Body

PHILADELPHIA - Most people know Chlamydia as the venereal disease that can cause infertility if left untreated. But for researchers studying the causative agent, Chlamydia trachomatis, it's a bacteria with intriguing properties. Rather than grow and replicate in the blood or other bodily fluids, C. trachomatis get inside cells where they multiply. In most people, this trait keeps the bacterium from being detected by the immune system, and helps the disease fly under the radar; not everyone infected with Chlamydia will show symptoms of the disease. But managing to stay alive inside an infected cell is no small feat for bacteria.

Researchers at Jefferson (Philadelphia University + Thomas Jefferson University) are studying the tricks developed by Chlamydia to survive inside its host cell. C. trachomatis pathogenicity relies on the creation of an intracellular parasitic niche called an "inclusion," which is made from the outer membrane of the host cell. When a human cell is infected with multiple Chlamydia, each bacterium will develop an individual inclusion, all of which will ultimately fuse together into one large inclusion. This unique fusion event depends on the chlamydial protein IncA. Although it is not yet clear how, researchers know that this bacterial fusion event is linked to Chlamydia's pathogenicity - its ability to cause disease in the host.

"It appears that when fusion is blocked, we see less disease," says cellular microbiologist Fabienne Paumet, PhD who was a co-senior author on the research.

Dr. Paumet teamed up with biochemist Gino Cingolani, PhD, at Jefferson an co-senior author, to determine an electron density map of the fusion protein, down to the exact location of atoms, using the time-intensive process of growing crystals out of the protein and zapping them with X-ray radiation in order to capture a reflection, with the exact location and size of the atoms.

Most of the time, cellular biologists like Dr. Paumet get in touch with x-ray crystallographers like Dr. Cingolani at the last stages of their work - to confirm their hypotheses based on biochemical data. This time, however, the Paumet/Cingolani team collaborated early on with the hope that the structure of IncA would provide clues about its function and suggest hypotheses testable experimentally in the laboratory. The crystal structure of lncA helped Dr. Paumet's team figure out how to create mutations that would test their ideas of how the molecule functioned.

"It's a collaboration that started a decade ago," says Dr. Cingolani.

Computational Biologist Juan Perilla, PhD, at the University of Delaware , then joined the team and generated computational simulations of how lncA interacts with itself. In combination with analysis of cells infected with Chlamydia expressing various IncA mutants , the researchers were finally able to find a region of IncA, that they called the 'clamp,' which is critical for controlling the fusogenic activity lncA inside infected cells.

Their results were published in Nature Communications on June 18th.

Although membrane-bound compartments of eukaryotic cells fuse all the time, it is very unusual for bacteria to have developed fusion machinery. "Identifying a bacterial protein that helps intracellular parasitic compartments fuse, gives researchers a new tool to probe key disease processes caused by bacteria," says Dr. Cingolani. "I have colleagues who are just drooling to apply this to their research on mycobacteria, where membrane fusion is key to tuberculosis."

More IVF cycles include embryo genetic testing, but little is known about patients' feelings following testing

'Older women know their time is limited'

The most common reason for miscarriage is a genetically abnormal embryo

Most embryos from older women aren't genetically normal, putting them at a higher chance of infertility and miscarriage

CHICAGO --- The most effective way to increase the odds that an embryo will successfully implant during in vitro fertilization (IVF) is genetic testing to see if the embryo is normal.

But the news often isn't good. By the time a woman is 44 years old, the vast majority of her embryos will be abnormal.

A new study asked women who had their embryos tested before IVF if they were glad or regretted the procedure?

Regardless of whether they had a normal embryo or not, 94 percent of patients surveyed were glad to have the information, a new study from Northwestern Medicine and New York University Langone Fertility Center reports.

This is the first study examining the risk of regret and anxiety following screening for chromosomal abnormalities in embryos before IVF.

The paper will be published June 21 in Human Reproduction, a journal of the European Society of Human Reproduction and Embryology.

"The traditional practice of IVF involves transferring an embryo, with an unknown likelihood of implantation, and finding out on the other end whether it will implant or result in a healthy pregnancy," said lead study author Dr. Kara Goldman. "We discovered that even after a negative outcome, most women found the information gained from embryo testing to be valuable for reproductive planning."

Goldman is an assistant professor of obstetrics and gynecology in reproductive endocrinology and infertility at Northwestern University Feinberg School of Medicine. She also is the Northwestern Medicine director of fertility preservation.

"Older women understand their time is limited," Goldman said. "If they lose three months because of a miscarriage, that's a lot of time. Most patients like the idea of having as much information in front of them as possible, so they don't have to go through the very difficult waiting period between the embryo transfer and the pregnancy test if the embryo wouldn't have resulted in pregnancy."

In genetic testing, clinicians check to see if there are too many or two few chromosomes, which will result in a miscarriage, an embryo that won't implant or a chromosomally abnormal fetus. The latter requires the parents to decide if they want to terminate the pregnancy.

A small but significant number of patients who had abnormal results, or did not get pregnant with one of their normal embryos, did feel regret after the testing procedure.

"This study identified where we need to better help patients in terms of mental health services," Goldman said. "We need to make sure we have our psychologists and doctors supporting patients when they have abnormal embryos and are preparing to make their subsequent treatment decisions.

"The most common reason for patients to drop out of IVF treatment before they are successful is the psychological burden," Goldman said. "Genetic testing of embryos is an area where we have thousands of patients using this technology and no one has studied the psychological burden of it."

IVF is used widely among patients with infertility, and in the United States nearly 2 percent of all babies born were conceived with IVF.

The study was conducted via an anonymous internet-based survey completed by 69 patients between January 2014 and March 2015 after screening for chromosomal abnormalities. The patients were from New York University Langone Fertility Center, where Goldman was on faculty prior to joining Northwestern. The survey included three validated questionnaires including the Brehaut Decision Regret Scale, short-form State-Trait anxiety inventory and health literacy scale.

(New York, NY - June 20, 2019) -- World Trade Center (WTC) responders with prostate cancer showed signs that exposure to dust from the World Trade Center site had activated chronic inflammation in their prostates, which may have contributed to their cancer, according to a study by Mount Sinai researchers in Molecular Cancer Research in June.

Inflammation has long been considered an important factor in prostate cancer progression. Researchers looked at the inflammatory and immune systems of World Trade Center responders to help prevent new prostate cancer cases in that group and to understand how other large-scale environmental exposures to multiple carcinogens may develop into cancer.

This is the first study of people who were exposed to the WTC dust and who subsequently developed prostate cancer. This research and further study of the expression of genes and pathways in other patients whose environmental exposures caused inflammation could lead to clinical trials that offer anti-inflammatory or immune-targeted therapies in similar cases.

"World Trade Center responders show an overall increase in cancer incidence, and specifically of certain cancer types such as prostate cancer," said Emanuela Taioli, MD, PhD, Director of the Institute for Translational Epidemiology at the Icahn School of Medicine at Mount Sinai and Associate Director for Population Science at The Tisch Cancer Institute. "It is important to address the reasons why this is happening in order to prevent new cases in this aging cohort. Our findings represent the first link between exposure to World Trade Center dust and prostate cancer."

This work pairs data from first responders and from a study of rats exposed to actual dust from Ground Zero. The dust samples, which contain metals and organic compounds such as polycyclic aromatic hydrocarbons and polychlorinated biphenyl, are unique because they are the only existing samples taken on September 11, 2001. All other dust samples were collected after a significant storm on September 14, 2001.

Both the human and rat prostate cancer tissues show an increase in cells that indicate inflammation, specifically immune cells called T helper cells. Studies of the rat tissue and prostate cancer tissue samples taken from responders indicated to the Mount Sinai researchers that chronic inflammation started occurring in the prostate after exposure to the World Trade Center dust, and that inflammation may have contributed to prostate cancer.

"Several years ago, I saw a first responder in his 40s who began having symptoms of prostatitis, a painful condition that involves inflammation of the prostate, soon after exposure to the World Trade Center dust," said William Oh, MD, Chief of the Division of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai and Deputy Director at The Tisch Cancer Institute. "He ultimately developed a high-grade prostate cancer several years later. It suggested to me that there might be a link between his exposure and cancer, but I knew that I would need to examine it systematically."

COLUMBUS, Ohio - A low-carb diet may have benefits for people at risk of developing type 2 diabetes even if they don't lose any weight, a new study suggests.

Researchers at The Ohio State University wanted to know what happens to obese people with metabolic syndrome, a precursor to diabetes, when they eat a diet low in carbohydrates but don't shed any pounds. They found that more than half of study participants no longer met the criteria for metabolic syndrome immediately following a four-week low-carb diet.

The new study included 16 men and women with metabolic syndrome, a cluster of factors that also put people at higher risk of heart disease and stroke. The conditions that contribute to metabolic syndrome include high blood pressure, high blood sugar, excess body fat around the waist and abnormally low 'good' HDL cholesterol or high triglyceride levels. About a third of American adults have the syndrome, according to the American Heart Association.

After eating a low-carb diet, more than half the participants - five men and four women - saw their metabolic syndrome reversed even though they were fed diets that intentionally contained enough calories to keep their weight stable.

Previous work in the Ohio State lab and elsewhere has shown that low-carb diets can be beneficial for people with metabolic syndrome and diabetes, but nutrition scientists and others have debated whether that's a product of the diet or a product of the weight loss typically seen when people reduce carbs, said the study's senior author, Jeff Volek, a professor of human sciences at Ohio State.

"There's no doubt that people with metabolic syndrome and type 2 diabetes do better on low-carb diets, but they typically lose weight and one of the prevailing thoughts is that the weight loss is driving the improvements. That was clearly not the case here," Volek said.

"Our view is that restricting carbs even without weight loss improves a host of metabolic problems. Obviously, quality of diet matters because quantity is locked down in this experiment."

The study appears today (June 20) in the Journal of Clinical Investigation Insight.

Over about four months, each study participant ate three month-long controlled diets - high-carb, moderate-carb and low-carb - with a two-week break between diets. The order in which the participants ate the diets was randomly assigned.

The research team, led by research scientist Parker Hyde, ensured that the participants would not lose weight by providing them with pre-prepared meals that contained an amount of calories equal to their energy expenditure.

After eating the low-carb diet, the participants had a variety of significantly improved health measures, particularly lower triglycerides and improved cholesterol readings. Despite the fact that the low-carb diet contained 2.5 times more saturated fat than the high-carb diet, it decreased saturated fat in the bloodstream and was associated with an increase in the size of cholesterol particles in the blood, which decreases the risk of cardiovascular disease, Hyde said.

The researchers also report evidence of increased fat-burning efficiency after a low-carb diet and an improvement in blood sugar. They did not see statistically significant improvements in blood pressure or insulin resistance.

Three participants no longer had metabolic syndrome after the moderate-carbohydrate diet and one no longer had the syndrome after the high-carb diet. Volek said that those results are likely explained by the fact that even these study diets - particularly the moderate-carb diet - represented a shift toward fewer carbs for study participants.

"Even a modest restriction is carbs is enough to reverse metabolic syndrome in some people, but others need to restrict even more," he said.

Because of the study design, waist circumference was not factored in as a contributor to metabolic syndrome. Had the participants been permitted to lose weight, it is likely that several more would have been considered free of the condition after the low-carb diet, Volek said.

This research doesn't address the potential long-term benefits and challenges of adopting a low-carbohydrate diet, and the researchers suggest that future long-term diet studies on people with metabolic syndrome need to include low-carb diets.

New research coming out of UBC's Okanagan campus demonstrates that upbeat music can make a rigorous workout seem less tough. Even for people who are insufficiently active.

Matthew Stork is a postdoctoral fellow in the School of Health and Exercise Sciences. He recently published a study examining how the right music can help less-active people get more out of their workout--and enjoy it more.

High-intensity interval training (HIIT)--brief, repeated bouts of intense exercise separated by periods of rest--has been shown to improve physical health over several weeks of training. But, cautions Stork, it can be perceived as gruelling for many people, especially those who are less active.

"While HIIT is time-efficient and can elicit meaningful health benefits among adults who are insufficiently active, one major drawback is that people may find it to be unpleasant. As a result, this has the potential to discourage continued participation," he says.

Previous research led by Stork and UBC Okanagan's Kathleen Martin Ginis has examined the effects of music during HIIT with recreationally-active people. Their latest study tested the effects of music with participants who were insufficiently-active, used a more rigorous music selection process and implemented a HIIT regimen that is more practical for less-active adults.

The study took place at Brunel University London and Stork worked with Professor Costas Karageorghis, a world-renowned researcher who studies the effects music has on sport and exercise. First, Stork gathered a panel of British adults to rate the motivational qualities of 16 fast-tempo songs. The three songs with the highest motivational ratings were used for the study.

"Music is typically used as a dissociative strategy. This means that it can draw your attention away from the body's physiological responses to exercise such as increased heart rate or sore muscles," says Stork. "But with high-intensity exercise, it seems that music is most effective when it has a fast tempo and is highly motivational."

Next, a separate group of 24 participants completed what has been referred to as the 'one-minute workout'--three 20-second all-out sprints, totaling 60 seconds of hard work. A short rest separated the sprints, for a total exercise period of 10 minutes including a warm-up and cool-down. Participants completed these HIIT sessions under three different conditions--with motivational music, no audio or a podcast that was devoid of music.

Participants reported greater enjoyment of HIIT. They also exhibited elevated heart rates and peak power in the session with music compared to the no-audio and podcast sessions.

"The more I look into this, the more I am surprised," he says. "We believed that motivational music would help people enjoy the exercise more, but we were surprised about the elevated heart rate. That was a novel finding."

Stork believes the elevated heart rates may be explained by a phenomenon called 'entrainment.'

"Humans have an innate tendency to alter the frequency of their biological rhythms toward that of musical rhythms. In this case, the fast-tempo music may have increased people's heart rate during the exercise. It's incredible how powerful music can be."

Stork's research indicates that for people who are deemed insufficiently active, music can not only help them work harder physically during HIIT but it can also help them enjoy HIIT more. And because motivational music has the power to enhance people's HIIT workouts, it may ultimately give people an extra boost to try HIIT again in the future.

"Music can be a practical strategy to help insufficiently active people get more out of their HIIT workouts and may even encourage continued participation."

Scientists have found a correlation between a disease involving chronic pain and alterations in the gut microbiome.

Fibromyalgia affects 2-4 percent of the population and has no known cure. Symptoms include fatigue, impaired sleep and cognitive difficulties, but the disease is most clearly characterized by widespread chronic pain. In a paper published today in the journal Pain, a Montreal-based research team has shown, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia. Approximately 20 different species of bacteria were found in either greater or are lesser quantities in the microbiomes of participants suffering from the disease than in the healthy control group.

Greater presence or absence of certain species of bacteria

"We used a range of techniques, including Artificial Intelligence, to confirm that the changes we saw in the microbiomes of fibromyalgia patients were not caused by factors such as diet, medication, physical activity, age, and so on, which are known to affect the microbiome," says Dr. Amir Minerbi, from the Alan Edwards Pain Management Unit at the McGill University Health Centre (MUHC), and first author on the paper. The team also included researchers from McGill University and Université de Montréal as well as others from the Research Institute of the MUHC.

Dr. Minerbi adds, "We found that fibromyalgia and the symptoms of fibromyalgia - pain, fatigue and cognitive difficulties - contribute more than any of the other factors to the variations we see in the microbiomes of those with the disease. We also saw that the severity of a patient's symptoms was directly correlated with an increased presence or a more pronounced absence of certain bacteria - something which has never been reported before."

Are bacteria simply the markers of the disease?

At this point, it's not clear whether the changes in gut bacteria seen in patients with fibromyalgia are simply markers of the disease or whether they play a role in causing it. Because the disease involves a cluster of symptoms, and not simply pain, the next step in the research will be to investigate whether there are similar changes in the gut microbiome in other conditions involving chronic pain, such as lower back pain, headaches and neuropathic pain.

The researchers are also interested in exploring whether bacteria play a causal role in the development of pain and fibromyalgia. And whether their presence could, eventually, help in finding a cure, as well as speed up the process of diagnosis.

Confirming a diagnosis and next steps towards finding a cure

Fibromyalgia is a disease that has proved difficult to diagnose. Patients can wait as long as 4 to 5 years to get a final diagnosis. But this may be about to change.

"We sorted through large amounts of data, identifying 19 species that were either increased or decreased in individuals with fibromyalgia," says Emmanuel Gonzalez, from the Canadian Center for Computational Genomics and the Department of Human Genetics at McGill University. "By using machine learning, our computer was able to make a diagnosis of fibromyalgia, based only on the composition of the microbiome, with an accuracy of 87 per cent. As we build on this first discovery with more research, we hope to improve upon this accuracy, potentially creating a step-change in diagnosis."

"People with fibromyalgia suffer not only from the symptoms of their disease but also from the difficulty of family, friends and medical teams to comprehend their symptoms," says Yoram Shir, the senior author on the paper who is the Director of the Alan Edwards Pain Management Unit at the MUHC and an Associate Investigator from the BRaiN Program of the RI-MUHC. "As pain physicians, we are frustrated by our inability to help, and this frustration is a good fuel for research. This is the first evidence, at least in humans, that the microbiome could have an effect on diffuse pain, and we really need new ways to look at chronic pain."

How the research was done

The research was based on a cohort of 156 individuals in the Montreal area, 77 of whom suffer from fibromyalgia. Participants in the study were interviewed and gave stool, blood, saliva and urine samples, which were then compared with those of healthy control subjects, some of whom lived in the same house as the fibromyalgia patients or were their parents, offspring or siblings.

The researchers' next steps will be to see whether they get similar results in another cohort, perhaps in a different part of the world, and to do studies in animals to discover whether changes in bacteria play a role in the development of the disease.

The majority of women who undergo surgery for suspected ovarian cancer do not have cancer. A novel blood test developed by researchers at Uppsala University and the Sahlgrenska Academy, University of Gothenburg, now offers the possibility of more precise diagnostics without the need for surgery. This could lead to a reduction in unnecessary surgery and to earlier detection and treatment for affected women. The study was recently published in Communications Biology.

Ovarian cancer is often discovered at a late stage and has a high mortality rate. Out of 10 patients, only 3-4 survive 5 years after treatment, and there has been no test specific enough to justify screening. Women with accidental findings of an ovarian cyst or with symptoms instead undergo ultrasound and if abnormalities are seen, surgery is the only way to make sure all cancers are detected. This means that many women are operated on without having cancer, resulting in unnecessary surgery and increased risks for women.

"We need to develop more accurate pre-surgery diagnostics. To detect one cancer, we operate on up to five women - yet this is currently the best option when abnormalities are detected by ultrasound and cancer is suspected. There is a great need for a simple blood test that could identify women who do not need surgery," says Karin Sundfeldt, Professor and Senior Consultant at the Department of Obstetrics and Gynecology, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg.

In the published study, the researchers have developed a biomarker test based on analysis of 11 proteins. The test, which is performed on a blood sample, is used where ultrasound has indicated abnormalities to identify women without cancer. For cases in which physicians chose to operate, the cancer rate could increase from one in five to one in three. This would greatly reduce unnecessary surgery and the risk of complications related to surgery.

The biomarker profile can also detect borderline cases and early stages of the disease.

"Our results are promising enough to consider screening for early discovery of ovarian cancer. In Sweden, we have long experience of screening for cervical cancer. I see great prospects of developing a strategy for screening for ovarian cancer as well, which could save lives and minimise the need for surgery to rule out cancer," says Ulf Gyllensten, Professor of Medical Molecular Genetics at the Department of Immunology, Genetics and Pathology at Uppsala University.

The paper, published in the open access journal Communications Biology (Springer Nature Publishing AG), presents a new test that has been developed in collaboration with Uppsala-based biotech company Olink Proteomics AB.

"We are now continuing to evaluate the test and are performing a large-scale study of samples collected at all hospitals from the western region and Halland healthcare system," says Gyllensten.

Sophia Antipolis, 20 June 2019: Patients with peripheral arterial disease should be given the option of pain-free exercise, according to a study published today in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).1

Around 200 million people worldwide have peripheral arterial disease (PAD), where arteries in the legs are clogged, restricting blood flow to the legs and raising the chances of stroke and heart attack. Smoking, diabetes, high blood pressure, and high cholesterol all increase the risk of PAD. Around 30% of patients have pain and cramping in their legs when they walk - referred to as intermittent claudication.

Exercise is a cornerstone of PAD management, together with smoking cessation, healthy diet, and weight loss.3 It improves symptoms, mobility and quality of life.

"For many years the standard exercise prescription for patients with PAD has been to walk towards, and push past, moderate to severe pain," said study author Edward Lin, of the University of Toronto, Canada. "Research has shown that this approach improves walking distance and quality of life.2 Naturally if you force patients to walk past their pain thresholds and continue to do so, they're going to get better at walking."

But he added: "Many patients with PAD exercise very little or not at all. It has been suggested that the pain component of conventional exercise programmes is a deterrent. More recent studies have shown that pain-free forms of exercise are equally effective, but patients are not always given the option."

This study compiled the best evidence and compared completion and adherence rates between traditional versus alternative exercise programmes of at least four weeks duration. Completion was defined as the proportion of participants who finished the programme, while adherence was the percentage of exercise sessions done.

In the study, traditional programmes consisted of walking until moderate to severe pain was induced, resting until the pain subsided, then repeating the process. Alternative exercises included walking without pain, arm ergometer (an exercise bike for the arms), resistance training, circuit training, lower limb aerobic exercise, and walking with poles.

A total of 84 studies and 4,742 patients were included in the analysis, encompassing 64 traditional walking programmes and 58 alternative exercise programmes. Completion rates were 6% higher in programmes with alternative forms of exercise compared to painful walking (80.8% versus 86.6%). Similarly, adherence was 8% greater in alternative programmes compared to painful walking (77.6% versus 85.5%).

"Pain played a major role in the completion and adherence rates," said Mr Lin. "Walking to pain is effective, but only if patients actually do it. Many clinicians and vascular surgeons still prescribe this type of exercise, but it's important to consider other types of activity, which have also been shown to work."

Mr Lin noted that there is insufficient referral of patients with PAD to cardiac rehabilitation and prevention programmes. An individualised exercise plan that patients are more likely to follow should be developed, considering their preferences for exercise and potential barriers.

"Pain is not a necessary part of exercise for patients with peripheral arterial disease," said Mr Lin. "If patients prefer not to walk to pain, they can be encouraged to do pain-free exercise they enjoy. This should increase the likelihood of maintaining long-term physical activity."

PHOENIX, Ariz. -- June 18, 2019 -- Results from a study of nearly 60,000 individuals suggest those at higher risk of developing Alzheimer's disease due to family history may demonstrate changes in memory performance as early as their 20s.

Researchers from the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and the University of Arizona gathered the data through an online word-pair memory test called MindCrowd, one of the world's largest scientific assessments of how healthy brains function.

Published today in the scientific journal eLife, study data suggests that those with a family history of Alzheimer's disease, and who are younger than 65, on average do not perform as well as their peers who do not have a family history of Alzheimer's, the most common form of dementia.

The study results suggest that the family history effect is particularly pronounced among men, as well as those with lower educational attainment, diabetes, and carriers of a common genetic change in APOE, a gene long associated with Alzheimer's disease risk.

While family history has previously been associated with the risk of Alzheimer's, this is the first study of its kind, and in these numbers, that indicates this risk can be detected up to four decades before the typical age of onset. The study looked at 59,571 MindCrowd participants aged 18-85, and the effect of family history was shown across every age group, up until age 65.

"In this study we show that family history is associated with reduced paired-associate learning performance as many as four decades before the typical onset of Alzheimer's disease," said Dr. Matt Huentelman, TGen Professor of Neurogenomics, and the study's senior author

Because there is no cure or proven way of slowing progressive memory-loss among those with Alzheimer's, early indicators of the disease can help those at risk to focus on ways to help stave off dementia.

"Risk reduction for Alzheimer's disease is now more critical than ever due to the continued lack of a cure or effective disease-slowing treatment," said Dr. Joshua S. Talboom, a Postdoctoral Fellow in TGen's Neurogenomics Division, and a member of Dr. Huentelman's lab.

"This study supports recommendations underscoring the importance of living a healthy lifestyle and properly treating disease states such as diabetes," said Dr. Talboom, the study's lead author. "Our findings specifically highlight the positive effects of such interventions for those with a family history risk of Alzheimer's, opening the door to the development of more targeted risk-reduction approaches to combat the disease."

In addition, this study underscores the utility of web-based participant recruitment to research studies like MindCrowd, facilitating large sample sizes in a cost- and time-effective fashion, said Dr. Lee Ryan, a University of Arizona Alzheimer's researcher, who along with the UA's Dr. Betty Glisky, helped Dr. Huentelman develop MindCrowd. Drs. Ryan and Glisky were contributing authors to the study.

"It should be acknowledged that that web-based studies are not without concerns. However, we propose that the advantage of considerably larger sample sizes and enriched participant diversity in online research mostly diminishes the potential disadvantages," Dr. Ryan said.

The MindCrowd study began in 2013. By August 2018, it had nearly 60,000 qualified participants, whose performance is reflected in the study. Today, more than 115,000 people, aged 18-95 -- from all 50 states and 150 nations around the world -- have completed the MindCrowd assessment.

MindCrowd cannot tell you if you have Alzheimer's. What it does give researchers is a set of data baselines about how people not suffering from the disease perform at different ages; among men and women, among those with quick and slow physical responses, among those who smoke and those who don't, and among many other demographic, lifestyle and health factors.

Establishing these baselines will help researchers to more properly evaluate Alzheimer's patients and usher in a new era of what the MindCrowd developers describe as Precision Aging.

Alzheimer's is a progressive neurological disorder that typically presents clinically as deficits in memory and thinking. It is estimated that more than 5 million Americans are living with Alzheimer's, and that by 2050 that number will nearly triple to almost 14 million.

How much do you exercise? Government guidelines suggest that, in order to stay healthy, adults should perform at least 150 minutes of moderate aerobic activity every week - that's exercise that gets your breathing and heart rate up.

A new study, published in The Journal of Physiology investigated a home-based high-intensity interval training (Home-HIT) programme and studied its benefits for clinically obese individuals with an elevated risk of heart disease. (Please click here: https://www.youtube.com/watch?v=TxG8BePiSxg&feature=youtu.be for a video about this research.)

Previous research has demonstrated that under controlled laboratory conditions, you can get the same benefits from three 20-minute exercise sessions, as from the Government-recommended 150 minutes. However, the question is whether data produced in highly controlled laboratory environments can be translated to the real world.

The research team at Liverpool John Moores University were interested in whether Home-HIT is a time-efficient strategy that helps to reduce other common exercise barriers such as difficultly with access to exercise facilities due travel time and cost.

In this study, 32 obese people completed a 12-week programme of either: 1) a supervised, lab-based cycling HIT programme, 2) the Government-recommended 150 minutes of moderate intensity exercise or 3) a home-based HIT programme of simple body weight exercises suitable for people with low fitness and low mobility, and performed without equipment. For all of these regimens, the exercise was performed three times per week.

The researchers measured a range of health markers in these participants, including body composition, cardiovascular disease risk, and the ability to regulate glucose. They found that the home-based HIT was as effective as both the Government-recommended 150 minutes and the supervised, lab-based HIT programme for improving fitness in obese individuals.

Sam Scott, first author of the study said:

"An exercise regimen, such as Home-HIT, that reduces barriers to exercise, such as time, cost, and access, and increases adherence in previously inactive individuals gives people a more attainable exercise goal and thus could help improve the health of countless individuals."

PHILADELPHIA--Many elderly patients with metastatic renal cell carcinoma (RCC)--who are often underrepresented in clinical trials to treat the kidney cancer--are seeing overall survival benefits from treatment with targeted therapies, according to a new study from Penn Medicine researchers published this month in JAMA Network Open. Analyzing 13 years of data on Medicare patients, the study found that the patients who received targeted therapies were more medically complex than those who received the older, more toxic treatments that were available earlier in the study period, indicating that newer treatments are offering hope to more people.

Since 2005, the U.S. Food and Drug Administration has approved 12 targeted therapies for the treatment of advanced RCC. However, clinical trials investigating these therapies often exclude sicker patients and those over the age of 65, leaving a gap in knowledge about the effectiveness of newer versus older treatments in this population, especially when they are treated in routine health care settings rather than in research studies.

"Our findings suggest that targeted therapies offered new treatment options to elderly and medically complex patients who may have otherwise foregone the treatments available 15 years ago given their high toxicity and limited benefit," said senior author Jalpa A. Doshi, PhD, a professor of Medicine in the Perelman School of Medicine at the University of Pennsylvania. "RCC is a cancer where people can often try other treatment options if the first one isn't effective, so even small gains may mean that a person might live long enough to try the next innovation. What's more, studies are showing that current treatments, including immunotherapies, are leading to even better outcomes than those that were observed during our study time frame."

Results also showed that targeted therapies offered a modest survival benefit as compared to older treatments, even though as a whole, the targeted therapy treatment group had characteristics that put them at risk for worse outcomes.

The researchers conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2000 to 2013 to examine overall survival and estimated overall survival improvements in over 1,100 patients with stage IV clear cell RCC who received any FDA-approved targeted therapy (63 percent of patients) or nontargeted therapy (37 percent of patients). Most patients were aged 65 or older, and approximately 13 percent were younger but eligible for Medicare due to disability prior to their RCC diagnosis.

The initial analysis found no statistically significant difference in survival between targeted and nontargeted therapies. However, a more in-depth analysis that used statistical techniques to mimic the more controlled conditions found in clinical trials--known as an instrumental variable analysis--revealed a three-month survival advantage with targeted therapies compared to older treatments. Estimated overall survival improvements with targeted therapy versus nontargeted therapies were also statistically significant--eight percent at one year, seven percent at two years, and five percent at three years.

"The more sophisticated statistical methods allowed us to see an unbiased picture of how the treatments compared in the real world," said first author Pengxiang Li, PhD, a senior research investigator at Penn Medicine. "The method helped control for unmeasured differences between the treatment groups, which cannot be adjusted using traditional approaches."

Despite the findings, the median survival benefits observed in this real-world patient population were smaller compared to the benefits seen in clinical trial participants enrolled in randomized studies of targeted therapies. The combined findings underscore that research studies summarize outcomes for groups of patients and may not accurately reflect how treatments will perform in the real world or what any individual patient can expect from treatment.

For example, in this study, half of the targeted therapy group had passed away within nine months, but 10 percent of people survived longer than 47 months. Among that group with better outcomes, targeted therapies offered an 11-month survival advantage over older treatments, the researchers reported.

"Treatment decisions involve weighing potential risks, benefits, and costs of treatment as well as quality-of-life considerations, which may vary from person to person depending on their medical situation and preferences. Good communication between patients and their treatment teams is essential, and knowing more about real-world outcomes can help with those discussions," said co-author Amy R. Pettit, PhD, adjunct fellow at the Penn Center for Public Health Initiatives.

The study not only demonstrates that an older, more medically complex population has benefitted from targeted therapies, but also highlights the importance of rigorous methods to evaluate the real-world impact of treatments on health outcomes, the researchers wrote.

A widely recognized biomarker for pancreatic disease, CA19-9, thought to be benign for decades, may in fact be a promoter for the development of these diseases, including pancreatic cancer. The unexpected results were revealed using genetically engineered mice and organoid models of pancreatic disease and may suggest new avenues for the treatment of pancreatic cancer - one of the deadliest human cancers. They may also offer a lesson that can be applied to the other cancer biomarkers that have not been ascribed roles in the etiology of disease. CA19-9, a glycan carbohydrate antigen present on many proteins, is commonly expressed at low levels within the pancreas. However, patients with pancreatic diseases, including cancer, often show increased levels of the antigen within their blood. As such, it has become one of the few biomarkers for these conditions, used for more than 30 years. Even so, how CA19-9 relates to disease pathogenesis is not well known. Because mice do not express CA19-9 on their own, a mouse model useful in studying this relationship has remained elusive. Danielle Engle and colleagues developed transgenic mouse models capable of reproducing the CA19-9 levels observed in human pancreatic cancer patients and, to their surprise, found that expression of CA19-9 in these mice resulted in severe pancreatitis and hyperactivation of epidermal growth factor receptor signaling, a known driver of pancreatic cancer. While CA19-9-mediated pancreatitis could be reversed using CA19-9 antibodies, the authors also found that CA19-9-expressing transgenic mice who also harbored an oncogene developed pancreatic cancer. "By understanding whether and how CA19-9 contributes to disease, we are now poised to apply this knowledge to improve the utility of CA19-9 both as a biomarker, but also as a new treatment strategy," said Engle. In a related Perspective, Christopher Halbrook and Howard Crawford discuss the study and its implications in more detail.

In 2017, the majority (58%) of the almost 27 000 newly reported hepatitis B cases in the European Union and European Economic Area were classified as chronic infections. This follows a consistent upward trend in reported chronic hepatitis B cases since 2008.

There is evidence of on-going transmission of hepatitis B and continued importation of cases to many European countries according to the available surveillance data for countries of the European Union and the European Economic Area (EU/EEA) for 2017. Incomplete data as well as varying national surveillance systems and practices however impair more detailed epidemiological analysis of reported data.

The majority of EU/EEA countries consistently reporting experienced a steady decline in newly reported acute hepatitis B infections from 1.1 per 100 000 population in 2008 to 0.6 in 2017. This reflects overall global trends and is most likely a result of successful national vaccination programmes: in these countries, the proportion of acute hepatitis B infections among people below 25 years of age declined from 20% in 2008 to 12% in 2017. The proportion of chronic cases under 25 declined from 21% in 2008 to 10% in 2017.

However, during the same time period notifications of chronic hepatitis B overall increased from 6.7 per 100 000 population to 10.2 in 2017 with the highest rates reported among the 25-34-year-olds. Overall, the reported data on chronic hepatitis B seems to mirror the intensity of local testing and screening policies - thus countries with comprehensive testing programmes in place appear to have the highest notification rates. The high number of chronic infections from northern Europe has a strong influence on trends with e.g. 62% of chronic hepatitis B cases in 2017 notified by the United Kingdom.

Incomplete data affects interpretation

Transmission data are key to understanding the epidemiology of hepatitis B. However, information on the transmission mode was only complete for roughly a third (29%) of the reported acute cases in 2017 and only 13% of the notified chronic cases. Hence, data are unlikely to be fully representative, and observed trends and differences between countries are hard to interpret.

For the 718 acute cases with complete information, heterosexual transmission was most commonly reported (27%), followed by nosocomial transmission (16%), sex between men (13%), non-occupational injuries (10%) and injecting drug use (10%). Italy, Poland and Romania accounted for 74% of the acute cases attributed to healthcare-associated hepatitis B infections in 2017.

Where this information was available, transmission from mother to child and in healthcare settings were the most commonly reported routes for chronic hepatitis B infection (41% and 28% respectively). Poland reported 90% of chronic cases related to nosocomial transmission.

Of the 12 018 cases (45%) with information on importation status, 3 778 (31%) were reported as imported. The influence of migration on hepatitis B epidemiology highlights the need for countries to develop evidence-based screening interventions that target the most affected migrant communities. It also highlights the importance of monitoring routine surveillance indicators of migration, such as importation status.

The relatively high number of 26 907 reported hepatitis B infections in 2017and especially chronic cases, in combination with the diversity in reported transmission routes across Europe suggest that countries need to maintain and strengthen local hepatitis prevention and control programmes.

The World Health Organization's European Action plan for the health sector response to viral hepatitis outlines ways to do this. Based on the information from the ECDC prevalence database, authorities can identify the key population groups and areas of high hepatitis prevalence for targeted efforts.

A global study looking at the role that iron plays in 900 diseases has uncovered the impact of both low and high iron levels - and the news is mixed.

People with high iron levels are not only protected against anaemia but are also less likely to have high cholesterol, according to an international study led by Imperial College London, the University of South Australia (UniSA) and University of Ioannina.

In a paper published today in PLOS Medicine, researchers used genetic and clinical data from approximately 500,000 people in the UK Biobank, looking at the role of iron status and its impact on health.

Iron deficiency is well documented, with approximately 1.2 billion people worldwide living with anaemia, leading to serious health problems if left untreated.

What is less known is the impact of excess iron where the body stores too much iron, which can lead to liver disease, heart problems and diabetes in extreme cases.

Around 25 to 65 per cent of differences between individuals in iron levels are due to genetic factors, according to UniSA geneticist Dr Beben Benyamin, joint first author of the paper.

"We used a statistical method, called Mendelian randomization that employs genetic data to better estimate the causal effect of iron status on 900 diseases and conditions. Through this, we found a link between excess iron and a reduced risk of high cholesterol," Dr Benyamin says.

"This could be significant given that raised cholesterol is a major factor in cardiovascular disease and stroke, causing around 2.6 million deaths each year according to the World Health Organization."

However, it's a double-edged sword: high iron levels could also lead to a greater risk of bacterial skin infections, such as cellulitis and abscesses.

Previous studies have found that bacteria need iron to survive and flourish, but the Biobank study is the first to use large scale population data to support the link between iron overload and bacterial skin infections.

Cellulitis affects around 21 million people each year, resulting in more than 17,000 deaths worldwide, making it a global health priority.

Co-lead author of the paper, Dr Dipender Gill from Imperial College London, says a great strength of the study is its ability to "rapidly and efficiently determine the effect of genetically-raised iron status on hundreds of clinically relevant outcomes using data that has already been captured".

"We identified the previously established protective effect of higher iron status on traits related to anaemia, and further showed protective effects related to risk of high cholesterol levels and detrimental effects on risk of skin and soft tissue infections."

Clinical trials have been undertaken to manipulate iron status in anaemic patients but, to date, no trials have targeted iron levels to prevent or treat skin infections or regulate cholesterol. Trial data is essential before iron manipulation is recommended for these disorders.

"In this study we have provided population-based evidence that iron is associated with certain diseases. The next step is to investigate whether direct manipulation of iron levels improve health outcomes though clinical trials," Dr Benyamin says.

Adolescents who see themselves as puny and who exercise to gain weight may be at risk of so-called muscularity-oriented disordered eating behaviors, say researchers led by UCSF Benioff Children's Hospitals.

The researchers found that 22 percent of males and 5 percent of females ages 18-to-24 exhibit these disordered eating behaviors, which are defined as including at least one of the following: eating more or differently to gain weight or bulk up, and use of dietary supplements or anabolic steroids to achieve the same goal.

Left unchecked, these behaviors may escalate to muscle dysmorphia, characterized by rigid diet, obsessive over-exercising and extreme preoccupation with physique, say the researchers in their study publishing in the International Journal of Eating Disorders on June 20, 2019.

"Some eating disorders can be challenging to diagnose," said first author Jason Nagata, MD, of the UCSF Division of Adolescent and Young Adult Medicine. "Unlike anorexia nervosa, which may be easily identified by parents or pediatricians, disordered eating to increase bulk may masquerade as healthy habits and because of this, it tends to go unnoticed."

Heart Failure, Depression, Social Isolation in Worst Cases

At its most extreme, it can lead to heart failure due to insufficient calories and overexertion, as well as muscle dysmorphia, which is associated with social withdrawal and depression, Nagata said.

The 14,891 young adults in the study, who came from throughout the United States, had been followed for seven years. The researchers wanted to see if the early data, when the participants' average age was 15, revealed something about their perceptions and habits that may serve as warning signs.

They found that boys who exercised specifically to gain weight had 142 percent higher odds of this type of disordered eating; among girls, the odds were increased by 248 percent. Boys who perceived themselves as being underweight had 56 percent higher odds; in girls the odds were 271 percent higher. Smoking and alcohol use in boys, and smoking in girls, increased odds moderately.

Additionally, being of black race bolstered odds by 66 percent in boys and 181 percent in girls.

Non-heterosexual identity, which the participants had been asked about when they reached adulthood, was not found to be a risk factor, the researchers said.

In young adulthood, 6.9 percent of males reported supplement use to gain weight or build muscle and 2.8 percent said they used anabolic steroids. Use by young women was significantly lower at 0.7 percent and 0.4 percent respectively.

"Supplements are a black box, since they are not regulated," noted Nagata. "In extreme cases, supplements can cause liver and kidney damage. Anabolic steroids can cause both long-term and short-term health issues, including shrunken testicles, stunted growth and heart disease."

Nagata said that clues that indicate behaviors may approach muscle dysmorphia include a highly restrictive diet that omits fats and carbohydrates, compulsive weighing and checking of appearance, and extensive time dedicated to exercise that may cut into social activities.