Archive for January, 2020

Yanlan Li,1,2,* Xiangning Li,1,3,* Jiayao Qu,1,3 Dixian Luo,1,3 Zheng Hu1,3

1Translational Medicine Institute, the First Peoples Hospital of Chenzhou Affiliated to University of South China, Hunan 432000, Peoples Republic of China; 2Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, University of South China, Hunan 421001, Peoples Republic of China; 3National & Local Joint Engineering Laboratory for High-Through Molecular Diagnosis Technology, The First Peoples Hospital of Chenzhou, Hunan 432000, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Zheng Hu; Dixian LuoTranslational Medicine Institute, National & Local Joint Engineering Laboratory for High-Through Molecular Diagnosis Technology, The First Peoples Hospital of Chenzhou, Hunan 432000, Peoples Republic of ChinaTel/Fax +86 735 2343902Email hu48005@163.com; luodixian_2@163.com

Purpose: Colorectal cancer (CRC) is one of the major contributors to cancer mortality and morbidity. Finding strategies to fight against CRC is urgently required. Mutations in driver genes of APC or -catenin play an important role in the occurrence and progression of CRC. In the present study, we jointly apply CRISPR/Cas9-sgRNA system and Single-stranded oligodeoxynucleotide (ssODN) as templates to correct a heterozygous TCT deletion mutation of -catenin present in a colon cancer cell line HCT-116. This method provides a potential strategy in gene therapy for cancer.Methods: A Cas9/-catenin-sgRNA-eGFP co-expression vector was constructed and co-transfected with ssODN into HCT-116 cells. Mutation-corrected single-cell clones were sorted by FACS and judged by TA cloning and DNA sequencing. Effects of CRISPR/Cas9-mediated correction were tested by real-time quantitative PCR, Western blotting, CCK8, EDU dyeing and cell-plated clones. Moreover, the growth of cell clones derived tumors was analyzed at nude mice xenografts.Results: CRISPR/Cas9-mediated -catenin mutation correction resulted in the presence of TCT sequence and the re-expression of phosphorylation -catenin at Ser45, which restored the normal function of phosphorylation -catenin including reduction of the transportation of nuclear -catenin and the expression of downstream c-myc, survivin. Significantly reduced cell growth was observed in -catenin mutation-corrected cells. Mice xenografted with mutation-corrected HCT-116 cells showed significantly smaller tumor size than uncorrected xenografts.Conclusion: The data of this study documented that correction of the driven mutation by the combination of CRISPR/Cas9 and ssODN could greatly remedy the biological behavior of the cancer cell line, suggesting a potential application of this strategy in gene therapy of cancer.

Keywords: CRISPR/Cas9, ssODN, targeted gene editing, -catenin, colon cancer

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Cas9 Mediated Correction of -catenin Mutation and Restoring the | OTT - Dove Medical Press

The first biotech IPO of 2020 is here, and its for a company founded by two marquee names in oncology.

Cambridge-based Black Diamond Therapeutics filed on Friday for an IPO worth up to $100 million, becoming the first biotech of the decade to announce their intention to go public. Theyll use their proceeds to bring theirnew oncogene approach into the clinic.

The fact that an oncology biotech will be the first IPO of the new decade should come as little surprise. The calendar may have changed but the basic incentives that have driven record investment into and revenue from cancer drugs havent. Last years first IPO Poseida Therapeutics was also a cancer-focused biotech.

The first company launched out of Versants Basel-based discovery engine in December 2018, Black Diamond leveraged a high-profile C-suite and emerging science to rapidly rake in cash: Nearly $200 million within a year of their emergence from stealth mode, including an $85 million Series C last month.

The biotech is run by David Epstein and Elizabeth Buck, two former developers of the cancer drug Tarceva. The tech is a form of targeted oncology called allosteric therapies. These therapies are similar to other oncogenic drugs, such as kinase inhibitors, that inhibit the main binding site of a protein fueling cancer. It just does so by inhibiting a different part of the protein that may have mutated.

Black Diamond has spent over a year mapping these mutations, before raising the Series C on the promise of pushing their BDTX-189 drug for HER2 and EGFR mutations into a Phase I/II trial.

They promise to use the bulk of their IPO proceeds for the same goal, with some of the rest going to a preclinical glioblastoma program.

I-Mab Biopharma

The same day as Black Diamonds filing, Shanghai-based oncology startup I-Mab Biopharma updated their filing with detailed information. Theyre expected to be the years first biotech to price, on January 16.

I-Mabsannouncementcame in October, but the new filing offers more detail into a company that hopes to become the first Chinese biotech to list on the Nasdaq exchange since Zai Lab debuted in 2017.

They expect to price between $13 and $14 per share and raise $87 million. They will use the proceeds largely to fund a long list of clinical trials, while slotting significant portions for building their own manufacturing facility in China and research facilities in the US.

The teeming number of assets has to do with I-Mabs unusual but thus-far successful model. The company has spread widely, licensing a long list of assets from more established biotechs. They conduct proof-of-concept trials in the US, and then use the data for trials inChina. Once the drug is clinically validated in the US, I-Mab retains Chinese rights for further development and global out-licensing.

Most of these assets are in oncology including lead multiple myeloma asset TJ202 although TJ101 is a long-acting hormone for pediatric growth deficiency and TJ301 is an IL-6 for autoimmune disorders.

Its a model thats already gained over $400 million in private funding. Their Nasdaq bid reflects the growing importance of China, not only as a burgeoning market for established pharma companies but as a growing hub for drug development.

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The first biotech IPO of the new decade has landed and of course it's another cancer drug developer - Endpoints News

Axovant Gene Therapies (NASDAQ:AXGT) was upgraded by Zacks Investment Research from a hold rating to a buy rating in a research note issued on Monday, Zacks.com reports. The brokerage presently has a $5.50 price target on the stock. Zacks Investment Researchs price objective would suggest a potential upside of 8.48% from the companys current price.

According to Zacks, Axovant Sciences Ltd. is a biopharmaceutical company which focuses on the acquisition, development and commercialization of therapeutics for the treatment of neurodegenerative disorders. Its product candidate includes RVT-101 which is in different clinical trial for the treatment of Alzheimers disease and other forms of dementia. Axovant Sciences Ltd. is based in Hamilton, Bermuda.

Several other brokerages also recently commented on AXGT. Chardan Capital increased their price target on Axovant Gene Therapies from $10.00 to $15.00 and gave the company a buy rating in a report on Monday, October 28th. ValuEngine upgraded Axovant Gene Therapies from a hold rating to a buy rating in a report on Friday. One equities research analyst has rated the stock with a hold rating and ten have issued a buy rating to the stock. Axovant Gene Therapies currently has an average rating of Buy and a consensus price target of $24.66.

AXGT stock traded up $0.16 during midday trading on Monday, hitting $5.07. 64,342 shares of the company traded hands, compared to its average volume of 72,781. Axovant Gene Therapies has a twelve month low of $3.81 and a twelve month high of $19.60. The company has a quick ratio of 1.41, a current ratio of 1.41 and a debt-to-equity ratio of 0.69. The business has a 50 day simple moving average of $5.18 and a 200-day simple moving average of $6.20. The stock has a market capitalization of $112.81 million, a price-to-earnings ratio of -0.63 and a beta of 1.18.

Axovant Gene Therapies (NASDAQ:AXGT) last announced its quarterly earnings results on Friday, November 8th. The company reported ($0.61) EPS for the quarter, beating the consensus estimate of ($1.15) by $0.54. Equities research analysts forecast that Axovant Gene Therapies will post -3.56 EPS for the current year.

Several institutional investors have recently made changes to their positions in AXGT. BlackRock Inc. acquired a new stake in shares of Axovant Gene Therapies in the second quarter worth $1,482,000. Jane Street Group LLC grew its stake in shares of Axovant Gene Therapies by 28.8% in the second quarter. Jane Street Group LLC now owns 46,455 shares of the companys stock worth $289,000 after acquiring an additional 10,375 shares during the last quarter. Barclays PLC acquired a new stake in shares of Axovant Gene Therapies in the third quarter worth $65,000. Finally, Tower Research Capital LLC TRC grew its stake in shares of Axovant Gene Therapies by 955.3% in the second quarter. Tower Research Capital LLC TRC now owns 4,221 shares of the companys stock worth $27,000 after acquiring an additional 3,821 shares during the last quarter. Institutional investors and hedge funds own 14.80% of the companys stock.

Axovant Gene Therapies Company Profile

Axovant Gene Therapies Ltd., a clinical-stage gene therapy company, focuses on developing a pipeline of product candidates for debilitating neurological and neuromuscular diseases. The company's current pipeline of gene therapy candidates targets GM1 gangliosidosis, GM2 gangliosidosis, Parkinson's disease, oculopharyngeal muscular dystrophy, amyotrophic lateral sclerosis, and frontotemporal dementia.

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Axovant Gene Therapies (NASDAQ:AXGT) Rating Increased to Buy at Zacks Investment Research - Riverton Roll

IN the summer of 2019, a mother in Nashville, Tennessee in the United States, with a seemingly incurable genetic disorder finally found an end to her suffering by editing her genome.

Victoria Grays recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research gene therapy.

I have hoped for a cure since I was about 11, the 34-year-old said.

Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency.

Over several weeks, Grays blood was drawn so that doctors could get to the cause of her illness stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 pronounced Crisper a new tool informally known as a molecular scissors.

The genetically-edited cells were transfused back into Grays veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary, but theoretically, she has been cured.

This is one patient. This is early results. We need to see how it works out in other patients, said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

But these results are really exciting.

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease beta thalassemia.

She had previously needed 16 blood transfusions per year. Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified. But Crispr, invented in 2012, made gene editing more widely accessible.

It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

Its all developing very quickly, said French geneticist Emmanuelle Charpentier, one of Crisprs inventors and the co-founder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Gene cures

Crispr was the latest breakthrough in a year of great strides in gene therapy, a medical adventure that started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not, such as making normal red blood cells in Grays case or making tumour-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies bringing the total to eight approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

Twenty-five, 30 years, thats the time it had to take, he said. It took a generation for gene therapy to become a reality. Now, its only going to go faster.

Just outside Washington, at the US National Institutes of Health (NIH), researchers are also celebrating a breakthrough period.

We have hit an inflection point, said US NIHs associate director for science policy Carrie Wolinetz.

These therapies are exorbitantly expensive, however, costing up to US$2 million (RM8.18 million) meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion and fighting a general infection.

You cannot do this in a community hospital close to home, said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to Massachusetts Institute of Technology (MIT) researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

In this Oct 10, 2018, photo, He speaks during an interview at his laboratory in Shenzhen, China. The scientist was recently sentenced to three years in prison for practicing medicine illegally and fined 3 million yuan (RM1.76 million). AP

Bioterrorism potential

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who dont necessarily share the medical ethics of Western medicine.

In 2018 in China, scientist He Jiankui triggered an international scandal and his excommunication from the scientific community when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA (deoxyribonucleic acid) of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV (human immunodeficiency virus), even though there was no specific reason to put them through the process.

That technology is not safe, said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr scissors often cut next to the targeted gene, causing unexpected mutations.

Its very easy to do if you dont care about the consequences, he added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species, e.g. malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesnt believe in the more dystopian scenarios predicted for gene therapy, including American biohackers injecting themselves with Crispr technology bought online.

Not everyone is a biologist or scientist, she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies crops?

Charpentier thinks that technology generally tends to be used for the better.

Im a bacteriologist -- weve been talking about bioterrorism for years, she said. Nothing has ever happened. AFP Relaxnews

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Gene editing breakthroughs that cured genetic diseases in 2019 - The Star Online

I call it peak bleak: its right about now when all of us beyond our thirties are really thinking that our skin looks particularly knackered. Its central heating, its illness, its being overtired, over worked and over partied and it makes for a combination of low-level dryness and dullness that no illuminating make-up seems to ameliorate (highlighter on a dehydrated cheekbone is never flattering). Hydrating sheet masks, richer moisturisers and glycolic peels make some strides to improve exhausted skin, but the thing Ive found to make the single biggest difference is microneedling.

Im not referring to deep derma rolling treatments here (brilliant as they are for long term rejuvenation, they do entail some down-time) but rather facials - and at-home facial treatments - that incorporate a level of gentle needling. What gives these facials the edge on less than young skin is twofold: firstly, as leading facialist Sarah Chapman explains, microneedling is electronic precision engineering, creating thousands of needle columns into the skin, each one penetrating into the dermis layer to rejuvenate your skin by supercharging collagen production, which in turn reduces the appearance of wrinkles, fine lines and improves the overall texture of your skin. Which goes to say that it gets right to the root cause of a bleak complexion and directly revs it up.

Secondly, needling is astoundingly effective at aiding absorption of serums applied both during and after treatment (thanks to those tiny channels that Chapman described) and, quite frankly, the more hydrating serum you can get your skin to suck up, the better in terms of improving its plumpness and luminosity in both the short and long term.

Treatment wise, the best facial that incorporates needling is Chapmans Stem Cell Collagen Therapy treatment, 210. Chapman calls it the ultimate youth-boosting facial, a punchy claim that I must say its hard to dispute. The needling itself feels like nothing more than an electric toothbrush being whisked over the skin as it pushes in concentrated doses of botanical stem cells and peptides, while the finishing Dermalux red-light therapy adds to the impressive post-treatment glow. Whether you're looking for a facial that really delivers pre- or post-party, or simply want a fix to rid you of lacklustre skin, this is the facial to book.

At home, I like to needle every other day with a gentle manual 0.2-0.3mm roller: freshly rolled skin sucks in serum incredibly satisfyingly, and the increased microcirculation it induces adds to the don't you look well effect. Environs CIT Roller, 59, and Nannette de Gaspes Art of Noir Roller Noir, 35, both manage to be effective yet gentle. Do not be tempted to buy a cheap roller on Amazon or eBay; the needles are often hooked, which can rip the skin leading to redness and inflammation.

Roller Noir

35.00

Skinesis Intense Hydrating Booster

64.00

B-Hydra Intensive Hydration Serum

40.00

Peptide Veil

115.00

Rolling can be done on bare skin, but I find it more effective and comfortable to apply a thick layer of hydrating serum first, slathering on three times the amount Id usually apply of either Skinesis Intense Hydrating Booster, 64, or Drunk Elephant B-Hydra Intensive Hydrating Serum, 44. Start at the forehead and roll over each area three or four times horizontally, three or four times vertically, then diagonally in each direction, before moving onto the cheeks and finally chin and neck. Finish with a thick veil of cream (Im loving Decree Peptide Emollient Veil, 115) and youll wake up to skin that is anything but bleak.

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Why microneedling facials really work to revive 40+ skin - harpersbazaar.com

Fertility expert Marcelle Cedars discusses the future of reproductive medicine.

By Ariel Bleicher UCSF Magazine

Advances in medicine and public health have dramatically extended the human lifespan. Our hearts, lungs, and other vital organs now last 79 years on average. For women, however, the ovaries which stop functioning at an average 51 years remain a stubborn exception. That may soon change, says fertility expert Marcelle Cedars, MD, during a conversation on the future of reproductive medicine.

There are two aspects. One is qualitative. As a woman ages, the quality of her eggs meaning their capacity to make a healthy baby declines. We understand very little about what causes this decline. If we understood that process better, we could dramatically impact fertility success rates.

The other aspect is quantitative. Women are born with a finite number of eggs, and they lose those eggs throughout their lifetime. In fact, that rapid decline in egg numbers starts even before birth. Theres a peak in utero of five to six million eggs. At birth, a woman has only about 1.5 million eggs; at the time of puberty, about 500,000. Through genetics research, were learning that the rate of this decline and the variability from woman to woman is largely driven by ones genes.

Exactly. But what if we could use your genetics and other biological data to understand your unique fertility risks and develop therapies specifically for you or for groups of women like you? This approach is called precision medicine. It has made a huge impact in the world of cancer in terms of improving survival rates. But in the field of reproductive health, precision medicine is still in its infancy.

Potentially. If we can pinpoint the mechanisms of ovarian aging, we could potentially develop a therapy that enables you to still have healthy eggs into your 50s, possibly your 60s. But just because we can do something doesnt always mean we should do it. We know that as women get older, pregnancies are more complicated. You have higher risk for things like high blood pressure, diabetes, and preterm labor. There are many downstream implications, both for the mothers health and the childs.

I dont think the goal should be to enable women to get pregnant into their 60s. Rather, we want women to have the best reproductive lifespan possible to be able to have children when they want to and to not have children when they don't want to and to have a society that supports women across that spectrum.

Were starting to believe that some of the same cellular mechanisms that underlie general aging might also control ovarian aging. This revelation makes the ovary even more interesting to study because its early demise could be a unique window into the bodys aging process. If we can identify cases of accelerated ovarian aging and understand the underlying causes, we might be able to improve not only reproductive function in individual women but also overall health and longevity for all women.

Samesex couples having genetically related children is probably on the horizon. Scientists are learning how to take skin cells or blood cells and turn them into stem cells, which can then be turned into eggs or sperm. Thats not science fiction; its already happening. We just need to figure out how to do it well and safely in humans.

Well probably also see germline engineering. Thats the process of editing genes in reproductive cells or embryos. It has the potential to cure disease before birth. This technology is here. But will society be ready to accept it? A lot of questions need to be answered before its put to use. In addition to technical hurdles, there are innumerable social issues. For instance, if we can eliminate a certain disease, will there be less focus on treatments for people who still have the disease? And what about access to care and social equity? Who would be able to afford these procedures? How will they be applied?

Restrictions are currently preventing the U.S. government from funding research that involves the manipulation of human embryos. As a result, funding for reproductive science is low, which has driven a lot of experts out of academia. If we want to see a revolution in reproductive health, like whats happening with precision cancer medicine, we need to invest in the development of scientific knowledge that will move this field forward.

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The End of Infertility Is in Sight - UCSF News Services

If your new year's resolutions includeorganizingthe skincare products taking over your medicine cabinet, checking the expiration dates on your makeup, and tossing those almostempty shampoo and conditioner bottles that have been taking up space in your shower since 2018, I've got some bad news for you:You're probably going to hit pause on reassessing your beauty routineuntil February.Thanks to January'snew beauty product launches, your collection is definitelygoing to grow this month.

Tatcha'sinnovative, travel-friendly serum stick will be the one skincare product you pack for every trip you take, while OLEHENRIKSEN'scleanseris like a refreshing fruit juice for your face. As for makeup, IT Cosmetics has created an uber-comfortable matte lipstick, and Hourglass' concealer is a long-wear formula that doesnotcrease.

Get exclusive discounts, celeb inspo, & more.

RELATED:All the Products Our Beauty Editors Loved Using in December

When it comes to haircare, the drugstore is the place to be. Celebrity hairstylist Kristin Ess has added fragrance-free products to her affordable namesake haircare line, and Pantenejust expanded its Gold Series Collection for natural hair with a hydrating, protective cream specifically formulated for braided styles.

While thesenew haircare, skincare, and makeup products are exciting, there's no question that having so many options can be overwhelming. That's why we've done the work topickout the top 20 worth spending your hard-earned coin on.

VIDEO:What Every Beginner Needs to Have in Their Makeup Kit

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The 20 Best New Beauty Products That'll Help You Kick 2020 Off Right - InStyle

Being jam-packed with various essential nutrients like folate, Vitamin A, beta carotene, etc., carrot and ginger can offer you both health and beauty benefits. These kitchen companions can help diabetics to control their blood sugar level and have many more medicinal uses. These vegetables are known to treat ailments like cough and cold, nausea, anxiety, etc. From strengthening your immune system to protecting your against cancer and boosting collagen production, carrot ginger juice can do it all for you. Below, we give you more than one reason to add this juice to your daily diet.

Being a rich source of vitamin A, carrot ginger juice helps in strengthening your immune response. This nutrient is required to form white blood cells in the bone marrow stem cells. Notably, WBC is a significant component of your bodys defence system. So, it is advised to drink this juice on a daily basis. You can add oranges in the juice to make it a bit tasty.

For a healthy skin texture and tone, vitamin C and E are needed. Carrot ginger juice is a rich source of both nutrients. Your skin requires collagen for better elasticity, texture, and strength. Vitamin C helps in the synthesis of this protein and holds the body together. Even if you have a skin wound, you can have this drink and get rid of the problem soon. On the other hand, vitamin E protects your skin from the harmful effects of UV rays.

Carrot ginger juice is a detox drink that is jam-packed with vitamin C, a nutrient that is already linked to providing protection against cancer. The juice contains a compound called gingerol, that can potentially reduce your risk of developing breast, ovarian, and stomach cancers. This is what research published in the European Journal of Pharmacology reveals.

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Want to Rev up Your Immunity And Improve Skin Health? Consume Carrot Ginger Juice - India.com

The reconstitution of the blood system in humans holds great therapeutic potential to treat many disorders, like blood cancers, sickle-cell anemia and others. Successful reconstitution requires the transplantation and engraftment of hematopoietic (or blood) stem cells (HSCs), which after reaching their niche, start producing all types of blood cells, including platelets, white and red blood cells.

In current clinical practice, this is carried out by infusing HSCs obtained from a matched donor who is immunologically compatible with the patient in need (allogeneic transplantation), or by the expansion of the patients own HSCs in the lab, and then re-infusing them back into the patient (ex-vivo, autologous transplantation).

However, the utility of both routes is currently limited by a number of factors. First, in the case of allogeneic transplantation, the scarcity of matched donors significantly increases the waiting time, which could be detrimental to the patient. Second, the ex vivo expansion of HSCs, whether allogeneic or autologous, has been a challenging task, due to the limited proliferative potential these cells exhibit in culture. These limitations have raised the need for other sources of HSCs that would alleviate the need for matched donors and yield functional HSCs in large quantities.

In 2007, Professor Shinya Yamanaka and colleagues demonstrated that somatic cells, like skin fibroblasts, could be reprogrammed back to a cellular state that resembled human embryonic stem cells (hESCs), which are a group of cells found in the blastocyst-stage human embryo and contribute solely to the development of the human fetus during pregnancy. The reprogrammed cells were termed, Induced Pluripotent Stem Cells (iPSCs).

In addition to their developmental potential, human ESCs and iPS cells display unlimited proliferative potential in culture, which makes them an ideal source of cells for regenerative medicine in general and for hematopoietic differentiation to obtain possibly unlimited quantities of HSCs. Therefore, there has been a growing interest to harness the potential of these cells for treating blood disorders.

However, advancement in deriving functional HSCs from human pluripotent stem cells has been slow. This has been attributed to incomplete understanding of the molecular mechanisms underlying normal hematopoiesis. In this review, the authors discuss the latest efforts to generate HSCs capable of long-term engraftment and reconstitution of the blood system from human pluripotent stem cells. Stem cell research has witnessed milestone achievements in this area in the last couple of years, the significance of which are discussed and analyzed in detail.

The authors additionally discuss two highly important families of transcription factors in the context of hematopoiesis and hematopoietic differentiation, the Homeobox (HOX) and GATA proteins. These are thought of as master regulators, in the sense of having numerous transcriptional targets, which upon activation, could elicit significant changes in cell identity. The authors hypothesize that precise temporal control of the levels of certain members of these families during hematopoietic differentiation could yield functional HSCs capable of long-term engraftment.

The authors conclude the review with a summary of future perspectives, in which they discuss how newly developed techniques, like the deactivated-Cas9 (dCas9) gene-expression control system, can be utilized during the course of hematopoietic differentiation of pluripotent stem cells for precise temporal control of the aforementioned master regulators to achieve functional HSCs.

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Making Blood On Demand: How Far Have We Come? - Eurasia Review

Victoria Beckham aims to "create a brand of the future" with Victoria Beckham Beauty.

The former Spice Girl launched her eponymous beauty brand last year, later expanding her label to include skincare, and the 45-year-old fashion designer says her intention was to create products that are sustainable and not made from toxic formulas, whilst being "inclusive" for all skin tones.

The mother-of-four told the February issue of Harper's Bazaar UK: "I've been obsessed with make-up and skincare and wellness for longer than I can remember."But I couldn't find what I wanted - clean beauty.

"What is that, even? It's a real grey area.

"I wanted to create a brand of the future - focusing on what's in the formulas but then also sustainability.

"The other thing that was key was making sure it was very inclusive - whether it's make-up or skincare, this is for every skin type and tone, and for both women and men."

In November, Victoria - who has Brooklyn, 20, Romeo, 17, Cruz, 14 and Harper, eight, with retired soccer star husband David Beckham - released her Cell Rejuvenating Priming Moisturiser in collaboration with Professor Augustinus Bader, the German stem-cell scientist behind The Cream, which was named as one of 2019's most popular skincare products.

Bader's product features a patented Trigger Factor Complex that works to jumpstart your skin's repair and renewal functions to heal skin faster and in turn, improve the appearance of fine lines and wrinkles, and as a fan of the cream herself, Victoria was thrilled to work with the scientist.

She said: "It's been a dream to develop, with Augustinus, a priming moisturiser that works to improve the health of my skin and gives me that fresh, natural glow that I love."

The priming moisturiser is a hybrid product that combines primer with moisturiser, and is inspired by Victoria's own skincare routine.

Victoria's product implements Bader's Trigger Factor Complex technology, as well as the lipids, vitamins, and amino acids found in his original cream, but with the added benefit of also smoothing skin so it's prepped for make-up application.

Bader explained: "It's the first priming moisturiser of its kind to care for your skin cells while also preparing your skin for makeup application."

The cream has a lightweight texture that can be work alone to give skin a radiant finish or under make-up, which according to Victoria, "will enhance your products."

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Victoria Beckham Dreams That her Beauty Line Will Become 'Brand of the Future' - Al Bawaba

How good does it feel to reach for chocolate or fast food after a particularly stressful day? We cant deny the instant satisfaction of biting into a greasy burger but that instant gratification may be doing more harm than good.

According to Dr. Anna Cabeca, physician and Amazon #1 best selling author of "The Hormone Fix," when we are first under some sort of stress in our fight, flight or freeze mode, our body releases cortisol (our stress hormone). Over time with the chronic persistent state of "fight, flight or freeze" our body produces very high amounts of cortisol. This results in a feeling of disconnection and burnout and inflammation, which only worsens with sugar and fat.

RELATED: How Famous Men Fight Stress

So how do we reverse and prevent burnout and the disconnect that comes with it while satisfying our urge to grab a snack after a long day? We spoke to health and nutrition experts to get their thoughts on the best foods to fight stress and dont worry, (some!) chocolate is actually OK.

While coffee may be your first inclination during a particularly stressful afternoon at the office, you may want to swap out the hard stuff for something a little more green. Green tea is one of the best foods/drinks for fighting stress and anxiety while increasing focus due it's L-Theanine content, explains Forrest Przybysz, MBA and owner of Nootropics Resource. L-Theanine is a natural amino acid found primarily in green and black teas that has been linked to several health benefits including reduced anxiety, lower stress levels, increased focus and better sleep quality.

According to Jared Heathman, MD, meals high in carbohydrates and sugar spike glucose, which initially gives us a rush of endorphins, which is why those greasy burgers are so satisfying after a long day. This can feel good initially, but the resulting crash can leave us feeling fatigued and irritable, explains Heathman, when our mind feels fatigued and irritable, it can't adequately cope with stress levels. This can lead to a worsening in our mood and anxiety. Eating high fiber foods like vegetables with each meal can assist in maintaining glucose uptake in a slow, steady fashion.

Organ meat from pasture-raised animals aresome of the most nutrient-dense foods you will find Beef Liver and heart especially, says Erik Levi, functional nutritional therapy practitioner, They are loaded with brain-healthy nutrients like B-Vitamins, choline, and omega 3, and high-quality protein.

Yes, plain old water may just be the key to feeling less stressed throughout your day. Dehydration leads to both mental and physical stress. Your body literally needs water to survive and when it doesn't get enough, metabolic processes begin to shut down and this can affect your well-being. Levi recommends getting at least 1/2 your body weight in ounces per day.

RELATED: Foods That Affect Your Bedroom Performance

See? You can still get your chocolate fix without sacrificing your mental wellbeing.Studies have tied the polyphenols and micronutrients in cacao to both stress relief and lower instances of cardiac disease keep your heart rate low, keep stress low. Look for at least 70 percentcacao, with low to no sugar chocolate for this effect.

This is one of the highest sources of good fats you're going to find. Although fat has been demonized for years, modern research has found that fat-rich foods like butter deliver lots of vitamin A-retinol, which is involved in hundreds of metabolic processes in the body, says Levi. Its also a good source of butyrate, which is a small-chain fatty acid made in the colon that helps your body's immune system and overall digestive health, which both help physically keep your stress level low.

This is another food that has been demonized through the years, but according to Levi, eggs from pasture-raised chickens who eat a real chicken diet and not grains are one of the best sources of choline you can find. Choline helps make dopamine in the brain, which you need more of to mentally deal with stress. You also get lots of omega-3 and B12. explains Levi.

Omega-3 fatty acids, which fish like salmon are excellent sources of, actively work to suppress the development of stress hormones, as well as feelings of depression. According to Jamie Bacharach, licensed medical acupuncturist and health expert, this is thanks to the anti-inflammatory effects of omega-3 fatty acids, which in supplement form have been proven to provide a 20 percentreduction in anxiety versus placebo groups. As salmon possesses high amounts of omega-3 fatty acids, it only needs to be enjoyed once a week or so in order to take advantage of its anti-stress benefits.

Complex carbohydrates like oatmeal can help to promote serotonin production, directly boosting feelings of happiness and diminishing feelings of stress, explains Bacharach. Unlike regular carbohydrates, a complex carb like oatmeal won't cause a spike in blood glucose, which can lead to a rise in feelings of stress or tension.

It's not a coincidence that turkey has a reputation for making people feel fatigued or relaxed. Turkey contains tryptophan, an amino acid which helps to regulate the production of serotonin a bodily chemical that promotes feelings of happiness and calm, says Bacharach. Tryptophan supplements in and of themselves have demonstrated in scientific studies that they can make people more agreeable, or less argumentative, helping to diminish feelings of anger or stress.

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Saturday Jan 4, 2020

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By January, many people are saturated with the parties, get-togethers, and drinking that comes with the holidays. Odds are at some point in the 2019 holiday season you had a bit of a hangover from too much champagne, egg nog, or cocktails.

In comes the dry-January trend to help bring in the new year by putting a brake on alcohol for the whole month. EDGE turned to NYC neuropsychologist, Dr. Sanam Hafeez, for insight into the benefits of taking a month-long booze-free challenge for a fresh start to the new year.

1. You Save Money On Alcohol.

According to Fortune magazine in 2018, overall price averages for alcoholic beverages increased thanks to craft cocktail trends. The same can be expected for 2019. A survey by OnePoll last year estimated that Americans' social spending around the holiday season more than doubles and alcohol is part of that spending. So if your wallet has felt the alcohol as much as you have this season, the math could be reason enough to pause the drinks and close your tab for a month.

"Think of the stress you could take off your back by cutting back on the money you spend on alcohol during January," says Dr. Hafeez. "An average person could hit the bar twice a week, spending about $30-$75 dollars depending on what drinks you are purchasing. Add tip, and your expenses for a night of drinking could reach or surpass $100 easily. Throughout a single month, this could cost you a good chunk of change." Add more money saved if you're also a weekend social drinker. Add way more money if you are inclined to purchase bottles in the VIP section for hundreds of dollars.

2. In The Absence of Alcohol, Your Skin Rejuvenates.

While alcohol consumption doesn't directly cause acne, it destabilizes hormone levels and immune functions, which lead to dull skin, breakouts, flushed complexion, and puffiness. If you like to "ros all day" or consume mixed drinks with more sugars, syrups, and other additives, you can start seeing the toll of these habits on the texture and tone of your skin. "A part of being successful when reducing alcohol intake is the compliments you receive, the energy you feel, and the changes you see in the mirror. These can all be fuel to help you live a healthier life in the new year," says Dr. Hafeez.

(Source:Getty Images)

3. Get A Headstart on Your Weight Loss Resolution.

Research in the Journal of Obesity says people who don't drink, eat less, simply because alcohol heightens the senses and numbs reasoning. It makes the sauce and cheese on a pizza or those late-night tacos tastier. When you remove alcohol intake, it diminishes the calories you consume.

Think about three beers or glasses of wine at about 150 calories each. Those calories add up. Dr. Hafeez explains that "any person seeking help with weight management has heard the advice 'don't drink your calories,' alcoholic beverages are some of the drinks that most easily overwhelm your caloric consumption. Drinking less, or not at all for a month, will leave you with improved blood sugar and cholesterol levels and help optimize your organ function, which will help you be more active and in a better mental state."

4. More Energy, More Creativity, More Endurance

The last thing you want is to be tired into the new year. "One great benefit of going alcohol-free is renewed energy. You will not be giving up your day to recover from last night's drinking. Waking up earlier will help you establish better morning habits that prime your brain for productivity and creativity," says Dr. Hafeez. "You will also see improved concentration and endurance as the day goes on because your energy level will not be in a deficit before the day even begins," she says.

5. Less Alcohol Can Lead to Improvement in Depression.

Depression is a mood disorder that can cause feelings of sadness, rage, grief, and emptiness. More than 16 million Americans suffer from Major Depression Disorder while anxiety disorders affect about 40 million adults according to the Anxiety and Depression Association of American.

"The problem comes when depression and anxiety, even at the mild levels, begin to be alleviated momentarily with alcohol. This can become dangerous because it will work in a negative cycle. Alcohol intake will get worse which will heighten the depression which will cause the person to drink more," explains Dr. Hafeez. The NYC psychologist explains that alcohol is actually a depressant and it affects the neurotransmitters in the brain.

"Seratonin is a neurotransmitter that helps us feel joyful and stabilizes our mood. Drinking alcohol can temporarily boost serotonin levels, therefore making you feel upbeat, but the long-term excessive consumption of alcohol can actually lower serotonin levels, and therefore either cause or worsen depression," she says.

6. Better Sleep

Alcohol affects your sleep pattern by inhibiting your REM sleep and affects your circadian rhythm. "REM sleep is incredibly important to the quality of your rest. When blocked by alcohol, you could lose out on the most restorative part of your sleep, which can affect the way you think, concentrate, and process information the next day," explains Dr. Hafeez. Another issue with alcohol is that it makes you wake up during the night to go to the bathroom.

"Alcohol is a diuretic, meaning an agent that prompts the passing of urine. This means that at nighttime, instead of sleeping throughout the night, you may need to get up repeatedly to relieve yourself. This will make it even harder to get the rest you need. In the absence of alcohol, your sleep is more comfortable and energizing," says Dr. Hafeez.

7. More Time for Yourself and New Friends

"It is important to note that when our friendships and relationships rely on social drinking, a booze-free month can affect how those interactions happen. While we have more time and energy, we might need to invest it in ourselves or new friends. This is not to say that you have to break up with your friends when you pause the alcohol, but it means you can try new activities and endeavors with new people and plant new friendships as well," explains Dr. Hafeez.

The NYC psychologist also talks about the opportunity to focus on you, explaining that "self-care is important yet often neglected over a good night out for drinks. Suddenly, happy hour is not an option, but a fitness class after work is, or a workshop on a topic that interests you. The time will add up, and you can use it to promote your self-confidence and personal development.

A Cautionary Note From The Expert.

"One thing to consider is that people who label themselves "social drinkers" may feel these improvements within days. Meanwhile, people who battle with alcoholism can often cause harm to themselves if they decide to stop drinking cold turkey. If you are a frequent/binge drinker, speak with your physician before abruptly ceasing alcohol consumption.

Committing to going without alcohol may reveal there actually is a bigger issue going on. "If someone can't last the week without alcohol and feels physical repercussions like nausea, headaches, night sweats, and tremors, or insomnia, consulting a doctor would be an important next step," cautions Dr. Hafeez.

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7 Reasons to Commit to a Booze-Free January - EDGEOnTheNet

erdikocak via Getty Images Intermittent fasting is a widely practiced diet plan that people use to lose weight, feel healthier and more.

Its no surprise that intermittent fasting is one of themost popular types of eating plans. You dont need to measure out food or buy any prepackaged shakes. There are no required weigh-ins or calorie counting. All you really have to do is not eat during certain hours. Its pretty simple.

There are different ways to go about it, of course. Most people do the 16:8 diet, in which you fast for 16 hours and then eat within an eight-hour window. Theres also the 5:2 diet, where you drastically cut back on calories just two days a week, and there are 24-hour fasts, where you dont eat anything one day each month.

Regardless of the method, significantly restricting when you eat can throw your body for a loop and cause a handful of odd side effects. Intermittent fasting may not be suitable for everyone. (People with a history of disordered eating, for example, should definitely avoid it.)

Its important to know what to expect before you jump into any new eating habit.Heres what happens to you mentally, physically and emotionally when youre fasting intermittently.

Many health experts, including personal trainerJillian Michaels, say that intermittent fasting actually isnt that great for weight loss. Thats because youre not necessarily eating less or cutting back on calories. There are just longer gaps in your day when youre not eating at all.

That said, many people do lose weight because they consume fewer calories during those restricted food hours.

Eating for only eight hours a day also makes it less likely that youre having a big meal right before bedtime.Our metabolism goes down when we sleep and we burn fewer calories.Nighttime eatinghas been linked to both obesity and diabetes.

Intermittent fasting really does keep you from doing some really bad things, which is to eat a big meal before you go to bed, said Dr.John Morton, a bariatric surgeon with Yale Medicine. Big meals before bed are probably the worst thing you can do when it comes to weight loss, he added.

A lot of people who fast experience hunger pangs, mainly when they start the program. Thats because our bodies are accustomed to using glucose a sugar that comes from the food we eat for fuel throughout the day. When its deprived of food (and, therefore, glucose), the body will essentially send signals saying, Hello, arent you forgetting something here?

Once your body gets into the groove of fasting, it will start burning stored body fat for energy rather than glucose. And as you spend more time in a fasted state, your body will get increasingly efficient at burning fat for energy.

In short, those hunger pangs should dissipate and your appetite will level out, Morton said. He added that fasters will ultimately have fewer cravings and hunger pangs the more consistently they fast.

In the meantime, that hungry feeling may drive some people to overeat. The natural tendency is when you havent eaten breakfast, you go, Since I didnt eat breakfast, Im going to eat more [for lunch], Morton noted.

If the hunger pangs are bad enough to interfere with your daily life, get something to eat. The idea is not to starve yourself.

Research has shown that fasting can cause some people to feel fatigued, dizzy, irritable and depressed.

In the beginning, your energy levels might be low because youre not getting the proper nutrients that you need, saidSharon Zarabi, a registered dietitian and bariatric program director at Lenox Hill Hospital in New York.

As your body gets used to intermittent fasting, your energy levels will pick back up. Your body becomes more efficient at using energy and this helps improve mood, mental ability and long-term performance, Zarabi said.

Theres even some evidence that suggests intermittent fasting can ultimately help fight depression and anxiety. The body releases a hormone called ghrelin when youre hungry or fasting, which in high amounts has been associated with an elevated mood.

Many people who partake in intermittent fasting note improved gut health. Fasting gives your gut a chance to rest and reset as your digestive system doesnt have to deal with uncomfortable effects of eating like gas, diarrhea and bloating.

Anytime you fast, youre giving your body a break from trying to metabolize what you just ate, Zarabi said. By fasting, we let the gut microbiome refresh, which in turn improves our overall digestive pathway.

Intermittent fasting has been linked to a lower risk of chronic diseaseslike diabetes and cardiovascular disease.

According torecent researchfrom Mount Sinai, this is because fasting reduces inflammation and reducing inflammation helps our bodies battle various chronic inflammatory diseases like diabetes, heart disease, cancer and inflammatory bowel diseases. Researchers are still working to figure out how and why this happens, but the evidence so far suggests that the fasting body produces fewer of the subset of monocytes, a kind of blood cell, that are known to damage tissue and trigger inflammation.

This is a big reason why people who fast intermittently may live longer and stay healthier.

Intermittent fasting can help lower your blood pressure, cholesterol and triglycerides the type of fat in our blood thats associated with heart disease. That is, if you lose weight in the process.

As long as youre losing weight, youre going to improve all those things, Morton said.

Before you start an intermittent fasting program, health experts recommend meeting with a dietitian or physician. Theres a critical distinction between fasting and starving, and if you ignore that, you could wreck your organs and immune system.

The bottom line: pay attention to your body and eat in a way that works best for you.

Related Video: In a 24/7 Food Culture, Periodic Fasting Gains Followers (Provided by The Associated Press)

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This Is Your Body On Intermittent Fasting - msnNOW

If you need to fidget whereas working, this can be a harmful illness .. In such an individual, contemplating it as weak spot of the physique, ignores it. Many instances it occurs that whereas performing some work, abruptly the individual's hand begins to tremble or typically whereas holding one thing mild, the individual's arms begin trembling. In such a scenario, the individual considers it a weak spot of the physique and ignores it. If your arms additionally tremble like this whereas working or whereas holding one thing, dont make the error of ignoring it even after forgetting it. That is as a result of it isnt due to weak spot in your physique however it may be one thing else.

For your data, inform me that the rationale for trembling arms and ft cant be the one weak spot.

->So today we are going to let you know about some such particular causes for trembling arms and ft, realizing about which youll be shocked. So, allow us to now clarify these causes intimately.

1. Significantly, trembling of arms could be a symptom of diabetes. For your data, inform me that when the quantity of sugar within the physique begins lowering, then the stress of the human physique will increase. Due to which the individual's arms tremble. So if potential, hold management of your sugar.

2. Apart from this, many instances an individual doesnt eat nutritious meals in his life. Yes, an individual doesnt eat such meals in his life, in order that the dearth of blood in his physique will be fulfilled. Due to which theres a scarcity of blood within the individual's physique. Significantly, as a consequence of anemia on this scenario, arms begin trembling.

3. Significantly, one of many predominant causes for shaking arms will be that your blood stress is just not regular. Yes, to your data, inform me that when BP abruptly will increase or decreases, even in such a scenario the arms of an individual begin trembling. Now its apparent that when your blood stress is just not underneath management, then trembling arms is certain to occur.

4. It is vital to notice that because of the improve of the hormone cartisol current within the physique, the stress of an individual will increase considerably. Now its apparent that when an individual is underneath stress in thoughts and physique, then its essential to have vibrations in his arms and legs. Please inform that as a consequence of this, the individual's arms begin to tremble.

However, in case your arms begin to tremble on a regular basis as an alternative of trembling, then you must instantly go to the physician, as a result of to disregard such a scenario means to play with your personal physique. That is why we are going to say that in case you ever see such a symptom in your self, then dont delay in going to the physician in any respect, as a result of later you might have to bear the implications.

Born to a PIO businessman, Parmesh loves travelling and writing about everything related to technology, entertainment, sports and business. He is from Istanbul and loves his Falafels and Hummus. Parmesh also has an expensive taste in wine and writes for various food magazines in Europe.

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If you need to fidget whereas working, this harmful illness can occur - OBN

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Controlling the Doses of Gene Therapy

Gene therapy is relatively new, with only a few approved therapies. The techniques typically involve taking a normal gene, inserting it into a hollowed-out virus, and injecting it into the patient, where the gene produces normal proteins that are otherwise abnormal. Researchers at The Scripps Research Institute developed a molecular switch that could potentially be embedded into gene therapies that would control dosing. They published their research in the journal Nature Biotechnology.

I think that our approach offers the only practical way at present to regulate the dose of a gene therapy in an animal or a human, said Michael Farzan, principal investigator of the research.

The researchers demonstrated the work by incorporating the switch into a gene therapy for anemia that produces the hormone erythropoietin. The switch suppressed expression of the gene to very low levels but could then increase the genes expression using injected control molecules called morpholinos. Morpholinos are already approved by the FDA as safe for other applications.

Machine Learning to Interpret Gene Regulation

Although big data is helpful in biological systems, the data sets are so complicated that interpreting the data is still difficult and complex. Researchers at Cold Spring Harbor Laboratory designed advanced machine learning algorithms that cut through the complexity, making the data from gene regulation more easy to understand for biologists. The algorithms are a form of artificial neural network (ANN) that appears to bridge the gap between computational tools and how biologists think.

Deep Learning Predicts Disease-Associated Mutations

Researchers at the University of Hong Kong developed a deep learning method to predict disease-associated mutations of the metal-binding sites in a protein. It is the first time a deep learning approach has been used to predict disease-associated metal-relevant site mutations of metalloproteins. Metal ions play important roles structurally or functionally in the pathophysiology of many human biological systems, such as zinc, iron and copper. Deficiencies in these can cause severe diseases. They utilized omics data to develop a training dataset, finding that a mutation in zinc-binding sites played a major role in breast, liver, kidney, immune system and prostate diseases, while calcium- and magnesium-binding sites are linked to muscular and immune system diseases, respectively. Iron-binding site mutations are associated with metabolic diseases.

The Science Behind Intermittent Fasting

There are, generally speaking, two types of intermittent fasting. One is daily time-restricted feeding, narrowing eating times to 6-8 hours per day, and 5:2 intermittent fasting, where individuals limit themselves to one moderate-sized meal two days a week. Research suggests that the reason this works is that they trigger metabolic switching, an evolutionary adaptation to periods of food scarcity. When people eat three meals a day plus snacks, the switching does not occur. The research study also found that intermittent fasting decreased blood pressure, blood lipid levels and resting heart rates. Additional studies also suggest it can improve brain health, such as learning and memory.

Many Younger Patients with Stomach Cancer Appear to Have Distinct Disease

Mayo Clinic researchers found that many people who developed stomach cancer under the age of 60 had genetically and clinically distinct disease from stomach cancer patients who were older. The new, early onset type of stomach cancer appears to grow and metastasize more quickly and has a worse prognosis. It is also more resistant to traditional chemotherapy. The investigators evaluated more than 75,225 cases from several databases to review stomach cancer statistics from 1973 to 2015. The average age of stomach cancer diagnosis is 68, but there appears to be growing occurrence in individuals in their 30s, 40s and 50s.

Dementia Vaccine Successful in Animal Trials

Investigators successfully tested an experimental vaccine to remove brain plaque and tau protein aggregates linked to Alzheimers disease in laboratory mice. The researchers from the Institute for Molecular Medicine and University of California, Irvine and Flinders University in South Australia, believe it supports clinical trials in humans, potentially in the next two years. The vaccine was a combination of two MultiTEP epitope vaccines, AV-1959R and AV-1980R, that target amyloid-beta and tau, respectively. It is formulated in AdvaxCpG, a polysaccharide adjuvant.

RNA-Targeting Approach Successfully Blocks Driver of Parkinsons Disease

Researchers at Scripps Research in Florida developed a compound that prevents production of an underlying cause of Parkinsons disease, an abnormal protein called alpha-synuclein. Dubbed Synucleozid, the protein halts the ribosome from detecting the messenger RNA (mRNA) template, preventing the translation of the disordered alpha-synuclein protein. This proof-of-concept study hints that the compound could become a potential Parkinsons drug candidate.

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Research Roundup: Controlling Gene Therapy and More - BioSpace

If you, or someone you know, has received a breast cancer diagnosis, it's likely you feel incredibly overwhelmed and have lots of questions about what happens next.

Its important to remember the resources which are available to support you through your breast cancer diagnosis and cancer treatment, including your doctors, cancer support groups and charities.

Weve worked with Breast Cancer Now to put together a guide explaining what to expect after your breast cancer diagnosis and what breast cancer treatment options you have.

No one knows your body better than you, so its important to regularly look and feel for any unusual breast changes and report anything different or new, such as a lump or a change to the skin, like puckering or dimpling, to your doctor as soon as possible.

If you suspect your have breast cancer symptomsarrange an appointment with your GP. At your appointment, your GP will examine your breast and may refer you to a specialist breast clinic for tests.

The Breast Cancer Nowwebsite says, Being referred to a breast clinic doesnt necessarily mean that you have breast cancer. It just means that more tests are needed to find out whats going on.

Once referred to a breast clinic you will have an examination and various tests of your breasts that may take several hours to complete. You can take a family member or friend to your appointment for support if you are worried. Though, some people prefer to attend their appointment on their own.

At the appointment the doctor or nurse may ask you questions about your family history to find if anyone in your family has had breast health problems previously. They will also ask questions about any other health problems you may have, and whether you are currently taking any medications.

What to expect after a breast cancer diagnosis | Credit: Getty

According to Breast Cancer Now, you will usually have a breast examination, followed by one or more of the following further tests and procedures.

During the initial examination the doctor will feel your breast when you are sitting down and lying down. They will also check the armpit area, as breast cancer can sometimes spread to your lymph nodes.

A mammogram is a breast x ray. During your appointment, a mammographer (an expert in taking breast x-rays) will ask you to undress to the waist and stand in front of the mammogram machine. Your breasts will be placed one at a time on the x-ray machine. The breast will be pressed down firmly on the surface by a clear plate.

An ultrasound scan uses sound waves to produce an image of the breast tissue. The scan is painless and generallydone in a few minutes, but can take longer.

Youll be asked to undress to the waist and lie on a couch with your arm above your head. To help gain a clear image, some gel will be spread over the area of the breast first. The person doing the scan will move a handheld scanning probe over the breast to look at the underlying breast tissue. The area under your arm may also be scanned.

A core biopsy will be carried outwhen your mammogram or ultrasound picks up something in your breast that needs analysing more closely. A corebiopsy involves taking a small part of your breast tissue through a small cut in your skin. You will have an injection to numb the area beforehand.The doctor will send the sample tissue to the laboratory for testing.

Fine needle aspiration will be carried outif your mammogram or ultrasound picks up something in your breast that needs analysing more closely. Fine needle aspiration is a process of taking a sample of cells from your breast using a syringe with a fine needle. This might feel a little uncomfortable, but the procedure doesnt last very long. The doctor will send the sample tissue to the laboratory for testing.

Once your doctor diagnoses your breast cancer, they will work out the extent of your cancer and determine what cancer stage you are in.

Carolyn Rogers, clinical nurse specialist at Breast Cancer Now said, Your cancer stage will be determined by the size of the cancer and how far it has spread. The grade is how different the cancer cells are to normalbreastcells and how quickly they are growing.

Your cancers stage and grade helps determine your prognosis and the best treatment options. There are different ways to stage breast cancer. Most hospitals use two main types of cancer staging systems including the TNM Staging System. and the number system.

You can read more about these on Breast Cancer Nows website.

TNM stands for Tumour, Node, Metastasis. This system describes the size of the initial cancer whether the cancer has spread to the lymph nodes, and a different part of the body.

T refers to the size of the cancer it can be 1, 2, 3 or 4, with 1 being the smallest

N refers to whether the cancer has spread to the lymph nodes it can be between 0 and 3 with 0 meaning no lymph nodes

M refers to whether the cancer has spread to another part of the body it can either be 0 meaning the cancer hasnt spread or 1 it has a spread

According to Cancer UK, here is a summary of the difference cancer stages graded by the number system.

Stage 1 means that a cancer is relatively small and contained within the organ it started in.

Stage 2means that the tumour is larger than in stage 1, but the cancer has not started to spread into the surrounding tissues.

Stage 3 means the cancer is larger. It may have started to spread into surrounding tissues and there are cancer cells in the lymph nodes in the area.

Stage 4 means the cancer has spread from where it started to another area in the body or organ.

Doctor showing a woman cancer test results on an wireless tablet / Credit: Getty

Carolyn Rogers explains, After all the necessary tests if you are diagnosed with breast cancer, the next step will be for a Multidisciplinary team (MDT), including surgeons, oncologists, breast care nurses and radiologists, to have a meeting to discuss and agree on a treatment plan for you.

This treatment plan and possible side effects of treatment will then be discussed with you. Treatment plans will vary depending on the features of your breast cancer.

The type of cancer you have and the features of the cancer Position of the cancer in the breast Other treatment youve had in the past or planning Your general health and fitness

Surgery is often the first treatment for women with breast cancer.

Carolyn Rogers further explains, Treatment will depend on the features of the breast cancer and may include surgery, chemotherapy, radiotherapy, hormone therapy and targeted therapy. You may be offered the option to take part in a clinical trial and your treatment team will explain this to you.

There are two types of breast cancer surgery:

Breast-conserving surgery:The cancer is removed along with a border of healthy breast tissue.

Mastectomy:All breast tissue is removed including the skin and nipple area.

Chemotherapy can be given before and after breast cancer surgery. Chemotherapy may be given before surgery to slow the growth of rapidly growing breast cancer or to shrink a larger breast cancer (this may mean breast-conserving surgery is an option, rather than a mastectomy).

Chemotherapy can also be given aftersurgeryforprimary breast cancerto reduce the risk of cancer coming back in the future.

Chemotherapy is a treatment that uses anti-cancer drugs to destroy cancer cells. It works by interfering with the cancer cells ability to divide and grow. Differentchemotherapy drugswork in different ways and a combination of drugs is often used. Chemotherapy affects cells throughout the body and can causeside effects such as hair loss, nausea and fatigue.

Radiotherapy uses high-energy x-rays to destroy cancer cells.Radiotherapy uses ionising radiation (high energy) to destroy any cancer cells that may have been left in the breast and surrounding area aftersurgery.

Radiotherapy is given after your breast cancer surgery to reduce the risk of breast cancer coming back in the future. If youre breast cancer treatment also involves chemotherapy, radiotherapy is usually given after the chemotherapy treatment.

Some breast cancers are stimulated by the hormone oestrogen. This means that oestrogen in the body helps the cancer to grow. This type of breast cancer is called oestrogen receptor positive (ER+).

If your breast cancer is oestrogen receptor positive, hormone therapy drugs such as tamoxifen, anastrozole and letrozole may be used to block the effect of oestrogen on the cancer cells.

All breast cancers are tested for oestrogen receptors using tissue from a biopsy or after surgery.If hormone receptors are not found, then hormone therapy will not be of any benefit.

As cancer researchers learn more about the cause of cancer, theyve developed new types of drugs that specifically target cancer cell changes.For some cancer types, targeted cancer drugs my work better compared to other treatments such as chemotherapy or radiotherapy.

This is a group of drugs that block the growth and spread of cancer. They target and interfere with processes in the cells that help cancer to grow. Targeted therapies can cause side effects such as flu like symptoms. The most common targeted therapies used for primary breast cancer are trastuzumab and pertuzumab. Whether you are offered this type of treatment will depend on the features of your breast cancer.

Breast cancer Now nurse offering advice on telephone / Credit: Breast Cancer Now

Carolyn Rogers said, Hearing the news you have breast cancer can be life-changing and telling your loved ones can be incredibly difficult. Who you tell and how you tell them is up to you. While you may find it difficult to talk openly about your cancer, especially at first, the support of those around you can be really helpful when you are going through breast cancer treatment.

If you have children, deciding what and how to tell them can be challenging. Its usually best to be honest. Breast Cancer Now offers some information about how to talk to children.

If you have questions about your breast cancer diagnosis, or you are worried about your breast health, you can call the Breast Cancer Now helpline for free on 0808 800 6000.

Macmillan Cancer Support also have advisers who you can contact online or on the phone if you have any questions about your breast cancer diagnosis, financial issues, or just want someone to talk to.

If youre worried about your breast cancer diagnosis,Breast Cancer Now offers a variety of free face-to-face support that provides the opportunity to meet others diagnosed, share experiences or concerns and hear from expert speakers providing a wealth of information, including Younger Women Together events for women diagnosed with breast cancer under 45 years old and Moving Forward courses, run in partnership with NHS hospitals, at the end of hospital treatment.

Read more here:
What to expect after a breast cancer diagnosis, including breast cancer stages and treatments - goodtoknow

The Fulton County Health Department has scheduled the following health clinics and services.

CANTON The Fulton County Health Department has scheduled the following health clinics and services. Please call the number listed with each service for an appointment or more information.

Maternal child health: Health screenings, WIC nutrition education and supplemental food coupons for women, infants and children. To make an appointment or for more information call 647-1134 (ext. 254). For Astoria clinic appointments call 329-2922.

Canton - Clinic - Monday, Jan 6 - 8-4 - Appt needed

Canton - WIC Nutrition Education - Tuesday, Jan 7 - 8-4 - Appt needed

Canton - Clinic/Immunizations - Tuesday, Jan 7 - 4-7 - Appt needed

Astoria - Clinic, WIC Nutrition Educ. - Wednesday, Jan 8 - 9-3 - Appt needed

Canton - Clinic - Thursday, Jan 9 - 8-4 - Appt needed

Adult Health Immunizations: Various vaccines are available. There is a fee for immunization administration. Medicaid cards are accepted. To make an appointment or for more information call 647-1134 (ext. 254).

Canton - Immunizations - Tuesday, Jan 7 - 8-4 Appt needed

Other times available by special arrangement at Canton, Cuba and Astoria.

Blood Lead Screening: Blood lead screenings are available for children ages one to six years. A fee is based on income. To make an appointment or for more information call 647-1134 (ext. 254). For Astoria appointments call 329-2922.

Family Planning: Confidential family planning services are available by appointment at the Canton office for families and males of child-bearing age. Services provided include physical exams, pap smears, sexually transmitted disease testing, contraceptive methods, pregnancy testing, education and counseling. Services are available to individuals of all income levels. Fees are based on a sliding fee scale with services provided at no charge to many clients. Medicaid and many insurances are accepted. After hours appointments are available. To make an appointment or for more information call the 647-1134 (ext. 244). *Program funding includes a grant from the US DHHS Title X.

Pregnancy testing: Confidential urine pregnancy testing is available at the Canton and Astoria offices. This service is available to females of all income levels. A nominal fee is charged. No appointment is needed. A first morning urine specimen should be collected for optimal testing and brought to the health department. Services are provided on a walk-in basis on the following days each week:

Canton: Every Wednesday & Thursday, 8-3:30 (for more information call 647-1134 ext. 244)

Astoria: Every Wednesday, 9-2:30 (for more information call 329-2922)

Womens Health: A womens clinic for pap tests, clinical breast examinations and vaginal examinations is available by appointment. There is a nominal fee for this service. Medicaid cards are accepted. Financial assistance is available for a mammogram. Cardiovascular screenings may be available to age and income eligible women. To make an appointment or for more information call 647-1134 (ext. 244).

Mammograms: Age and income eligible women may receive mammograms at no charge. Speakers are available to provide information to clubs and organizations. For more information or to apply for financial assistance, call 647-1134 (ext. 254).

Mens Health: Prostate specific antigen (PSA) blood tests are available for men for a fee. To make an appointment or for more information call 647-1134 (ext. 224).

Sexually Transmitted Disease (STD) Clinic: Confidential STD and HIV testing services are available by appointment to males and females at the Canton office. Services include physical exams to identify STDs, a variety of STD testing, HIV testing, education, counseling, medications and condoms. There is a nominal fee for services. Services are available to individuals of all income levels. Medicaid cards are accepted. To make an appointment or for more information call 746-1134 (ext. 224).

HIV Testing and Counseling: Confidential HIV testing and counseling services are available by appointment through the sexually transmitted disease (STD) clinic at the Canton office. To make an appointment or for more information call 647-1134 (ext. 224).

Tuberculosis (TB) Testing: TB skin tests are available at no charge by appointment. To make an appointment or for more information call 647-1134 (ext. 254).

Blood Pressure Screenings: The Fulton County Health Department provides blood pressure screenings at no charge on a walk-in basis during the following times:

Astoria - Screening - Wednesday, Jan 8 - 9-12 - Walk in

Health Watch Wellness Program: The Health Watch Program provides low cost lab services. Through this program adults can obtain venous blood draws for a variety of blood tests. Blood tests offered without a doctors order Comprehensive Metabolic Panel (CMP), Complete Blood Count (CBC), Lipid Panel, Prostate Specific Antigen (PSA) test, Hepatitis C test, and Thyroid Stimulating Hormone (TSH). A wide variety of blood tests are also available with a doctors order. There is a charge at the time of service. To make an appointment or for more information call 647-1134 (ext. 254).

Dental Services: The Dental Center offers a variety of basic dental services to children and adults. An appointment is needed. Medicaid and Kid Care cards are accepted. To make an appointment or for more information call 647-1134 (ext. 292).

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Health Department announces services for the week of Jan 6 - Canton Daily Ledger

If your heart feels like its doing something out of the ordinary, you might find yourself frantically Googling to figure out whats going on. Chances are, youre experiencing whats commonly known as heart palpitations, which is a catchall term for feeling like your heart is acting weird. Seriously.

Your heart beats because it has the very important job of sending oxygen-rich blood and nutrients to every part of your body. It also sends the carbon dioxide your body produces as a waste product to your lungs so you can expel it. When theres a glitch in this system, you might experience a palpitation. Heart palpitations may feel like your heart is beating too quickly, beating irregularly, fluttering in a strange way, or thumping hard in your chest, according to the Mayo Clinic.

Generally when we talk about palpitations, it means youre aware of your heart beating, and it feels like its not normal, Shephal Doshi, M.D., director of cardiac electrophysiology at Providence Saint Johns Health Center in Santa Monica, Calif., tells SELF.

If you ask four people with heart palpitations to describe them, you might get four varying answers. When people say, I have heart palpitations, they can mean so many different things that you have to tease out some details as to what exactly they feel, Sanjiv Patel, M.D., cardiologist at MemorialCare Heart & Vascular Institute at Orange Coast Medical Center in Fountain Valley, Calif., tells SELF. Which is all to say that the symptoms of heart palpitations arent cut and dry.

When to worry about heart palpitations depends on a few factors. In reality, heart palpitations usually arent a sign your hearts decided to give up the ghostbut in some cases, they can be a cause for concern. Heres how to tell the difference.

Most of the time when people feel palpitations, their heart is not doing anything bad, Dr. Doshi says. There are tons of reasons your heart can go a little wonky, and most of them are nothing to worry about.

Typically, your heart knows when to squeeze based on electrical impulses from a group of cells known as your sinoatrial (SA) node, according to the National Heart, Lung, and Blood Institute (NHLBI). These cells are housed in your hearts right chamber, also known as its right atrium. If your SA node starts sending wonky electrical impulses, you might experience heart palpitations.

Anything that increases the adrenaline in your body can affect these electrical impulses, Dr. Doshi says. That includes stress, panic attacks, caffeine, having a cold or flu, being sleep-deprived, and taking medications that contain stimulants. Your heart has receptors that pick up on heightened adrenaline, so any surges of this hormone can cause it to act differently.

Things that make your heart work harder can also cause palpitations, Dr. Doshi says. Thats why experiencing palpitations during or after a tough workout isnt immediately a reason to worry. Same goes for having them during pregnancy, when your blood volume goes up and your heart has to pump out that extra fluid.

Getty Shot of a unrecognisable young man holding his chest in discomfort with his hands due to pain in that areaTheres also a chance you might think you have heart palpitations, but actually dont. Some people are very attuned to their bodies, feel their hearts beating faster and think its a palpitation, but its still beating at a normal speed of up to 100 beats a minute, Dr. Patel says.

For example, these impulses go offbeat due to arrhythmias, which are basically short circuits in your hearts electrical system. Arrhythmias can make your heart beat irregularly and feel strange, along with weakness, dizziness, feeling light-headed, fainting, shortness of breath, and chest pain, among others.

While arrhythmias often arent dangerous and can be treated in many ways, sometimes they can be life-threatening. Only a doctor can tell you for sure, but any symptoms besides the strange heart sensations are typically a clue that your arrhythmia may be more serious, says the NHLBI. If you think youre experiencing any strange symptoms along with your heart palpitations, seek medical attention immediately.

Other times, heart palpitations can be a sign that somethings up with a different organ, like your thyroid gland. Your thyroid produces hormones like thyroxine and triiodothyronine, which influence many of your bodys systems, according to the Mayo Clinic. If your thyroid is on overdrive (aka, you have hyperthyroidism), it will generate too much thyroxine, which kicks up your bodys metabolism. This can lead to a rapid or irregular heartbeat, along with symptoms like an increased appetite and sudden weight loss.

You may also experience heart palpitations if you have a physical abnormality like a weaker or larger heart than usual, which you typically wouldnt know about unless it showed up during some kind of medical exam.

You may be wondering when to worry about heart palpitations, especially when most of the time, theyre NBD. One-off heart palpitations that just last a few seconds are a normal part of having a heart. That said, experiencing them regularly is not. If heart palpitations happen every time you do [a certain activity], like walk half a mile or lift something, thats not a random event and you should be evaluated, Dr. Patel says.

If your heart palpitations come along with any symptoms like dizziness, feeling unsteady, fainting, or chest discomfort or pain, thats a sign your hearts functioning may be compromised. That warrants further investigating to make sure its nothing dangerous, Dr. Doshi says.

Your medical history also comes into play, especially if you have a history of health conditions involving your heart. A healthy 30-year-old has less reason for concern than a 60-year-old with heart disease, Dr. Doshi says.

With that said, if your heart palpitations are random, dont come with other symptoms, and youre in great health, they might still feel too weird to ignore. Theres no law against seeing your doctor just to be on the safe side. They can test your heart to make sure its working as it should so you can skip worrying about your health the next time your heart skips a beat.

Video: Exactly how often you really need to see different kinds of doctors (Provided by Self) Provided by Conde Nast Entertainment LLC

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This Is When You Should Actually Worry About Heart Palpitations - msnNOW

ROCHESTER, Minn. A litany of high-impact health stories stood out in 2019, nearly all of them with endings that remain to be written.

These included record-breaking opioid settlements, a new treatment for cystic fibrosis, the promise and peril of large IT brands like Google and Apple moving into the healthcare space, and a devastating outbreak of serious lung disease in healthy young persons from vaping illicit THC.

But in terms of the health story with the greatest potential for taming sickness and the ballooning cost of healthcare, a case can be made for the recognition by health officials in 2019 of the ketogenic diet as a first line-treatment for type 2 diabetes.

The ketogenic diet, as many by now know, is a low-carb diet on steroids, a calorically-unrestricted eating pattern in which just 10-20% of daily calories (or less than 50 grams) come from carbohydrates, with dietary fat making up the majority of remaining energy (roughly 70% of daily calories).

Type 2 diabetes, on the other hand, is an acquired metabolic disorder affecting 340,000 Minnesotans and 30 million Americans, one that currently extracts $250 billion in direct costs each year in the US, and which can lead to heart disease, hypertension, Alzheimers, amputation, blindness and cancer.

Because it is often accompanied by obesity, type 2 diabetes is routinely attributed to overeating and lack of exercise, but a more precise description of its mechanism comes down to an elevation of the bodys emergency hormone insulin. Given that the body only releases insulin in response to dietary carbohydrates, type 2 diabetes is arguably a food-borne illness, with the food in question being carbohydrates. That is the rationale, in any event, for treating the predominant illness of our time with a ketogenic diet.

We need to recognize that conventional diets have not worked well, and reduce the scientific barriers to studying novel approaches, like the ketogenic diet, says Dr. David Ludwig, an endocrinologist at Boston Childrens Hospital and professor of pediatrics at Harvard Medical School, in an email to Forum News Service. These long-term studies will provide the definitive data to understand effectiveness for various chronic conditions, and potential side-effects.

Ludwig recently authored a paper in the Journal of Nutrition compiling the evidence for ketogenic diets, past and present, a paper complete with a section heading noting there is no human requirement for dietary fiber or carbohydrate. A century ago, he reminds readers, the ketogenic diet was a standard of care in diabetes, used to prolong the life of children with type 1 diabetes and to control the symptoms of type 2 diabetes in adult.

It was only following the discovery of insulin in the 1920s, Ludwig writes, that high carbohydrate diets gave us our present day medication protocols for type 2 diabetes, treatments anchored by the use of pricey commercial insulin analogs and daily ingestion of glucose-control medications.

Ludwig says he wrote the article to counter a spate of negative articles (that) have been rewritten about the ketogenic diet by nutrition experts, articles focusing on rare side-effects.

Viable approach

The case for keto in 2019 kicked off in May, when the American Diabetes Association released a Consensus Report calling low carbohydrate or very low carbohydrate diets a a viable approach for certain patients with T2D, including those hoping to reduce medications.

Describing the diets as among the most studied eating patterns for type 2 diabetes, the nations diabetes authorities added the caveat that ketogenic therapy for diabetes generally requries medical oversight to prevent hypoglycemia. In other words, keto can work so effectively in diabetics that should patients fail to carefully taper medications with medical guidance as their condition improves, they can become dangerously overmedicated.

June of 2019 saw the release of still more arguments for keto, in the form of second-year trial results by researchers from Indiana University Health and Verta Health. Their non-randomized clinical trial of the diet produced data showing that more than half of 262 patients studied had reversed their illness on a remote-monitored ketogenic diet, with many having discontinued the need for all medications except for Metformin.

While noting that the Verta Health results should be interpreted with caution, Ludwig says these exceptional outcomes at two years, with many participants coming off diabetes medications and improving blood glucose control, highlights the exciting possibility that diabetes can be reversed without bariatric surgery.

The arrival of keto for type 2 diabetes comes along at a time when the standard of care is increasingly coming up short. The year saw widespread shortages and price hikes for insulin, leading politicians to threaten price control legislation and stirring insurers to issue competing press releases touting their full- or highly discounted insulin coverage packages.

As endocrinology researchers from Mayo Clinic recently wrote in the journal BMJ, the body of evidence shows no meaningful benefit for intensive glucose-lowering regimens when it comes to the health outcomes that matter most to patients. And as researchers from Norway confirmed in 2018, telling high-risk individuals the advice to eat more fiber and polyunsaturated fat, plus the familiar five servings of fruit and vegetables with plentiful intake of beans, wholegrain and low-fat dairy, produced no improvement either.

For its part, the device industry is taking steps to build a ketogenic diabetes care product line, offering portable ketone breath meters and continuous glucose monitors allowing patients to see the effects on their blood sugar of carbohydrate rich foods in real time.

Still to be determined is whether dietary officials will heed the call by groups like the Low-Carb Action Network to include a true low-carbohydrate diet in the next installment of the dietary guidelines. Under the current USDA definition, diets up to 45% carbohydrates, are deemed low-carbohydrate, a too-high allowance for carbohydrates potentially washing out the ability of researchers to accurately test the intervention for disease reversal and prevention.

Its new research on an old method. As Ludwig notes, before insulin was discovered, a very-low-carbohydrate diet was considered the standard of care for diabetes. From this perspective, modern nutrition science may be in the process of rediscovering the wheel, so to speak.

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Health story of the 2019: Keto can help with Type 2 Diabetes - Southernminn.com

Although the general story of ghostwriting in trials of psychiatric drugs is now pretty well known, the details of the corruption in specific trials are still emerging into the public record, often a decade or more after the original sin of fraudulent publication. The latest study to finally see the full light of day is GlaxoSmithKlines study 352.

Perhaps the most infamous ghostwritten study is GSKs study 329, which, in a 2001 report published in the American Journal of Psychiatry, falsely touted paroxetine (Paxil) as an effective treatment for adolescent depression. The company paid over $3 billion in penalties for fraud.

That same year, study 352 made its first appearance in the research literature. That was when Charles Nemeroff, who in the years ahead would become the public face of research misconduct, authored an article on the efficacy of paroxetine for bipolar disorder. It has taken 18 years for the full story of that corruption to become known, the final chapter recently emerging when a large cache of study 352 documentsemails, memos, and other internal correspondence between the key playerswas made public.

The documents reveal a web of corruption that went beyond the fraud of ghostwriting into the spinning of negative results into positive conclusions, and the abetting of that corruption by an editor of the scientific journal that published the article. The documents also reveal a whitewashing of the corruption by the University of Pennsylvania.

However, it was the publication of these documents that provided Jay Amsterdam, an investigator in the trial who turned whistleblower after he smelled a rat, with a chance to say case closed. Amsterdam and Leemon McHenry have now published two articles that provide a step-by-step deconstruction of the studythe ghostwriting, the spinning of results, the betrayal of public trust.

Here is the story of that whistleblowing.

Starting in the late 1970s, Amsterdam became a go-to guy for studying pharmaceutical interventions, especially antidepressants. By the time he got involved with study 352, he was running a prestigious bipolar disorder clinic at the University of Pennsylvanias Perelman School of Medicine. Hed published over 100 peer-reviewed articles, and had served as editor and author on multiple textbooks about mood disorders. He was a working psychiatrist, a lecturer and professor, and a full-time researcher.

Amsterdam received his MD in 1974 from Jefferson Medical College in Philadelphia. While still a post-doc, he began working almost immediately with the top researchers investigating treatments for mood disorders. William Dysonone of the early promoters of lithium for bipolar disorderwas one of Amsterdams mentors, as was Dysons colleague, Joseph Mendels. Dyson opened the bipolar disorder clinic that Amsterdam would eventually run.

In the early 1980s, hormone function was one of the chief hypotheses in mood disorders, and Amsterdam became a leading researcher in the burgeoning field of psychoendocrine studies. He conducted a number of studies on melatonin, among many other hormones. By the mid-1980s, Amsterdam was working under Karl Rickels, an ex-Nazi soldier who had been one of the chief investigators on pharmacological treatments for mental health since the 1950s. Amsterdam describes Rickels as a brusque, almost abrasive figure who worked almost exclusively with pharmaceutical industry money, investigating the efficacy of the drugs, but who remained proud of the fact that he did not have his papers ghostwritten. You should always write your own articles, he told Amsterdam. You know, no one has ever written an article for me.

During this time, Amsterdam was investigating various pharmaceutical treatments for depression and bipolar disorder, including tricyclic antidepressants, lithium, and newer SSRI antidepressants like fluoxetine (Prozac). By the late 1980s, Amsterdam had become a leading researcher in psychoimmunovirology, conducting some of the earliest studies on the hypothesis that exposure to viral disease was a cause of psychological disorders. While its unlikely that this is a cause for most psychological problems, some viral diseases like the Borna disease virus and the Epstein-Barr virus have been correlated with a slight increase in the likelihood of psychological problems. He began studying whether lithium might work by suppressing the effects of viral disease.

By 1993, Amsterdams mentor Dyson had passed away, and Amsterdam became the director of the bipolar disorders clinic at Penn. At the time, his clinic was a perfect fit for the needs of the pharmaceutical industry. It was large, so he had a pool of potential participants for trials. Amsterdam also describes the clinic as offering access to treatment-nave, or drug-free, patients with depression and bipolar disorders, who were good enrollees in industry studies.

Amsterdam was happy to work with the industry at that time. One year, he offered his entire crop of mood disorder research participants to Eli Lilly for their study on fluoxetine (Prozac) for relapse prevention. According to Amsterdam, he told them theyd have to pay all his operating costs for the year. Well take care of you, Lillys spokesperson responded. Amsterdam says, I gave them 139 patients, well-diagnosed, well-treated. And actually, my clinic was the only site that differentiated Prozac from placebo for relapse prevention. I really gave them their moneys worth.

Amsterdam was also on industry panels for over a dozen pharmaceutical companies, giving sponsored talks. It wasnt until the early 2000s that industry representatives began urging him to deviate from his prepared talks. Once he began to experience pressure to spin his results in favor of the drug, he said, I stopped giving talks.

But he never saw it as systemic corruption. Instead, each time, it looked like one company, or one representative, was under pressure to deliver better results, and so put the pressure on him to tell a better story about the companys drug. I was never anti-pharma, he said. He was happy to take their money, as long as he could continue to deliver accurate data.

In the 1990s, all was going well for Amsterdam. And he thought little about it when, in 1995, Rickels asked if he could help out a junior colleague at Penn, Laszlo Gyulai. Gyulai was involved in a study for GlaxoSmithKline (then SmithKlineBeecham) of paroxetine (Paxil) to see if it would improve depressive symptoms in patients with bipolar disorder who were already taking lithium. According to Amsterdam, Gyulais clinic had less than a dozen patients, so it was no surprise that he was struggling to recruit participants for the study. Rickels framed it as a favorhe was embarrassed by Gyulais recruitment numbers and wanted Amsterdams help.

I (told Rickels) that I would be willing to be an investigator on the study, Amsterdam recalled. I said that I would be willing to recruit patients and help him if I am the co-principal investigator, if my names listed as co-principal investigator on the consent form, if Laszlo turns over 80% of the revenue for each patient I recruit. If I end up being one of the principal recruiters in the study, I want to be acknowledged as an author, I want to see the data, I want to co-write the paper.

Rickels agreed, and soon GSKs people contacted Amsterdam and helped set up his clinic as the 19th site for the research study. Gyulai had recruited just seven patients over a few years. Amsterdam recruited 12 in just a few monthsno surprise again, since his clinic served over a thousand patients.

Amsterdam was deeply involved in the work with those 12 patients, prescribing their medications, checking their dose, giving the assessment measures to see how well the medications were working. Then, just a few months later, the study was cancelled by GSK.

Amsterdam called up his contact at GSK, research director Cornelius Pitts. But Pitts just told him to stop enrolling participants. I couldnt get any information about why it came to an end, Amsterdam said.

Even a year later, when Amsterdam asked Gyulai where the data from that study was, Gyulai told him we dont have it yet. Amsterdam moved on with his life. It was just one of many projects I was working on.

In 2001, Amsterdam was working on a grant proposal to the NIMH to study fluoxetine (Prozac) as a treatment for bipolar disorder when a member of his research lab mentioned that a study was about to be published in The American Journal of Psychiatry on a similar subjectSSRIs for bipolar disorderthat could provide solid background for the grant-writing process.

Amsterdam hunted down the paper, and quickly realized that some of the listed authors were from his own department at Penn. One was Dwight Evans, chair of psychiatry at Penn. Another was Laszlo Gyulai.

Amsterdam called Evans office and requested a copy of the article from his secretary. Soon the fax machine spit out the cover page, which had a handwritten note at the top. Dear Jay, with compliments. Dwight.

As Amsterdam read the study, he was overwhelmed by a sense of dj vu. I started reading the abstract, and I said to myself, this sounds really familiar. And then I kept reading and Im thinkingI did this study! And Im looking and looking, and I cant find my name. And then I began to get suspicious.

The lead author on the study was Charles Nemeroff, and while Nemeroff had yet to become publicly identified for his regular participation in ghostwriting exercises, Amsterdam knew that he was part of what many liked to call the psychiatric mafia,psychiatrists that had close ties to industry. So that aroused his questions about the integrity of the article. Even more to the point, he couldnt understand why Gyulai was listed as an author.

As far as Amsterdam knew, Gyulai had only enrolled a handful of patients, and so he wondered whether Gyulai had somehow overstated his involvement in the study. Had he falsified data, or plagiarized another researchers work to do so?

Amsterdam called up his department chairDwight Evansto report his concerns. The universitys policy required that the provost or assistant provost for research be informed that such a concern had been raised and should be investigated. But in this instance, Evans told him that he and Rickels would investigate the matterno need, apparently, to take this matter to the university higher-ups. Evans asked Amsterdam what he wanted from the investigation.

I said, Id like an apology and I want Laszlo Gyulai to be sanctioned for plagiarism, Amsterdam told him.

In a letter dated April 3, 2001, Rickels informed Amsterdam of what he had learned from his investigation. Yes, Amsterdam was a co-investigator in the trial, and he had enrolled more patients than Gyulai; and yes a ghostwriting firm, STI, had written two drafts of the paper before it asked Gyulai if he would agree to be the papers first author; yes, STI had later replaced Gyulai with Nemeroff as the first author; and yes, there were academic investigators in the trial who had never reviewed or even seen the submitted manuscript.

Although the letter seemed like an admission of scientific fraud, given the evident ghostwriting of the paper, there was no departmental censure of Gyulai. Amsterdam then wrote both Evans and Rickels to express his displeasure. Am I to assume that it is okay in this department for a junior faculty member to abscond with data from a full professor and publish it without any ramifications? he asked.

Although Gyulai was never sanctioned, he did send Amsterdam a letter of apology. In it, Gyulai wrote that he understood Amsterdams concerns about plagiarism, but stated that he (Gyulai) was the primary investigator of the Penn site and did some work on early drafts of the article. Gyulai complained that first authorship was taken away from me and that he wished that GlaxoSmithKline had allowed Amsterdam to have input on the paper.

At that point, Amsterdam let it go. He wouldnt revisit the study again until 2010, when his own professional life came under attack.

In 2008, Senator Charles Grassley (R-Iowa) of the US Senate Finance Committee began to investigate financial conflicts of interest in scientific research. Paul Thacker, an investigative journalist, was the point man for Grassleys investigation and his 2010 committee report, which resulted in significant changes to the rules used by academic institutions to define research misconduct.

The picture of corruption that emerged thanks to Grassleys investigation, and other investigations into industry-funded trials, told of how academic medicine had been horribly corrupted, with psychiatry the specialty that was most compromised.

Pharmaceutical companies would hire ghostwriting firms to manipulate data and write articles spinning the results. The drug companies would then get academic psychiatrists, who were described by the companies as thought leaders, to agree to be the authors of the study in order to lend credibility to those misleading results. These same experts would then be paid to give talks promoting the companys drug. They would be paid handsomelyin some cases, hundreds of thousands of dollarsto serve the pharmaceutical companys commercial interests in this way.

Charles Nemerofflead author on the study 352 paperbecame the poster boy for this type of research misconduct. At the time, Nemeroff was an internationally-famous researcher with hundreds of publications and awards. He was chair of the psychiatry department at Emory University.

Grassleys investigation helped put a dollar amount on this corruption. He reported that Nemeroff was receiving millions of dollars from the pharmaceutical industry, and failing to disclose that pay according to conflict-of-interest rules. As reported in The New York Times, Nemeroff was found in 2008 to have violated federal research ethics rules by hiding $1.2 million, which, if appropriately disclosed, would have prevented him from being the primary investigator on the government grants he was also receiving.

It was business-as-usual for Nemeroff, whod already weathered two scandals in which hed promoted new treatments in scientific journals without disclosing in one case that he owned the patent on that treatment or that in the second case that he was being paid by the company behind the treatment.

After yet another investigation, Nemeroff was found to have violated Emorys policies, and was forced to resign from his position there. But he immediately moved to the University of Miami, where he soon began the process again.

According to Thacker, Nemeroff continued to receive tens of thousands of dollars from various pharmaceutical companies, while also receiving additional government grant money to test their products. In his case, it seemed that there was little financial penalty for violating federal rules and engaging in research misconduct.

In the 2000s, Amsterdam was becoming increasingly ill. He was almost completely blind, as he suffered from a severe form of glaucoma, but he was still trying to lecture, conduct research, and see patients. During this time, he conducted research on the class of antidepressants known as MAOIs (monoamine oxidase inhibitors), which have been less utilized due to concern about drug interactions with other antidepressants and certain cold medicines, and dietary restrictions such as alcohol and cheese. However, Amsterdam believes that MAOIs are less dangerous than previously believed.

In 2003, he was working with Somerset Labs to test their MAOIs. He did a trial that showed the drug beat the placebo, and they wanted to publish the results. He began to draft the article, but they suggested he outsource it to a ghostwriting company. They told him they were paying this company $30,000 to write the article, so there was no need for him to do it. But Amsterdam remembered Rickels advice: always write your own articles. He wrote the article himself, then sent it to the company.

It was during this time that he began to slowly move away from taking pharmaceutical industry money. He began to drop off the industry panels, as the reps asked him to spin his results more and more when giving talks. This pressure went against his grain as an objective academic.

I could see that pharma had changed. My respect for it had changed, too, he says. I dont want to do shitty research, which is what the drug company research is now.

Science is not the discovery of that new drug. Thats hubris. Science is the replication of that finding, over and over again. I hear colleagues saying we want to show that this drug works. I say, no, you want to show that the placebo theyre testing it against doesnt work. And when I started to say that to industry people, they stopped giving me studies.

By 2006, Amsterdam had had enough. He was done taking pharmaceutical industry money, and funded his research after that entirely with government grant money.

He also began to investigate iatrogenic harms of antidepressantsthe notion that the drugs used to treat the condition are, instead, making it more chronic and resistant to future treatment. He began asking questions: Why did those who continued to take the drug long-term have more risk of relapse than those who decided to stop taking the drug? Why did those who tried more drugs have higher risk of relapse?

According to Amsterdam, People that get repeated antidepressant treatment develop a tolerance to drugs, and, probably as a result of this, weve created the field of treatment resistant depression.

He says that would have been an unthinkable conclusion when he was taking industry money: The pharmaceutical industry would have shut down that research in every way possible.

In the spring of 2010, Amsterdams professional life began to fall apart. Later that year, as he struggled to understand why his career at Penn suddenly came under attackan attack seemingly led by his chairman Dwight Evanshe came to see it as connected to the complaint hed made nine years earlier about the ghostwriting of study 352.

The first shot was fired on April 6, 2010, when Evans suddenly called Amsterdam and told him to go to the Office of Affirmative Action immediately. What did I do? Amsterdam asked. Evans responded by telling him not to ask questions. Just go there.

At his meeting with the head of the affirmative action office, Amsterdam was told he was being investigated for several complaints made against him. However, the head of the office wouldnt tell him any details. Youll learn in due time, Amsterdam was told. I have nothing in writing but youll know from the questions youre asked.

This was the start of what became something of a Kafkaesque experience for Amsterdam. A flood of complaints were suddenly directed at him, all of them emanating from Evans office, and yet he was never formally told of these complaints, or their specifics. Instead, he would be called into the Office of Affirmative Action and questioned about numerous different subjects. Amsterdam inferred from these sessions that the complaints included allegations of retaliation against his staff, racial discrimination, unapproved research activities, photocopying sensitive documents, continuing medical education fraud, and sexual harassment against staff members.

One of the more bizarre episodes occurred on May 13, 2010. Amsterdam was summoned to the affirmative action office by associate director Patrice Miller. As she wrote later that day in an official letter, she did not find any information to support a finding of sexual harassment. While Amsterdam may have been glad to hear this, he was also perplexed. This was the first time that he was aware that a complaint of this type had been made.

The most serious complaint made against Amsterdam was that hed had an inappropriate relationship with a female patient. If this complaint were substantiated, he could have lost his license to practice.

Mad in America spoke to that woman. She confirmed every aspect of Amsterdams relating of this matter to MIA. She is a professional artist and asked that MIA not use her name.

She first met Jay Amsterdam around 1993, when she became his patient through the clinic. Severely depressed, she was a participant in many clinical trials of different drugs as they attempted to find something that worked for her. Most drugs didnt, although some worked for a time before their effects wore off. Eventually, after escaping an emotionally abusive relationship and continuing drug trials, she found her mental health becoming more stable. She attributes a lot of her improvement to Amsterdam. He was such a great doctor, she said. He saved my life, you knowfinally not being depressed.

Because she had been in treatment for many years, she remained in contact with Amsterdam, whom she describes as approachable, friendly, and very professional. Amsterdam was a fan of her artwork, and bought some of her paintings.

In 2010, she learned about the allegations against Amsterdam that supposedly involved her. I was absolutely floored, she said. Nauseated, floored. You know, I considered him a dear friend. He saved my life.

According to both this woman and Amsterdam, the allegation arose from a misrepresentation of some off-the-cuff language he had used in an email to her. Amsterdam had recently purchased one of her paintings, and in the email, he referred to the painting as booty (colloquially, to refer to an item of value). The investigative committee pointed to that word as having a sexual connotation, and thus evidence that Amsterdam had an inappropriate relationship with this female patient.

More than anything I felt terrible for Jay and [his wife] Debbie, she told MIA. This was ridiculous. It was uncalled for, mean-spirited, fabricated.

She wanted to sue Penn, but couldnt find lawyers willing to take on a case like this against the stone wall of Penns legal team. They defamed me, she said, and they should have been punished for it.

Furthermore, during Penns investigation of this matter, someone in Evans office photocopied and circulated her private medical information to various members of the university administration. This, of course, was a violation of HIPAA laws. They stole my emails, my health records, the woman said.

Amsterdam provided Mad in America with documents detailing the history of allegations and complaints made against him, and written records showing that there was an absence of any resolution substantiating the complaints. Even so, the stress of the situation, the sheer volume of complaints, and the feeling that everyone in the university was targeting him for some unknown reason led to a worsening of Amsterdams health in 2011. Acting upon his doctors advice, he took a medical leave.

Once on leave, Amsterdam struggled to figure out why his professional life had suddenly collapsed around him. Although he was now unable to see, his wife Debbie helped him search the internet for information about Penn and Evans. One day, she found an article about a court case in Philadelphia that led him into a larger dive into Evans involvement in the ghostwriting scandal.

In this case, a child had been born with a congenital heart defect after the mother used paroxetine while pregnant. The family sued GSK, accusing the company of hiding data about the harms of the drug. GSK lost the case, and ended up paying a $2.5 million penalty.

GSK, it seemed, had engaged in research misconduct. That article led Amsterdam and his wife to other articles citing UK psychiatrist David Healy, who had testified against GSK in the trial. In one article, Healy named several academic researchers who were on pharmaceutical executives speed-dial lists. One name immediately jumped out to Amsterdam as soon as his wife read it aloud: Dwight Evans.

Now, for Amsterdam, the light bulb was starting to turn on.

In the spring of 2010, when Amsterdam had been hit by the first complaint, Senator Charles Grassley was readying the release of his report on medical ghostwriting. In that report, which was released on June 24, 2010, Grassley noted that during his investigation he had asked Penn Medical School about its policies on ghostwriting, and Penn had informed Grassley that it had policies against plagiarism and it considered [ghostwriting] to be the equivalent of plagiarism.

This inquiry from Grassley surely would have raised anxiety in Penns psychiatry department. Not only had Amsterdam charged Gyulai with stealing his data, but Evans was also listed as an author of the Study 352 report, and yet Rickels, in a letter to Amsterdam, had told of how the paper had been ghostwritten by STI.

Moreover, as Evans likely knew in the spring of 2010, Grassley and his lead investigator, Paul Thacker, already had their sights set on him related to another instance of his authoring a ghostwritten paper. This instance of ghostwriting became public that fall, when Thacker, in a letter to NIH director to Francis Collins, told of how Evans had signed off on an editorial written by Scientific Therapeutics Information (STI), with the ghostwriting firm billing GlaxoSmithKline for its services.

Thacker wrote:

According to the documents, Sally Laden of STI wrote an editorial for Biological Psychiatry in 2003 for Drs. Dwight Evans, Chairman of the Department of Psychiatry at the University of Pennsylvania School of Medicine, and Dennis Charney, then an employee at the NIH and now Dean of Research at the Mt. Sinai School of Medicine at New York University.

In an email to a GSK employee, Ms. Laden wrote, Is there a problem with my invoice for writing Dwight Evans editorial for the [Depression and Bipolar Support Alliance]s comorbidity issue to Biological Psychiatry? Yet, when published, the authors Evans and Charney only stated, We acknowledge Sally K. Laden for editorial support.

In his letter, Thacker urged Collins to approve new policies that would recognize ghostwriting and plagiarism as research misconduct. He encouraged Collins to consider enforcement mechanisms such as disciplinary action and dismissal for the researchers involved.

Evans was now on the hot seat. Thackers complaint to Collins told of plagiarism for hire. Yet, Penn, in response to Thackers new revelation, took no action against Evans. As Thacker said in a subsequent article published a few months later, Penn just blew it off as though it were a matter of no account.

Thacker, in his latest article, publicly named Evans and Penn as an example of the corruption in academic medicine that needed to be cleaned up. Students should really be pissed off that professors get away with this type of fraud when students receive steep penalties, he wrote. What makes this all even more bizarre and insulting is that Dr. Evans is on the board of Penns Scattergood Program for the Applied Ethics of Behavioral Healthcare, a program dedicated to healthcare ethics.

Once Amsterdam learned of Thackers articles, he could put together a timeline that provided a likely explanation for why he had been hit with all those complaints in the spring of 2010. All of those complaints had emanated from Evans office, at a moment when Evans had reason to be worried about Grassleys investigation of ghostwriting, and if Thacker continued his digging, he might stumble upon the very studystudy 352that Amsterdam had complained about in 2001. And thator so it would seemwould mean big problems for Penn and Evans.

I think what happened is that Evans got all wigged out, Amsterdam said. He remembered the fact that he plagiarized, in 2001, an article in The American Journal of Psychiatry. And he knew that I knew, and that I knew he swept it under the rug by not taking it to the university, with his crony, Rickels. And he knew that if I were called to testify before Congress, I would tell them what happened.

Amsterdam didnt wait for Grassleys call. On July 8, 2011, he filed a whistleblower complaint with the federal Office of Research Integrity (ORI) alleging that Evans and the other authors had committed plagiarism by placing their names on that ghostwritten paper published in 2001.

Given Rickels 2001 letter to Amsterdam, which confessed that STI had written the initial drafts of the article, and that many academic investigators in the trial hadnt reviewed or seen the submitted article, it seemed that Penn would need to censure Evans. The ghostwriting element was clear. Even Gyulai had stated in his letter of apology that the ghostwriting firm had given first authorship to Nemeroff, and Penn had told Grassley that it considered agreeing to author a ghostwritten article to be a form of plagiarism.

But Penn just dismissed Amsterdams complaint with a wave of its institutional hand.

In a letter to Amsterdam dated December 5, 2011, the university admitted that the two researchers had published ghostwritten articles, and while it noted that the ghostwriting firms authors should have been listed on the publications, it decided that there had been no misconduct because Penn, at that time, did not have a formal policy prohibiting faculty and researchers from appending their names to ghostwritten work.

In its statement to the press, the university was even more adamant. A Science article published on March 2, 2012 had this headline: Penn Clears Two Faculty Psychiatrists of Research Misconduct Charges.

There was, the university stated in its press release, no plagiarism and no merit to the allegations of research conduct because Gyulai and Evans had helped conduct the research and analyze the results and contributed to the paper, which had presented the research findings accurately. As for Amsterdam, the university stated, he should not have been listed as a co-author or in the acknowledgements, because his role did not meet the journals guidelines for authorship.

The universitys response to Amsterdams whistleblowing did not impress Thacker and the leaders of the Project on Government Oversight. POGO sent a letter to the office of the President of the United States stating that the president of Penn, Amy Gutmann, had ignored the evidence against Evans. They just blew it off, Thacker wrote.

At that time, Gutmann was the chair of Obamas Bioethics Commission, and Thacker asked how she could be expected to function capably in that position, given this brush-off. Dr. Gutmanns bona fides on bioethicsto borrow a phrase from Penns own spokespersonappear to be unfounded.

After filing his complaint with the federal office of Research Integrity, Amsterdam teamed up with bioethicist Leemon McHenry to write a peer-reviewed article about the 2001 paper. They looked at the way the data from study 352 had been analyzed, and then how it was presented in the article itself. Their article was published in 2012 in the International Journal of Risk & Safety in Medicine. In it, Amsterdam and McHenry wrote that they show how primary and secondary outcome analyses were conflated, turning a negative clinical trial into a positive studywith conclusions and recommendations that could adversely affect patient health.

The study, they wrote, was designed to test GSKs drug, paroxetine (Paxil) against both an older antidepressant, imipramine, and a placebo control. The participants were people with a bipolar disorder diagnosis who were taking a full dose of lithium, but not responding to lithium treatment. The goal was to see if Paxil could improve depression when lithium wasnt working.

However, the study was plagued with problems from the start. The researchers struggled to enroll enough participants (hence the recruitment of Amsterdam, to gain access to his prestigious bipolar disorders clinic). Even with Amsterdams help, the researchers didnt enroll enough participants to meet the original requirement.

Still, GSK continued the study. Each of the 117 participants was randomly assigned to one of three groups: Paxil, imipramine, or placebo. The original test was to see how the groups did, on average, on both the Hamilton Rating Scale for Depression (HRSD, a common measure of depression severity), and the Clinical Global Impression Severity scale (CGI/S, a subjective, 7-point scale of how ill a clinician considers their patient).

The researchers also used the Young Mania Rating Scale (YMRS) to assess whether Paxil caused manic or hypomanic episodesa well-known harmful side effect of SSRIs.

However, the results showed no beneficial effect for either Paxil or imipramine. Improvement was no better than placebo on any of the scales used.

This was a failed study. But rather than publish that finding, GSKs ghostwriters looked for other ways to put a positive spin on the study. Finally, a statistician working for GSK hit on an idea that might produce a positive resultssplitting the participants into two groups, one on high doses of lithium, and one on low doses of lithium.

This was a post-hoc analysis (conducted after the study was over), so the researchers couldnt actually randomize participants to receive a specific dose. Moreover, all the participants were stabilized on a dose that was considered within the normal range. Nonetheless, the statistician arbitrarily separated those with a slightly higher dose from those with a slightly lower dose.

However, even then, the statistician couldnt find an effect when looking at how many people experienced a response to the drugs. Response in this case was defined as having a HDRS score of 7, or a CGI/S score of 2. Neither Paxil nor imipramine were significantly better than placebo and that was true for both the high-lithium and the low lithium group.

However, GSKs statistician still had one more data-mining exercise to try. The average change on the HDRS and the CGI/S scales for both Paxil and imipramine was greater than for placebo, and this difference was statistically significant.

Although the published report of Study 352 did note that no statistically significant differences in response rates were seen among those receiving paroxetine, imipramine, or placebo, it was the average change on the two scales that was featured in the abstract of the article, which was used to support this bottom-line conclusion: Antidepressant therapy may be beneficial for patients who cannot tolerate high serum lithium levels or who have symptoms that are refractory to the antidepressant effects of lithium.

This post-hoc data mining is known to be unethical, and if presented as a bottom-line finding, a type of research fraud. The joke within research circles is that if you torture the data long enough you can always find the result you want, and it was that process of data manipulation that Amsterdam and McHenry documented in their analysis of the study.

There were other research sins to be found in the published article. For instance, the researchers didnt report the YMRS data that was used to assess the risk of drug-induced mania/hypomania, which is a scientific sin of omission, one that in company-sponsored trials was regularly used to hide adverse effects of the sponsors drug.

Go here to see the original:
The Whistleblower and Penn: A Final Accounting of Study 352 - James Moore

For the second year in a row, changes to the Abilene City Commission and its staff have been one of the top events of 2019.

This is the second of a two-part series on the top 10 news events of 2019.

The top five which were published Monday were flooding, the Dwight D. Eisenhower Museum, downtown Abilene, economic developments and murals.

The next five include new faces in city government, child care, historical places, Patty OMalley and the Lebold Mansion.

New faces

On May 6 the Abilene City Commission voted 4-0 to terminate the services of its city manager Austin Gilley.

The commission had placed Gilley on paid, indefinite leave at the April 22 meeting.

Just over a month after the termination, the city commission voted Jane Foltz, director of the Abilene Parks and Recreation Department, as interim city manager.

The commission also approved former interim Abilene City Manager Dennis Kissinger as a part-time consultant.

Not only did the city commission change its leadership in 2019, it changed its look.

With the resignation of Terry Chaput, 23-year-old Trevor Witt was appointed in late 2018 to fill the three years left of Chaputs term.

In August Commissioner Sharon Petersen resigned. Former commissioner Angie Casteel was named commissioner.

In the November city commission election, the leading vote getter was Brandon Rein, age 24. Voters also voted incumbents back to the commission, Dee Marshall for four years and Mayor Tim Shafer, two years.

The new commission will be sworn in Jan. 13.

The Abilene Board of Education also has new faces. Greg Brown is the new superintendent. Robert Keener and Veronica Murray were elected to the board in the last election while Gregg Noel and Mark Wilson did not seek reelection.

While their faces have been around the Great Plains Theatre for a while, Mitch Aiello and Layne Roate were introduced as the new co-artistic directors.

Child Care

In early October, 20 families involving 25 children up to the age of 12 were informed that Learn & Grow Depot would no longer provide child care for them starting Jan. 1.

Learn & Grow, a child care facility, planned to continue to provide child care only for employees of Memorial Health System effective Jan. 1.

Learn & Grow is owned and operated by Memorial Health System.

The mission of Learn & Grow Depot has always been to take care of employees children. We currently have employees children on the waiting list and cannot provide that benefit, parents were informed in a letter.

Parents were told that a lack of licensed teachers was the reason Learn & Grow was only going to accept kids from Memorial Health System employees.

Chuck Scott, director of the Dickinson County Economic Development Corporation, told Dickinson County commissioners that child care was at a critical stage with Land Pride starting to add employees at its Abilene West facility.

In a meeting hosted by the economic development corporation, the community was told the number of children needing child care in Dickinson County was estimated at 365 last year.

There is a bigger need than what people recognize, Scott said. It is not a 10 or 20 person need. We are talking in the 300s of children out there that we need to provide a place for.

This is not just a Dickinson County issue, said Tanya Koehn with Child Care Aware. There are meetings like this all over happening.

In mid November it was announced that Robin Hansen, owner of Abilene Childcare Learning Center, was expanding and agreed to lease the Learn & Grow facility to provide child care for hospital staff and members of the community.

Historic Abilene

Both Old Abilene Town and the Dickinson County Historical Society made headlines.

Old Abilene Town hosted can can dancers, gun fighters and evening events in the Alamo Saloon throughout the summer. Just recently it hosted Cowboy Christmas.

The biggest event for Old Abilene Town was another successful Chisholm Trail Days. Much as they did in the 1800s, longhorn cattle were herded through the street and onto rail cars.

In looking a 2020, Old Abilene Town has plans to open a National Old West Trails museum.

We want to move ourselves from not just a tourist destination, but a tourist attraction and all the great things that can happen down in that district, Michael Hook, president of the Historic Abilene, Inc., board of trustees told the Dickinson County Commission.

Several educational programs are planned in 2020, including a Cowboy Camp in July, hosted by OAT and the Community Foundation of Dickinson County.

The Dickinson County Heritage Society changed its name and hosted Heritage Day in September.

A change in the bylaws reducing the number on the Board of Trustees of the Dickinson County Historical Society to seven was voted down by its members during its annual meeting on Nov. 26.

The membership of the society voted to continue to operate under the bylaws adopted in 2018. Those bylaws say the Board of Trustees shall consist of 18 members. It also requires 10 trustees for a quorum.

The membership also elected six new trustees at a standing room only two-hour meeting.

Six new board members were elected at that meeting. Duane Schrag, Cindy Wedel, Gail Whitehair, Mid Hanson, Nanc Scholl and James Holland became board members on Wednesday.

Patty OMalley

More people now are aware that one of the nicest places in Kansas is located in Abilene, thats according to a panel of judges with Readers Digest.

Patty OMalleys Cedar House was named Kansas nominee in the 2019 Nicest Places in America 2019 Readers Digest contest.

Living in the Nicest Place in America means you live in communities that are committed to kindness, trust and health. Life extension is the health solutions expert that is translating scientific research into everyday insights for people wanting to live their healthiest lives. Together, were looking for the community health heroes who are committed to supporting and inspiring communities to live a happier, healthier life, Readers Digest said on its web page in announcing The 50th Nicest Places in America.

Readers Digest tells the story of Patti OMalley and the creation of the rehab center at Cedar House.

It is heartbreaking and heartwarming at the same time, OMalley said. This has been a long six years of a lot of people saying it cant be done. This is some affirmation for all those years. We have made progress and the hope is that now we can do more to help more women.

OMalley built herself a new home while turning what would become Cedar House into a six-bed facility that focuses on hope, healing and giving back to the surrounding community of Abilene, a rural town of some 7,000, famous for being the childhood home of President Dwight D. Eisenhower.

Cedar House now boasts a local food bank and a micro-farm with a greenhouse, which delights locals with its exotic flora.

Lebold Mansion

A killer ghost visited the Lebold Mansion in March.

The vengeful ghost of Mary Wallace haunted the mansion, killing some of its guests.

Those events were in the short film The Haunting of Pottersfield. The film was based on the true story of Lavinia Fisher who is considered to be Americas first female serial killer.

Director and writer Andre Dixon brought actors and a film crew to the mansion.

The film has been nominated for four awards at the Indie Short Fest in Las Angeles: Best Horror Short, Best First Time Director (Andre Dixon), Best Sound Design (Alex Gregson) and Best Special Makeup (Marcus Koch).

But Lebold Mansion events didnt end when the crew left.

Once declared the finest dwelling house west of Topeka by an 1883 history of Kansas, the Lebold Mansion, 106 N. Vine, has had more than its share of ups and downs.

It started as a stone dugout, the first residence in Abilene, built by Timothy Hersey in 1857.

About 40 people crowded into the Dickinson County Commission room in May when the Lebold Mansion and property at 310 S.E. Second Street were sold at a sheriffs office to the Dickinson County Bank of Enterprise for $380,227.78.

This stately mansion boasts as being one of the Eight Architectural Wonders of Kansas. The 10,106 square foot building with five bedrooms and 3-1/2 baths is currently listed for sale.

Contact Tim Horan at editor@abilene-rc.com.

More:
The next five top events of 2019 | News - Abilene Recorder Chronicle

Improved computed tomography (CT) techniques could better recognize manufacturing flaws and structural damage to aerospace composites, improving future aircraft.

University of Texas aerospace engineering researchers will improve reconstruction algorithms and software techniques to produce breakthroughs in computed tomography scanning, which will lead to improved recognition of manufacturing flaws and structural damage of composites. The University of Texas Advanced Materials and Structures Lab uses state-of-the-art facilities.

Andrew Makeev, professor in the University of Texas at Arlingtons Department of Mechanical and Aerospace Engineering, received a $900,000 grant from the Army Research Lab to address the Armys need for better structural diagnostics and life assessment in composite aircraft parts. Makeev, who also directs UTAs Advanced Materials and Structures Lab, will lead the project.

He said UTAs effort will focus on developing effective tools for high-resolution, one-sided computational tomography- or CT-based non-destructive inspection or NDI. One-sided scanning will improve the versatility of CT-based microstructural material characterization and structural diagnostics to virtually unlimited object in-plane dimensions, and help the development of game-changing NDI systems, Makeev said.

Currently, composite aircraft structures are susceptible to damage precursors like porosity and voids, and sustaining fiber-waviness. Those discontinuities may evolve into structural damage in the form of cracks and delamination or composite layer splitting.

X-ray CT has proven to be the only 3D industrial nondestructive inspection which has reliable micro resolution and allows for automated interpretation of the inspection results including the listed flaws. However, the current micro-focus CT technology is based on full scanning or 360 degrees around the object, which limits the technology to small cross sections and prevents accommodation of large structures.

Even small objects, which can be scanned in the existing micro-CT facilities, sometimes do not allow for sufficient magnification of the microstructure during the full scanning. However, available limited-angle reconstructions lose definition and often become erroneous during one-sided inspections.

We believe that to advance composite aircraft structural certification, the analysis must capture manufacturing complexity and variability of flight-critical components and structure, Makeev said. Recent improvement in computing power and advances in X-ray CT reconstruction make it possible to develop high-resolution, one-sided CT inspection technology breaking through the object size limits of X-ray CT. It also offers the long-sought automation for composite aircraft structures.

Inspection of large composite components in a single run addresses a timely and critical need, said Erian Armanios, chair of the Department of Mechanical and Aerospace Engineering. Dr. Makeevs research provides CT software solutions that can combine high degree of automation with high degree of accuracy key end user requirements.

The U.S. Army and helicopter industry are facing the challenge of replacing more than 6,300 military vertical lift aircraft. Earlier this year, Makeev received a separate $600,000 grant from Boeing to assess durability and damage tolerance of composite structures for composite airframe life extension.

Makeev has shouldered many research projects with companies that are especially focused on composite materials and structures. He has current or past grants with Boeing, Lockheed Martin Aeronautics, Sikorsky Aircraft and Bell Helicopter Textron. During his six-year tenure at UTA, Makeev has been conducting pioneering theoretical and experimental work sponsored by the U.S. Army, U.S. Navy, U.S. Air Force and aerospace industry at an average rate of $1 million per year in external funding. His work includes integration of design and manufacturing processes to improve performance of composites, advanced material technologies, material characterization, structural diagnostics and prognostics.

For more information: http://www.uta.edu

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Analysts forecast that Sealed Air Corp (NYSE:SEE) will post sales of $1.30 billion for the current quarter, according to Zacks. Three analysts have made estimates for Sealed Airs earnings, with the highest sales estimate coming in at $1.30 billion and the lowest estimate coming in at $1.29 billion. Sealed Air reported sales of $1.26 billion in the same quarter last year, which would suggest a positive year over year growth rate of 3.2%. The business is expected to announce its next quarterly earnings report on Thursday, February 6th.

On average, analysts expect that Sealed Air will report full-year sales of $4.79 billion for the current financial year, with estimates ranging from $4.78 billion to $4.80 billion. For the next financial year, analysts expect that the business will report sales of $5.01 billion, with estimates ranging from $4.91 billion to $5.20 billion. Zacks Investment Researchs sales calculations are an average based on a survey of research analysts that follow Sealed Air.

Sealed Air (NYSE:SEE) last posted its quarterly earnings results on Wednesday, November 6th. The industrial products company reported $0.64 earnings per share (EPS) for the quarter, topping the Thomson Reuters consensus estimate of $0.62 by $0.02. The firm had revenue of $1.22 billion for the quarter, compared to analyst estimates of $1.23 billion. Sealed Air had a net margin of 7.55% and a negative return on equity of 135.60%. The firms quarterly revenue was up 2.7% compared to the same quarter last year. During the same quarter in the previous year, the business posted $0.61 earnings per share.

In other news, CFO James M. Sullivan bought 5,000 shares of the stock in a transaction on Thursday, November 7th. The shares were purchased at an average price of $38.75 per share, for a total transaction of $193,750.00. Following the completion of the purchase, the chief financial officer now directly owns 17,028 shares of the companys stock, valued at approximately $659,835. The purchase was disclosed in a filing with the SEC, which is available through this link. 0.53% of the stock is currently owned by company insiders.

Several institutional investors and hedge funds have recently bought and sold shares of the company. Evoke Wealth LLC bought a new stake in shares of Sealed Air in the 3rd quarter valued at approximately $1,469,000. Man Group plc increased its stake in shares of Sealed Air by 91.7% during the 3rd quarter. Man Group plc now owns 125,245 shares of the industrial products companys stock worth $5,199,000 after purchasing an additional 59,911 shares during the last quarter. Michael & Susan Dell Foundation increased its stake in shares of Sealed Air by 28.7% during the 3rd quarter. Michael & Susan Dell Foundation now owns 14,760 shares of the industrial products companys stock worth $613,000 after purchasing an additional 3,294 shares during the last quarter. Squarepoint Ops LLC bought a new position in shares of Sealed Air during the 3rd quarter valued at $4,082,000. Finally, Voloridge Investment Management LLC increased its holdings in shares of Sealed Air by 391.5% during the 3rd quarter. Voloridge Investment Management LLC now owns 41,538 shares of the industrial products companys stock valued at $1,724,000 after acquiring an additional 33,087 shares during the last quarter. 94.05% of the stock is owned by institutional investors.

Shares of NYSE:SEE opened at $38.26 on Friday. The companys fifty day moving average is $38.61 and its two-hundred day moving average is $41.11. The company has a market cap of $5.91 billion, a P/E ratio of 15.30, a price-to-earnings-growth ratio of 1.31 and a beta of 1.03. Sealed Air has a 12-month low of $34.92 and a 12-month high of $47.13.

About Sealed Air

Sealed Air Corporation provides food safety and security, and product protection solutions worldwide. It operates in two segments, Food Care and Product Care. The Food Care segment offers integrated packaging materials and equipment solutions to provide food safety, shelf life extension, and total cost optimization for perishable food processors in the fresh red meat, smoked and processed meats, poultry, and dairy markets under the Cryovac, Cryovac Grip & Tear, Cryovac Darfresh, Cryovac Mirabella, Simple Steps, and Optidure brands.

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Sealed Air Corp (NYSE:SEE) Expected to Announce Quarterly Sales of $1.30 Billion - Slater Sentinel

Sealed Air Corp (NYSE:SEE) has been assigned an average rating of Hold from the fourteen brokerages that are currently covering the stock, MarketBeat reports. Three research analysts have rated the stock with a sell rating, eight have assigned a hold rating and two have given a buy rating to the company. The average twelve-month price objective among analysts that have issued a report on the stock in the last year is $44.61.

Several research firms recently issued reports on SEE. Robert W. Baird reaffirmed a buy rating and set a $50.00 price target on shares of Sealed Air in a research note on Monday, November 18th. ValuEngine downgraded shares of Sealed Air from a sell rating to a strong sell rating in a research note on Thursday. KeyCorp raised shares of Sealed Air from an underweight rating to a sector weight rating in a research note on Wednesday, November 6th. They noted that the move was a valuation call. Wells Fargo & Co reaffirmed a hold rating on shares of Sealed Air in a research note on Monday. Finally, Citigroup dropped their price target on shares of Sealed Air from $45.00 to $42.00 and set a neutral rating on the stock in a research note on Thursday, October 17th.

In related news, CFO James M. Sullivan acquired 5,000 shares of the firms stock in a transaction on Thursday, November 7th. The stock was bought at an average cost of $38.75 per share, with a total value of $193,750.00. Following the acquisition, the chief financial officer now directly owns 17,028 shares in the company, valued at $659,835. The acquisition was disclosed in a document filed with the Securities & Exchange Commission, which is available through this link. 0.53% of the stock is owned by company insiders.

A number of hedge funds have recently made changes to their positions in the business. Motco acquired a new position in shares of Sealed Air in the 2nd quarter valued at about $29,000. Doyle Wealth Management acquired a new position in shares of Sealed Air in the 2nd quarter valued at about $40,000. CSat Investment Advisory L.P. boosted its holdings in shares of Sealed Air by 34.1% in the 2nd quarter. CSat Investment Advisory L.P. now owns 1,234 shares of the industrial products companys stock valued at $53,000 after buying an additional 314 shares during the period. Penserra Capital Management LLC boosted its holdings in shares of Sealed Air by 556.0% in the 3rd quarter. Penserra Capital Management LLC now owns 1,804 shares of the industrial products companys stock valued at $74,000 after buying an additional 1,529 shares during the period. Finally, Massey Quick Simon & CO. LLC acquired a new position in shares of Sealed Air in the 3rd quarter valued at about $96,000. 94.07% of the stock is owned by institutional investors.

Sealed Air stock traded down $0.16 during midday trading on Friday, hitting $38.54. 30,675 shares of the stock were exchanged, compared to its average volume of 972,233. Sealed Air has a 1 year low of $32.33 and a 1 year high of $47.13. The firm has a market cap of $5.99 billion, a P/E ratio of 15.42, a P/E/G ratio of 1.41 and a beta of 1.00. The company has a 50 day moving average price of $39.18 and a two-hundred day moving average price of $41.51.

Sealed Air (NYSE:SEE) last released its quarterly earnings results on Wednesday, November 6th. The industrial products company reported $0.64 earnings per share (EPS) for the quarter, topping the Thomson Reuters consensus estimate of $0.62 by $0.02. Sealed Air had a net margin of 7.55% and a negative return on equity of 135.60%. The firm had revenue of $1.22 billion for the quarter, compared to the consensus estimate of $1.23 billion. During the same quarter in the previous year, the firm posted $0.61 EPS. The firms quarterly revenue was up 2.7% on a year-over-year basis. On average, equities research analysts anticipate that Sealed Air will post 2.78 EPS for the current fiscal year.

The business also recently disclosed a quarterly dividend, which will be paid on Friday, December 20th. Shareholders of record on Friday, December 6th will be issued a dividend of $0.16 per share. This represents a $0.64 annualized dividend and a yield of 1.66%. The ex-dividend date is Thursday, December 5th. Sealed Airs dividend payout ratio is currently 25.60%.

About Sealed Air

Sealed Air Corporation provides food safety and security, and product protection solutions worldwide. It operates in two segments, Food Care and Product Care. The Food Care segment offers integrated packaging materials and equipment solutions to provide food safety, shelf life extension, and total cost optimization for perishable food processors in the fresh red meat, smoked and processed meats, poultry, and dairy markets under the Cryovac, Cryovac Grip & Tear, Cryovac Darfresh, Cryovac Mirabella, Simple Steps, and Optidure brands.

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Sealed Air Corp (NYSE:SEE) Receives Average Recommendation of Hold from Brokerages - Riverton Roll

Sealed Air (NYSE:SEE)s stock had its hold rating restated by analysts at Wells Fargo & Co in a report issued on Monday, December 9th, AnalystRatings.com reports.

A number of other analysts have also weighed in on SEE. KeyCorp upgraded Sealed Air from an underweight rating to a sector weight rating in a report on Wednesday, November 6th. They noted that the move was a valuation call. Citigroup reduced their price target on Sealed Air from $45.00 to $42.00 and set a neutral rating on the stock in a research report on Thursday, October 17th. ValuEngine raised Sealed Air from a strong sell rating to a sell rating in a research report on Tuesday, November 19th. Finally, Robert W. Baird reaffirmed a buy rating and set a $50.00 price target on shares of Sealed Air in a research report on Monday, November 18th. One equities research analyst has rated the stock with a sell rating, eight have given a hold rating and three have given a buy rating to the companys stock. Sealed Air currently has a consensus rating of Hold and an average price target of $44.33.

Sealed Air stock traded down $0.61 during mid-day trading on Monday, reaching $38.26. 1,144,692 shares of the company were exchanged, compared to its average volume of 989,617. The business has a fifty day moving average of $38.61 and a 200 day moving average of $41.11. The firm has a market cap of $5.91 billion, a P/E ratio of 15.30, a PEG ratio of 1.31 and a beta of 1.03. Sealed Air has a 12-month low of $34.92 and a 12-month high of $47.13.

Sealed Air (NYSE:SEE) last posted its earnings results on Wednesday, November 6th. The industrial products company reported $0.64 earnings per share for the quarter, topping analysts consensus estimates of $0.62 by $0.02. The company had revenue of $1.22 billion during the quarter, compared to analyst estimates of $1.23 billion. Sealed Air had a negative return on equity of 135.60% and a net margin of 7.55%. Sealed Airs revenue was up 2.7% on a year-over-year basis. During the same quarter in the prior year, the business earned $0.61 earnings per share. As a group, equities research analysts predict that Sealed Air will post 2.78 EPS for the current fiscal year.

In other news, CFO James M. Sullivan bought 5,000 shares of the businesss stock in a transaction that occurred on Thursday, November 7th. The shares were purchased at an average cost of $38.75 per share, with a total value of $193,750.00. Following the transaction, the chief financial officer now directly owns 17,028 shares in the company, valued at $659,835. The transaction was disclosed in a legal filing with the Securities & Exchange Commission, which is accessible through this link. 0.53% of the stock is owned by corporate insiders.

Several hedge funds and other institutional investors have recently added to or reduced their stakes in SEE. FMR LLC increased its position in shares of Sealed Air by 3.1% in the 1st quarter. FMR LLC now owns 88,646 shares of the industrial products companys stock valued at $4,083,000 after acquiring an additional 2,697 shares during the period. Steward Partners Investment Advisory LLC acquired a new stake in Sealed Air during the 2nd quarter worth about $152,000. Los Angeles Capital Management & Equity Research Inc. grew its position in Sealed Air by 4.6% during the 2nd quarter. Los Angeles Capital Management & Equity Research Inc. now owns 143,346 shares of the industrial products companys stock worth $6,132,000 after purchasing an additional 6,285 shares during the period. First Trust Advisors LP acquired a new stake in Sealed Air during the 2nd quarter worth about $3,762,000. Finally, Aperio Group LLC grew its position in Sealed Air by 1.7% during the 2nd quarter. Aperio Group LLC now owns 64,135 shares of the industrial products companys stock worth $2,743,000 after purchasing an additional 1,064 shares during the period. 94.05% of the stock is currently owned by hedge funds and other institutional investors.

About Sealed Air

Sealed Air Corporation provides food safety and security, and product protection solutions worldwide. It operates in two segments, Food Care and Product Care. The Food Care segment offers integrated packaging materials and equipment solutions to provide food safety, shelf life extension, and total cost optimization for perishable food processors in the fresh red meat, smoked and processed meats, poultry, and dairy markets under the Cryovac, Cryovac Grip & Tear, Cryovac Darfresh, Cryovac Mirabella, Simple Steps, and Optidure brands.

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Sealed Air (NYSE:SEE) Stock Rating Reaffirmed by Wells Fargo & Co - Riverton Roll