A genetic defect could hold the key to preventing or delaying the onset of a debilitating eye disease that can lead to vision loss and blindness.
MacTel (macular telangiectasia type 2) affects one in 1,000 Australians. Symptoms include slow loss of vision, distorted vision and trouble reading. Because early signs of the disorder are subtle, it is difficult to diagnose.
Researchers have identified an additional seven regions in the human genome that increase the risk of developing the condition, including a rare DNA mutation in the PHGDH gene, which will help clinicians to better diagnose and treat it.
The study builds on earlier WEHI research, which pinpointed that MacTel was associated with low levels of serine, an amino acid used in many pathways of the body.
Led by WEHI Professor Melanie Bahlo in conjunction with Dr Brendan Ansell, Dr Victoria Jackson and Dr Roberto Bonelli and published in Communications Biology, the research provides a new genetic risk calculator for predicting retinal disorders. The research was conducted in collaboration with The Lowy Medical Research Institute, USA and Moorfield’s Eye Hospital, UK.
At a glance MacTel is primarily caused by slight changes to the levels of several fundamental amino acids in an individual’s blood Researchers identified a further, rare, PHGDH gene mutation, which makes people five times more susceptible to developing MacTel, as well as seven other new genetic regions. Understanding the genetic mutations that cause MacTel will allow clinicians to better screen for the condition and potentially prevent it from developing.PHGDH increases MacTel risk

Sugar is added to many common foodstuffs, and people in Switzerland consume more than 100 grams of it every day. The high calorie content of sugar causes excessive weight and obesity, and the associated diseases. But does too much sugar have any other harmful effects if consumed regularly? And if so, which sugars in particular?
Even moderate amounts of sugar increase fat synthesis
Researchers at the University of Zurich (UZH) and the University Hospital Zurich (USZ) have been investigating these questions. Compared to previous studies, which mainly examined the consumption of very high amounts of sugar, their results show that even moderate amounts lead to a change in the metabolism of test participants. “Eighty grams of sugar daily, which is equivalent to about 0,8 liters of a normal soft drink, boosts fat production in the liver. And the overactive fat production continues for a longer period of time, even if no more sugar is consumed,” says study leader Philipp Gerber of the Department of Endocrinology, Diabetology and Clinical Nutrition.
Ninety-four healthy young men took part in the study. Every day for a period of seven weeks, they consumed a drink sweetened with different types of sugar, while the control group did not. The drinks contained either fructose, glucose or sucrose (table sugar which is a combination of fructose and glucose). The researchers then used tracers (labeled substances that can be traced as they move through the body) to analyze the effect of the sugary drinks on the lipid metabolism.
Fructose and sucrose double fat production beyond food intake
Overall, the participants did not consume more calories than before the study, as the sugary drink increased satiety and they therefore reduced their calorie intake from other sources. Nevertheless, the researchers observed that fructose has a negative effect: “The body’s own fat production in the liver was twice as high in the fructose group as in the glucose group or the control group — and this was still the case more than twelve hours after the last meal or sugar consumption,” says Gerber. Particularly surprising was that the sugar we most commonly consume, sucrose, boosted fat synthesis slightly more than the same amount of fructose. Until now, it was thought that fructose was most likely to cause such changes.
Development of fatty liver or diabetes more likely
Increased fat production in the liver is a significant first step in the development of common diseases such as fatty liver and type-2 diabetes. From a health perspective, the World Health Organization recommends limiting daily sugar consumption to around 50 grams or, even better, 25 grams. “But we are far off that mark in Switzerland,” says Philipp Gerber. “Our results are a critical step in researching the harmful effects of added sugars and will be very significant for future dietary recommendations.”
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Nearly every older adult was prescribed a prescription drug that increased their risk of falling in 2017, according to new University at Buffalo research.
The study found that the percentage of adults 65 and older who were prescribed a fall- risk-increasing drug climbed to 94% in 2017, a significant leap from 57% in 1999. The research also revealed that the rate of death caused by falls in older adults more than doubled during the same time period.
Even minor falls may be dangerous for older adults. Falls that are not fatal can still result in injuries — such as hip fractures and head traumas — that may drastically lower remaining quality of life. Each year, nearly $50 billion is spent on medical costs related to fall injuries among older adults, according to the Centers for Disease Control and Prevention.
The alarming results solidify the importance of interventions to de-prescribe potentially inappropriate drugs among older, frailer patients, says Amy Shaver, PharmD, lead investigator and postdoctoral associate in the UB School of Public Health and Health Professions.
“Our study indicates two trends increasing concurrently at a population level that should be examined at the individual level. Our hope is it will start more conversations on health care teams about the pros and cons of medications prescribed for vulnerable populations,” says Shaver.
Additional investigators in the UB School of Pharmacy and Pharmaceutical Sciences include Collin Clark, PharmD, clinical assistant professor; David Jacobs, PharmD, PhD, assistant professor; Robert Wahler Jr., PharmD, clinical associate professor; and Mary Hejna, PharmD, pharmacy resident at Kaleida Health.

AdvertisementContinue reading the main storySupported byContinue reading the main storyCritic’s NotebookThis Is Your Brain on PelotonThe exercise bike company’s virtual classes represent an intense new genre of content: a total curation of the mind.March 16, 2021, 10:00 a.m. ETI think I’ve discovered the key to an active lifestyle. His name is Cody Rigsby, and he looks like a piece of Disney fan art — the kind where cartoon princes are rendered as photo-realistic living boys.Today our prince sits alone in a dusky blue exercise studio, thighs pumping atop a gleaming black stationary bicycle. He wears a precise haircut and a Peloton tank top that reveals the Mickey Mouse tattoo inked into the muscle of his upper arm, which is very large. Over the next half an hour, he will lead a virtual spinning class, curate a playlist of early-aughts pop songs and deliver an extemporaneous speech on topics including: Oprah’s interview strategy; the merits of the British girl group Little Mix; historical dramas (“I have tried to watch ‘The Crown’ so many times and I just can’t, y’all”); multiple sclerosis awareness; women (“thank you for being fierce”) and Ashlee Simpson’s 2004 single “Pieces of Me,” which moves Rigsby to lead the class in a nostalgic meditation.“It’s 2004,” Rigsby tells us. “You just bought a studded belt from PacSun. You’re feeling different and cool. Resistance: 40 to 50. Cadence: 75 to 80. Hands out long, hips stay back, rise up.” Rigsby jogs atop the bike and stares deeply into the camera. “You aren’t like the other kids,” he continues. “You didn’t shop at Abercrombie. You shopped at PacSun. Because you were unique.”Before I met Cody Rigsby, I thought Peloton, the bourgeois exercise bike company that employs him, was about a slavish devotion to a techno-religious sect. I didn’t realize that it could also be about celebrities, accessories and the reimagining of the high school social hierarchy. Suddenly I was interested. I dislike exercise, so when I do it, I want my brain to feel as anesthetized as possible. And after I signed up for Peloton’s 30-day free trial of virtual content and hopped on the dusty Schwinn in my in-laws’ basement, I was zonked.Logging on to one of Rigsby’s sessions feels like syncing up with a human iPhone, always swiping toward some new distraction. It keeps me just stimulated enough to alleviate the monotony and discomfort of exercise without prompting me to do any of my own mental work. Peloton is known for selling its ludicrously expensive bikes, but you don’t have to buy one to stream its classes. The company’s more significant offering is this: the total curation of the mind.Exercise-as-entertainment is an American institution. See: Jack LaLanne, Richard Simmons, “The Biggest Loser.” The fitness guru’s sphere of influence has typically been centered on the body, with some wiggle room for related self-help psychobabble and musical appreciation. Now Peloton, which pumps out dozens of streaming classes a day, has introduced topicality and specificity to the genre. The company offers rides themed around Black History Month, Women’s History Month and the life philosophy of the television producer Shonda Rhimes.In the extended Peloton universe, which besides the spinning classes also includes guided meditations, stretches, strength training and more, the instructors have carved out their own microgenres. The luminescent Ally Love is the queen of seated choreography. Jess King has developed a series she calls “The Jess King Experience,” incorporating campy costumes, dramatic camera angles, a DJ sidekick and extreme drama-kid vibes.And Rigsby has the energy of a messy podcast host; as he rides, he might lead the class in a skills ranking of defunct boy bands (“Indisputably, Kevin is the hottest Backstreet Boy”) or break down the previous night’s television event. The day after Oprah’s royal exit interview, Rigsby began his class like this: “I’m bringing Meghan Markle energy into the ride, OK?”Peloton may offer a magnetic trainer in every flavor, but they’re all in sync with the company’s overarching value system. The content is aimed at a class of people who can either afford to own a Peloton Bike ($1,895 or $2,495), or want to take virtual classes ($39 a month) alongside people who do. It tends to promote a palatable multiculturalism without being overtly political. (“I always think of the Peloton bike as a Trojan horse of diversity and acceptance,” Rigsby said last year. “I want to be able to change people’s hearts and open their minds to what a gay man is.”) But above all, Peloton worships at the altar of consumer technology.While yoga blooms from a philosophical and spiritual tradition, spinning is about your relationship to the machine. You become one with the equipment; you literally clip yourself in. If a traditional bike ride offers some thrill from breezing around outside, Peloton represents a total mastery of the natural environment. The Peloton user submits to the uncharted terrain of Cody’s World; he decides when we are cruising down a flat road and when we are huffing up a hill.Though we are isolated in our homes, we are bound together through a shared tactile experience with the product: thousands of legs twirling at the same pace, thousands of fingers twirling the knob just so. Part of the hypnotic appeal of the Peloton instructor monologue is how seamlessly the commentary slips into jargon about cadence and resistance. Through their physical prowess, the instructors lay claim to a broader social and even moral authority, and their classes suggest that the act of using the Peloton itself releases positive energy into the world.On the right side of the screen, a roiling leader board ranks us by our level of physical exertion, and each user’s self-selected awareness hashtag rises and falls based on how hard she drives her body: #PeloForWine, #WilliamsSyndrome, #WearADamnMask. Since I don’t own the fancy company bike, my own hashtag — #FreeBritney — languishes out of view. Every class also functions as an infomercial for the Peloton line of equipment; I’ve found myself lusting after a Peloton bike just to inch closer to the imagined subject to whom the instructors speak.Does this all sound a little terrifying? In most contexts, sure. I would not, for instance, want to be seated next to a Peloton instructor on an airplane. The first thing John Foley, Peloton’s C.E.O., does when he wakes up in the morning is drink water from his hands “until I feel like I’m going to throw up,” and my rational brain is skeptical of this person. But exercise encourages a special kind of mental gymnastics. When I’m working out, I suddenly welcome a parasocial relationship with a sweetly annoying person who can carry on his end of the conversation for 45 minutes straight, and my flowing endorphins ensure that I will be pair-bonded with him when the session’s up.Social media companies work to stratify our personalities, isolating out various impulses and pumping in stimuli to satisfy them: Twitter me is wryly critical, Instagram me is a basic mom, and Peloton me is a capitalist shill in thrall to power. (Twitter me would hate Peloton me.) Recently the frothiest moments from Peloton workout videos have been skimmed off the app and floated to other social networks, where they are read differently. On TikTok, instructors are set loose as memes; on Twitter, they are pinned down and politically scrutinized.I first noticed Rigsby when he went a little bit viral by delivering a sermon on Britney Spears’ longtime conservatorship as her song “Lucky” bumped in the background. Soon after that rant was celebrated on TikTok, another clip hit Twitter that sounded an alarm about Rigsby’s rise: He seemed to be employing Black vernacular, as laundered through white gay culture, while jokingly threatening a cartoon toddler, the “Rugrats” heel Angelica Pickles. This is the kind of absurd cultural performance that raises suspicions on Twitter but, shifted just one tab over, powers an appealingly thoughtless workout. Even when Rigsby is being lightly dragged across the internet, plenty of people are following close behind, demanding a link to the ride.AdvertisementContinue reading the main story

Ketone bodies are generally an alternative energy source during starvation, but in newborns, ketogenesis is active regardless of nutritional status. In a recent study from Kumamoto University (Japan), researchers analyzed the effects of ketogenesis in mice and found that it has a protective effect on cells by maintaining the function of mitochondria. They expect that this effect can be used in future therapies for protecting mitochondria and organs.
Ketones, along with glucose and fatty acids, are metabolites used as energy sources. In particular, ketones are known to be an alternative energy source during periods of fasting or starvation. However, ketogenesis is known to be active in the neonatal period regardless of the number of calories consumed during nursing, and role it plays in newborns is not well understood.
To search for answers, researchers generated ketogenesis-deficient mice that lacked the gene for HMG-CoA Synthase 2 (HMGCS2), an important enzyme ketogenesis. Their analysis showed that, in the absence of ketone bodies, the mice developed a severely fatty liver during the neonatal period.
Focusing on the mitochondria, they showed that enzymatic reactions in the mitochondria, mainly the Krebs cycle, were impaired. Nutrients are converted to acetyl CoA during the Krebs cycle, which is then converted to citric acid and seven other acids to produce energy. In the search for the cause of the dysfunction, researchers confirmed that the accumulation of the substrate acetyl CoA (due to insufficient ketogenesis) impairs the functions of proteins in the mitochondria by adding excessive acetylation.
“During a rapid increase in fatty acid intake with postnatal nursing, active ketogenesis under normal conditions has a protective effect by preventing excessive acetylation of mitochondrial proteins and maintaining mitochondrial function,” said study leader Dr. Yuichiro Arima. “We believe that this result will be used in therapeutic applications for mitochondrial and organ protection in the future.”
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Hair grows from stem cells residing in hair follicles. During aging, the capability of hair follicles to grow hair is successively lost, leading to hair thinning and ultimately hair loss. In a new study, researchers from Tokyo Medical and Dental University (TMDU) and the University of Tokyo identified a novel mechanism by which hair follicles lose their regenerative capabilities.
Hair follicles are mini-organs from which new hair constantly grows. The basis for new hair growth is the proper function of hair follicle stem cells (HFSCs). HFSCs undergo cyclic symmetric and asymmetric cell divisions (SCDs and ACDs). SCDs generate two identical cells that go on to have the same fate, while ACDs generate a differentiating cell and a self-renewing stem cell. The combination ensures that the stem cell population continues to exist, yet how those contribute to the loss of HFSC function due to aging is not yet completely understood.
“For proper tissue function, symmetric and asymmetric cell divisions have to be in balance,” says corresponding author of the study Emi Nishimura. “Once stem cells preferentially undergo one of either or, worse yet, deviate from the typical process of either type of cell division, the organ suffers. In this study, we wanted to understand how stem cell division plays into hair grows during aging.”
To achieve their goal, the researchers investigated stem cell division in HFSCs in young and aged mice by employing two different types of assays: Cell fate tracing and cell division axis analyses. In the former, HFSCs were marked with a fluorescent protein so they could be followed over time, while in the latter the angle of HFSC division was measured. Strikingly, the researchers were able to show that while HFSCs in young mice underwent typical symmetric and asymmetric cell divisions to regenerate hair follicles, during aging they adopted an atypical senescent type of asymmetric cell division.
But why does the mode of cell division change so drastically during aging? To answer this question, the researchers focused on hemidesmosomes, a class of protein that connect the cells to the extracellular matrix (ECM; proteins surrounding cells). Cell-ECM have long been known to confer polarity to cells, i.e., that the cells can sense their localization within a given space through the action of specific proteins. The researchers found that during aging both hemidesmosomal and cell polarity proteins become destabilized, resulting in the generation of aberrantly differentiating cells during division of HFSCs. As a result, HFSCs become exhausted and lost (leading to hair thinning and hair loss) over time.
“These are striking results that show how hair follicles lose their ability to regenerate hair over time,” says first author of the study Hiroyuki Matsumura. “Our results may contribute to the development of new approaches to regulate organ aging and aging-associated diseases.”

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Children who are exposed to abuse before they are eleven years old, and those exposed to abuse both in childhood and adolescence may be more likely to develop conduct problems (such as bullying or stealing) than those exposed to abuse in adolescence only and those who are not exposed to abuse, according to a study published in the open access journal BMC Psychiatry.
A team of researchers at the Universities of Bath and Bristol examined data on 13,793 children and adolescents (51.6% boys), who were followed from ages four to 17 years, included in the Avon Longitudinal Study of Parents and Children, a cohort of children born in South-West England in the early 1990s.
Andreas Bauer, the lead author said: “Conduct problems refer to antisocial behaviors in childhood and/or adolescence, such as fighting, bullying, lying or stealing. They are associated with various negative outcomes, including mental and physical health problems, and it is important to understand their possible causes and to develop effective prevention and intervention programs. Although we know that child abuse is an important factor linked to conduct problems in children, much less is known about when child abuse is most harmful and how it relates to the development of serious behaviour problems over time.”
From the children included in this study, the authors identified three groups who developed elevated levels of conduct problems. There was an early-onset persistent group who developed conduct problems in childhood which continued into adolescence (4.8% of the sample), an adolescence-onset group who developed conduct problems in adolescence (4.5%) and a childhood-limited group who developed conduct problems in childhood only (15.4%). The majority of children (75.3%) did not develop serious conduct problems.
Andreas Bauer said: “We assessed whether abuse was more common in the backgrounds of these three groups than in those who did not develop conduct problems. Our findings showed that abuse was more common in the early-onset persistent group who showed conduct problems in childhood and adolescence, and also in the adolescence-onset group who developed conduct problems in adolescence.”
The authors also looked at the timing of child abuse, comparing those who were exposed to abuse only in childhood or only in adolescence with those exposed to abuse in childhood and adolescence. They found that children exposed to abuse in both childhood and adolescence were 10 times more likely to be in the early-onset persistent conduct problems group and 8 times more likely to be in the adolescence-onset conduct problems group. Abuse in childhood was associated with a 4- to 6-fold increase in risk for showing early-onset persistent or adolescence-onset conduct problems. In contrast, abuse in adolescence only was not linked to an increased risk of showing severe conduct problems.
Conduct problems were measured at ages 4, 7, 8, 10, 12, 13, and 17, by asking parents to rate their child’s behavior over the last six months. At age 22, individuals were asked to report physical, psychological, or sexual abuse experienced in childhood (before age 11 years) and adolescence (between ages 11-17 years). Complete data for conduct problems as reported by parents and children, and physical, psychological, and sexual abuse as reported by children was available for 3,127 participants. Out of those, one in five (19.6%) participants reported experiencing some form of abuse, with 11.3%, 8.9%, and 8.1% of participants reporting physical, psychological, and sexual abuse, respectively.
A limitation of the study is that experiences of abuse in childhood and adolescence were measured when the participants were aged 22 years, so there may be issues with recall biases and issues surrounding disclosure of earlier abuse. Relying on parent-reported conduct problems in adolescence may have underestimated the level of behavioral problems, as parents may not be aware of their child’s behavior outside the home.
Andreas Bauer said: “Our results suggest that abuse is more common in the backgrounds of young people with conduct problems and that conduct problems starting in adolescence may be linked to adverse experiences in childhood, rather than being an exaggerated form of teenage rebellion or due to peer pressure. Preventing child abuse may also help protect children from developing serious behaviour problems. However, it is important to note that many young people who experience abuse do not develop conduct problems, and conduct problems can also occur in the absence of child abuse.”
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Slow walkers are almost four times more likely to die from COVID-19, and have over twice the risk of contracting a severe version of the virus, according to a team of researchers from the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre led by Professor Tom Yates at the University of Leicester.
The study of 412,596 middle-aged UK Biobank participants examined the relative association of body mass index (BMI) and self-reported walking pace with the risk of contracting severe COVID-19 and COVID-19 mortality.
The analysis found slow walkers of a normal weight to be almost 2.5 times more likely to develop severe COVID-19 and 3.75 times more likely to die from the virus than normal weight fast walkers.
Professor Yates, Lead Researcher for the study and a Professor of Physical Activity, Sedentary Behaviour and Health at the University of Leicester said:
“We know already that obesity and frailty are key risk factors for COVID-19 outcomes. This is the first study to show that slow walkers have a much higher risk of contracting severe COVID-19 outcomes, irrespective of their weight.
“With the pandemic continuing to put unprecedented strain on health care services and communities, identifying individuals at greatest risk and taking preventative measures to protect them is crucial.”
A further key finding from this research was that normal weight slow walkers are more at risk for both severe COVID-19 and COVID-19 mortality than fast walkers with obesity. Furthermore, risk was uniformly high in normal weight slow walkers and slow walkers with obesity.
Professor Yates continued:
“Fast walkers have been shown to generally have good cardiovascular and heart health, making them more resilient to external stressors, including viral infection but this hypothesis has not yet been established for infectious disease.
“Whilst large routine database studies have reported the association of obesity and fragility with COVID-19 outcomes, routine clinical databases do not currently have data on measures of physical function or fitness.
“It is my view that ongoing public health and research surveillance studies should consider incorporating simple measures of physical fitness such as self-reported walking pace in addition to BMI, as potential risk predictors of COVID-19 outcomes that could ultimately enable better prevention methods that save lives.”
The study ‘Obesity, walking pace and risk of severe COVID-19 and mortality: analysis of UK Biobank’ was published on 26 February 2021 in the International Journal of Obesity. The analysis was restricted to England and outcomes were assessed during the first wave of the pandemic.
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Researchers at the University of Surrey have found that non-invasive skin swab samples may be enough to detect COVID-19.
The most widely used approach to testing for COVID-19 requires a polymerase chain reaction (PCR) test, which involves taking a swab of the back of the throat and far inside the nose.
In a paper published by Lancet E Clinical Medicine, chemists from Surrey teamed up with Frimley NHS Trust and the Universities of Manchester and Leicester to collect sebum samples from 67 hospitalised patients — 30 who had tested positive for COVID-19 and 37 who had tested negative. The samples were collected by gently swabbing a skin area rich in sebum — an oily, waxy substance produced by the body’s sebaceous glands — such as the face, neck or back.
The researchers analysed the samples by using liquid chromatography mass spectrometry and a statistical modelling technique called Partial Least Squares — Discriminant Analysis to differentiate between the COVID-19 positive and negative samples.
The Surrey team then found that patients with a positive COVID-19 test had lower lipid levels — or dyslipidemia — than their counterparts with a negative test. The accuracy of the study’s results increased further when medication and additional health conditions were controlled.
Dr Melanie Bailey, co-author of the study from the University of Surrey, said:
“Unfortunately, the spectre of future pandemics is firmly on the top of the agenda for the scientific community. Our study suggests that we may be able to use non-invasive means to test for diseases such as COVID-19 in the future — a development which I am sure will be welcomed by all.”
Matt Spick, co-author of the study from the University of Surrey, said: “COVID-19 damages many areas of metabolism. In this work, we show that the skin lipidome can be added to the list, which could have implications for the skin’s barrier function, as well as being a detectable symptom of the disease itself.”
Dr George Evetts, Consultant in Anaesthesia & Intensive Care Medicine at Frimley Park Hospital, said: “Investigating new methods of diagnosis and surveillance in a new disease such as COVID-19 that has had such a devastating effect on the world is vital. Sebum sampling is a simple, non-invasive method that shows promise for both diagnostics and monitoring of the disease in both a healthcare and a non-healthcare setting.”
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