Archive for October, 2019

My first diagnosis was stage IIIC breast cancer, which is as close as you can get to stage IV without actually being stage IV, which is terminal. At that point, IIIC, youre still considered curable.

My oncologist told me that I had triple-negative breast cancer, which can be more aggressive and more difficult to treat than other forms of breast cancer. (Triple-negative breast cancer doesnt respond to some common breast-cancer treatments, such as hormone therapy.)

I went through chemotherapy and then had a double mastectomy in May of 2018. The lump was in one breast, but I felt like I would always worry that wed missed something if I hadnt had both removed. I have three sonsnow 12, 13, and 16and every step of the way, Ive wanted to do whatever I could to heal myself and be here for them.

I made the most of my (bald) 44th birthday.

The mastectomy was followed by a second round of chemotherapy, which was followed by radiation. And then my oncologist said, Youve done all the treatment thats reasonable at this point. Now you need to go back to your normal life and watch for any symptoms. Well check you out every three to six months.

After recovering from the radiation, I went back to work the first week in December. I worked for a month and then was diagnosed with stage IV cancer the first week of January.

The cancer had metastasized to my liver and lungs. I did even more chemotherapy, but a follow-up scan showed that the tumor in my liver had doubled in size in the three months since my last scan. Following treatment, some tumors will shrink or disappear. The 14-centimeter tumor in my liver didnt react that way; its there, not getting smaller. There really isnt much room left in my liver. For now, my best-case scenario is that the cancer doesnt spread further.

It was really hard to tell my kids. Ive always wanted to be really honest with them. I was honest about what I had and that it was serious. Theyre old enough that they can do their own research. There was no point in trying to mislead them from the beginning. Also, I tried to be lighthearted.

I want my sons to know and remember how much I love them. Im glad that theyre at a point where theyll remember me. And my husband can remind them.

My eldest son has thanked me a couple of times for handling things so well. He feels like the fact that Im not complaining a lot or acting down or sad or depressed has been really helpful. I really try to stay positive and make the most out of all the moments that I still do have with them.

It was hard for them to see me go bald again. Having my hair grow back was a big milestone for my kids. My youngest, especially, was so excited when my hair started to grow back. He would measure it and rub my headhe really celebrated me starting to look more normal again.

More here:
This Mom Has Terminal Breast Cancer, But Shes Still Fighting for Her Kids - Glamour

Animal sociability through microbes

Accumulating evidence suggests that the microbiota living in and on animals has important functions in the social architecture of those animals. Sherwin et al. review how the microbiota might facilitate neurodevelopment, help program social behaviors, and facilitate communication in various animal species, including humans. Understanding the complex relationship between microbiota and animal sociability may also identify avenues for treating social disorders in humans.

Science, this issue p. eaar2016

Increasingly, it is recognized that the microbes resident in the gastrointestinal tract can influence brain physiology and behavior. Research has shown that the gastrointestinal microbiota can signal to the brain via a diverse set of pathways, including immune activation, production of microbial metabolites and peptides, activation of the vagus nerve, and production of various neurotransmitters and neuromodulators in the gut itself. Collectively, this bidirectional pathway is known as the microbiota-gut-brain axis. In the absence of a microbiota, germ-free and antibiotic-treated mice exhibit alterations to several central physiological processes such as neurotransmitter turnover, neuroinflammation, neurogenesis, and neuronal morphology. Perhaps as a result of these neurological alterations, the behavior of rodents lacking a microbiotaespecially social behavioris remarkably different from that of rodents colonized with bacteria. Conversely, supplementation of animals with certain beneficial live bacteria (e.g., Bifidobacterium and Lactobacillus) can lead to notable improvements in social behavior both in early life and in adulthood. Collectively, these results suggest that microbial signals are important for healthy neurodevelopment and programming of social behaviors in the brain. Although research on the functional and ecological implications of the gut microbiota in natural populations is growing, from an evolutionary perspective it remains unclear why and when relationships between microbes and the social brain arose. We propose that a trans-species analysis may aid in our understanding of human sociability.

Sociability comprises a complex range of interactive behaviors that can be cooperative, neutral, or antagonistic. Across the animal kingdom, the level of sociability an animal displays is variable; some are highly social (e.g., primates, termites, and honey bees), living within cooperative communities, whereas others have a mostly solitary existence (e.g., bears). Consequently, although studies on germ-free and antibiotic-treated animals have yielded insights into how the microbiota may influence social behaviors, they are perhaps too reductionist to fully appreciate the complex relationship between symbiotic bacteria in the gastrointestinal tract and host sociability when considering a broader zoological perspective. Some social interactions have evolved to facilitate horizontal transmission of microbiota. Observations across both invertebrate and vertebrate species suggest that factors such as diet and immunity generate selection pressures that drive the relationship between microbiota and social behavior. Although microbiota may influence behaviors endogenously through regulation of the gut-brain axis, some animal species may have evolved to use symbiotic bacteria exogenously to mediate communication between members of the same species. Hyenas, for example, produce an odorous paste from their scent glands that contains fermentative bacteria that is suggested to facilitate social cohesion among conspecifics. This complex relationship between animals and microbiota raises the hypothesis that microbes may have influenced the evolution of the social brain and behavior as a means to propagate their own genetic material.

Understanding the factors that affect the development and programming of social behaviors across the animal kingdom is important not only in terms of rethinking the evolution of brain physiology and behavior, but also in terms of providing greater insight into disorders of the social brain in humans [including autism spectrum disorders (ASDs), social phobia, and schizophrenia]. Evidence for a link between the microbiota and these conditions is growing, and preclinical and emerging clinical data raise the hypothesis that targeting the microbiota through dietary or live biotherapeutic interventions can improve the associated behavioral symptoms in such neurodevelopmental disorders. Larger clinical trials are required to confirm the efficacy of such interventions before they are recognized as a first-line treatment for neurodevelopmental disorders. Although such connections between gut bacteria and neurodevelopmental disorders are currently an intriguing area of research, any role for the microbiota in the evolution of social behaviors in animals does not supersede other contributing factors. Rather, it adds an additional perspective on how these complex behaviors arose.

The bidirectional pathway between the gut microbiota and the central nervous system, the microbiota-gut-brain axis, influences various complex aspects of social behavior across the animal kingdom. Some animals have evolved their own unique relationship with their gut microbiota that may assist them in interacting with conspecifics. The relationship between the gut microbiota and social behavior may help to explain social deficits observed in conditions such as autism spectrum disorders (ASDs) and could potentially lead to the development of new therapies for such conditions.

Sociability can facilitate mutually beneficial outcomes such as division of labor, cooperative care, and increased immunity, but sociability can also promote negative outcomes, including aggression and coercion. Accumulating evidence suggests that symbiotic microorganisms, specifically the microbiota that reside within the gastrointestinal system, may influence neurodevelopment and programming of social behaviors across diverse animal species. This relationship between host and microbes hints that host-microbiota interactions may have influenced the evolution of social behaviors. Indeed, the gastrointestinal microbiota is used by certain species as a means to facilitate communication among conspecifics. Further understanding of how microbiota influence the brain in nature may be helpful for elucidating the causal mechanisms underlying sociability and for generating new therapeutic strategies for social disorders in humans, such as autism spectrum disorders (ASDs).

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Microbiota and the social brain - Science Magazine

If you tend to wake up feeling like all you need is "just one more hour" of sleep, youre probably pretty stoked about "falling back" an hour this Halloweekend, marking the end of Daylight Saving Time. After all, when you change your clocks (or, let your iPhone do it for you) to switch back to standard time, you're gifted with an extra hour of sleep basically the best thing since the advent of the snooze button, right?

Well, according to experts, while you may gain that extra hour this weekend, the end of DST can actually have some pretty negative effects on your sleep and overall health.

In fact, although around 70 countries currently participate in DST, several are now pushing to scrap the practice altogether, citing general unpopularity and public health concerns. (One scary example? Scientists found that the pedestrian risk for being struck and killed by a car at 6 p.m. in November, when DST ends, is 11 times higher than the risk at 6 p.m. in April, when DST begins.)

Because at least for now DST isnt going anywhere in the U.S., its important to know what lies ahead. Here, experts weigh in on how Daylight Saving Time affects your health and mood and how you can squash symptoms related to the transition.

RELATED: We Tried 4 Products Designed to Help You Sleep Better

Youve probably already guessed this one, but the reason your sleep suffers as a result of the time change comes down to light (or lack thereof), says Clifford Segil, DO, a neurologist at Providence Saint John's Health Center.

"We get used to going to sleep a few hours after it gets dark, which is disrupted when all of sudden it's dark earlier than we are used to, Dr. Segil says. "Its hard for many people to continue to fall asleep at the same time or to maintain good sleep for the same amount of time as they did before a time change."

Someone whos regularly logging plenty of sleep will be able to adapt more easily to the shift. However, it can feel like the last straw if you are already dealing with not-so-great sleep habits, says Caroline Rasmussen, a meditation teacher, herbalist, and founder of brain health company, Antara.

The fix: Light cues can help your body's internal clock adjust more quickly to the time change, Dr. Segil says. If you wake up and its still dark, try to mimic morning light by turning on a nearby light or salt lamp, Dr. Segil says. He adds that the type of light isn't as important as the duration of time spent in the light and the volume of light the more the better. The same goes for when nighttime darkness begins to creep in; turn on a lamp at your desk if you can so your system knows it's not time for bed.

Maintaining a consistent sleep schedule aiming to hit the hay and wake up at the same time each day can also shorten the time it takes to feel back to normal after a time change, Dr. Segil adds.

As a result of poor sleep, your mood, productivity level, and concentration may all suffer, Dr. Segil says. Beyond feeling irritable and sluggish, theres a more serious mental health risk at play, too.

A 2016 study published in Epidemiology showed that depression diagnoses have a tendency to spike as people make the transition out of DST and into standard time. The studys authors noted that they believe the shift is related to the "psychological distress associated with the sudden advancement of sunsetwhich marks the coming of winter and a long period of short days."

This could be related to a larger condition that affects people during the winter months Seasonal Affective Disorder (aka SAD). People who experience SAD notice an increase in depressive symptoms in early fall or winter that experts say is linked to decreased exposure to light.

"The change in light information created by the time change directly influences the level of stress hormones in the body," Rasmussen says. If you already have chronically elevated cortisol levels, the time change can have an even more noticeable, negative impact on mood, she adds.

RELATED: 8 Signs You Might Have Seasonal Affective Disorder

The fix: If you think you have SAD, seek help from a mental health expert, who may recommend medication or light therapy; a 2009 study showed using a light box daily for 20 to 40 minutes resulted in significant and immediate mood improvement in people with SAD.

If its an overall feeling of irritability or stress you're experiencing, you may also want to consider adding in relaxing habits, like sipping tea. Not only is the act soothing, but Rasmussen says tea also contains L-theanine, an amino acid that can help keep stress at bay. On the supplement home front, consider popping an adaptogen, like tulsi or ashwagandha, which can help ease anxiety.

"Adaptogens help balance the stress response system for example by restoring the normal sensitivity of our cortisol receptors so that the adrenals aren't forced to pump out overly high levels of the hormone to achieve the same physiological effect," Rasmussen says.

Surprisingly, the time change and subsequent disruption of our circadian patterns can also have downstream effects on everything from our levels of inflammation to our eating habits, Rasmussen says.

"The brain is programmed for a 24-hour day, and when our internal clocks are disrupted, it leads to a domino effect, disrupting many bodily functions, including your appetite, body temperature, bowel function, and even heart and lung function," explains David Cutler, M.D., a California-based family medicine physician. Because these functions are all controlled by the brains internal clock, the end of DST can take your body on a bit of a roller coaster, he adds.

Translation: If you notice you're way hungrier than usual or that your digestion is out of wack DST may actually be partially to blame.

The fix: While there are some health factors out of your control, it never hurts to help your body along by taking care of it with diet and exercise. Aim to stick to your regular workout schedule at least 150 minutes per week of moderate-intensity aerobic activity per week or 75 minutes of vigorous aerobic activity and save protein-heavy meals (which involve more digestion and may disrupt your sleep) for earlier in the day, Rasmussen says.

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How the End of Daylight Saving Time Can Affect Your Health - Yahoo Lifestyle

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Sen. Edward J. Markey (D-MA) and Rep. Earl Blumenauer (D-OR) reintroduced Tuesday legislation is designed to reduce the nations nuclear weapons budget by $75 billion over the next decade.

The Smarter Approach to Nuclear Expenditures (SANE) Act would enhance national security and cut what they deem redundant and destabilizing nuclear programs.

The United States should fund education, not annihilation; that is our future, Markey said. We need sanity when crafting Americas budget priorities and more and improved nuclear weapons defies common sense. The SANE Act cuts nuclear weapons and delivery systems that we dont need so we can invest in the people and programs that will make America safe and prosperous in the future.

The bill reduces the purchase of Columbia-class submarines from 12 to eight, cutting the existing ICBM fleet from over 400 to 150, and trims deployed strategic warheads from approximately 1,500 to 1,000; cancels development of a new air-launched cruise missile and an associated warhead life extension program; and lowers to 80 the purchase of new B-21 long-range bombers.

These disastrous weapons will never be the answer to solving our complex and ever-changing national security threats, especially with a reckless administration in charge of the codes, Blumenauer said. We should not be investing trillions of dollars of our budget on an outdated and irresponsible nuclear arsenal. There are far more important programs and initiatives that will actually help and protect the American people. This legislation will put us on the path towards a safer, nuclear-free future.

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Bill seeks to cut nuclear weapons budget - Homeland Preparedness News

Canaccord has raised its target price for Perseus from $1.05 per share to $1.20 per share (current price: 84 cents per share).

() operates two gold mines in West Africa, Edikan and Sissingu, and is developing its third mine - Yaour.

The companys share price has outperformed most of its gold producer peers since August, which can be attributed to a growing recognition of its improved operational stability and a diversified production base.

has increased its target price for Perseus to $1.20 per share (from $1.05 per share) on incorporation of Canaccords updated gold price deck and revisions to FY20 forecasts.

Following is an extract from Canaccords research update:

SepQ production in line, beat on costs: Group production of 66koz was broadly in line with CGe of 68koz, with AISC of US$922/oz lower than CGe of US$1,022/oz on improved unit costs at both operating assets. The result implies a run rate in line with H1'FY20 guidance which at this stage looks comfortably achievable, in our view. SepQ operational cashflow was strong at US$30m, with cash and bullion at quarter end of A $179m.

Edikan - lower feed grade driven by mining sequence: Edikan produced 44.1koz at AISC of US$1,027/oz, vs CGe of 49.4koz at US$1,031/oz. Production was lower on milled grade (0.91g/t vs CGe 1.03g/t) and slightly lower recovery. The grade performance was a function of mining sequence with grades expected to improve over the remainder of FY20. AISC was slightly higher on lower production offsetting lower mining and processing unit rates.

Sissingue - beat on production and costs: Sissingue produced 21.7koz at AISC of US $709/oz, vs CGe of 18.6koz at US$870/oz. Production was higher on plant throughput (453kt vs CGe 380kt) driven by better than expected mining rates following successful implementation of wet season mitigation controls. AISC was lower on higher production, compounded by lower unit rates.

Outlook: FY20 guidance is unchanged at 260-300koz at AISC of US$800-975/oz, and is weighted with a 54% split in favour of H2. Our FY20 production forecast increases slightly to 280koz at AISC US$955/oz (from CGe 277koz at US$989/oz) on incorporating higher grades at both Edikan and Sissingue in 2HFY20.

Growth - Yaoure progressing in line with forecasts; mine life extension opportunities at Sissingue : Yaoure site earth works were largely unaffected by the wet season and progressed in line with plan. Contractors began mobilising to site late in the SepQ with full construction of the processing plant expected to commence this month. Targeted construction finish and first gold pour remains on schedule for DecQ'20.

At Sissingue, regional exploration at the Zanikan prospect has identified multiple mineralised structures over a strike of 500m. Highlights from drilling include 12m at 4.5 g/t from 60m, 10m at 5 g/t from 136m and 8m at 60 g/t from 80m. While early stage, Zanikan presents as possible new satellite for Sissingue, incrementally adding to the remaining ~4 year reserve life.

Our target price increases to A$1.20/sh (from A$1.05/sh) on incorporation of our updated price deck (2019-2025 average gold price +5% to US$1,548/oz, LT +5% to US $1,603oz; LT AUD:USD -4% to 0.68) and revisions to our FY20 forecasts.

PRU has outperformed most of its gold producer peers since August, which we attribute to a growing recognition of PRU's improved operational stability and now diversified (i.e. lower risk) production base. We continue to see PRU as undervalued on both an absolute and relative basis, and maintain our BUY rating.

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Perseus Mining has target price raised by Canaccord Genuity - Proactive Investors Australia

Sealed Air Corp (NYSE:SEE) has been given an average recommendation of Hold by the fourteen ratings firms that are covering the firm, Marketbeat Ratings reports. Four analysts have rated the stock with a sell recommendation, seven have assigned a hold recommendation and two have assigned a buy recommendation to the company. The average 12 month price objective among brokerages that have issued a report on the stock in the last year is $43.70.

A number of equities analysts recently weighed in on the stock. Citigroup reduced their target price on shares of Sealed Air from $45.00 to $42.00 and set a neutral rating for the company in a research note on Thursday, October 17th. Wells Fargo & Co upped their target price on shares of Sealed Air from $42.00 to $43.00 and gave the stock a market perform rating in a research note on Tuesday, August 6th. KeyCorp restated a sell rating and set a $39.00 price objective on shares of Sealed Air in a research note on Friday, August 2nd. Finally, ValuEngine downgraded shares of Sealed Air from a sell rating to a strong sell rating in a research note on Thursday, October 10th.

NYSE SEE traded down $0.38 on Thursday, reaching $41.31. The company had a trading volume of 63,752 shares, compared to its average volume of 722,588. The firm has a market capitalization of $6.45 billion, a price-to-earnings ratio of 16.52, a price-to-earnings-growth ratio of 1.56 and a beta of 1.08. Sealed Air has a 1-year low of $30.47 and a 1-year high of $47.13. The companys fifty day moving average is $40.88 and its 200-day moving average is $42.86.

The firm also recently disclosed a quarterly dividend, which will be paid on Friday, December 20th. Stockholders of record on Friday, December 6th will be paid a dividend of $0.16 per share. The ex-dividend date of this dividend is Thursday, December 5th. This represents a $0.64 dividend on an annualized basis and a dividend yield of 1.55%. Sealed Airs dividend payout ratio is 25.60%.

Several institutional investors have recently bought and sold shares of SEE. Motco acquired a new position in shares of Sealed Air during the 2nd quarter worth about $29,000. Doyle Wealth Management bought a new stake in shares of Sealed Air in the 2nd quarter valued at about $40,000. CSat Investment Advisory L.P. raised 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 purchasing an additional 314 shares during the period. Massey Quick Simon & CO. LLC bought a new stake in shares of Sealed Air in the 3rd quarter valued at about $96,000. Finally, Rockefeller Capital Management L.P. raised its holdings in shares of Sealed Air by 51.4% in the 2nd quarter. Rockefeller Capital Management L.P. now owns 2,894 shares of the industrial products companys stock valued at $124,000 after purchasing an additional 983 shares during the period. Institutional investors own 96.58% of the companys stock.

Sealed Air Company Profile

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.

Further Reading: Understanding the two types of arbitrage

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Sealed Air Corp (NYSE:SEE) Given Average Recommendation of Hold by Brokerages - Mitchell Messenger

SEATTLE, Oct. 31, 2019 /PRNewswire/ -- RareCyte announces an addition to the RarePlex Staining Kit product line, enabling customers to evaluate HER2 and ER expression on circulating tumor cells (CTCs) in their own laboratory. HER2 and ER are biomarkers that direct treatment recommendations for invasive breast cancer, and liquid biopsy offers a blood-based method to evaluate biomarker expression for insight into receptor status, response to treatment, and potentially therapy selection in clinical research.

The RarePlex HER2/ER CTC Panel Kit includes all the reagents necessary for immunofluorescent detection of CTCs along with HER2 and ER expression. When combined with the RareCyte platform for CTC analysis, the RarePlex HER2/ER CTC Panel Kit enables the first blood-to-result breast-specific CTC assay deployable in customer laboratories.

The HER2/ER Panel Kit was validated based on rigorous requirements set to clinical standards with guidance from CLIA and industry experts. Tad George, PhD, Sr. VP of Biology R&D at RareCyte noted "Our approach to CTC assay development and validation is centered on creating deployable products that combine the sensitivity, specificity, and precision required for multi-center trials, not only for CTC enumeration but also for classifying CTCs based on their biomarker phenotypes."

Dr. Minetta Liu, MD, Professor and Research Chair in the Department of Oncology at Mayo Clinic recently presented her work with the HER2/ER CTC Panel Kit at the Advances in Circulating Tumor Cells Conference in Corfu, Greece. "Our early work with this assay has revealed interesting patterns of HER2/ER expression that vary widely across patients. Efforts will now focus on defining thresholds for HER2 and ER positivity that are specific to CTCs. This platform will facilitate important investigations into the clinical significance of CTC heterogeneity relative to standard tissue-based definitions of HER2 positive and/or hormone receptor positive advanced breast cancer."

The HER2/ER Panel Kit is available for purchase and more information on the HER2/ER Panel Kit and the RareCyte platform is available at rarecyte.com.

RareCyte products are for research use only. Not for use in diagnostic procedures.

About RareCyte, Inc.

RareCyte offers next generation instruments, consumables and reagents for the analysis and capture of rare cells from blood and tissue, enabling its foundational liquid biopsy and tissue analysis platform. The company has deep experience in developing advanced precision life science systems used in cutting-edge labs worldwide. Our customers perform innovative research, bring new therapeutics to market, and perform a wide-range of single cell applications in oncology, prenatal testing, and infectious disease. For more information about RareCyte, visitrarecyte.com.

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RareCyte expands liquid biopsy offering with the release of a HER2/ER breast cancer CTC Panel Kit - Daily Record-News

Abbie Duggar is having a rough time. The 27-year-old, who is expecting her first child with husband John David Duggar, 29, has been battling severe morning sickness, the dad-to-be told Us Weekly. He called the experience scary.

Abbie who is due early next year was diagnosed with hyperemesis gravidarum, John David explained. Its a type of serious morning sickness that causes extreme nausea and vomiting. It can lead to dehydration, weight loss, and can sometimes requires hospitalization.

It hit her hard, and she was down for probably seven weeks with severe morning sickness, he told the magazine. She got diagnosed with hyperemesis gravidarum, and she was hospitalized a couple times. We made multiple visits to the ER for dehydration. She couldnt eat, pretty much, or drink, or anything. So she was actually on IVs and had IVs at home. So that was a pretty scary time.

While Abbies illness was alarming, John David stepped up to care for his wife and make sure she was as comfortable as possible.

I keep her water filled up, and her snacks for her, the Counting On star explained. I keep her eating and just comfortable. Anything I can get for her, I try to. I run to the store, [get] whatever she needs, just keep her as comfortable as possible when shes feeling bad.

Abbie says shes been grateful for her husbands help. Hes cooked for me. Hes cleaned. Hes just been an angel, she said.

Hyperemesis gravidarum affects fewer than 3% of pregnant women, according to WebMD. Many people had never heard of it until 2012, when the royal family revealed that Kate Middleton was suffering from the condition during her pregnancy with Prince George. The duchess had to be admitted to the hospital for treatment. She experienced the condition again during her second and third pregnancies.

Since then, a number of celebrities have opened up about their struggle with the condition. Amy Schumers hypermesis was so serious she had to be hospitalized.

I have hyperemesis and it blows, the comedian wrote on Instagram. Very lucky to be pregnant but this is some bullsh*t!

Amber Rose also experienced the extreme nausea and vomiting associated with the condition. Im tired and I just want to barf all day. Its just not fun. But its totally worth it, she said in an Instagram video.

Doctors arent entirely sure what causes hyperemesis gravidarum, though it might be related to changes in hormone levels, according to the Cleveland Clinic. Symptoms usually begin in the first trimester and include vomiting multiple times per day, losing a significant amount of weight, dizziness and lightheadness, and dehydration.

Women whove experienced the condition describe not being able to keep down most food, being unable to get out of bed, and feeling so awful they considered ending the pregnancy.

Treatment for hyperemesis gravidarum can include anti-nausea medications, intravenous fluids, and ginger. Some women may need to be hospitalized if the condition is severe.

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'Counting On': Pregnant Abbie Duggar Is Battling the Same Condition That Afflicted Kate Middleton - Showbiz Cheat Sheet

SAN DIEGO, Oct. 30, 2019 /PRNewswire/ -- Eurofins Discovery, a leading partner to drug discovery and development scientists, today announced a Founding Partner sponsorship agreement with BioLabs San Diego. The agreementprovides support for BioLabs, San Diego's premium wet lab and shared office facilities for early stage life science entrepreneurs and offers resident companies access to Eurofins Discovery's global expertise in products and services to fast-track their development programs in therapeutics, diagnostics, and life science tools.

Eurofins Discovery provides a specialized portfolio that is critical to driving drug programs through the early phases from target discovery to the clinic. Christina Shasserre, SVP of Eurofins Discovery, comments, "Our group has been recognized for over 40 years as the industry leader providing researchers with the largest and most technically deep portfolio for drug discovery. This portfolio was built by the same kind of pioneers that we are looking to foster in the BioLabs facilities. By sharing our significant expertise in drug discovery and offering products and services through our global laboratory network, we hope to accelerate the time it takes to discover innovative therapies and technologies."

Eurofins Discovery and BioLabs will work together to develop a new BioLabs-managed site that will promote the thriving startup community in San Diego. It will be equipped specifically for therapeutic, diagnostic and life science technology companies and will capitalize on the Eurofins Discovery team's high-quality, actionable insights in pre-clinical strategy and scientific research across the drug discovery continuum."We are excited by this opportunity to partner with BioLabs San Diego and work with companies developing first-in-class therapeutic tools and products," says Justin Mika, SVP of Strategy and Business Development for Eurofins Discovery and General Manager of Eurofins DiscoverX Services. "Eurofins Discovery is committed to working with early stage companies to provide turn-key solutions for the drug discovery, screening and life science markets. In addition, some of our team members are sharing the space at the BioLabs San Diego Towne Centre facility to support closer engagement and collaboration with company founders and scientists daily. We look forward to helping entrepreneurs improve the productivity and effectiveness of their research so they can get their innovative products to market more quickly and cost-efficiently."

Adam Milne, vice president of operations for BioLabs says he welcomes Eurofins Discovery as a Founding Sponsor. "The leadership of Eurofins Discovery is committed to serving companies that benefit from the BioLabs San Diego co-working space model, which provides shared wet lab and office facilities and a suite of services. We see the potential to develop further program offerings like the Eurofins-BioLabs Innovation Center with Eurofins Discovery as we work collaboratively to help member companies that are developing therapeutics, diagnostics and life sciences tools get to proof of concept and move to the next stage of product development."

Abegale Colmenar, site director for BioLabs San Diego, says, "We appreciate the support from Eurofins Discovery for our work to create a vibrant community for the most promising life sciences startups. The added benefit of their global industry knowledge will be a plus for our member companies, and a demonstration of the value that BioLabs offers startups that want to scale and grow."

Eurofins Discovery will partner with BioLabs in its 2 San Diego locations in the University Town Centre (UTC) area. BioLabs, San Diego at Campus Pointe by Alexandria offers flexible and fully equipped co-working space designed for early stage companies needing access to shared workstations and wet lab space. BioLabs, San Diego - Towne Centre is designed for entrepreneurs seeking office space, as well as for early-stage companies that want the benefits of being part of BioLabs' creative innovation ecosystem but do not require the full wet-lab facilities offered at Campus Pointe.

For further informationwww.eurofinsdiscoveryservices.com http://www.eurofins.com

About Eurofins DiscoveryEurofins Discovery, a business operating under the Eurofins BioPharma Services division, has supported Drug Discovery research for over 40 years. Eurofins is recognized as the industry leader for providing drug discovery researchers the largest and most diverse portfolio of standard and customin vitrosafety & pharmacology assays and panels for drug screening and profiling. In addition toin vitrosafety pharmacology strengths, we also offer a broad portfolio of over 3500 drug discovery services and 1800 products. These includein vitroassays, cell-based phenotypic assays, safety pharmacology and efficacy, ADME toxicology, medicinal chemistry design, synthetic chemistry, and custom proteins and assay development capabilities. We support a variety of drug discovery targets such as GPCRs, Kinases, Ion Channels, Nuclear Hormone Receptors and other proteins & enzymes. The Eurofins Discovery capabilities, expertise, knowledge and skill sets enable the company to provide clients the benefit of being able to work with a single outsourcing provider (CRO) for all their drug discovery programs.

About BioLabs and BioLabs San Diegowww.BioLabs.iotwitter:@BioLabSD and @BioLabs

BioLabs is a membership-based network of shared lab facilities located in the nation's key biotech innovation clusters, designed exclusively for high-potential, early-stage life science companies. It offers co-working environments that pair premium, fully-equipped and supported lab and office space with unparalleled access to capital and industry partners. This fertile, supportive ecosystem allows nascent companies to shift their focus from startup operations to innovation so they can reach their scientific potential quickly and achieve business success. Companies can start with a single bench, and scale up as they grow. Visitwww.BioLabs.io to learn more and apply for space.

Notes for the editor:

Eurofins a global leader in bio-analysisEurofins Scientific through its subsidiaries (hereinafter sometimes "Eurofins" or "the Group") is a scientific leader in food, environment, pharmaceutical and cosmetics products testing and in agroscience CRO services. It is also one of the global independent market leaders in certain testing and laboratory services for genomics, discovery pharmacology, forensics, CDMO, advanced material sciences and for supporting clinical studies. In addition, Eurofins is one of the leading global emerging players in specialty clinical diagnostic testing. With about 45,000 staff in more than 800 laboratories across 47 countries, Eurofins offers a portfolio of over 200,000 analytical methods for evaluating the safety, identity, composition, authenticity, origin and purity of biological substances and products, as well as for innovative clinical diagnostic. The Group objective is to provide its customers with high-quality services, accurate results on time and expert advice by its highly qualified staff.

Eurofins is committed to pursuing its dynamic growth strategy by expanding both its technology portfolio and its geographic reach. Through R&D and acquisitions, the Group draws on the latest developments in the field of biotechnology and analytical chemistry to offer its clients unique analytical solutions and the most comprehensive range of testing methods.

As one of the most innovative and quality oriented international players in its industry, Eurofins is ideally positioned to support its clients' increasingly stringent quality and safety standards and the expanding demands of regulatory authorities around the world.

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Pictured here is the logo for the University of California San Francisco (UCSF) medical center ... [+] embedded into the wall of a building in the Mission Bay neighborhood of San Francisco, California, July 11, 2018. (Photo by Smith Collection/Gado/Getty Images)

Imagine that you are at work and thirsty. How easy is it to get a soda or some other sugary drink? Not too easy? Easy? Very easy? Open-your-eyes-and-it-will-be-in front-of-you-easy?

How then might this affect your chances of drinking a sugary drink rather than water and how might this affect your health?

Well, a study just published in JAMA Internal Medicine showed what happened after a big employer banned the sales of sugar-sweetened beverages. Significant changes occurred and, spoiler alert, things didnt go to waist.

The big employer was the University of California, San Francisco (UCSF), which is the second-largest employer in San Francisco and the fourth-largest in the Bay Area with over 24,000 employees, according to UCSF. As part of the UCSF Healthy Beverage Initiative, the mega-medical center has banned the sales of all sugary drinks across all of their venues since November 1, 2015. After that date, no cafeteria, no vending machine, no food truck, no restaurant, and no store on a UCSF campus could sell sodas or any other drink with added sugar. Not in a box, not with a fox, not with a mouse, there was no such drinks sold in the house.

It can be common to find cans of soda being sold at healthcare facilities. Photographer: Carla ... [+] Gottgens/Bloomberg

Now this didnt mean that UCSF employees had to smuggle sodas in brown paper bags into their workplaces and pretend that they were drinking very brownish water. People could still bring whatever non-alcoholic drinks they wanted onto the UCSF campus. They could also step out of their immediate workplaces into the surrounding neighborhoods to buy sugary beverages. Because, after all, how many times have you heard a person complain about not being able to find soda in a major American city?

Therefore, before this sales ban went into effect, a research team at UCSF (Elissa S. Epel, PhD, Alison Hartman, Laurie M. Jacobs, PhD, Cindy Leung, ScD, MPH, Michael A. Cohn, PhD, Leeane Jensen, MPH, Laura Ishkanian, MPH, Janet Wojcicki, PhD, MPH, Ashley E. Mason, PhD, Robert H. Lustig, MD, MSL, Kimber L. Stanhope, PhD,MS, RD, and Laura A. Schmidt, PhD, MSW, MPH) thought that this would be a great opportunity to measure the impact of such a workplace ban. As Epel, first author of the study, a health psychologist, and Professor in the UCSF Department of Psychiatry said, Many hospitals have recently been implementing bans on selling sugar-sweetened beverages, but no one had really evaluated the effects on consumption and health.

The research team recruited 214 UCSF employees for the study that began on July 28, 2015, about three months before the ban had gone into effect. All of the study participants had to be regular sugar-sweetened beverage drinkers, consuming at least 360 mL or 12 fluid ounces a day. Thats the size of an average aluminum beverage can.

At the start of the study, the research team interviewed and examined each participant, taking a bunch of measurements. Physical measurements included each participants height, weight, waist-to-hip ratio, waist circumference, and sagittal diameter. Your sagittal abdominal diameter (SAD) has nothing to do with how much of a Sagittarius you are or how sad you happen to be. It is the distance from the small of your back to your upper abdomen, which gives a sense of how much fat that you may have in your gut.

The team also asked each participant how many sugar-sweetened beverages he or she consumed each day and did blood tests to assess each participants level of insulin sensitivity. Insulin is the hormone normally secreted by your pancreas that helps regulate sugar in your body and sugar move from your bloodstream into the your cells.

Additionally, the researchers randomly chose half of the participants to undergo a motivational intervention. This motivational intervention wasnt quite like the live in a van down the river Chris Farley as Matt Foley speech from Saturday Night Live. Instead, health educators interviewed each selected participant at the beginning of the study. During this fifteen-minute encounter, the educator quantified the amount of sugar that the participant was drinking each day and provided guidance and educational materials on how to reduce sugar intake. The intervention also included five minute follow-up phones calls one week after the initial interview and one month and six months following the beginning of the sales ban. The motivational intervention was similar to the interventions used to make people aware of the dangers of alcohol dependence.

By the way, this Kasier Permanente video, which was not part of the study, shows how much sugar sugary drinks can have:

How sweet then were the results of the study? Well, just ten months after the ban had started, the average daily consumption of sugar-sweetened beverages had gone down from 1050 mL (or 35 fluid ounces) to 540 mL (or 18 fluid ounces) per participant. That was a 510-mL (or 17 fluid ounces or almost a can-and-a-half) drop, which amounted to a 48.6% decrease. The participants who had received the motivational intervention experienced on average a greater drop (762 mL, 25.4 fluid ounces, or two cans worth) than those who had not (246.0 mL or 8.2 fluid ounces).

Thats not all folks. Those who had decreases in daily sugar-sweetened beverage consumption also tended to have decreases in their insulin resistance as measured by lab tests. Insulin resistance is not a political movement but is a situation in which the cells in your body begin ignoring what insulin is trying to do. With insulin resistance, the cells in your muscles, fat, and liver essentially say, bye Felicia, when insulin says take up some sugar from the blood. As a result, your blood sugar levels begin creeping upwards, which can be a major step towards badness such as developing fatty liver disease or diabetes.

Then theres the waist from this study or rather waists. The average waistline measurements decreased by 2.1 cm. Again, just 10 months after the ban had started, noticeable loosening of pants or similar garments occurred in a number of participants. Thats big, or rather less big.

Epel explained that the study period was too short to see significant changes in weight but abdominal fat is sensitive to sugar intake, and we saw significantly reduced waist lines.

Of note, significant decreases in waist sizes occurred among not only those who were in the obesity or overweight categories but also those who fell into the lean category, which was having a body mass index (BMI) less than 25. This was a reminder that even though you may appear lean or skinny, looks can be deceiving. It also matters how much fat you may have sitting in your abdomen.

Ten months is significant because it was long enough for each participant to go through different seasons, as much as seasons exist in San Francisco. The research team wanted to make sure that any observed changes were sustained and not just typical fluctuations that may occur throughout the year. In fact, the observed changes persisted through not just 10 months but 12 months after the ban had begun.

Of course, 12 months is not 15 months, which is not two years, which is not a decade. So, yes, the study did have its limitations and could not tell you if the changes were sustainable over several years. The study also did not track what concurrently happened with other habits such as eating and exercise. Moreover, different workplaces can be quite different, so the question remains: would such a ban have the same effects elsewhere.

Schmidt, the senior author of the study and a Professor of Health Policy at UCSF, did say that their team has started a controlled study in Sutter Health, a large health care system in the Bay Area, that will address some of these limitations and help better nail down the mechanisms involved. So stay tuned.

Nonetheless, this is yet more evidence that your work environment really matters. This is not surprising, since you do spend on average a third of your time at work, maybe more if you are a doctor or a doctor going through training. What you are exposed to at work can really affect what you eat and drink. After all, you are still like a baby in that you tend to put whats close to you into your mouth. The food and beverages that are around you comprise whats called your food and beverage environment.

In fact, changing the beverage environment at work could have a spill-over effect as well, so to speak. People in the study really drank less sugar-sweetened beverages, not just at work, said Epel. They were making equal reductions at home and at work.

Schmidt likened removing soda from workplaces to taking cigarettes out of workplace vending machines. Schmidt is certainly not the first person to find similarities between sugary beverages and tobacco. A number of people have called sugar the new tobacco, including the authors of aCMAJ (Canadian Medical Association Journal) commentary. As I have written previously for Forbes, a report from Vital Strategiesraised concerns that soda companies are using the same marketing strategies that Big Tobacco companies have used.

Sugar does have at least one thing in common with nicotine, it can be addictive. Epel included the following video on food addiction on her UCSF Aging, Metabolism, and Emotion Research website:

Addiction is one reason why sugar exposure at work can affect what you consume at home. As Epel explained, there is deeply ingrained moral ethic of personal responsibility. While theoretically that sounds good, the reality is our brain is vulnerable to addiction. We need to help people be well by creating the right environments. In other words, you are what you are exposed to every day.

Speaking of exposure, marketing is another possible cause of such spill-over effects. If you are exposed to soda is great messages at work, that could potentially influence what you buy elsewhere. No matter how hard you try to separate work life from home life, influences invariably will bubble over in both directions.

While some other healthcare institutions, such as the Cleveland Clinic, the University of Michigan Health System, the Baylor Health Care System, and the Geisinger Clinic, have instituted sugar-sweetened beverage sales bans as well, there are still many healthcare institutions that continue to pour some sugar on their employees. Schmidt pointed out that institutions arrange pouring rights with soda companies. The institutions will then co-brand and market sugar-sweetened beverages. This could be money-makers for institutions, making them more likely to continue to go with the flow.

To re-purpose the words of Alanis Morissette, isnt it ironic for healthcare institutions to help sell sugar-sweetened beverages? After all, many such beverages have no demonstrated nutritional value over water and are in essence liquid sugar, in the words of Epel. As Epel related, you have institutions that are training people to be health professionals and employing people to treat patients but at the same time are serving them sugary beverages.

Its not as if employees at UCSF resisted the ban. Rather, UCSF employees appreciated the care for their health. They were very positive about the ban. In fact, the only people who expressed any concerns were some visitors who didnt understand the culture and wanted to buy sugar-sweetened beverages during their visit, according to Epel.

Of course, healthcare employers arent the only employers that could institute such a ban. Schmidt referred to such bans as low-hanging fruit, as opposed to low-hanging sugar-sweetened fruit drinks. Policy changes such as soda taxes have run into political obstacles. Having employers change their food and beverage environments is a way of getting around such obstacles.

Indeed, employers could have lots of incentive to make such changes. Studies such as one published in a 2014 issue of JAMA Internal Medicine have linked excess sugar consumption to a variety of health problems including obesity, diabetes, cardiovascular disease, cancer, and early death, even for those who fall into the normal weight category. What employers then would want their employees to be as sick as possible? Schmidt pointed out that if you can avert new cases of illness, you can save a lot of money.

The fact that UCSF not only instituted the ban but also provided financial support for the study suggests that employers could help lead the way in curbing sugar-sweetened beverage consumption. Employers may want to pore through this UCSF study before they decide about pouring rights and what to essentially pour on their employees.

Continue reading here:
UCSF Banned Sugary Drink Sales, Here Is What Happened Next - Forbes

Abstract

Leber congenital amaurosis (LCA), one of the leading causes of childhood-onset blindness, is caused by autosomal recessive mutations in several genes including RPE65. In this study, we performed CRISPR-Cas9mediated therapeutic correction of a disease-associated nonsense mutation in Rpe65 in rd12 mice, a model of human LCA. Subretinal injection of adeno-associated virus carrying CRISPR-Cas9 and donor DNA resulted in >1% homology-directed repair and ~1.6% deletion of the pathogenic stop codon in Rpe65 in retinal pigment epithelial tissues of rd12 mice. The a- and b-waves of electroretinograms were recovered to levels up to 21.2 4.1% and 39.8 3.2% of their wild-type mice counterparts upon bright stimuli after dark adaptation 7 months after injection. There was no definite evidence of histologic perturbation or tumorigenesis during 7 months of observation. Collectively, we present the first therapeutic correction of an Rpe65 nonsense mutation using CRISPR-Cas9, providing new insight for developing therapeutics for LCA.

Leber congenital amaurosis (LCA) is a hereditary retinal degenerative disease that leads to childhood-onset blindness (1). Among the genes causing LCA, CEP290, GUCY2D, CRB1, and RPE65 are those most frequently mutated. In particular, about 6% of LCA cases are caused by mutations in RPE65 (2). To date, no substantial treatments or cures for LCA have been developed, except for voretigene neparvovec (Luxturna, Spark Therapeutics), which is approved by the U.S. Food and Drug Administration (FDA). This approach is based on RPE65 gene delivery by adeno-associated virus (AAV) to the retina in patients who lack the functional RPE65 protein (35). On the basis of preclinical studies performed in RPE65 null dogs (6, 7) and mice (8, 9), initial clinical trials tested the adverse events and therapeutic outcomes of AAV containing the human RPE65 complementary DNA (cDNA) (35). Although normal vision was not achieved, these trials showed that subretinal injection of AAV had an acceptable local and systemic adverse event profile and improved visual function (10). Nevertheless, because gene therapy cannot totally correct the mutated sequence and has a limitation in the cargo size of the AAV (~4.8 kb) when AAV is used, there are still unmet needs in the gene therapy area for broader clinical application.

CRISPR-Cas9 is a genome editing tool that can lead to the insertion of genes or the deletion of mutations (1115) by homology-directed repair (HDR) or by nonhomologous end joining (NHEJ), respectively. Although the frequency of HDR is generally lower than that of NHEJ, the ability of HDR to correct pathogenic mutations permanently has great potential for curing various genetic disorders (1618). For example, intravenously infused AAV expressing the Cas9 machinery and the donor DNA reversed the disease-causing mutation and rescued the disease phenotypes in two different mouse models of metabolic diseases (1618).

In this context, we hypothesized that CRISPR-Cas9 could represent another therapy for LCA and tested the therapeutic outcomes of CRISPR-Cas9mediated HDR in rd12 mice, a model of human LCA that bears a disease-associated premature stop codon in Rpe65. We used CRISPR-Cas9 technology to correct the nonsense mutation in this model and found that HDR and in-frame NHEJ in response to CRISPR-Cas9mediated DNA cleavage led to the recovery of retinal functions and protection from retinal degeneration. The results from this proof-of-concept study demonstrate the feasibility of our approach and imply that CRISPR-Cas9mediated HDR could be expanded to other ophthalmologic diseases in which HDR might be needed.

To use CRISPR-Cas9 technology to treat LCA, we first screened single guide RNA (sgRNA) sequences targeting Rpe65 exon 3 in the region that corresponds to the C-to-T nonsense mutation locus using mouse embryonic fibroblasts (MEFs) from rd12 mice (fig. S1A). Of nine potential candidates tested, the TS4 sgRNA was selected for further studies because it generated double-strand break (DSB) at the nearest locus from the premature stop codon and resulted in highly efficient insertion or deletion (indel) rates, as determined by targeted deep sequencing when transfected with SpCas9 protein as riboneucleoprotein (RNP) complex (fig. S1B). Next, we examined the correction frequencies by HDR induced by the TS4 sgRNA and Rpe65 donor in rd12 MEFs. Synonymous mutations were introduced into the donor sequence to prevent cleavage of the donor itself or recleavage of the repaired Rpe65 locus after correction (Fig. 1, A and F). Single-stranded oligodeoxynucleotide (ssODN) was used as an Rpe65 donor and induced correction in a range of 3 to 6% (Fig. 1, B, C, and F). When NHEJ was analyzed by deep sequencing, TS4 sgRNAmediated indels were dominated by deletions, and approximately one-fourth of the mutations corresponded to in-frame indels (Fig. 1, D and E). Among the in-frame indels, one-codon deletions accounted for 5.6% of the total reads (Fig. 1F). Because the in-frame indels could result in the removal of the premature Rpe65 stop codon from rd12 mice, we suggest that NHEJ-mediated editing might also contribute to the therapeutic effects of CRISPR-Cas9. These data indicate that we identified an optimized sgRNA sequence for therapeutic, CRISPR-Cas9mediated genome editing to treat LCA.

(A) A schematic drawing of Rpe65 in rd12 MEF. Red text, sequence of the premature stop codon; orange arrow, TS4 sgRNA target sequence; blue text, protospacer adjacent motif (PAM). (B) TS4 sgRNAinduced indel frequencies measured by targeted deep sequencing (n = 4). ssODN dose (in microgram scale) are indicated in parenthesis. (C) Correction frequencies in the rd12 mutation measured by targeted deep sequencing (n = 4). (D) The mean values of the number of deep sequencing reads in different categories show the pattern of indels induced by the TS4 sgRNA (n = 4). Of the total reads, about 61% contain deletions. Ins, insertion; Del, deletion; WT, wild type. (E) Mean percent values of different types of in-frame and out-of-frame indels induced by the TS4 sgRNA (n = 4). 3N, one codon; 3N + 1, one codon + 1 nucleotide; 3N + 2, one codon + 2 nucleotides. (F) Nucleotide sequences showing types of editing induced by the TS4 sgRNA and 1.5 g of ssODN in rd12 MEF (n = 4). Violet triangle, position of the DSB induced by the TS4 sgRNA; red text, sequences of the stop codon in rd12 MEF; blue text, PAM sequences; green text, synonymous mutations in the donor template; underlined sequences, nucleotides encompassing the premature stop codon and their corresponding amino acid sequences. Error bars indicate SEM. **P < 0.01; ***P < 0.001 by Kruskal-Wallis test with Dunns multiple comparison test.

To evaluate the therapeutic efficacy of CRISPR-Cas9mediated editing of the Rpe65 nonsense mutation in a disease model, we changed one nucleotide in TS4 to design the TS4rd12 sgRNA, which perfectly matches the sequence of the Rpe65 exon 3 mutation locus in rd12 mice. All required editing components were incorporated into two separate AAVs (AAV-SpCas9 and AAV-TS4rd12 sgRNA-Rpe65-donor, hereafter referred to as AAV-TS4rd12-donor), and in vivo delivery was carried out using the dual AAV system (Fig. 2A). We optimized the ratio of AAV components by varying their concentrations to obtain maximized genome editing results. A low dose [a total of 2 1010 vector genomes (vg) per eye] or high dose (a total of 2 1011 vg per eye) of AAVs was administered via subretinal injection into 3-week-old rd12 mice. After 4 weeks of AAV treatment, the targeted region of Rpe65 was analyzed by deep sequencing using cells from the retina and retinal pigment epithelium (RPE). Subretinal injection resulted in indel rates in the retina and RPE that reached ~20% but varied depending on various parameters (Fig. 2, B and C). Low-dose subretinal injection induced low and high indel rates in the retina and RPE, respectively. This result indicates that subretinal AAV administration is more efficient in the RPE versus the retina; this conclusion was further verified by the finding of a higher AAV copy number per diploid cell (Fig. 2D and fig. S2) in the RPE. Because a previous study showed that the use of a high (10:1) ratio of sgRNAs and donor to Cas9 induced a further increase in the frequency of a correction in a mouse model of liver disease (18), an excessive amount of AAV-TS4rd12-donor relative to AAV-SpCas9 (AAV-SpCas9:AAV-TS4rd12-donor ratio of 0.1:1.9) was tested, but it resulted in a lower frequency of indels in both tissues after subretinal administration (Fig. 2, B and C). Collectively, these data suggest that subretinal delivery is an efficient method of inducing in vivo Rpe65 editing and that the Cas9-to-sgRNA ratio is critical for optimized editing.

(A) A schematic drawing of the dual AAV strategy for CRISPR-Cas9mediated therapeutic correction of the nonsense mutation in Rpe65 in rd12 mice. The premature stop codon in Rpe65 (red text) is generated by a C-to-T mutation in exon 3. The U6 and EFS promoters in the AAV vector were used to express the sgRNA together with the donor template and SpCas9, respectively. Green text, synonymous mutations in the donor template. Therapeutic gene correction could be derived from HDR-mediated precise correction (HDR) or in-frame NHEJ (Inf-NHEJ). (B and C) Indel frequencies measured by targeted deep sequencing in the retina (B) and RPE (C) of rd12 mice at 4 weeks after injection of high-dose (a total of 2 1011 vg per eye) and low-dose (a total of 2 1010 vg per eye) AAV. SpCas9toTS4 sgRNA-Rpe65-donor ratios are indicated in parentheses. (D) Correlation between the indel frequency and AAV copy number per diploid cell (n = 10). A high dose of 1:1 ratio of SpCas9 and TS4 sgRNA-Rpe65-donor was injected subretinally. (E) Frequencies of therapeutic HDR at the site of the C-to-T mutation in the retina and RPE of rd12 mice at 4 weeks after injection. (F) Ratio of HDR to indel frequencies. A high or low dose of SpCas9 and TS4 sgRNA-Rpe65-donor at a 1:1 ratio was injected subretinally (n = 4). (G) Mean values of the number of deep sequencing reads including insertions, deletions, or HDR in AAV-treated RPE (n = 10). A high dose of 1:1 ratio of SpCas9 and TS4 sgRNA-Rpe65-donor was injected subretinally. Rpe65mut, nonedited; Ins, insertion; Out-f-Del, out-of-frame deletion; Inf-Del, in-frame deletion. (H) Nucleotide sequences showing the Rpe65 donor template and changes induced by the TS4 sgRNA in AAV-treated RPE (n = 10). A high dose of 1:1 ratio of SpCas9 and TS4 sgRNA-Rpe65-donor was injected subretinally. Violet triangle, position of the DSB induced by the TS4 sgRNA; red text, sequences corresponding to the premature stop codon in rd12 mice; blue text, PAM sequences; green text, synonymous mutations in the donor template; underlined sequences, nucleotides encompassing the premature stop codon and their corresponding amino acid sequences. *P < 0.05; **P < 0.01; ***P < 0.001 by Kruskal-Wallis test with Dunns multiple comparison test (B, C, and E) and Mann-Whitney U test (F).

Subsequently, we analyzed HDR events near the pathogenic C-to-T mutation in Rpe65 in the retina and RPE after AAV treatment in rd12 mice. HDR events were observed in the RPE but not in the retina (Fig. 2E). Although indel frequencies were comparable between low-dose AAV and high-dose AAVtreated RPE when a 1:1 ratio of AAV-SpCas9 to AAV-TS4-donor was used (Fig. 2C), HDR events were more frequent in the high-dose AAVtreated group (high dose, 1.17 0.31%; low dose, 0.59 0.22%) (Fig. 2E), as similarly observed in the CRISPR-mediated correction of the ornithine transcarbamylase gene in hepatocytes (18). Moreover, analysis of the HDR-to-indel ratio revealed that HDR events were approximately three times more frequent in the high dosetreated group (Fig. 2F). Successful HDR (1.01 0.38%) was also induced by the application of a 0.5:1.5 ratio of AAV-SpCas9 to AAV-TS4-donor (Fig. 2E). It should be noted that most HDR events resulted in a precise correction of the T-to-C mutation, so that the resulting protein sequences were identical to that of wild-type Rpe65 (Fig. 2H). We additionally characterized NHEJ-mediated editing in the RPE and found that in-frame deletions occurred at a frequency of 3.83%; 1.61% were one-codon deletions that resulted in the removal of the premature stop codon in rd12 mice (Fig. 2, G and H). The 1-codon-Del-2 type (CGT-deletion) was also predicted as one of the top three end-joining categories (table S1) by inDelphi, the machine learning model that predicts SpCas9-mediated template-free genome editing (19). In addition, substantial in-frame editing was achieved in human RPE65 with the use of various sgRNAs in human embryonic kidney (HEK) 293 cells, suggesting the clinical potential of our approach (fig. S3, A to C).

To investigate the therapeutic effects of HDR-mediated Rpe65 gene correction in rd12 mice, we performed electroretinography after dark adaptation at 6 weeks and 7 months after subretinal AAV injection (Fig. 3A). AAV treatment led to the recovery of Rpe65 expression in RPE cells at 6 weeks after injection (Fig. 3B). Furthermore, AAV treatment resulted in increased Rpe65 gene expression in RPE cells at 7 months after injection (Fig. 3C). In electroretinography, rd12 mice demonstrated severely attenuated dark-adapted light responses compared with age-matched normal C57BL/6 mice (20). In contrast, there were definite responses to bright stimuli (0 dB) by which both rod and cone responses are provoked after dark adaptation in the AAV-treated rd12 mice at 6 weeks after the subretinal injection (Fig. 3, D to F, and fig. S4), whereas there were no responses to dim stimuli (25 dB) (fig. S5). The electrical responses were maintained up to 7 months after the initial injection (Fig. 3, G and H). The estimated a- and b-wave amplitudes were 21.2 4.1% and 39.8 3.2% of those of normal C57BL/6 mice. These functional recoveries were accompanied by anatomical changes in which HDR-mediated Rpe65 gene correction prevented the loss of neuronal cells in the outer nuclear layer of the retina in rd12 mice (Fig. 3, I and J).

(A) Overview of animal experiments. Time points for subretinal injection and electroretinography are indicated. P0, postnatal day 0; ERG, electroretinography; w, weeks. (B) RPE65 protein expression in the RPE layer of rd12 mice at 6 weeks after the injection. Scale bar, 10 m. (C) The relative expression of Rpe65 mRNA in the RPE cells of rd12 mice at 7 months after the injection (n = 4). (D) Representative electroretinographic responses to bright stimuli (0 dB) after dark adaptation from normal C57BL/6 and rd12 mice at 6 weeks after the injection. (E to H) Amplitudes of electroretinographic responses to bright stimuli (0 dB) after dark adaptation (n = 4). (E and G) Amplitudes of the a-wave at 0 dB at 6 weeks (E) and 7 months (G) after the injection. (F and H) Amplitudes of the b-wave at 0 dB at 6 weeks (F) and 7 months (H) after the injection. (I) Representative hematoxylin and eosin (H&E) images of retinal tissues from rd12 mice at 7 months after the injection. Scale bar, 20 m. (J) The number of layers of outer nuclear layer nuclei in rd12 mice at 7 months after the injection (n = 4). Normal, C57BL/6; rd12, rd12 mice without treatment; rd12-AAV, rd12 mice treated with subretinal injection of a high dose of 1:1 ratio of SpCas9 and TS4 sgRNA-Rpe65-donor. *P < 0.05; **P < 0.01; ***P < 0.001 by Kruskal-Wallis test with Dunns multiple comparison test. DAPI, 4,6-diamidino-2-phenylindole; GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer.

To globally characterize potential off-target sites recognized by the TS4rd12 sgRNA, we performed Digenome-seq, a genome-wide unbiased off-target detection method (21), using genomic DNA from rd12 mice. This analysis showed several potential off-target sites (Fig. 4A). We validated the 29 potential off-target sites with the highest Digenome-seq cleavage scores using targeted deep sequencing. Six genomic loci were shown to be actively targeted by the TS4rd12 sgRNA in the retina of rd12 mice (Fig. 4B), and these off-target sites were consistently found to be targeted in the RPE (Fig. 4C). All of the active off-target sites are located in intronic or intergenic regions (table S2). In a subsequent off-target analysis for all 33 homologous sites that differed from the TS4rd12 sgRNA sequence by up to three nucleotides, no meaningful indel mutations were observed at the predicted genomic loci in AAV-treated rd12 mice (fig. S6). In addition, there was no definitive evidence of histologic perturbation or tumorigenesis for 7 months in these mice (Fig. 4D).

(A) Genome-wide Circos plot showing in vitro cleavage sites in the rd12 mouse genome in the absence (gray) or in the presence (blue) of TS4 sgRNA. On-target cleavage is indicated by the red arrow. (B) Targeted deep sequencing results for the top 29 Digenome-seq candidates in AAV-treated retina (n = 3). Nucleotides in red and orange indicate sequences that are mismatched relative to the on-target site, and nucleotides in blue indicate PAM sequences. (C) Reanalysis of the active off-targets by targeted deep sequencing in AAV-treated RPE (n = 3). (D) Representative whole mount of RPE tissues from rd12 mice at 7 months after treatment with or without the dual AAV system encoding SpCas9 and the donor template. Scale bar, 10 m.

In this study, we deployed CRISPR-Cas9mediated HDR as a new treatment for LCA. We showed that dual AAVmediated delivery of CRISPR-Cas9 and an Rpe65 donor sequence can lead to the correction of a disease-causing mutation in Rpe65 and an improvement in retinal function in a mouse model of LCA. In addition to this improvement, our study showed a level of functional recovery that exceeds the measured gene correction level. The results are provocative because in postmitotic cells, HDR events are generally known as rare. However, our observations are supported by recent studies showing CRISPR-Cas9mediated HDR events in postmitotic neurons (22) and muscles (23). Our results are also supported by previous studies in which CRISPR-Cas9 treatment for certain autosomal recessive diseases, such as Duchenne muscular dystrophy (23) and retinitis pigmentosa (24), resulted in functional improvement beyond the level expected from the gene correction frequency. Together, these results suggest that HDR can be activated in these postmitotic cells and that therapeutic outcomes exceeding that expected from the editing level could be achieved in some cases.

Gene therapy works by using viruses as a means of overexpressing wild-type copies of defective, disease-associated genes. For instance, Luxturna, the FDA-approved gene therapy for LCA, uses AAV2 to express functional RPE65 to replace the mutant, LCA-associated RPE65 protein. Different types of viruses, such as lentivirus and retrovirus, can also be used for gene therapy, but AAV is clinically validated (35, 25, 26). Although AAV is very attractive for gene therapy because it does not integrate into the host genome, its limited cargo packaging capability hinders its application in many cases. Therefore, for some ocular diseases such as Stargardt disease or Usher syndrome, which require the delivery of large DNA fragments, our approach using CRISPR-Cas9mediated HDR could be suitable therapeutically. In addition, because the desired wild-type sequence can be introduced at the genomic site where the gene should exist, replacing the mutant sequence by HDR, the HDR-corrected cells can express the introduced genes at the endogenous level. In this study, CRISPR-Cas9 was randomly introduced into the eye by subretinal injection in rd12 mice because mice lack a macula, the center and core of vision in humans. The injection resulted in a frequency of gene correction of nearly 3% by HDR and in-frame NHEJ (Fig. 2, E, F, and H) and led to substantial improvement in electroretinography measurements (Fig. 3, D to H). We expect that these results in mice can be further improved in human patients with LCA because ophthalmologists can selectively perform subretinal injection near the macular area, enabling focused editing around this structure to achieve even more restoration of vision.

The deep sequencing in our study provides a detailed description of the types of indels generated and the extent of off-target mutations produced, which was extensive. Although the active off-target sites that we detected were within intronic or intergenic regions, this level of off-target effects could undermine the therapeutic potential of our approach using CRISPR-Cas9mediated genome editing. As the first study to use CRISPR-Cas9 to treat LCA, we used wild-type SpCas9, the conventional and most commonly used form of Cas9. To reduce the frequency of off-target mutations, high-fidelity versions of Cas9 [HFCas9, eCas9, HypaCas9 (27), SniperCas9 (28), or self-targeting AAV (29)] or inducible-editing (30) could be tried as an alternative. We tested SniperCas9 (28), a high-fidelity version of SpCas9 that was developed by our group in the C2C12 cell line. We found that SniperCas9 was associated with a significant reduction in indel frequencies at the off-target sites recognized by SpCas9 (fig. S7). In addition, SniperCas9 showed comparable activity against the mRosa26 target, indicating that its low level of off-target effects does not come at the expense of on-target activity. These results suggest that various approaches might be tried to reduce off-target mutations in further studies. In addition, the off-target mutations detected in this study might not be found in the clinic because of differences between the human and mouse genomes. Moreover, it is noteworthy that there were no definite morphological changes in the RPE at 7 months after the subretinal injection, suggesting that the off-target mutations do not exert definite harmful effects (Fig. 4D).

In conclusion, we provide a new, CRISPR-Cas9based approach for treating LCA. To our knowledge, no previous reports have shown in vivo HDR-mediated correction in animal models of ophthalmologic diseases. Our permanent therapeutic genome editing approach could be used alone, or together with gene therapy or protein therapy, to treat LCA.

MEFs were maintained in Dulbeccos modified Eagles medium (DMEM) supplemented with glucose (4.5 g/liter), 4 mM glutamine, 1 mM sodium pyruvate, 10% fetal bovine serum, penicillin (100 U/ml), and streptomycin (100 mg/ml). RNPs and 120-mer ssODN were transfected using Neon Transfection following the manufacturers procedures (Life Technologies). Briefly, 2.5 105 cells were mixed with materials for transfection and were subjected to electrical shock using 10-l tips on the Neon system for 30 ms at 1350 V for one pulse. Five days after transfection, the cells were harvested, and genomic DNA was extracted using a DNeasy Blood and Tissue kit (Qiagen). For transfections of HEK293 cells, cells were seeded at 2 105 cell per well into 24-well plates the day before transfection. One microgram of plasmids encoding human optimized SpCas9 and sgRNA was mixed with 2 l of Lipofectamine 2000 (Invitrogen) in 200 l of Opti-MEM, left for 20 min, and then added to cells that had reached 70% confluence in 500 l of DMEM. After overnight incubation, the medium was replaced with 500 l of fresh medium, and genomic DNA was extracted after 5 days of transfection.

Eight-week-old male C57BL/6 mice and mating pairs of rd12 mice (stock no. 005379, the Jackson laboratory) were purchased from Central Laboratory Animal and maintained under a 12-hour dark-light cycle. rd12 mice were mated with each other to produce offspring with a homozygous mutation in the Rpe65 gene. All animal experiments were performed following guidelines from the Association for Research in Vision and Ophthalmology statement for the use of animals in ophthalmic and vision research and approved by Institutional Animal Care and Use Committees of both Seoul National University and Seoul National University Hospital.

To quantify indel frequency, on-target and off-target regions were amplified by polymerase chain reaction (PCR) from genomic DNA extracted from transfected cells, retina, or RPE using the primer sets summarized in table S2. To quantify HDR frequencies, PCRs were first performed from genomic DNA (50 ng) using primers outside of the Rpe65-homology arm, after which products were further amplified to generate amplicons for deep sequencing. The produced amplicons were barcoded during subsequent PCR with Illumina TrueSeq adaptors. The products were purified with a PCR purification kit (Geneall) and were then pooled in equimolar ratio. The final libraries were paired-end sequenced using the Illumina Miseq platform according to the manufacturers protocol. Indel frequencies were quantified using Cas-Analyzer (www.rgenome.net) (31). Quantification of specific patterns such as in-frame or out-of-frame indels, one-codon deletions, and precise HDR were determined by manual counting.

Potential off-target sites were identified using an in silico tool, Cas-OFFinder (32). Mouse genomic sites containing up to 3base pair (bp) mismatches were considered as off-target sites and further confirmed by targeted deep sequencing using the primers shown in table S3.

Genomic DNA was purified from the retina of rd12 mice with a DNeasy Tissue kit (Qiagen) according to the manufacturers instructions. Genomic DNA (8 g) was incubated with purified Cas9 protein (100 nM) and sgRNA (300 nM) in a reaction volume of 400 l for 8 hours at 37C in a buffer [100 mM NaCl, 40 mM tris-HCl, 10 mM MgCl2, and bovine serum albumin (100 g/ml; pH 7.9)]. Digested genomic DNA was purified again with a DNeasy Tissue kit (Qiagen) after RNase A (50 g/ml) was added to remove sgRNA. To check targeted in vitro DNA cleavage, digested genomic DNA was mixed with 2 SYBR Green Master Mix and analyzed by real-time quantitative PCR (qPCR) using forward primer 5-GGACATTCTACATATGAATCCAGG-3 and reverse primer 5-TAACATTCTCAGGTGGCTGTGCAA-3. The fraction of target sites that were cleaved was measured using the comparative CT method (33).

For Digenome-seq, genomic DNA (1 g) was sonicated to produce fragments in the 400- to 500-bp range using the Covaris system (Life Technologies) and blunt ended using End Repair Mix (Thermo Fisher). Fragmented DNA was ligated with adapters to produce libraries, which were then subjected to whole-genome sequencing (WGS) using a HiSeq X Ten Sequencer (Illumina) at Macrogen. WGS was performed at a sequencing depth of 30 to 40, and the DNA cleavage score was calculated using a previously published scoring system (34).

Sequences of the elongation factor 1a short (EFS) promoter and human optimized SpCas9 with a nuclear localization signal, hemagglutinin (HA) tag, and bovine growth hormone poly-A tail were synthesized and subcloned into an AAV2 inverted terminal repeat (ITR)based plasmid using Not I restriction sites. For the other AAV vector, sequences of the U6 promoter, TS4 sgRNA, and Rpe65 donor were also synthesized and subcloned into the AAV2 ITRbased plasmid using the same restriction sites. In the Rpe65 donor sequences, five nucleotides were substituted without causing codon changes to prevent possible TS4 sgRNAmediated cleavage and to precisely distinguish knocked-in sequences from endogenous genomic sequences. Recombinant AAV particles were produced using a helper adenovirus-free packaging system. Briefly, HEK293 cells were cotransfected with pAAV-ITR-EFS-SpCas9 or pAAV-ITR-TS4rd12-sgRNA-Rpe65-donor, AAV9-capsid plasmid, and helper plasmid. After 3 days of transfection, the cells were lysed and the virus particles were purified by iodixanol gradient ultracentrifugation and concentrated to obtain titers greater than 1013 vg/ml.

After deep anesthesia, AAV9-SpCas9 and AAV9-TS4 sgRNA-Rpe65-donor (a total of 2 1010 or 2 1011 vg in 1 l of phosphate-buffered saline) were mixed and injected into the subretinal space of the mouse eye through the vitreous cavity using a customized Nanofil syringe with a 33-gauge blunt needle (World Precision Instrument) under an operating microscope (Leica), as previously described (35).

qPCR to determine the AAV genome copy number was performed using genomic DNA extracted from the retina or RPE. After measuring the genomic DNA concentration using a Quantus fluorometer together with the Quantifluor Dye system (Promega), 50 ng of genomic DNA was subjected to qPCR analysis using an AAVpro titration kit (Takara). Thermocycling conditions were as follows: 95C, 2 min followed by 35 cycles of 95C, 5 s; 60C, 30 s. The number of AAV genome copies was calculated against a standard curve. The number of diploid mouse cells was calculated using a conversion factor of ~1.6 104 diploid cells per 100 g of genomic DNA.

Mice were dark adapted for over 16 hours. After deep anesthesia, pupils were dilated with an eye drop containing phenylephrine hydrochloride (5 mg/ml) and tropicamide (5 mg/ml). Full-field electroretinography was performed using the universal testing and electrophysiologic system 2000 (UTAS E-2000, LKC Technologies). The scotopic responses were recorded with a flash of 0 dB at a gain of 2 k using a notch filter at 60 Hz and were bandpass filtered between 0.1 and 1500 Hz. The amplitudes of the a-wave were measured from the baseline to the lowest negative-going voltage, whereas the peak b-wave amplitudes were estimated from the trough of the a-wave to the highest peak of the positive b-wave.

At 6 weeks after AAV-mediated delivery of SpCas9 and TS4 sgRNA-Rpe65-donor, paraffin blocks were prepared from enucleated eyes. Thin sections were immunostained with anti-HA antibody (1:1,000; cat. no. 3F10, Roche) and anti-Rpe65 antibody (1:1,000; cat. no. sc-73616, Santa Cruz Biotechnologies), followed by treatment with Alexa Fluor 488 or 594 immunoglobulin G (IgG; 1:500; Thermo Fisher). Nuclear staining was performed using 4,6-diamidino-2-phenylindole dihydrochloride (Sigma-Aldrich). The slides then were observed under a fluorescence microscope (Leica).

Total RNA was isolated using TRI Reagent (Molecular Research Center) from RPE cells of rd12 mice at 7 months after AAV-mediated delivery of SpCas9 and TS4 sgRNA-Rpe65-donor. cDNAs were prepared with a High-Capacity RNA-to-cDNA Kit (Thermo Fisher). Real-time PCR was performed with the StepOnePlus Real-Time PCR System (Thermo Fisher) using TaqMan Fast Advanced Master Mix (Thermo Fisher) with Gene Expression Assays (Thermo Fisher) for gene expression analyses. Product IDs of the gene expression assays for genes are as follows: for Rpe65, Mm00504133_m1; for Gapdh, Mm99999915_g1; and for Rn18s, Mm03928990_g1. The relative expression levels of the Rpe65 gene were normalized to those of Gapdh and Rn18s. All procedures were performed in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines.

At 7 months after AAV-mediated delivery of SpCas9 and TS4 sgRNA-Rpe65-donor, paraffin blocks were prepared from enucleated eyes. Thin sections were then prepared for hematoxylin and eosin (H&E) staining.

At 7 months after AAV-mediated delivery of SpCas9 and TS4 sgRNA-Rpe65-donor, RPE-choroid-scleral complexes were prepared from enucleated eyes. Then, the complexes were immunostained with antiZO-1 antibody (5 g/ml; cat. no. 61-7300, Thermo Fisher), followed by treatment with Alexa Fluor 594 IgG (1:500; Thermo Fisher). Nuclear staining was performed using 4,6-diamidino-2-phenylindole dihydrochloride (Sigma-Aldrich). The slides then were observed under a fluorescence microscope (Leica).

All group results are expressed as means SEM, if not stated otherwise. Statistical significance as compared to untreated controls is denoted with * (P < 0.05), ** (P < 0.01), and *** (P < 0.001) in the figures and figure legends. Statistical analyses were performed using GraphPad PRISM 5, and the specific tests are mentioned in the figure legends.

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/10/eaax1210/DC1

Fig. S1. Screening of sgRNAs targeting the Rpe65 gene in rd12 MEFs.

Fig. S2. Delivered AAV copies between retina and RPE.

Fig. S3. Analysis of human RPE65 editing.

Fig. S4. Electroretinographic responses to bright stimuli (0 dB) after dark adaptation from normal C57BL/6 and rd12 mice at 6 weeks after the injection (n = 4).

Fig. S5. Electroretinographic responses to dim stimuli (25 dB) after dark adaptation from normal C57BL/6 and rd12 mice at 6 weeks after the injection.

Fig. S6. Analysis of TS4 sgRNA off-target effects.

Fig. S7. Comparison of off-target frequency between wild-type SpCas9 and SniperCas9.

Table S1. Summary of predictions at the target site with sgRNA by the inDelphi approach.

Table S2. Active off-target sites.

Table S3. Primers used in this study.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: We thank J. K. Lee (ToolGen Inc.) for the gift of SniperCas9-expressing vector. Funding: This research was supported by the Ministry of Food and Drug Safety (17172MFDS213), the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (2017M3A9B4061406), the Bio and Medical Technology Development Program of the National Research Foundation funded by the Korean government, MSIP (NRF-2015M3A9E6028949 and 2017M3A9B4062654 to Je.H.K.), the Creative Materials Discovery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2018M3D1A1058826 to Je.H.K.), the Development of Platform Technology for Innovative Medical Measurements funded by the Korea Research Institute of Standards and Science (KRISS-2018-GP2018-0018 to Je.H.K.), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A6A3A04004741 to D.H.J.). J.M.L. was supported by the Korea Bio Grand Challenge program through the National Research Foundation of Korea funded by the Ministry (NRF-2018M3A9H3020844) and BioYouCell. Author contributions: D.H.J. drafted the manuscript and performed/analyzed the animal experiments. D.W.S. drafted the manuscript and performed/analyzed the genome editing experiments. C.S.C. and S.W.P. performed the animal experiments. U.G.K. and K.J.L. performed the genome editing experiments. K.L. and Ji.H.K. edited the manuscript. D.K. performed the Digenome-seq. S.K. and J.-S.K. revised the manuscript. Je.H.K. and J.M.L. designed the study and revised the manuscript. Competing interests: D.W.S., U.G.K., K.J.L., and S.K. are employed by ToolGen. J.M.L. was formerly employed by ToolGen. D.W.S., U.G.K., J.M.L., D.H.J., and Je.H.K. are inventors on a patent application related to this work filed by ToolGen Inc., Seoul National University Hospital, and Seoul National University R&D Foundation (KIPO no. 10-2018-0115678 and PCT no. PCT/KR2018/011522, filed on 28 September 2018). The authors declare no other competing interests. Data availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper are available from authors upon request.

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CRISPR-Cas9mediated therapeutic editing of Rpe65 ameliorates the disease phenotypes in a mouse model of Leber congenital amaurosis - Science Advances

DALLAS, Texas, October 29, 2019 (LifeSiteNews) LifeSiteNews has obtained a certified copy of the complete ruling in the case of seven-year-old James Younger, whose mother wanted him to undergo a gender transition against his fathers wishes.

Mr. Jeffrey Younger was fighting to prevent his ex-wife Dr. Anne Georgulas from transitioning James into Luna. The custody battle over James and his twin, Jude, garnered national attention after initially being ignored by the mainstream media. LifeSiteNews and The Texan were the only news outlets present for the entire trial.

Judge Kim Cooks ultimately ruled that Dr. Georgulas will not be able to transition the child into a girl without Mr. Youngers consent, and placed a gag order on both parents preventing either of them from talking about the case with media until James and Jude turn 18.

Judge Cooks made it clear she was not happy with the media attention the case received, and Dr. Georgulas lawyers brought up Mr. Youngers speaking to the media. He said he felt the public had a right to know what was going on in the medical field.

Judge Cooks did not uphold the jurys ruling that the current order be modified to provide one of the parents with sole managing conservatorship. She ruled that Mr. Younger and Dr. Georgulas will be joint managing conservators. They will both need to agree on all medical, dental, and psychological/psychiatric care. If a counselor determines it is appropriate, Mr. Younger will be granted 50/50 custody in January or June 2020. Judge Cooks also mandated family counseling for the entire family.

Judge Cooks is the same judge who, in 2017, awarded Dr. Georgulas the exclusive right, after notifying the Father, to consent to psychiatric and psychological treatment of the children and the exclusive right, after notifying the Father, to consent to medical, dental, and surgical treatment involving invasive procedures.

The court also mandated counseling to address specifically outlined issues and issued an injunction against the parents making disparaging remarks regarding the other parent in the presence of the children or in the childrens listening.

Judge Cooks gave the amicus attorney, Mr. Stacy Dunlop, the power to make medical decisions for the boys if Mr. Younger and Dr. Georgulas cannot agree.

If the parents cannot come to an agreement, they will make an appointment with Stacy Dunlop, the Parenting Coordinator, who will resolve the dispute by making a decision on behalf of the parents if they still disagree, the ruling says.

Specifically on medical, psychological, psychiatric, and dental issues, Mr. Dunlop will resolve the dispute by making a decision on behalf of the parents if they still disagree after discussing the disagreement with Stacy Dunlop.

Dr. Georgulas has the exclusive right to the services and earnings of the children, and the exclusive right to receive child support.

The ruling also outlines the courts 68 findings. The court found that there has been no abuse, neglect, or family violence by either parent to the children or from one parent towards the other. The court found, the mother made no request to surgically or chemically transition the childs sex or to chemically castrate the child.

Evidence presented in court indicated Dr. Georgulas had referrals to the GENECIS transgender childrens clinic. Dr. Georgulas also testified that she consulted with the GENECIS clinic about James. Dr. Georgulas expert witnesses testified about the alleged benefits of affirming transgenderism in children, including the use of puberty blockers and cross-sex hormones.

The court found that, the State of Texas has no compelling interest to justify such interference as to entering Orders requiring the Father to affirm Luna and honor her [sic] choices, both inside and outside the home. In other words, Mr. Younger will not be forced to use female pronouns to refer to his son.

One of the court findings highlighted a statement from Dr. Albritton, the custody evaluator, that Dr. Georgulas was over and above affirming. The court also found that the Mother has exceeded the scope of the exclusive rights and duties provided in the prior order.

The ruling also said that the state has not mandated the transition of James directly: No Texas judge or Texas court nor the 255th family court of appeal has ordered the chemical castration, puberty blockers, hormone blockers, or any transgnder reassignment surgery on this child.

Gov. Greg Abbott, Sen. Ted Cruz, and Rep. Dan Crenshaw all of Texas and many conservative leaders weighed in on the case after it went viral.

Sen. Rand Paul, R-KY, tweeted: We dont let kids drink alcohol til 21. People want to move smoking age to 21. But we will allow a 7 year old to have his life and body altered like this? This is child abuse and the state should side with the father who is trying to protect the child.

The certified copy of the ruling can be read HERE.

Follow all LifeSiteNews coverage of the James Younger case here.

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Here are the important details of the James Younger verdict (FULL RULING) - Lifesite

The eating pattern means the clock, not your body, dictates when you eat. TanyaJoy/Getty Images

The trend:

When it comes to Dorsey's fasting style, the CEO chooses to eat one time daily at 6:30 p.m., at which point he'll consume a protein (either fish, chicken, or steak) and some vegetables (an arugula or spinach salad, asparagus, or Brussels sprouts). Then he'll have a dessert of mixed berries or dark chocolate, which he consumes before 9 p.m.

On weekends, Dorsey fasts until Sunday evening. When he breaks his fast, he'll have bone broth and some red wine, though Dorsey didn't specify how often he consumes alcohol.

"It really has increased my appreciation for food and taste because I'm deprived of it for so long during the day," Dorsey told fitness authorBen Greenfield in April during an episode of Greenfield's podcast.

Dorsey's approach isn't the only way to go about intermittent fasting though. There are four popular types, according to the Cleveland Clinic, including a twice-weekly fast and a time-restricted method where a dieter eats only between 11 a.m. and 7 p.m., or between or noon and 8 p.m.

The science behind it:

Some research suggests intermittent fasting can help with weight loss better than restricting overall calories while eating throughout the day.

At the same time, research has found people have trouble sticking to intermittent fasting for the long term compared to other weight-loss plans.

According to the Cleveland Clinic, intermittent fasting isn't entirely proven as a helpful diet, but it does work for some people if they learn how to incorporate it into their lives without feeling deprived.

When it comes to Dorsey's more extreme style of fasting, some professionals see it as disordered eating. And, doing it over a long period of time could be especially detrimental to mental and physical health.

"Humans are mammals that need certain amounts of food and fluid to maintain our physiological [functions] and energy to do things we want to do in the world," Dr. Jennifer Gaudiani, an internal-medicine doctor who specializes in eating disorders, previously told Business Insider.

"When people undercut their need for food with radical under-eating, the body doesn't care about the reasoning. It is just going react to save your life," Gaudiani said.

That reaction will include feelings of mental sharpness because the body is trying to determine when and where from it will get its next meal, according to Gaudiani, which could explain Dorsey's mention of increased mental acuity during the Greenfield interview.

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7 health trends Silicon Valley tech bros are obsessed with, from dopamine fasting to the keto diet - INSIDER

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Cardiac Biomarker Diagnostic Kits Market to Witness a Growth Rate of CAGR of 5.4% from 2018 to 2026 - Health News Office

A group of researchers say they have pinpointed the ancestral homeland of all humans alive today: modern-day Botswana.

In a new study published in the journal Nature, scientists analysed mitochondrial DNA genetic information that gets passed down the female line from more than 1,200 people across myriad populations in Africa.

By examining which genes were preserved in people's DNA over time, the anthropologists determined that anatomically modern humans emerged in what was once a lush wetland in Botswana, south of the Zambezi River.

Though scientists agree that modern humans (Homo sapiens sapiens) arose in Africa around 200,000 years ago, they have remained uncertain about exactly where on the continent that evolutionary milestone occurred.

The new study offers an answer to that question and also undermines the idea that our ancestors emerged in East Africa, as limited fossil evidence suggests.

The anthropologist Vanessa Hayes, the senior author of the new paper, said in a press conference that the findings suggested "everyone walking around today" could trace their mitochondrial DNA back to this "human homeland."

To trace the geographic origin of our ancestors, Hayes and her colleagues examined mitochondrial DNA (mtDNA) from people living in southern Africa, such as the Khoisan.

mtDNA, which is passed down the maternal line, is often used to trace human ancestry because it isn't mixed with paternal DNA. That means it changes less over time and leaves a clearer link to distant relatives.

When it comes to mtDNA, modern humans all share a group of genes called the L macro-haplogroup.

This L-branch is split into two subgroups: L1-6 and L0. The latter can be found in the peoples of southern Africa, and that's what Hayes' team analysed. Eva Chan, a coauthor of the study, said this was the "by far the largest L0 study to date."

By pulling on that genetic string, the researchers were able to figure out that every person alive today descended from a woman who lived in modern-day Botswana about 200,000 years ago.

The region this ancestor came from, called the Makgadikgadi-Okavango paleo-wetland, was near the modern Okavango Delta and peppered with lakes and greenery.

The team's analysis, which also included reconstructions of what the area's climate was like at the time, revealed that Homo sapiens sapiens lived in this homeland for about 70,000 years.

Then, as the climate changed, our ancestors dispersed in two waves: First, a group spread northeast 130,000 years ago, then others left in a second migration to the southwest 110,000 years ago.

According to Hayes, these migrating groups likely followed herds of animals out of the region.

This timeline runs counter to the one some scientists have created based on fossil evidence, however.

The oldest-ever specimens of anatomically modern humans skulls and other fossils dating back 195,000 years were found in Ethiopia, which led many anthropologists to think of eastern Africa (rather than southern Africa, as the new study suggests) as the birthplace of our modern ancestors.

The new genetic analysis also offers credence to the idea that all modern humans evolved in one place in Africa before migrating to current-day Europe, Asia, and Australia what's known as the "Out of Africa" hypothesis rather than evolving separately in multiple places around the world at the same time.

According to the study authors, the two-wave migration out of Botswana "paved the way for modern humans to later migrate out of Africa, and ultimately across the world."

But the anthropologist Ryan Raaum, who researches African population genetics at Lehman College, thinks the new study has a significant flaw. According to Raaum, the researchers didn't go back far back enough on the genetic timeline.

Though Hayes' research pinpointed where the L0 haplogroup originated, he said, the mitochondrial DNA of most people in the world can be traced back to the L1-6 subgroup of the L-branch, not L0.

So to find a "single origin" for our species, Raaum said, researchers should find a genetic predecessor who lived before the genetic split between L0 and L1-6 occurred.

"Where I get a little lost in the weeds is when they expand out to argue that these data indicate a southern African origin for anatomically modern humans," he told Business Insider. "The data do not."

Raaum added that he didn't like the phrase "ancestral homeland" in general, since modern humans likely had multiple homelands scattered around the African continent.

"I increasingly think that there probably wasn't a single population in which modern humans evolved. If that is the case, there is no 'homeland'," he said.

Another issue with Hayes' team's findings is that an mtDNA analysis examines only maternal DNA.

Two parts of the cell carry DNA: the nucleus, where most of our genetic material resides, and the mitochondria.

Nuclear DNA (nDNA) is inherited from both parents and is what passes along the Y chromosome; mitochondrial DNA, on the other hand, is passed down from only the mother.

nDNA is rare in the fossil record, which is why studies like Hayes' often don't examine it. But that means such research can't examine the entire genome of our ancestral populations.

In 2014, anthropologists pinpointed the oldest known modern-human lineage based on Y chromosome data. This population was at most 160,000 years old and in central western Africa.

So every person alive today likely descended from a man who lived in a different part of the continent than the homeland Hayes and her colleagues suggest.

Hayes noted that a full genome analysis could yield different results: "There could be other origins and other lineages it's a possibility," she said during the press conference.

But whether or not Botswana was the cradle of life for everyone alive today, the new research certainly suggests this part of Africa was an oasis for our ancestors a significant addition to our understanding of human evolution.

"People want know where they came from," Hayes said.

This article was originally published by Business Insider.

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It is society that needs fixing, not intersex bodies activists at the Voices4 London demo talk candidly on Intersex Awareness Day

I look forward to a time when parents arent made to feel the need to hide from their child that they are intersex. I look forward to a day when intersex variations are not treated as disorders that need fixing,Rachelle Newman, anintersex activist, said at the London rally onIntersex Awareness Day 2019.

This day was established in 2003 by US intersex activists Emi Koyama and Betsy Driver to commemorate the first public intersex demonstration in 1996. 23 years on, the fight is still ongoing. Intersex is an umbrella term used to describe people born with biological variations in their sex characteristics that dont fit male or female categories. These variations may be present in peoples chromosomes, hormones, genitals and/or internal sex organs, like testes or ovaries. Intersex traits can also be linked to genetic mosaicism, where some cells in the body have XX chromosomes and others XY.

Medicine has traditionally viewed intersex people as needing to be fixed with involuntary medical intervention, also known as Intersex Genital Mutilation (IGM), simply to make their bodies conform to traditional notions of male or female. Many cases of IGM change the appearance or sexual function of a childs genitals and are carried out at a very young age, without consent and often with no transparency regarding the details.

On Saturday October 26, peaceful direct action groupVoices 4 Londonresponded to an international call by theIntersex Justice Projectto organise events in support of The End Intersex Surgery Campaign. Members of the LGBTQIA+ community gathered in Soho Square Gardens in London to offer support and attention to the intersex activists leading the rally. Through the pouring rain, the crowd listened asNewman was joined by Martin Di Maggio and Valentino Vecchietti to call for an end to non-consensual forced surgery, brandishing hand-painted signs with slogans such as Your Body, Your Choice, Your Rights, Delay is Okay, and Intersex Stories Not Surgeries.

This was followed by a short impromptu march, accompanied by shouts of Your Body, Your Choice. The group gathered in front of the sexual health clinic, 56 Dean Street, to celebrate that the intersex flag was flying there for the first time ever in recognition of Intersex Awareness Day. The services are also currently amending their equalities policy to include intersex people.

Here, we spoke with four intersex activists who were present at the rally about what intersex justice looks like.

What one pervasive myth or misunderstanding around the lived experiences of intersex people do you most wish you could address widely?

Rachelle Newman:That we dont exist. There are many activists doing amazing work to improve intersex visibility yet sadly many people still do not know what the word intersex means. I want intersex people to be able to say Im intersex and receive a response not much more than ah okay, cool!.

Whats something about your experience as an intersex person, that you wish people were aware of and understood?

Rachelle Newman:In regards to my personal experience, I wish society as a whole was more aware of and understood the mental health impacts that resulted from my treatment. Being told I was infertile at age 11 was the worst day of my life but I wish people would also understand the impacts of the events that followed. For example, the dread I would feel thinking about my biannual appointments, having to expose my chest to a doctor without knowing why, the daily reminder of taking tablets I did not understand the purpose of and the internal dialogue with myself as I discovered and wondered why my body was different, why I had scars. I wish people would understand the shame imposed on myself and many other intersex individuals from a young age and the negative repercussions of this.

If you could say something to your younger self, what would you say?

Rachelle Newman:You are not alone. One day it will all make sense. You will become strong and when you share the part of yourself that you have been ashamed of for so long you will receive more acceptance than you can imagine. You will learn to love the things you thought you couldnt.

Whats something about your experience as an intersex person, either generally or specifically within the UK, that you wish people were aware of and understood?

Martin Di Maggio: That we have no protection against molestation and sexual abuse, doctors do and have legally gotten away with sexual abuse because they claim they are only doing medical testing. Yet many of us have experienced intrusive examinations that had a doctor done them on an endosex (non-intersex) woman theyd be imprisoned, yet with us, the law doesnt even protect us and doctors go free. Look up the case of Aivar Bracka.

What are your thoughts on the Gender Recognition Actwithin the context of how it might impact intersex people and, especially, children?

MartinDi Maggio:I think that parents being able to put an X marker on a childs birth certificate means nothing for intersex children as long as we dont have protection against IGM. Having X as an intersex child would perhaps just make us more vulnerable to unwanted medical attention.

What is one misunderstanding around the lived experiences of intersex people that you most wish you could address widely?

Izzy MacCallum: One misunderstanding/assumption that Ive noticed a lot of people have is that they think being intersex is necessarily referring to someones genitalia. In reality, there are a wide variety of traits and sex characteristics that can mean someones biology doesnt fit the typical definitions of male or female. Maybe someone has XY chromosomes and testes but a vagina and no uterus. Or someone has an extra chromosome, like XXY, or they could have mosaic genetics. People can have no ovaries or testes or one of each you see what Im getting at.

Whats something about your experience as an intersex person, either generally or specifically within the UK, that you wish people were aware of and understood?

Izzy MacCallum: The argument that these non-consensual surgeries are done to ease the social discomfort of intersex people not only denies the individual bodily autonomy, but it actually perpetuates social discomfort. Intersex people challenge the social norms and understandings of sex and gender as a binary, and by keeping sex and gender within a binary frame it can be used to enforce and maintain social and historical forms of oppression. It is society that needs fixing, not intersex bodies.

If you had to pinpoint it and youre comfortable sharing it, whats the one external or personal thing that has most positively impacted your life so far?

Valentino Vecchietti:I grew up feeling so alone and scared, and filled with shame. But as an adult, finding connection with other intersex people, and finding acceptance and love amongst my friends, has been an amazing and moving journey for me.

How do you think the Gender Recognition Act could betterprotect intersex people and, especially, children?

Valentino Vecchietti:Current medical protocols for intersex kids dont support our human right to bodily integrity and bodily autonomy.We need ethical, patient-centred, healthcare and medical treatment, which must include the option of correcting birth certificates.

If you could say something to your younger self, what would you say?

Valentino Vecchietti:You will find love, you will find friends, you can belong.

Read more:
Intersex people on how they want to be treated and accepted - Dazed

I used to think that the brain was the most wonderful organ in my body. Then I realized who was telling me this.

Emo Philips, American Comedian

A research letter in JAMA Cardiology captures the same idea, substituting cardiologist for brain and physician for organ in my body.

Researchers begin by noting that new medications for diabetes also modify the course of heart disease; and that there are increasing numbers of patients with new-onset Type 2 diabetes. They then look at new-onset cases of Type 2 diabetes by state comparing them to the available supply of cardiologists, endocrinologists (physicians caring specifically for diabetes among other hormone-related conditions), and nephrologists (physicians who care for kidney disease). Low and behold, with three times more cardiologists than either endocrinologists or nephrologists, who is well-positioned to participate in diabetes care given their numbers and distribution relative to diabetes cases? Yes, cardiologists.

In addition to their sheer numbers, cardiologists bring other values to the table. Cardiologists see more patients with diabetes than endocrinologists; cardiologists are more frequently consulted in the hospital for issues involving patients with diabetes increasing the teachable moments. And finally, diabetes is becoming less glucocentric and more about global risk reduction. Frankly, who knows more about reducing risk, cardiologists just ask them.

All right, I must confess, I have a conflict of interest here. As a vascular surgeon, I have watched cardiologists claim that they can care for vascular disease, the area I trained in for six years because they are good with wires and balloons and they fix coronary arteries that are very small and important, so the big arteries that I care for are easy. Arteries are arteries after all unless, of course, you are a vascular surgeon that, for some bizarre reason, feels that you should fix a coronary artery with a balloon and stent; then, those arteries are different.

There is an invited commentary from a primary care physician; more specifically, an individual specializes in general internal medicine. He points out that patients often require coordinated, collaborative care, and there is a push to create a medical home, business-speak for having one consistent primary care physician. To extend that medical home metaphor, he points out that other specialists, part of the medical neighborhood, have much to offer, but that the decision to involve the neighbors, like cardiology, nephrology, or endocrinology involved should be made by the patient and their immediate real and medical family.

Collaboration and communication are not easy, even in this day of smartphones and text. It is challenging to coordinate a discussion about a patient using text messaging.; If you think that a physician has a time advantage when calling another physician, then you havent witnessed the dance of competing office staff trying to eliminate any waiting time for their doc - someone has to wait on the line. As a result, coordinating care often means prolonging decisions, increasing patient wait times, and in some instances, anxiety. Who is best qualified to coordinate the neighborhood? I agree with the commentator, the generalist has the best view, seeing more than the heart disease or glucose management.

Why are cardiologists so interested in expanding their lane? Why are they not content, supporting the hard work of primary-care physicians? As we move deeper into team medicine, not everyone can be the quarterback coordinating the play; even that gifted receiver, the one in this instance caring for your heart.

Source: Implications of Specialist Density for Diabetes Care in the United States JAMA Cardiology DOI: 10.1001/jamacardio.2019.3796

Optimizing the Physician Workforce for Care of Patients with Type 2 Diabetes JAMA Cardiology DOI: 10.1001/jamacardio.2019.3827

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If Diabetes Leads to Heart Disease, Should Cardiologists Care For Diabetes? - American Council on Science and Health

Posted: Oct 28, 2019 / 05:26 PM GMT-0600 / Updated: Oct 29, 2019 / 11:47 AM GMT-0600

Everyone wants to lose weight and keep it off, but even with exercise and diet, that can be hard. Dr. Kristen Kells, DC, BSc, Chiropractic Physician.

Dr. Kells started her successful weight loss center in Colorado. She explained how her patients saw results, hit their target weight and were able to keep the weight off! Kells herself struggled with weight resistance.

Dr. Kells and her team specialize in weight loss resistance treatment. Triggers that can keep you from losing the weight are symptoms such as brain fog, hormone disregulation, fatigue, belly fat and craving carbs. There are many factors that can contribute to this and everyones body is different so the approaches are client specific.

Kristin DeHerrera, a client of Dr. Kells weight loss program over the last 3 months has already lost an astonishing 45lbs. She says it works because you dont need to do anything too special outside your daily life to make things work. I like the real life aspect of it That I just have to take whats out there and make it work.

If you are struggling to keep the weight off and feel that you have tried every trick in the book, call (385) 217-6368 for a free consultation or visit drkellsweightloss.com.

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IOWA CITY A growing percentage of younger women are getting breast cancer with rates among 20-somethings increasing the fastest, according to new University of Iowa-led research.

Although the overall number of affected women in that age range remains well below other age groups, the rate of 20 to 29-year-olds diagnosed with stage 1 to stage 3 breast cancer increased about 2 percentage points a year during the 15-year study period, according to research published in the September issue of the Journal of the National Cancer Institute Cancer Spectrum.

Breast cancer rates for women in their 30s and 40s also increased from 2000 to 2015, although not as fast, inching up about .3 percentage points a year.

The study looked not only at incidence rates but survival rates and found that, in addition to seeing the largest annual percentage increase, the diagnosed 20-somethings had lower 10-year survival rates than their 30-to-40-year-old peers.

Reasons for the worse outcomes could be multifold and include that younger women often experience diagnosis and care delays in part because breast-cancer screening is less common among that age group.

Physicians might be less suspicious of malignancy in younger patients even when they show up in clinic with a breast lump, according to researchers.

Detecting cancerous growth in younger women also can be more challenging due to their dense breast tissue, according to the studys lead author, UI professor of epidemiology Paul Romitti.

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Romitti said the findings could have important clinical and self-care implications encouraging increased education and self-checks at a younger age.

Try to avoid care delays with these women, Romitti said. Be aware that because theyre traditionally not screened to make sure that when patients report a lump in their breast, its checked.

Brooke McKinnon of Coralville said shes glad her physician did, when last December she went in for her annual gynecology appointment. At age 27, the UI graduate and Hawkeye rowing athletic trainer hadnt yet had a mammogram.

But during her appointment, the doctor felt a lump and given that McKinnons mother not even two years before had been diagnosed with breast cancer the physician encouraged her to get a full work-up, while trying to calm her nerves.

Shes like, You know, young women get cysts in their breasts sometimes. She said, Dont get yourself worked up, but lets just get it checked out, McKinnon said.

That guarded reassurance did infiltrate McKinnons thinking as she waited four long weeks between that original appointment and when they could get her in for more imaging and tests.

I kind of convinced myself that Im too young to have breast cancer and this is not cancer and Ill be fine, she recalled.

But ultrasound and biopsy results revealed McKinnon despite her young age did have cancer grade 1B invasive ductal carcinoma. She got the call on a Monday morning and by that afternoon she had an appointment with the breast surgeon.

They mapped out a plan for a lumpectomy and more tests, and just after Christmas she learned her cancer hadnt spread and therefore was considered stage 1.

That was the best news you could get, she said.

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McKinnon still endured chemotherapy and continues to undergo hormone therapy in that her cancer cells grew in response to estrogen and progesterone.

Being premenopausal complicates treatment for younger patients, especially those such as McKinnon who havent had children but want to.

Having my own kid is very important to me, so I did IVF (in vitro fertilization) before even starting chemotherapy, she said.

When McKinnon was diagnosed, she was engaged with a wedding date planned for the coming summer. They managed one embryo from the IVF, and she took a drug to protect her ovaries during her cancer treatment in hopes shell be able to conceive without IVF in the future.

After her follow-up radiation, McKinnon today is cancer free and has a good prognosis not to mention a wedding still on the books for June.

Learning that her age group is getting breast cancer at a faster clip than others, she said, was shocking.

Its unsettling, she said.

The UI research in addition to assessing incidence and survival rates by age range looked at different types of breast cancers and variations by race and ethnicity.

Survival rates were lower among those who identified as non-Hispanic blacks and Hispanics, compared with non-Hispanic whites and Asian/Pacific Islanders.

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Some of those differences could be tied to variations in access to health care, according to Romitti, who is continuing his research by focusing on Iowa women in hopes of identifying life factors that might contribute to incidence and survival rates.

But based on what this initial research has found, his colleague and co-author at Wake Forest School of Medicine, Alexandra Thomas, stressed physicians should reject assumptions that younger women with lumps in their breasts dont have cancer.

We want physicians to be alerted to the rising cancer incidence among this population, Thomas said.

Comments: (319) 339-3158; vanessa.miller@thegazette.com

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More women are getting breast cancer in their 20s, University of Iowa research shows - The Gazette

When Kimberly Zieselman was 41, she got hold of her medical records from Massachusetts General Hospital. What she found was shocking.

The words "male pseudo hermaphrodite" were written on her chart.

Zieselman discovered she was born with XY chromosomes. Until that moment, she had no idea she was born intersex, an umbrella term used to describe people born with male and female anatomical characteristics.

As a teenager, Zieselman came to discover, doctors had performed surgery on her reproductive organs in an effort to conform her anatomy to fit one mold a move that had serious psychological ramifications for her later on in life, she said, and that was done without her complete, informed consent.

Like, Zieselman, many intersex adults who underwent procedures as babies have dealt with painful consequences later in life. Now 53, Zieselman has become a part of a growing movement within the intersex community speaking out against surgeries performed on intersex babies. Unless surgery is medically necessary, activists say, doctors should not interfere. Some activists are lobbying their state governments to pass legislation to ban surgeries that are medically unnecessary such legislation has already been proposed in California and Connecticut.

In the medical community, though, many say the issue should not be legislated, and that medical decision-making for children should remain parents responsibility after consulting with medical professionals.

A 2000 study in the American Journal of Human Biology found that 1.7 percent of babies are born intersex. There are many variations of intersex that manifest as differences in external genitals, internal reproductive organs and sex chromosomes. Another term used is DSD, which stands for Differences of Sex Development.

In Zieselmans case, she has Complete Androgen Insensitivity Syndrome, or CAIS. She was born with external female anatomy and internal testes. This means her body doesnt respond to testosterone and instead converts it to estrogen. In 1982, when Zieselman was 15, doctors removed her testes and told her and her parents that it was a partial hysterectomy, when, in fact, she never had a uterus or ovaries. All she knew was that she would never menstruate or be able to get pregnant.

My parents were told I was born with partially formed reproductive organs, Zieselman said.

She felt betrayed.

I realized I had been lied to by the medical community, by doctors who had been involved in this surgery and diagnosis. The truth was hidden even from my parents, she said.

Zieselman believes her doctors thought they were doing what was in her best interest at the time. But she disagrees.

The procedure, she said, meant having to take hormone replacements for the rest of her life. She maintains that had doctors not removed her gonads, she wouldnt have to take estrogen supplements. The psychological toll of learning the truth about her surgery was also devastating.

Its that feeling of being told youre not good enough. That there is something wrong with your body, that it is something to be shameful of and something to hide. And the fact that youre lied to. It was so shameful that the doctors didnt even tell your parents the whole story, she said.

Learning she is intersex was a turning point for Zieselman. The married mother of two who lives outside of Boston is now the executive director of InterACT, an advocacy group for intersex youth. Shes also publishing a memoir next spring, titled "XOXY."

Activists and medical professionals alike acknowledge that in rare, severe cases involving the reproductive organs like when there is no passage for urine, or when the bladder is on the outside of the body surgery is imperative.

Activists say that the types of surgeries that they condemn are not medical emergencies. Its common for infants with atypical genitalia to undergo procedures within the first year of their lives to make their anatomy look more traditionally male or female. Some baby girls undergo clitoral reduction, a cosmetic surgery, solely for appearance reasons. In 2013, the U.N. Human Rights Council deemed these procedures cruel.

But Jack Elder, chief of pediatric urology at Massachusetts General Hospital, said the term "medically necessary" can be interpreted differently, and he thinks legislation gets in between the physician and patient.

How can somebody else, an outside group, a legislative body, decide what is medically necessary or unnecessary when we're dealing with genital ambiguity? Elder said.

Elder says he and his colleagues dont dictate what parents should do. Instead, he encourages parents of his patients to educate themselves on the pros and cons of having their infant undergo surgery.

We're just trying to help parents and provide some guidance. They might say, What do you think I should do?" he said. "You've got to make a decision at some point, because when they hit puberty, its going to create issues, and the surgery is a lot more involved.

As the debate around these surgeries grows fiercer, pediatric urologists have found themselves being increasingly questioned about their practices surrounding surgeries on intersex babies. WGBH News reached out to three other hospitals in and around Boston and pediatric urologists declined, two of which cited the sensitive nature of the topic.

In March 2018, the Societies for Pediatric Urology and the American Urological Association issued a joint statement on pediatric decision-making. They said they believe medical decision-making for children should remain parents' responsibility after consulting with medical professionals and should not be legislated. The statement also said that children should be involved in these decisions.

In Nov. 2018, the Massachusetts Medical Societys Committee on LGBTQ Matters submitted a report to MMS, recommending hospitals create teams designed to assess the needs of intersex babies and proposing that MMS advocate for a delay of surgery.

Parents who have just welcomed a newborn can find themselves overwhelmed with a multidisciplinary team made up of pediatric urologists, endocrinologists and pediatric gynecologists and social workers.

A Boston-area mother, who asked not to be named to protect the identity of her child, has a daughter with an intersex condition who was treated at a different Boston hospital three years ago. Within a couple days of their daughters birth, she and her husband met with a team of 15 people.

[It] is very overwhelming, and everyone is telling you different things: She doesnt have a uterus, there are testes," she remembered. "They started talking about her vagina hole size and talking about intercourse for her one day. It was hard to talk about my daughters sexual health when she was just born.

She and her husband felt some pressure to have their daughters gonads removed. They connected with an intersex support group in search of advice.

We heard adults telling us that they felt violated, that they had to have multiple surgeries. We were shocked at the horror stories we heard, she said.

When she called their daughters pediatric urologist with their decision not to have their daughters testes removed, she said he was visibly unhappy with their decision. He abruptly ended the meeting.

In the beginning when we made the decision, we were still skeptical. Like, is this real? We were nervous that we only talked with people who were unhappy and rightfully so. But the more we talk about it, the more we feel really strongly against surgeries, she said.

Their daughter could develop secondary male characteristics once she hits puberty, but this is a possibility her parents have accepted. They believe their daughter should decide what she wants to do with her body when shes older.

Dina Matos, executive director of the CARES Foundation, an organization based in New Jersey that offers support for people with Congenital Adrenal Hyperplasia the most common DSD said the organization is not for or against genital reconstructive surgery and that their role is to educate parents and patients.

We always encourage people to get more than one opinion. The one thing we highlight most importantly, is if they decide that surgery is indicated with their child, that they seek out an expert," Matos said. "It really takes the surgeon with significant experience, and we really only refer to three or four surgeons in the country right now.

Meredith Nierman/WGBH News

For some, surgery is never an option. Tatenda Ngwaru, an intersex activist from Zimbabwe, recently moved to the suburbs of Boston.

Some people tried to burn down my father's house and kill all of us. And this was done just because of me, because I have a big mouth, Ngwaru said.

When Ngwaru was born, doctors mistook her enlarged clitoris for a penis. She was raised as a boy for the first 10 years of her life, until doctors discovered she had ovaries. It was what she calls an aha moment she never felt like a boy. But in her small town, going from son to daughter was out of the question.

It had always been treated as an abomination, as bad. Back then they used to say we're the ones who will give bad luck to the community, Ngwaru said.

Her parents, stunned by this news, didnt want her to be bullied, so they urged her to continue wearing a boys uniform throughout high school. It was agonizing.

I remember sleeping at night sometimes and thinking, Couldn't morning just come so that we can get it over with? Or maybe morning shouldn't come at all, because I didn't want to deal with daylight and having to be out and pretending and hiding something. There's nothing as painful as an untold story that you have to hide inside, she said.

Ngwaru waited until she was at college in a different part of Zimbabwe to live as a woman and started Zimbabwes first intersex advocacy organization. But trouble soon followed. She was attacked, her office was raided and her family was threatened.

So she fled for the U.S., seeking asylum from gender persecution. And she thought things would be different here.

I thought, they are promoting transgender lives on their TV shows. Clearly, they must know about intersex. I had a rude awakening. Nobody seemed to know what intersex is. And in America what was most shocking for me are the surgeries that had been done on infants, she said.

Zieselman said she wants attitudes to shift in the way they recently have for transgender people.

With transgender children, what the standard of practice has become is to do reversible procedures first and provide a lot of psycho-social support to the child and family, so no irreversible decisions are made too quickly until the child is really sure about what they want," she said. "Why arent we using the same standard of practice for intersex children?

Massachusetts voters may someday see a push for legislation banning medically unnecessary surgeries on infants. Zieselman said she is in discussion with state lawmakers about proposing a bill "to protect intersex children."

All humans have bodily differences, and if theres nothing making them sick or interfering with their health, then theres no reason to modify them," she said. "Intersex people can grow up without surgery and be happy and healthy.

Correction: A previous version of this story misspelled Kimberly Zieselman's name.

See the rest here:
Medically Necessary Or 'Cruel'? Inside The Battle Over Surgery On Intersex Babies - wgbh.org

(MENAFN - Arab Times) Gynecomastia is a problem that occurs in some men in whichbreast tissue develops. It is often caused by some type of disruption to theendocrine system. This is the system of the body which consists of glands thatsecrete various hormones, so any thing that upsets the homeostatic balance ofparticular sex hormones can result in gynecomastia.

There are some cases where a man may not have extra breasttissue because of hormonal problems but rather from having too much fat thataccumulates behind the areolae of the chest. This condition is sometimesdistinguished from gynecomastia and is called lipomastia or adipomastia.

Interestingly gynecomastia is not uncommon in newborn maleinfants and is found in from 60 to 90% of newborn baby boys, but thecondition usually goes away on its own. It can occur in about 1/3 of menbetween 25 and 45 and it becomes more prevalent with age.

How steroids causehormonal problems

One of the major factors associated with the development ofgynecomastia in men is the use of anabolic steroids, causing as many as 25% of allcases in men. Steroid abuse has long been a problem in the sports world,and the concern is that there are unpleasant side effects with these drugs.

The steroids often alter the balance of estrogen andandrogen hormones in people. A man usually has a lot of the androgen hormoneslike testosterone and very little estrogen, but the steroids affect theconcentrations. This hormonal imbalance is believed to be the main causativefactor of gynecomastia in men.

Not all of the steroid drugs necessarily cause breastdevelopment, but those that do often do so because they can cause a change inhormone levels. The synthetic steroid mimics the effect of naturally producedtestosterone. Testosterone is the hormone most associated with muscledevelopment in boys at puberty, and it can lead to increased muscle mass asboys mature during adolescence. Unfortunately the body tends to convert theartificial testosterone found in anabolic steroids into estrogen after a whilewhich then leads to breast tissue development.

What can be doneabout gynecomastia ?

The most permanent solution to the problem of gynecomastiais to have breast reduction surgery as is done at such places as theVera Clinicin Turkey. A surgeon canremove the excess breast tissue from the chest area to create a more masculineappearance. A man does have to be healthy enough to undergo surgery though, sothis is something to keep in mind and why consulting with a physician is a goodfirst step in looking for treatment options.

For some men, the breast cancer drug Tamoxifen has provedhelpful in treating their gynecomastia condition. If a man has breast tissuebecause of being overweight, the first step should be to try to lose weight bystarting an exercise program and following a healthy diet. In the end this canonly benefit you even if you later decide on breast reduction surgery.

MENAFN3010201900960000ID1099198024

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The link between anabolic steroids and gynecomastia in men - MENAFN.COM

Early detection is the best defense to managing breast health.

October is Breast Cancer Awareness Month and a good reminder to schedule your mammogram, perform a self-check in the shower or ask your doctor about your risk factors.

Its important for every woman to know what shes up against regarding breast cancer, says Jessica Bensenhaver, M.D., director of the breast cancer program at Henry Ford Cancer Institute, but the most important things you can do are to be a self-advocate and attend your annual screening.

Breast cancer is one of the most frequently diagnosed cancers in women in the United States. Overall, one in eight women will be diagnosed with breast cancer in her lifetime. However, risk increases with age. According to Dr. Bensenhaver, at age 30, 1 in 217 women are likely to get breast cancer. At age 40, the figure is 1 in 67.

Since breast cancer is treatable at any age when discovered early, routine screenings should be an important part of every womans health plan.

Although most women with breast cancer have no family history of the disease, those with an immediate family member on either parents side should notify their doctor.

Age and family history are among the risk factors women cant control. Others include:

BRCA1 and BRCA2 gene mutations that mean an eight out of 10 chance of getting breast cancer at some point in your life

Race/ethnicity. According to Dr. Bensenhaver, Caucasian women are traditionally more likely to get breast cancer than African Americans. However, if youre younger than 45, African American women are at a higher risk

Breast density. In addition to increasing your risk of breast cancer, having dense breast tissue can make diagnosis of a lump or tumor through standard mammography more challenging. In Michigan, women must legally be notified if their breasts are dense. Sometimes it is recommended that women with dense breasts undergo additional screening methods, like ultrasound or screening tomosynthesis, also known as 3D mammograms

In addition to scheduling regular screenings, women should be familiar with their breasts and see a doctor immediately if they feel a lump, experience persistent pain or observe changes in skin color or texture.

Since worrying about breast cancer can weigh heavily on the mind, the Henry Ford Cancer Institute encourages women to be proactive about their breast health. Dr. Bensenhaver said to lower your overall risk of breast cancer:

Numerous studies have shown that obesity can increase your risk for many types of cancer, including breast cancer. According to the National Cancer Institute, postmenopausal women who are obese have a 20 to 40% increased risk of developing breast cancer.

Consuming one alcoholic drink per day increases your chances of getting breast cancer by at least 5 percent, according to the American Cancer Institute for Cancer Research. Two to three drinks per day raises your risk by 20%.

Although no one knows why, studies show that women who breastfeed have a lower risk of breast cancer. Even just a couple of months of breastfeeding can lower your risk.

In 2002, researchers discovered a connection between Hormone Replacement Therapy (HRT) and increased breast cancer risk. Although HRT can ease postmenopausal symptoms, talk to your doctor about the possible risks and avoid it if possible.

To take the private, at-home assessment, simply visit HenryFord.com/BreastCancerRisk to answer questions about your current health status and fitness levels as well as your family history. The assessment will generate a personalized report that you can download and share with your doctor.

Talking to your doctor is a critical part of the process. Your physician can answer your questions and help you navigate through massive amounts of information available about breast cancer health online. As you try to determine how to reduce your controllable risks, your doctor can cut through all the what ifs to provide compassionate care and straightforward information.

Despite their best efforts, the fact is that some women will face a breast cancer diagnosis. The Henry Ford Cancer Institute has one of the nations leading breast cancer programs, featuring specially trained breast radiologists who read all mammograms and imaging results.

Henry Ford also has the most advanced technologies available to detect and diagnose breast cancer and offers mammography locations throughout southeast and south central Michigan, with day, evening and weekend hours available. Visit HenryFord.com/Mammography for locations and to schedule your mammogram.

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Don't wait: Schedule your breast cancer screening at Henry Ford Cancer Institute - Dearborn Press and Guide

Conley recently created a GoFundMe page to help cover his future medical bills. Despite this, he said he feels uncomfortable putting his personal life on public display, especially since he hasn't yet come out to his grandmother.

But accessing affordable, supportive health care, he said, has been a challenge. He has rescheduled the surgery twice due to insurance confusion and financial stress.

Because of N.C. State Health Plan's policy, the $9,000 estimated cost of the surgery, and potentially all future trans-related health care, will fall on Conley. He said he has saved his own money, but it will not be enough without crowdsourcing.

He also said it has been difficult to find trans-positive health care providers and surgeons.

This is just one example of how transgender people are left out of the discourse, Ezra Wright, a member of UNCs Sexuality and Gender Alliance said.

There is minimal representation and few doctors that perform gender affirmation surgery, they said.

Anne Stephens, a clinical medicine physician at Campus Health, said she understands that LGBTQ+ healthcare should not have a singular approach.

There is a range of ways individuals may choose to transition and express their gender, she said. Changes may be social factors like name and clothing style, or more medical-based changes with male or female hormone medication. The medical side of student transitions is what she and her colleagues aim to help with.

Conley said that pursuing gender confirmation surgery is the right choice for him. However, medical transitions mark a small piece of the deeper LGBTQ+ identity.

The idea that as a transgender person you need to be transitioning is not true, Wright said. It has nothing to do with validity.

They said that the story of gender does not end with surgery that surgery is not the core of the transgender experience.

Its like gender, Wright said. Transitioning is treated as binary its not.

The transgender and LGBTQ+ experience, Conley said, is somewhat shaped by cultural exceptions and the media. He said that it is extremely important that support for the transgender community be genuine.

There are a lot of people at this University that I have found to be my best supporters, he said. But Im not sure that this University as a whole is cognizant of the struggles that trans people face."

Conley said that there is a prevalence of token queer people or token people of color in the media and University public relations.

In terms of University treatment of trans individuals, he said, a motto that they should go by is 'representation, not exploitation.'

He said acknowledging the successes, not just the dangers and violence, in the LGBTQ+ community is a necessary shift in mindset. He said the resilience of the transgender community is shown through the presence of transgender people in academia, healthcare, the arts and other industries.

Why should someone have to die in order for people to care? he said. The ultimate act of resistance is still being alive.

Conley said he is still discovering his own identity and his advocacy work.

I don't want my narrative to be pigeonholed into being a single-story narrative," he said. There is not a before or an after to my transition, as I am learning.

Conley is often afraid that his identity defines him and his body.

Sometimes when I look in the mirror, I still see a stranger," he said. "I will always be living in a state of transition."

Conleys view of top surgery is not cosmetic.

It's one step closer to becoming someone I recognize to be myself, he said. And quite honestly, it will be a life-saving procedure like any other surgery someone may have.

@alliemkelly

university@dailytarheel.com

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When N.C. healthcare wouldn't cover his top surgery, Owen Conley turned to GoFundMe - The Daily Tar Heel

LOS ANGELES, Oct 23 (Reuters) - One toke for the road could end up being a total bummer for drivers who smoke pot, with several companies in the United States preparing to market cannabis breathalyzers as legalized marijuana spreads across the country.

Law enforcement agencies will require breathalyzers to detect marijuana as they are "faced with the necessity of stopping more and more motor vehicles being operated under the influence of THC," said Brett Meade, a retired police chief and a senior program manager for Washington-based non-profit group the Police Foundation.

Nearly a dozen U.S. states allow recreational marijuana consumption and 33 states permit pot for medical use. But all states prohibit driving under the influence of marijuana.

Oakland, California-based Hound Labs is one of the companies developing a breathalyzer to detect THC - the component in marijuana that gets people high - and plans to market it in 2020.

23 PHOTOS

Legal recreational marijuana sold in California

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Customers buy recreational marijuana at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

Marijuana is displayed for sale at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

A customer browses marijuana products for sale at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

Customers queue for recreational marijuana outside the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

A customer browses screens displaying recreational marijuana products for sale at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

A woman holds marijuana for sale at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

Marijuana edibles are displayed for sale at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

Eron Silverstein, 51, (R) shops for marijuana at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

Marijuana products are displayed for sale at the MedMen store in West Hollywood, California U.S. January 2, 2018. REUTERS/Lucy Nicholson

Customers purchase marijuana at Harborside, one of California's largest and oldest dispensary dispensaries of medical marijuana, on the first day of legalized recreational marijuana sales in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

People wait in line at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana sales in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

A customer waits at the counter to purchase marijuana as others wait in line at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

Andrew DeAngelo (L) and his brother Steve DeAngelo (R), co-founders of Harborside, one of California's largest and oldest dispensaries of medical marijuana, celebrate after a ceremonial ribbon cutting on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

An employee hugs a customer as others wait in line at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

An employee finds marijuana for a customer at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

Employees wait behind the counter at Harborside, one of California's largest and oldest dispensaries of medical marijuana, as a large clock counts down to the store's official opening at 6am on the first day of legalized recreational marijuana in Oakland, California, U.S. January 1, 2018. REUTERS/Elijah Nouvelage

Different strains of marijuana are seen for sale at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

A couple poses behind a cardboard Instagram frame while waiting in line at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

Employees prepare to open at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

Steve DeAngelo (C) makes the first legal recreational marijuana sale to Henry Wykowski at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana sales in Oakland, California, U.S. January 1, 2018. REUTERS/Elijah Nouvelage

Michael Sherman purchases marijuana at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana sales in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

A customer peers at different marijuana strains in a glass case at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

Marijuana is seen for sale at Harborside, one of California's largest and oldest dispensaries of medical marijuana, on the first day of legalized recreational marijuana sales in Oakland, California, U.S., January 1, 2018. REUTERS/Elijah Nouvelage

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Construction companies could be a big part of its market, said Hound Labs Chief Executive Officer Mike Lynn.

"Nobody wants a crane operator 50 stories up to be smoking a joint," he told Reuters.

Lynn, a physician, said pregnancy tests, which can detect minute quantities of hormone, inspired him to tackle the challenge of measuring THC on users' breath.

Separately, Cannabix Technologies Inc based in the Vancouver suburb of Burnaby is testing a pair of devices at different price points.

Its THC Breath Analyzer could be cheap enough at a few hundred dollars per unit to potentially allow parents interested in testing their teenager before turning over the keys to the family car, said Cannabix CEO Rav Mlait.

The U.S. court system would need to consider how to treat evidence from THC breathalyzers.

Assuming a motorist who tested positive with a THC breathalyzer was impaired behind the wheel could be "problematic," said Stanford University law professor Robert MacCoun.

Unlike with alcohol, scientific research has not yet established firm correlations between the amount of marijuana people consume and how impaired they become, MacCoun said in an email.

Paul Armentano, deputy director of the National Organization for the Reform of Marijuana Laws, expressed similar concerns.

But he welcomed breathalyzers as an improvement over existing tests used by police and employers, such as urine analysis that is unable to determine whether marijuana was used recently with the potential for impairment, or days or weeks in the past. Breathalyzers are likely to only detect a user who consumed cannabis within the last few hours.

"A test like that would frankly make sense," Armentano said. "Just like we wouldn't allow employees to have a couple drinks and show up to work." (Additional reporting by Jane Ross in Newark, California; editing by Bill Tarrant and Bill Berkrot)

More from Aol.com: Body of missing Alabama girl found; 2 charged with murder Video allegedly shows police officer roughing up 11-year-old girl NM woman playing 'Pokmon Go' with boyfriend shot dead

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That last toke for the road could be a downer with pot breathalyzers coming - AOL

Texas government officials are parroting right-wing media misinformation about trans youth, including during an appearance on Fox News, as the state is attempting to launch a child abuse investigation into a custody battle over a transgender child whose parents disagree about affirming her gender identity. Anti-trans figures have consistently portrayed the affirmation of trans youth as child abuse.

Right-wing media outlets have dubiously framed the custody battle as a debate over medical intervention -- despite the fact that the child would not be undergoing any such procedures in the near future. They have also pushed misinformation about medical interventions that are widely supported by medical professionals, inaccurately calling them chemical castration -- a false claim which has also been repeated by the Texas attorney general office.

The custody battle is between Anne Georgulas and Jeffrey Younger, two divorced Texas parents of a trans child who goes by Luna and uses female pronouns. Three mental health professionals have diagnosed Luna with gender dysphoria, and Georgulas has accepted her as trans. However, Younger has rejected Lunas gender identity, insisting she is not trans and referring to her by her former name (commonly referred to as a deadname). According to court documents, Younger has engaged in increasingly aggressive behavior, including physical force, toward Georgulas and emotionally abusive behavior toward the child. He has also launched an online campaign, fundraiser, and petition all using the name Luna formerly used.

On October 24, a judge ruled that the parents would share joint custody of Luna despite a jury ruling that Georgulas should have sole custody earlier this week. The judges decision came after major outcry from right-wing media figures and Texas elected officials, including Rep. Dan Crenshaw (R-TX) and Sen. Ted Cruz (R-TX).

Right-wing media led an extensive misinformation campaign about the custody battle, which Texas government officials relied on to justify launching an investigation.

Abbott announced on October 23 that the Texas Office of the Attorney General and Department of Family and Protective Services are looking into the custody case. Government officials in the state usedthat misinformation to justifythe potential investigation. Following the announcement, Texas Assistant Attorney General Jeffrey Mateer sent a letter and issued a press release requesting that the state Department of Family and Protective Services conduct a thorough investigation into possible child abuse to protect the boy in question [from] permanent and potentially irreversible harm by his mother.

Mateer is an allied attorney with the extreme anti-LGBTQ group Alliance Defending Freedom; at least four other ADF allied attorneys worked in the Texas attorney generals office in 2018. In 2017, Mateers federal judicial nomination was withdrawn after some of his extreme anti-LGBTQ comments were uncovered. Notably, Mateer claimed that the existence of trans youth proves that Satans plan is working, and he advocated for the harmful and debunked practice of conversion therapy.

On October 24, Texas Lt. Gov. Dan Patrick went on Fox News The Ingraham Angle, a friendly show for anti-LGBTQ viewpoints, and claimed that at seven, you can't make that decision that will change their life forever -- that you cannot come back, particularly if you go through the full treatment into their teen years. During the segment, Ingraham also called gender-affirming carechild abuse. In another segment from Foxs The Daily Briefing with Dana Perino on October 25, Patrick suggested the legislature would explore the issue in its next session.

The language in Mateers comments and Patricks interviews comes directly from right-wing media, which have taken the custody battle and falsely reframed it to be about supposedly irreversible medical procedures. In fact, therapists have not recommended any medical interventions for Luna, but rather would allow her to dress and otherwise identify as a girl. The Washington Post has noted:

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Right-wing media built the Texas government investigation into custody battle over trans child - Media Matters for America