to preserve your ability to have children,your surgeon will remove the ovaries,the fallopian tubes,the uterus, nearby lymph nodes and a fold of fatty abdominal tissue(Omentum).

d. Surgery for advanced cancer:If your cancer is advanced,your doctor may recommend surgery to remove as much of the cancer as possible.Sometimes chemotherapy is given before or after surgery in this situation.

e.Chemotherapy: Chemotherapy is a drug treatment that uses chemicals to kill fast-growing cells in the body,including cancer cells.Chemotherapy drugs can be injected into a vein or taken by mouth.Chemotherapy is often used after surgery to kill any cancer cells that might remain.It can also be used before surgery.In certain situations, chemotherapy drugs may be heated and infused into the abdomen during surgery (Hyperthermic Intraperitoneal Chemotherapy).The drugs are left in place for a certain amount of time before they're drained.Then the operation is completed.

f.Targeted therapy: Targeted drug treatments focus on specific weaknesses present within cancer cells. By attacking these weaknesses,targeted drug treatments can cause cancer cells to die.

If you're considering targeted therapy for ovarian cancer,your doctor may test your cancer cells to determine which targeted therapy is most likely to have an effect on your cancer.

g.Hormone therapy: Hormone therapy uses drugs to block the effects of the hormone estrogen on ovarian cancer cells.Some ovarian cancer cells use estrogen to help them grow,so blocking estrogen may help control the cancer.

Hormone therapy might be a treatment option for some types of slow-growing ovarian cancers.It may also be an option if the cancer comes back after initial treatments.

h.Immunotherapy: Immunotherapy uses the immune system to fight cancer.The body's disease-fighting immune system may not attack cancer cells because they produce proteins that help them hide from the immune system cells. Immunotherapy works by interfering with that process.Immunotherapy might be an option for treating ovarian cancer in certain situations.

i.Supportive(Palliative)care: Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness. Palliative care specialists work with you, your family and your other doctors to provide an extra layer of support that complements your ongoing care.Palliative care can be used while undergoing other aggressive treatments,such as surgery and chemotherapy.When palliative care is used along with all of the other appropriate treatments, people with cancer may feel better and live longer.Palliative care is provided by a team of doctors,nurses and other specially trained professionals. Palliative care teams aim to improve the quality of life for people with cancer and their families.This form of care is offered alongside curative or other treatments you may be receiving.

Coping and support

A diagnosis of ovarian cancer can be overwhelming.In time you'll find ways to cope with your feelings,but in the meantime,you might find it helpful to:

a.Find someone to talk with:You may feel comfortable discussing your feelings with a friend or family member, or you might prefer meeting with a formal support group. Support groups for the families of people with cancer also are available.

b.Let people help:Cancer treatments can be exhausting.Let people know what would be most useful for you.

c.Set reasonable goals:Having goals helps you feel in control and can give you a sense of purpose.But choose goals that you can reach.

d.Take time for yourself:Eating well, relaxing and getting enough rest can help combat the stress and fatigue of cancer.

e.Preparing for your appointment:Start by making an appointment with your family Physician or gynecologist if you have any signs or symptoms that worry you.If your primary care Physician suspects that you have ovarian cancer,you may be referred to a specialist in female reproductive cancers(Gynecological Oncologist).A gynecological oncologist is an obstetrician-gynecologist(OB-GYN)who has additional training in the diagnosis and treatment of ovarian cancer and other gynecological cancers.

f.What you can do: Be aware of any pre-appointment restrictions,such as not eating solid food on the day before your appointment.

g.Write down your symptoms,including any that may seem unrelated to the reason why you scheduled the appointment.

h.Write down your key medical information, including other conditions.

i.Write down key personal information, including any major changes or stressors in your life.

j.Make a list of all your medications,vitamins or supplements.

k.Ask a relative or friend to accompany you, to help you remember what the doctor says.

l.Write down questions to ask your doctor:

l What's the most likely cause of my symptoms?

l What kinds of tests do I need?

l What treatments are available,and what side effects can I expect?

l What is the prognosis?

l If I still want to have children,what options are available to me?

l I have other health conditions.How can I best manage them together?

l In addition to the questions that you've prepared to ask your doctor,don't hesitate to ask other questions that occur to you.

m.What to expect from your doctor:Your doctor is likely to ask you a number of questions.Being ready to answer them may make time to go over points you want to spend more time on.You may be asked:

l When did you first begin experiencing symptoms,and how severe are they?

l Have your symptoms been continuous or occasional?

l What,if anything,seems to improve or worsen your symptoms?

l Do you have any relatives with ovarian or breast cancer?

l Are there other cancers in your family history?

Original post:
Introduction to Ovarian Cancer - Rising Kashmir

Recommendation and review posted by Bethany Smith

Mridula George, MD, discusses efforts to address unmet needs in HER2-low breast cancer.

Mridula George, MD, medical oncologist, Stacy Goldstein Breast Cancer Center, Rutgers Cancer Institute of New Jersey, assistant professor of medicine, Rutgers Robert Wood Johnson Medical School, discusses efforts to address unmet needs in HER2-low breast cancer.

The phase 3 DESTINY-Breast04 trial (NCT03734029) investigated fam-trastuzumab deruxtecan-nxki (Enhertu) vs. physicians choice of chemotherapy in patients with unresectable or metastatic HER2-low breast cancer. This study was pivotal because there is currently no treatment for this subgroup of patients, George says.

DESTINY-Breast04 met its primary end point of progression free survival, plus the secondary end point of overall survival in the subgroup of patients with hormone receptorpositive disease, George explains.

Future research could explore potential combinations withtrastuzumab deruxtecan, such as CDK4/6 inhibitors, George continues. The HER2-low space will generate more clinical trials to better understand treatment options for this subtype of breast cancer, George concludes.

Here is the original post:
Dr. George on Efforts to Address Unmet Needs in HER2-Low Breast Cancer - OncLive

Recommendation and review posted by Bethany Smith

The Iowa Board of Nursing has suspended the license of a nurse who allegedly had sex with a former psychiatric patient.

At its January meeting, the board voted to suspend the license of Shawn Sandersfeld of Muscatine indefinitely and ordered a mental-health and chemical-dependency evaluation.

Once that evaluation is completed, Sandersfeld must submit to any treatment that is recommended and, after showing proof of 12 months sobriety, may resume practice while serving a 12-month period of probation. Sandersfeld must also complete a three-day course on professional boundaries and ethics and submit to case-manager evaluations pertaining to competency and the ability to interact professionally with co-workers and patients.

The sanctions are tied to allegations by the board Sandersfeld was working as a psychiatric mental health nurse at an unspecified hospital in 2019 and provided nursing services to a particular patient who was discharged in July 2019.

According to the board, from August 2019 through June 2021, the patient lived at Sandersfelds home and the two engaged in a sexual relationship during that time.

According to the Iowa Board of Nursing, these other nurses have recently faced sanctions from the board:

Patrick Jones, Waterloo Jones agreed to immediately relinquish all rights to practice nursing in the state of Iowa and surrendered his license. He can apply for reinstatement in 12 months. According to the board, Jones was employed at a care facility, unspecified by the board, from September 2019 until July 2021.

At some point during his employment, the board alleged, Jones sent electronic communication to staff that created an uncomfortable work environment. According to the board, Jones communicated conversations that were sexual in nature with a patient and he engaged in sexual actions with a patient.

James Dickerson, Neola The board ordered Dickerson to immediately stop providing any treatment to patients with a complex mental health diagnosis until he received certification as a psychiatric nurse practitioner. The board also fined Dickerson $1,000 and ordered him to undergo five hours of consultation with a nurse practitioner. The settlement stemmed from charges that Taylor exceeded his scope of practice and dispensed drugs to individuals whose care was not within his specialized, licensed area of practice.

Miranda Figueroa, Omaha Figueroa agreed to immediately relinquish all rights to practice nursing in the state of Iowa and surrendered her license. She can apply for reinstatement in 12 months. Last October, the board charged her with an inability to safely practice nursing as a result of a physical or mental condition. At that time, the board indicated it had sought provider approval for Figueroa to safely practice nursing and that no provider had given that approval.

Kristine Wikner, McGregor Wikner agreed to undergo 10 hours of educational instruction on nursing documentation. In October, the board alleged she was working at a nursing home in 2020 when a family member was admitted to the facility. Although she was instructed not to access her family members medical records, she allegedly went into her relatives medical chart and changed some of the information entered there by another worker.

Nathan Tucker, Sioux City Tucker agreed to undergo 60 hours of educational instruction on critical thinking and nursing procedures. The board alleged that in October 2020, while working at a hospital emergency department, Tucker administered intravenous medication to patients on three occasions without a physicians order, failed to assess the IV sites, and failed to provide accurate information to a physician.

Terry Seitz, Williamsburg Seitz agreed to immediately relinquish all rights to practice nursing in the state of Iowa and surrendered her license. She can apply for reinstatement in 12 months. In September 2020, she was allegedly working at an unspecified facility when she had to be transported by emergency services to a hospital where she tested positive for amphetamines, marijuana and non-prescription opioids.

Mona Taylor, Rock Island, Ill. Taylor agreed to immediately relinquish all rights to practice nursing in the state of Iowa and she surrendered her license. She can apply for reinstatement in 12 months. The factual circumstances that triggered the action have yet to be made public. The board states that it filed a statement of charges against Taylor in October 2021, but that statement of charges has yet to be published by the board.

Kori March, Sioux City March agreed to undergo 60 hours of educational instruction pertaining to professional ethics and what the board called nurses legal advisor. Last fall, the board alleged that while working at an unspecified long-term care facility between 2018 and 2021, she performed intravenous therapy functions without having the IV-therapy certification required of licensed practical nurses.

Jennifer Mayberry, Waukee Mayberry agreed to have her license placed on probation for 18 months, during which time she must abstain from the use of alcohol and illicit drugs, submit to case-manager evaluations and chemical screening, and undergo mental health counseling. Last summer, the board alleged that during a pre-employment health screening in 2021, Mayberry tested positive for amphetamine and methamphetamine.

Derrick Miller, West Branch Miller agreed to have his license placed on probation for 12 months and to undergo six hours of educational instruction on medication safety. Last fall, the board alleged that in February 2021, while working at an unspecified nursing home, Miller lost the keys to the homes medication cart, left the unlocked cart unattended, and then left medication at a residents bedside without a doctors order to do so.

Eleven months earlier, Miller allegedly gave oxycodone to a resident who had not complained of pain and did not request the medication. In 2014, Millers license was indefinitely suspended pending completion of board-ordered treatment and verification of 12 continuous months of sobriety, followed by 12 months of license probation. The 2014 sanctions stemmed from charges of misappropriation of medications and being involved in the unauthorized manufacture or use of a controlled substance.

Ronda Eick, Waterloo The board issued Eick a warning and ordered her to undergo 34 hours of educational instruction on COVID-19 and medical documentation. Last fall, the board alleged that while Eick was working at an assisted living center in 2021, she received a text message from a co-worker who stated that he or she had COVID-19. Eick did not notify human resources, the facilitys clinical coordinator or the staffs health nurse of that information.

A few days earlier, two residents of the center had tested for COVID-19, with one showing a positive result and the other showing an inconclusive result. According to the board, Eick falsely reported that one of the two residents had tested negative for COVID-19. In 2008, the board ordered Eick to complete 15 hours of educational instruction related to ethics. That sanction stemmed from her pleading guilty to a criminal charge of theft tied to allegations that she stole money collected by colleagues for the benefit of a co-worker.

McKinsey Schurr, LeClaire The board issued Schurr a warning for excessive use of alcohol after it allegedly received information that Schurr had an alcohol-use disorder. The board charged Schurr with excessive use of alcohol that may impair a licensed nurses ability to practice.

Rhonda Adkins, Grinnell Adkins agreed to under 30 hours of educational instruction on professional ethics. Last fall, the board alleged Adkins was employed as a home care nurse in 2021 when she falsified patient records and employee timecards to indicate she was providing care for a patient on dates when she did not actually work.

Jennifer Evins, Rock Island, Ill. Evins agreed to immediately relinquish all rights to practice nursing in the state of Iowa and surrendered her license. She can apply for reinstatement in 12 months. Last fall, the board alleged that in 2020, Evins was convicted of a crime related to the profession of nursing and the theft of patient medications.

As a result of the criminal conviction, Evins license was placed on probation in October 2020 and she was barred from using alcohol while on probation. In June 2021, she allegedly tested positive for alcohol use and later admitted she had been drinking.

Amanda Bendon, Dubuque Bendon agreed to undergo up to 10 hours of educational instruction on ethics and legal liability. The board had alleged that Bendonwas working at an unspecified medical clinic in 2020 when she removed a vial of Pentacel from the clinic, took it home and administered it to her child without a prescription and without permission from the clinic. Pentacel is used as a vaccine for immunization against diphtheria, tetanus and other conditions.

Jennifer Mastin, Walnut Mastin agreed to undergo up to 10 hours of educational instruction on ethics and legal liability and have her license placed on 12 months probation. The board had alleged that on more than one occasion while working at an unspecified care center, Mastin disposed of medication without the required witness; removed two narcotics from the inventory and administered only one dose; and failed to document the administration of narcotics to residents.

Tricia Venzke, Ames Venzke agreed to undergo 30 hours of educational instruction on managing difficult patients. The board had alleged that in 2021, while dealing with a combative hospital patient, Venzke reacted physically inappropriately to the patient.

Miranda Depyer, Graettinger Depyer agreed to undergo seven hours of educational instruction on professional accountability and critical thinking skills. The board had alleged that in April of last year, Depyer responded to an ambulance call for a woman in labor. While en route to a hospital, Depyer allegedly gave the woman a dose of Pitocin a natural hormone sometimes used to induce labor without a physicians order.

Read more here:
Iowa nurses sanctioned for sex with patients, meth use and other violations - Iowa Capital Dispatch

Recommendation and review posted by Bethany Smith

Transcript:

Lori Wirth, MD: Maybe you could describe for us what the typical thyroid cancer diagnosis and brief course of typical treatment is for the garden variety thyroid cancer.

Bryan McIver, MD: Most thyroid cancer presents as a lump in the neck, and that lump is often something that is felt on a routine physical exam. Sometimes its picked up on a scan done for other reasons. For example, if somebody gets their carotid artery scanned and the lump in the thyroid gland is found by accident. Occasionally, of course, the disease is found having already spread, and so sometimes a lump on the side of the neck is found and it turns out to be a lymph node involving that cancer. The typical course of treatment is to diagnose and confirm that it is cancer using a biopsy, typically a fine needle biopsy under ultrasound guidance. That biopsy leads to the diagnosis and that leads to a surgical treatment.

The most common surgery is to remove either part or all of the thyroid gland and some of the surrounding lymph nodes. Then, for patients with more advanced disease, with more aggressive disease, additional treatment with things like radioactive iodine is commonly used, and then treatment, as well, with thyroid hormone. When I think about cancer, I think about 3 main ways to treat cancer: surgery to remove it, radiation treatment to burn it, and chemotherapy to poison it. We use that same technique in thyroid cancer. We remove it surgically, we use radioactive iodine as our primary radiation therapy, and we use chemotherapy in the form of thyroid hormone. This is done because thyroid hormone in a slightly higher dose than the body expects to see can suppress the growth of thyroid cancer, and actually, in some cases, prevent it from recurring in the future. Its important for us to think about it in those 3 modalities.

Lori Wirth, MD: Then, of course, there is a subset of differentiated thyroid cancer that recurs despite those 3 modalities of treatment, and thats really what the program today is focused on, a more advanced differentiated thyroid cancer. There are some cancers that just have a more aggressive biology that will, despite having surgery, thyrotomy suppression, and radioactive iodine, still come back. Generally, those are considered radioactive iodine-refractory differentiated thyroid cancers. Thats really what were talking about today. Im a medical oncologist. When I think of chemotherapy, I dont think of levothyroxine so much as IV [intravenous] chemotherapy, or oral multikinase targeted therapies, or other cancer drugs that we use. They are gene-specific therapies that have a role in some subset of thyroid cancers. Bryan, of course, you are an endocrinologist, so our specialties are a little bit different. What do you think of in terms of the general role for the endocrinologist in taking care of patients with more advanced radioactive iodine-refractory differentiated thyroid cancer, and the role with the patient, and the role with the other physician team members taking care of those patients?

Bryan McIver, MD: Thats a really important question, Lori, for us to address. When I think about thyroid cancer when I first trained 25 years ago, we didnt have the options for these more advanced targeted kinase inhibitors and other true chemotherapies. We were really restricted to surgery, radioactive iodine, and thyroid hormone. I learned during my career to care for patients from diagnosis all the way through to the end of the journey, and unfortunately sometimes that journey was the end of life because the cancer could actually kill people. Its not a good cancertheres no such thing as good cancerbut certainly thyroid cancer is not always the rosy picture that people paint. A significant minority of our patients do get recurrences that we cant control through these traditional means, or get disease that have spread, and they require more advanced therapy.

The most amazing thing during the last 10 years has been the development of so many new chemotherapy drugs, typically taken by mouth, often very effective at suppressing the cancer growth, sometimes for years and even longer. The endocrinologist has to learn to think like an oncologist and begin to recognize that some patients need systemic therapy, and then either learn how to treat those patients with those systemic therapies, or work in partnership with a medical oncologist who is used to using these drugs. I always think that a medical oncologists skillset is poisoning people without killing them. At the end of the day, we use these poisons, theyre going to have side effects and theyre going to have issues, but they can be highly effective in controlling this disease for which weve otherwise run out of options. My job is to recognize when its time to bring in those other skillsets. I do that with surgeons because I dont operate. I do it with the radiation doctors because I dont administer the radioactive iodine. I do it with medical oncology colleagues because I dont prescribe chemo [chemotherapy]. Some people just say that I dont do anything, which is actually accurate.

Lori Wirth, MD: Bryan, Im curious, when you share a patient with a medical oncologist, what kind of a working relationship do you tend to have with a medical oncologist, as well as with the individual patient?

Bryan McIver, MD: I think the best way to describe the relationship I have with my medical oncology team is one of mutual respect. We both recognize that we have distinct skillsets, and we can bring those skillsets to bare to help manage the patient. I understand the cancer and I understand how to manage the early stages of that journey for this patient. Often by the time theyre coming to need chemotherapy and advanced treatments, Ive known this patient for years, and what I dont do is then abandon them and just send them off to a medical oncologist. We work together in a multidisciplinary clinic where we see the patients together. Once a decision is made to initiate therapy, we involve our pharmacist, who is an important team member to help understand side effect management and dose management. My medical oncology colleague does all of the difficult work of modulating the dose and getting patients to tolerate the drugs effectively, and then we jointly follow that patient in our multidisciplinary setting to review the scans, review the tumor markers, and ensure that thyroid hormone levels are appropriately managed, and thats an ongoing relationship again for the duration of the journey.

Lori Wirth, MD: I really like your answer, because if I had been asked that question, I would have answered it in a very similar way except from the medical oncologist point of view. The other reason I really liked the answer is that I think you captured very nicely how helpful it is to have a really robust multidisciplinary team taking care of patients with advanced iodine-refractory thyroid cancer.

Transcript edited for clarity.

Excerpt from:
General Principles of Management of DTC and Role of the Health Care Team - Curetoday.com

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This time, I have to wait. The day after my regular screening mammogram, the nightmare begins, quietly. I learn through the patient portal system that I have to go back for diagnostic imaging of the questionable calcifications on the left, and possible architectural distortion on the right. There is a number to call.

I call right away. I cannot have the second mammogram and ultrasound, Im told, until December 13 five weeks away! The system, not a friendly doctor as Id once had, has just told me that I might have cancer or even two different kinds of cancers, one in each breast but I wont find out for at least five weeks because this hospital is fully booked.

Fully booked? I cant believe this wait can be blamed totally on COVID-19. I suspect preexisting, patient-unfriendly hospital bureaucracy as well.

Waiting for anything can be agonizing. For a loved one to call. For a college acceptance. For a needed paycheck. Stressful, but normal. Waiting for medical test results? Excruciating. And, to my mind, at least somewhat avoidable.

Granted, growing cells in culture or analyzing pathology specimens takes time. But when the system chugs along at its own sluggish pace, when doctors or their surrogates dont call back promptly, when online patient portals give only partial information? Thats unforgivable. And would be fixable, if patients, not bureaucracy, always came first.

The basic dictum of medicine is primum non nocere: First, do no harm. But being made to wait for weeks to find out if you have cancer, or any other serious disease for that matter, is harm it evokes fear of the unknown. The oldest and strongest emotion of mankind is fear, and the oldest and strongest kind of fear is fear of the unknown, is how horror writer H. P. Lovecraft put it. Philosopher and writer Joseph Campbell interpreted the struggle with what he called our greatest fear this way: Many of us would enter a tigers lair before we would enter a dark cave.

As humans, we crave information to help us understand everything that comes at us every day. What underlies the fear of the unknown is the perceived absence of information at any level of consciousness, wrote psychologist R. Nicholas Carleton, who has studied the phenomenon, in a 2016 paper. And unpredictability makes it worse. In experimental settings, people show more stress if there is a 50 percent chance of receiving an electric shock than if there is a 100 percent chance, according to a 2016 study published in Nature Communications journal.

On the surface, this does not make rational sense we should be only half as anxious if theres only half the risk. But thats not how our minds work. With uncertainty, the brain, particularly the fear center, the amygdala, revs up into a state of hypervigilance.

And so, I wait. I meditate. I swim. I do my relaxation tape. I swim some more, 2 miles at a time. I use a meditation app on my phone. I wait.

Some days, I can concentrate on work. Other days, Im imagining a double mastectomy, reconstruction, Stage 4 cancer. I Google madly, pore over reliable websites, print out reams of cancer data. And I fume. Cancer wasnt in my lifes plan. Its not in anybodys. Im stunned by my own anger. Why would I expect to be any luckier than anybody else?

And Im angry at the hospital that did the mammography. Couldnt the mammography center predict how many questionable scans like mine are likely on any given day, then plan to save slots the following day for subsequent tests?

I call my primary care physician who, God bless her, works the system and gets me in for the second round of mammograms sooner, just a week away.

November 11, 2:45 p.m.

Breast imaging at a different top Boston hospital.

Two gentle radiologists do more mammography and ultrasound. We have to do some sampling, says the senior radiologist. Im afraid I have to use a scary word 'mass on the right. The left seemed less worrisome.

I lose it. You mean I could have two different cancers? At least I can ask the doctors in front of me right away.

Its possible, she says.

I ask for my husband. He comes in, strokes my back. Double biopsies are scheduled, 18 days away. We go out to eat. I have a martini and a half. He does, too. The fear is running away with me.

I go home and log onto the hospitals online patient portal. I need more information. I click on the little envelope icon that suggests I might be able to initiate contact with the radiologist whose name appears on the test results. No luck shes not listed as one of my available contacts.

I try calling. No luck. The hospital switchboard has no record of anyone by this name. I ask about the other radiologist, but she also seems to be unknown to the hospital. I persist. I learn that shes gotten married and uses a different last name now, not yet updated in the system. When we finally connect by phone, she repeats the results I already have but doesnt elaborate on them to me thats for another doctor to do.

I wait some more. I meditate. Im up to 2-mile swimming sessions now.

November 29, 10:15 a.m.

Biopsy day finally.

Again, two radiologists. They patiently describe the biopsy procedure to me, step by step, then narrate the procedure as they continue their work. The lab tech stands where I can see her and chats kindly with me throughout. Thanks to lidocaine, the procedures are almost painless.

Loaded up with ice packs and care instructions, my husband and I leave, get home, and crash. We sleep for two hours. We know it will be three to five days before we get the results. Compared with the past month, that feels bearable.

December 1

As I drive home from an errand, one of the radiologists calls. I pull over, get out a pencil and paper.

The left side is benign. The right, she tells me, has invasive tubular cancer.

Ive never heard of tubular cancer and, Googling later in the day, learn that its rare and not too bad. I am remarkably calm, so happy to know. Knowing even something awful is so much easier than not knowing. Im free of that horrid anxiety, the prison of fear.

The minute I get home, I tell my husband, then swing into action. I e-mail some doctors Id been lucky to meet over decades of medical reporting for the Globe, asking for help. Whats invasive tubular cancer? How bad is it? Am I going to die? They e-mail right back, cutting short the weeks it couldve taken to get the information they give me.

One oncologist source is especially reassuring. This is the most nothing of all breast cancers, he tells me, with zero chance of threatening your life. I know I still have to have surgery and nobody has told me yet whos in charge. A surgeon? I have no idea whom to call now. Still, Im delirious.

Im also curious about the hormone receptor status of my cancer, knowing from all my years of reporting that many breast cancers feed on estrogen, or progesterone, or both, and that will affect my treatment plan. Back to the patient portal. My test results file says information on hormone status will be forthcoming as an addendum. No addendum follows. I e-mail my primary care doctor again. She gets the results and tells me: The cancer is positive for both hormones. Why the patient portal can tell me I have cancer but not tell me the hormone receptor status is a mystery. Hospital bureaucracy again?

Then, suddenly, Im in the system at the Dana-Farber Cancer Institute, a place Ive written about for decades. I never thought Id be a patient there.

Now, phone calls are returned quickly.

Appointments are set up efficiently. Nurses call with questions. A COVID test is set up. Im no longer lost in medical limbo, unable to get information, unable to figure out whos in charge.

Im optimistic. A plan is in place. Ill be OK.

And the next time my mammogram rolls around, Im calling Bonnie beforehand.

Judy Foreman was the Health Sense columnist for the Globe for many years and the author, most recently, of CRISPRd, a medical thriller. Send comments to magazine@globe.com.

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They said I might have breast cancer. Why would I need to wait weeks for a biopsy? - The Boston Globe

Recommendation and review posted by Bethany Smith

Blood sugar less than 40, Pre diabetes tremendously increases the chance of developing type 2 diabetes The excellent news is that, in case you have prediabetes, you probably can forestall or delay the onset of full blown type 2 diabetes by making lifestyle modifications Hyperglycemia In DiabetesThese embrace eating a nutritious diet, reaching and maintaining a wholesome weight, and exercising often Insulin is vital to patients with type 1 diabetes they can not stay without a source of exogenous insulin Without insulin, sufferers with kind 1 diabetes develop severely elevated blood sugar levels. Bariatric blood sugar checker on arm surgical procedure has been shown to attain remission in some individuals with Type 2 diabetes This is a significant surgery that has its own dangers and issues If you haven t been diagnosed with diabetes, you should see your healthcare provider in case you have any symptoms of diabetes If you already have been identified with diabetes, you need to contact your provider if your blood glucose levels are outside of your target range, if current symptoms worsen or when you develop any new symptoms In addition to the problems with a rise in insulin resistance, the release of insulin by the pancreas may also be defective and suboptimal. Today, a broad range of computerized diabetes gadgets are available to help folks higher handle their blood sugar ranges whereas research towards a treatment for diabetesmoves forward In kind 1 diabetes, the body s immune system attacks the insulin producing islet cells within the pancreas The islet cells sense glucose in the blood and produce the appropriate quantity of insulin to normalize blood sugars. There are two major types of diabetes mellitus, kind 1 and type 2 More men than ladies have diabetes in the US, and the disease can affect males in one other way than girls Warning signs of diabetes that men have and ladies do not embrace low testosterone low t , sexual problems, impotence blood sugar level of 373 , decreased curiosity in sex, and retrograde ejaculation Treatment for type 1 diabetes is insulin, and treatment for kind 2 diabetes are life style adjustments like eating a healthy diet, getting exercise every day, and if needed, diabetes drugs The regular vary human blood sugar level chart of blood glucose levels for individuals with diabetes is between 80 and one hundred thirty milligrams per deciliter mg dL.

My blood sugar is 129, While there are heaps of ingredients that can be used to make a scrumptious soup, we ve chosen 9 of our favorites These wholesome soups are sure that can help you keep on monitor along with your diabetes management and weight reduction goals Cheri shares what Continuous Glucose Monitor is and what components blood sugar home remedy ayurvedic have an effect on your glucose levels that can, in turn, affect your overall well being Did you realize that roughly 80 percent of dieters who shed pounds find yourself regaining it Find out the way to create and sustain wholesome habits to keep up your goal weight after hitting your weight loss targets Oats have medium to excessive quantities of dissolvable fiber, which is crucial for blood sugar control. Participants who consumed alcohol with meals exhibited a 14 per cent decrease risk of kind 2 diabetes compared to consuming alcohol without eating meals Study members who consumed alcohol with meals exhibited a 14 per cent decrease risk of type 2 diabetes compared to consuming alcohol with out consuming food The course is the best, I learnt a lot, a beautiful refresher and Brilliant update on newest blood sugar 74 and 54 remedies Approximately 3 to 8 pc of all pregnant girls in the United States are diagnosed with gestational diabetes When the physique loses the power to make insulin or can only make a really small amount of insulin. The numbers below represent values within the hypoglycemic vary and blood sugar spike after breakfast require motion to convey blood sugar ranges up into a traditional range If low blood sugar is extreme, individuals may need to go to the hospital to help elevate their glucose stage or miss work because of the unwanted effects In the quick term, excessive blood sugar ranges can zap your energy, trigger extreme thirst and urination, and blur your vision High blood sugar ranges also can lead to dehydration, dry and itchy pores and skin, and infections. Other risk elements can embody having sure infections or diseases of the pancreas Glucose is a vital nutrient that provides vitality for the right functioning of the physique cells However, glucose cannot enter the cells alone and desires insulin to aid in its transport into the cells Without insulin, the cells turn out to be starved of glucose energy regardless of the presence of ample glucose in the bloodstream In sure kinds of diabetes, the cells inability to utilize glucose offers rise to the ironic scenario of hunger in the midst of plenty.

Blood pressure blood sugar cholesterol, This occurs whether as a outcome of the pancreas just isn t offering adequate quantity of insulin or target tissues aren t responding to insulin Diabetes is more prone to develop in households with known diabetes historical past I actually have been a relentless uninteresting headache on my forehead for the past 3 weeks with intermittent nausea Especially if there may be increased thirst, urination and weight reduction. But when someone has diabetes, this finely tuned system will get thrown out of whack In sort 2 diabetes which accounts for 90 to 95 of diabetes in adults, based on the CDC the body both can t make enough insulin or can t utilize insulin properly, based on the NIDDK If somebody has prediabetes, their blood glucose might be larger than regular however not fairly in the type 2 diabetes range but, per the NIDDK And in type 1 diabetes, the body doesn t make insulin or makes little or no Clients across the life span with diabetes have various clinical presentations. Keeping blood glucose above 4 mmol l for folks on insulin or certain medications for type 2 diabetes is necessary to prevent hypos occurring, which can be dangerous If a person with diabetes has a meter, take a look at strips and is testing, it s important to know what the blood glucose level means A steady glucose monitor, on the left, is a tool that measures your blood sugar each couple of minutes using a sensor inserted underneath the skin. Wait for 30 60 minutes without consuming, and test once more to see if your blood sugar has dropped to a stage that is safe for train Strenuous activity and train encourage your physique to produce glucose to gasoline your muscle tissue The patient should begin by discussing the excessive blood sugar stage with their doctor The doctor will be able to carry out a quantity of tests to offer them a better view of the patient How Is Diabetes Treateds diabetes Normally, the kidneys assist to filter out extra blood glucose by rising the amount of urine removed from the physique.

Low blood sugar of 40, The prognosis of diabetes is said to the extent to which the condition is stored underneath control to forestall the event of the issues described in the previous sections Some of the extra severe issues of diabetes corresponding to kidney failure and cardiovascular disease, could be life threatening Acute complications such as diabetic ketoacidosis can be Patient Discussion About Diabeteslife threatening As mentioned above, aggressive control of blood sugar levels can forestall or delay the onset of complications, and many individuals with diabetes lead lengthy and full lives Diabetes experts feel that these blood glucose monitoring units give patients a major amount of independence to handle their illness process and they are an excellent software for schooling as nicely. They keep a daily document of findings and are taught to regulate insulin dosage accordingly More current glucose monitoring devices can draw blood from different places on the body, such as the forearm The patient, physician, nurse, and dietician should carefully consider the patient s life type, dietary wants, and skill to comply with the proposed dietary prescription. More than 90 of the diabetics in the United States are Type II diabetics Sometimes referred to as age onset or adult onset diabetes, this form of diabetes happens most frequently in people who find themselves overweight and who do not train It can additionally be more common in folks of Native American, Hispanic, and African American descent People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures also usually have a tendency to develop Type II diabetes than those who remain of fasting blood sugar accu chek their unique nations. But, research suggests that consuming processed foods can enhance blood glucose High blood glucose, also called hyperglycemia, happens when there is too much sugar in the bloodstream Low blood sugar, or hypoglycemia, is the results of too little glucose in the bloodstream Hyperglycemia usually occurs as a result of your body doesn t produce sufficient insulin or can t correctly use the out there insulin to remove the glucose from the bloodstream CGMs are extra expensive than the standard finger prick glucose meters as About Ascensia Diabetes Carea outcome of more superior know how used in Early Signs And Symptoms Of DiabetesCGMs.

Bad blood sugar levels chart, Do you ve trouble losing weight, regardless of how hard you try to shed these undesirable pounds Find out extra concerning the weight loss plateau and what you are able to do about it From acupuncture to chiropractic treatments and homeopathy to holistic therapeutic, complementary and various drugs is rising in blood sugar level to a1c recognition Read on to be taught extra about Ayurveda, a therapeutic system that originated in India 1000 s of years in the past Did you know that menopause can have an effect on your metabolic well being, and vice versa Read on to know the connection between metabolic well being and menopause, and the method to manage metabolic health throughout your menopausal journey. For most girls, blood sugar ranges will return to regular after giving start And should you ve had gestational diabetes, you will want to be examined regularly since you might be at a lot greater danger for growing kind 2 diabetes later in life GLYCEMIC INDEX is a scale which helps to rank carbohydrate rich meals, relying on how they have an result on blood glucose levels, by evaluating them to glucose You may have to change your therapy or way of life to maintain your blood sugar ranges within a healthy range For typically healthy individuals who haven t eaten for eight hours or more, a normal blood sugar level is between mg dL. Some widespread legumes are lentils, beans, peas, and chickpeas Legumes are also excessive in fiber, which helps keep blood sugar from spiking because the fiber slows the breakdown of the meals Try making a hearty lentil soup or having a chickpea hummus to dip veggies into. I was normal but because I lost a lot of weight and felt too thirsty and urinate incessantly, I went to see a doctor In the morning I have a tendency to simply have porridge oats with skimmed milk My larger readings tend to be pre breakfast though the levels are coming down Is it attainable to get any graphical method of say weekly or some instances 10 days irregular days with NORMAL graphical lineSoas to check and be precautionary by diabetic patient itself Since diabetic food regimen is restrictive, you should change your view from focusing on the things you can t eat to specializing in the entire scrumptious issues you possibly can eat.

Blood sugar level is 265, Treatment of kind 2 diabetes primarily involves life style adjustments, monitoring of your blood sugar, together with diabetes drugs, insulin or each We publish material that s researched, cited, edited and reviewed by licensed medical professionals The info we provide just isn t meant to be a substitute for skilled medical advice, prognosis or therapy. You use a blood glucose meter to check your blood sugar This gadget uses a small drop of blood from your finger to measure your blood sugar degree You can get the meter and supplies in a drug retailer or by mail In addition to making meals selections that are blood sugar aware, train is a method to assist decrease your blood sugar When you re bodily active, your muscles burn sugar for power and use it for muscle constructing and restore This helps pull sugar from the blood, decreasing blood sugar ranges. There is a paucity of randomised controlled studies that specifically investigate pharmacological therapy of African American diabetic sufferers Type 2 diabetes is a typical condition that causes the level of sugar in the blood to turn out to be too excessive At least every year, get a blood test to check your cholesterol and triglyceride ranges Furthermore, half of all ladies with gestational diabetes will go on to develop kind 2 diabetes, in accordance with 153 blood sugar to a1c the CDC. They usually are not supposed to diagnose, cure, prevent or deal with any disease or condition This program and its companies shouldn t be used for the monitoring or administration of diabetes The NutriSense applications and services are to assist members uncover and attain their well being potential DKA could be deadly if left untreated, so anyone experiencing these signs should seek care immediately.

Smart blood sugar fix book, Most Read Food Labelsfruits naturally have blood sugar level of 700 a low glycemic index due to the fructose and fiber they include Verywell Health s content is for informational and academic functions solely Our web site just isn t meant to be an various to professional medical advice, diagnosis, or treatment Lark Diabetes Coach comes with a complete home glucometer equipment that s shipped to you and is simple to arrange The Lark app walks you through setup and reminds you when to take your blood sugar. It must be mentioned right here that there are a variety of conditions in which an A1c worth may not be correct For example, with significant anemia, the purple blood cell depend is low, and thus the A1c is altered This may be the case in sickle cell disease and different hemoglobinopathies Frequent infections usually tend to occur in folks with untreated or poorly controlled diabetes Nausea and vomiting also can happen in patients with untreated diabetes Some untreated diabetes patients also complain of fatigue. It consists of cinnamon, which is a strong antioxidant which will assist regulate your blood sugar levels Drinking in excess affects your body s capacity to produce insulin Specifically, too much alcohol can cause inflammation to the pancreas, which impairs your body s ability to emit insulin To drink sparsely, stick to 1 to 2 drinks per day at most. A meter can let you know what your ranges are in about 5 seconds Another choice is by taking an oral glucose tolerance test , which takes longer but may also provide extra accurate outcomes A person s individual level will rely upon many components together with how old they are, their ethnicity, their weight and top, and the activity they ve performed lately Blood sugar ranges can be checked by pricking a finger to get a drop of blood and placing it on a glucose meter.

Blood sugar levels 6 8, For this reason, a decrease dose of 300 mg is usually recommended Berberine is thought to help with blood sugar as a outcome of it may enhance insulin sensitivity and help sugar pass into your muscles easier This evaluate additionally noted that taking berberine alongside diabetes treatment lowered participant s blood sugar significantly more than simply medication alone If you have already got diabetes and are on medicine, focus on these dietary supplements together with your doctor Some ingredients can intrude with diabetes treatment since both are performing the same job. The plentiful, unutilized glucose is wastefully excreted within the urine Fluctuations in blood glucose ranges can lead to blurred imaginative and prescient In 2015, four7 of the whole burden of disease could have been prevented by reducing publicity to the modifiable risk factor high blood plasma glucose levels Crucial to diabetes management is common blood glucose monitoring This helps you to understand the connection between blood glucose, meals, exercise and insulin in your physique. Amount of glucose in blood measured regularly by patients with diabetes high blood sugar normal baby Tell your diabetes care staff should you ever have a severe hypo that caused you to have a seizure or fit Tell your diabetes care team should you ever have a extreme hypo that triggered you to lose consciousness It primarily affects people withdiabetes, particularly in the event that they take insulin. If your urine test reveals that ketones are current, call your doctor, who can give you further directions You might have to go to the emergency room to hunt remedy instantly The ADA says that if you have ketones current within the physique, you should not train In this case, exercise may cause your blood sugar levels to spike even blood sugar reading of 46 greater Blood sugar exams are used for prognosis Medterms Medical Dictionaryand management of diabetes.

Blood sugar count of 127, Research has shown that unsaturated fatty acids could play a part in blood sugar control via lowered insulin resistance In diabetes, the physique does not produce enough insulin to allow the cells to absorb sufficient sugar from the blood Or the physique might have enough insulin, however the cells do not respond to it In both instances, this results in there being an excessive amount of sugar in the blood, which, over time can result in critical well being points, corresponding to vision loss, heart disease, and kidney illness Much of the food you eat is broken down into sugar , which will get released into the bloodstream When blood sugar will increase, the pancreas, an organ responsible for digestion and blood sugar regulation, releases the hormone insulin. These check results can fairly aptly take a look at you for diabetes Below mentioned are the conventional blood sugar levels of fasting, before a meal, after food intake, and at bedtime in an age wise category Blood sugar or glucose is launched after consumption and breakdown of carbohydrates throughout food consumption It is the main sugar that is present in your bloodstream and its regulation is undertaken by pancreatic secretions Normal blood sugar levels chart for many adults ranges from eighty to 99 mg of sugar per deciliter before a meal and 80 to one hundred forty mg per deciliter after meals. Obesity is a leading danger issue for diabetesCalculate your BMIto see whether you re at a healthy weight If you re obese or overweight, start making small adjustments to your consuming habits and get extra bodily activity Even a small quantity of weight loss 7 , or about 14 pounds for a 200 pound How Is High Blood Sugar Diagnosedwoman can delay or even forestall type 2 diabetes Over time, this further glucose can lead to prediabetes or diabetes kaiser permanente blood sugar chart Diabetes puts you in danger for other serious and life threatening health issues, such asheart disease, stroke, blindness, and kidney injury Kidney damage from diabetes is identified blood sugar during pregnancy chart as diabetic nephropathy. Discover the remedy options for individuals with sort 2 diabetes, together with medicines and life style improvements Toe amputation is a typical process carried out by a wide variety of healthcare providers One of the most common indications for toe amputation is patients with a diabetic foot Toe amputation is normally carried out as a final resort when medical treatment fails, or the toe can t be salvaged Complications of toe amputation embody pain, swelling, bruising, blood clotting, and hematoma.

Lower blood sugar type 1, The latest sort of steady glucose monitor has an implanted sensor that can detect blood sugar ranges for as much as three months A transmitter worn on the physique sends blood sugar information wirelessly from the sensor to a smartphone app If you re taking insulin to handle type 2 diabetes, your health care supplier may recommend blood sugar drops after alcohol blood sugar testing several times a day, relying on the type and quantity of insulin you use Testing is often recommended before meals and at bedtime when you re taking multiple daily injections You might have to check solely earlier than breakfast and typically earlier than dinner or at bedtime if you use just an intermediate or a long acting insulin A good begin in how to preserve normal blood glucose is How are you able to reduce your blood sugar levels in this article. When blood sugar levels are excessive, it could point out that the physique does not have sufficient insulin or glucose reducing medicine Levels could also be elevated as a outcome of a big meal, if you have an sickness or infection, are careworn, or are inactive If you might be newly diagnosed, it could take some time to get you under this vary. Type 1 and kind 2 diabetes are the commonest forms of the illness, but there are additionally different kinds, similar to gestational diabetes, which happens throughout pregnancy, as well as different varieties From diet and train to treatment and care, there are tons of practical things you can do every day to make your life simpler Small changes in your diet and exercise could make a big distinction with prediabetes The most typical types of diabetes are type 1, sort 2, and gestational diabetes Over time, having too much glucose in your blood may cause well being issues. Taking too much medication taking too much insulin medication may cause a low blood sugar level These drugs are known as sulphonylureas or glinides An overproduction of insulin may cause the body to panic and improve its resistance to insulin, that means the blood sugar will not absorb properly Cells could develop a tolerance to insulin, making it necessary for the pancreas to produce and launch more insulin to lower your blood sugar ranges by the required quantity Eventually, the body can fail to produce sufficient insulin to maintain up with the sugar coming into the body Blood sugar supplements can be part of diabetes or prediabetes administration strategies.

Fasting blood sugar of 114, Inflammatory beta cell destruction in diabetes by professor Thomas Mandrup Poulsen During this module we Professor Mandrup Poulsen will guide you thru cytokines mediated destruction of the pancreatic beta cells moreover their potentiality as drugs targets Incretin biology is now applied in treating topics with diabetes and just lately approved by the FDA for weight reduction Don t hesitate to start out watching the videos as a end result of in this module you ll learn all concerning the incretin lead by Professor Jens Juul Holst The University of Copenhagen is the oldest University in Denmark based in 1479, and with over 38,000 college students and more than 9,000 employees The objective of the University is to conduct research and provide education to the best tutorial degree. 11Lai LL, Wan Yusoff WNI, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK Screening for non alcoholic fatty liver disease in sufferers with type 2 diabetes mellitus utilizing transient elastography Exercise and a nutritious diet are useful in both sort 1 and sort 2 diabetes mellitus A food plan low in saturated fats, refined carbohydrates, high fructose corn syrup, and high in fiber and monounsaturated fats needs to be encouraged Aerobic train for a length of ninety to 150 minutes per week is also helpful. The fasting glucose test is usually repeated on one other day to confirm the results With Type II diabetes, the situation might not turn into evident until the affected person presents for medical treatment for some other condition A patient might have heart disease, persistent infections of the gums and urinary tract, blurred imaginative and prescient, numbness in the ft and legs, or slow healing wounds Every cell in the human physique needs power in order to perform The body s major energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates Glucose from the digested meals circulates within the blood as a prepared energy supply for any cells that want it. Injections are given subcutaneously, that is, slightly below the skin, utilizing a small needle and syringe Injection websites could be wherever on the physique where there s looser skin, including the upper arm, stomach, or upper thigh Home blood glucose monitoring kits are available so sufferers with diabetes can monitor their own ranges A small needle or lancet is used to prick the finger and a drop of blood is collected and analyzed by a monitoring gadget Some patients may test their blood glucose levels several times throughout a day and use this info to adjust their doses of insulin.

Blood pressure blood sugar chart, Soon after diagnosis, you may additionally likely meet with a diabetes educator and a dietitian to get more information on managing your diabetes Regular exercise might help forestall prediabetes and sort 2 diabetes, and it could possibly help those that already have diabetes to maintain up higher blood sugar management A minimum of 30 minutes of reasonable train corresponding to brisk walking most days of the week is recommended Aim for at least a hundred and fifty minutes of moderate cardio exercise every week Following your diabetes therapy plan takes round the clock dedication Careful management of diabetes can cut back your risk of serious even life threatening complications. Although the disordered carbohydrate metabolism is usually mild, immediate detection and remedy are necessary to keep away from fetal and neonatal morbidity and mortality Women identified with gestational diabetes mellitus should have lifelong testing a minimum of each three years For all other patients, testing should start at age forty five years, and if outcomes are regular, patients ought to be examined at a minimal of every 3 years. Saturated fats ought to be limited to lower than 7 of total caloric intake, and trans fatty acids minimized A regular, consistent stage of day by day train is prescribed, and participation in a supervised train program is recommended All individuals with diabetes should check for ketones during instances of acute sickness or stress and when blood glucose levels are consistently elevated Persistent hyperglycemia in uncontrolled diabetes mellitus can cause a number of issues, each acute and chronic Diabetes mellitus is amongst the main causes of cardiovascular disease , blindness, kidney failure, and amputation of decrease limbs Acute problems embody hypoglycemia, diabetic ketoacidosis, hyperglycemic hyperosmolar state, and hyperglycaemic diabetic coma. This results in elevated urine glucose, which in turn results in extreme loss of fluid and electrolytes in the urine Lack of insulin also causes the lack to retailer fats and protein along with breakdown of present fats and protein stores This dysregulation, leads to the method of ketosis and the discharge of ketones into the blood Ketones flip the blood acidic, a situation referred to as diabetic ketoacidosis Symptoms of diabetic ketoacidosis embrace nausea, vomiting, and abdominal ache.

Diabetic high blood sugar ac1, Racial and ethnic minorities in the USA obtain lower quality health care Take time to take a blood sugar level of 150 look at your toes daily for any red patches If you may have sores, blisters, breaks within the pores and skin, infections, or build up of calluses, see a foot physician, known as a podiatrist In response to the COVID 19 pandemic, some pharmaceutical firms have launched initiatives to assist individuals with diabetes acquire the medications and The new recommendations apply to people with a excessive BMI and goal to establish silent cases of diabetes so that docs might prescribe fasting blood sugar of 88 immediate therapy. It is characterised by a sudden onset and happens more regularly in populations descended from Northern European countries than in these from Southern European countries, the Middle East, or Asia In the United States, approximately three individuals in 1,000 develop Type I diabetes This type also known as insulin dependent diabetes as a result of people who develop this type need to have every day injections of insulin At the identical time that the body is attempting to eliminate glucose from the blood, the cells are ravenous for glucose and sending indicators to the physique to eat more meals, thus making sufferers extraordinarily hungry To provide energy for the ravenous cells, the body additionally tries to transform fat and proteins to glucose. Since Type 1 is an immune system disease, immunotherapy holds promise as a method to use treatment to show off the elements of the immune system that trigger Type 1 illness Kidney harm that can result in kidney failure or the need for dialysis or transplant Like many other countries, the principal pre cursor to the development of sort 2 diabetes is obesity Standards of medical care in diabetes 2013Diabetes Care,36 Suppl 1 , S11 66 Learnhow to eat healthier and get extra bodily exercise. To account for the advanced sampling design of this study, we used SUDAAN software to acquire estimates of prevalence and the standard errors in accordance with the Taylor linearisation technique Estimates were weighted to mirror age, intercourse, and urban rural, distribution of provinces of the adults dwelling in China Weighting coefficients had been derived Diet Weight Managementfrom the 2010 Chinese population census knowledge, and the sampling scheme of our survey was to acquire a nationwide estimate Standard errors were calculated with acceptable statistical techniques with data from the advanced survey design Categorical information are introduced as percentages and 95 confidence intervals and have been analysed by a 2 take a look at or Fisher s precise test, as appropriate A binomial logit regression was used to look at the association of danger factors with the odds of complete diabetes and prediabetes.

Fasting blood sugar level 348, In this interview, we speak to Dr Gareth Hollands about his latest analysis that investigated using medical imaging to scale back well being risks and encourage habits change Since the molecular weight of glucose, C6H12O6, is about a hundred and eighty g mol, when calculated the entire quantity of glucose normally in circulating human blood is around threethree to 7g While selecting a Blood Sugar monitor CGM, different parameters have to be taken care of, which differ from individual to individual. This is the start of gaining a deeper understanding of how one can live a healthier life with all of the tools, well being suggestions, and food concepts you need Wherever you re at together with your diabetes, know that you have got choices and that you simply don t have to be held again Symptoms embrace excessive excretion of urine , thirst , constant starvation, weight reduction, vision modifications, and fatigue Type 1 diabetes previously known as insulin dependent, juvenile or childhood onset is characterized by poor insulin manufacturing and requires day by day administration of insulin In 2017 there have been 9 million folks with kind 1 diabetes the majority of them reside in high income nations. Michael Menna, DO, is board certified in emergency medication Verywell Health articles are reviewed fluctuating blood sugar icd 10 by board certified physicians and healthcare professionals Medical Reviewers affirm the content material is thorough and accurate, reflecting the latest evidence based analysis Content is reviewed before publication and upon substantial updates Nuts excessive in unsaturated fat embrace walnuts, almonds, pistachios, pecans, and peanuts. Can Diabetes Cause BlindnessIf you ve diabetes or are in danger for diabetes, make sure your train regimen just isn t inflicting health issues If you re feeling faint, have chest ache, really feel in want of breath, or notice blisters or pain in your toes, cease and name your physician In whole, you want to train 150 minutes or extra each week.

A1c to blood sugar chart, In addition, prediabetes is one other essential analysis that signifies an elevated threat of creating diabetes Diabetes mellitus is a gaggle of physiological dysfunctions characterised by hyperglycemia ensuing directly from insulin resistance, insufficient insulin secretion, or Definition Of Glucoseextreme glucagon secretion Type 1 diabetes is an autoimmune disorder leading to the destruction of pancreatic beta cells Type 2 diabetes , which is far more widespread, is primarily a problem of progressively impaired glucose regulation as a result of a mixture of dysfunctional pancreatic beta cells and insulin resistance The objective of this article is to review the basic science of kind 2 diabetes and its issues, and to discuss Prevention And Risk Factorsthe latest remedy pointers The overarching objective of these efforts is to determine the genetic underpinnings of this disease and translate that knowledge into medical and therapeutic interventions. Hyperosmolar high low blood sugar chart syndrome is caused by sky high blood sugar that turns blood thick and Pectin And Diabetessyrupy Your doctor also will monitor your blood sugar degree throughout labor If your blood sugar rises, your child may launch high ranges of insulin which may result in low blood sugar proper after start. More than 90 of the diabetics in the United States are Type II diabetics Sometimes referred to as age onset or adult onset diabetes, this type of diabetes happens most frequently in people who are chubby and who do not train It is also extra frequent in people of Native Medical Technologies GuidanceAmerican, Hispanic, and African American descent People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures additionally are extra doubtless to develop Type II diabetes than those who remain of their original nations. The kidneys concentrate on getting the extra glucose out of the low blood sugar of 62 bloodstream A high level of glucose means the kidneys might not be succesful of successfully adjust the patient s blood sugar ranges In turn, these organs will flip to flush out the excess glucose It s natural for blood sugar levels to go up and down, but when extreme levels occur incessantly, they will lead to varied issues that could jeopardize a person s quality of life If your blood sugar ranges continue to increase, signs can become worse and you might turn out to be confused and lethargic You also could turn into unconscious in case your blood sugar ranges are very excessive.

Signs of high blood sugar, A type of DM that has traits of each sorts 1 and 2 The patient could have episodes magnesium and blood sugar balance of diabetic ketoacidosis however marked insulin resistance and an overweight body type Difficulties In Diagnosing DiabetesIt is the most common complication of CF other than these circumstances that affect the lungs It is caused by destruction of islet cells as well as a decrease in sensitivity of the liver and muscles to the What Happens If My Blood Glucose Level Is Highactions of insulin The illness usually first turns into clinically obvious in younger adults. A diabetic diet doesn t have to be sophisticated and you don t have to give up all of your favorite meals The first step to creating smarter selections is to separate the myths from the details about consuming to forestall or control diabetes You can t change your beloved ones historical past, but it s still essential for you and your doctor to know if diabetes runs in your family Your danger for diabetes is larger if your mother, father, or sibling has diabetes Having some situations, such as polycystic ovary syndrome, can mean you are extra vulnerable to growing diabetes. Heart illness is easiest to treat when it s caught early It s very important to see your doctor on an everyday basis If your cholesterol is higher than the recommended level, your physician will discuss to you about way of life changes and medicine to help get your cholesterol under management. Wait for 30 60 minutes without consuming, and check once more to see in case your blood sugar has dropped to a level that is protected for train Strenuous activity and exercise encourage your physique to produce glucose to gasoline your muscle tissue The affected person should is 189 blood sugar bad begin by discussing the high blood sugar level with their physician The doctor will have the ability to perform a few tests to give them a better view of the patient s diabetes Normally, the kidneys assist to filter out extra blood glucose by rising the quantity of urine removed from the body.

Blood sugar home remedy ayurvedic, The only information she gave me was to alter his food regimen and get the degrees checked again in three months Is that a normal response or is there something else I must be doing I even have no best what the numbers said and I m just really confused Having a quantity of meals per day will help diabetics in maintaining optimal glucose blood ranges. Weight loss can appear overwhelming, however portion control and maintaining a healthy diet foods are an excellent place to start If the insulin can not do its job, the glucose channels can not open correctly Glucose builds up in the blood as a substitute of getting into cells for power High blood glucose levels trigger the health problems linked to diabetes, also recognized as issues Prediabetes is a condition the place blood sugar ranges are higher than normal, however are not but excessive enough to be recognized as sort 2 diabetes Although not everybody with prediabetes will develop sort 2 diabetes, many individuals will. A type of DM that has traits of each sorts 1 and 2 The patient could have episodes of diabetic ketoacidosis however fasting blood sugar of 105 marked insulin resistance and an overweight body type It is the most common complication of CF other than these circumstances that affect the lungs It is caused by destruction of islet cells as well as a decrease in sensitivity Why Is My Blood Glucose Level High How Does This Happenof the liver and muscles to the actions of insulin The illness usually first turns into clinically obvious in younger adults. A blood pattern for a random plasma glucose test may be taken at any time This doesn t require as much planning and is subsequently used within the diagnosis of kind 1 diabetes when How Well Is Your Type 2 Diabetes Treatment Plan Workingtime is of the essence Type 1 Diabetes Quiz What are the causes of kind 1 diabetes Take this quiz and problem your data of causes, symptoms, diagnosis and coverings for this common situation, blood pressure blood sugar charts previously generally identified as juvenile diabetes Mantra Care aims at providing inexpensive, accessible, and skilled well being care therapy to people across the globe Skipping or delaying meals lack of food, both skipping or delaying meals, could cause the insulin levels to drop too low after a while.

Blood sugar and body ache, It s additionally a good suggestion to avoid sitting for too lengthy aim to stand up blood sugar level at 470 and transfer when you ve been sitting for greater than 30 minutes Anyone older than age forty five is suggested to receive an preliminary blood sugar screening, after which, if the results are regular, to be screened every three years thereafter Your call is confidential, and there is no stress to commit to treatment until you re prepared. This is a blood take a look at that determines your common blood sugar degree for the past two to a few months It measures how much blood sugar is hooked up to hemoglobin, which is a protein in your pink blood cells that carries oxygen An A1C level of 65 or greater on two separate exams signifies that you have got diabetes Below 57 indicators that you simply don t have these well being points. However, they aren t going to be a whole cure for your situation Blood sugar supplements contain a wide range of elements While most supplements use berberine or cinnamon to reduce your blood sugar levels, this is not true for all supplements Some use a wide range of different components which have varying levels of effectiveness With a one hundred pc satisfaction assure, there isn t any reason to not give this complement a strive. You doubtless know the the cause why maintaining a wholesome weight is important to your longevity and high quality of life It hangs out Diabetes And Exercisein the bloodstream and ensures the macronutrients, notably carbs and fats, are metabolized correctly One study suggests that low chromium levels trigger glucose intolerance, incapability to make use of glucose for power and different metabolic issues If the Signos app sends you a glucose spike notification after consuming, take a brisk stroll or attempt one of our 10 minute workouts to deliver your blood sugar down extra quickly I am new at this diabetes and that i don t undestand diabetesearly within the morning my blood sugar someday in the 90 s could additionally be a hundred some morningsand through the day 122 never 200.

My blood sugar is 140, Clean the gadget and run quality control checks as directed Use a blood pattern size as directed within the user s information Touch and hold the sting of the test strip to the drop of blood Most of these gadgets still require finger stick checks to calibrate the machine. Bmj Open Diabetes Research CarePath To Improved HealthIf you are identified with diabetes, you will want toeat healthily, take common exerciseand carry out regular blood checks to make sure your blood glucose ranges stay balanced Type 2 diabetes mellitus accounts for round 90 of all circumstances of diabetes In T2DM, the response to insulin is diminished, and that is defined as insulin resistance During this state, insulin is ineffective and my blood sugar is 295 is initially countered Increases Blood Sugar Uptake Into Muscle Cellsby a rise in insulin manufacturing to hold up glucose homeostasis, however over time, insulin production decreases, resulting in T2DM. Diagnostic standards for diabetes associated disorders are introduced in desk 1 Treatment was defined because the proportion of individuals taking drugs for diabetes among those diagnosed with the disease Control was defined because the proportion of people with an HbA1c concentration of less than 70 among patients with diabetes who were taking medicine Conclusion The prevalence of diabetes has elevated slightly from 2007 to 2017 among adults residing in China The findings point out that diabetes is an important public well being problem in China. Yourblood sugarneeds to be in the right vary for you to be healthy At least some glucose is important on your muscle, liver, and another cells to use as fuel so they can operate Many folks s glucose will not ever fall below 60, even with prolonged fasting When you diet or fast, the liver retains your ranges regular by turning fats and muscle into sugar When you ve diabetes, your blood sugar levels could additionally be constantly high.

Blood sugar level is 105, Chronic microvascular issues are nephropathy, neuropathy, and retinopathy, whereas continual macrovascular issues are coronary artery disease , peripheral artery illness , and cerebrovascular disease It is estimated that yearly 1four to 47 of middle aged folks with diabetes have a CVD occasion The name of this situation is a bit deceptive, since diabetes insipidus has nothing to do with diabetes attributable to high blood sugar ranges, apart from the symptoms of thirst and passing massive volumes of urine Depending on the cause, diabetes insipidus can be handled with drugs, vasopressin replacement and a low salt food plan If a person with sort 1 diabetes skips a meal, exercises heavily or takes an excessive amount of insulin, their blood sugar levels will fall blood sugar 159 then 400 The signs embrace tremor, sweating, dizziness, hunger, headache and change in temper. Diabetes Tests For Diabetesalso can develop because of pancreatic disease, alcoholism, malnutrition, or different severe sicknesses that stress the physique A low socioeconomic status for most African Americans hinders access to health care As the Knowledge Portal is being mined and analyzed, the partnership is in search of to fill in knowledge gaps by executing particular analyses of the information Specifically, researchers are investigating targets of specific curiosity by sequencing DNA from select people Take benefit of actions developed by leaders within the subject of diabetes Listen to engaging talks on probably the most urgent issues in diabetes analysis, treatment and care. It should not be used instead of the recommendation of your physician or other certified healthcare supplier With alcohol and blood sugar, blood sugar can enhance, then decrease to a dangerous point This occurs as a outcome of alcohol is excessive in sugar, causing an initial spike. Cinnamon is the obvious instance of this and has essentially the most scientific analysis available to back it up However, other ingredients exist as nicely, corresponding to berberine Most supplements out there embrace certainly one of these components, however blood sugar level at 400 this isn t at all times necessarily true.

Morning blood sugar level chart, Valuable when a quick analysis of diabetes is required and in emergency settings As it s a blood test involving venipuncture, it can t be carried out in patients suffering from bleeding disordersIt can be utilized any time in the course of the day and no fasting is required The ease of doing it in home settings makes it a patient centric testExercising before an RBS test can lead to an inaccurate studying Moreover, directions need to follow diligently while performing a hone test The strategy of random blood sugar testing does not take greater than 5 10 minutes. Type 2 diabetes develops gradually over years as your body s insulin becomes much less effective at managing your blood glucose ranges As a end result, your pancreas produces increasingly insulin, and eventually the insulin producing cells put on out and turn out to be ineffective Type 2 diabetes is a combination of low insulin and ineffective insulin. As if the problem isn t extreme enough, irritation results in insulin resistance, Increased Blood Sugar Levels May Decrease Benefits Of Aerobic Exercisewhich only worsens hyperglycemia Risk elements that lead to cardiovascular problems are numerous, and excessive blood sugar is certainly one of them Although evidence on this topic is still relatively scarce, preliminary findings do show that hyperglycemia is a vital prognostic consider acute coronary heart failure Take breaks during a sedentary workday, add fasting blood sugar of 90 a walk around the block to your morning routine, or strive a model new type of exercise These actions bring great profit in both the brief and long term while helping cut back your total stress Including common energy training and cardio train will assist to blood sugar level of 33 lower glucose values, as well. Tuberculosis Skin Test The tuberculosis skin test is based on the fact that infection with M Tuberculosis produces a delayed type hypersensitivity skin response to certain elements of the bacterium The standard recommended tuberculin test is run by injecting 01mL of 5 TU PPD into the highest layers of skin of the forearm Reading the skin check means detecting a raised, thickened native area of skin reaction, referred sleepy with blood sugar 354 to as induration The area of induration around the website of injection is the response to tuberculin An estimated 72 million people within the United States have diabetes and don t even know it.

Blood sugar level before breakfast, A blood sugar stage vary between 140 and 199 mg What Is The Glucose Tolerance Test Like Do I Have To FastdL indicates prediabetes Keeping monitor of blood sugar levels fasting blood sugar of 107 is essential for people with diabetes Recording your blood glucose and sugar readings in a printable blood sugar chart is a convenient approach to determine patterns If you re chubby, shedding just 5 of your body weight could make a difference in your blood sugar control if you have Who Is Given Glucose Tolerance Test Gttprediabetes or sort 2 diabetes. It is dissolved in options that are given intravenously to extend a person s blood sugar levels The pancreas additionally produces a hormone called glucagon, which does the other of insulin, elevating blood sugar levels when wanted According to the Johns Hopkins University Sol Goldman Pancreatic Cancer Research Center, the two hormones work together to maintain glucose balanced Blood sugar supplements could interact with certain medicines If you re on a separate treatment on your blood sugar levels, a few of these dietary supplements could work together Having blood sugar that s too low is probably lethal. Strive for a food regimen of largely entire foods filled with plenty of vegetation and extra low glycemic foods than excessive If and when you do determine to eat higher glycemic carbs, pair them with protein and some fiber to help slow down your glucose response Sugar moving into your cells out of your blood from storage is definitely what gives you the vitality to maneuver Normal postprandial blood sugar stage is between 70 and 199 mg dl or three9 to 109 mmol l where 199 mg dl 109 mmol l is a borderline value and will already point out diabetes We randomly check my 4 year old daughters glucose and it has never been underneath 7 mmol L My household has a powerful history of diabetes and I had gestational diabetes along with her brother and sister, but not once I was pregnant with her. If your blood sugar studying is over four hundred mg dL, there is a likelihood that you have a false studying particularly should you aren t experiencing any signs For instance, if there were meals particles on your fingers otherwise you used outdated or improperly saved take a look at strips, you might have gotten an inaccurate studying The quantity of carbohydrates you are consuming isn t balanced with your insulin medicine dosage Without insulin, your body begins to interrupt down fat, triggering the manufacturing of chemical compounds referred to as ketones, according to the ADA Diabetes has changed every different condition to turn out to be the quickest rising way of life disease, globally Some people normal blood sugar level ada are more inclined Type 1 Diabetes High Blood Sugar Symptoms Hyperglycemia Symptomsto develop diabetes than others.

My blood sugar is 127, While the significance of constructing food choices that will keep blood sugar levels in Monthly Blood Sugar Logcheck can t be understated, it s also essential to note that finding what works is an individual alternative We share these concepts on meals that won t spike your blood sugar as a information and inspiration when everyday meals decisions are made Below are 10 foods that won t spike your blood sugar levels and some ideas for incorporating them into your meals. Insulin acts as the key that Send Article To Google Driveunlocks the cell wall door, which permits glucose to enter your body s cells Glucose supplies the fuel or energy tissues and organs must correctly perform People who use Low Carb Program have achieved weight loss, improved HbA1c, lowered medications and kind 2 diabetes remission Pan, A, Lucas, M, Sun, Q, van Dam, R, Franco, O, Manson, J, Hu, F. Although there are theories as to how these issues may be connected, none has but been proved This could also be because you tend to exercise much less, lose muscle mass and gain weight as you age But sort 2 diabetes is also rising among kids, adolescents and youthful adults. Diabetes can happen low blood sugar vs anxiety temporarily during pregnancy, and reviews counsel that it happens in 2 to 10 of all pregnancies Significant hormonal adjustments throughout being pregnant can result in diabetes high blood sugar 300 blood sugar elevation in genetically predisposed people Blood sugar elevation during being pregnant is identified as gestational diabetes Gestational diabetes often resolves once the child is born.

158 blood sugar diabetic blood sugar level 362 before breakfast, Strive for a diet of mostly complete meals crammed with loads of crops and extra low glycemic meals than high If and whenever you do decide to eat higher glycemic carbs, pair them with protein and some fiber to assist slow down your glucose response Sugar transferring into your cells out of your blood from storage is actually what provides you the vitality to maneuver Normal postprandial blood sugar degree is between 70 and 199 mg dl or 39 to 109 mmol l the place 199 mg dl 109 mmol l is a borderline value and will already point out diabetes We randomly take a look at my 4 year old daughters glucose and it has never been under 7 mmol L My household has a strong historical past of diabetes and I had gestational diabetes with her brother and sister, however not after I was pregnant along with her. Do you ve trouble losing weight, regardless of how hard you try to shed these undesirable pounds Find out extra concerning the weight loss plateau and what you are able to do about it From acupuncture to chiropractic treatments and homeopathy to holistic therapeutic, complementary and various drugs is rising in recognition Read on to be taught extra about Ayurveda, a therapeutic system that originated in India 1000 s of years in the past Did you know that menopause can have an effect on your metabolic well being, and vice versa Read on to know the connection between metabolic well being and menopause, and the method to manage metabolic health throughout your menopausal journey. Food and drinks that are excessive in carbohydrates are most impactful on blood sugar stage blood sugar levels recording chart What we eat provides us most of the vitamins our physique wants and sometimes, does not need That is to not say that food is a significant explanation for blood sugar level increasing or decreasing too dramatically When the body doesn t produce sufficient of the insulin hormone, blood sugar levels begin to extend. The number of occasions that you examine your blood sugar will rely upon the kind of diabetes that you ve got and the sort of medicine you re taking to treat your diabetes For example, individuals who take insulin may must check more typically than individuals who do not take insulin Talk together with your health care group about how often to verify your blood sugar If you sweat throughout work or train, that fluid needs to be replaced so you want to drink extra.

Fasting blood sugar at 160, Your doctor may also discuss with you about taking medication to delay or stop sort 2 diabetes Our bodies flip plenty of the meals we eat into sugar, known as glucose, which gives us vitality To use glucose as energy, our body needs insulin, a hormone that helps glucose get into our cells If you ve diabetes, your body may not make enough insulin, could not use insulin in the proper method, or both. This therapy also appears to assist with the secretion of the high blood sugar levels australia incretin hormone, which may contribute to improvements in glucose tolerance Oral hypoglycemic drugs may be effective if your situation is currently at a mild state, however a extra tailored approach may be needed in any other case Recognizing the symptoms of excessive blood sugar is important When blood glucose levels are excessive, a person must take applicable action This is the case with each sort 1 diabetes and type 2 diabetes. Resistance coaching, similar to energy workouts, has been proven to enhance blood sugar control For folks with diabetes, being aware of how meals will influence blood sugar is an on a daily basis feat Managing blood sugar has each short blood sugar level dangerous 100 term and long term advantages, together with lowering the risk of diabetes related complications When making meals choices while managing blood sugar ranges, you will want to choose ones that won t cause your blood sugar to increase rapidly and considerably Look for whether or not meals have advanced or easy carbohydrates and opt for advanced carbohydrates when potential Blood tests are extra widespread urine tests for measuring blood sugar. Diabetes mellitus is derived from the Submit A Response To This ArticleGreek word diabetes meaning siphon to pass through and the Latin word mellitus that means honeyed or sweet This is as a outcome of in diabetes excess sugar is present in blood as well as blood sugar 205 before bed the How Do You Treat Hypoglycemiaurine Among ladies with moderate baseline depressive signs, these receiving the lower dose had nominally decrease depression scores at follow up than those within the larger dose cohort Among women with extreme baseline depressive symptoms, the advance in follow up depression scores was the identical regardless of dose There was no distinction within the dosing impact of vitamin D3 supplementation for the therapy of depressive symptoms in ladies with T2D who present with important symptoms and low vitamin D Regardless of the dose, participants temper improved over time.

Tea for blood sugar balance, Binge ingesting extreme alcohol will eventually trigger a resistance to insulin Alcohol causes an increase in insulin The Bsd 5 2 Flexible Intermittent Fastingsecretion, which Intermittent Fasting For Improved Brain Healthmeans too much insulin is being launched in comparability to glucose being consumed and subsequently will go to waste Whilst the liver and muscular tissues produce some glucose, most comes from the foods we eat. Try mixing these fruits into oatmeal for a hearty breakfast or into Greek yogurt for a satisfying snack Emily is a health communication blood sugar level of 275 advisor, author, and editor at EVR Creative, specializing in public health research and well being promotion Getting 2 or extra of the values proven is indicative of gestational diabetes Any of the following are indicative of gestational diabetes If you had been not diabetic, you in all probability wouldn t know that your sugar was low as a end result of you wouldn t check and since you wouldn t symptoms, and you wouldn t act. If your blood sugar studying is over four hundred mg dL, there is a likelihood that you have a false studying particularly should you aren t experiencing any signs For instance, if there were meals particles on your fingers otherwise you used outdated or improperly saved take a look at strips, you might have gotten an inaccurate studying The quantity of carbohydrates you are consuming isn t balanced with your insulin medicine dosage Without insulin, your body begins to interrupt down fat, triggering the manufacturing of chemical compounds referred to as ketones, according to the ADA Diabetes has changed every different condition to turn out to be the quickest rising way of life disease, globally Some people are more inclined best rated blood sugar app to develop diabetes than others. Many meals have kinds of carbohydrates referred to as starches and sugars When you eat foods with most of these carbohydrates, your physique breaks them down into glucose, which is a kind of straightforward sugar, and releases the glucose into your bloodstream Aside from glucose produced by your liver, meals is the principle source of plasma glucose If you ve been told to look at your blood sugar levels, you could really feel a bit overwhelmed There is a lot of information to know, and it s onerous to keep track of all of the totally different numbers and what they mean Having a glucagon package handy is a lifesaver in case of low blood sugar levels.

Blood sugar level is 58, This will involve a small prick in your finger so blood sugar level of 272 receive a blood pattern Managing blood sugar ranges weekly diabetes blood sugar chart is easy to do at house if you understand the best measures to take Treatments are different for top and low blood sugar ranges Causes of low blood sugar ranges are very completely different and are as necessary to concentrate on, as they re in fact simpler to manage. The most appropriate choice is to consult your physician relating to this matter in order that they can guide you based on your health condition requirements Following are a few of the Common blood sugar level at 400 and important factors to consider whereas shopping for a CGM DisclaimerAll content on this website, together with dictionary, thesaurus, literature, geography, and different reference knowledge is for informational functions only. Several way of life factors can affect prediabetes, together with stress Here s everything you need to find out about the method it impacts the situation, and what you can do about it Find out what unhealthy weight reduction is and learn extra about its unwanted effects and what you can do to prevent them Check out a variety of the widespread and not so common reasons you re doubtless feeling drained Questions To Ask Your Doctorafter eating and browse our suggestions to assist prevent fatigue after meals. With Diabetes kind 1 body s cells that produce insulin are destroyed A person would want to use insulin injections to control their situation The next chart displays all possible blood sugar ranges along with a brief rationalization of what the indicators are A regular degree for a healthy person is somewhere between 72 mg dL 38 to 4 mmol L and 108 mg dL 5eight to 6 mmol L Blood sugar levels might fluctuate because of other reasons Check his fasting blood sugar within the morning to see if being extra active improves his blood sugar.

Kid blood sugar levels chart, So do people globally who reside in colder, northern climates Furthermore, sort 1 diabetes onset is more likely to happen in the winter blood sugar level of 85 months It has been observed to be triggered by viral infections A recent study found that individuals who saved a meals diary misplaced twice as a lot weight as those that didn t A written document helps you establish problem areas such as your afternoon snack or your morning latte where you re getting more energy than you realized It also increases your consciousness of Increased Ggt Concentrations In Patients With Dysglycemiawhat, why, and the way a lot you re consuming, which helps you cut back on senseless snacking. My sugar level in the early morning is 61 to six8 simply within the early morning During the day and after lunch in 2 hours never above 6 What does that mean If my fathers all examine Learn How Different Activities Affect Your Glucose Levels Now You Knowup values are regular only sugar value before lunch What Are The Different Types Of Diabetesis153 and after lunch is 307is it possible Learning the means to use natural means to keep both inside normal ranges My age is 52 and my sugar level is 229 so plz suggest me my sugar level normal or exceeded. Intramuscular injection may be simpler in uncommon cases of DKA or dehydration for the explanation that absorption fee is even larger The effectiveness, though, is normally a drawback in circumstances of hyperglycemia as a end result of the insulin could additionally be absorbed too readily and end in a drastic drop in blood sugar This signifies that apple juice has the potential to spike your blood sugar more than consuming the plain fruit would Non processed low sugar foods decrease the level of glucose going in the physique Where potential, try to obtain levels of between 4 and seven mmol L earlier than meals and underneath 85 mmol L after meals The goal stage for HbA1c is beneath forty eight mmol mol or 65 in the old units. With an increase in age, the prevalence of DM also increases About 25 of the population above sixty five years of age has diabetes You would possibly find that including a second drug doesn t convey your blood sugar underneath control.

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A recent study found no difference in invasive diseasefree survival between patients with HER2-negative breast cancer who took a full-strength aspirin daily and those who did not.

Although prior research has suggested that daily aspirin use may have antitumor effects, a recent study found no difference in invasive diseasefree survival between patients with HER2-negative breast cancer who took a full-strength aspirin daily and those who did not. Although inflammation may still play a key role in cancer, its also important to remember that aspirin may have different effects in other cancers, such as colon, or in a different setting, such as primary vs secondary prevention, study author Wendy Y. Chen, MD, MPH, a medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, explained during a presentation of the data.

The study (NCT02927249), which was presented at the February 2022 American Society of Clinical Oncology (ASCO) Plenary Series,1 included more than 3000 patients under 70 years with HER2-negative breast cancer who were randomly split into 2 groups: half received 300 mg of aspirin every day, and the other received a placebo (FIGURE 1 ). The main goal of the study was to compare invasive diseasefree survival. Aspirin users had a slightly worse survival than those patients who received placebo, Chen said. Findings showed that the aspirin users had a higher amount of disease events than the placebo group (111 compared with 90, respectively), although the difference was not statistically significant and the types of events were relatively balanced between the 2 groups, the investigators explained.

There was also a similar amount of severe AEs between the arms. The incidence of grade 3 or higher [AEs] was similar for aspirin vs placebo. Further, there were no grade 4 cardiac, hematologic, or gastrointestinal events in the aspirin group, Chen said.

However, another expert involved in the ASCO Plenary Series noted that the characteristics of the patient population may play a role in the outcomes that were observed. From these data, we can conclude that this high event rate among a postmenopausal, overweight population who had hormone receptor positive, high-risk disease was to be expected. And this is exactly the group that one would want to try to intervene upon, because wed expect this group to have high levels of inflammation, said Angela DeMichele, MD, MSCE, coleader of the Breast Cancer Research Program and director of the Breast Cancer Clinical Trials Unit at Penn Medicines Abramson Cancer Center in Philadelphia, Pennsylvania.

Additionally, DeMichele pointed out that about 44% of patients dropped out in the early stages of the trial, although the reasons why were not made known and could be interesting to consider. Study participants reported on whether they were adherent to taking their aspirin or placebo daily, and DeMichele noted, Self-report can be notorious for overestimates of adherence.

Despite potential reasons for the poorer aspirin outcomes, this was not the first study to show that aspirin use may not improve cancer-related outcomes.

In 2018, findings from the Aspirin in Reducing Events in Elderly trial (ASPREE; NCT01038583)1 were published, and they showed worse outcomes for patients who were over age 70 years and who took daily aspirin.

Aspirin users [in the ASPREE trial] were found to have an increased risk of deaththat was mainly driven by increased risk of cancer deaths. Of note, 19% had a prior history of cancer, Chen said.

The United States Preventive Services Task Force recommends daily aspirin for the prevention of colorectal cancer in individuals aged 50 to 59 years who have a 10-year cardiovascular risk of 10% or higher. However, the jury is out when it comes to the risks and benefi ts of aspirin use in older adults.

What we can take away from this study... is that at this time, aspirin should not be used simply to prevent breast cancer recurrence. For those situations in which there are other options, decisions about aspirin use for other indications should include an individualized risk/benefit discussion between physician and patient, DeMichele said.

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Daily Aspirin Fails to Improve Disease-Free Survival in Breast Cancer - Targeted Oncology

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Spring is the time for new beginnings, cleaning out your dusty musty basement, battling seasonal allergies, and, of course, discovering the latest TikTok trends.

With potentially permanent daylight savings on the table, that extra time spent luxuriating in the sunshine could mean more time to scroll (and scroll and scroll) through the latest health fads on the platform for better or for worse.

For a long time, menstrual cycles were considered taboo, and discussing them is still seen as inappropriate in many parts of the world. Organizations and online resources like Clue or Flo are seeking to normalize period-talk. Pixar has jumped on boardtoowith itslatest film, Turning Red, which depicts a 13-year-old's experience getting her first period. With a 95% rating on Rotten Tomatoes, it's clear that the public is willing to talk about periods.

Many people feel shame around discussing their periods, but this is something that social media has actually handled positively (for once).

Karan Raj, MD, a National Health Service surgeon and educator at Imperial College London, UK, uses his TikTok account to educate his followers and explain health concerns and issues using his platform. Raj stitched this video from someone else that was captioned, "When you're on your [period] and feel the stab in your booty."

In his video, Raj uses anatomical diagrams to explain exactly what's going on with this pain in the butt. The pain, which Raj explains is called proctalgia fugax, is caused by a type of hormone released during menstruation called prostaglandins. Prostaglandins tell the uterus to contract and shed its lining, but the uterus isn't the only part of the body receiving that message from the prostaglandins.

"The prostaglandins also cause contraction of the rectum, pelvic floor muscles, and muscles around the anal canal," Raj tells viewers. "These intense contractions can cause muscle spasms and anal cramps."

This video from Elliott Norris (@callmebelly) shows him preparing an unusual sleep aid. It's one of many videos of people trying the same trend, usually with the tag #lettucewater attached.

Like Elliott explains, the rumor is that boiling romaine lettuce and then drinking the water is a way to help one fall asleep faster, or sleep better at night. At the end of the video, Elliott even said that it worked for him. So where does this come from, and is it just a placebo?

Videos on TikTok recreating this trend cite a 2017 study titled, "Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep" (there's even a New York Times article about it). The star of the study is lactucarium, a milky white substance that's found in lettuce, usually visible if you squeeze it or break the stalks. The study suggests that lactucarium has "sedative-hypnotic" properties after lettuce extract was used in tandem with pentobarbital on mice, and it was found that the mice's sleep latency then decreased.

In an article from Parade discussing the trend, Rachel Salas, MD, MEd, weighs in. Salas is the assistant medical director at Johns Hopkins Center for Sleep and Wellness in Baltimore, so you could say she knows a thing or two about sleep. Her response to the mice study was that its limitations made the results not entirely reliable.

According to Salas, there was no control group, the extract the mice were given is much more concentrated than what's found in lettuce, and the mice were given a sedative that was going to make them sleepy anyway: "The mice were drugged to put the animals to sleep soon after they took the lettuce water."

So while Salas thinks it's good that people are open to talking about sleeping solutions, "lettuce tea" just doesn't have any evidence to back up what people claim it does.

Everyone knows how popular pimple popping, blackhead squeezing, and cyst squashing are on social media. Dermatologist Sandra Lee, better known as Dr Pimple Popper, used her YouTube platform of the same name which boasts over 7.42 million subscribers to cinch a reality television show on TLC. Viewers on TikTok are no different and love the satisfying (and often gross) relief of clearing out a nasty pimple or two.

In this stitched TikTok from emergency medicine physician Fayez Ajib, DO, aka @lifeofadoctor, Ajib reacts to an original video of someone popping a ganglion cyst with a textbook.

There are plenty of other videos on TikTok of people using books to smack ganglion cysts, which develop on the wrist. People have looked for remedies for ganglion cysts since the 1700s, at which point many strange options arose, as discussed in BBC Future. The one that still holds up, however, is smacking the cyst with a heavy book, like a Bible (hence the ganglion cyst's nickname, "Bible bump").

In his video, Ajib explains why smacking the cyst is a bad idea, even if it appears to temporarily resolve the issue.

"Not only have people broken the delicate bones in their wrist from getting hit," Ajib says, "but they actually have a high chance of recurrence. A doctor will actually remove the sac itself rather than just draining it from being hit."

The lessons we glean from TikTok remain the same: leave it up to the professionals.

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LAS VEGAS, April 01, 2022 (GLOBE NEWSWIRE) -- Healthy Extracts Inc. (OTCQB: HYEX), a leading innovator of clinically proven plant-based products for heart and brain health, reported results for the fourth quarter and full year ended December 31, 2021.

Q4 Financial Highlights

Full Year 2021 Financial Highlights

2021 Operational Highlights

Management Commentary

Our record performance in 2021 was driven by the strong ramp up in sales through both our wholesale distribution and direct-to-consumer channels, which includes subscription options, commented Duke Pitts, president of Healthy Extracts. These results also reflect our rapidly expanding customer base, with estimated customer lifetime value or CLV now exceeding $500. Our growth in CLV and subscriptions demonstrates that once customers discover our products, they come back for more.

The growth was also supported by the continued expansion of our portfolio of natural products for heart and brain health. This included the mid-year launch of UBN ACTIVATE, representing our entrance into the multi-billion dollar brain health supplements market. Then in the fourth quarter, we introduced UBN RELIEF, which is specially formulated to reduce the symptoms associated with migraine headaches. In fact, we recently reported clinical study results that demonstrate UBN RELIEF naturally alleviates migraine symptoms. We believe such peer-reviewed, published clinical research highly differentiates our products in the marketplace and assures our customers they will see results. Like with ACTIVATE, we believe RELIEF is like no other product available today, and we see these products creating a tremendous market opportunity that supports the continued ramp up in sales over the months to come.

One of the most exciting events of 2021 was the introduction of our exclusive line of Whitney Johns natural health and fitness formulations. Backed by Whitneys tremendous personal endorsement and brand marketing strength, we see this new line dramatically elevating our social engagement, strengthening our brand identity, and especially accelerating our revenue growth at minimal cost. We believe major brand influencers like Whitney will help our formulations reach millions of new consumers and enable us to secure prime shelf placements at major retailers nationwide.

While we were able to grow our direct sales business at a fast pace in 2021, we saw reduced sales in our wholesale business due to the COVID-19 pandemic. This turned around at the beginning of this year with a large follow-on purchase order for our exclusive Citrus Bergamot SuperFruit from XYMOGEN, a major distributor to healthcare practitioners of clinical-grade nutraceuticals. This and similar follow-on wholesale orders demonstrates the growth of our B2B distribution segment is back on track for this year.

To support the further growth across all of our segments, we recently appointed Scott Landers as EVP of sales and marketing. He brings to us more than 20 years of exceptional executive experience and accomplishment, including the successful launch of new products and services for KPMG, IBM, DISH Network, CenturyLink, NEC and other industry leaders.

To add further fuel to our growth in 2022, we have in the works a number of new clinically-backed formulations for additional health offerings like hormone support and gut health. Combined with our expanding sales channels, including Amazon, where we have become a very active seller, we believe we are well on course for at least a doubling of our organic revenue growth in 2022. This excludes the potential positive impact of our active M&A program.

We also expect to realize certain advantages from our supply chain management and significant post-acquisition overhead reductions we implemented last year, which we see supporting a transition to cash flow positive in the second half of this year.

Q4 Financial Summary

Net revenue in the fourth quarter of 2021 increased 77% to $672,000 from $380,000 in the previous quarter and up 394% compared to $136,000 in the same year-ago quarter.

Gross profit totaled $48,000 or 7.2% of net revenue as compared to negative $1.3 million in the same year-ago quarter. The increase in gross profit was primarily due to the increased focus on Amazon marketplace along with a reduction in written off inventory.

Operating expenses increased 85% to $712,000 compared to $386,000 in the same year-ago quarter.

Net income totaled $535,000 or $0.00 per basic and diluted share compared to a net loss of $1.6 million or ($0.01) per basic and diluted share in the same year-ago period.

Cash totaled $222,000 as of December 31, 2021, as compared to $59,000 on December 31, 2020. In the first quarter of 2022, the company eliminated virtually all of its convertible debt.

Full Year 2021 Financial Summary

Net revenue in the full year 2021 increased 15% to a record $1.5 million from $1.3 million in 2020. The increase was due primarily to increased sales from heart health products and the focus on Amazon marketplace.

Gross profit was $695,000 or 47.4% of net revenue, compared to negative $578,000 in 2020.

Operating expenses decreased $471,000 to $2.6 million from $3.1 million in 2020. The decrease in operating expenses is primarily attributable to an impairment of assets of $1.6 million in 2020, partially offset by an increase in general and administrative expenses in 2021.

Net loss totaled $2.0 million or $(0.01) per basic and diluted share, as compared to a loss of $2.6 million or $(0.01) per basic and diluted share in 2020.

About Healthy Extracts Live Life Young AgainHealthy Extracts Inc. is a platform for developing or acquiring science-forward, clinically proven, plant-based proprietary products in select high-growth categories within the multibillion-dollar nutraceuticals market.

The companys subsidiaries, BergametNA and Ultimate Brain Nutrients (UBN), offer nutraceutical natural heart and brain health supplements. This includes the only heart health supplement containing Citrus Bergamot SuperFruit. This superfruit is known to have the highest quality and concentration of polyphenols and flavonoids, and with healthy heart benefits backed by more than 17 clinical studies.UBN KETONOMICS proprietary formulations have been clinically shown to improve brain health, including memory, cognition, focus and neuro-energy. UBN is pursuing intellectual property license opportunities for monetizing its IP portfolio of multiple issued and pending patents. For more information visit: healthyextractsinc.com, bergametna.com or tryubn.com. Forward-Looking Statements and Safe Harbor NoticeAll statements other than statements of historical facts included in this press release are "forward-looking statements" (as defined in the Private Securities Litigation Reform Act of 1995). Such forward-looking statements include our expectations and those statements that use forward-looking words such as "projected," "expect," "possibility" and "anticipate." The achievement or success of the matters covered by such forward-looking statements involve significant risks, uncertainties and assumptions. Actual results could differ materially from current projections or implied results. Investors should read the risk factors set forth in the Company's Annual Report on Form 10-K filed with the SEC on February 19, 2021, and future periodic reports filed with the SEC. All of the Company's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements.

The Company cautions that statements and assumptions made in this news release constitute forward-looking statements and make no guarantee of future performance. Forward-looking statements are based on estimates and opinions of management at the time statements are made. The information set forth herein speaks only as of the date hereof. The Company and its management undertake no obligation to revise these statements following the date of this news release.

Food and Drug Administration DisclosureThe product and formulation featured in this release is not for use by or sale to persons under the age of 12. This product should be used only as directed on the label. Consult with a physician before use if you have a serious medical condition or use prescription medications. A doctors advice should be sought before using this and any supplemental dietary product. These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease. BergametNA, Ultimate Brain Nutrients, UBN, Citrus Bergamot SuperFruit and F4T are registered trademarks of Healthy Extracts Inc.

Healthy Extracts Company ContactDuke Pitts, PresidentHealthy Extracts Inc.Tel (720) 463-1004Email contact

Investor Contact:Ronald Both or Justin LumleyCMA Tel (949) 432-7566Email contact

Media Contact:Tim RandallCMATel (949) 432-7572

HEALTHY EXTRACTS, INC.CONSOLIDATED STATEMENT OF OPERATIONS

HEALTHY EXTRACTS, INC.CONSOLIDATED BALANCE SHEETS(Audited)

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Healthy Extracts Reports Fourth Quarter and Full Year 2021 Results - GlobeNewswire

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Blood sugar levels normal blood sugar for adolescent covid 19, There is no perfect formula for exercising to reduce your blood sugar. Maintaining healthy blood sugar levels is important to your overall health, so remember to check your blood sugar frequently. Keeping your blood sugar levels under control can help reduce this risk. It features a unique combination of ingredients like licorice, cayenne, and juniper berry.

Blood sugar spikes to avoid, The incidence of gestational diabetes increased with age, peaking at 31 for females aged 45 49. Depending on your age and any other health conditions, your doctor may advise you to keep your blood sugar level in a range that they consider will be safe and healthy for you. Although lacking Gestational Diabetes Treatmentsa high quality national cohort to estimate the incidence of diabetes, our findings could add value to the assessment of diabetes epidemics in mainland China. Find out what happens when your Can Intermittent Fasting Impact Your Blood Pressurblood sugar levels are too high, as well as potential outcomes when they rise above 400 milligrams per who blood sugar range chart deciliter mg dL.

Low blood sugar muscle building, Anything under elevated blood sugar in child 70mg dl is known as low blood sugar or hypoglycemia. Whether you ve eaten recently or not, a blood sugar level higher than 200 mg dL may indicate you could have diabetes. Blood sugar must be carefully regulated to ensure that the body functions properly. As mentioned above, aggressive control of blood sugar levels can prevent or delay the onset of complications, and many people with diabetes lead long and full lives.

Blood improving blood sugar control before sugar average of 3050, The health information contained herein is provided for general education purposes only. Currently, information and communication technologies are considered as an integral part of clinical trials. Note the number of grams of sugar per serving as well as the total number of servings. Studies have also found that later or irregular sleeping schedules are correlated with higher blood sugar, even in non diabetic people.

Blood sugar levels in children, Additionally, it increases insulin level in the blood in a holistic way. Using Advisor Pro allows physicians and nurses to provide true patient centered care and everyone can receive the same top level of treatment wherever they are and whoever their caregiver is. Drinking moderately isn t likely to lead to type 2 diabetes, but excessive drinking over time fasting blood sugar of 135 can prediabetes blood sugar levels canada be a trigger for its development. For a new patient with diabetes, you should check blood sugar levels regularly.

Blood sugar levels of 600, It is caused by an absolute or relative deficiency of insulin and What Is The Treatment For Gestational Diabetes Mellitusis characterized, in more severe cases, by chronic hyperglycemia, glycosuria, water and electrolyte loss, ketoacidosis, and coma. Insulin deficiency diabetes This is when the dog s body isn t producing enough insulin. Over time, high blood glucose levels stiff neck blood sugar change can damage the body new blood sugar levels chart s organs. The pancreas tries to create more insulin for the glucose to use, but the body does not respond to it properly, called insulin resistance.

Acylovir raise blood sugar a1c, With blood sugar levels mmol chart this in place, researchers are now honing in on the final step of the process turning pancreatic endocrine cells into beta blood sugar level of 109 cells. So, if you have diabetes, drink alcohol and take insulin as a medicine, you may experience hypoglycemia. This occurs when cells starved for glucose begin to break down fats for energy, a process my blood sugar is 145 that creates chemicals called ketones, which make the blood more acidic. Normal blood sugar level for any individual before meals is between 80 to130 mg dL.

Gestational diabetes blood sugar chart, The questionnaire was designed to assess self care behaviours which can be related to the measure of HbA1c, so that the data are suitable for mediational analyses. I very much enjoy T Tapp though I am new to it and was excited to see another naturally minded person talking about it. Check out our dedicated platform and share your diabetes story. buy blood sugar the book This helps you to understand the relationship between blood glucose, food, exercise and insulin in your body.

Blood sugar support metabolism blend, These are not oral forms of insulin they are 145 average blood sugar a1c sulfonylureas, chemically related blood sugar reading at 30 to the sulfonamide antibiotics. Keep in mind blood sugar level age 80 that you cannot have the same reading throughout the day. Prediabetes is a condition where blood sugar levels are higher than normal, but are not yet high enough to be diagnosed as type 2 diabetes. The urine is convert blood sugar to ac1 checked for microalbumin or overt protein losses, an early indication of nephropathy.

Blood sugar vs a1c chart, Since T1DM is a disease primarily due to the absence of insulin, insulin administration through daily injections, or an insulin pump, is the mainstay of treatment. Even seemingly small problems can lead to organ damage and sepsis and can prove fatal. The French DESIR study of people diagnosed with prediabetes confirmed what the studies cited above have found. Blood Glucose Monitoring In Home CareIn her free time, she monitors her wildly fluctuating heartbeat whilst watching Arsenal FC.

Importance of blood sugar balance, GD greatly increases the risk of developing diabetes in your next pregnancy and in the future when you are no longer pregnant. Experts are still learning about all the factors that On The Video Below Dr Marlene Merritt Share A Few Tips To Fix Blood Sugarcan contribute to high blood glucose. You will need to track your blood sugar and do things to keep it under control. If you re on some sort of other diabetic medication, you should work closely with your doctor to use the correct dosages.

How What Is Low Blood Glucoseto reduce blood sugar level immediately, A random blood sugar test is the testing of the blood sugar level at any time or random time of the day. Type II diabetics should use Blood Sugar Blaster, according to Dr Carter, to assist control diabetes. Testing is usually recommended before meals and at bedtime if you Who Gets Diabetesre taking multiple daily injections. Before sleep values should be between 110 mg dL 61 mmol L and 200 mg dL 111 mmol L.

High blood sugar over 350, The small amount of refined honey in the recipe satisfies your sugar cravings but won t spike your blood sugar, because it is balanced with fats. The prevalence of total diabetes was higher in men than in women. When there isn t enough glucose stored to maintain normal blood sugar levels, the body can also produce its own glucose from noncarbohydrate sources. Oral diabetes medications are sometimes taken in combination with insulin.

Good blood sugar level a1c, After 80 90 of the beta cells are destroyed, hyperglycemia develops and diabetes may be diagnosed. The operation results in significant weight loss, remission of type 2 diabetes in nearly 80 percent of patients, and improvement of diabetes in an additional 15 percent. Diabetes mellitus is a group of physiological dysfunctions characterized by hyperglycemia resulting directly from insulin resistance, inadequate insulin secretion, or excessive glucagon secretion. 3 hour blood sugar 188 It s important to manage diabetes because, over time, it can cause serious health problems like heart disease, stroke, kidney disease, eye problems, and nerve is 83 blood sugar bad damage that may lead to amputation.

Elderly blood sugar levels chart, Foot care patient self care by maintaining foot hygiene wearing appropriate footwear seeking professional care for ulcer management and regular examination of feet by health professionals. Some options may include supplements such as Garcinia Cambogia, which has shown results for increasing insulin sensitivity. Diabetes is diagnosed based on a fasting blood sugar at 102 fasting blood glucose level of 126 milligrams blood sugar lelal 8 5 per deciliter mg dL or higher. One of the challenges of managing diabetes is maintaining consistent blood sugar levels.

157 blood sugar to a1c, These infections may ultimately require toe, foot or leg amputation. Insulin remains fasting blood sugar level 97 the mainstay of treatment for patients with type 1 diabetes. The glucose in your blood serves as a primary source of energy for all the cells in your body. If you suspect you may have high blood glucose already, Zanini says that any changes in your health count as cause to see your doctor.

Blood sugar testing iphone app, Further, iPS cells non fasting blood sugar 120 are genetically identical to the original patient, so all of Normal Blood Sugar Levels For Adults With Diabetesthe mutations that predisposed an individual Alcohol Intake And Diabetesto T1D are present. More than one in three adults in High Blood Sugar, Diabetes, And Your Bodythe United States has prediabetes, and the majority of them don t know it, according to the Centers for Disease Control and Prevention. A plant based blood sugar droped to 20 diet leads to twice as much weight loss as a traditional diabetes diet. When the blood glucose elevates , insulin is released from the pancreas.

Blood sugar high after cheese, Your doctor will also check your kidney function, including estimated glomerular filtration rate e GFR , with a blood test. If you re younger, have had diabetes for a shorter amount of time or are not taking any medicine for your diabetes, your glucose goals might be Blood Sugar Levels Chartmorning blood sugar of 173 a little tighter, or lower. blood sugar dropped to 35 Eye damage this is termed diabetic retinopathy and occurs due to damage of the fine blood vessels of the retina in the eye due to long term exposure to high blood sugar. If you choose animal products for protein, make sure you re choosing high quality animal protein sources that are unprocessed and low in saturated fat.

After eating blood sugar Blood Sugar Levels Chart Low, Normal, And High Ranges165, Finally, diabetes can make it harder to get pregnant and raises your risk of pregnancy complications. It means that in most cases, data were collected using paper based records and in a small number of studies funded by pharmaceutical and biotechnology companies, this process was completed electronically. African Sexual Function And DiabetesAmericans have a high rate of diabetic complications, because of poor glycaemic control and racial disparities in health care in the USA. Don t be embarrassed to reach out to your doctor for help in any of these areas.

Blood sugar levels, But these readings may not be as accurate as readings from high blood sugar levels chart the fingertips, especially after a meal or during exercise, when blood sugar levels change more frequently. In the United States, approximately three people in 1,000 develop Type I diabetes. For pregnant women who have pre existing diabetes or develop diabetes Blood Sugar Rising Preview With Spanish Subtitlesduring pregnancy, ADA guidelines are generally lower. As a result, they stress the body s insulin making machinery less, and so may help prevent type 2 diabetes.

Take blood sugar New Study Sheds Light On The Role Of The Brain When Completing Mathematical Sumspecs card, Anyone taking medication should consult Testing Blood Glucosetheir doctor before incorporating StrictionD in to your daily life. You are more likely to develop type 2 diabetes if you are 45 years old or older, have a family history of diabetes, or are overweight. Also, it is better to have an A1C test because it tests your blood sugar over a longer course. A registered dietitian can help you create a meal plan that fits your health goals, food preferences and lifestyle.

T1d blood sugar at 300, Ketogenic diets may be an ideal diet for people with type 1 diabetes as well. A1C testing also avoids the problem of day to day variability of glucose values as it reflects the average plasma glucose over the previous 2 to 3 months. It is also important to remember that these devices can be used intermittently with fingerstick measurements. Being blood sugar reading of 136 overweight is strongly linked to Normal Hba1c For Person Without Diabetesthe development of type 2 diabetes, but not everyone with type 2 is overweight.

Blood sugar icd 10 code, deibetes blood sugar conversion charg Despite low blood sugar of 40 their former classifications as juvenile or adult, either type of diabetes can occur at any age. Without insulin, there is no key So, the sugar stays in the blood and builds up. The test looks at the percentage of glycated hemoglobin in your red blood blood sugar level is 265 cells. Sharing your frustrations and your triumphs with people who understand what you re going through can be very helpful.

Normal blood sugar level australia, Insulin It is a hormone secreted by the beta cells of your pancreas and is important for the metabolism With Excellent Accuracy2,3, Manage Your Diabetes Betterof glucose that is derived from foods that you eat. Oatmeal and barley are especially good whole Molar Mass Of Glucosegrain options for most people with blood sugar three month average high blood sugar. Early on the road to developing high blood sugar and getting High Blood Pressurediagnosed with type 2 diabetes, an insulin resistant person usually has too much insulin in the blood. It is only by measuring both incidence and prevalence that a better understanding of the extent of diabetes can be achieved.

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Introduction

Prostate cancer (PCa) is the most common malignancy and the second most common cause of cancer-related deaths affecting men in developed countries.1 PCa incidence has risen over the recent decades. Factors responsible for this rise include aging population, obesity due to western dietary habits, and increasing use of prostate-specific antigen (PSA) testing.2 Prostate cells, normal or cancerous, are dependent upon androgens for survival and growth. Consequently, androgen deprivation therapy (ADT) (also called hormone therapy by some clinicians) is still the mainstay of PCa treatment. Surgical (bilateral orchiectomy) or chemical (pharmaceutical) interventions resulting in the reduction of serum testosterone or blockade of the androgen receptor, are referred to as ADT. Antiandrogens alone like flutamide, enzalutamide, and apalutamide (the modern derivatives) are not considered ADT but are used in combination with surgical or chemical castration. ADT was initially achieved by orchiectomy as the testes are the principal source of circulating androgens (producing nearly 95% of total); the remaining 5% are produced by the adrenal glands. Luteinizing hormone-releasing hormone (LHRH) agonists are the most widely used contemporary ADT modality usually offered when patients are diagnosed either with recurrent cancer after first-line treatment (such as radical prostatectomy or radiation treatment) for local disease or with advanced (incurable) disease at presentation.3 This review provides for the practicing clinician and medical provider not only a systemic overview on the evolution and the oncologic dynamics in patients undergoing traditional ADT, but also the clinical aspects and indications for the emerging new pharmaceutical ADT modalities.

The HypothalamicPituitaryGonadal axis functions as a single system or entity due to direct interaction and feedback (Figure 1). Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH), is secreted from the hypothalamus by GnRH-expressing neurons and stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the anterior portion of the pituitary gland which then stimulates the gonads for producing estrogen and testosterone. The therapeutic principle of Androgen Deprivation Therapy (ADT) in prostate cancer (PCa) has been established and not changed much over the last 80 years since Charles B. Huggins demonstrated the testosterone dependency of PCa.4 Huggins and Hodges first reported the dramatic clinical effects of suppressing serum testosterone levels (Figure 2) in men with advanced prostate cancer in 1941.5 Following bilateral orchiectomy of eight subjects with prostate cancer, serum acid phosphate levels decreased indicating decreased activity of the cancer. Five subjects with prostate cancer injected with stilbestrol also showed decreased serum levels of acid phosphatase while three subjects injected with testosterone propionate had an increase in serum acid phosphatase levels. For this pioneering work in treatment of advanced and metastatic prostate cancer Huggins was awarded the Nobel Prize for Medicine in 1966.

Figure 1 The hypothalamus-pituitary-testicular axis.

Figure 2 Molecule structure of testosterone.

In 1938 diethylstilbestrol (DES, Figure 3) also known as stilbestrol or stilboestrol, was discovered and then introduced for medical use in 1939.6 DES is an estrogen and it suppresses luteinizing hormone-releasing hormone (LHRH) (Figure 4) production at the level of the hypothalamus. In the past, it was widely used for a variety of indications, including treatment of metastatic prostate cancer (chemical castration) and hormonal support during pregnancy for women with recurrent miscarriage. DES has excellent bioavailability and is well tolerated when taken by mouth.7

Figure 3 Molecule structure of diethylstilbestrol (DES).

Figure 4 Molecule structure of luteinizing hormone-releasing hormone (LHRH).

In 1959 the Veterans Administrative Cooperative Urological Research Group (VACURG) was established which further evolved ADT in the treatment of advanced prostate cancer. The VACURG used prospective randomized clinical trials for investigating the role of monotherapy of estrogen versus combined therapy of orchiectomy plus estrogen in advanced prostate cancer patients.8 The major conclusions were: 1.) A daily dose of 3 mg DES was considered the optimal dose and became the accepted regimen for pharmacologic castration. 2.) A lower DES dose (1 mg) was associated with reduced cardiovascular toxicity but did not reliably achieve castrate levels of testosterone. 3.) No survival advantage of early versus delayed initiation of hormonal therapy in advanced disease. Up to the 1970s DES as hormonal therapy was widely accepted as the treatment for advanced and metastatic prostate cancer. However, its main adverse effects were increased risks of blood clots and cardiovascular events.9

Furthermore, reports in the 1970s revealed that DES caused clear-cell carcinoma of the vagina, a rare tumor in girls and women who had been exposed to this medication in utero. Due to these discoveries and the significant cardiovascular side effects DES essentially disappeared from the pharmaceutical market.10

Both surgical and pharmacologic castration resulted in dramatic palliation of painful bony metastatic lesions, and improved quality of life in prostate cancer patients. In 1971 Schally and associates purified the decapeptide gonadotropin-releasing hormone (LHRH).9 Studies showed that constant exposure to LHRH ultimately suppressed testosterone serum levels by desensitizing pituitary cells through downregulation of the LHRH receptors.11 Modification of the sixth amino acid position of the LHRH molecule was significantly more potent.12 The monthly depot of leuprolide (Figure 5) was the first LHRH agonist granted FDA approval for advanced prostate cancer. In a randomized clinical trial, leuprolide was equivalent to 3 mg of DES in reducing serum testosterone to castrate levels, but with much lower cardiovascular toxicity.13 Ultimately in the 1980s Leuprolide replaced DES and orchiectomy as the preferred approach to androgen deprivation.

Figure 5 Molecule structure of leuprolide.

Over the following decades substitutions at the sixth amino acid position yielded a variety of more LHRH agonists (goserelin, triptorelin, and histrelin), which then also became commercially available in the United States. These LHRH agonists are differentiated by their route of administration (intramuscular injection vs subcutaneous injection vs subcutaneous implant) and frequency of administration (112 months). All these LHRH agonists have similar therapeutic effectiveness in lowering serum testosterone to castrate levels, but also have a similar profile of adverse effects. One study directly compared different LHRH agonists.14 Overall improved survival with triptorelin compared with leuprolide, 97% vs 90.5% at 9 months (P = 0.033). Although not statistically significant, triptorelin seemed to better maintain castrate levels of testosterone over a 9-month interval.

The luteinizing hormone-releasing hormone (LHRH) agonists offered true medical castration but showed clinical issues due to testosterone surge and tumor flare when first administered. The flare phenomenon is attributed to the surge of serum testosterone levels caused by the initial stimulation of LHRH receptors. The introduction of antiandrogens was considered to ease this clinical issue by inhibiting the stimulation effect at the level of the androgen receptor.15 Despite initial expectations, the combined medical therapy of antiandrogens and LHRH agonists did not improve cancer-specific survival. The costs, inconvenience of therapy, added toxicity, and the introduction of the saturation model were considered the main reasons why the combined treatment never became standard of care. A 2017 literature review concluded that there is no evidence of testosterone flare following initiation of an LHRH agonist.16 It was proposed that this is due to the limited ability of androgens to stimulate prostate growthalso known as the saturation model.16 The saturation model, introduced in 2009, showed tumor growth increased when exposed to low levels of androgen, however after reaching a certain threshold, androgens no longer affected tumor growth. In the current literature there is still an ongoing and controversial debate on the validity of this saturation model.17

The introduction of Gonadotropin-releasing hormone (GnRH) antagonists offered a solution for the above mentioned flare phenomenon. This new drug class proved a rapid reduction of serum testosterone to castrate level without the initial testosterone surge and tumor flare. However, the long-term clinical benefits are still debated. A recent meta-analysis study comparing GnRH agonists and antagonists in patients with metastatic prostate cancer, showed that GnRH antagonist use was associated with a lower risk for all-cause mortality and cardiovascular events, respectively. However, this study did not find any significant differences between groups in PSA progression, musculoskeletal events, fractures or serious adverse events such as hepatic failure.18

In summary, ADT has come a long way since its introducing by Huggins for treatment of advanced and metastatic prostate cancer 80 years ago. Whereas surgical ADT via orchiectomy has become obsolete, medical ADT plays still a main role in the repertoire of treatment options for patients with recurrent, progressive and advanced prostate cancer.

LHRH/GnRH agonists, such as leuprorelin/leuprolide, goserelin, and triptorelin, are by far the most commonly utilized forms of ADT in clinical practice in the treatment of PCa, targeting the LHRH/GnRH receptor in the anterior pituitary gland and administered as an intramuscular or subcutaneous injection. They stimulate the receptor, creating a temporary surge in LH and testosterone levels followed by downregulation of the receptor over the next 23 weeks with a subsequent reduction in LH and suppression of testosterone production by the testes.19 They achieve serum testosterone levels below castration (<50 ng/dL) within 46 weeks with a subsequent reduction in the PSA level.20 The most common adverse effects (AE) associated with treatment are hot flashes, fatigue, sexual/erectile dysfunction, testicular atrophy, cognitive decline, increased risk of diabetes and cardiovascular events, and decreased bone mineral density associated with joint disorders and/or osteoporosis that needs to be monitored periodically with bone density scanning.21

LHRH/GnRH antagonists, such as degarelix, abarelix, and relugolix, are newer agents that competitively bind to the LHRH/GnRH receptor, inhibiting downstream LH signaling and suppressing testosterone secretion from the testes. LHRH/GnRH antagonists are not associated with an initial surge of serum testosterone, and castration levels are achieved within 23 days, so they are a good therapeutic option for the initiation of ADT in a newly diagnosed PCa patient.22 While degarelix is only available as a 1-month subcutaneous dose with a higher risk of adverse skin reactions, relugolix is a daily oral agent, although a food effect can reduce exposure by 50%.23 The side effect profile of LHRH/GnRH antagonists is similar to that of LHRH/GnRH agonists although since degarelix reduces FSH more than the LHRH/GnRH agonists (90 vs 50%), these lower levels of FSH may be cardioprotective, especially in men with preexisting cardiovascular disease, and may produce less muscle mass loss.24

Antiandrogens, such as bicalutamide, flutamide, and nilutamide, are some of the oldest drugs that inhibit binding of dihydrotestosterone (DHT) to the androgen receptor (AR).25 Since they do not reduce serum levels of testosterone, they can be considered as monotherapy in nonmetastatic patients who want to preserve libido and avoid the metabolic and sexual side effects of traditional ADT.26 They are, however, less effective than surgical castration or LHRH agonists/antagonists in metastatic prostate cancer (PCa) and are typically utilized concurrently with these agents for dual androgen blockade, especially during initiation of treatment with LHRH agonists to prevent clinical manifestations of testosterone surge within the first month.27 Table 1 summarizes single use versus combined use of ADT drugs and antiandrogens.

Table 1 List of ADT Drugs and Antiandrogens That Can Be Used in Combination

After long-term testosterone suppression, reactivation of AR pathways in some cell populations occur from multiple mechanisms including production of androgens by the adrenal glands and PCa cells themselves, androgen-independent activation of the AR, and AR gene amplification or overexpression.28 In this state, elimination of testosterone production from the testes is no longer sufficient to fully suppress PCa tumor cell growth, and another generation of antiandrogens is available for further testosterone suppression typically below 20 ng/dL.29

Abiraterone (in combination with traditional ADT) reduces androgen production from all sources including the testes, adrenal glands, and PCa cells through selective and irreversible inhibition of the enzyme 17-hydroxylase/C17,20-lyase (CYP17), which can suppress testosterone levels even lower than with traditional LHRH/GnRH agonists alone. In the LATITUDE and STAMPEDE study, the addition of abiraterone acetate and prednisone to standard ADT significantly increased overall survival (OS) and radiographic progression-free survival (PFS) in men with newly diagnosed, metastatic, castration-sensitive PCa.30,31 In the LATITUDE study, OS was significantly longer in the abiraterone acetate plus prednisone group compared to the placebo group (median OS: 53.3 vs 36.5 months) when administered in combination with standard ADT.32 In a meta-analysis of both studies, abiraterone plus prednisone with standard ADT resulted in a 38% risk reduction of death compared to placebo with standard ADT for metastatic hormone-sensitive PCa.33 In addition to the expected AEs associated with testosterone suppression, abiraterone may also produce side effects associated with mineralocorticoid toxicity (ie, hypertension, hypokalemia, and fluid retention) and liver function abnormalities.34 Those patients with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia need to be monitored more closely while on treatment.

Enzalutamide, another third-generation antiandrogen, competitively binds to the AR at the androgen-binding site, inhibiting nuclear translocation and interaction of the AR with chromosomal DNA, which prevents further transcription of tumor-associated Androgen genes. This prevention of AR-dependent transcription causes decreased cell proliferation and induces cell death. Enzalutamide blocks the action of testosterone at the cellular level regardless of where it is derived from and, in conjunction with traditional ADT, can be utilized for newly diagnosed, metastatic, castration-sensitive PCa.35 In the ENZAMET trial, enzalutamide with traditional ADT was associated with significantly longer PFS and OS compared to traditional ADT alone in men with metastatic, hormone-sensitive PCa (3-year OS: 80 vs 72%).36 In addition to the commonly expected AEs for an AR inhibitor, seizures and posterior reversible encephalopathy syndrome have also been seen on rare occasions, likely due to the drug crossing the bloodbrain barrier.37 Seizure occurred in 0.4% of patients receiving treatment, but in patients with predisposing factors, seizures were reported in 2.2% of patients.

Apalutamide, another oral, nonsteroidal third-generation antiandrogen that blocks the action of testosterone by blocking the ligand-binding domain of the AR, was also designed to supersede the current androgen pathway inhibitors by overcoming AR-related resistance mechanisms. Like enzalutamide, it blocks androgen-receptor nuclear translocation, inhibits DNA binding, and obstructs AR-mediated transcription. In patients with non-metastatic, castrate-resistant PCa, according to the SPARTAN trial, metastasis-free survival (MFS) and time to symptomatic progression were significantly longer with apalutamide compared with placebo in combination with standard ADT (median MFS was 40.5 months in the apalutamide group versus 16.2 months in the placebo group).38 At median 52-month follow-up, median OS was markedly longer with apalutamide than placebo (73.9 vs 59.9 months).39 In the TITAN trial of patients with metastatic, castration-sensitive PCa, OS and PFS were significantly longer with the addition of apalutamide to standard ADT compared with placebo (OS at 24 months was 82.4% in the apalutamide group versus 73.5% in the placebo group).40 The most common adverse reactions with apalutamide were fatigue, hypertension, rash, and diarrhea.

The second and third generation antiandrogen drugs typically cost more than first-generation ADT drugs such as leuprolide or antiandrogens (bicalutamide) because they are not generic and usually patent-protected.

Surgical removal of both testicles (bilateral orchiectomy) remains a viable option as an alternative to chemical castration to eliminate testicular production of testosterone. Surgical castration may be associated with significantly lower risks of peripheral arterial disease and cardiac-related complications compared to chemical castration.41 Chemical castration, however, has largely replaced bilateral orchiectomy in clinical practice in the treatment of PCa because of the ease of administration, reversibility, and the avoidance of disfiguring surgery with its associated aesthetic and psychological consequences for patients.

ADT is a mainstay second-line treatment of prostate cancer once primary curative treatment, such as radiotherapy or radical prostatectomy, has failed. ADT blocks the HPG axis (for details see chapter 1), upon which testosterone production depends this in turn starves androgen-dependent elements of a tumor. However, patients response to ADT is not uniform. Klotz et al 2015 performed a secondary analysis on data from the PR-7 trial, which had examined intermittent vs continuous ADT. They first excluded all patients who underwent intermittent ADT, then stratified the remaining men into three groups based on their nadir testosterone levels: a) <20ng/dL, b) 2050ng/dL, and c) >50ng/dL. They found that men who reached a nadir level of 2050ng/dL and >50ng/dL were at hazard ratios of 1.62 (95% CI 1.202.18) and 1.90 (95% CI 0.984.70) of developing castrate resistant prostate cancer compared to men who had reached a nadir below 20ng/dL (P<0.015). The same group of researchers also found that the median time to development of CRPC for the three subgroups (<20ng/dL, 2050ng/dL, and >50ng/dL) were 10.0, 7.21, and 3.62 years respectively.42 Morote et al 2007 studied patients with non-metastatic disease who were on ADT either as a primary treatment, or as an adjuvant treatment after radical prostatectomy. They showed that men who had testosterone levels above 50ng/dL after reaching their nadir were at higher risk for androgen-independent progression (defined as 3 consecutive rising PSA levels) (HR 2.8, 95% CI 1.35.9, P<0.008).43

It is a common clinical experience that patients on ADT will develop CRPC at some point in the future, even with low, castrate serum levels of testosterone. Montgomery et al 2008 demonstrated that testosterone levels within the tumor tissue of anorchid men had elevated intra-tumoral testosterone levels (0.74 ng/gm, 95% CI 0.590.89) when compared to tumor tissue samples from untreated eugonadal men (0.23ng/gm, 95% CI 0.030.44, P<0.0001). In addition, tumor tissue from anorchid men also had significantly increased levels of steroidogenic enzymes. The authors concluded that prostate tumors are capable of sustaining themselves through autocrine/paracrine signaling and endogenous androgen production, even when blocking the HPG axis with ADT.44

Adrenal androgens are another source of androgens missed by the central blockade of LHRH. Brendler 1973 reviewed cases of adrenalectomy and hypophysectomy in reactivated prostate cancer after failing castration therapy (nowadays we would call this CRPC). Symptomatic improvement in the adrenalectomy group was 65%, with a similar rate for hypophysectomy patients.45 However, these improvements were short lived, as the prostate cancer in these patients would apparently adapt to a more androgen poor environment. In 1983, Labrie et al revisited the clinical idea of total androgen blockade when studying 87 men with metastatic prostate cancer, some of whom had received previous hormonal therapy and some not. All patients were treated with LHRH and RU-23908, an AR blocker. The results showed that serum prostatic acid phosphatase (PAP) dropped to normal levels in 97% of patients who had not previously received hormonal treatment and had an elevated PAP prior. They also noted positive objective radiologic responses in 100% of treatment-nave patients, with several patients experiencing a complete disappearance of all bone lesions on imaging. They also noted that patients with previous systemic estrogen therapy showed a 55% response with PAP drop and an 80% response on bone imaging, respectively. The authors also found that men who had previously undergone hormonal therapy had a fast diminishing response to total androgen blockade, and they concluded that this clinical phenomenon was likely due to a selection process of tumor cell clones less dependent on systemic testosterone support.46 In 1991, Labrie et al published results of a prospective study based on a similar regimen as described earlier by substituting flumatide for RU-23908. They found that 93% of patients had a positive objective response, with 30% of patients experiencing objective regression of all bone lesions.47 In 1997, Ansari et al conducted a trial in which 100 men with metastatic castrate sensitive prostate cancer were randomized into either orchiectomy alone or orchiectomy plus flutamide. The results showed no significant difference in overall survival at 3 years, with orchiectomy alone at 45.83% and orchiectomy plus flutamide at 48.07%. This pattern held to the 5 year follow-up, with orchiectomy and orchiectomy plus flutamide at 20.83% and 23.07%, respectively.48

The next step forward came with abiraterone, a CPY17 inhibitor. It was first described in 1994 by Barrie et al as one of several novel compounds found to inhibit 17-hydroxylase/C17,20 lyase. When testing several of these compounds on mice, there were significant reductions in the weight of the prostate (50%), seminal vesicles (75%), and testes (25%) (P<0.01 for all).49 The first human trial was done by ODonnell et al in 2004. They tested different doses of abiraterone in men with advanced CRPC who were either still receiving or had received ADT. They found significant reductions in serum testosterone levels in all patients, with no grade III adverse events.50 In 2008, Attard et al performed a Phase I clinical trial of 21 patients who had known mCRPC. They found that 66% of patients experienced a reduction of PSA by 30% or more. In addition, serum testosterone became undetectable in all patients within 8 days of their first dose, and 8/11 patients who had required analgesics at baseline had reduced analgesic requirements after receiving abiraterone.51 There was a further improved response rate reported by Tran et al in 2009 in a phase I/II trial for enzalutamide: 43% of patients had a sustained reduction in PSA by 50% or more.52

The idea of maximum androgen blockade has been a goal for men with metastatic prostate cancer for decades. As mentioned earlier, Brendler described some positive therapeutic results in both patients who had undergone hypophysectomy to inhibit ACTH and thereby adrenal androgens, and in patients who had undergone adrenalectomy for the same reason. However, this success typically came at a high cost. The next step forward on maximum androgen blockade came with Labrie in 1983, when he described the use of both LHRH and a first-generation AR blocker. His results in CRPC were impressive, with many patients experiencing both objective responses on imaging as well as symptomatic relief. Newer anti-androgen pharmaceuticals like abiraterone and enzalutamide have shown impressive objective response rates in prospective and randomized FDA trials, and have evolved to be part of the updated AUA guidelines in the treatment repertoire for asymptomatic and symptomatic mCRPC.

The timing of androgen deprivation therapy (ADT) in the management of recurrent and advanced prostate cancer has been controversial for many years. This is mainly due to a lack of adequate randomized clinical trials comparing early vs delayed ADT in patients with recurrent PSA following failure of local curative treatment. To date the available studies and current guidelines are stating that early use of ADT to be only beneficial in symptomatic patients with recurrent or metastatic disease. The EAU recommends ADT only in symptomatic patients requiring palliative treatment.53 In the following we summarize the current practice guidelines on timing of ADT in patients with recurrent prostate cancer after failing local curative treatment.

Messing et al performed one of the first landmark studies addressing the timing of androgen deprivation therapy (ADT) and its effect on survival in patients with node positive prostate cancer following radical prostatectomy and pelvic lymphadenectomy. This randomized controlled trial enrolled 100 patients between 1988 and 1993 who had previously undergone surgery and had histologically proven nodal metastasis. The patients were randomly assigned to receive either immediate ADT or active surveillance with ADT intervention only given on proven symptomatic recurrences or detection of distant metastasis. This study revealed superiority of immediate ADT compared to delayed ADT: Significantly improved overall survival (hazard ratio 1.84 [95% CI 1.013.35], p=0.04), disease specific survival (4.09 [1.769.49], p=0.0004) and progression free survival (3.42 [1.965.98], p<0.0001). The main points of criticism for this study were the low number of recruited patients and that this study did not involve patients with high-risk local disease without node involvement leading to uncertainty of optimal ADT timing for this category of patients.54 Additionally, this debate emphasized the need for further clinical research on optimal ADT timing in patients with PSA recurrence following local curative treatment.

The EAU/ESTRO/SIOG guidelines for localized prostate cancer state that routine use of ADT should be avoided in nonmetastatic patients with the exception for symptom control. This clinical recommendation is based on the EORTC Trial 30,891 which compared immediate versus deferred ADT in T0-4 N0-2 M0 prostate cancer patients unsuitable for local curative treatment. While this trial did not address PSA recurrence following local curative intervention (i.e RP vs RT), it did, however, provide evidence for the benefit of immediate ADT in patients at increased risk of cancer-specific mortality. This study included patients with high baseline PSA (>50ng/mL) and/or a PSA Doubling Time <12 months. The authors stated that patients not meeting these high-risk inclusion criteria were indeed more likely to die of other causes unrelated to prostate cancer.55

Similar to the European guidelines, the AUA/ASTRO/SUO guidelines do also not recommend early initiation of ADT without proven metastatic disease in patients who have failed maximal local therapy.56 This recommendation is mainly based on the observational study by Garcia-Albeniz et al in 2006 where eligible patients had previously been recruited for the Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE). These patients had failed prior local curative treatment and had been treated either with immediate or deferred ADT. The study revealed no survival benefits for immediate ADT vs deferred ADT initiation in patients with recurrent PSA. The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.521.60), which would be translated into a similar 5-year survival (difference between groups: 2.0% (95% CI: 10.0 to 5.9%). This suggests that in the absence of randomized control studies early ADT initiation does not provide a major survival benefit compared to deferred ADT therapy.57

Van den Bergh and colleagues performed a systematic literature review to assess the effectiveness of ADT in patients with PSA recurrence following local curative treatment. This meta-analysis found that the benefit of early/immediate ADT for nonmetastatic prostate cancer recurrence remains unproven. The conclusion was that early ADT should be reserved for patients with the highest risk of progression based on PSADT or Gleason Score, but having a long life expectancy. This falls in line with the current standard of care recommendations of the EAU/ESTRO/SIOG and AUA/ASTRO/SUO.58

Overall, currently there is a lack of randomized controlled trials (RCT) assessing the impact of early compared to delayed ADT in the management of recurrent prostate cancer following local curative therapy, which has led to the continued controversial debate on this subject. To date no RCT has addressed or shown the benefit of specific ADT timing in patients with recurrent PSA. Bruchovsky and colleagues proposed the idea of Intermittent Androgen Deprivation Therapy as a means to reduce side effects and improve quality of life. However, further research is needed for clarification of the optimal timing of reexposure of prostate cancer cells to androgens and its impact on delaying androgen resistance, which may also be influenced by early or delayed ADT.59 This situation has led to the clinical practice that early ADT is provided only to symptomatic patients in particular when weighing the long-term risks associated with ADT. Unfortunately, due to the lack of adequate RCTs we still are waiting for clear answers regarding the oncological benefits of early vs delayed ADT in asymptomatic patients with recurrent or advanced prostate cancer.53

Since the 1940s, androgen deprivation therapy (ADT) has been the foundational treatment for prostate cancer. Bilateral orchiectomy, the original form of ADT, is still used worldwide, in particular in the developing world. Medical ADT options are the standard of care when available. It is well documented in the literature that ADT is associated with numerous significant adverse effects which include hot flashes, loss of libido, erectile dysfunction, loss of muscle mass and strength, fatigue, anemia, breast enlargement and tenderness, mood swings, osteoporosis and bone fractures, obesity, cardiovascular disease, insulin resistance and diabetes. Some studies also see ADT associated with cognitive decline and dementia (for details see Chapter 9 of this review).

Intermittent androgen deprivation therapy (iADT) is a cyclic therapy with cessation of ADT (also called treatment holidays by some clinicians) allowing serum androgen recovery. The clinical idea is based on animal studies showing that iADT delayed tumor progression.60 Furthermore, the rationale for iADT is based on balancing drug-related toxicity and oncologic benefits. As continuous ADT (cADT) is associated with substantial side effects, which may increase with duration of therapy, many clinicians consider iADT as an alternative providing reduced morbidity, and thus improved quality of life, with the possible oncological benefit of delaying castration-resistant PCa.

The PR-7 trial, a landmark study, randomized patients for iADT and cADT with biochemical recurrence after either failing primary local treatment or salvage external radiotherapy.61 Eligible patients had PSA levels 3 ng/mL and no evidence for metastatic disease. The overall survival in patients that underwent iADT was 8.8 years compared to 9.1 years in patients that underwent cADT (HR=1.02, 95% CI= 0.861.21) indicating no significant difference. Furthermore, this study showed a non-inferiority P-value of 0.009 for iADT in overall survival. The study also revealed that other causes of death unrelated to PCa were more common in those receiving cADT, leading to the conclusion that intermittent therapy may not only reduce drug-related morbidity, but even mortality associated with cADT toxicity. Furthermore, patients with high-grade disease showed no improved overall cancer-specific survival when receiving cADT.

The ICELAND study published in 2016 is considered one of the main studies on iADT vs cADT in patients with relapsing prostate cancer.62 This prospective study included 102 different locations in 20 European countries and followed more than 700 participants randomized either to iADT or cADT. The authors found no difference in overall survival between the two groups, and they also emphasized the obvious reduced drug cost benefit of iADT over cADT.

The SWOG trial initiated by Dr. Hussain enrolled patients with metastatic, hormone-sensitive disease.63 All patients received an initial 7-month induction course of ADT. Patients with responding PSA levels 4 ng/mL were subsequently randomized to iADT or cADT (770 to iADT and 765 to cADT). The Kaplan-Meier curves were very similar, the hazard ratio was 1.10 with a confidence interval of 0.99 to 1.23. The pre-specified upper boundary of the confidence interval for non-inferiority was 1.20. Therefore, neither superiority nor non-inferiority could be concluded. However, the study data showed improved quality of life outcomes in the iADT arm: Better erectile function, improved bone density, less ischemic and thrombotic events.

A meta-analysis of seven studies with a total of 4810 patients treated with iADT or cADT between the years 2009 and 2015 showed no significant difference regarding cardiovascular events (risk ratio (RR): 0.95; confidence interval (CI) 95%=0.831.08) and thromboembolic events (RR: 1.05; CI 95%=0.851.30). However, iADT was associated with lower cardiovascular-related mortality.64

Another meta-analysis of randomized controlled trials (RCTs) assessed the risks of disease progression, all-cause, and cancer-specific mortality.65 Eight RCTs with 4664 patients were included in this report. It did not find any statistical difference in overall mortality and cancer-specific mortality between iADT and cADT. Again, the authors observed a better quality of life outcome for iADT, and therefore, they concluded that patients should be informed of the potential benefits of iADT.

Dason et al found that iADT was non-inferior to cADT in the primary setting of biochemical recurrence after radiation treatment of non-metastatic local prostate cancer. In the metastatic prostate cancer setting, iADT was also found to be non-inferior to cADT. Additionally, the authors reported that many ADT-related symptoms improved or resolved during the off-cycle with iADT.66

The results of a retrospective Japanese study on PSA recurrence after radical prostatectomy supported the hypothesis that iADT may delay castration-resistance in PCa.67 The iADT group had a significantly higher 5-year non-recurrence rate (92.9% vs 57.9%, p <0.001) and a better 10-year overall survival rate (95.9% vs 84.3%, p = 0.47) than the cADT group.

When summarizing the presented and pooled data, iADT provides better quality of life, whereas cancer-specific mortality shows interchangeable findings for iADT and cADT. Some studies even show improved overall survival for iADT patients likely due to reduced medication-related toxicity. Significantly reduced drug costs are also a strong rationale for iADT. Over more than one decade, iADT has evolved as the first option for patients after failing first-line local treatment in the absence of extensive metastatic disease. Although there are no well-defined recommendations or guidelines, the AUA/ASTRO/SUO website makes the following statement:

if ADT is initiated in the absence of metastatic disease, intermittent ADT may be offered in lieu of continuous ADT. (Conditional Recommendation; Evidence Level: Grade B)68

iADT may be considered after at least 912 months of ADT or until PSA nadir has been reached (in an ideal clinical scenario with PSA < 0.1 ng/mL). The off-treatment period varies depending on PSA monitoring and PSA rising, but also on patients and physicians preference. Again, there are no well-defined recommendations or guidelines at what PSA threshold ADT should be resumed. Some clinicians restart ADT when PSA doubling time (PSADT) is less than 6 months or when serum PSA has reached a level of 610 ng/mL. Some clinicians and medical providers set this threshold even far above 10 ng/mL.

Radiation Therapy (RT) and its part in prostate cancer (PCa) management has continued to evolve as this Technology has improved over time, and research has led to a better understanding of the oncologic disease dynamics. Radiation therapy for prostate cancer consists of targeted energy beams such as External Beam Radiation Therapy (EBRT) or implantable radioactive seeds such as Brachytherapy, which destroy and thus eliminate neoplastic cells. While there are diverse subcategories of radiation-based therapies (such as Intensity Modulated Radiation Therapy, Proton Beam Therapy, and Low/High Dose Rate Implants), the risk and benefits of each as well as other factors such as the patients preference ultimately guide the decision of the selected type of therapy. There are varying degrees of early and late mainly gastrointestinal and genitourinary complications caused by RT which underscore the need for shared decision making between treating physicians and PCa patients.56,69

The current AUA/ASTRO/SUO guidelines for management of advanced prostate cancer recommend primary radiotherapy in combination with ADT as a treatment option for selected patients with hormone sensitive prostate cancer and low volume metastatic disease (mHSPC). This is only a conditional recommendation with Grade C (low) level evidence and is mainly based on two preliminary Phase III trials (HORRAD and STAMPEDE Arm H) showing some benefit of combined therapy in these patients.56 These studies are still ongoing and may provide additional information to guide clinical practice in the upcoming years.

However, the AUA/ASTRO/SUO do not recommend combined therapy on localized, low risk prostate cancer except for the management of prostatic size reduction in selected patients undergoing brachytherapy.69 This recommendation stems from the randomized, phase III trial by Jones et al in 1979 which failed to show any overall survival benefit in low risk prostate cancer patients receiving EBRT with ADT vs EBRT alone; the 10-year overall survival was 64% to 67% (hazard ratio, 1.07; 95% CI, 0.83 to 1.39). In this trial the greatest clinical benefit of combined therapy was seen in the intermediate prostate cancer group: overall survival improved from 54% to 61% (hazard ratio, 1.23; 95% CI, 1.02 to 1.49).70

In the HORRAD trial prostate cancer patients with bone metastasis showed no overall survival benefit with the combination of ADT and Radiation Therapy. This study was a multi-Center randomized controlled trial on primary metastatic prostate cancer (20042014), and 432 patients were randomized to ADT with Radiation Therapy vs ADT alone. The median survival was not statistically different: 45 months (95% confidence interval [CI], 40.449.6) in the ADT plus radiation therapy group, and 43 months (95% CI: 32.653.4) in the control group (p=0.4). The overall survival was also not found different (hazard ratio [HR]: 0.90; 95% CI: 0.701.14; p=0.4).71

In the STAMPEDE phase III trial (Arm H) more than 2000 patients with metastatic prostate cancer on lifelong ADT were randomized to receiving additional radiation therapy. Radiation Therapy did improve failure-free survival (HR 0.76, 95% CI 0.680.84; p<0.0001), but not overall survival (0.92, 0.801.06; p=0.266). However, radiation therapy showed a trend to improve overall survival in those patients with low metastatic burden (73% vs 81% at 3 years).72

Shipley et al performed the landmark trial on the benefits of combining ADT and Salvage Radiation Therapy for post prostatectomy patients with persistent/recurrent PSA. These patients had either pT2 disease with positive surgical margins or pT3 disease without nodal involvement. This double blind, placebo-controlled trial recruited 760 eligible patients between 1998 and 2003 who underwent 24 months of ADT (Bicalumatide) in addition to salvage radiation therapy. This study showed in the ADT plus radiation arm significant higher rates in overall survival, but also decreased incidence of metastasis and cancer-related deaths compared to radiation therapy alone.73

The clinical trial done by Warde et al confirmed the unequivocal benefits of combining ADT and Radiation therapy in the management of nonmetastatic, locally advanced high-risk prostate cancer. This randomized, phase III trial included 1205 patients with high-risk pT2 and pT3/T4 prostate cancer over a 10-year period (19952005) who were randomized either to Radiation Therapy + ADT or ADT alone. The results showed an explicit overall survival benefit when receiving the combination therapy (74% vs 66%).74

Based on current guidelines Low and Intermediate Risk local Prostate Cancer may be treated with EBRT alone.69 However, the still ongoing EORTC 22991 trial with over 800 patients randomized to radiation therapy alone vs radiation therapy plus ADT showed at 7.2 years median follow-up that the radiation therapy plus ADT arm had significantly improved biochemical disease-free survival (DFS) (HR, 0.52; 95% CI, 0.41 to 0.66; P = 0.001) as well as clinical progression free survival (PFS) (HR, 0.63; 95% CI, 0.48 to 0.84; P = 0.001). Overall survival data is still pending. These results suggest an overall benefit with combination therapy in improving biochemical and clinical disease-free survival.75

A meta-analysis by Spratt et al revealed that ADT and radiation treatment sequencing may also be an important aspect. Adjuvant ADT post radiation therapy improved Metastasis Free Survival (MFS) and Progression Free Survival (PFS) compared to Neoadjuvant ADT without increasing long-term toxicity. The authors reviewed two randomized Phase II Trials (Ottawa 0101 and RTOG 9413) in the management of localized prostate cancer, and concluded that delaying radiation therapy to perform neoadjuvant ADT did not lead to additional tumor control or reduced toxicity and may actually be inferior to adjuvant ADT.76

Summarizing the present and available data, it appears that the combined therapy (RT + ADT) is of greatest benefit in patients with high-risk local disease. In addition, some patients with hormone sensitive prostate cancer and low volume metastatic disease may also benefit from combination therapy.

Docetaxel, a taxane-based systemic chemotherapy agent, was one of the first additional agents to emerge as a treatment with strong evidence for an overall survival (OS) benefit in patients with metastatic, castrate-sensitive prostate cancer in addition to standard ADT. In the CHAARTED trial, patients with metastatic, hormone-sensitive prostate cancer were randomized to treatment with either traditional ADT alone (which consisted of surgical castration with orchiectomy or medical castration with LHRH agonists such as leuprolide) versus ADT plus docetaxel, which they received as 75 mg/m2 every 21 days for six cycles.77 Median OS was 13.6 months longer (57.6 vs 44.0 months, HR: 0.61) in the ADT plus docetaxel group compared to traditional ADT alone.77 The survival benefit of adding docetaxel to ADT was even more pronounced in high-volume disease (defined as the presence of visceral metastases and/or greater than or equal to four bone lesions with at least one beyond the spine and/or pelvis) with median survival increased by 17.0 months compared to ADT alone (HR: 0.60).77 Additional benefits in the ADT plus docetaxel group included a longer time to the development of castrate-resistant disease, higher rate of decline of the PSA to <0.2 ng/mL at 12 months, and a lower incidence of prostate cancer-related death.77

Another trial called the STAMPEDE trial was published assessing the role of docetaxel in the metastatic hormone-sensitive prostate cancer space.78 When comparing the ADT plus docetaxel group to ADT alone, STAMPEDE again suggested an overall survival benefit with ADT and docetaxel for the subset of patients with metastatic disease (HR: 0.80).78 Patient selection in this trial notably included not only men with metastatic disease (61% of participants), but also patients with node-positive and high-risk localized disease.78

In a meta-analysis performed with the combined data from GETUG-AF15, CHAARTED, and STAMPEDE, men with metastatic castrate-sensitive disease across all three studies had a statistically significant overall survival benefit with the addition of docetaxel to traditional ADT (HR: 0.72).79 The combined data from all three trials yielded an overall 27% risk reduction of death for prostate cancer patients with metastatic disease (HR: 0.73), and a 33% risk reduction of death in high-volume, metastatic, castrate-sensitive prostate cancer patients (HR: 0.67).79

Abiraterone acetate is an androgen biosynthesis inhibitor. Another analysis of the STAMPEDE trial utilized standard ADT alone versus ADT with abiraterone (1000 mg) daily with prednisolone (5 mg daily) to assess its role in men with metastatic, castrate-sensitive prostate cancer, nodal disease, or high-risk localized disease.31 Over a three-year follow-up, overall survival was 83% in the abiraterone plus ADT group vs 76% in the ADT alone group (HR: 0.63).31

In the LATITUDE trial, patients were randomly assigned to ADT alone versus ADT with abiraterone (1000 mg) daily with prednisolone (5 mg daily).30 After a median follow-up of 30.4 months, overall survival was significantly longer in the abiraterone + ADT group than in the ADT alone group (not reached versus 34.7 months, HR: 0.62).30 Progression-free survival was 33.0 months in the abiraterone + ADT group and 14.8 months in the ADT along group (HR: 0.47).30

Enzalutamide is a potent androgen-receptor inhibitor. In the ARCHES trial, 1150 men with metastatic, hormone-sensitive prostate cancer were randomized 1:1 to receive either 160 mg enzalutamide daily plus ADT or ADT plus placebo.80 Sixty-three percent of the study participants had high-volume disease, defined as either visceral metastases or 4 bony metastases with at least one outside the spine/pelvis.80 The risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT compared to placebo plus ADT (HR: 0.39).80 This benefit was similarly seen regardless of disease volume or prior docetaxel chemotherapy. Enzalutamide plus ADT significantly reduced the risk of PSA progression, initiation of new antineoplastic therapy, first symptomatic skeletal-related event, castration resistance, and reduced risk of pain progression compared to ADT with placebo.80

Another contemporary trial evaluating enzalutamide in the metastatic, hormone-sensitive prostate cancer space, ENZAMET, randomized 1125 men with metastatic, castrate-sensitive prostate cancer to treatment with enzalutamide 160 mg daily + ADT versus traditional ADT alone.36 At median follow-up of 34 months, overall survival was improved in the enzalutamide + ADT group compared to the ADT alone group (HR: 0.67).36 Better outcomes with enzalutamide + ADT were also seen in PSA and clinical progression-free survival (HR: 0.39 and 0.40, respectively) compared to ADT alone.36 Enzalutamide was associated with significantly longer progression-free and overall survival than standard care with traditional ADT in men with metastatic, hormone-sensitive prostate cancer.36

Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. In the TITAN trial, over 1000 patients with metastatic, castration-sensitive prostate cancer were randomized to receive apalutamide (240 mg per day) with traditional ADT or placebo with ADT.40 A total of 10.7% had received previous docetaxel therapy, 62.7% had high-volume disease, and 37.3% had low-volume disease.40 Progression-free survival at 24 months was 68.2% in the apalutamide with ADT group versus 47.5% in the placebo with ADT group (HR: 0.48).40 Overall survival at 24 months was also greater with apalutamide + ADT than with placebo + ADT (82.4% versus 73.5%, HR: 0.67).40

All four agents (docetaxel, abiraterone, enzalutamide, and apalutamide) have been FDA-approved for the treatment of metastatic, castration-sensitive prostate cancer and are now listed as category 1 recommendations within the NCCN guidelines.81 Treatment choice between agents for metastatic, hormone-sensitive prostate cancer is a challenge, and there is currently no clear consensus on preferential initial selection or sequencing of these agents. There is, however, a moderate degree of uncertainty in the role of chemotherapy in low-volume disease patients.82 Marchioni et al systematically reviewed the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and found that no treatment was superior to docetaxel in terms of overall survival.83 However, abiraterone (HR: 0.89), enzalutamide (HR: 0.90), and apalutamide (HR: 0.90) showed nonstatistically significant lower overall mortality rates when compared to docetaxel.83 Abiraterone (HR: 0.71), enzalutamide (HR: 0.61), and apalutamide (HR: 0.74) also showed statistically significant lower disease progression rates when compared to docetaxel.83

Despite its effectiveness, nearly all patients on ADT will progress to castrate resistant prostate cancer (CRPC).84 CRPC is defined as biochemical or radiologic progression of disease in spite of castrate level testosterone (<50ng/dL). In the past, ADT was stopped after a cancer became castrate resistant however, Taylor showed in 1993 that there was a survival benefit of 26 months with continued ADT.85 Since then, the AUA has recommended continuing ADT in both metastatic and non-metastatic CRPC.86 In 2015, Merseburger reviewed the rationale for continuing ADT as a backbone of treatment after development of CRPC, and found no trials to this point that compared either abiraterone or enzalutamide with ADT versus without. The SPARE trial done in Germany is comparing abiraterone monotherapy with abiraterone plus ADT however, the final results are still pending. Hen comparing clinical studies Merseburger et al noticed that patients with CRPC who were started on abiraterone with prednisolone benefited from continued ADT, as the LH surge after discontinuing ADT overcame the inhibition of abiraterone. Similarly, they found that there was limited data comparing enzalutamide alone versus enzalutamide with ADT all previously published phase III trials on enzalutamide had continuation of ADT as an inclusion criteria.87

In this context the NCCN guidelines state that androgen receptor activation and autocrine/paracrine androgen synthesis are potential mechanisms of recurrence of prostate cancer during ADT (CRPC), and they recommend continuation of traditional ADT.88 Harris et al 2009 studied mechanisms of androgen persistence in prostate cancer despite ADT they found that prostate cancer cells could bypass castration with multiple mechanisms, including upregulation of the androgen receptor and synthesis of DHT in prostate cancer cells.89 Dai et al 2017 discusses changes to the androgen receptor itself as prostate cancer is treated. The androgen receptor is an intracytoplasmic steroid hormone receptor that functions as a nuclear transcription factor after an androgen binds to its ligand binding domain. In men with prostate cancer treated with ADT, mutations in the androgen receptor are seen in 1030%. On of the most common involves the loss of the ligand binding domain (the target of enzalutamide), which uncouples transcription of the targets of the androgen receptor from its activation by androgens.90 As outlined below, these pathways provide targets for newer hormonal therapies.

For a CRPC to be considered non-metastatic, it must meet the criteria of castrate resistance without radiologic evidence of metastasis on CT or technetium-99m bone scan. Once non-metastatic CRPC (nmCRPC for short) has been confirmed, the next important clinical variable is PSA doubling time (PSADT).

In patients with a PSADT greater than 10 months, the AUA and NCCN recommend continued ADT to maintain castrate level. Serial PSAs should be drawn every 36 months for adequate monitoring PSADT. Additionally, imaging should be obtained every 612 months for re-staging and to rule out development of metastatic disease.

In patients with a PSADT less than 10 months, the AUA and NCCN recommend continued ADT with a non-steroidal anti-androgen such as apalutamide, darolutamide, or enzalutamide. Smith et al 2018 showed a difference in median metastasis-free survival of 40.5 months vs 16.2 months in the apalutamide vs placebo group (P<0 0.001), as well as a significant benefit in time to symptomatic progression, with a hazard ratio of 0.45 (95% CI, 0.320.63 - P<0.001).91 Similar benefits for enzalutamide were shown by Hussain et al in 2018, with a difference in median metastasis free survival of 36.6 months for enzalutamide versus 14.7 months for placebo (P<0.001).92 Fizazi et al 2019 showed a similar benefit for darolutamide, with median metastasis free survival at 40.4 months versus 18.4 months for placebo (hazard ratio 0.41, 95% CI 0.340.50, P<0.001).93 Finally, a review by Mori et al 2020 showed that apalutamide and enzalutamide were more effective than darolutamide in regards to metastasis free survival and PSA-progression free survival, while darolutamide had an overall lower rate of adverse events.94

A patient is considered to have progressed from nmCRPC to metastatic CRPC (mCRPC) when metastatic disease is confirmed on imaging. Depending on previous treatments, the patient may have several options for ADT. Importantly, both the AUA and NCCN recommend continuation of traditional ADT with either GnRH/LHRH agonists or antagonists. Further treatment options depend on prior treatment.

In men with mCRPC without any prior novel hormone therapies (including abiraterone, apalutamide, enzalutamide, or darolutamide) several different treatment options are recommended - these include abiraterone with a steroid, docetaxel, and enzalutamide. Abiraterone is an inhibitor of cytochrome P-450c17, which ultimately manifests in inhibition of 17-hydroxylase and 17,20-lyase. Ryan et al 2013 examined abiraterone with steroid versus placebo in patients with mCRPC on ADT, who had not been previously treated with chemotherapy. Median overall survival was not reached in the abiraterone plus steroid group, while it was 27.2 months in the placebo group (HR 0.75, 95% CI 0.610.93, P<0.01). They also benefit in radiographic progression free survival, with 16.5 months versus 8.3 months in the placebo group (Hazard ratio 0.53, 95% CI 0.450.62, P<0.001).95 De Bono et al 2011 examined the role of abiraterone in mCRPC after treatment with chemotherapy and noted an overall survival of 14.8 months for abiraterone plus prednisolone versus 10.9 months for placebo, with a hazard ratio of 0.66 (95% CI 0.560.79, P<0.001). The same study also noted a benefit to progression free survival according to radiographic imaging, with 5.6 months on abiraterone versus 3.6 months with placebo (HR 0.67, 95% CI 0.590.78, P<0.001).96

Similar results were found with the AR blocker enzalutamide in mCRPC. Beer et al 2014 examined enzalutamide in mCRPC before use of chemotherapy. They showed a benefit in in cancer-specific survival, where 72% on enzalutamide and 65% in the placebo group (Hazard ratio 0.71, 95% CI 0.600.84, P<0.001). Additionally, radiographic progression free survival was 65% in the enzalutamide group versus 14% in the placebo group (Hazard ratio 0.19, 95% CI 0.150.23, P<0.001).97 Scher et al showed similar benefits when enzalutamide was used after receiving chemotherapy for mCRPC, with a difference in survival of 18.4 months for enzalutamide versus 13.6 months for placebo (HR 0.63, 95% CI 0.530.75, P<0.001). The same study showed a benefit in radiographic progression free survival, with 8.3 months versus 2.9 months (HR 0.40, 95% CI 0.350.47, P<0.001).98

The conclusion of the above a data is that ADT is still standard of care in nmCRPC and mCRPC alike, even with the introduction of new modalities.

ADT has been associated with undesirable side effects ranging from musculoskeletal decline to autoimmune disorders. The aim of this narrative is to summarize and update the adverse effects of ADT with studies published within the past 6 years.

It is well documented that ADT is associated with decreased bone mineral density (BMD) and an increased risk of developing osteoporosis and bone fractures. In one study, BMD decreased by 2.5%, 4.28%, 5.34%, and 6.16% after 6, 12, 18 and 24 months respectively following initiation of ADT.99 Patients on ADT also had an increased risk for any fracture (HR=1.4, CI=1.281.53), hip fractures (HR= 1.38, CI=1.201.58), and major osteoporotic fractures (HR=1.44, CI 1.281.61).100

Subsequent studies also illustrated the effect of ADT on muscle strength and volume. A 2016 study showed a decrease in self-reported physical functioning in men receiving ADT. Objective measurements of both grip strength and chair rise showed that grip strength was significantly diminished after 12 months of receiving ADT (P=0.01), and chair rise performance was significantly worse at both 6 and 12 months (P=0.02, P=0.003).101 Another study has confirmed differences in muscle volumes, measured by MRI, in patients on ADT. The levator ani muscle volume in men receiving ADT was significantly lower than in men of the control group (P=0.002). These men lost 16% of their initial baseline muscle volume when compared to the control. Patients on ADT had significant muscle loss in the gluteus maximus, iliopsoas, and quadriceps (P=0.017, P=0.013, P=0.031) along with increased intramuscular fat in the gluteus maximus (P=0.003).102

Metabolic syndrome is a set of symptoms that increase the risk of stroke, cardiovascular disease, and type II diabetes mellitus (DM). There is an increased risk of developing DM in prostate cancer patients treated with ADT than patients not treated with ADT (HR=1.49, CI= 1.341.66).103 ADT was also associated with higher risk of complications in patients previously diagnosed with DM. Patients on ADT had a 17% increased risk of developing diabetic retinopathy, 14% higher risk for diabetic neuropathy, and twice as likely to have diabetic amputations.104

In longitudinal cohort study of 190 men undergoing ADT, mean triglycerides (P<0.001), HDL cholesterol (P<0.001), and waist circumference (P<0.001) were significantly increased 6 months and 12 months after initiating ADT.105 Although HDL cholesterol is known to improve cardiovascular Health, an increase in overall cholesterol and triglycerides have negative effects as shown in the next two studies. Patients on ADT were at a higher risk of coronary heart disease and myocardial infarctions (OR=2.07, P<0.01).106 ADT also increased the risk for ischemic stroke (HR= 3.32, CI-1.149.67, P=0.028) when compared to non ADT users.107

The effect of ADT on cognitive function is still controversial. In one study, patients on ADT had more cognitive deficits in language ability, short-term memory, mental flexibility, and inhibitory control (P<0.05) when compared to a control group.108 A literature review and meta-analysis found an increased risk of new dementia onset (of any cause) and Alzheimer disease in patients on ADT (HR=1.21, CI=1.111.33; HR=1.16, CI=1.071.72).109 However, study results are conflicting as another retrospective study using the Taiwan Longitudinal Health Insurance Database in 5340 patients found no significant difference in Alzheimer or Parkinsons disease between patients receiving ADT and patients who did not receive ADT (HR=1.76, CI=0.555.62; HR=1.13, CI=0.582.20).110 When summarizing the reported data, several investigators think that there is a trend of cognitive decline under ADT, but they also agree that further prospective clinical studies are necessary.

A diagnosis of prostate cancer can be devastating patients and their families, and published data has shown that ADT can further increase psychiatric stress, and therefore, its impact must be considered when choosing the best alternative of therapy. The self-reported depression scores were higher in patients on ADT at 12 and 15 months when compared to patients with BPH or post prostatectomy.111 Furthermore, 43.1% of patients on ADT experienced higher incidence of anxiety when compared to control (P<0.001). This study also showed a correlation between longer duration of therapy and higher risk of anxiety (HR= 1.16, CI=2.041.29, P=0.01).112

Androgens can affect hematopoiesis and immunology. Patients on ADT are at increased risk of developing iron deficiency anemia (HR=1.62, CI 1.242.12).113 A retrospective study showed the association between ADT and the risk of developing any hematologic disorder including anemia and hematologic malignancy when compared to patients who underwent radical prostatectomy (HR=1.60, CI=1.291.97; HR 1.98, CI=1.62, 2.42). This associated risk even increased with longer duration of ADT (P<0.001).114

A study in 2016 analyzed the association between ADT and community acquired pneumonia: 62.2% of patients on ADT had respiratory events compared to 54.5% patients who did not receive ADT and 47.8% of patients who underwent one-sided orchiectomy (P<0.001). Patients with more than 11 doses of ADT were at increased risk for developing sinusitis, bronchitis, and pneumonia (HR=1.13; HR=1.26; HR=1.15; all P<0.001).115

The association between ADT and autoimmune diseases apparently depend on the type of disease. Whereas patients on ADT had a 23% increased risk of developing rheumatoid arthritis (HR1.23, CI 1.091.40),116 ADT seems to have a protective role in developing inflammatory bowel diseases: A decreased risk for ulcerative colitis (HR= 0.52, CI= 0.280.99) and Crohns disease (HR=0.38, CI 0.111.37).117

Although ADT is an effective treatment for prostate cancer, it comes with many risks and potentially harmful side effects. Therefore, a detailed risk-benefit discussion should be provided to the patient before initiating this form of treatment.

Bone mineral density (BMD) testing in patients on ADT is underutilized, and many men are unaware how to monitor and maintain good bone health. Clinical investigators have recommended to address patient education on risks of osteoporosis and strategies to improve bone health while on ADT. A 2018 study showed that a bone health pamphlet and support from a bone-health care coordinator resulted in a significantly higher percentage of men undergoing BMD testing when compared to men who underwent usual care (P<0.001). This bone health pamphlet given by the family physician also resulted in a significantly higher percentage of BMD testing (P=0.047).118

Lifestyle modifications including smoking cessation and reduced alcohol intake are recommended for patients on ADT.119 In addition, recent studies have confirmed the benefits of exercise on muscle and bone health for men on ADT. A 2019 study compared BMD in ADT patients who were randomized into immediate exercise and delayed exercise (6 months of usual activity followed by a 6-month exercise program). There was significant preservation of lumbar spine BMD in the immediate exercise group when compared to the delayed exercise group. There were no significant differences in whole body, spine, or hip BMD. Lean mass, appendicular skeletal muscle, and muscle density were preserved in the immediate exercise group after 6 months, while the delayed exercise group recovered after 12 months.120 A 2018 randomized and controlled trial evaluated the effect of home-based exercise intervention on bone-health outcomes. Although there was no difference in bone health, this study showed significantly improved muscle strength in the home-based exercise group when compared to the placebo intervention of stretching exercise.121 Improved muscle strength not only improves vitality in patients on ADT, but may also improve some of the metabolic side effects of ADT. There is some evidence of reduced risks of accidental falls and fractures in patients on ADT when participating in exercising programs, however there is a lack of robust prospective and randomized clinical trials to support this hypothesis.

The National Osteoporosis Foundation recommends a daily calcium intake of 1200 mg and vitamin D supplement of 8001000 IU/d for all men over the age of 50.122 A 2015 study analyzed whether the recommended vitamin D supplementation of 800IU/d increased blood levels of 25-OH vitamin D in patients receiving ADT. Regression analysis showed vitamin D supplementation was associated with increased 25-OH vitamin D serum levels supporting the current recommendation of 800 IU/d for men receiving ADT.123

Two controlled studies have analyzed the effect of zoledronic acid on BMD in patients undergoing ADT. In one study with 32 ADT patients diagnosed with nonmetastatic prostate cancer and osteopenia or osteoporosis received zoledronic acid for 12 months or no treatment. The patients on zoledronic acid treatment were significantly older than the control group and had lower BMD at baseline. BMD of the lumbar spine and hip were significantly increased in the patients on zoledronic acid following 12 months of treatment.124 Similar results were found in a 2-year trial of 76 men showing increased BMD in the lumbar spine and hip when on zoledronic acid versus the control. However, there was no difference in bone microarchitecture measured by high-resolution peripheral quantitative computed tomography indicating that zoledronic acid may slow but does not prevent unbalanced bone modeling.125 These studies have small sample size and inconsistencies in dosing of zoledronic acid, which limit the scientific value, and therefore, larger prospective and randomized clinical trials are needed.

Denosumab, a RANKL inhibitor, has been shown to have similar clinical efficacy when compared to alendronate (Fosamax). One study divided patients into 4 groups: 1) treated with denosumab, 2) treated with alendronate, 3) no treatment, 4) previously treated with alendronate and switched to denosumab. After 1 year, the patients who were treated with denosumab or alendronate had increased bone mass in the lumbar spine and femoral neck when compared to the control. Men treated with denosumab had significantly higher bone mass in the total hip while there was no significant change in men treated with alendronate.126 A subsequent 2017 study on denosumab showed significantly increased bone turnover markers and BMD when compared to alendronate; furthermore, a decreased rate of vertebral fractures were observed.127

Osteonecrosis of the jaw is the most common significant adverse effect of zoledronic acid and denosumab. A retrospective study in 2021 analyzed the incidence of agent-related jaw osteonecrosis in prostate cancer patients: 27.5% developed this feared osteonecrosis of the jaw within 5 years of treatment with a bone-modifying agent.128

Maintaining bone health in prostate cancer patients on ADT is an important clinical aspect as musculoskeletal side effects are common with ADT. The use of vitamin D, calcium, and bone modifying drugs should be properly discussed with patients on ADT in order to protect bone health.

The authors report no conflicts of interest in this work.

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):1029.

2. Ito K. Prostate cancer in Asian men. Nat Rev Urol. 2014;11(4):197212.

3. Connolly RM, Carducci MA, Antonarakis ES. Use of androgen deprivation therapy in prostate cancer: indications and prevalence. Asian J Androl. 2012;14(2):177186.

4. Debruyne F. Hormonal therapy of prostate cancer. Semin Urol Oncol. 2002;20(3 Suppl 1):49.

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Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA

Michael B. Miller,William G. Iacono,Matt McGue,Robert F. Krueger&James J. Lee

Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK

Augustine Kong

Department of Economics, New York University, New York, NY, USA

Kevin Thom&David Cesarini

Center for Experimental Social Science, New York University, New York, NY, USA

David A. Hinds&David Cesarini

Department of Economics, University of Southern California, Los Angeles, CA, USA

Patrick Turley

Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA

Mark Alan Fontana&Patrick Turley

Interdisciplinary Center for Economic Science and Department of Economics, George Mason University, Fairfax, VA, USA

Jonathan P. Beauchamp

Human Genetics Department, UCLA David Geffen School of Medicine, Los Angeles, CA, USA

Daniel J. Benjamin&Alexander I. Young

Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, New York, NY, USA

Mark Alan Fontana

The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Tune H. Pers,Pascal Timshel,Tarunveer S. Ahluwalia&Thorkild I. A. Srensen

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

Tune H. Pers&Pascal Timshel

Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, the Netherlands

Cornelius A. Rietveld,S. Fleur W. Meddens,Ronald de Vlaming&A. Roy Thurik

Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands

Cornelius A. Rietveld,Ronald de Vlaming&A. Roy Thurik

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

Cornelius A. Rietveld,Ronald de Vlaming,Najaf Amin,Frank J. A. van Rooij,Cornelia M. van Duijn,Henning Tiemeier,Andr G. Uitterlinden&Albert Hofman

Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia

Guo-Bo Chen,Zhihong Zhu,Andrew Bakshi,Anna A. E. Vinkhuyzen,Jacob Gratten&Jian Yang

Icelandic Heart Association, Kopavogur, Iceland

Valur Emilsson,Albert V. Smith&Vilmundur Gudnason

Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavk, Iceland

Valur Emilsson

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

S. Fleur W. Meddens,Christiaan de Leeuw&Danielle Posthuma

Amsterdam Business School, University of Amsterdam, Amsterdam, the Netherlands

S. Fleur W. Meddens&Mal P. Lebreton

New York Genome Center, New York, NY, USA

Joseph K. Pickrell

Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands

Abdel Abdellaoui,Jouke-Jan Hottenga,Gonneke Willemsen&Dorret I. Boomsma

Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

Tarunveer S. Ahluwalia,Klaus Bnnelykke,Johannes Waage&Hans Bisgaard

Steno Diabetes Center, Gentofte, Denmark

Tarunveer S. Ahluwalia&Johannes Waage

Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden

Jonas Bacelis&Bo Jacobsson

Research Unit of Molecular Epidemiology, Helmholtz Zentrum Mnchen, German Research Center for Environmental Health, Neuherberg, Germany

Clemens Baumbach&Christian Gieger

Institute of Epidemiology II, Helmholtz Zentrum Mnchen, German Research Center for Environmental Health, Neuherberg, Germany

Clemens Baumbach&Christa Meisinger

deCODE Genetics/Amgen, Inc., Reykjavik, Iceland

Gyda Bjornsdottir,Gudmar Thorleifsson,Bjarni Gunnarsson,Bjarni V. Halldrsson,Kari Stefansson&Unnur Thorsteinsdottir

Department of Cell Biology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands

Johannes H. Brandsma&Raymond A. Poot

Istituto di Ricerca Genetica e Biomedica U.O.S. di Sassari, National Research Council of Italy, Sassari, Italy

Maria Pina Concas,Simona Vaccargiu&Mario Pirastu

Psychology, University of Illinois, Champaign, IL, USA

Jaime Derringer

Institute for Computing and Information Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands

Tessel E. Galesloot&Lambertus A. L. M. Kiemeney

Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

Giorgia Girotto,Dragana Vuckovic,Ilaria Gandin,Paolo Gasparini&Nicola Pirastu

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Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals - Nature.com

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A Mercer University professors podcast highlighting women in science, technology, engineering and math has been recognized among the best in its niche.

Dr. Sabrina Walthall, associate professor of science in the College of Professional Advancement, hosts the STEM Lab Podcast, which was ranked No. 13 among the Best 45 Women in STEM Podcasts. The ranking by Feedspot, a web content reader, was based on traffic, social media followers, domain authority and freshness.

Dr. Walthall said she created the STEM Lab Podcast two years ago to highlight women, especially those from marginalized groups, in STEM.

I realized that the news media only seemed to highlight women who, of course, had done something just spectacular and over the top, she said. But I knew a lot of women, who I either went to graduate school with or met at conferences, who were doing great things. These are a lot of women already in the community, doing work in their own community, but no one really knows.

And so, I just felt the podcast was a great way to put the story out there.

Each episode, released monthly, features an interview with a woman who uses science, technology, engineering or math in her work. Episodes have featured two women who hold both M.D. and Ph.D. degrees, a registered nurse, an environmental neuroepidemiologist and a viral immunologist. A recent episode featured an unconventional woman in STEM a celebrity cake artist.

The baker was very unconventional, which I love because I dont think people think of STEM in that way, and then just talking to her I realized, All you do is STEM all day long, Dr. Walthall said.

Her podcast also dives into the challenges women, in particular marginalized women, face in STEM. One of her favorite episodes was an interview with Dr. Ansley Booker, director of diversity and inclusion initiatives at Mercer.

In order for STEM to move forward, we really have to look at diversity, equity and inclusion, Dr. Walthall said.

Representation of women in STEM varies widely, according to a recent Pew Research Center analysis of the STEM workforce.

While women make up half of those employed in STEM careers, they are overrepresented in health-related jobs but underrepresented in other fields, such as the physical sciences, computing and engineering. Meanwhile, Black and Hispanic workers (male and female) are underrepresented in the STEM workforce across the board, the analysis shows.

A lot of times the reason all this is happening, and why I also try to work with girls in STEM, is because of gender stereotypes, Dr. Walthall said. Its just been ingrained in us since we were young that certain careers belong to men and are masculine, and certain careers belong to women.

And you dont always hear of young girls being told that they should grow up to be a scientist or that they can be the engineer or that maybe they can be the mathematician.

She said she hopes a young girl might hear the STEM Lab Podcast and discover she can be like the women being interviewed.

Dr. Walthalls own love for STEM began when she was young. She became fascinated with science after being assigned a report on the heart.

I learned the heart was not the shape of the candy box, but it was the size of our fist, and that fascinated me, she said. And I just remember learning all the information and just going around the house, spouting it to anybody who would listen to it.

She went on to earn a bachelors degree in biology from Emory University and a doctorate in biochemistry and molecular genetics from the University of Alabama at Birmingham. She completed her postdoctoral training with the UAB Community for Outreach Development where she worked on rebuilding science education at the K-12 level in Alabama and discovered her passion for the science of teaching and learning.

Through a National Science Foundation fellowship, she was able to go into an Alabama high school and teach genetics. She realized she really enjoyed it.

I would always make a story out of the science because thats the way Ive always seen science. Its really, literally, a cartoon in my head, she said. I realized I could start a concept in a fun way and then build up to where we understand it truly scientifically, but I had to start them somewhere.

In addition to her work at Mercer, prior to the COVID-19 pandemic, Dr. Walthall volunteered with the Real Impact Center, a Macon-based nonprofit dedicated to exposing girls to STEM careers.

She enjoyed the work so much that she incorporated it into her courses as a service-learning project, which included college students working with youth during events like STEM-tastic Saturdays and a Macon STEM Pop-Up.

The STEM Lab Podcast is available on Apple and Google Podcasts, Anchor, Spotify and YouTube.

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Mercer professor's podcast among the best about women in STEM - Mercer University

Recommendation and review posted by Bethany Smith

There arent enough hours in the day, Marian Andersen says.

Marian Andersen with her dog, Ashley. She reads four newspapers daily and enjoys watching all kinds of sports. Gonzaga is her pick to win the NCAA basketball tournament.

At 93, shes still reading four newspapers daily. Magazines and books also keep her busy.

Im not giving up on newspapers, she said.

She couldnt wait for the NCAA basketball tournament to start she picked Gonzaga to win it all. Baseball is another love, and with a fall trip to Texas, shes seen every major league stadium.

Shes also a huge Nebraska football fan. People are astounded to learn shes been attending games for 90 years. Her father took her to her first one when she was 3 years old.

Marian Andersen at age 5. She went to her first Nebraska football game at the age of 3.

Her social calendar is packed she enjoys playing bridge and attending the movies. Thank goodness for younger friends, she said, since many of her older ones have sadly passed away.

One of the amazing things about Marian is her positive attitude and zest for life and her genuine interest in other people, longtime assistant Jackie Wrieth said. Not only does she want to know everything about you, but also about your kids and grandkids and she remembers it all.

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A mutual friend always said if youre attending a banquet you want to sit at Marian Andersens table. Shes one of a kind.

Marian Andersen and her husband, former Omaha World-Herald publisher Harold W. Andersen, at the Ak-Sar-Ben pre-coronation in October 1994.

Life has always been full for Andersen, who still lives in her home with a cocker spaniel, Ashley. Ashley doesnt cook, Andersen jokes, but shes great company.

Shes got family here, too. Son David, his wife, Leslie, and three grandkids live in the Omaha area as well as San Francisco. Daughter Nancy Andersen and her three sons live in Denver.

Her husband, the late Harold W. Andersen, was publisher of The Omaha World-Herald from 1966 to 1989. Although she didnt have a full-time career, Marian didnt sit home on the sideline. As a longtime community volunteer, she has been a pioneer.

She was the first woman chairman of the University of Nebraska Foundation and the first woman board chair for the Red Cross in Omaha.

Marian Andersen, center, leaves the stage with her daughter Nancy Andersen, left, and son David Andersen after she was honored during the United Way of the Midlands Excellence in Impact event in 2017.

She was on the board and co-chair of the committee that hired the first woman president of the national Public Broadcasting System. The Andersens made significant contributions locally and nationally to PBS.

She was also pleased recently to make the acquaintance of Ava Thomas, The World-Heralds second woman publisher.

Im all for women to break that glass ceiling, she said.

Together, she and Harold supported a long list of organizations.

She was named the United Way of the Midlands Citizen of the Year in 1994. With her husband, she was a co-founder of the Alexis de Tocqueville Society, a group of contributors who donate a minimum of $10,000 to the annual United Way campaign.

She also received the Distinguished Nebraskalander Award from the Nebraskaland Foundation and was named outstanding sustainer by the Junior League of Omaha. She was a past president of Planned Parenthood and co-chairman of the Nebraska Shakespeare Festival.

Marian Andersen in 1974. She was an active volunteer.

Brian Hastings, the president and CEO of the Nebraska Foundation, said Marian Andersen has a long history of supporting the foundation. She is its longest-serving trustee, since 1962, served as the chair of the board of directors in 1984 and 1985 and was the first woman to do so.

She liked to say she broke the glass ceiling for her husband, Harold, who became chair of our board later, in 1991 through 1993, Hastings said. She and Harold were the volunteer chairs of a comprehensive campaign that ran from 1993 through 2000. The goal was to raise $250 million for the University of Nebraska. It raised $727 million due to Marian and Harolds leadership. She is one of the foundations and universitys most ardent and faithful supporters.

Andersen said shes just always been a leader, from when she was student council president at Lincoln High and president of Kappa Kappa Gamma sorority at the University of Nebraska-Lincoln, where she also was a Phi Beta Kappa.

Marian Andersen in 1951. She said she's always been a leader.

I never was intimidated, she said.

After she married at 23, which at that time she said was almost an old maid, she and her husband saw the world. They visited 60 countries and every state.

Another great love of Andersens is tennis, and shes been to the grand slam of tournaments: the Australian Open, the U.S. Open, Wimbledon and the French Open.

During womens history month, Andersen said shes most proud of two things.

I think my family, she said, and the fact that I have maybe made a difference in some of the organizations.

Marian Andersen and her dog, Ashley, at her home in Omaha. She jokes that Ashley cant cook, but shes good company.

2. Standing Bear

c. 1829-1908

Native leader

A renowned Ponca chief, Standing Bear, in 1879, became the first Native to be legally recognized as a person.

In 1877, the federal government forced the Ponca from their northeast Nebraska land to Indian Territory in what is now Oklahoma. A year later, honoring the wish of his 16-year-old son to be buried along the Niobrara River, Standing Bear led a band of tribe members back to Nebraska.

Arrested for leaving the reservation, Standing Bear stood trial at Fort Omaha, his lawyers filing a writ of habeas corpus contesting the detention. The judge ruled in favor of Standing Bear and the U.S. Supreme Court upheld the ruling.

4. George W. Norris

1861-1944

Politician

Called the very perfect, gentle knight of American progressive ideals by President Franklin D. Roosevelt, Norris served five terms in the U.S. House of Representatives (1903-13) and five terms in the U.S. Senate (1913-43), all save the final term as a Republican.

An Ohio native, Norris moved to Beaver City in 1885 to practice law. He established an office in McCook in 1899, practicing law before beginning his political career.

Norris promoted the unicameral Legislature in Nebraska, approved by voters in 1934, and led the creation of the Tennessee Valley Authority, and the Rural Electrification Act, both championing public power.

5. Wm. Jennings Bryan

1860-1925

Politician

A famed orator and leader of the populist wing of the Democratic Party, Bryan was the Democratic presidential nominee three times in 1896, 1900 and 1908. He served two terms in Congress from Nebraska and was Secretary of State under Woodrow Wilson.

Born in Salem, Illinois, The Great Commoner settled in Lincoln in 1887 to practice law. Known for his oratory, Bryan was a champion of free silver and delivered his famous Cross of Gold speech in 1896.

Touring the country as a public speaker, Bryan worked for peace, Prohibition and womens suffrage and opposed the teaching of evolution, joining the prosecution in the famed Scopes Monkey Trial in 1925.

6. John Neihardt

1881-1973

Poet

The writer, poet and historian is best known for "Black Elk Speaks," the biography of the Oglala Lakota holy man Neihardt published in 1932.

Born in Illinois, Neihardt moved to Wayne in 1892 as an 11-year-old. Bancroft became his home in 1901. He became a published author at age 19, started his major work, "The Cycle of the West," at 31 and became Nebraska's Poet Laureate at 40.

At 45, he was literary editor for the St. Louis Post-Dispatch, and at 68 became poet-in-residence and lecturer in English at the University of Missouri. He returned to Nebraska in his 80s, continuing to write until his death at 92.

9. Charles Dawes

1865-1951

Vice president

Dawes (above with pipe) pursued two careers in his lifetime, one in business/finance, the other in public service, with the two coming together in 1925 when he won the Nobel Peace Prize while serving as Calvin Coolidge's vice president.

Dawes moved to Lincoln in 1887, where he practiced law until 1894. Purchases of gas companies in LaCrosse, Wisconsin, and near Chicago started investments that made him rich. The Republican activist took his first government position in 1898.

A self-taught musician, he composed what eventually became the pop standard "It's All in the Game."

10. Ted Sorensen

1928-2010

Presidential adviser

In 1953, the Lincoln native and University of Nebraska College of Law graduate became chief legislative aide for Sen. John F. Kennedy and, after the 1960 election, became President Kennedys chief aide and speechwriter.

Responsible for crafting Kennedys famous inaugural address, Sorensen served as a key adviser during the 1962 Cuban missile crisis and penned the letter to Soviet Premier Nikita Khrushchev that defused the crisis.

After his White House years, Sorensen joined a prominent New York City law firm and built an international law practice.

11. J. Sterling Morton

1832-1902

Politician

Founder of Arbor Day, Morton moved to Nebraska City in 1854 and became editor of the local paper. He served as acting governor in 1858 and again in 1861 and was U.S. Secretary of Agriculture from 1893-1897.

12. Tom Osborne

1937-

Football

The Hastings native played professional football before becoming a Nebraska assistant coach in 1964. Named head coach in 1972, Osborne led the Huskers for 25 years, winning three national championships. He served in Congress from 2001-2007 and as UNL athletic director from 2007-2013.

13. John J. Pershing

1860-1948

Military

In 1891, Army officer Pershing became professor of military science at the University of Nebraska where he earned his law degree in 1893. Black JackPershing served in the Spanish-American War and became the leading American commander in World War I.

14. Harold Edgerton

1903-1990

Engineer

Fremont-born Edgerton grew up in Aurora and received his engineering degree from the University of Nebraska in 1925. In 1927, he began working with stroboscopes and in 1937 began collaborating with a photographer to make his motion capture images.

15. Loren Eiseley

1907-1977

Nature Writer

The Lincoln native began writing while attending the University of Nebraska. In 1947, he began teaching at the University of Pennsylvania. In the 1940s, he began writing his acclaimed nature essays and books combining natural science with literature.

16. Dick Cavett

1936-

Television

Born in Gibbon, Cavett grew up in Lincoln before attending Yale University. Hired as a writer for The Tonight Show in 1960, Cavett also worked in stand-up comedy before landing The Dick Cavett Show, which ran from 1968 to 2007.

17. Bob Kerrey

1943-

Politician

Winning the Congressional Medal of Honor for his service in Vietnam, Lincolns Kerrey was elected governor in 1982, became a U.S senator in 1989 and was a Democratic presidential candidate in 1992. He also served on the 9/11 Commission.

18. Henry Fonda

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'Break that glass ceiling': Omahan Marian Andersen has relished a life filled with firsts - Kearney Hub

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If your bad cramps aren't caused by a workout or period pain, there can be another reason: pelvic inflammatory disease (PID). According to the Centers for Disease Control and Prevention (CDC), PID is the infection of the female reproductive organs, and can result from untreated sexually transmitted diseases (STDs) or the use of an improperly placed intrauterine device (IUD).

The only way to avoid PID is to avoid all sexual activity. If you are sexually active, use protection or be smart about your choice of partners, making sure they also test negative for STDs. If you notice abnormal bleeding or severe cramping in the abdomen, it is best to get a diagnosis, as it is always better to treat a disease in its earlier stages because the cause could be PID.

WebMD shared that "PID is an infection of the organs of a women's reproductive system. They include the uterus, ovaries, fallopian tubes, and cervix." This affects about 770,000 women in the U.S. every year, and can ultimately also affect fertility. Consult a doctor if you are sexually active and experience severe pain in your tummy that seems more unusual than period cramps. It can be treated with antibiotics, but serious cases may require hospitalization.

Ultimately, no matter what is causing them, we've got you covered with the best ways to relieve stomach cramps.

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What Does It Mean When When You Have Bad Cramps? - The List

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Insects are often seen as pests, but many species can provide new sources of food, materials, and even ways to clean up plastic waste. Here are 10 companies in this space that we think are worth watching.

Many people think of insects simply as pests that eat crops and carry diseases such as malaria. While this is true in some cases, insects have also been an inspiration to scientists for many years. Biotechs and researchers are now applying this knowledge to create new and sustainable food sources for both humans and animals, as well as fertilizers to grow other foods.

The unique biology and chemistry found in insects has inspired the creation of packaging materials, bioplastics, glue, and other biomaterials. Some scientists have even found moth larvae that eat plastic and other, more early-stage research, is looking at ways to repurpose spider venom to treat pain or create insecticides for use on plants.

The number of biotech companies working in the insect or yellow biotechnology space is constantly increasing. Here are 10 firms we think are worth paying attention to.

Founded: 2005

Headquarters: Madrid, Spain

Madrid-based Algenex uses insects and insect cells to produce proteins needed to develop drugs, vaccines, and diagnostics. Jos Escribano founded the company in 2005 and is now CSO.

The company has two main products: CrisBio and TopBac. The former, validated by the EMA last year, uses chrysalises of the cabbage looper moth Trichoplusia ni as living bioreactors to produce medicinal proteins. Living insects can regulate their own temperature and oxygen levels, making them easier than cells to manufacture at scale. The insects are infected with a modified virus, harmless to humans, known as a baculovirus. Prior to infection, the virus is genetically engineered to ensure production of the desired protein. The chrysalises can then produce enough protein to extract in less than a week.

The other product, TopBac, is a DNA sequence that contains instructions necessary to express certain genes in cells. It can be used to improve both the productivity and quality of the proteins produced by the insect cells.

The company has already produced more than 200 types of medicinal proteins used for human and animal diagnostics and therapeutics. Funded by Columbus Venture Partners, Chamber Ventures, and Vita Advisory, the company raised a 8.75M Series B round in 2020 and a 4M Series A financing in 2019.

Founded: 2011

Headquarters: Paris, France

nsect was founded in 2011 in Paris by a group of scientists and environmental activists. The company uses insects to produce high-protein products for animal and fish food, as well as the fertilizer industry, in a sustainable and environmentally friendly way.

The company has created technology that allows vertical production of the yellow mealworm beetle Tenebrio molitor. In 2019, nsect raised 110M in Series C funding the largest-ever amount for agriculture technology outside of the USA to fund the construction of the worlds largest automated insect farm. This was extended to 343M in 2020, bringing its total funding to approximately 391M. Last year, the company acquired Dutch mealworm breeding company Protifarm to expand its reach across Europe.

In January 2021, the European Food Safety Authority concluded that mealworms are safe for human consumption, a positive development for nsects mission to enter the human food market.

Last month, nsect announced the launch of nfabre, an industrial program dedicated to the genetics of these insects. The initiative is designed to bring expertise from different fields together to develop improved phenotyping and genotyping tools, as well as more efficient industrial processes.

Founded: 2002

Headquarters: Abingdon, UK

A spin-off from the University of Oxford founded in 2002, Oxitec genetically engineers mosquitoes with a self-limiting gene to help control diseases such as malaria and dengue. By introducing a gene that kills the female offspring of mosquitoes, the company has claimed massive success in reducing local populations of disease-carrying mosquitoes in locations including Brazil, India, and Panama.

Since its founding, Oxitec has diversified and is applying similar technology to pest insects that attack crops such as the diamondback moth, a massive problem for vegetable farmers, and others such as the soybean looper and the fall armyworm. According to the company, the advantage of this technology is that, unlike chemical insecticides, it does not kill harmless insects like bees and other pollinators.

Oxitec was acquired by US-based Intrexon Corporation in 2015, acting as a separate subsidiary. In 2020, Intrexon sold off Oxitec and other non-healthcare assets to another US company, Third Security.

Founded: 2009

Headquarters: Dongen, The Netherlands

Protix was founded by Kees Aarts and Tarique Arsiwalla in 2009. The company uses a combination of high-tech control systems, artificial intelligence, breeding programs, and robotics to produce lipids, proteins, and pure from larvae of the black soldier fly (Hermetia illucens). It also plans to expand to crickets, locusts, and mealworms in the future.

The company opened its first industrial-scale factory in 2019 in Bergen op Zoom and has a number of different animal food products on the market used to make nutritious food for pets, chickens, and fish. The firm also produces a fertilizer from the byproducts of its industrial process.

Protix started a collaboration with the animal breeding specialist Hendrix Genetics in 2018 and recently announced that they have successfully bred black soldier flies with bigger larvae that will increase yield in their insect farms.

Last month, Protix attracted a 50M investment from BNP Paribas, Monaco Asset Management, and the Luxembourg-based European Circular Bioeconomy Fund. The company has now accrued over 120M in total funding and plans to expand internationally.

Founded: 2014

Headquarters: Salamanca, Spain

Tebrio, previously known as MealFood Europe, was founded by Adriana Casillas and Sabas de Diego in 2014. Similar to nsect, Tebrio focuses on transforming the T. molitor mealworm beetle into different ingredients for a wide variety of uses.

Tebrio has three main product streams: sustainable fish, pet, and animal feed; biofertilizer for plants that also acts as an insect repellant; and chitosan extracted from the insects to make biodegradable plastic that can dissolve in water. Chitosan has many other uses; for example, it can be used for water treatment, as a base for coagulants, or for medical uses as an antibacterial component of dressings and bandages.

In 2020, the company closed a Series A funding round co-led by Caixa Capital Risc and the Spanish Centre for Industrial Technological Development (CDTI). While the total amount of the round was undisclosed, Tebrio announced the cash would allow the firm to develop a 50M insect breeding project.

Founded: 2017

Headquarters: Karmei Yosef, Israel

Smart Resilin is an Israeli biotech, set up in 2017, that is harnessing the power of resilin in its products. Resilin is a rubber-like protein found in the outer skin of most insects that helps them jump large distances and fly by allowing their wings to beat.

The company was spun out of the Hebrew University of Jerusalem by a team including materials scientist and serial entrepreneur Professor Oded Shoseyov, now CSO of the company. The researchers behind the company succeeded in identifying the genetics of resilin production and engineered bacteria to produce the protein.

Experiments have shown that resilin can be very useful in industry. For example, as an addition to glue, resilin improves elasticity and fatigue resistance. The company also plans to use it for other applications such as manufacturing training shoes. Resilin is also biodegradable, sustainable, and compostable, making it attractive for consumers.

Founded: 2016

Headquarters: Meath, Ireland

Hexafly is another company on the list that focuses on the black soldier fly (H. illucens). The company feeds its insects waste materials from breweries so the farm is totally waste-free. Founded by Alvan Hunt and John Lynam, Hexafly is based in Meath, Ireland and runs the countrys only vertical insect farm.

The company makes animal and fish food with their products from proteins and oils extracted from the flies, as well as dried grubs. The team also makes frass, a natural fertilizer for plants that can double up as a pesticide, for example, by reducing the impact of aphids.

The company received 2.2M seed funding in 2018 and has since then set up a pilot plant and received 3M in Series A funding.

Founded: 2020

Headquarters: Jarfalla, Sweden

Norbite, was founded in 2020 by Nathalie Berezina, previously nsect CTO/CSO. The firm was founded based on observations of the greater wax moth (Galleria mellonella) that showed caterpillars of this species are capable of eating plastic.

While the initial observations of the plastic-munching caterpillars occurred accidentally, they have now been confirmed. Greater wax moth larvae can consume around 80% of plastics including polyethylene and polystyrene, which have a similar chemical formulation to the wax they normally consume.

While it is still early days for Norbite, the company hopes to build a plant capable of processing 30,000 tons of plastic within five years. Many industrial biotechs find scaling up a challenge and Norbite will need to overcome major technical and economic obstacles to breed these insects on a wide scale and make its plastic degradation proposal an affordable reality.

Founded: 2016

Headquarters: Kongens Lyngby, Denmark

BioPhero was founded in 2016 by Irina Borodina as a biotechnology spin-out from the Technical University of Denmark. The company uses yeast fermentation technology to produce sustainable and safe insecticide replacements with the same makeup as insect pheromones. Applying pheromones to crops can mask the pheromones that female insects use to attract males, stopping them from mating.

The company currently targets four main pests with its pheromones, the cotton bollworm (Helicoverpa armigera), the diamondback moth (Plutella xylostella), rice stem borers (Chilo suppressalis and Scirpophaga incertulas), and the fall armyworm (Spodoptera frugiperda).

In March last year, BioPhero announced a 15.6M Series A funding round led by DCVC Bio with participation from FMC Ventures, as well as existing investors Syngenta Group Ventures and Novo Holdings.

Founded: 2021

Headquarters: Limburg, The Netherlands

Sib was named after a Costa Rican deity who taught people to work together with nature. It is still at the seed funding stage and was founded last year in the Netherlands by Costa Ricans Daniela Arias and Alejandro Ortega.

Sib is focused on the development and supply of insect-based food ingredients and water-soluble proteins from crickets and yellow mealworms.

The company will carry out technological processing of the insects in the Netherlands at the Brightlands Chemelot Campus in Limburg. The insect farming itself will take place in Costa Rica to ensure a fair deal for farmers in the developing country.

Sibs technology, named Entowise, allows fine separation of nutritional components such as protein, fats, and cytosine from powdered insects. The technology is precise enough that it could be used to extract vitamins such as B12 from insects.

Cover image via Elena Resko

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The Top 10 Insect-Powered Biotech Companies - Labiotech.eu

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Accusations of unfairness surround trans athletes such as the swimming champion Lia Thomas, far right, in womens sport

RICH VON BIBERSTEIN/GETTY IMAGES

The governments dithering over whether to ban conversion therapy has left policy on this sensitive issue in utter confusion. A double U-turn saw the prime minister at first cast aside a pledge that he would outlaw attempts to change peoples sexual orientation, before reinstating the commitment with measures to ensure it would not affect counselling offered to those suffering from body dysmorphia who want to transition to the opposite sex.

Lobby groups on all sides shrilly condemn discrimination. Mr Johnson had previously described all conversion therapy as abhorrent. However, feminists fear that womens rights are now in jeopardy. And the general public is bemused by arguments that seem as obscure as they are virulent. It is time common sense was brought to the trans debate.

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The Times view on the trans debate: Back to Basics - The Times

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Increasing Application of Stem Cells in Cosmetic Anti-aging Is Expected to Boost the Demand of Anti-aging Products and Therapies Market.

Anti-Aging Products and Therapies Market size is estimated to reach $93.2 billion by 2027, growing at a CAGR of 7.72% during the forecast period 2022-2027. Anti-Aging Products and Therapies are the products and therapeutics which defer, halt or hinder the aging process. Liposuction Surgery is an anti-aging therapy that is a fat elimination process that targets to destroy surplus stubborn fat from the hard-to-shift areas. Liposuction should be thought of as a sculpting process that can alter the curves of the body or face. A Tummy Tuck or Abdominoplasty is an anti-aging therapy that will eliminate surplus fat and skin from around the waist and eliminate surplus skin to leave a flatter, reduced body profile and younger-looking abdomen. Chemical peeling, also termed as chemexfoliation or derma-peeling, is an anti-aging therapy utilized to enhance the countenance of the skin in which a chemical solution is enforced on the skin, which brings about the blister and finally peels off. The novel, enhanced skin is normally smoother and less wrinkled than the old skin. The novel skin also is temporarily more sensitive to the sun. Anti-Pigmentation Therapy may include the application of anti-blemish and anti-pigmentation cream which is a blend of herbal concentrates that enhance the clearness of the skin.

The compelling technological developments in conjunction with emerging R&D activities have led to the launch of anti-aging treatments like liposuction, breast implants, and plastic surgeries are set to drive the Anti-Aging Products and Therapies Market. The increased awareness regarding aging amidst the youth and mature grown-ups is set to propel the growth of the Anti-Aging Products and Therapies Market during the forecast period 2022-2027. This represents the Anti-Aging Products and Therapies Industry Outlook.

Anti-Aging Products and Therapies Market Segment Analysis By Product:

The Anti-Aging Products and Therapies Market based on the product can be further segmented into Anti-Wrinkle Products, Anti-Stretch Mark Products, Hair Color Products, UV Absorption, and Others. The Anti-Wrinkle Products Segment held the largest market share in 2021. This growth is owing to the expanding population of the elderly requiring anti-wrinkle products. Typical anti-aging techniques include liposuction and chemical peeling. The heightened awareness regarding the accessibility of anti-wrinkle products is further propelling the growth of the Anti-Wrinkle Products segment.

Furthermore, the Anti-Stretch Mark Products segment is estimated to grow with the fastest CAGR of 8.41% during the forecast period 2022-2027 owing to the proliferating application of anti-stretch products in cases of stretch marks brought about by obesity and pregnancy in conjunction with more progressive products launched by key players for the treatment of stretch marks apart from the application of typical anti-aging techniques like chemical peeling.

Anti-Aging Products and Therapies Market Segment Analysis By Therapy:

The Anti-Aging Products and Therapies Market based on therapy can be further segmented into Liposuction, BOTOX, Rejuvenation & Dermal Fillers, Hormone Replacement Therapy, Gene Therapy, Sclerotherapy, Hair Restoration Services, Abdominoplasty, Anti-Pigmentation Therapy, Breast Augmentation, and Others. The Liposuction Segment held the largest market share in 2021. This growth is owing to the surging application of liposuction procedures largely attributed to their great recognition attained on social media. The goal of liposuction is esthetic. The proliferating technological progress and heightened awareness regarding liposuction procedures are further propelling the growth of this segment.

Furthermore, the BOTOX segment is estimated to grow with the fastest CAGR of 8.7% during the forecast period 2022-2027 owing to the surging application of botox injections largely ascribed to the health advantages offered like treatment of eye ailments like crossed eyes, smoothening wrinkles thereby minimizing signs of aging and offering alleviation for frequent migraine patients apart from the application of other anti-aging techniques like chemical peeling.

For More Information AboutAnti-Aging Products and Therapies Market @

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Anti-Aging Products and Therapies Market Segment Analysis By Geography:

The Anti-Aging Products and Therapies Market based on geography can be further segmented into North America, Europe, Asia-Pacific, South America, and the Rest of the World. North America (Anti-Aging Products and Therapies Market) held the largest share with 36% of the overall market in 2021. The growth of this region is owing to the accessibility of well-developed infrastructure in the region. The soaring application of anti-aging therapies like liposuction and chemical peeling in the U.S. is further driving the growth of the Anti-Aging Products and Therapies Market in this region. The existence of key players like Merck in the U.S. in the region is further propelling the growth of the Anti-Aging Products and Therapies Market in the North American region.

Furthermore, the Asia-Pacific region is estimated to be the region with the fastest CAGR rate over the forecast period 2022-2027. This growth is owing to factors like soaring consumption of skincare products and cosmetics in emerging economies like India in the Asia-Pacific region. The detection of early signs of aging requiring the application of anti-aging techniques like chemical peeling is further fuelling the progress of the Anti-Aging Products and Therapies Market in the Asia-Pacific region

Anti-Aging Products and Therapies Market Drivers

Surging Advantages Of Chemical Peeling Are Projected To Drive The Growth Of Anti-Aging Products and Therapies Market:

Chemical peeling, also termed chemexfoliation or derma peeling, is a clinical process that utilizes plant-based chemical solutions to exfoliate the skin. Relying on the requirement of the client, a dermatologist may suggest a peel from a series of strengths: superficial peels that attain superficial layers of the skin or deeper ones that infiltrate numerous microlayers of skin. A chemical peeling treatment is a skin invigorating process, which utilizes gentle acids extracted from organic sources of changing strengths to exfoliate the upper layers of the skin in a regulated manner, succeeded by conversion of novel healthier layers. Chemical peeling assists in curbing acne breakouts by eliminating surplus sebum, dead skin cells, and dirt. It equalizes the texture of the skin by healthy skin invigoration. It enhances the complexion by minimizing dark spots and discoloration. The surging advantages of chemical peeling are therefore fuelling the growth of the Anti-Aging Products and Therapies Market during the forecast period 2022-2027.

Increasing Application Of Stem Cells In Cosmetic Anti-Aging Is Expected To Boost The Demand Of Anti-Aging Products and Therapies Market:

Typical anti-aging techniques include chemical peeling and liposuction. Stem cells are being utilized with heightening frequency in cosmetic medicine. Stem cells can be injected directly into the skin on the face and other areas. This has been demonstrated to minimize wrinkles, skin discoloration, and advance skin revitalization. It can also minimize the appearance of scars, stretch marks, and advance skin tightening. Investigations demonstrate that including stem cells in additional cosmetic surgeries like Liposuction, Fat Transfer Natural Breast Augmentation, and Awake Tummy Tuck, quicken healing and provide a superior cosmetic outcome. Adding stem cells to resurfacing lasers has been demonstrated to improve the ultimate outcomes as well. This is likely true when augmented with radiofrequency skin tightening as well. The increasing application of stem cells in cosmetic anti-aging is driving the growth of the Anti-Aging Products and Therapies Market during the forecast period 2022-2027.

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Anti-Aging Products and Therapies Market Challenges

Limitations Of Recognized Anti-Aging Treatments Are Hampering The Growth Of The Anti-Aging Products and Therapies Market:

Vitamin E is regarded as one of the most recognized skin anti-aging agents, both as an oral and topical treatment. However, Vitamin E is not regarded safe at the time of pregnancy. Consuming vegetables will not hurt the baby. However, it is presently unclear at what levels Vitamin E supplements become hazardous to unborn babies. Nearly all physicians suggest not to consume more than 400 IU/day. To be entirely efficient as an anti-aging product, vitamin E needs to be consumed orally creams with vitamin E can smoothen and contribute elasticity. However, the actual advantages come from pills and not everyone likes to take pills. Another technique is Botox. Botox is good but not all-inclusive. It is not efficient at combating those wrinkles around the mouth or wrinkles brought about by sun damage. In addition, it will not perform for everyone in an identical manner. These issues are hampering the growth of the Anti-Aging Products and Therapies Market.

Anti-Aging Products and Therapies Market Landscape:

Product launches, mergers and acquisitions, joint ventures, and geographical expansions are key strategies adopted by players in the Anti-Aging Products and Therapies Market. Key companies of this market are:

GaoxinMerckIMEIKBohus BioTechLG Life ScienceGaldermalAllerganIpsenLanzhou InstituteCynosure

Recent Developments

In January 2022, Chanel has introduced a series of skincare and cosmetic products described by Vogue as its most environmentally conscious to date, inclusive of its earliest refillable beauty product. The series of products, termed No. 1 de Chanel, is housed in packaging with no exterior plastic wrapping and no interior paper leaflets. Chanel has also discarded all plastic constituents in the bottles and jars, choosing glass instead and persuading customers to recycle the packaging once it is vacant.

In October 2021, Cynosure declared the Canadian (Health Canada) clearance of its best-in-class Potenza radiofrequency (RF) microneedling system providing clinicians incomparable versatility and customized treatments for patients with its one-of-a-kind Fusion Tip. The novel standard in RF microneedling, the Potenza devices four modes (monopolar or bipolar, conveyed at either 1 MHz or 2 MHz frequency), provides more personalized microneedling treatments for patients than ever before, which permits practitioners to convey both shallow and deep treatments on a single system. The devices monopolar RF mode conveys energy across a big area of tissue for deep heating and skin tightening by way of soft tissue coagulation, not only on the face but also anywhere on the body.

In October 2020, Cynosure declared the U.S. and Canadian introduction of FlexSureTM, the most-recent inclusion to its best-in-class TempSure 300-watt platform and the worlds earliest wrappable radiofrequency (RF) applicator for malleable, hands-free, non-invasive RF treatments. With its rare peel-and-stick single-application applicators, the body-boosting FlexSure treatment conveys deep tissue heating to numerous body parts, inclusive of the abdomen, flanks, back, arms, buttocks, thighs, and above the knees. Accessible in numerous sizes, each equipped with six customizable zones and real-time temperature-sensing capacities, the FlexSure device permits practitioners to carry out constant, quick, and efficient treatments in just 15 minutes per body area.

Key Takeaways

Geographically, North America Anti-Aging Products and Therapies Market accounted for the highest revenue share in 2021 and it is poised to dominate the market over the period 2022-2027 owing to the soaring awareness of aging signs resulting in the application of anti-aging therapies like liposuction and increasing obesity in the North American region.

Anti-Aging Products and Therapies Market growth is being driven by the expanding population of the elderly, surging demand for cosmetic products, and the emerging beauty consciousness amidst youth worldwide resulting in the application of anti-aging therapies like liposuction. However, the binding rules and regulations imposed by the government in endorsing novel products and the fluctuations in the accessibility of raw materials are directly impacting the ultimate price of products which is one of the major factors hampering the growth of the Anti-Aging Products and Therapies Market.

Anti-Aging Products and Therapies Market Detailed Analysis on the Strength, Weakness and Opportunities of the prominent players operating in the market will be provided in the Anti-Aging Products and Therapies Market report.

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Anti Aging Market

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Anti-Aging Products and Therapies Market Size Estimated to Reach $93.2 Billion by 2027 - Digital Journal

Recommendation and review posted by Bethany Smith

image:zebrafish notochord nuclei at 15-somite stage. Grey: nuclear DNA (DAPI). Color: histone H3K9me3 view more

Credit: Phong Nguyen, Franka Rang & Kim de Luca. Copryight Hubrecht Institute.

How is the activity of genes regulated by the packaging of DNA? To answer this question, a technique to measure both gene expression and DNA packaging at the same time was developed by Franka Rang and Kim de Luca, researchers from the group of Jop Kind (group leader at the Hubrecht Institute and Oncode Investigator). This method, EpiDamID, determines the location of modified proteins around which the DNA is wrapped. It is important to gather information about these modifications, because they influence the accessibility of DNA, thereby affecting the gene activity. EpiDamID is therefore valuable for research into the early development of organisms. The results of the study are published in Molecular Cell on April 1st 2022.

In order to fit DNA into the nucleus of a cell, it is tightly packed around nuclear proteins: histones. Depending on the tightness of this winding, the DNA can be (in)accessible to other proteins. This therefore determines whether the process of gene expression, translation of DNA into RNA and eventually into proteins, can take place.

DNA packaging determine gene activity

The tightness of DNA winding around histones is regulated by the addition of molecular groups, so-called post-translational modifications (PTMs), to the histones. For example, if certain molecules are added to the histones, the DNA winding is loosened. This makes the DNA more accessible for certain proteins and causes the genes in this part of the DNA to become active, or expressed. Furthermore, proteins that are crucial for gene expression can directly recognize and bind the PTMs. This enables transcription: the process of DNA copying.

The regulation of gene expression, for instance through PTMs, is also known as epigenetic regulation. Since all cells in a body have the same DNA, regulation of gene expression is needed to (de)activate specific functions in individual cells. For instance, heart muscle cells have different functions than skin cells, thus require different genes to be expressed.

Analysis of single cells using EpiDamID

To understand how PTMs affect gene expression, first authors Franka Rang and Kim de Luca designed a new method to determine the location of the modifications. Using this approach, called EpiDamID, researchers can analyze single cells, whereas previous methods were only able to measure a large group of cells. Analysis on such a small scale results in knowledge on how DNA winding differs per cell, rather than information on the average DNA winding of many cells.

EpiDamID is based on DamID, a technique which is used to determine the binding location of certain DNA-binding proteins. Using EpiDamID, the binding location of specific PTMs on histone proteins can be detected in single cells. Compared to others, a great advantage of this technique is that researchers need very limited material. Furthermore, EpiDamID can be used in combination with other methods, such as microscopy, to study regulation of gene expression on different levels.

Future prospects

Following the development of this technique, the Kind group will focus on the role of PTMs from the point of view of developmental biology. Because single cells are analyzed using EpiDamID, only a limited amount of material is needed to generate enough data. This allows researchers to study the early development of organisms from its first cell divisions, when the embryo consists of only a few cells.

###

Publication

Rang, F. J.*, de Luca, K. L.*, de Vries, S. S., Valdes-Quezada, C., Boele, E., Nguyen, P. D., Guerreiro, I., Sato, Y., Kimura, H., Bakkers, J. & Kind, J. Single-cell profiling of transcriptome and histone modifications with EpiDamID. Molecular Cell, 2022.

*Authors contributed equally

Jop Kind is group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research and Oncode Investigator.

About the Hubrecht Institute

The Hubrecht Institute is a research institute focused on developmental and stem cell biology. It encompasses 21 research groups that perform fundamental and multidisciplinary research, both in healthy systems and disease models. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on Utrecht Science Park. Since 2008, the institute is affiliated with the UMC Utrecht, advancing the translation of research to the clinic. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). For more information, visit http://www.hubrecht.eu.

Experimental study

Cells

Single-cell profiling of transcriptome and histone modifications with EpiDamID

1-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Original post:
Learning from the single cell: A new technique to unravel gene regulation - EurekAlert

Recommendation and review posted by Bethany Smith

Cell and gene therapies are poised to have a major impact on the landscape of modern medicine, carrying the potential to treat an array of different diseases with unmet clinical need.

However, the number of approved, clinically adopted cell and gene therapies is mere compared to the amount that are currently in development. A major barrier for the translation of such therapies is the safe integration of therapeutic genes into the human genome. The insertion of therapeutic genes bears the risk of off target effects, or integration of the gene into an unintended location.

A number of different strategies have been proposed to mitigate this effect. The most recent body of work comes from a collaboration between Harvards Wyss Institute for Biologically Inspired Engineering, Harvard Medical School (HMS) and the ETH Zurich in Switzerland.

Published in Cell Report Methods, the research focused on identifying safe spots in the genome. These locations, known as genomic safe harbors (GSHs), are areas in the genome that meet the following criteria: they can be accessed easily by genome-editing strategies, are within a safe distance from genes that possess functional properties and permit expression of a therapeutic gene, only once it has landed in the harbor. A simple analogy is deciding which harbor to dock a boat there are many considerations, and these depend on the type of boat you are sailing, the weather conditions and ease of access.

The research team adopted computational strategies that enabled the identification of 2,000 predicted GSHs. From this initial identification, they successfully validated two of the sites both in vitro and in vivo using reporter proteins.

Technology Networks interviewed the studys first author, Dr. Erik Aznauryan, research fellow in the laboratory of Professor George Church at Harvard Medical School. Aznauryan dives into further detail on the history of GSH research, the methods adopted to validate the GSH sites and the potential applications of this research.

Molly Campbell (MC): Can you talk about the history of genomic safe harbor research, and how they were discovered?

Erik Aznauryan (EA): Three genomic sites were empirically identified in previous studies to support stable expression of genes of interest in human cells: AAVS1, CCR5 and hRosa26. All these examples were established without any a-priori safety assessment of the genomic loci they reside in.

Attempts have been made to identify human GSH sites that would satisfy various safety criteria, thus avoiding the disadvantages of existing sites. One approach developed by Sadelain and colleagues used lentiviral transduction of beta-globin and green fluorescence protein genes into induced pluripotent stem cells (iPSCs), followed by the assessment of the integration sites in terms of their linear distance from various coding and regulatory elements in the genome, such as cancer genes, miRNAs and ultraconserved regions.

They discovered one lentiviral integration site that satisfied all of the proposed criteria, demonstrating sustainable expression upon erythroid differentiation of iPSCs. However, global transcriptome profile alterations of cells with transgenes integrated into this site were not assessed. A similar approach by Weiss and colleagues used lentiviral integrations in Chinese hamster ovary (CHO) cells to identify sites supporting long-term protein expression for biotechnological applications (e.g., recombinant monoclonal antibody production). Although this study led to the evaluation of multiple sites for durable, high-level transgene expression in CHO cells, no extrapolation to human genomic sites was carried out.

Another study aimed at identifying GSHs through bioinformatic search of mCreI sites regions targeted by monomerized version of I-CreI homing endonuclease found and characterized in green algae as capable to make targeted staggered double-strand DNA breaks residing in loci that satisfy GSH criteria. Like previous work, several stably expressing sites were identified and proposed for synthetic biology applications in humans. However, local and global gene expression profiling following integration events in these sites have not been conducted.

All these potential GSH sites possess a shared limitation of being narrowed by lentiviral- or mCreI-based integration mechanisms. Additionally, safety assessments of some of these identified sites, as well as previously established AAVS1, CCR5 and Rosa26, were carried out by evaluating the differential gene expression of genes located solely in the vicinity of these integration sites, without observing global transcriptomic changes following integration.

A more comprehensive bioinformatic-guided and genome-wide search of GSH sites based on established criteria, followed by experimental assessment of transgene expression durability in various cell types and safety assessment using global transcriptome profiling would, thus, lead to the identification of a more reliable and clinically useful genomic region.

MC: If GSHs do not encode proteins, or RNAs with functions in gene expression, or other cellular processes what is their function in the genome?

EA: In addition to protein coding, functional RNA coding, regulatory and structural regions of the human genome, other less well understood and inactive DNA regions exist.

A large proportion of the human genome seems to have evolved in the presence of a variety of integrating viruses which, as they inserted their DNA into the eukaryotic genome over the course of million years, lead to an establishment of vast non-coding elements that we continue to carry to this day. Furthermore, partial duplications of functional human genes have resulted in the formation of inactive pseudogenes, which occupy space in the genome yet are not known to bear cellular functions.

Finally, functional roles of some non-coding portions of the human genome are not well understood yet. Our search of safe harbors was conducted using existing annotation of the human genome, and as more components of it are deciphered the identification of genomic regions safe for gene insertion will become more informed.

MC: Are you able to discuss why some regions of the genome were previously regarded as GSHs but are now recognized as non-GSHs?

EA: In the absence of other alternatives, AAVS1, CCR5 and hRosa26 sites were historically called GSHs, as they supported the expression of genes of interest in a variety of cell types and were suitable for use in a research setting.

Their caveats (mainly, location within introns of functional genes, closely surrounded by other known protein coding genes as well as oncogenes) however prevent them from being used for clinical applications. Therefore, in our paper we dont call them GSHs, and refer to our newly discovered sites as GSHs.

MC: You thoroughly scanned the genome to identify candidate loci for further study as potential GSHs. Can you discuss some of the technological methods you adopted here, and why?

EA: We used several publicly available databases to identify genomic coordinates of structural, regulatory and coding components of the human genome according to the GSH criteria we outlined in the beginning of our study (outside genes, oncogenes, lncRNAs etc.,). We used these coordinates and bioinformatic tools such as command lines bedtools to exclude these genomic elements as well as areas adjacent to them. This left us with genomic regions putative GSHs from which we could then experimentally validate by inserting reporter and therapeutic genes into them followed by transcriptomic analysis of GSH-integrated vs non-integrated cells.

MC: You narrowed down your search to test five, and then two GSHs. Can you expand on your choice of reporter gene when assessing two GSHs in cell lines?

EA: Oftentimes in research you go with what is available or what is of the most interest to the lab you are currently working in.

Our case was not an exception, and we initially (up until the T cell work) used the mRuby reporter gene as it was widely available and extensively utilized and validated in our lab at ETH Zurich back then.

When I moved to the Wyss Institute at Harvard, I began collaborating with Dr. Denitsa Milanova, who was interested in testing these sites in the context of skin gene therapy particularly the treatment of junctional epidermolysis bullosa caused by mutations in various anchor proteins connecting different layers of skin, among which is the LAMB3 gene. For this reason, we decided to express this gene in human dermal fibroblasts, together with green fluorescent protein to have a visualizable confirmation of expression. We hope we would be able to translate this study into clinics.

MC: Can you describe examples of how GSHs can be utilized in potential therapeutics?

EA: Current cell therapy approaches rely on random insertion of genes of interest into the human genome. This can be associated with potential side effects including cancerous transformation of therapeutic cells as well as eventual silencing of the inserted gene.

We hope that current cell therapies will eventually transition to therapeutic gene insertions precisely into our GSHs, which will alleviate both described concerns. Specific areas of implementation may involve safer engineering of T cells for cancer treatment: insertion of genes encoding receptors targeting tumor cells or cytokines capable of enhancing anti-tumor response.

Additionally, these sites can be used for the engineering of skin cells for therapeutic (as discussed earlier with the LAMB3 example) as well as anti-aging applications, such as expression of genes that result in youthful skin phenotype.

Finally, given the robustness of gene expression from our identified sites, they can be used for industry-scale bio-manufacturing: high-yield production of proteins of interest in human cell lines for subsequent extraction and therapeutic applications (e.g., production of clotting factors for patients with hemophilias).

MC: Are there any limitations to the research at this stage?

EA: A primary limitation to this study is the low frequency of genomic integration events using CRISPR-based knock-in tools. This means that cells in which the gene of interest successfully integrated into the GSH must be pulled out of the vastly larger population of cells without this integration.

These isolated cells would then be expanded to generate homogenous population of gene-bearing cells. Such pipeline is not ideal for a clinical setting and improvements in gene integration efficiencies are needed to help this technology easier translate into clinics.

Our lab is currently working on developing genome engineering tools which would eventually allow to integrate large genes into GSHs with high precision and efficiency.

MC: What impact might this study have on the cell and gene therapy development space?

EA: This study will hopefully lead to many researchers in the field testing our sites, validating them in other therapeutically relevant cell types and eventually using them in research as well as in clinics as more reliable, durable and safe alternatives to current viral based random gene insertion methods.

Additionally, since in our work we shared all putative GSHs identified by our computational pipeline, we hope researchers will attempt to test sites we havent validated yet by implementing the GSH evaluation pipeline that we outlined in the paper. This will lead to identification of more GSHs with perhaps even better properties for clinical translation or bio-manufacturing.

MC: What are your next steps in advancing this work?

We hope to one day translate our successful in vitro skin results and start using these GSHs in an in vivo context.

Additionally, we are looking forward to improving integration efficiencies into our GSHs, which would further support clinical transition of our sites.

Finally, we will evaluate the usability of our GSHs for large-scale production of therapeutically relevant proteins, thus ameliorating the pipeline of manufacturing of biologics.

Dr. Erik Aznauryan was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

View original post here:
Sailing the Genome in Search of Safe Harbors - Technology Networks

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7 Easy Ways to Transition Your Skin Care Routine for Spring - Vancouver Magazine

Recommendation and review posted by Bethany Smith

The following discussion of our financial condition and results of operationsshould be read in conjunction with our audited consolidated financial statementsand related notes and other financial information included elsewhere in thisAnnual Report on Form 10-K. The discussion contains forward-looking statements,such as our plans, expectations and intentions (including those related toclinical trials and business and expense trends), that are based upon currentexpectations and that involve risks and uncertainties. Our actual results maydiffer significantly from management's expectations. The factors that couldaffect these forward-looking statements are in Item 1A of Part I of this report.This discussion should not be construed to imply that the results discussedherein will necessarily continue into the future, or that any expectationsexpressed herein will necessarily be indicative of actual operating results inthe future. Such discussion represents only the best present assessment by ourmanagement.

Business Overview

We have generated aggregate product revenues from our two commercial businessesof $7.2 million and $7.1 million for the years ended December 31, 2021 and 2020,respectively. We currently have no revenue generated from our principaloperations in therapeutic and clinical product development.

Our products are based on multi-decade experience with human cell culture and aproprietary type of pluripotent stem cells, human parthenogenetic stem cells("hpSCs"). Our hpSCs are comparable to human embryonic stem cells ("hESCs") inthat they have the potential to be differentiated into many different cells inthe human body. However, the derivation of hpSCs does not require the use offertilized eggs or the destruction of viable human embryos and also offers thepotential for the creation of immune-matched cells and tissues that are lesslikely to be rejected following transplantation. Our collection of hpSCs, knownas UniStemCell, currently consists of 15 stem cell lines. We have facilitiesand manufacturing protocols that comply with the requirements of GoodManufacturing Practice (GMP) standards as promulgated by the U.S. Code ofFederal Regulations and enforced by the United States Food and DrugAdministration ("FDA").

COVID-19 Pandemic

The impact of the COVID-19 pandemic has been and will likely continue to beextensive in many aspects of society, which has resulted in and will likelycontinue to result in significant disruptions to the global economy, as well asbusinesses and capital markets around the world. Impacts to our business haveincluded a reduction in sales volume primarily from media sales in ourbiomedical market segment and professional channel sales in our anti-agingmarket segment, temporary or reduced occupancy of portions of our manufacturingfacilities, and disruptions or restrictions on our employee's ability to travelto such manufacturing facilities which caused minor delays in manufacturing. Ourmanufacturing facilities continue to operate as they are deemed essentialsuppliers in accordance with laws applicable to California and Maryland. We havetaken precautionary measures to better ensure the health and safety of ourworkers, including staggering employees' shifts and isolating at-risk employees.

The scope and duration of these delays and disruptions, and the ultimate impactsof COVID-19 on our operations, are currently unknown. We are continuing toactively monitor the situation and may take further precautionary and preemptiveactions as may be required by federal, state or local authorities or that wedetermine are in the best interests of public health and safety. We cannotpredict the effects that such actions, or the impact of COVID-19 on globalbusiness operations and economic conditions, may continue to have on ourbusiness, strategy, collaborations, or financial and operating results.

Market Opportunity and Growth Strategy

Therapeutic Market - Clinical Applications of hpSCs for Disease Treatments

With respect to therapeutic research and product candidates, we focus onapplications where cell and tissue therapy is already proven but where there isan insufficient supply of safe and functional cells or tissue. We believe thatthe most promising potential clinical applications of our technology are: 1)Parkinson's disease ("PD"); and 2) traumatic brain injury ("TBI"). Using ourproprietary technologies and know-how, we are creating neural stem cells fromhpSCs as a potential treatment of PD, TBI and stroke.

Our most advanced project is the neural stem cell program for the treatment ofParkinson's disease. In 2013 we published in Nature Scientific Reports the basisfor our patent on a new method of manufacturing neural stem cells which is usedto produce the clinical-grade cells necessary for future clinical studies andcommercialization. In 2014 we completed the majority of the preclinical researchestablishing the safety profile of NSC in various animal species includingnon-human primates. In June 2016 we published the results of a 12-monthpre-clinical non-human primate study, which demonstrated the safety, efficacyand mechanism of action of the ISC- hpNSC. In 2017 we dosed four patients inour Phase I trial of ISC-hpNSC, human parthenogenetic stem cell-derived neuralstem

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cells for the treatment of Parkinson's disease. We reported 12-month resultsfrom the first cohort and 6-month interim results of the second cohort at theSociety for Neuroscience annual meeting (Neuroscience 2018) in November 2018. InApril 2019, we announced the completion of subject enrollment, with the 12thsubject receiving a transplantation of the highest dose of cells. There havebeen no safety signals or serious adverse effects seen to date as related to thetransplanted ISC-hpNSC cells.

In August 2014 we announced the launch of a stroke program, evaluating the useof ISC-hpNSC transplantation for the treatment of ischemic stroke using arodent model of the disease. The Company has a considerable amount of safetydata on ISC-hpNSC from the Parkinson's disease program and, as there isevidence that transplantation of ISC-hpNSC may improve patient outcomes as anadjunctive therapeutic strategy in stroke, having a second program that can usethis safety dataset is therefore a logical extension. In 2015 the Companytogether with Tulane University demonstrated that NSC can significantly reduceneurological dysfunction after a stroke in animal models.

In October 2016 we announced the results of the pre-clinical rodent study,evaluating the use of ISC-hpNSC transplantation for the treatment of TBI. Thestudy was conducted at the University of South Florida Morsani College ofMedicine. We demonstrated that animals receiving injections of ISC-hpNSCdisplayed the highest levels of improvements in cognitive performance and motorcoordination compared to vehicle control treated animals. In February 2019, wepublished the results of the pre-clinical study in Theranostics, a prestigiouspeer-reviewed medical journal. The publication titled, "Human parthenogeneticneural stem cell grafts promote multiple regenerative processes in a traumaticbrain injury model," demonstrated that the clinical-grade neural stem cells usedin our Parkinson's disease clinical trial, ISC-hpNSC, significantly improvedTBI-associated motor, neurological, and cognitive deficits without any safetyissues.

Anti-Aging Cosmetic Market - Skin Care Products

Our wholly-owned subsidiary LSC develops, manufactures and offers for saleanti-aging skin care products based on two core technologies: encapsulatedextract derived from hpSC and specially selected targeted small molecules. LSC'sproducts include:

LSC's products are regulated as cosmetics. LSC's products are sold domesticallythrough a branded website, Amazon, ecommerce partners and through theprofessional channel (including dermatologists, plastic surgeons, medical, dayand resort spas).

Biomedical Market - Primary Human Cell Research Products

Our wholly-owned subsidiary LCT develops, manufactures and commercializesapproximately 200 human cell culture products, including frozen human "primary"cells and the reagents (called "media") needed to grow, maintain anddifferentiate the cells. LCT's scientists have used a standardized, methodical,scientific approach to basal medium optimization to systematically produceoptimized products designed to culture specific human cell types and to elicitspecific cellular behaviors. These techniques can also be used to produceproducts that do not contain non-human animal proteins, a feature desirable tothe research and therapeutic markets. Each LCT cell product is quality testedfor the expression of specific markers (to assure the cells are the correcttype), proliferation rate, viability, morphology and absence of pathogens. Eachcell system also contains associated donor information and all informed consentrequirements are strictly followed. LCT's research products are marketed andsold by its internal sales force, OEM partners and LCT brand distributors inEurope and Asia.

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Results of Operations

Comparison of the Years Ended December 31, 2021 and 2020

Product sales revenue for the year ended December 31, 2021 was $7.2 million,compared to $7.1 million for the year ended December 31, 2020. The increase wasprimarily attributable to a $342 thousand increase in sales in our biomedicalmarket segment, largely offset by a $294 thousand decrease in sales in ouranti-aging market during 2021 compared to 2020.

Our biomedical product sales continue to recover from the impacts of COVID-19 aspurchasing activity from our largest original equipment manufacturer customersincreases.

Our professional skin care products, which are largely marketed to medicalprofessionals and spas that offer walk-up retail, experienced a significantdecline in customer demand due to COVID-19 and the related restrictions as thesebusinesses have continued with limited or reduced operations during the yearended December 31, 2021. The impact of these restrictions was mitigated in-partby expanding our offering of professional skin care products through ourecommerce channel. Anti-aging product sales through our ecommerce channelremained consistent year-over-year.

Cost of Sales

Cost of sales for the year ended December 31, 2021 was $2.9 million, compared to$2.8 million for the year ended December 31, 2020. The increase was primarilyattributable to an increase in costs as a result of an increase in productsales. Profit margins have deteriorated for the year ended December 31, 2021 ascompared to 2020, largely as a result of rising raw materials and labor relatedcosts, and a scarcity of certain materials, principally plastics. In response,we have increased our supply of raw materials on hand and have, where possible,sourced materials from alternative vendors.

Cost of sales consists primarily of salaries and benefits associated withemployee efforts expended directly on the production of the Company's products,as well as related direct materials, general laboratory supplies and anallocation of overhead. We aim to continue refining our manufacturing processesand supply chain management to improve the cost of sales as a percentage ofrevenue for both LCT and LSC.

General and Administrative Expenses

General and administrative expenses for the year ended December 31, 2021 was$4.1 million, compared to $4.4 million for the year ended December 31, 2020. Thedecrease was primarily attributable to a decrease in personnel-related costs andstock-based compensation of $522 thousand, a $87 thousand decrease in consultingand servicing fees, and a $26 thousand decrease in investor relations fees,partially offset by an increase in impairment of intangible assets of$184 thousand, a $57 thousand increase in director and officer liabilityinsurance premiums, a $24 thousand increase in human resource related expenses,a $16 thousand gain on foreign currency exchange rate conversion, and a$15 thousand increase in filing fees.

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Selling and Marketing Expenses

Selling and marketing expenses for the year ended December 31, 2021 was$1.4 million, compared to $1.8 million for the year ended December 31, 2020. Thedecrease was primarily attributable to a $178 thousand decrease inpersonnel-related costs, sales commissions and stock-based compensation,primarily as a result of headcount reductions and grants from 2018 which wereissued and fully vested in 2021, and a $211 thousand decrease in marketing,advertising, and building related expenses, partially offset by a $17 thousandincrease in consulting and creative service fees. The reduction in marketing,advertising, and building related expenses was largely attributable to travelrestrictions as a result of COVID-19.

Research and Development Expenses

Research and development expenses for the year ended December 31, 2021 was$0.7 million, compared to $1.0 million for the year ended December 31, 2020. Thedecrease was primarily attributable to a $247 thousand decrease inpersonnel-related costs and stock-based compensation primarily as a result ofheadcount reductions and grants from 2018 which were issued and fully vested in2021, a $89 thousand decrease in materials and supplies related to clinicaltrial expenses, a $46 thousand decrease in consulting services, partially offsetby a $45 thousand increase in building and utilities related expenses and a$44 thousand decrease in our research and development tax credit related toqualifiable expenditures from our research and development activities of ourAustralia subsidiary, Cyto Therapeutics, which reduced research and developmentexpenses for years ended December 31, 2021 and 2020.

Our research and development efforts are primarily focused on the development oftreatments for Parkinson's disease, traumatic brain injury, liver diseases,stroke, and the creation of new GMP grade human parthenogenetic stem cell lines.These projects are long-term investments that involve developing both new stemcell lines and new differentiation techniques that can provide higher puritypopulations of functional cells. Research and development expenses are expensedas incurred and are accounted for on a project-by-project basis. However, muchof our research has potential applicability to each of our projects. As wecompleted Phase 1 of our clinical in June 2021, we do not anticipate significantinvestment in research and development efforts related to therapeutic andclinical product development efforts for the foreseeable future, or until suchtime that we initiate a Phase 2 clinical trial.

Other Income, Net

Other income, net, for the year ended December 31, 2021 was $1.0 million,compared to other income, net, of $94 thousand for the year endedDecember 31, 2020. The increase was primarily attributable to forgiveness of ourFirst Draw Loan and Second Draw Loan from the PPP, collectively totaling$1.1 million, partially offset by a decrease of $207 thousand for the change inthe fair value of the warrant liability during the prior year period. Thewarrants expired unexercised in March 2021 and, as such, no further change inthe fair value of the warrant liability will be recognized.

Liquidity and Capital Resources

As of December 31, 2021, we had an accumulated deficit of approximately$110 million and have, on an annual basis, incurred net losses and negativeoperating cash flows since inception. Substantially all of our operating losseshave resulted from the funding of our research and development programs andgeneral and administrative expenses associated with our operations. We incurrednet losses of $0.9 million and $2.7 million for years ended December 31, 2021and 2020, respectively. As of December 31, 2021, we had cash of $171 thousand,compared to $689 thousand as of December 31, 2020.

In May 2020, we received a first draw loan of $654 thousand from the PPP ("FirstDraw Loan") which provided additional liquidity to support our currentoperations. In March 2021, we received a second draw loan of $474 thousand fromthe PPP ("Second Draw Loan"). In June 2021, we applied for and receivedforgiveness of unpaid principal and accrued interest from our First Draw Loan inthe amount of $661 thousand. In August 2021, we applied for and receivedforgiveness of unpaid principal and accrued interest from our Second Draw Loanin the amount of $476 thousand. As of December 31, 2021, we are not eligible toreceive any additional funding, or have any further obligations, related to thePPP.

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Cash Flows

Comparison of the Years Ended December 31, 2021 and 2020

The following table provides information regarding our cash flows for the yearsended December 31, 2021 and 2020 (in thousands):

Net cash used in operating activities $ (1,297 ) $ (341 )Net cash used in investing activities

Operating Cash Flows

For the year ended December 31, 2021, net cash used in operating activities was$1.3 million, resulting primarily from our net loss of $899 thousand and netchanges in operating assets and liabilities of $823 thousand, consistingprimarily of an increase in accounts receivable of $441 thousand, inventory,net, of $268 thousand, and decrease in operating lease liabilities of $342thousand, partially offset by net non-cash adjustments of $425 thousand. For theyear ended December 31, 2020, net cash used in operating activities was$341 thousand, resulting primarily from our net loss of $2.7 million and changein fair value of warrant liability of $207 thousand, offset by non-cashadjustments of stock-based compensation expense of $1.3 million, operating leaseexpense of $265 thousand and depreciation and amortization of $253 thousand,coupled with net changes in operating assets and liabilities of $623 thousand.

Investing Cash Flows

Net cash used in investing activities for the year ended December 31, 2021 was$45 thousand, compared to $108 thousand for the year ended December 31, 2020.The decrease was attributable to a decrease in payments for patent licenses of$58 thousand and purchases of property and equipment of $5 thousandyear-over-year.

Financing Cash Flows

Net cash provided by financing activities for year ended December 31, 2021 was$0.8 million, compared to $0.7 million for the year ended December 31, 2020. Forthe year ended December 31, 2021, net cash provided by financing activitiesconsisted of $474 thousand in proceeds from our second draw loan under thePaycheck Protection Program, coupled with proceeds from a note payable from arelated party of $350 thousand. For the year ended December 31, 2020, net cashprovided by financing activities consisted of $654 thousand in proceeds from ourfirst draw loan under the Paycheck Protection Program.

Liquidity and Going Concern

Management continues to evaluate various financing sources and options to raiseworking capital to help fund our current research and development programs andoperations. We will need to obtain significant additional capital from sourcesincluding exercise of outstanding warrants, equity and/or debt financings,license arrangements, grants and/or collaborative research arrangements tosustain our operations and develop products. Unless we obtain additionalfinancing, we do not have sufficient cash on hand to sustain our operations atleast through one year after the issuance date. The timing and degree of anyfuture capital requirements will depend on many factors, including:

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Our failure to raise capital or enter into applicable arrangements when neededwould have a negative impact on our financial condition. Additional debtfinancing may be expensive and require us to pledge all or a substantial portionof its assets. Further, if additional funds are obtained through arrangementswith collaborative partners, these arrangements may require us to relinquishrights to some of its technologies, product candidates or products that we wouldotherwise seek to develop and commercialize on its own. If sufficient capital isnot available, we may be required to delay, reduce the scope of or eliminate oneor more of its product initiatives.

We currently have no revenue generated from our principal operations intherapeutic and clinical product development through research and developmentefforts. In addition, as we completed Phase 1 of our clinical in June 2021, wedo not anticipate significant investment in research and development effortsrelated to therapeutic and clinical product development efforts for theforeseeable future, or until such time that we initiate a Phase 2 clinicaltrial. There can be no assurance that we will be successful in maintaining ournormal operating cash flow and obtaining additional funds and that the timing ofour capital raising or future financing will result in cash flow sufficient tosustain our operations at least through one year after the issuance date.

Based on the factors above, there is substantial doubt about our ability tocontinue as a going concern. The consolidated financial statements were preparedassuming that we will continue to operate as a going concern. The consolidatedfinancial statements do not include any adjustments to reflect the possiblefuture effects on the recoverability and classification of assets or the amountsand classification of liabilities that may result from the outcome of thisuncertainty. Management's plans in regard to these matters are focused onmanaging our cash flow, the proper timing of our capital expenditures, andraising additional capital or financing in the future.

Critical Accounting Policies and Estimates

Our discussion and analysis of our financial condition and results of operationsis based upon our consolidated financial statements, which have been prepared inaccordance with accounting principles generally accepted in the United States.The preparation of these financial statements requires us to make estimates andassumptions that affect the reported amounts of assets, liabilities, revenues,expenses and related disclosures. On an on-going basis, we evaluate ourestimates and assumptions and we base our estimates on historical experience andon various other assumptions that are believed to be reasonable under thecircumstances, the results of which form the basis for making judgments aboutthe carrying values of assets and liabilities that are not readily apparent fromother sources. Actual results may differ from these estimates under differentassumptions and conditions.

Our significant accounting policies are more fully described in Note 1 to ourconsolidated financial statements included elsewhere in this Annual Report onForm 10-K. Our most critical accounting estimates include current andnon-current inventory, intangible assets, and stock-based compensation. Wereview our estimates and assumptions periodically and reflect the effects ofrevisions in the period in which they are deemed to be necessary. We believethat the following accounting policies are critical to the judgments andestimates used in preparation of our consolidated financial statements.

Intangible Assets

Our intangible assets consist of acquired patent licenses and capitalized legalfees related to the acquisition, filing, maintenance, and defense of patents andtrademarks. Amortization begins once the patent is issued by the appropriateauthoritative bodies. In the period in which a patent application is rejected orefforts to pursue the patent are abandoned, all the related accumulated costsare expensed. Our patents and other intangible assets are amortized on astraight-line basis over the shorter of the useful life of the underlyingpatent, which is generally 15 years, or when the intangible asset is rejected orabandoned. All amortization expense and impairment charges related to intangibleassets are included in general and administrative expense in our consolidatedstatements of operations.

Allowance for Excess and Obsolete Inventory

Our inventory, particularly within our biomedical market, consists of certainproducts that have a long or, when frozen, indefinite shelf life. In addition,future demand for our products is uncertain. Accordingly, at each reportingperiod, we estimate a reserve for allowance for excess and obsolete inventory.This estimate is computed using historical sales data and inventory turnoverrates, which are subjective in nature and fluctuate between periods. Theestablishment of a reserve for excess and obsolete inventory establishes a

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new cost basis in the inventory with a corresponding adjustment to cost ofsales. If we are unable to sell such inventory, any related reserves are reducedin the period of sale.

Stock-Based Compensation

We are required to measure and recognize compensation expense for allstock-based payment awards made to employees and consultants based on estimatedfair value. We estimate the fair value of stock options granted using theBlack-Scholes option-pricing model.

The determination of fair value of stock-based awards using the Black-Scholesoption-pricing model requires the use of certain estimates and subjectiveassumptions that affect the amount of stock-based compensation expenserecognized in our consolidated statements of operations. These include estimatesof the expected volatility of our stock price, expected option life, expecteddividends and the risk-free interest rate. Estimated volatility is a measure ofthe amount by which our stock price is expected to fluctuate each year duringthe expected life of the award. The expected option life is calculated using themid-point method as prescribed by accounting guidance for stock-basedcompensation. We determined expected dividend yield to be 0% given that we havenever declared or paid any cash dividends on our common stock, and we currentlydo not anticipate paying such cash dividends. The risk-free interest rate isbased upon United States Treasury securities with remaining terms similar to theexpected term of the share-based awards. If any of the assumptions used in theBlack-Scholes model change significantly, stock-based compensation expense maydiffer materially from what we have recorded in the current period.

Recently Issued Accounting Pronouncements

A description of recently issued accounting pronouncements that may potentiallyimpact our financial position and results of operations is disclosed in Note 1to our consolidated financial statements included in this Annual Report on Form10-K.

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INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com

Recommendation and review posted by Bethany Smith

Cell therapy research is the process of developing and testing whole cells that can be delivered to a patient to treat or cure a disease. Bone marrow transplants are one of the earliest cell therapies developed where bone marrow cell from a healthy person are used to repopulate the bone marrow of patients with some cancers. Newer cell therapies are cells that may be harvested from altered to target a disease or may be cells that are produced in a laboratory. The cell therapy is infused or transplanted into the patient as a treatment for a disease.

Genes are responsible for creating the proteins that control cellular processes. In many diseases, genetic instructions to code for the protein are missing or defective. Gene therapy research is the process by which scientists develop and test a DNA or RNA molecule that could be delivered back to the patient to treat the disease. Scientists first identify the impacted gene and the nature of the defect in patient cells. Depending on the nature of the defect, a gene therapy can be developed that is a proper copy of the gene or suppresses the defective copy of the gene from being used by the cell. The gene therapy is then put inside of a vector or a nanoparticle that can target the therapy to the proper cells when it is administered to the patient. Once delivered to the patient, the gene therapy provides genetic instructions for that can be used by the cell to correct or minimize the impact of the defect.

Researchers work with contract research organizations, like Charles River, by using gene and cell therapy services to prove efficacy and safety through various study types prior to submitting to agency for approval for first-in-human clinical trials. During and after approval of human trials, researchers continue to work with contract research organizations for clinical trial support, extended nonclinical safety studies and manufacturing support. Additional steps and studies are taken following clinical trials to ensure safety in the manufacturing stages before market release.

Link:
Cell and Gene Therapy Services | Charles River

Recommendation and review posted by Bethany Smith