Mediterranean diet tied to 30 percent risk reduction for diabetes in Women's Health Study

by Brigham and Women's Hospital

Credit: CC0 Public Domain

The Mediterranean (MED) diet—rich in olive oil, fruits, vegetables, legumes, nuts and seeds—is a recommended way to reduce the risk of heart disease, type 2 diabetes and other adverse health outcomes. But exactly how and why the MED diet lowers risk for type 2 diabetes has remained unclear. In a study conducted by investigators from Brigham and Women's Hospital, researchers examined outcomes for more than 25,000 participants in the Women's Health Study, a longitudinal cohort study that followed female health professionals for more than 20 years. In a paper published in JAMA Network Open, the investigators report that women who adhered to a more MED-like diet had a 30 percent lower rate of type 2 diabetes than women who did not. The team examined several biomarkers to look for biological explanations for these results, finding key mechanisms including insulin resistance, body mass index, lipoprotein metabolism and inflammation.

28 november 2020--"Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity," said corresponding author Samia Mora, MD, MHS, of the Brigham's divisions of Preventive Medicine and Cardiovascular Medicine and an associate professor at Harvard Medical School. "A lot of the benefit we see can be explained through just a few pathways. And it's important to note that many of these changes don't happen right away—while metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades."

The Women's Health Study (WHS) enrolled female health care professionals between 1992 and 1995, collecting data through December 2017. It was designed to evaluate the effects of vitamin E and low-dose aspirin on risk of heart disease and cancer. Additionally, participants were asked to complete food frequency questionnaires (FFQs) about dietary intake when the study began and answer other questions about lifestyle, medical history, demographics and more. More than 28,000 women provided blood samples at the beginning of the trial.

Mora and colleagues leveraged data from the FFQs and blood samples to investigate the relationship between the MED diet, type 2 diabetes and biomarkers that might explain the connection. To do so, they assigned each participant a MED diet intake score from 0 to 9, with points assigned for higher intake of fruits, vegetables, whole grains, legumes, nuts and fish, moderate intake of alcohol, and lower intake red meat or processed meat. The team measured a range of biomarkers, including traditional ones such as cholesterol, and more specialized ones that can only be detected using nucleic magnetic resonance. These included lipoproteins—molecules that pack and transport fats and proteins—and measures of insulin resistance, a condition in which muscle, liver and fat cells do not respond to normal amounts of insulin. Insulin resistance is often a precursor to diabetes.

Of the more than 25,000 participants in the WHS, 2,307 developed type 2 diabetes. Participants with higher MED intake at the beginning of the study (scores greater than or equal to 6) developed diabetes at rates that were 30 percent lower than participants with lower MED intake (scores less than or equal to 3). This effect was seen only among participants with a body mass index greater than 25 (overweight or obese range) and not among participants whose BMI was less than 25 (normal or underweight).

Biomarkers of insulin resistance appeared to be the biggest contributor to lower risk, followed by biomarkers of body mass index, high-density lipoprotein measures and inflammation.

"Most of this reduced risk associated with the Mediterranean diet and type 2 diabetes was explained through the biomarkers related to insulin resistance, adiposity, lipoprotein metabolism and inflammation," said first author Shafqat Ahmad, Ph.D., a researcher in the Molecular Epidemiology Unit at Uppsala University, Sweden, who helped conduct the study while working at the Brigham. "This understanding may have important downstream consequences for the primary prevention of diabetes disease."

One of the strengths of the study was its length—unlike many previous studies that have only looked at short-term effects of diets, the WHS followed participants for up to 25 years to see who developed type 2 diabetes. But the authors note several limitations, including that study participants were predominantly white and well educated, and all were female health professionals. In addition, dietary intake was self-reported and only examined at the start of the study. Biomarkers were also only measured when participants entered the study.

Mora emphasizes that insights into the biology that explains how the Mediterranean diet may help protect against diabetes could be helpful in preventive medicine and for physicians speaking to patients about dietary changes.

"Even small changes can add up over time," she said. "And there may be many biological pathways that lead to a benefit. One of the best things patients can do for future health is to improve their diet, and now we are beginning to understand why."

More information: Ahmad F et al. "Association of the Mediterranean Diet With Onset of Diabetes in the Women's Health Study" JAMA Network Open (2020). DOI: 10.1001/jamanetworkopen.2020.25466

Provided by Brigham and Women's Hospital 

 The danger of Z-drugs for dementia patients

by University of East Anglia

Credit: CC0 Public Domain

Strong sleeping pills known as 'Z-drugs' are linked with an increased risk of falls, fractures and stroke among people with dementia—according to research from the University of East Anglia.

27 nov 2020--Sleep disturbance is common among people with dementia and the impact for patients and their families is significant.

To date there are no proven effective treatments available, however people with dementia are often prescribed Z-drugs (zopiclone, zaleplon, and zolpidem).

But a new study published today reveals that stronger doses of these drugs are linked with an increased risk of adverse effects.

These adverse effects were found to be similar or greater than those for higher dose benzodiazepines or 'benzos' - which are also used to treat sleep disturbance, and are known to have several adverse effects.

The team say that patients already taking higher doses of Z-drugs should not stop taking their medication suddenly, however they should seek a review with their GP.

Prof Chris Fox, from UEA's Norwich Medical School, said: "As many as 90 percent of people with dementia suffer sleep disturbances and it has a big impact on their mental and physical health, as well as that of their carers.

"Z-drugs are commonly prescribed to help people sleep—however these medicines were never licensed for dementia and they have been associated with adverse events such as falls and fracture risks in older people.

"We wanted to find out how they affect people with dementia, who are frequently prescribed them to help with sleep disturbance."

The team analysed data from 27,090 patients in England diagnosed with dementia between January 2000 and March 2016. The average age of the patients was 83 and 62 percent were women.

They looked at the adverse events for 3,532 patients who had been prescribed Z-drugs and compared them to people suffering sleep disturbance who had not been prescribed sedatives, and patients who had been prescribed benzodiazepines.

They also looked to see whether Z-drug dosage played a part in adverse outcomes.

Prof Fox said: "We studied a range of adverse outcomes including fractures, falls, deep vein thrombosis, stroke and death—over two years. And we were particularly interested to see whether higher doses led to worse outcomes."

Higher dose Z-drugs and benzodiazepines were defined as prescriptions equivalent to >7.5mg zopiclone or >5mg diazepam daily.

"For patients prescribed Z-drugs, 17 percent were given higher doses. And we found that these patients on higher doses were more at risk of falls and fractures, particularly hip fractures, and stroke—compared with patients who were not taking any medication for sleep disturbance," said Prof Fox.

Those on lower doses however (<3.75mg zopiclone or equivalent) were not found to have an increased risk of adverse outcomes.

And there were no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs.

Prof Fox said: "This research shows us that higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered.

"Patients already taking higher dose Z-drugs should not stop taking their medication, but we recommend that they should make an appointment to see their GP for a review," he added.

Prof Clive Ballard, of the University of Exeter Medical School, who collaborated on the study, said: "Our findings serve an important caution regarding the harms of sleeping tablets in people with dementia.

"This research is a very timely and unfortunately necessary reminder that sedative medications are not a helpful way to manage social isolation during COVID-19.

"Our study also highlights the importance of research to develop non-drug approaches to help people with dementia to sleep—whether they are at home or in residential care."

Dr. Ian Maidment, Reader in Clinical Pharmacy at Aston University and lead pharmacist on the study stated: "Z-drugs are widely used to treat insomnia in people living with dementia, but are only recommended as a short-term treatment for the maximum of four weeks. Our work shows the importance of clinicians including GPs and pharmacists reviewing patients on long-term Z-drugs."

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More information: 'Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study' is published in the journal BMC Medicine on November 24, 2020.

Provided by University of East Anglia 

 WHO Guideline Development Group advises against use of remdesivir for COVID-19

by British Medical Journal

3D print of a spike protein of SARS-CoV-2, the virus that causes COVID-19--in front of a 3D print of a SARS-CoV-2 virus particle. The spike protein (foreground) enables the virus to enter and infect human cells. On the virus model, the virus surface (blue) is covered with spike proteins (red) that enable the virus to enter and infect human cells. Credit: NIH

The antiviral drug remdesivir is not suggested for patients admitted to hospital with COVID-19, regardless of how severely ill they are, because there is currently no evidence that it improves survival or the need for ventilation, say a WHO Guideline Development Group (GDG) panel of international experts in The BMJ today.

20 november 2020--The recommendation is part of a living guideline, developed by the World Health Organization with the methodological support of MAGIC Evidence Ecosystem Foundation, to provide trustworthy guidance on the management of COVID-19 and help doctors make better decisions with their patients.

Living guidelines are useful in fast moving research areas like COVID-19 because they allow researchers to update previously vetted and peer reviewed evidence summaries as new information becomes available.

Remdesivir has received worldwide attention as a potentially effective treatment for severe COVID-19 and is increasingly used to treat patients in hospital. But its role in clinical practice has remained uncertain.

Today's recommendation is based on a new evidence review comparing the effects of several drug treatments for COVID-19. It includes data from four international randomised trials involving over 7,000 patients hospitalised for COVID-19.

After thoroughly reviewing this evidence, the WHO GDG expert panel, which includes experts from around the world including four patients who have had COVID-19, concluded that remdesivir has no meaningful effect on mortality or on other important outcomes for patients, such as the need for mechanical ventilation or time to clinical improvement.

The panel acknowledged that the certainty of evidence is low and said the evidence did not prove that remdesivir has no benefit; rather, there is no evidence based on currently available data that it does improve important patient outcomes.

But given the remaining possibility of important harm, as well as the relatively high cost and resource implications associated with remdesivir (it must be given intravenously), they judged this to be an appropriate recommendation.

They also support continued enrolment into trials evaluating remdesivir, especially to provide higher certainty of evidence for specific groups of patients.

In a linked feature article, US journalist Jeremy Hsu asks what now for remdesivir, given that it is unlikely to be the lifesaving drug for the masses that many have hoped for?

The full story of remdesivir will not be known until manufacturer Gilead releases the full clinical study reports, writes Hsu, but much will depend on whether future studies are designed to test remdesivir's potential effectiveness.

In the meantime, he says alternative treatments, such as the well known, cheap, and widely available corticosteroid dexamethasone, that has been proved to reduce mortality among severely ill COVID-19 patients, are now impacting discussions about remdesivir's cost-effectiveness.

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More information: François Lamontagne et al, A living WHO guideline on drugs for covid-19, BMJ (2020). DOI: 10.1136/bmj.m3379

Journal information: British Medical Journal (BMJ) 

 Future doctors need more nutrition education

by Griffith University

Credit: Pixabay/CC0 Public Domain

Medical students need more support to increase their nutrition knowledge and skills before they graduate a Griffith University study has found.

17 november 2020--The five-year study published in the journal BMJ Nutrition, Prevention and Health, examined over 100 New Zealand medical students' self-reported nutrition knowledge at three time points during their medical training by asking them to complete the same survey at the end of year 2, year 4 and year 5 of their degree.

"While the students modestly increased their nutrition knowledge and skills between year 2 and year 4, the overall results were still very low,'' says lead author Associate Professor Lauren Ball from Menzies Health Institute Queensland.

"There was a clear desire for more nutrition education from all students. A key strategy to support healthy eating is to incorporate nutrition into healthcare service and doctors are expected to provide nutrition advice to patients to improve their diet when necessary. But to provide nutrition care, doctors require adequate nutrition knowledge, skills and attitudes to support the integration of such care into routine practice with patients."

Associate Professor Ball said it was recognized that graduating medical students lack nutrition knowledge and skills to actively support dietary behavior change in patients.

"This is the first study to describe how medical students' self-perceived nutrition competence changes over time during medical training. These results show that further supporting medical students to increase their knowledge and skills in this area is essential. While the study was conducted in New Zealand, Australian students face the same challenges as their counterparts across the ditch because medical programs are accredited by the same body, with identical mandatory components. Given the recognized link between nutrition and health, one approach to consider is making nutrition education compulsory for medical training."

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More information: Jennifer Crowley et al. How does self-perceived nutrition competence change over time during medical training? A prospective longitudinal observational study of New Zealand medical students, BMJ Nutrition, Prevention & Health (2020). DOI: 10.1136/bmjnph-2020-000080

Provided by Griffith University 

 Link between Alzheimer's disease and gut microbiota is confirmed

by University of Geneva

Credit: Unsplash/CC0 Public Domain

Alzheimer's disease is the most common cause of dementia. Still incurable, it directly affects nearly one million people in Europe, and indirectly millions of family members as well as society as a whole. In recent years, the scientific community has suspected that the gut microbiota plays a role in the development of the disease.

16 november 2020--A team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) in Switzerland, together with Italian colleagues from the National Research and Care Center for Alzheimer's and Psychiatric Diseases Fatebenefratelli in Brescia, University of Naples and the IRCCS SDN Research Center in Naples, confirm the correlation, in humans, between an imbalance in the gut microbiota and the development of amyloid plaques in the brain, which are at the origin of the neurodegenerative disorders characteristic of Alzheimer's disease. Proteins produced by certain intestinal bacteria, identified in the blood of patients, could indeed modify the interaction between the immune and the nervous systems and trigger the disease. These results, published in the Journal of Alzheimer's Disease, make it possible to envisage new preventive strategies based on the modulation of the microbiota of people at risk.

The research laboratory of neurologist Giovanni Frisoni, director of the HUG Memory Centre and professor at the Department of Rehabilitation and Geriatrics of the UNIGE Faculty of Medicine, has been working for several years now on the potential influence of the gut microbiota on the brain, and more particularly on neurodegenerative diseases. "We have already shown that the gut microbiota composition in patients with Alzheimer's disease was altered, compared to people who do not suffer from such disorders," he explains. "Their microbiota has indeed a reduced microbial diversity, with an over-representation of certain bacteria and a strong decrease in other microbes. Furthermore, we have also discovered an association between an inflammatory phenomenon detected in the blood, certain intestinal bacteria and Alzheimer's disease; hence the hypothesis that we wanted to test here: could inflammation in the blood be a mediator between the microbiota and the brain?"

The brain under influence

Intestinal bacteria can influence the functioning of the brain and promote neurodegeneration through several pathways: they can indeed influence the regulation of the immune system and, consequently, can modify the interaction between the immune system and the nervous system. Lipopolysaccharides, a protein located on the membrane of bacteria with pro-inflammatory properties, have been found in amyloid plaques and around vessels in the brains of people with Alzheimer's disease. In addition, the intestinal microbiota produces metabolites—in particular some short-chain fatty acids—which, having neuroprotective and anti-inflammatory properties, directly or indirectly affect brain function.

"To determine whether inflammation mediators and bacterial metabolites constitute a link between the gut microbiota and amyloid pathology in Alzheimer's disease, we studied a cohort of 89 people between 65 and 85 years of age. Some suffered from Alzheimer's disease or other neurodegenerative diseases causing similar memory problems, while others did not have any memory problems," reports Moira Marizzoni, a researcher at the Fatebenefratelli Center in Brescia and first author of this work. "Using PET imaging, we measured their amyloid deposition and then quantified the presence in their blood of various inflammation markers and proteins produced by intestinal bacteria, such as lipopolysaccharides and short-chain fatty acids."

A very clear correlation

"Our results are indisputable: certain bacterial products of the intestinal microbiota are correlated with the quantity of amyloid plaques in the brain," explains Moira Marizzoni. "Indeed, high blood levels of lipopolysaccharides and certain short-chain fatty acids (acetate and valerate) were associated with both large amyloid deposits in the brain. Conversely, high levels of another short-chain fatty acid, butyrate, were associated with less amyloid pathology."

This work thus provides proof of an association between certain proteins of the gut microbiota and cerebral amyloidosis through a blood inflammatory phenomenon. Scientists will now work to identify specific bacteria, or a group of bacteria, involved in this phenomenon.

A strategy based on prevention

This discovery paves the way for potentially highly innovative protective strategies—through the administration of a bacterial cocktail, for example, or of pre-biotics to feed the "good" bacteria in our intestine. "However, we shouldn't be too quick to rejoice," says Frisoni. "Indeed, we must first identify the strains of the cocktail. Then, a neuroprotective effect could only be effective at a very early stage of the disease, with a view to prevention rather than therapy. However, early diagnosis is still one of the main challenges in the management of neurodegenerative diseases, as protocols must be developed to identify high-risk individuals and treat them well before the appearance of detectable symptoms."

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More information: Moira Marizzoni et al. Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer's Disease, Journal of Alzheimer's Disease (2020). DOI: 10.3233/JAD-200306

Journal information: Journal of Alzheimer's Disease 

Provided by University of Geneva 

 

Common SARS-CoV-2 mutation may make coronavirus more susceptible to a vaccine

by University of North Carolina at Chapel Hill

Credit: Unsplash/CC0 Public Domain

A new study published in Science confirms that SARS-CoV-2 has mutated in a way that's enabled it to spread quickly around the world, but the spike mutation may also make the virus more susceptible to a vaccine.

13 november 2020--The new strain of coronavirus, called D614G, emerged in Europe and has become the most common in the world. Research at the University of North Carolina at Chapel Hill and the University of Wisconsin-Madison shows the D614G strain replicates faster and is more transmissible than the virus, originating in China, that spread in the beginning of the pandemic.

There were bright spots in the study findings: While the D614G strain spreads faster, in animal studies it was not associated with more severe disease, and the strain is slightly more sensitive to neutralization by antibody drugs.

The study published Nov. 12 provides some of the first concrete findings about how SARS-CoV-2 is evolving.

"The D614G virus outcompetes and outgrows the ancestral strain by about 10-fold and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission," said Ralph Baric, professor of epidemiology at the UNC-Chapel Hill Gillings School of Global Public Health and professor of microbiology and immunology at the UNC School of Medicine.

Baric has studied coronaviruses for more than three decades and was integral in the development of remdesivir, the first FDA-approved treatment for COVID-19.

Researchers believe the D614G strain of coronavirus dominates because it increases the spike protein's ability to open cells for the virus to enter. These crown-like spikes give the coronavirus its name.

The D614G mutation causes a flap on the tip of one spike to pop open, allowing the virus to infect cells more efficiently but also creating a pathway to the virus' vulnerable core.

With one flap open, it's easier for antibodies—like the ones in the vaccines currently being tested—to infiltrate and disable the virus.

For the recent study, Baric Lab researchers—including first author Yixuan J. Hou—worked in collaboration with Yoshihiro Kawaoka and Peter Halfmann, both virologists on faculty at the University of Wisconsin-Madison.

"The original spike protein had a 'D' at this position, and it was replaced by a 'G,'" Kawaoka said. "Several papers had already described that this mutation makes the protein more functional and more efficient at getting into cells."

That earlier work, however, relied on a pseudotyped virus that included the receptor-binding protein but was not authentic. Using reverse genetics, Baric's team replicated a matched pair of mutant SARS-CoV-2 viruses that encoded D or G at position 614 and compared basic property analysis using cell lines, primary human respiratory cells, and mouse and hamster cells.

Kawaoka and Halfmann contributed their unique coronavirus study model, which uses hamsters. The University of Wisconsin-Madison team—including Shiho Chiba, who ran the hamster experiments—performed replication and airborne transmission studies with both the original virus and the mutated version created by Baric and Hou.

They found that the mutated virus not only replicates about 10 times faster—it's also much more infectious.

Hamsters were inoculated with one virus or the other. The next day, eight uninfected hamsters were placed into cages next to infected hamsters. There was a divider between them so they could not touch, but air could pass between the cages.

Researchers began looking for replication of the virus in the uninfected animals on day two. Both viruses passed between animals via airborne transmission, but the timing was different.

With the mutant virus, the researchers saw transmission to six out of eight hamsters within two days, and to all the hamsters by day four. With the original virus, they saw no transmission on day two, though all of the exposed animals were infected by day four.

"We saw that the mutant virus transmits better airborne than the [original] virus, which may explain why this virus dominated in humans," Kawaoka said.

The researchers also examined the pathology of the two coronavirus strains. Once hamsters were infected, they presented essentially the same viral load and symptoms. (The hamsters with the mutated strain lost slightly more weight while sick.) This suggests that while the mutant virus is much better at infecting hosts, it doesn't cause significantly worse illness.

Researchers caution that the pathology results may not hold true in human studies.

"SARS-CoV-2 is an entirely new human pathogen and its evolution in human populations is hard to predict," Baric said. "New variants are continually emerging, like the recently discovered mink SARS-CoV-2 cluster 5 variant in Denmark that also encodes D614G.

"To maximally protect public health, we must continue to track and understand the consequences of these new mutations on disease severity, transmission, host range and vulnerability to vaccine-induced immunity."

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More information: Yixuan J. Hou et al, SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo, Science  12 Nov 2020:eabe8499. DOI: 10.1126/science.abe8499

Journal information: Science 

 

LipiDiDiet finds broadly sustainable effects of nutrient intervention in early Alzheimer's

by Saarland University

Credit: CC0 Public Domain

Trial participants who received a multinutrient formulation over an extended period of time showed a significantly less rapid deterioration in cognitive performance than the patients in a control group, who received only a placebo. These findings are from an ongoing European study LipiDiDiet in which 311 patients in eleven hospitals have been monitored for three years. The research results have been published in the highly ranked international journal Alzheimer's & Dementia, the Journal of the Alzheimer's Association.

05 november 2020--The early stages of Alzheimer's disease are characterized by a decline in brain and memory function, with short-term memory loss particularly affected. Patients and their families recognize these symptoms long before dementia occurs. "By examining the cerebrospinal fluid and by using magnetic resonance brain imaging techniques that can show the hippocampal shrinkage that is so typical of Alzheimer's disease, we are able to identify patients who are at this early (prodromal) stage," explains Tobias Hartmann, Professor of Experimental Neurology at Saarland University, who coordinates the European LipiDiDiet project. LipiDiDiet is a broad-based, long-term study of over three hundred participants who originally showed initial symptoms of memory impairment. The study was designed to investigate the effects of treating patients with a specially formulated medical food.

The previously published preliminary results showed that this nutrition-based intervention has a positive impact on the progression of the disease. "But it is only now, after three years of treatment, that we are seeing how extensive the significant differences between trial participants who received the active nutrient drink and those in the control group really are," explains Hartmann. Participants in the control group were given a placebo drink that was identical in terms of taste, texture and appearance. Neither the patients, nor the doctors and researchers knew who had been given the placebo and who had received the multinutrient drink. "We found that there was 20 percent less brain shrinkage in patients with Alzheimer's disease who received the nutrient cocktail than in those in the control group, which represents a significant slowing in the rate of brain atrophy. More importantly, we have demonstrated that over the three years of treatment, patients who were given the multinutrient drink suffered between 40 and 70 percent less cognitive impairment than those who received the placebo," says Hartmann.

"The positive effects of the treatment were most pronounced in those patients who began taking the multinutrient formulation at the earliest prodromal stage of Alzheimer's disease. We were particularly surprised to discover that these positive effects increased the longer treatment continued and that this finding was observed not only with respect to memory, but also with other cognitive abilities," explains Professor Hartmann. Compared with those in the control group, the subjects who received the multinutrient drink were better able to master typical day-to-day challenges, such as paying a bill, remembering a route or dealing with emergencies.

The multinutrient formulation given to the Alzheimer's patients in the LipiDiDiet study was the commercially available medical food "Fortasyn Connect," which contains a specific combination of essential fatty acids, vitamins and other nutrients. Specifically, Fortasyn Connect contains docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate, choline, vitamins B12, B6, C, E, and folic acid, phospholipids and selenium. Earlier preclinical research by the LipiDiDiet consortium and other laboratories, such as the Massachusetts Institute of Technology (MIT), has shown that these nutrients can reduce a number of the changes typically seen in the brains of Alzheimer's disease patients. Subsequent clinical studies demonstrated positive results from memory and EEG measurements that indicate increased brain activity in the trial participants that were given the nutrient drink.

Globally, around 47 million people are currently suffering from Alzheimer's disease or a similar neurodegenerative dementia, for which there is at present no known cure. Over the next 20 years, scientists expect this number to double, with forecasts suggesting that there will be around 130 million sufferers in 2050. "Despite significant research efforts, we still do not have any medications that can cure early-stage Alzheimer's disease. Some of these drugs are able to provide temporary relief for certain symptoms, but after a while the patients usually return to their earlier pre-treatment state. In light of this, the positive effects that we have been able to achieve with our special multinutrient drink are a major success. Our hope is that the significantly slower progression that we see in our patients will continue so that they can maintain their independence well into old age," says Tobias Hartmann.

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More information: Hilkka Soininen et al. 36‐month LipiDiDiet multinutrient clinical trial in prodromal Alzheimer's disease, Alzheimer's & Dementia (2020). DOI: 10.1002/alz.12172

Provided by Saarland University 

 What the public hopes and fears about the use of AI in health care

by P. Alison Paprica, Melissa McCradden, The Conversation

The growing use of artificial intelligence in health care should be driven by careful consideration of what is important to members of the public. Credit: Shutterstock

There has been increasing interest in using health "big data" for artificial intelligence (AI) research. As such, it is important to understand which uses of health data are supported by the public and which are not.

04 november 2020--Previous studies have shown that members of the public see health data as an asset that should be used for research provided there is a public benefit and concerns about privacy, commercial motives and other risks are addressed.

However, this general support may not extend to health AI research because of concerns about the potential for AI-related job losses and other negative impacts.

Our research team conducted six focus groups in Ontario in October 2019 to learn more about how members of the general public perceive the use of health data for AI research. We found that members of the public supported using health data in three realistic health AI research scenarios, but their approval had conditions and limits.

Robot fears

Each of our focus groups began with a discussion of participants' views about AI in general. Consistent with the findings from other studies, people had mixed—but mostly negative—views about AI. There were multiple references to malicious robots, like the Terminator in the 1984 James Cameron film.

"You can create a Terminator, literally, something that's artificially intelligent, or the matrix … it goes awry, it tries to take over the world and humans got to fight this. Or it can go in the absolute opposite where it helps … androids … implants.… Like I said, it's unlimited to go either way." (Mississauga focus group participant)

Additionally, several people shared their belief that there is already AI surveillance of their own behavior, referencing targeted ads that they have received for products they had only spoken privately about.

Some participants commented on how AI could have positive impacts, as in the case of autonomous vehicles. However, most of the people who said positive things about AI also expressed concern about how AI will affect society.

"It's portrayed as friendly and helpful, but it's always watching and listening.… So I'm excited about the possibilities, but concerned about the implications and reaching into personal privacy." (Sudbury focus group participant)

Supporting scenarios

In contrast, focus group participants reacted positively to three realistic health AI research scenarios. In one of the scenarios, some perceived that health data and AI research could actually save lives, and most people were also supportive of two other scenarios which didn't include potential lifesaving benefits.

A CBC report on the future of AI in health care.

They commented favorably about the potential for health data and AI research to generate knowledge that would otherwise be impossible to obtain. For example, they reacted very positively to the potential for an AI-based test to save lives by identifying origin of cancers so that treatment can be tailored. Participants also noted practical advantages of AI including the ability to sift through large amounts of data, perform real-time analyzes and provide recommendations to health care providers and patients.

"When you can reach out and have a sample size of a group of ten million people and to be able to extract data from that, you can't do that with the human brain. A group, a team of researchers can't do that. You need AI." (Mississauga focus group participant)

Protecting privacy

The focus group participants were not positively disposed towards all possible uses of health data in AI research.

They were concerned that the health data provided for one health AI purpose might be sold or used for other purposes that they do not agree with. Participants also worried about the negative impacts if AI research creates products that lead to lack of human touch, job losses and a decrease in human skills over time because people become overly reliant on computers.

The focus group participants also suggested ways to address their concerns. Foremost, they spoke about how important it is to have assurance that privacy will be protected and transparency about how data are used in health AI research. Several people stated the condition that health AI research should create tools that function in support of humans, rather than autonomous decision-making systems.

"As long as it's a tool, like the doctor uses the tool and the doctor makes the call…it's not a computer telling the doctor what to do." (Sudbury focus group participant)

Involving members of the public in decisions about health AI

Engaging with members of the public took time and effort. In particular, considerable work was required to develop, test and refine realistic, plain language health AI scenarios that deliberately included potentially contentious points. But there was a large return on investment.

The focus group participants—none of whom were AI experts—had some important insights and concrete suggestions about how to make health AI research more responsible and acceptable to members of the public.

Studies like ours can be important inputs into policies and practice guides for health data and AI research. Consistent with the Montréal Declaration for Responsible Development of AI, we believe that researchers, scientists and policy makers need to work with members of the public to take the science of health AI in directions that members of the public support.

By understanding and addressing public concerns, we can establish trustworthy and socially beneficial ways of using health data in AI research.

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Provided by The Conversation 

 

Coronavirus mutation may have made it more contagious: study

by University of Texas at Austin

Adicionar legenda

The number of virus strains present in each zip code in Houston during the second wave of COVID-19 cases in summer 2020. Number of strains is represented by a spectrum of colors from blue (0 strains) to red (50 strains). Credit: Houston Methodist/University of Texas at Austin.

A study involving more than 5,000 COVID-19 patients in Houston finds that the virus that causes the disease is accumulating genetic mutations, one of which may have made it more contagious. According to the paper published in the peer-reviewed journal mBIO, that mutation, called D614G, is located in the spike protein that pries open our cells for viral entry. It's the largest peer-reviewed study of SARS-CoV-2 genome sequences in one metropolitan region of the U.S. to date.

02 november 2020--The paper shows "the virus is mutating due to a combination of neutral drift—which just means random genetic changes that don't help or hurt the virus—and pressure from our immune systems," said Ilya Finkelstein, associate professor of molecular biosciences at The University of Texas at Austin and co-author of the study. The study was carried out by scientists at Houston Methodist Hospital, UT Austin and elsewhere.

During the initial wave of the pandemic, 71% of the novel coronaviruses identified in patients in Houston had this mutation. When the second wave of the outbreak hit Houston during the summer, this variant had leaped to 99.9% prevalence. This mirrors a trend observed around the world. A study published in July based on more than 28,000 genome sequences found that variants carrying the D614G mutation became the globally dominant form of SARS-CoV-2 in about a month. SARS-CoV-2 is the coronavirus that causes COVID-19.

So why did strains containing this mutation outcompete those that didn't have it?

Perhaps they're more contagious. A study of more than 25,000 genome sequences in the U.K. found that viruses with the mutation tended to transmit slightly faster than those without it and caused larger clusters of infections. Natural selection would favor strains of the virus that transmit more easily. But not all scientists are convinced. Some have suggested another explanation, called "founder's effects." In that scenario, the D614G mutation might have been more common in the first viruses to arrive in Europe and North America, essentially giving them a head start on other strains.

The spike protein is also continuing to accumulate additional mutations of unknown significance. The Houston Methodist-UT Austin team also showed in lab experiments that at least one such mutation allows spike to evade a neutralizing antibody that humans naturally produce to fight SARS-CoV-2 infections. This may allow that variant of the virus to more easily slip past our immune systems. Although it is not clear yet whether that translates into it also being more easily transmitted between individuals.

The good news is that this mutation is rare and does not appear to make the disease more severe for infected patients. According to Finkelstein, the group did not see viruses that have learned to evade first-generation vaccines and therapeutic antibody formulations.

"The virus continues to mutate as it rips through the world," Finkelstein said. "Real-time surveillance efforts like our study will ensure that global vaccines and therapeutics are always one step ahead."

The scientists noted a total of 285 mutations across thousands of infections, although most don't appear to have a significant effect on how severe the disease is. Ongoing studies are continuing to surveil the third wave of COVID-19 patients and to characterize how the virus is adapting to neutralizing antibodies that are produced by our immune systems. Each new infection is a roll of the dice, an additional chance to develop more dangerous mutations.

"We have given this virus a lot of chances," lead author James Musser of Houston Methodist told The Washington Post. "There is a huge population size out there right now."

Several other UT Austin authors contributed to the work: visiting scholar Jimmy Gollihar, associate professor of molecular biosciences Jason S. McLellan and graduate students Chia-Wei Chou, Kamyab Javanmardi and Hung-Che Kuo.

The UT Austin team tested different genetic variants of the virus's spike protein, the part that allows it to infect host cells, to measure the protein's stability and to see how well it binds to a receptor on host cells and to neutralizing antibodies. Earlier in the year, McLellan and his team at UT Austin, in collaboration with researchers at the National Institutes of Health, developed the first 3-D map of the coronavirus spike protein for an innovation that now factors into several leading vaccine candidates' designs.

The researchers found that SARS-CoV-2 was introduced to the Houston area many times, independently, from diverse geographic regions, with virus strains from Europe, Asia, South America and elsewhere in the United States. There was widespread community dissemination soon after COVID-19 cases were reported in Houston.

An earlier version of the paper was posted last month to the preprint server medRxiv.

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More information: Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area, mBIO, DOI: 10.1128/mBio.02707-20 , mbio.asm.org/content/11/6/e02707-20

Provided by University of Texas at Austin

 

Spread of a novel SARS-CoV-2 variant across Europe in summer 2020

by University of Basel

Spread of a novel SARS-CoV-2 variant across Europe in summer 2020. Credit: University of Basel

Researchers from Basel and Spain have identified a novel SARS-CoV-2 variant that has spread widely across Europe in recent months, according to an un-peer-reviewed preprint released this week. While there is no evidence of this variant being more dangerous, its spread may give insights into the efficacy of travel policies adopted by European countries during the summer.

02 november 2020--In Europe alone, hundreds of different variants of the new coronavirus SARS-CoV-2 are currently circulating, distinguished by mutations in their genomes. However, only very few of these variants have spread as successfully and become as prevalent as the newly identified variant, named 20A.EU1.

The researchers at the University of Basel, ETH Zürich in Basel and the SeqCOVID-Spain consortium analyzed and compared virus genome sequences collected from COVID-19 patients all across Europe to trace the evolution and spread of the pathogen (see box). Their analysis suggests that the variant originated in Spain during the summer. The earliest evidence of the new variant is linked to a super-spreading event among agricultural workers in the north-east of Spain. The variant moved into the local population, expanding quickly across the country, and now accounts for almost 80% of the sequences from Spain.

"It is important to note that there is currently no evidence the new variant's spread is due to a mutation that increases transmission or impacts clinical outcome," stresses Dr. Emma Hodcroft of the University of Basel, lead author of the study. The researchers believe that the variant's expansion was facilitated by loosening travel restrictions and social distancing measures in summer.

Similar pattern as in spring in Spain

"We see a similar pattern with this variant in Spain as we did in the spring," advises Professor Iñaki Comas, co-author on the paper and head of the SeqCOVID-Spain consortium. "One variant, aided by an initial super-spreading event, can quickly become prevalent across the country."

From July, 20A.EU1 moved with travelers as borders opened across Europe, and has now been identified in twelve European countries. It has also been transmitted from Europe to Hong Kong and New Zealand. While initial introductions of the variant were likely from Spain directly, the variant may then have continued to spread onward from secondary countries.

Currently, 20A.EU1 accounts for 90% of sequences from the UK, 60% of sequences from Ireland, and between 30 and 40% of sequences in Switzerland and the Netherlands. This makes this variant currently one of the most prevalent in Europe. It has also been identified in France, Belgium, Germany, Italy, Latvia, Norway, and Sweden.

Travel facilitated the spread

Genetic analysis indicates that the variant travelled at least dozens and possibly hundreds of times between European countries. "We can see the virus has been introduced multiple times in several countries and many of these introductions have gone on to spread through the population," says Professor Tanja Stadler of ETH Zürich, one of the study's principal investigators, "This isn't a case of one introduction just happening to do well."

Though the rise in prevalence of 20A.EU1 corresponds with the increasing number of cases observed in many European countries this autumn, the study's authors caution against interpreting the new variant as a cause for the rise in cases. "It is not the only variant circulating in recent weeks and months," says Professor Richard Neher of the University of Basel, one of the study's principal investigators. "Indeed, in some countries with significant increases in COVID-19 cases, like Belgium and France, other variants are prevalent."

Analysis of the summertime SARS-CoV-2 prevalence in Spain and travel data show that these factors may explain how 20A.EU1 spread so successfully. Spain's relatively high number of cases and popularity as a holiday destination may have allowed multiple opportunities for introductions, some of which may have grown into larger outbreaks through risky behaviors after returning home.

The study's authors highlight the importance of evaluating how border controls and travel restrictions worked in containing SARS-CoV-2 transmissions over the summer, and the role travel has played. "Long-term border closures and severe travel restrictions aren't feasible or desirable," explains Hodcroft, "but from the spread of 20A.EU1 it seems clear that the measures in place were often not sufficient to stop onward transmission of introduced variants this summer. When countries have worked hard to get SARS-CoV-2 cases down to low numbers, identifying better ways to 'open up' without risking a rise in cases is critical."

Assessing the phenotype of the new variant

The new variant was first identified by Hodcroft during an analysis of Swiss sequences using the 'Nextstrain' platform, developed jointly by the University of Basel and the Fred Hutchinson Cancer Research center in Seattle, Washington. 20A.EU1 is characterized by mutations that modify amino-acids in the spike, nucleocapsid, and ORF14 proteins of the virus.

Though the present state of knowledge does not indicate 20A.EU1's spread was due to a change in transmissibility, the authors are currently working with virology labs to examine any potential impact the spike mutation, known as S:A222V, may have on the SARS-CoV-2 virus' phenotype. They also hope to soon receive access to data that would allow them to assess any clinical implications of the variant.

Also, the study's authors emphasize the importance of monitoring the rise of new variants like 20A.EU1 closely: "It is only through sequencing the viral genome that we can identify new SARS-CoV-2 variants when they arise and monitor their spread within and between countries," adds Neher, "But the number of sequences we have varies widely between countries, and we might be able to identify rising variants sooner with faster and more regular sequencing efforts across Europe."

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More information: Emma B Hodcroft et al. Emergence and spread of a SARS-CoV-2 variant through Europe in the summer of 2020, (2020). DOI: 10.1101/2020.10.25.20219063

Provided by University of Basel