Body

A molecular "trick" that kept our ancient ancestors from starving may now be contributing to the obesity epidemic, a new study finds.

In starvation times, researchers say, animals were more likely to survive if they could hoard and stretch out their stored energy. Even if an animal secured a rare feast, evolution smiled on the storage of excess fuel as fat, given the likelihood of a quick return to starvation.

"We discovered an anti-starvation mechanism that has become a curse in times of plenty because it sees cellular stress created by overeating as similar to stress created by starvation - and puts the brakes on our ability to burn fat," says lead study author Ann Marie Schmidt, MD, the Dr. Iven Young Professor of Endocrinology at NYU School of Medicine.

Published online July 16 in Cell Reports, the current study reveals that the natural function of a protein called RAGE on the surface of fat cells is to stop the breakdown of stored fat in the face of stress. Its existence may partly explain why 70 percent of American adults are overweight or obese, according to the American Heart Association (AHA). In March 2017, the AHA announced a grant to help researchers find the elusive "metabolic brake."

The AHA funding followed a 2016 study that found contestants from America's Greatest Loser gained back their lost pounds after the show ended. Why did their metabolisms slam to a halt in the face of weight loss, as if their bodies were bent on returning to obesity?

A Brake on Fat Burning

According to the authors, the most efficient way for evolution to create an anti-starvation mechanism was from ancient systems that helped animals use food for cellular energy and recover from injury. Also wired into these primal mechanisms was the hormone adrenalin, which signals for the conversion of fat into energy as animals run from predators, or into body heat when they get cold.

This convergence -- through the same signaling proteins -- means that RAGE may block "fat burning" called for when we starve, freeze, get injured, panic, or ironically, overeat.

According to the new study and experiments done elsewhere in human tissues, RAGE is turned on by the advanced glycation endproducts (AGEs), which form when blood sugar combines with proteins or fats - most often in aging, diabetic and obese patients. Other molecules also activate RAGE, such as those released when cells die and spill their contents into intracellular spaces in response to stress.

A disturbing possibility, says Schmidt, is that many proteins and fats have come to activate "the RAGE break" as they warp and stack up (as toxic oligomers) in people that eat more than their ancestors did.

The current study found that removing RAGE from fat cells caused mice to gain up to 75 percent less weight during three months of high-fat feeding, despite equal amounts of food consumption and physical activity, than mice with the RAGE brake on. Transplanting fatty tissue lacking RAGE into normal mice also decreased weight gain as they were fed a high-fat diet.

In both sets of experiments, the deletion of RAGE from fat cells released the braking mechanisms that restrained energy expenditure. Once freed up, energy expenditure rose, contributing to the reduced body weight gain in mice with the fatty diet.

The new study complements the team's discovery of experimental compounds that attach to the "tail" of RAGE. From there, they prevent RAGE from turning down the action of protein kinase A, a key player in the chain reaction that ends with a protein called UCP1 turning fat into body heat.

The research team plans - once they optimize the design of these "RAGE inhibitors" - to examine whether the agents can keep bariatric surgery patients, and patients undergoing medical weight loss regimens, from regaining lost weight.

Importantly, RAGE is much more active during metabolic stress (e.g. starving or overeating) than in everyday function, which suggests it can be safely interfered with through drugs, the authors say.

"Because RAGE evolved out of the immune system, blocking it may also reduce the inflammatory signals that contribute to insulin resistance driving diabetes," says Schmidt. "Further, such treatments may lessen the system-wide inflammation linked to risk for atherosclerosis, cancer, and Alzheimer's disease."

Researchers at Lund University in Sweden have investigated the link between osteoarthritis and mortality in an epidemiological study. It was shown that the risk of dying from cardiovascular disease was higher for people with osteoarthritis than for the rest of the population.

Using population registers, the researchers studied approximately 469 000 people living in Skåne, Sweden, who in 2003 were between 45 and 84 years old and followed them through to 2014. The group included 16 000 patients with knee arthritis, 9 000 with hip arthritis, 4 000 with wrist arthritis and 5 500 with other forms of osteoarthritis. They had all been diagnosed in 2003 or before.

"We looked at the cause of death for those who died between 2004 and 2014 and who had previously been diagnosed with osteoarthritis and compared the results with the rest of the population in the same region. The groups were not different in terms of most causes of death, but we saw the risk of mortality from cardiovascular disease was higher for those with an osteoarthritis diagnosis. The risk did not increase in the short term after the osteoarthritis diagnosis, but the longer a person had had osteoarthritis, the higher the risk of mortality from cardiovascular diseases compared with the background population, e.g. if a person had a knee arthritis diagnosis for 9 to 11 years, the risk was 16 per cent higher", says Martin Englund, professor at Lund University and physician at Skåne University Hospital, who led the study.

This means that for every 100 000 inhabitants who have had osteoarthritis for 9-11 years, 40 more die of cardiovascular diseases per year, compared with the population without osteoarthritis (in corresponding gender and age distribution).

The study did not investigate the mechanisms behind osteoarthritis and cardiovascular disease and the causal link is not fully known. However, Martin Englund has a theory on the reason behind the results.

"Osteoarthritis causes pain, which often results in people not being as mobile and becoming sedentary instead. Thus, there is a risk of weight gain, which we know leads to secondary diseases, including cardiovascular diseases. There are also other background factors in common for osteoarthritis and cardiovascular disease. Inflammation can be a contributory cause of osteoarthritis, and can also lead to an increased risk of cardiovascular disease. Regardless, it's important to be physically active and keep body weight in check. In many countries there are special education programs for those suffering from osteoarthritis where you can get information on the disease as well as help and exercise advice", concludes Martin Englund.

CLEVELAND, Ohio (July 15, 2019)--Sleep disturbances are a frequent complaint of women in the menopause transition and postmenopause. A new study demonstrates that women with premature ovarian insufficiency (POI) who are receiving hormone therapy have poorer sleep quality and greater fatigue than women of the same age with preserved ovarian function. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

It is estimated that 40% to 50% of menopausal and postmenopausal women complain about sleep problems. Sleep problems include difficulty falling asleep and/or staying asleep, as well as waking up too early. Complicating matters is the fact that women with insomnia generally complain more about body pain, headaches, daytime dysfunction, mood disorders, fatigue, and decreased work productivity. Although some of the problems are related to other common symptoms of menopause such as hot flashes, not all sleep issues can be traced back to these root causes.

Although numerous studies have been conducted about the sleep patterns of menopausal and postmenopausal women in general, this newest study from Brazil is thought to be the first to specifically evaluate the sleep quality in women with POI. This condition differs from premature menopause because women with POI can still have irregular or occasional periods for years and might even become pregnant. The Brazilian study found that women with POI who are receiving hormone therapy have poorer sleep quality, largely as a result of taking longer to fall asleep. These women were also found to have a higher fatigue index and were more likely to use sleep-inducing medications compared with comparably aged women who still had full ovarian function.

Study results appear in the article "Sleep quality and fatigue in women with premature ovarian insufficiency receiving hormone therapy: a comparative study."

"This study shows that women with POI have poor sleep quality despite the use of hormone therapy. Another interesting finding from the study is that total sleep quality in women with POI was directly related to the number of children they had and overall was similar to sleep quality in women without POI. This speaks to the scope of the problem when it comes to sleep disturbances and the important and often under-recognized factors that contribute to sleep complaints being more common in women than in men," says Dr. Stephanie Faubion, NAMS medical director.

Researchers from BYU and the Netherlands' Delft University of Technology may have figured out the secret to get people to buy more fresh produce: dress veggies up in black.

A new study by industrial design professor Bryan Howell and Dutch colleague Hendrick Schifferstein looks at how the backgrounds of grocery store displays impact the attractiveness of vegetables. After testing an array of colors and neutral shades, they found the best bet is to go back in black.

"If the goal is to boost sales of fresh produce in retail stores, it makes sense that vendors present them in an attractive and appetizing manner," Howell said. "In the design world, black has always been the cool color, but I didn't know it would carry over into the vegetable world."

For the study, 46 participants assessed five vegetables on various shades of backgrounds between black and white. The study participants gave attractiveness and perceived expensiveness ratings for each veggie -- mushroom, bell pepper, carrot, tomato, eggplant -- against each background.

The researchers had already tested the vegetables against a larger spectrum of colored backgrounds, but found that cool, warm, orange and blue hued backgrounds were not optimal for presentation. The goal of the research was to see if there was one color that brought out the shine in most vegetables. The big winner was black.

Yellow peppers were rated as the most attractive and expensive across all the white, grey and black backgrounds, while carrots generally rated the least attractive and expensive. However, carrots got the biggest boost in ratings when paired with a black background, even jumping eggplants and mushrooms in attractiveness.

The finding lines up with previous studies that find black to be associated with high quality and expensiveness in multiple contexts. "I did a lot of color studies when I worked at Dell Computers and black was always the answer for computing products," Howell added.

Researchers said consumers generally finding vegetables more attractive on very dark backgrounds may be of direct relevance to current food retailers. Designers should utilize these insights to improve vegetable packaging or presentation to effectively achieve the marketing goals of food industry managers.

"I think stores can do a much better job at presenting their vegetables than they do," Howell said. "This is a bit of fun research that can help."

University of Otago, Christchurch researchers played a key role in new global research showing the causes of the eating disorder anorexia are likely metabolic as well as psychological.

The findings, published in Nature Genetics, are likely to give hope to patients, their families, and new direction to clinicians and scientists looking for better treatments for the disease with the highest mortality rate of any psychiatric disorder.

They suggest people are born with a biological predisposition to developing the disease that affects function of the brain as well as the metabolic system, and considering both these factors is important when exploring new avenues to treat it.

Anorexia Nervosa Genetics Initiative (ANGI) researchers sampled the DNA of almost 17,000 patients and compared this with over 55,000 "control cases" (without anorexia nervosa) recruited from 17 countries across North America, Europe and Australasia. The lead researcher was Professor Cynthia Bulik from the University of North Carolina (USA) and the Karolinska Institute (Sweden) who worked with more than 100 other scientists, including lead researchers from New Zealand - the University of Otago, Christchurch's clinical psychologist and senior lecturer Dr Jenny Jordan and genetics Professor Martin Kennedy.

The ANGI team found eight genetic variants significantly associated with anorexia nervosa, showing the origins of this serious disorder appear to be both metabolic and psychological. The researchers also found:

The genetic basis of anorexia nervosa overlaps with traits associated with people's ability to metabolise fats and sugars, and body mass index.

Genetic factors associated with anorexia nervosa influence physical activity, which could explain the tendency for people with anorexia nervosa to be highly active despite their low calorie intake.

The genetic basis of anorexia nervosa overlaps with other psychiatric disorders such as obsessive-compulsive disorder, depression, anxiety, and schizophrenia.

University of Otago, Christchurch researcher Dr Jenny Jordan says current treatments for anorexia nervosa are primarily psychological therapies that help patients with the critical but difficult task of regaining weight and re-establishing normal eating. There are no specific medications for anorexia nervosa.

"The ANGI findings give us a new way of looking at this disease. For example, many people diet but only a few develop anorexia nervosa with very low levels of weight and sometimes extreme levels of exercise. The findings that there are genetic differences relating to metabolism in people with anorexia in our study helps make sense of that. It may also help explain in part why recovery is such a struggle. These findings, that it is not just a psychiatric condition, will be hugely validating for many with anorexia nervosa and their families, Dr Jordan says.

University of Otago, Christchurch's Professor Martin Kennedy says the findings indicate that people are born with a genetic predisposition for developing the disease. What this means is that they are more prone to developing the disorder, although not everyone with those patterns of DNA will do so.

"Our hope is these fundamental genetic insights will point to better ways of preventing the disorder, and better medications that target the underlying biology. Nobody chooses to succumb to this awful disease, and we need these kinds of new insights to help people survive and move on with their lives."

Most people have probably been stung by a bee and while it can be painful, it's especially dangerous for the many that are at risk of suffering a life threatening allergic reaction.

Australian researchers have successfully completed a human trial on a vaccine designed to eliminate the risk of a severe allergic reaction to European honeybee stings.

The clinical trial at Flinders University and the Royal Adelaide Hospital included 27 adults with a history of allergic reactions to bee stings.

The vaccine used in the trial contained a unique sugar-based ingredient called an adjuvant, developed in Australia, which is designed to help the body neutralise the bee venom at a faster rate.

Professor Nikolai Petrovsky says the adjuvant used to enhance the bee sting vaccines has now been successfully given to over a thousand individuals across a range of different vaccines including in the current bee sting allergy trial.

"Our technology is like adding a turbocharger to a car and in this case makes the bee allergy vaccine much more powerful, allowing the immune system to better neutralise the bee venom and prevent allergic symptoms," says Professor Petrovsky.

Associate Professor Robert Heddle, lead investigator in the trial, says the aim was to see if the Advax adjuvant would safely speed up and improve bee sting immunotherapy.

"The results of the study were very promising and confirmed the safety of this approach to improving bee sting immunotherapy."

Dr Anthony Smith, an investigator in the trial, says while a commercial bee venom therapy is already available, it requires patients to have over 50 injections over a 3 year period to build up their immune system.

"The current treatment option for serious bee venom allergies is lengthy and cumbersome, so I hope this enhanced bee venom therapy brings about faster, but longer lasting protection to bee stings for allergic individuals."

The Advax adjuvant which enhances the bee sting vaccines was developed in Adelaide by Vaxine Pty Ltd and has also been used to develop vaccines for seasonal and pandemic influenza, hepatitis, malaria, Alzheimers disease, cancer and other diseases.

A team of researchers from the SingHealth Duke-NUS Academic Medicine Centre's Viral Research and Experimental Medicine Centre (ViREMiCS) found that immune cells undergoing stress and an altered metabolism are the reasons why some individuals become sick from viral infections while others do not, when exposed to the same virus.

The findings, published in top medical journal Nature Medicine, have important implications for the prevention and treatment of infectious diseases caused by flaviviral infections such as dengue fever, congenital Zika syndrome and yellow fever. Flaviviral infections, a family of virus infections transmitted by mosquitoes and ticks, are major health concerns as they spread rapidly and lack licensed treatments.

Most viral infections result in a range of outcomes even when individuals are infected with the same amount of virus in their blood. For example, up to two-thirds of all dengue virus infections result in no symptoms, while the remaining one-third go on to develop dengue fever and even fewer progress to severe dengue. Understanding why this happens could lead to new ways of preventing disease and reduce the burden of some viral diseases.

"We investigated why some individuals do not get sick despite being infected with the same virus, while others develop symptoms and infections. Understanding the molecular events that lead to development of symptoms could lead to new prevention and treatment methods for infectious diseases worldwide," said Professor Ooi Eng Eong, Deputy Director of the Emerging Infectious Diseases (EID) Programme, Duke-NUS Medical School and Professor, SingHealth Duke-NUS Global Health Institute. Prof Ooi is also Co-director of ViREMiCS, Professor at the Saw Swee Hock School of Public Health and the Department of Microbiology & Immunology, National University of Singapore and the corresponding author of this study.

The team conducted two clinical trials involving more than 100 healthy adults using the yellow fever vaccine, one of the most effective vaccines in the world with an excellent safety profile. The team analysed the blood profiles of the volunteers immediately before and after vaccination, and found that individuals whose blood cells had increased levels of stress from protein production and altered metabolism before vaccination went on to develop flu-like symptoms after vaccination. Increased stress and altered metabolism resulted in earlier than expected activation of the immune response that was linked with development of symptoms.

"Our findings show that increased levels of stress and altered metabolism of an individual's immune cells are factors that make one prone to developing symptoms during an infection. Correspondingly, this tells us that immune cells and metabolic pathways could be useful targets to develop treatments for yellow fever or other flaviviral infections," said Associate Professor Jenny Low, Senior Consultant at the Department of Infectious Diseases, Singapore General Hospital and Co-Director of ViREMiCS. Dr Low is also Associate Professor at Duke-NUS' EID Programme and co-corresponding author of this study.

These findings also imply that preventing conditions known to place cells under increased stress and altered metabolism, such as obesity, could prevent disease from viral infections.

The team is currently starting another clinical trial in 2020 to test if suppressing the early immune response can reduce the likelihood of getting sick from a viral infection.

Findings released today by a commission into health inequities experienced by people with mental illness lays bare their drastic physical health challenges, and recommends changes to health policy and treatment innovations to tackle what is regarded as a "human rights scandal".

Today's publication - The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness - is the culmination of over 12 months of research conducted by a taskforce of more than 30 international experts, led by researchers from NICM Health Research Institute at Western Sydney University, The University of Manchester, UNSW Sydney, King's College London and Orygen National Centre of Excellence in Youth Mental Health.

The researchers' ground-breaking report has four key aims including: establishing extent of physical health disparities in people with mental illness; highlighting key modifiable factors that drive poor health, presenting initiatives for health policy and clinical services to address these issues, and identifying promising areas for future research into novel solutions.

The Lancet Psychiatry Commission found a broad range of mental illnesses are associated with a lifelong burden of obesity, diabetes, and cardiovascular disease - which contributes towards a gap in life expectancy of around 20 years for people with mental illness. Key risk factors include higher rates of smoking, sleep disturbance, physical inactivity, unhealthy diet, the side effects of many psychiatric medications, and a lack of access to adequate physical healthcare.

Recommendations include adopting an 'early intervention' approach towards protecting physical health from initial stages of illness, and the provision of multidisciplinary lifestyle treatments, targeting a range of health behaviours, such as physical activity and healthy eating. Alongside this, recommendations for better integration of physical and mental healthcare, and evidence-based use of both psychiatric and cardioprotective medications for people with mental illness, are also provided.

The chair of the commission, Dr Joseph Firth, senior research fellow at NICM Health Research Institute, Western Sydney University and honorary research fellow at The University of Manchester, said the study was an important step towards addressing the entrenched and profound physical health inequities experienced by people with mental illness.

"The disparities in physical health outcomes for people with mental illness are currently regarded as a human rights scandal," Dr Firth said.

"Patients with serious mental illness are two to three times as likely to have obesity, diabetes and cardiovascular diseases - which impact on quality of life and recovery, while contributing towards a 20-year gap in life expectancy currently experienced by this underserved population.

"These comorbidities begin to arise early on, and affect people with mental illness across the entire lifespan. Clearly, protecting the physical health of people with mental illness should be considered an international priority for reducing the personal, social and economic burden of these conditions."

Lifestyle section lead of the commission and UNSW Sydney academic, Dr Simon Rosenbaum, said that lifestyle interventions to improve physical health must become a core component of mental healthcare, from the very initiation of treatment.

"Our commission found that although there is increasing attention towards the lifestyle risk factors in mental illness, there is still a widespread lack of implementation of evidence-based lifestyle interventions for these populations.

"We must take 'what works' from effective interventions for improving physical activity, diet and cardiovascular health in the general population and find innovative and cost-effective ways for making these interventions a standard part of care for those treated for mental illness."

Dr Brendon Stubbs, co-senior author of the commission and National Institute for Health Research Clinical Lecturer at King's College London, said, "The high rates of preventable physical health conditions in people with mental illness has to stop. Through this commission we have set out ambitious goals to provide an opportunity and directions to help people with mental illness improve their physical health and not only add years to their life, but also add life to their years."

NICM Health Research Institute's Professor Jerome Sarris, a co-author in the commission, said that the large disparities in physical health experienced by people with mental illness is an ongoing and possibly worsening health issue in some areas and that urgent action was needed to protect this vulnerable population.

"The connection between physical and mental health is now more recognised than ever. Although this inequity is increasingly gaining attention, further investment, intervention and research are urgently required to address the premature mortality and lifelong burden of poor physical health associated with mental illness," Professor Sarris said.

The commission also involved researchers from The University of Adelaide, University of York, The University of Queensland, and over a dozen other institutions, in addition to clinicians, and key stakeholders from a wide range of backgrounds and professional or personal experience in the topic.

What The Study Did: Researchers in this observational study looked at whether physical activity moderates the association of β-amyloid levels, a biomarker of Alzheimer disease, with cognitive decline and neurodegeneration over time in clinically normal older adults.

Author: Jasmeer P. Chhatwal, M.D., Ph.D., of Massachusetts General Hospital, Harvard Medical School in Boston, is the corresponding author.

(doi:10.1001/jamaneurol.2019.1879)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Review indicates that menstrual cups are a safe option for menstruation management

Around 70% of women wanted to continue using menstrual cups once they were familiar with how use them, but practice, peer support and training are key to initiation

Although there are 199 brands of menstrual cup, and cups are available in 99 countries, awareness is low - cups were only mentioned in 21 of 69 websites containing educational materials on puberty from 27 countries

Preliminary evidence on the cost and waste savings associated with using menstrual cups suggests that they could be beneficial

The first systematic review and meta-analysis of the international use of menstrual cups, including 43 studies and data from 3,300 women and girls - published in The Lancet Public Health journal, suggests they are safe and result in similar, or lower, leakage than disposable pads or tampons.

Four studies within the review (293 participants) compared leakage between different sanitary products, and found that levels were similar between menstrual cups and pads and tampons, while one found that leakage was significantly less.

Globally, menstruation can affect girls' schooling and women's experience of work, increase their disposition to urogenital infections if they use poor quality sanitary products, and even make both women and girls a target of sexual violence or coercion when they don't have the funds to buy them. There are an increasing number of initiatives in both high- and low-income countries to combat 'period poverty', so it is essential that policy makers know which sanitary products to include in menstrual health programmes and puberty education materials.

"Despite the fact that 1.9 billion women globally are of menstruating age - spending on average 65 days a year dealing with menstrual blood flow, few good quality studies exist that compare sanitary products," says senior author Professor Penelope Phillips-Howard from the Liverpool School of Tropical Medicine, UK. "We aimed to address this by summarising current knowledge about leakage, safety, and acceptability of menstrual cups, comparing them to other products where possible." [1]

The study combines data from medical studies and grey literature - such as conference abstracts, reports and theses - for which participants reported their experiences of menstrual cups or their willingness to use them. The authors selected 43 studies involving 3,319 participants in both low- and middle-income countries (LMICs) (15 studies) and high-income countries (28 studies). They also compiled global information on the availability and costs of menstrual cups, conducted preliminary estimates on waste savings, and examined puberty education materials to assess the extent to which menstrual cups are referred to as an option.

The authors note that the quality of the studies included was low, and call for more, quality research in this area, and note that further studies are needed on cost-effectiveness and environmental effects between different menstrual products. In the review, some of the information was taken from reports not published in peer-reviewed journals and the focus of some studies was to evaluate other topics. Some data were from older studies, when reporting requirements were less stringent, or with menstrual cups that are no longer available. Most of the studies depended on self-reporting, which might have overestimated use of the menstrual cup.

Menstrual cups collect blood flow, rather than absorbing it as with pads and tampons. Like tampons, they are inserted into the vagina, before being emptied every 4-12 hours. There are currently two types: a vaginal cup which is generally bell-shaped, and a cervical cup which is placed around the cervix high in the vagina like a diaphragm for contraception. The materials used to make them are medical grade silicone, rubber, latex or elastomer and can last up to 10 years.

The current review identifies the products usually used in LMICs, which include cloths, cotton wool, tissue paper and other pieces of material, as well as disposable pads. Leakage and chaffing are a common concern.

Four studies in the review, involving 293 participants, made direct comparisons of leakage between menstrual cups and disposable pads or tampons. Leakage was similar in three studies and significantly less among menstrual cups for one study. In some studies, leaking was associated with abnormally heavy bleeding, unusual anatomy of the uterus, need of a larger cup size, incorrect placement of the cup, and the cup becoming full.

There was no increased risk of infection associated with using menstrual cups among European, North American, and African women and girls. There were five reported cases of toxic shock syndrome following their use, but the overall number of menstrual cup users is unknown, so it is not possible to make comparisons of the risk of toxic shock syndrome between menstrual cups and other products. In four studies involving a total of 507 women, use of the menstrual cup showed no adverse effects on vaginal flora. In studies that examined the vagina and cervix during follow-up, no tissue damage was identified from use of a menstrual cup.

Difficulty in removing cups, requiring professional assistance, was reported twice for vaginal cups and 47 times for cervical cups. Some women use them in combination with intrauterine devices and, in 13 cases, removing the cup was associated with an IUD becoming dislodged. They suggest that the combination of an IUD and use of a menstrual cup might need further study. The authors identified five women who reported pain, three who reported vaginal wounds, six who reported an allergy or rash and nine who reported urinary tract complaints.

Results from 13 of the studies suggest that around 70% of women wanted to continue using menstrual cups once they were familiar with how to do so. Interview-based studies revealed that practice, peer support and training are key to participants finding them successful. In six qualitative studies, participants suggested that adopting the menstrual cup required a familiarisation phase over several menstrual cycles. The authors note that information and follow-up on correct use might need to form a part of menstrual health programmes.

The review suggests that awareness of menstrual cups as an option is low. Three studies in high-income countries found that only 11-33% of women are aware of them. Among 69 websites containing educational materials on puberty in 27 countries, 77% mentioned disposable pads and 65% mentioned tampons, while only 30% mentioned menstrual cups and 22% mentioned reusable pads.

Preliminary evidence on the cost and waste savings associated with using menstrual cups suggests that over 10 years, a single menstrual cup could cost much less than pads or tampons. The authors identified 199 brands of cup being available in 99 countries, with a wide range of prices from US$ 0.72 to $46.72. A cup could cost roughly 5% or 7% of the cost of using 12 pads (on average US$ 0.31 each) or tampons (on average US$ 0.21 each) per period. Plastic waste might also be reduced. Over 10 years, a cup is estimated to create 0.4% of the plastic waste generated by single-use pads or 6% of that produced by using tampons. The authors note that the cost and waste estimates are only illustrative, and do not account for the combined use of menstrual products, inflation, or production costs.

Given the limited number of reports on the use of menstrual cups, the authors also caution that other potential issues cannot be excluded, including use of menstrual cups in combination with IUDs. Further international research will be needed to provide more information on acceptability, to monitor adverse events, to assess best practice to shorten the familiarisation phase, and to more reliably assess cost-effectiveness and environmental effects.

Writing in a linked Comment, Dr Julie Hennegan from the Johns Hopkins Bloomberg School of Public Health, USA, says: "For consumers purchasing menstrual products, the results highlight cups as a safe and cost-effective option. Critically, findings indicate that menstrual education resources are not providing a comprehensive overview of products to support informed choices. Authors found that awareness of menstrual cups was low, and that only 30% of websites with educational materials on menarche included information about menstrual cups."

What The Study Did: A single-center study of 453 children in Germany with multiple sclerosis (MS) investigated the association of obesity with pediatric MS risk and with the response of first-line therapy in children with MS.

Author: Peter Huppke, M.D., of Georg August University in Göttingen, German, is the corresponding author.

(doi:10.1001/jamaneurol.2019.1997)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

An Australian study has demonstrated that cannabis-based medication helps tackle dependency on cannabis, one of the most widely used drugs globally.

A paper about the University of Sydney and NSW Health clinical trial provides the first strong evidence that so-called cannabinoid agonist medication - which targets receptors in the brain - could reduce the rate of relapse.

The paper published today in the American Medical Association's JAMA Internal Medicine.

Lead author Conjoint Professor Nick Lintzeris - of the University of Sydney's Faculty of Medicine and Health and Director of Drug & Alcohol Services, South East Sydney Local Health District - said the study should give hope to people with dependency on cannabis, which is a leading cause of drug treatment episodes in Australia.*

"We've never had the evidence before that medication can be effective in treating cannabis dependency - this is the first big study to show this is a safe and effective approach," Professor Lintzeris said.

"The principles are very similar to nicotine replacement; you are providing patients with a medicine which is safer than the drug they're already using, and linking this with medical and counselling support to help people address their illicit cannabis use."

The cannabis concentrate, which comprises equal proportions of cannabidiol (CBD) and the psychoactive tetrahydrocannabinol (THC), is sprayed under the tongue and avoids the health impacts associated with smoking cannabis such as respiratory issues.

Nabiximols has been primarily used to treat pain symptoms associated with multiple sclerosis and is licensed in Australia. Alternative medical cannabis products exist but these are only available through special access schemes and unlike the trial medication, also require Therapeutic Goods Administration (TGA) approval.

This large 12-week outpatient clinical trial of 128 participants taking nabiximols medication followed an earlier study by the same research team that had previously shown nabiximols reduce withdrawal symptoms in a short-term hospital treatment program. "The latest study published today is even more important in that it shows that nabiximols can be effective in helping patients achieve longer term changes in their cannabis use," Prof Lintzeris explains.

Co-author of the paper Professor Iain McGregor, the academic director of the University's Lambert Initiative for Cannabinoid Therapeutics, noted: "Worldwide we are seeing medicinal cannabis patients transition away from the traditional smoked route of cannabis administration; this new study... complements this trend by showing that an oral spray can be an effective substitute for smoked cannabis in heavy recreational users seeking treatment for their cannabis use."

Professor Lintzeris said an important element of this National Health and Medical Research Council-supported trial was that only cannabis users were recruited who had previously unsuccessfully tried to curb their use.

"Our study is an important step in addressing the lack of effective treatments - currently, four in five patients relapse to regular use within six months of medical or psychological interventions."

Trial and medication snapshot:

- During the clinical trial, participants had an average dose of about 18 sprays a day, with each spray of 0.1mL comprising 2.7mg of THC and 2.5mg of CBD.

- Participants treated with nabiximols used significantly less illicit cannabis than patients randomly allocated to placebo medication.

- The medicine was combined with cognitive behavioural therapy (CBT) and other therapeutic support for a holistic approach.

- Health and behavioural benefits of cannabis replacement include that patients are taken out of their usual patterns of use.

- This first large outpatient randomised controlled trial of the cannabis extract medication noted suppression of withdrawal and cravings, with improvements in physical and psychological well-being.

A new study published in the Journal of the International AIDS Society shows that the World Health Organization's (WHO) 2015 recommendation for immediate treatment of all people living with HIV has become the standard of care across HIV clinics in countries around the world. While most countries have adopted the WHO's "Treat All" recommendation, the extent to which these guidelines had been translated into practice at HIV clinics around the world was previously unknown.

Based on a survey conducted at more than 200 HIV care and treatment sites in the 41 countries that participate in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium, this study found that site-level uptake of the Treat All practice is almost universal. While studies of prior changes in HIV treatment guidelines had shown delays in implementation, this study found the roll-out of Treat All practices has been rapid, with a median lag of one month between national policy change and site-level introduction. The study also found that sites in low- and lower-middle income countries generally initiate patients on HIV treatment within 14 days of confirming HIV diagnoses. The study found no significant differences in introduction of Treat All at the service delivery level by geographic region, country income level, urban/rural location or other facility characteristic, which suggests that gaps in treatment access have narrowed. However, the study also found that the majority of HIV care and treatment sites in low-resource settings do not have the capacity for routine viral load monitoring once a patient starts HIV treatment.

The study was led by researchers at the CUNY Institute for Implementation Science in Population Health (ISPH) at the CUNY Graduate School of Public Health and Health Policy (CUNY SPH).

"These findings are promising, in terms of the ability to broadly improve access to earlier treatment in low-resource settings, which will improve health outcomes among people living with HIV and prevent new infections," said Ellen Brazier, the study's lead author.

Dr. Denis Nash, distinguished professor of epidemiology at CUNY SPH and the study's senior author, noted that widescale and rapid introduction of Treat All at the service delivery level may reflect the fact that its guidelines are simpler to implement in low resource settings than prior guidelines, which required assessing each patient's immune status to determine if they were eligible to start HIV treatment. However, he cautioned that limited capacity for laboratory testing remains a concern.

"Many of the sites that are initiating patients on antiretroviral therapy do not have adequate resources to monitor key patient outcomes through viral load testing, including treatment failure or the development of drug resistance," said Nash. "This is an issue that requires urgent attention, as it is critical to assess and optimize longer term HIV care outcomes in the Treat All era."

(New York, NY - July 15, 2019) -- Mount Sinai researchers working as part of an international team have discovered previously unknown breastfeeding patterns of an extinct early human species by studying their 2-million-year-old teeth, providing insights into the evolution of human breastfeeding practices, according to a study published in Nature in July.

Breastfeeding is a critical aspect of human development, and the duration of exclusive nursing and the timing of introducing solid food to the diet are also important determinants of health in human and other primate populations. Many aspects of nursing, however, remain poorly understood.

Using high-tech methods pioneered at Mount Sinai, the scientists analyzed teeth from Australopithecus africanus (A. africanus), an early human ancestor that lived about 2 to 3 million years ago in South Africa and had both human and apelike features. Scientists reconstructed diet histories using the teeth, measuring preserved chemical biomarkers. The growth patterns of teeth, which resemble tree rings, allow investigators to determine concentrations of barium, an element found in milk, in teeth over time, which yields information about their nursing and dietary patterns.

Researchers found the species breastfed for up to one year and then had six monthly cycles of food scarcity, which could have caused them to fall back to increased breastfeeding or find other food sources.

"Seeing how breastfeeding has evolved over time can inform best practices for modern humans by bringing in evolutionary medicine. Our results show this species is a little closer to humans than the other great apes which have such different nursing behaviors," said one of the study's first authors, Christine Austin, PhD, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai and member of Mount Sinai's Institute for Exposomic Research. "These are important findings from an evolutionary perspective, because humans have long childhoods and short breastfeeding periods while apes have longer breastfeeding periods than humans do. We're still in the dark about why or when we made that change and what the effect of more recent major changes in breastfeeding, with agriculture and industrialization, could have on mothers' and babies' health."

Mount Sinai's Institute for Exposomic Research looks into how to develop biomarkers of exposure, and a prime one is measuring chemicals in teeth. Diet is a big part of the exposome--someone's environmental exposure history--and nutritional stress is an exposure that is important to measure to understand overall health after exposures, Dr. Austin said.

"For the first time, we've gained new insight into the way our ancestors raised their young, and how mothers may have adapted to seasonal food shortages with breastfeeding," said the study's lead first author, Renaud Joannes-Boyau, PhD, head of the Geoarchaeology and Archaeometry Research Group (GARG) at Southern Cross University in Australia.

Experiments performed in mice, in which the main pathogenic markers of the disease have been evaluated, show that the progression of the disease is prevented when the function of this protein is inactivated.

Alzheimer's disease is characterized by a progressive and irreversible loss of cognitive abilities. "Treatment of the disease represents an unresolved challenge that needs alternative approaches to those currently on trial; there is need of new perspectives that take into account the complexity of the disease. Given its multifactorial origin, these new approaches should be designed against factors that act simultaneously in more than one of the pathological processes of the disease" explains Paola Bovolenta, CSIC researcher at the Molecular Biology Center 'Severo Ochoa' (Joint centre of the CSIC and the Autonomous University of Madrid).

This study identifies that the protein SFRP1 (Secreted Frizzled Related Protein 1) is one of those factors. SFRP1 acts in multiple processes and its elevated levels are pathogenic. "We believe that our results represent an innovation in the field of Alzheimer's disease. We demonstrate that the neutralization of SFRP1 could be a promising therapeutic alternative. This is something that we now need to explore in depth. We also believe that the measure of SFRP1 levels in the cerebrospinal fluid or in serum may represent a useful diagnostic marker in the future, "adds Pilar Esteve, co-responsible of the study and member of the Center for Molecular Biology Severo Ochoa '.