Culture

Eating sardines regularly helps prevent type 2 diabetes

The health benefits of sardines and oily fish are widely known: their high levels of unsaturated fats help to regulate cholesterol levels and prevent the onset of cardiovascular diseases. However, the benefits don't end there. A study led by Diana Diaz Rizzolo, lecturer and researcher of the Universitat Oberta de Catalunya's (UOC) Faculty of Health Sciences and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), has discovered that the regular consumption of sardines helps to prevent the onset of type 2 diabetes. Nutrients found in high quantities in sardines - such as taurine, omega 3, calcium and vitamin D - help to protect against this disease which, according to CIBERDEM's Di@betes study, affects around 14% of the Spanish population over the age of 18.

"Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes. This is a huge scientific discovery. It is easy to recommend this food during medical check-ups, and it is widely accepted by the population", explained Diana D. Rizzolo.

Researchers from the Diabetes and Obesity Research Laboratory and the Primary Care Research Group, both from IDIBAPS; the IMIM, the Fatty Acid Research Institute (EUA), the Universitat de Barcelona, CIBERDEM and the Department of Endocrinology and Nutrition of the Hospital Clínic de Barcelona also participated in the research project. The results of the study were published openly in the prestigious Clinical Nutrition journal.

Two cans of sardines a week

The study enrolled 152 patients aged 65 years and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dl) from three different Primary Care centres. All of these patients were put on a nutritional programme that sought to reduce the risk of them developing the disease, but only the intervention group added 200 grams of sardines to their diet every week (two cans of sardines in olive oil). To facilitate this consumption, and with thanks to the Alicia Foundation, these study participants received a list of recipes including canned sardines. Participants were advised to eat the sardine whole, without removing the bones, as these are particularly rich in calcium and vitamin D.

Of the group that did not include sardines in their diet, 27% of the members were at a high risk of suffering from diabetes (measured via the FINDRISC questionnaire). After one year, 22% found themselves in the same category. Of the group that included sardines in their diet, 37% of the members were at a high risk of suffering from diabetes at the start of the study. After one year, only 8% remained at a very high risk. Improvements were also seen in other important biochemical parameters, such as a reduced insulin resistance index (HOMA-IR), increased "good" cholesterol (HDL), increased hormones that accelerate the breakdown of glucose (adiponectin) and decreased triglycerides and blood pressure, amongst others.

The study was carried out on participants aged 65 and above because the incidence of diabetes is much higher in elderly people than in the young population: "As we get older, restrictive diets (in terms of calories or food groups) can help to prevent the onset of diabetes. However, the cost-benefit ratio is not always positive, as we found in other studies", stated doctor Rizzolo. "However, the results lead us to believe that we could obtain an equally significant preventive effect in the younger population."

The protective role of food, but not of supplements

The fact that foods such as sardines - which are rich in taurine, omega 3, calcium and vitamin D - have a clear protective effect against the onset of diabetes does not mean that taking these supplements in isolation will have the same effect. "Nutrients can play an essential role in the prevention and treatment of many different pathologies, but their effect is usually caused by the synergy that exists between them and the food that they are contained in. Sardines will therefore have a protective element because they are rich in the aforementioned nutrients, whereas nutrients taken in isolation in the form of supplements won't work to the same extent", claimed Rizzolo.

Researchers have begun studying the effect of sardines on the intestinal microbiota in a second phase of the study, "since it affects the regulation of many biological process, and we need to understand if they have played a part in this protective effect against diabetes 2", she added. They have also initiated studies on the modulation of the expression of certain genes related to inflammation, which could play a role in the onset of diabetes 2 and various other diseases.

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Universitat Oberta de Catalunya (UOC)

Lancaster University team's 'eggstraordinary' paper revealed at major conference

image: Image shows one of the specially-designed rooms in 'The Egg', where participants are invited to interact with each other and their surroundings. The authors' avatars can be seen in the bottom left of the image.

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Dr Miriam Sturdee, Lancaster University

The world's first-ever 'academic paper which is not a paper' is due to be presented by a Lancaster University research team at the premier international conference on human-computer interaction.

Dr Joseph Lindley, a researcher at Lancaster University's ImaginationLancaster design-led research laboratory, Dr Miriam Sturdee, from the University's School of Computing and Communications, Senior Research Associate Dr David Green and Research Associate Hayley Alter have been invited to take part in the 2021 ACM CHI Virtual Conference on Human Factors in Computing Systems in May.

Using the innovative 'Gather Town' online video-calling and conferencing platform, they have experimented in setting up a conference paper as an interactive but virtual space.

The unique part of this type of video-calling is the ability for multiple people to hold separate conversations in parallel, and to walk in and out of those conversations just as easily as they would in a real room.

"So, with this, you can actually walk 'in' to the paper. Each 'room' is a page or section within the paper where you can read the text, but also talk to other conference delegates about it," explains Dr Lindley, a lecturer in design research.

Quirky egg-themed graphics (eggs are used as they are a symbol of new life) give the 'page-spaces' character as different destinations, while the menu page is inspired by Piet Mondrian's map-like painting, 'Broadway Boogie Woogie'.

"The beauty with this approach is that you don't have to read from start to finish, you can experience it in any order you like," Dr Lindley explains.

Instead of hearing a formal presentation, participants will be asked to don their choice of avatar before being invited into the two-dimensional spaces to meet, chat and 'explore' the egg.

"This is the world's first paper that is not an actual paper," says Dr Lindley. "It's a video conferencing platform that hosts 20 interconnected 'rooms' with a 'poster' in each one. People can mill about and discuss each poster and, by leaving additional comments they can effectively help to keep 'writing' the paper as they go.

"This prototype is about collapsing barriers between video conferencing, research conferences, and publication traditions. It's about exploring creative ways of using technology and bringing them together."

"It's looking at how the research landscape will evolve. The pandemic is making people look at that again."

"We are now in a state of comprehensive flux as 'new normals' emerge, begin to solidify, and may evolve into an--as yet undetermined--futures.

"This 'not paper' is a facet and exploration of that flux as it relates to publication and conference culture, video conferencing systems, and how we both conduct, and share, research."

Step inside the paper if you dare...

https://gather.town/app/EpkqTfKctHPjRS0m/the_egg (NOTE: Please use a Chrome or Firefox based browser).

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Lancaster University

Better healthcare guidance needed for trans people

Clinical practice guidelines for dealing with the physical and mental health of transgender people highlight the current lack of a solid research base which must be improved, according to a new study published in the journal BMJ Open.

A team of researchers from Anglia Ruskin University (ARU) and King's College London searched world literature for all international clinical practice guidelines on the healthcare needs of gender minority and trans people.

Results showed that higher quality guidelines tended to focus mainly on HIV, and most others were on transition-related interventions. There were noticeable gaps in the topics of guidelines, with none addressing primary care or more general health needs of gender minority and trans people. There was little information on mortality and quality of life, and there was no patient-facing material.

Sex hormones in trans people can affect susceptibility to some conditions, including various cancers. However, the authors found little research on how much these hormones affect rates and treatment regimens. There was also no advice on how these hormones affect rates, hospitalisations and mortality due to COVID-19.

Researchers concluded that gaps can be filled by better research, resulting in improved healthcare guidance for gender minority/trans people.

This was the first review of its kind to examine international clinical practice guidelines addressing gender minority/trans health.

Catherine Meads, Professor of Health at ARU and senior author of the paper, said: "We were pleased to find high quality guidelines on HIV from the World Health Organisation, but disappointed there was little else on the long term physical and mental health of trans people.

"There are clear gaps in clinical practice guidance related to gender minority and trans people, and as such clinicians should proceed with caution and explain any uncertainties to patients, who should also be engaged in the process of updating practice guidelines. More needs to be done to ensure that patient-facing material relevant to trans people is made available.

"We've presented the study at the main international specialist societies, who are due to update their guidance, and we hope this will encourage them to aim as high as the WHO."

Sara Dahlen, of King's College London, who co-ordinated the project, said: "We didn't know what we'd find until we looked. We hope future guidelines for trans and gender minority people will look to the examples of high-quality so they can improve healthcare."

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Anglia Ruskin University

Researchers find association between financial strain due to COVID-19 and depression

image: Ran Barzilay, MD PhD, child and adolescent psychiatrist at Children's Hospital of Philadelphia and research scientist at the Life Brain Institute.

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CHOP

Philadelphia, May 6, 2021--Researchers have found an independent association between COVID-19-related income loss and financial strain and depression, according to the latest study from the COVID-19 Resilience Project, run by the Lifespan Brain Institute (LiBI) of Children's Hospital of Philadelphia (CHOP) and Penn Medicine. This association was found in two separate cohorts - one primarily in the United States and one in Israel - and the depressive symptoms worsened over time in participants who were hit financially, above and beyond pandemic-related anxiety. The findings were published today in the Journal of Affective Disorders.

"This study is an important first step in understanding the unique association between pandemic-related income loss and financial strain and depression, which we observed in two entirely unrelated cohorts," said senior author Ran Barzilay, MD, PhD, an assistant professor at LiBI. "Our findings may suggest that the 'financial COVID-19' could have a serious impact on mental health, and this is especially relevant as the post-vaccine world faces the challenges of COVID-19's long-term financial impact."

To analyze the link between financial strain and mental health during the pandemic, researchers at LiBI collected data longitudinally from participants via a survey that asked questions related to COVID-19-related worries, financial changes (like losing a job or getting a pay cut), and mental health. In parallel, a separate, similar study was conducted at the Sheba Medical Center in Israel, led by Nimrod Hertz-Palmor. Participants in the first, predominately American cohort provided initial answers between April 6 and May 5, 2020 and provided follow up answers between May 12 and June 21, 2020. The Israeli cohort responded between March 18 and 26, 2020 and again between April 22 and May 7, 2020.

Across these two independent studies, the researchers found a specific link between financial factors and depression, above and beyond anxiety, which was greater than the association between COVID-19 health-related worries and depression. The researchers also found that participants from both cohorts who reported a decrease in their income over the study period reported an increase in depressive symptoms over time.

"The fact that the findings were similar in two different cohorts - from two different cultures, using different research measures - supports the generalizability of these findings and may suggest that the financial COVID-19 is a specific risk factor for depression globally," Barzilay said.

Notably, the findings were independent of pre-COVID-19 income, suggesting people from all backgrounds who report stress about their financial situation during the pandemic, including those with high income, are vulnerable to the effects of the financial crisis on mental health. Although anxiety also increased with prolonged income loss, the association did not increase to the same extent.

"Given what we know about the connection between depression and suicidality, healthcare providers should actively probe patients for a change for the worse in their income and ask them specifically about their stress regarding the financial impact of COVID-19, as these individuals are at higher risk for mental health deterioration," Barzilay suggests. "We have collected similar data at five different time points from April 2020 to April 2021, and we will continue to study this issue to better understand what makes up resilience during the pandemic and how we can identify and support those at risk for adverse mental health outcomes."

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Children's Hospital of Philadelphia

Defective epithelial barriers linked to two billion chronic diseases

image: Straight and clear epithelial barrier of healthy bronchial epithelial cells (at the top) and leaky and damaged asthmatic epithelial cells (at the bottom).

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(Image: Cezmi Akdis)

Epithelial cells form the covering of most internal and external surfaces of the human body. This protective layer acts as a defense against invaders - including bacteria, viruses, environmental toxins, pollutants and allergens. If the skin and mucosal barriers are damaged or leaky, foreign agents such as bacteria can enter into the tissue and cause local, often chronic inflammation. This has both direct and indirect consequences.

Chronic diseases due to defective epithelial barriers

Cezmi Akdis, Director of the Swiss Institute of Allergy and Asthma Research (SIAF), which is associated with the University of Zurich (UZH), has now published a comprehensive summary of the research on epithelial barrier damage in Nature Reviews Immunology. "The epithelial barrier hypothesis proposes that damages to the epithelial barrier are responsible for up to two billion chronic, non-infectious diseases," Professor Akdis says. In the past 20 years, researchers at the SIAF alone published more than 60 articles on how various substances damage the epithelial cells of a number of organs.

Rise in allergic and autoimmune conditions

The epithelial barrier hypothesis provides an explanation as to why allergies and autoimmune diseases have been increasing for decades - they are linked to industrialization, urbanization and westernized lifestyle. Today many people are exposed to a wide range of toxins, such as ozone, nanoparticles, microplastics, household cleaning agents, pesticides, enzymes, emulsifiers, fine dust, exhaust fumes, cigarette smoke and countless chemicals in the air, food and water. "Next to global warming and viral pandemics such as COVID-19, these harmful substances represent one of the greatest threats to humankind," emphasizes Akdis.

Asthma, Alzheimer's et al.

Local epithelial damage to the skin and mucosal barriers lead to allergic conditions, inflammatory bowel disorders and celiac disease. But disruptions to the epithelial barrier can also be linked to many other diseases that are characterized by changes in the microbiome. Either the immune system erroneously attacks "good" bacteria in healthy bodies or it targets pathogenic - i.e. "bad" - invaders. In the gut, leaky epithelial barriers and microbial imbalance contribute to the onset or development of chronic autoimmune and metabolic diseases such as diabetes, obesity, rheumatoid arthritis, multiple sclerosis or ankylosing spondylitis. Moreover, defective epithelial barriers have also been linked to neurodegenerative and psychiatric diseases such as Parkinson's disease, Alzheimer's disease, autism spectrum disorders and chronic depression, which may be triggered or aggravated by distant inflammatory responses and changes in the gut's microbiome.

Prevention, intervention - and more research

"There is a great need to continue research into the epithelial barrier to advance our understanding of molecular mechanisms and develop new approaches for prevention, early intervention and therapy," says Akdis. Novel therapeutic approaches could focus on strengthening tissue-specific barriers, blocking bacteria or avoiding colonization by pathogens. Other strategies to reduce diseases may involve the microbiome, for example through targeted dietary measures. Last but not least, the focus must also be on avoiding and reducing exposure to harmful substances and developing fewer toxic products.

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University of Zurich

Many consumers misinterpret food date labels, yet use them with confidence

image: Example of an illustrated message.

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Journal of Nutrition Education and Behavior

Philadelphia, May 6, 2021 - Misunderstanding food date labeling is common and educational communications are needed to improve consumer understanding, according to a new study in the Journal of Nutrition Education and Behavior, published by Elsevier.

Does it mean "spoiled - throw it out," or "might not taste as good as it could anymore?" Food date labels (e.g., "USE By August 16") can play an important role in helping consumers make informed decisions about food, and ultimately prevent unsafe consumption and waste of food. Researchers surveyed 2,607 adults in the United States to assess consumer understanding of the streamlined 2-date labeling system and explore the relative effectiveness of educational messages in increasing understanding.

"Our study showed that an overwhelming majority of consumers say that they use food date labels to make decisions about food and say they know what the labels mean," said Catherine Turvey, MPH, Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA. "Despite confidently using date labels, many consumers misinterpreted the labels and continued to misunderstand even after reading educational messaging that explained the labels' meaning."

Less than half (46 percent) of study respondents knew that the "BEST If Used By" label specifically indicates that food quality may deteriorate after the date on the label. Less than one-quarter (24 percent) of study respondents knew that the "USE By" label means that food is not safe to eat after the date on the label.

Researchers explored if framing the messages with values like saving money or avoiding waste, would impact the effectiveness of messages at increasing consumer understanding. None of the seven value frames tested was significantly more effective at increasing understanding than another, but all messages significantly increased consumer's general understanding of the labels.

After viewing educational messages, 37 percent of consumers still did not understand the specific meaning of the "BEST If Used By" label and 48 percent did not understand the specific meaning of the "USE By" label.

"Responses to the survey suggest that date labels are so familiar that some consumers believe they are boring, self-explanatory, or common sense despite misunderstanding the labels," said Ms. Turvey. "Unwarranted confidence and the familiarity of date labels may make consumers less attentive to educational messaging that explains the food industry's labeling system."

Future communication campaigns will have to capture the attention of people who think they already know what date labels mean, find the information tedious, or are satisfied with a rough understanding of labels. Educating consumers about the meaning of the labels has growing implications for food waste and food safety as the 2-date labeling system becomes more widely adopted and gains support from non-profits and government institutions.

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Elsevier

Achieving high COVID-19 vaccine coverage levels by summer can prevent millions of cases

(MAY 6, 2021) New York, NY - With around 30 percent of the U.S. population now fully vaccinated, the rate of daily vaccinations has started to slow, raising concerns that greater efforts and investments may be needed to reach higher coverage levels. A study published in the Journal of Infectious Diseases on May 6 shows the lives, hospitalizations, and costs that can be saved by even relatively small increases in vaccination coverage and reaching higher vaccination coverage levels sooner (e.g., by the end of the summer versus fall/winter).

The study was led by researchers from PHICOR (Public Health Informatics, Computational, and Operations Research) at CUNY Graduate School of Public Health & Health Policy, the National School of Tropical Medicine at Baylor College of Medicine, and Johns Hopkins Center for Health Security. The team developed a computer simulation model of the entire U.S. and the spread of the COVID-19 coronavirus throughout the country. Using the model, the team could simulate vaccinating different proportions of the population at different rates with different types of COVID-19 vaccines. Like real people, each of these virtual people could become infected with the virus and develop different symptoms over time and, depending upon the severity of those symptoms, visit clinics, emergency departments, or hospitals. These in turn would have associated costs, allowing the tracking of various medical costs and productivity losses.

The study showed that going from a 30 percent vaccination coverage to a 40 percent coverage could save 24.3 million cases and $33.1 billion in direct medical costs and productivity losses. Going from a 50 percent to 70 percent coverage could save 9.5 million cases and 10.8 billion in direct medical costs and productivity losses.

In fact, even relatively small increases in vaccine coverage can prevent thousands of cases and lives and hundreds of millions in costs. For example, results from the model showed each 1 percent increase between 40 and 50 percent of the U.S. population being vaccinated by the fall can prevent 1.6 million cases, 60,190 hospitalizations, and 7,100 deaths and save $674.2 million in direct medical costs and $1.5 billion in productivity losses. Each 1 percent increase between 50 and 70 percent can prevent 473,900 cases, 17,600 hospitalizations, 2,000 deaths, and 537 million in direct medical costs and productivity losses.

The study also emphasized the importance of reaching higher coverage levels as soon as possible. For example, speeding up vaccinations to reach a 50 percent coverage by July 2021 instead of October 2021 could save an additional 5.8 million cases, 215,790 hospitalizations, 26,370 deaths, $3.5 billion in direct medical costs, and $4.3 billion in productivity losses.

Results suggested that getting as many people fully vaccinated as possible before the early winter would be particularly important. The model incorporated changes in the transmission of the virus that occurred with the changing seasons in 2020, when surges occurred during the winter months, and projected what may happen in 2021. For example, when 50 percent of the U.S. population is vaccinated by October 2021 instead of the end of December 2021, 6.6 million cases, 252,260 hospitalizations, 29,380 deaths, $4.0 billion direct medical costs, and $8.0 billion productivity losses were saved.

"The results of this study can give policymakers, community leaders, and other decision makers a sense of how much can be invested into vaccinating those who may be harder to get vaccinated," explained Sarah Bartsch, MPH, the study's lead author and project director for PHICOR. "Such investments may end up paying for themselves. For example, the potential cost savings exceed the $1.5 billion Biden Administration community outreach and media campaign. Our results show that increasing total vaccination coverage by just one percent could cover the costs of this effort."

"The longer it takes to reach higher vaccination coverage levels and herd immunity thresholds, the more the virus can spread," said Bruce Y Lee, senior author of the study, executive director of PHICOR, and CUNY SPH professor. "It may be particularly important to reach higher coverage levels before the late fall to prevent another winter surge."

Additionally, the study showed how increasing vaccination coverage levels was more valuable than using vaccines with higher effectiveness. For example, we found that achieving a 70 percent coverage with a 70 percent effective vaccine can save 2.1 million cases and 5.5 billion in medical costs and productivity losses compared to achieving a 50 percent coverage with a 90 percent effective vaccine over the same period. This shows the value of using all Covid-19 vaccines that are available to get more people vaccinated as soon as possible, rather than focusing only on those with the highest effectiveness. Moreover, as more contagious variants circulate, potentially decreasing the effectiveness of the existing Covid-19 vaccines, this can help address concerns about continuing with the existing vaccines or waiting for an updated version.

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CUNY Graduate School of Public Health and Health Policy

Fear of losing health insurance keeps 1 in 6 workers in their jobs

image: The survey finds the fear is even more pronounced among Black workers, who are 50% more likely to remain in an unwanted job than their White and Hispanic counterparts (21% to 14% and 16%, respectively).

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West Health-Gallup Survey, March 2021

WASHINGTON, DC - MAY 6, 2021 - One out of every six adult workers (16%) in the United States are staying in jobs they might otherwise leave out of fear of losing their employer-sponsored health insurance, according to a new West Health-Gallup survey of more than 3,800 U.S. adults.

The survey finds the fear is even more pronounced among Black workers, who are 50% more likely to remain in an unwanted job than their White and Hispanic counterparts (21% to 14% and 16%, respectively).

But the most likely to stay in a job they would rather leave are those workers in households earning less than $48,000 a year -- roughly 3 in 10 (28%) say they will not leave and risk losing their health benefits. Workers in lower income households are nearly three times more likely to stay in an unwanted job than are workers living in households earning at least $120,000 per year. According to a report by the Congressional Research Service, 37% of U.S. households earned less than $50,000 in 2019. Approximately 158 million people receive health insurance via their own employer or via the employer of a household member.

"Healthcare costs have become so high that many Americans are unwilling to risk any disruption in their coverage even if that means higher and higher premiums and deductibles and sticking with a job they may not like," said Tim Lash, chief strategy officer for West Health, a family of nonprofit and nonpartisan organizations dedicated to lowering healthcare costs to enable successful aging. "Americans are increasingly concerned that they will get priced out of the U.S. healthcare system and are struggling to hang on in any way they can."

Earlier this year, an estimated 46 million or 18% of the U.S. population reported that they could not afford healthcare if they needed it today. In this latest survey, three times as many Americans or approximately135 million adults, are worried that they will eventually be priced out of healthcare if they are not already.

Specifically, more than half of respondents report they are "concerned" or "very concerned" the cost of healthcare services (53%) and prescription drugs (52%) will become unaffordable. More Americans worry about rising healthcare costs even more than losing one's home (25%) or job (29%).

Black and Hispanic adults have modestly elevated concerns about the rising costs of healthcare compared to White adults. Two-fifths (42%) of respondents, in turn, report concern that they would not be able to pay for a major health event, including 49% of Hispanic adults and 47% of Black adults.

Majorities Support Select Government Action to Contain Cost of Care

Substantial concerns about the rising cost of care and medicine likely play a role in explaining why most respondents in the survey support the federal government taking a bigger role in lowering healthcare costs regardless of their political affiliation, racial background, or type of insurance.

About three-quarters favor setting limits on prescription drug price increases (77%), capping hospital prices in areas with few or no other hospitals (76%), and having the government negotiate lower prices for some high-cost drugs without lower-priced alternatives (74%).

Another 65% support placing government limits on prices for out-of-network care (65%). Those with private insurance were just as likely as those on public health plans including Medicare and Medicaid to favor government intervention.

"Polling data from West Health and Gallup continue to demonstrate that most Americans are supportive of an elevated government role in curtailing the rising costs of care," said Dan Witters, Gallup senior researcher. "How elected officials respond to this is unfolding, but there seems to be substantive public support for a number of specific proposals that are on the table."

This latest West Health-Gallup survey was conducted by web between March 15 and March 21, 2021 with 3,870 adults, ages 18+, living in all 50 U.S. states and the District of Columbia as part of the Gallup Panel. For results based on this sample of national adults, the margin of sampling error at the 95% confidence level is +2.2 percentage points for response percentages around 50% and is +1.3 percentage points for response percentages around 10% or 90%, design effect included. For reported sub-groups, the margin of error will be larger, typically ranging from ±3 to ±4 percentage points.

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West Health Institute

The origin of reproductive organs

image: Studying embryonic development in mice and monkeys, researchers led by Kotaro Sasaki of Penn Vet discovered that a layer of cells known as the posterior intermediate mesoderm (far left) gives rise to the bipotential gonad (far right) early on in mammalian development. The bipotential gonad typically develops into either ovaries or testes. Understanding the molecular details of this process could help in intervening in disorders of sexual development.

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Courtesy of Kotaro Sasaki

Early in human development, during the first trimester of gestation, a fetus may have XX or XY chromosomes that indicate its sex. Yet at this stage a mass of cells known as the bipotential gonad that ultimately develops into either ovaries or testes has yet to commit to its final destiny.

While researchers had studied the steps that go into the later stages of this process, little has been known about the precursors of the bipotential gonad. In a new study published in Cell Reports and co-led by Kotaro Sasaki of Penn's School of Veterinary Medicine, an international team lays out the detailed development of this key facet of sexual determination in two mammalian models.

"Using single-cell transcriptome data, we can get a lot of information about gene expression at each developmental stage," says Sasaki. "We can define what the default process is and how it might go awry in some cases. This has never been done in traditional developmental biology. Now we can understand development in molecular terms."

Disorders of sex development (DSD) occur when internal and external reproductive structures develop differently from what would be expected based on an individuals' genetics. For example someone with XY chromosomes might develop ovaries. These conditions often affect fertility and are associated with an increased risk of germ cell tumors.

"These disorders oftentimes create psychological and physical distress for patients," Sasaki says. "That's why understanding gonadal development is important."

To understand atypical development, Sasaki and colleagues in the current study sought to layout the steps of typical development, working with a mouse model and a monkey model.

The researchers began by examining mouse embryos throughout embryonic development, using molecular markers to track the location of different proteins suspected to be involved in the formation of reproductive structures. They noticed that by day nine of a mouse's embryonic development, a structure called the posterior intermediate mesoderm (PIM) lit up brightly with the marker for a gene critical to the development of gonads, kidneys, and the hormone-producing adrenal glands, which are located adjacent to the kidneys.

Zeroing in on the PIM and its progeny cells, the team found that, by day 10.5, these also expressed a marker known to be associated with the bipotential gonad.

"People have previously studied the origin of the urogenital organs and the kidney and based on that believed that their origins were very close," Sasaki says. "So our hypothesis was that the PIM was the origin of the gonads as well as the kidneys."

To identify the origin of the gonad, they performed lineage tracing, in which scientists label cells in order to track their descendents, which indeed supported the connection between the PIM and the gonads.

To further confirm that the PIM played a similar role in an organism closer to humans in reproductive biology, the researchers made similar observations in embryos from cynomolgus monkeys. Though the developmental timing was different from the mouse, as was expected, the PIM again appeared to give rise to the bipotential gonad.

Digging even deeper into the molecular mechanism of the transition between the PIM and bipotential gonad, the researchers used a cutting-edge technique: single-cell sequencing analysis, whereby they can identify which genes are being turned on during each developmental stage.

Not only were they able to identify genes that were turned on--many of which had never before been associated with reproductive development--but they observed a transition state between the PIM and bipotential gonad, called the coelomic epithelium. Comparing the mice and monkey embryos, the researchers came up with a group of genes that were conserved, or shared between the species. "Some of these genes are already known to be important for the development of mouse and human ovaries and testes," Sasaki says, "and some have been implicated in the development of DSDs."

He notes that in roughly half of patients with DSDs, however, the genetic cause is unknown. "So this database we're assembling may now be used to predict some additional genes that are important in DSD and could be used for screening and diagnosis of DSDs, or even treatment and prevention."

The study also illuminated the relationship between the origin of the kidneys, adrenal glands, and gonads. "They all originate from the PIM, but the timing and positioning is different," Sasaki says.

The adrenal glands, he says, develop from the anterior portion of the PIM, or that section closer to the head and arise early, while the kidney arises later from the posterior portion of the PIM. The gonadal glands span the PIM, with some regions developing earlier and others later.

In future studies, Sasaki and colleagues would like to continue teasing out the details and stages of gonadal development. Sasaki's ultimate goal is to coax a patient's own stem cells to grow into reproductive organs in the lab.

"Some patients with DSDs don't have ovaries and testes, and some cancer patients undergo chemotherapy and completely lose their ovary function," Sasaki says. "If you could induce a stem cell to grow into an ovary in the lab, you could provide a replacement therapy for these patients, allowing them to regain normal hormone levels and even fertility. With a precise molecular map to the developing gonad in hand, we are now one step closer to the this goal."

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University of Pennsylvania

Not so wicked after all?

Although the fairy tale of the wicked stepmother is a tale as old as time, the effects of blending children with their new stepfamilies may not be as grim as once thought.

In fact, new research shows that stepchildren are not at a disadvantage compared to their peers from single-parent households and actually experience better outcomes than their halfsiblings -- good news for the more than 113 million Americans that are part of a steprelationship.

Led by East Carolina University anthropologist Ryan Schacht and researchers from the University of Utah, the study, "Was Cinderella just a fairy tale? Survival differences between stepchildren and their half-siblings," is available in the May edition of the Philosophical Transactions of the Royal Society B.

The study challenges the "Cinderella effect" theory. The effect contends that conflict within stepfamilies over physical, financial and emotional resources leads to higher mortality risks for stepchildren, and is a main factor in higher rates of abuse and neglect. The phenomenon suggests that stepparents play a major role in this abuse, hoarding resources for their biological children and leading to negative outcomes for stepchildren.

Schacht proposes that previous studies have placed blame for the negative outcomes associated with parental loss on stepparents yet have done so through an an "apples-to-oranges comparison." Specifically, they compare of the long-term outcomes of children who have suffered trauma like parental loss versus children from stable households. When the team compared stepchild outcomes more appropriately among those children who too have experienced the economic and emotional hardships associated with parental loss, they found no difference. Specifically, the introduction stepparenents did not increase stepchild mortality.

"The idea of a stepparent, especially the stepmother, as being an agent of evil seems to be a story as old as time," Schacht said. "It's easy to sell the Cinderella effect's result because we've been told these stories about the problems that stepfamilies experience for hundreds of years.

"We're not denying that some stepchildren suffer," he said. "However, if we truly believe it is the stepparent that is the source of negative outcomes for a stepchild, then we need to compare similar environments and experiences. A child that hasn't lost a parent through death or divorce hasn't experienced the same trauma that a stepchild has; comparing those two experiences and blaming the stepparent for diverging outcomes isn't a fair comparison."

The study compared the mortality of stepchildren whose parents remarried after the death of a spouse to children whose parents did not remarry and found three key findings:

* Parental mortality has a negative effect on children under 18 years old, especially for infants losing a mother;

* Children whose parents remarried after the loss of a spouse did not suffer a mortality rate any greater than children whose parents did not remarry; and

* Stepchildren received a protective effect when a halfsibling was introduced to their new family.

"The metrics of what makes a family successful -- household stability, relationship stability and economic stability -- are achieved by stepparents investing in their stepchildren to make that a reality. Coming in with an antagonistic approach doesn't make sense if stepparents want their relationship to succeed."

The research team analyzed a data set of more than 400,000 children from Utah from 1847-1940. Schacht said the time period provided an opportunity to analyze stepchild mortality rates in families during a natural fertility period where families were larger in size and most stepfamilies were formed due to the death of a parent.

The study adds that children who have suffered parental loss have more in common with their peers from single-parent households, facing many of the same educational, economic and health care disparities.

Schacht hopes the study will shed a light on public policy funding for interventions for families that have suffered parental loss.

Credit: 
East Carolina University

Archaeal enzyme that produces membrane lipids is spectacularly promiscuous

image: This illustration shows the production of various cardiolipins and phospholipids by incorporation of environmental compounds as lipid head group.

Image: 
Marten Exterkate, University of Groningen

Cells of all life forms are surrounded by a membrane that is made of phospholipids. One of these are the cardiolipins, which form a separate class due to their unique structure. When studying the enzyme that is responsible for producing cardiolipins in archaea (single-cell organisms that constitute a separate domain of life), biochemists at the University of Groningen made a surprising discovery. A single archaeal enzyme can produce a spectacular range of natural and non-natural cardiolipins, as well as other phospholipids. The results, which show potential for biotechnological applications, were published in the Journal of Biological Chemistry.

The phospholipids that are most abundant in cell membranes contain a hydrophilic head to which two hydrophobic tails are connected. Cardiolipins - so-called because they were first identified in heart cells - are slightly different since they are made up of a single head group that is attached to four lipid tails. 'We know which enzymes are responsible for cardiolipin production in bacteria and eukaryotes, but not in archaea,' says Marten Exterkate, who is the first author of the JBC paper.

Odd head group

His interest in these cardiolipins stems from his work on a synthetic minimal cell. 'Our group at the University of Groningen focuses on cell membrane growth, based on the enzymatic production of new phospholipids from basic building blocks.' Since cardiolipins are present in cell membranes of organisms from all domains of life, they are desired components of the synthetic cell. Exterkate wanted to know which enzymes are responsible for cardiolipin production in archaea. 'The lipids that form the cell membrane of archaea are structurally different from those in the other two domains of life,' Exterkate explains. 'Furthermore, while the other domains have one dominant type of cardiolipin, archaea appear to produce different kinds of cardiolipins, with head groups that contain, for example, only a single negative charge or different kinds of sugars or sulphate groups. Currently, we know next to nothing about how they are synthesized.'

By searching the genomes of archaeal species, Exterkate found several gene candidates for cardiolipin synthase. The most promising one from the archaea Methanospirillum hungatei was expressed in a standard laboratory strain of the E. coli bacterium, and the resulting enzyme was isolated and characterized. 'When we mixed the enzyme with potential building blocks, it produced the expected cardiolipin species. But then we noticed something really surprising: another cardiolipin with a very odd head group.' This turned out to be a molecule from the buffer solution in which the reaction took place.

Alarm bells

'All the alarm bells started ringing,' Exterkate recalls. 'If the enzyme can incorporate this buffer molecule as a lipid head group, what else could it do?' As it turned out, the enzyme was able to produce all kinds of variant cardiolipins and other phospholipids, containing both natural and non-natural head groups. 'Some enzymes are promiscuous; they can use slightly different variants of their normal substrates. But this enzyme is promiscuous in the extreme.' It can produce lipids that, in bacterial cells, for example, require many different enzymes.

This is the first identified enzyme with the ability to produce an entire range of different cardiolipins. Exterkate: 'Other archaea have similar genes, which are probably also suited to producing different cardiolipins, indicating that the variety in archaeal cardiolipins could be synthesized by the same enzyme.' Apart from being a surprising discovery, the new enzyme could be interesting for the production of self-designed membranes. This is useful because head groups in membrane phospholipids affect the overall properties of the membrane and the function of enzymes that are incorporated in it. 'The biotechnology industry could perhaps use this enzyme to artificially engineer membranes for specific purposes,' says Exterkate.

Osmoregulation

The discovery of this promiscuous enzyme also raises the question of why archaeal cells need all these different cardiolipins. So far, the textbooks refer to cardiolipins as one particular molecule. It is becoming clear, though, that cardiolipins form a class of molecules. Exterkate and his colleagues suspect that the enzyme is involved in osmoregulation. 'Depending on the environment, the enzyme can switch the production towards different phospholipids and in doing so, alter the functionality of the membrane.'

The enzyme could also turn out to be a bonus for the synthetic cell that Exterkate and his colleagues are working on. 'We planned to produce a membrane with a minimalistic phospholipid composition, so we wouldn't need to add lots of genes for different enzymes. Now, we can potentially produce lots of different phospholipids using only a single enzyme.'

Reference: Marten Exterkate, Niels A.W. de Kok, Ruben L.H. Andringa, Niels H.J. Wolbert, Adriaan J. Minnaard, Arnold J.M. Driessen: A promiscuous archaeal cardiolipin synthase enables construction of diverse natural and unnatural phospholipids. Journal of Biological Chemistry, first online as accepted 20 April

Credit: 
University of Groningen

India's polio vaccination provides valuable insights for mass vaccination campaigns

image: As India urgently scales up its vaccination campaign for the COVID-19 virus, a new study which examined the country's successful program to eliminate polio provides guidance on how this and future mass immunization campaigns can be successful, especially in vaccinating hard to reach groups. The study, conducted by students and faculty with the Reach Alliance, a research initiative based at the University of Toronto's Munk School of Global Affairs & Public Policy, says that medicine alone is insufficient for the elimination of disease.

Image: 
Reach Alliance.

Lessons Learned from India's Polio Vaccination Program Provide Valuable Insights for Future Mass Vaccination Initiatives.

Toronto - As India urgently scales up its vaccination campaign for the COVID-19 virus, a new study which examined the country's successful program to eliminate polio provides guidance on how this and future mass immunization campaigns can be successful, especially in vaccinating hard to reach groups.

The study, conducted by students and faculty with the Reach Alliance, a research initiative based at the University of Toronto's Munk School of Global Affairs & Public Policy, says that medicine alone is insufficient for the elimination of disease.

The World Health Organization declared India polio-free in 2014. While the country had the medical ability to eliminate polio for decades, new managerial strategies were necessary to achieve polio elimination among India's hardest to reach, including within religious minorities and impoverished communities.

"We found that the barriers to vaccination were deeply rooted in larger issues of social trust and political vulnerability," says, Anita M. McGahan, University Professor and the George E. Connell Chair in Organizations & Society at the University's Rotman School of Management and Munk School. "Many of these same issues will need to be dealt with by governments and health agencies globally in order to vaccinate the most vulnerable today against COVID-19."

The study found that managerial strategies were necessary to achieve polio elimination among India's hardest to reach. Namely, these strategies were the bundling of basic healthcare services when marketing the vaccine, which tackled existing essential healthcare concerns in the communities; engaging stakeholders in vulnerable communities including religious leaders, local media outlets, employers of migrant workers, and private health providers; and, implementing accountability mechanisms among healthcare workers which improved the accuracy of both polio surveillance and vaccination data.

Credit: 
University of Toronto, Rotman School of Management

The COVID-19 pandemic: Even mild disease impacts mental health

May 6, 2021 -- A significant level of symptoms of depression, anxiety and post-traumatic stress may follow COVID-19 independent of any previous psychiatric diagnoses, according to new research by Columbia University Mailman School of Public Health with colleagues at Universidade Municipal de São Caetano do Sul in Brazil. Exposure to increased symptomatic levels of COVID-19 may be associated with psychiatric symptoms after the acute phase of the disease. This is the largest study to evaluate depressive, anxiety, and post-traumatic stress symptoms in tandem among patients who had mild COVID-19 disease. The findings published online in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry shed light on a significant subpopulation at risk for mental symptoms.

"These results are important because the vast majority of COVID-19 patients are classified as mild cases, facing long periods of at-home isolation," said João Mauricio Castaldelli-Maia, MD, PhD, NIDA-INVEST Postdoctoral Fellow in the Department of Epidemiology at Columbia Mailman School. "It is probable that the increased prevalence of psychiatric symptoms post-COVID-19 is a consequence of the psychological context of the disease, and patients should be closely monitored for the development of psychiatric symptoms after COVID-19 treatment discharge."

Nasal swabs were collected from residents within a section of Sao Paulo, Brazil, 18 years of age or older with suspected COVID-19 symptoms. Patients were tested at their homes under the supervision of trained healthcare personnel. Those who tested positive for COVID-19 -- with at least two of the following symptoms: fever, cough, sore throat, change in/loss of smell -- and were classified as mild cases -- were further assessed for the presence of psychiatric symptoms approximately two months later.

Significant levels of depressive, anxiety and post-traumatic stress symptoms were reported by 26 percent, 22 percent, and 17 percent, respectively. For comparison purposes, previous estimates of post-traumatic stress levels within Brazil were 8.5% demonstrating that the prevalence within individuals presenting with mild COVID-19 increased versus past estimates.

In general, survivors of critical illnesses have a high level of mental symptoms after the condition improves. Depression, anxiety and post-traumatic stress disorder are among the most reported psychiatric events in patients with these conditions, according to the researchers. The ongoing COVID-19 pandemic has disrupted the lives of many across the globe, resulting in an increased burden of physical and mental health consequences. Brazil, to date, is one of the most affected countries, reaching around 412,000 deaths by early May 2021.

"These findings echo warnings from the previous SARS outbreak, when survivors of SARS infections experienced increased psychological distress, persisting one year or more subsequent to the outbreak, and similar findings were observed following the occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2015," observed Silvia Martins, MD, PhD, associate professor of Epidemiology at Columbia Mailman School.

"Early mental health intervention such as psychotherapy and supportive groups could play an important role in preventing incident mental health problems for post-COVID sufferers," said Castaldelli-Maia. "While further investigations for the possible neurobiological mechanisms linking COVID-19 and mental health conditions are warranted, healthcare systems must prepare for an influx of individuals experiencing psychological distress as a result of the COVID-19 pandemic."

Credit: 
Columbia University's Mailman School of Public Health

Blocking viruses' exit strategy

image: Marburg virus-like-particles (in green, which are not infectious) "bud," or exit from the surface of a host cell. A host protein (in yellow) helps the VLPs bud. Research by Penn Vet researchers and colleagues have identified a compound that can reduce the ability of the Marburg virus to spread in an animal model by blocking the host-viral interaction.

This image was obtained from the PennVet Microscopy Core Facility directed by Dr. Bruce Freedman and managed by Dr. Gordon Ruthel.

Image: 
Penn Vet Microscopy Core Facility

The Marburg virus, a relative of the Ebola virus, causes a serious, often-fatal hemorrhagic fever. Transmitted by the African fruit bat and by direct human-to-human contact, Marburg virus disease currently has no approved vaccine or antivirals to prevent or treat it.

A team of researchers is working to change that. In a new paper in the journal Antimicrobial Agents and Chemotherapy, investigators from Penn's School of Veterinary Medicine, working together with scientists from the Fox Chase Chemical Diversity Center and the Texas Biomedical Research Institute, report encouraging results from tests of an experimental antiviral targeting Marburg virus. The compound blocks the virus from departing infected cells, thus putting the brakes on the spread of infection. Their findings are the first to show that this novel class of inhibitors can be effective against the infection in an animal model.

In addition, due to possible similarities in virus-host interactions between Marburg and SARS-CoV-2, the team has conducted experiments on the culprit behind the coronavirus pandemic. While preliminary and thus-far-unpublished, their initial tests show signs of promise.

"It really is exciting," says Ronald Harty, a co-corresponding author of the research and a professor at Penn Vet. "These viruses are quite different but may be interacting with the same host proteins to control efficient egress and spread, so our inhibitors may be able to block them both."

While many antivirals target the virus itself, the drug candidates that Harty and colleagues have been developing for years are known as "host-oriented." They prevent virus-host interactions by blocking the proteins in host cells that viruses hijack during late stages of infection.

Not only does this approach help avoid the likelihood that a virus would evolve to resist such a therapy, but it also increases the chance that a drug could be used against multiple viruses, as many rely on the same host cell machinery to reproduce and spread.

The Marburg and Ebola viruses use the VP40 protein to interact with a host protein called Nedd4 to complete the process of "budding" off a host cell. This stage of infection, which is key to viral spread, is the one the research team has targeted.

In previous studies, they had tested a variety of small molecule inhibitors of this process using laboratory tests that relied on non-infectious and more-benign viral models. Those assays helped them land on a leading candidate, FC-10696, for further study.

In the current work, they zeroed in on this candidate with rigorous evaluations. First, they tested the inhibitor to ensure it would be safe and retained long enough in the body to have an effect. Next, because the live Marburg virus is too dangerous to study safely in anything but a Biosafety Level 4 (BSL-4) laboratory, they used an assay to look at what are known as virus-like particles, or VLPs, which can bud off of a host cell like the live virus but are not infectious.

Using the Biosafety Level 2 laboratory at Penn, "it's a very quick way we can test these inhibitors," Harty says.

After seeing a dose-dependent response to FC-10696 on VLP budding in cells in a cell-culture dish, the researchers tested the compound using the real Marburg virus. These studies were done in a BSL-4 lab at Texas Biomedical Research Institute and found the compound inhibited the budding and spread of live Marburg virus in two human cell types, including in macrophages, an immune cell type commonly infected by the virus.

Finally, they evaluated the compound in mice that had been exposed to Marburg virus. Those mice treated with FC-10696 took longer to display disease symptoms and had a reduced viral load.

"These are the first promising in vivo data for our compounds," Harty says. "Whereas the control group all became sick very quickly and died, with the treated animals there was one survivor and others showed delayed onset of clinical symptoms. It's showing that our inhibitors are having an effect."

A portion of the VP40 protein in Marburg and Ebola viruses that enables budding is known as a PPxY motif. SARS-CoV-2 also happens to have this motif on its Spike (S) protein, which it uses to infect human cells. In a follow-up experiment that is not yet published, the researchers found evidence that FC-10696 was able to inhibit budding of the SARS-CoV-2 coronavirus in human lung epithelial cells.

"The SARS-CoV-2 studies are ongoing, and they're very exciting," Harty says.

Credit: 
University of Pennsylvania

Healthy young adults who had COVID-19 may have long-term impact on blood vessels and heart health

New research published in Experimental Physiology highlight the possible long term health impacts of COVID-19 on young, relatively healthy adults who were not hospitalized and who only had minor symptoms due to the virus.

Increased stiffness of arteries in particular was found in young adults, which may impact heart health, and can also be important for other populations who may have had severe cases of the virus. This means that young, healthy adults with mild COVID-19 symptoms may increase their risk of cardiovascular complications which may continue for some time after COVID-19 infection.

While SARS-CoV-2, the virus known for causing the COIVD-19 pandemic, is mainly characterized by respiratory symptoms, other studies have recently shown changes to blood vessel function among young adults 3-4 weeks after being infected with SARS-CoV-2 (Ratchford et al., 2021).

This has also been observed months after infection in older adults as well (Riou et al. J Clin Med. 2021).

The research team at Appalachian State University found that the virus may have detrimental effects to arteries throughout the body, including in the carotid artery which supplies the brain with blood.

This draws comparisons between SARS-CoV-2 and other acute bacterial and viral infections which alter arterial stiffness such as rheumatic fever, Kawasaki disease, pneumonia, H. Pylori, and lupus, all of which may persist long after symptoms have resolved.

The researchers tested young adults 3-4 weeks after being infected with SARS-CoV-2. They used an ultrasound on the carotid artery and took recordings of that image for 10-15 heart beats.

These recordings were analyzed on a computer software to find measures of carotid stiffness. For the control group, they used data from young healthy adults who were studied prior to the COVID-19 pandemic.

As far as limitations of this study goes, the researchers do not know if the SARS-CoV-2 group had any innate decrements in arterial stiffness prior to contracting the virus.

They also did not control for menstrual cycle or variations in contraceptive use in either group. However, previous research has indicated that contraceptive use and menstrual cycle fluctuations among young healthy females may not influence the outcome measures they were studying.

The researchers are following these young adults for 6 months after initial infection with SARS-CoV-2 to observe if and when the arterial health of these individuals is improving.

The results of the longitudinal study will be interesting, as these adults' symptomology may improve, yet their arterial health may not be recovering as quickly, which may have significance for their heart health.

Further investigations should aim to study a more diverse patient population over time, especially older adults who are more susceptible to the virus and who may have underlying conditions such as heart disease, diabetes, and hypertension.

Dr. Steve Ratchford, the senior author on the paper said: "These findings suggest a potential long-term impact of COVID-19 on young, relatively healthy adults who may otherwise think the virus may not be affecting them."

Credit: 
The Physiological Society