Culture

Abusive alcohol drinking considerably impacts human health. Alcoholism, better defined as Alcohol Use Disorders (AUD), includes a group of pathological entities related to alcohol-induced damage. Individuals with AUD exhibit compulsive alcohol drinking and negative emotional states when alcohol drinking ceases. In the most severe AUD forms, the individuals lose control over consumption despite a decided will to stop. Some controversial issues have arisen as to whether the definition of AUD can help to delimit and characterize clinical entities related to abusive alcohol ingestion.

The World Health Organization (WHO) reports that approximately 3,3 million people (5,9% of global deaths) die yearly because of harmful alcohol consumption (According to WHO, as of 4 February 2021, there have been 2,25 million deaths caused by COVID-19, globally). Besides, alcohol is directly responsible for 5 % of disabling diseases and injuries worldwide.

Authorized agencies have officially approved very few pharmacological treatments to treat AUD (for example, disulfiram, opioid antagonists, acamprosate, baclofen, or topiramate). Many patients are reluctant to treatment for different reasons based on their features (age, gender, ethnicity, genetic and epigenetic background) and their alcohol drinking behavior.

Currently, no silver bullet shall rescue humankind from the burden of alcohol on health. Notwithstanding, a better understanding of ethanol's repercussion on molecular cell targets is imperious to plan out pharmacological strategies that ameliorate or block alcohol detriment.

Despite limited favorable results, efforts continue to find drugs acting on causes and effects observed in AUD, including relapse, withdrawal, stress, or anxiety. Nowadays, clinical studies in phases I and II explore the effectiveness of drugs in AUD treatment. Examples of compounds investigated are glutamate and GABA modulators, neuropeptide antagonists, or regulators of neuroimmune responses. Some drugs administered for the treatment of mental disorders have proved efficient in the treatment of AUD. For example, aripiprazole, an antipsychotic drug, and agomelatine, a melatonergic antidepressant, showed beneficial effects by preventing alcohol relapse and craving.
The influence of alcohol on epigenetic mechanisms is a relatively new explored field that offers new avenues for research in the field. The term epigenetics includes chemical changes in DNA, proteins (histones, mainly), mRNAs, and non-coding RNAs with regulatory capacity that control gene expression.

This study provides an in-depth review of recent research that reveals the impact of alcohol on the biochemical mechanisms responsible for epigenetic control within cells. Besides, it analyzes candidate drugs that may counteract the impact of alcohol on epigenetic mechanisms and serve to advance new and tailored pharmacological treatments. Research carried out in animal models and humans (with the obvious ethical limitations imposed on human research) provides valuable information on the epigenetic regulatory processes intercepted by alcohol. The design and laboratory synthesis of new drugs aimed at specific molecular targets offers significant advances in this field.

LA JOLLA--(March 31, 2021) Clinicians using a new viral screening test can not only diagnose COVID-19 in a matter of minutes with a portable, pocket-sized machine, but can also simultaneously test for other viruses--like influenza--that might be mistaken for the coronavirus. At the same time, they can sequence the virus, providing valuable information on the spread of COVID-19 mutations and variants. The new test, dubbed NIRVANA, was described online today by a multi-institution team of scientists in the journal Med.

"This is a virus detection and surveillance method that doesn't require an expensive infrastructure like other approaches," says Juan Carlos Izpisua Belmonte, co-corresponding author and a professor in Salk's Gene Expression Laboratory. "We can accomplish with one portable test the same thing that others are using two or three different tests, with different machines, to do."

Around the world, more than 100 million people have been infected with SARS-CoV-2, the virus that causes COVID-19. A staggering 500,000 Americans have died from COVID-19 to date. Testing the population is key to stopping the spread of the virus. In addition, tracking the spread of new SARS-CoV-2 variants--some of which could respond differently to treatments or vaccines--is critical.

Today, the standard approach to determining whether a nasal swab is positive for COVID-19 is to run a polymerase chain reaction (PCR) test to detect genetic material from the SARS-CoV-2 virus. If the sample is negative, however, patients and clinicians don't get any information on what might be causing the coronavirus-like symptoms--unless they run separate PCR tests, using different swab samples, for other viruses. And if the sample is positive for SARS-CoV-2, they don't learn which COVID-19 variant a patient is infected with unless another set of tests is run; those require a large and expensive next-generation gene-sequencing machine.

Last summer, Mo Li, an assistant professor of bioscience at King Abdullah University of Science and Technology in Saudi Arabia, was pondering ways he could lend his expertise in genetic engineering and nanopore sequencing to combatting the COVID-19 pandemic. Li, who previously spent six years as a Salk postdoctoral researcher in the Izpisua Belmonte lab, wondered whether a gene-detection approach called isothermal recombinase polymerase amplification (RPA) coupled with real-time nanopore sequencing might be more useful--and faster, cheaper and more portable--than the current COVID-19 testing approach. He teamed up with Izpisua Belmonte to find out.

Unlike PCR, which cycles through lower and higher temperatures to separate DNA strands and copy them, RPA uses proteins--rather than temperature changes--to accomplish the same thing in only 20 minutes. The technology lets researchers copy longer stretches of DNA, and probe for multiple genes at the same time.

"We quickly realized that we could use this technique to not only detect SARS-CoV-2, but other viruses at the same time," says Li.

In the new paper, Li and Izpisua Belmonte describe a small, portable device that can screen 96 samples at the same time using the RPA assay. They call the method NIRVANA, for "nanopore sequencing of isothermal rapid viral amplification for near real-time analysis."

The scientists designed NIRVANA to simultaneously test samples for COVID-19, influenza A, human adenovirus, and non-SARS-CoV-2 human coronavirus. In just 15 minutes, the researchers report, the device begins to report positive and negative results. And within three hours, the device finalizes results on all 96 samples--including the sequences of five regions of SARS-CoV-2 that are particularly prone to accumulate mutations leading to new variants such as the B.1.1.7 variant identified in the UK.

Li and Izpisua Belmonte tested NIRVANA on 10 samples known to be positive for SARS-CoV-2, 60 samples of unknown SARS-CoV-2 status, as well as samples of municipal wastewater harboring the SARS-COV-2 virus and others. In all cases, the assay was able to correctly identify which viruses were present. The sequencing data also allowed them to narrow down the origin of SARS-CoV-2 in positive samples; differentiating strains from China and Europe, for instance.

"The design of this assay is really flexible, so it's not just limited to the examples we've shown," says Li. "We can easily adapt it to tackle another pathogen, even something new and emergent."

With the small size and portability of the NIRVANA workflow, it could be used for fast virus detection at schools, airports or ports, the researchers say. It also could be used to monitor wastewater or streams for the presence of new viruses.

"The pandemic has provided two important lessons: first, test widely and quickly, and second, know your variants. Our NIRVANA method provides a promising solution to these two challenges not only for the current pandemic but also for possible future ones," says Izpisua Belmonte, who holds the Roger Guillemin Chair at Salk. Market analysis would be required to determine whether the initial cost of commercialization--and the constant tweaks to the test needed to make sure it detected new variants or new viruses of interest--are worth it, Belmonte adds.

AURORA, Colo. (March 31, 2021) - A new study published in Frontiers in Psychiatry finds that patients with Obsessive Compulsive Disorder (OCD) as well as other psychiatric comorbidities, such as autism spectrum or tic disorders, may respond well to Deep Brain Stimulation (DBS).

DBS is a minimally invasive neurosurgical procedure that uses coordinates to target certain areas of the brain, implanting electrodes that can help regulate abnormal brain activity. DBS procedures are rare for OCD in the United States; only a couple hundred patients have received this treatment for OCD management since its FDA approval in 2009 via a Humanitarian Device Exemption. The effectiveness of DBS for OCD has been well-documented in literature, but the interplay with comorbid disorders has not been as thoroughly explored.

"This study helps us understand more about real-world use of DBS for OCD," says Rachel Davis, MD, associate professor in the CU Department of Psychiatry and study principal investigator. "Most patients seeking treatment don't only have OCD, comorbidities are more the rule than the exception. So it's important to understand how this life-changing procedure can benefit our more typical patients."

Davis and clinicians at the University of Colorado Anschutz Medical Campus retrospectively examined five patients seeking DBS for OCD between 2015 and 2019. Patients exhibited comorbidities including substance use disorder, eating disorder, autism spectrum disorder, major depression, ADHD, and tic disorder. Three patients were awake during DBS surgery, allowing clinicians to check for response to stimulation (improved mood, increased energy, and reduction in anxiety), an additional way to confirm correct electrode placement. After surgery, Davis assessed response and determined the correct settings by asking patients about changes in mood, energy, and anxiety. Improvement in these areas tend to be associated with reduction in OCD symptoms later on. Change over time was monitored with a variety of IRB-approved questionnaires, gauging changes in mood, anxiety, depression and other quality of life elements affected by OCD.

Overall, these patients experienced significant improvement in OCD and mood symptoms. A standard scale for assessing symptom severity and treatment response in OCD, the Yale-Brown Obsessive-Compulsive Scale (YBOCS), measures degree of distress and impairment caused by obsessions and compulsions. A good clinical response is considered to be greater than a 35% reduction. In this study, patients averaged a 44% reduction on this scale; four out of five experienced full response with the fifth having a partial response, with approximately 25% reduction in OCD symptoms. Patients also reported an average of 53% reduction in depression symptoms.

"For these treatment-refractory OCD patients, our Psychiatric DBS program, led by Dr. Davis, is finally providing relief," says John Thompson, PhD, associate professor of neurosurgery at the University of Colorado School of Medicine and one of the co-authors on this manuscript. "While DBS for OCD is rare, this study is a glimpse at its potential. There is much yet to be learned about the complex interplay between circuit modulation and co-morbid symptom management in OCD patients treated with DBS."

The pandemic is affecting every country, but not every country has equal access to the lifesaving COVID-19 vaccines. Recent estimates show that high-income countries -- which have just one-fifth of the global adult population -- have purchased more than half of the world's total vaccine doses, resulting in disparities for low- and middle-income countries.

A new study by researchers at Virginia Commonwealth University investigates a key question: Will the U.S. population support donating part of its COVID-19 vaccine stockpile to less prosperous countries?

"COVID-19 is a true global pandemic that has touched every nation on Earth. Borders closed, economic consequences and an incredible level of human suffering, with now more than half a million people who have died of COVID in the U.S. and many more worldwide," said lead author Jeanine Guidry, Ph.D., an assistant professor in the Richard T. Robertson School of Media and Culture in the College of Humanities and Sciences and director of the Media+Health Lab at VCU. "COVID-19 has shown how interconnected we all are, and to defeat it we will need to work together on a global scale."

For the study, "U.S. Public Support for COVID-19 Vaccine Donation to Low- and Middle-Income Countries during the COVID-19 Pandemic," the researchers conducted a survey of 788 U.S. adults that assessed the support of different population groups for donating vaccines, as well as in what quantity and in what time frame.

It found that older respondents were both less likely to endorse higher levels of COVID-19 vaccine donations and were more likely to want to wait until all in the U.S. who want the vaccine have received it.

"We know that while COVID affects everybody, the majority of the people who die from it are people who are older," Guidry said. "So this finding may reflect that vulnerability."

It also found that respondents who identified as Democrats were more likely to endorse more and faster COVID-19 vaccine donations to low- and middle-income countries than Republicans.

"It is possible that those who identify as Democrats were more likely to support higher levels of donation because it may be connected to a belief in health care as a human right and health care for all," Guidry said.

People without health insurance also were less likely to support donation, and wanted to wait until everyone in the U.S. who wants a vaccine has received it.

The study also found that people who rated higher on the "social dominance orientation" scale were both less likely to endorse higher levels of COVID-19 vaccine donations as well as more likely to want to wait until all in the U.S. who want the vaccine have received it. Social dominance orientation is a personality trait measuring a person's support for social hierarchy and belief that their group is superior to others.

"Social dominance orientation may actually be a fundamental driver of support for vaccine donations during the pandemic," said Paul Perrin, Ph.D., a co-author on the study and an associate professor in the Department of Psychology at VCU. "When people believe in their heart that some individuals are inherently better than others and should therefore be afforded more societal privileges, that is a deep worldview that can color many of their other belief systems."

The study's results also have some encouraging signs, said co-author Bernard Fuemmeler, Ph.D., a professor in the Department of Health Behavior and Policy in the VCU School of Medicine.

"Despite some of the differences we observed with respect to age, party affiliation or social dominance, it is encouraging that, for the most part, there was a majority support for donating as much as 10% of vaccines we have available in the U.S. to other countries," he said. "Despite some hesitancy among a minority of the sample, many we surveyed recognized the importance of closing the gap. Policymakers should be encouraged that proposals to donate the vaccine will be met with acceptance."

The study's findings could be valuable to policymakers, health care providers and public health communication professionals working to persuade and target key segments of the U.S. public to support the donation of vaccines to countries that lack the resources to develop and purchase sufficient quantities.

"Our goal is to provide indications about how we can best communicate to the public. How can we best say: 'OK, we need to [donate vaccines] but we want your buy-in. We want your support,'" Guidry said. "Having support for these decisions is going to be critically important. [This study] provides an important starting point."

Researchers from Queen Mary University of London have shown for the first time that animal DNA shed within the environment can be collected from the air.

The proof-of-concept study, published in the journal PeerJ, opens up potential for new ecological, health and forensic applications of environmental DNA (eDNA), which to-date has mainly been used to survey aquatic environments.

Living organisms such as plants and animals shed DNA into their surrounding environments as they interact with them. In recent years, eDNA has become an important tool to help scientists identify species found within different environments. However, whilst a range of environmental samples, including soil and air, have been proposed as sources of eDNA until now most studies have focused on the collection of eDNA from water.

In this study, the researchers explored whether eDNA could be collected from air samples and used to identify animal species. They first took air samples from a room which had housed naked mole-rats, a social rodent species that live in underground colonies, and then used existing techniques to check for DNA sequences within the sampled air.

Using this approach, the research team showed that airDNA sampling could successfully detect mole-rat DNA within the animal's housing and from the room itself. The scientists also found human DNA in the air samples suggesting a potential use of this sampling technique for forensic applications.

Dr Elizabeth Clare, Senior Lecturer at Queen Mary University of London and first author of the study, said: "The use of eDNA has become a topic of increasing interest within the scientific community particularly for ecologists or conservationists looking for efficient and non-invasive ways to monitor biological environments. Here we provide the first published evidence to show that animal eDNA can be collected from air, opening up further opportunities for investigating animal communities in hard to reach environments such as caves and burrows."

The research team are now working with partners in industry and the third sector, including the company NatureMetrics, to bring some of the potential applications of this technology to life. Dr Clare added: "What started off as an attempt to see if this approach could be used for ecological assessments has now become much more, with potential applications in forensics, anthropology and even medicine."

"For example, this technique could help us to better understand the transmission of airborne diseases such as Covid-19. At the moment social distancing guidelines are based on physics and estimates of how far away virus particles can move, but with this technique we could actually sample the air and collect real-world evidence to support such guidelines."

The project was supported by Queen Mary's Impact Acceleration Accounts (IAAs), strategic awards provided to institutions by UK Research and Innovation (UKRI) that support knowledge exchange (KE) and help researchers generate impact from their research.

Key Points

The PURE study is the first multinational study exploring the association between unprocessed and processed meat intakes with health outcomes in low-, middle-, and high-income countries.

The consumption of unprocessed red meat and poultry was not found to be associated with mortality nor major cardiovascular disease events.

In contrast, higher processed meat intake was associated with higher risks of both total mortality and major cardiovascular disease.

Rockville, MD - Red meat is a major source of medium- and long-chain saturated fatty acids, which may lead to an increased risk of cardiovascular disease. Processed meat, which has been modified to improve taste or extend its shelf-life, has also been associated with an increased risk of cardiovascular disease. Dietary guidelines therefore recommend limiting the consumption of both red and processed meat based on studies that have linked them to higher risks of cardiovascular disease. These studies, however, have come primarily from populations in North America and Europe, limiting their global applicability.

Published in The American Journal of Clinical Nutrition (AJCN), "Associations of Unprocessed and Processed Meat Intake with Mortality and Cardiovascular Disease in 21 countries (PURE): A Prospective Cohort Study," has helped to rectify a major research gap, helping us better understand the global health impact of meat and meat product consumption. Dr. Romaina Iqbal, first author of the study noted, "evidence of an association between meat intake and cardiovascular disease is inconsistent. We therefore wanted to better understand the associations between intakes of unprocessed red meat, poultry, and processed meat with major cardiovascular disease events and mortality."

In order to conduct their research, the authors of this study worked with data from the Prospective Urban Rural Epidemiological (PURE) study, a long-term study launched in 2003 by Dr. Salim Yusuf, Director of Population Health Research Institute, Canada, and Principal Investigator of the PURE study. The PURE study has tracked the dietary habits and health outcomes of more than 164,000 participants from 21 low-, middle-, and high-income countries across five continents.

According to Dr. Mahshid Dehghan, one of the study's authors and Investigator at the Population Health Research Institute of McMaster University and Hamilton Health Sciences, "the PURE study is the first multinational study that provides information on the association between unprocessed and processed meat intakes with health outcomes from low- and middle-income countries. Moreover, the PURE study examines substantially more diverse populations and broad patterns of diet, enabling us to provide new evidence."

Participants' dietary habits were recorded via the use of food frequency questionnaires. In addition, data was collected on participants' mortality and major cardiovascular disease events, enabling the study authors to determine the associations between meat consumption patterns and cardiovascular disease events and mortality.

Upon completing their analysis, the study authors "did not find significant associations between unprocessed red meat and poultry intake with mortality or major cardiovascular disease." By contrast, processed meat intake was associated with higher risks of total mortality and major cardiovascular disease.

The authors believe that additional research may enhance our current understanding of the relationship between meat consumption and health outcomes. For example, it isn't clear what study participants with lower meat intakes were eating instead of meat, and if the quality of those foods differed between countries. These substitutions may have implications in further interpreting the associations between meat consumption and health outcomes. Nonetheless, the authors believe their findings "indicate that limiting the intake of processed meat should be encouraged."

Tomatoes are an important and popular crop, but the tasty ketchup, salsa and pasta sauce they yield comes at a price: overuse of chemical fertilizers. Now, researchers report in ACS' Journal of Agricultural and Food Chemistry they have recruited a fungus to bolster fertilizer efficiency, meaning tastier tomatoes can be grown with less fertilizer.

Tomato plants have a long growth period and need more nutrients -- particularly nitrogen and phosphorus-- than many other crops. Supplying these nutrients through a chemical fertilizer is inefficient, because the nutrients can leach away, evaporate or get trapped in insoluble compounds in the soil, among other problems. Some farmers react by overusing fertilizers to boost tomato yield, but this results in poor fruit quality, fertilizer waste, soil deterioration and environmental pollution. Another option is to apply microbes that free nitrogen and phosphorus from the soil for the crop to absorb, though this technique generally hasn't performed well in farm fields. However, Jianguo Huang and colleagues previously succeeded in using a fungus to enhance nutrient uptake and growth in field-raised eggplants. In their latest study, they wanted to find out if the microbe could work with ketchup tomato crops.

The researchers used the HG2011 strain of Ceriporia lacerata, a white-rot fungus with applications in medicine, wastewater treatment, and sugar and biofuel production. Known to grow on trees and other plants and in soil, it deploys proteases, phosphatases and other enzymes to obtain nutrients from its environment. In the process, it converts elements and compounds into forms that plants can use. In the new study, the team showed the fungus promoted enzyme activity in the soil, and improved tomatoes' nutrient uptake and yield in both fertilized and unfertilized soils. The results suggest that compost from this fungus has potential as a cheap supplement that could reduce the need for chemical fertilizer. The fungus -- which doesn't harm tomatoes -- also enhanced nutrition and flavor by increasing the tomatoes' sugar-acid ratio, as well as their soluble sugar and vitamin C content, according to the researchers.

Hamilton, ON (March 31, 2021) - A global study led by Hamilton scientists has found a link between eating processed meat and a higher risk of cardiovascular disease. The same study did not find the same link with unprocessed red meat or poultry.

The information comes from the diets and health outcomes of 134,297 people from 21 countries spanning five continents, who were tracked by researchers for data on meat consumption and cardiovascular illnesses.

After following the participants for almost a decade, the researchers found consumption of 150 grams or more of processed meat a week was associated with a 46 per cent higher risk of cardiovascular disease and a 51 per cent higher risk of death than those who ate no processed meat.

However, the researchers also found moderate levels of consumption of non-processed meats had a neutral effect on health.

"Evidence of an association between meat intake and cardiovascular disease is inconsistent. We therefore wanted to better understand the associations between intakes of unprocessed red meat, poultry, and processed meat with major cardiovascular disease events and mortality," said Romaina Iqbal, first author of the study and an associate professor at the Aga Khan University in Karachi, Pakistan.

"The totality of the available data indicates that consuming a modest amount of unprocessed meat as part of a healthy dietary pattern is unlikely to be harmful," said Mahshid Dehghan, investigator for the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences.

The Prospective Urban Rural Epidemiology (PURE) study was launched in 2003 and is the first multinational study that provides information on the association between unprocessed and processed meat intakes with health outcomes from low, middle and high-income countries.

"The PURE study examines substantially more diverse populations and broad patterns of diet, enabling us to provide new evidence that distinguishes between the effects of processed and unprocessed meats," said senior author Salim Yusuf, executive director of the PHRI.

Participants' dietary habits were recorded using food frequency questionnaires, while data was also collected on their mortality and major cardiovascular disease events. This allowed researchers to determine the associations between meat consumption patterns and cardiovascular disease events and mortality.

The authors believe that additional research may improve current understanding of the relationship between meat consumption and health outcomes. For example, it is unclear what study participants with lower meat intakes were eating instead of meat, and if the quality of those foods differed between countries.

Non-meat food substitutes may have implications in further interpreting the associations between meat consumption and health outcomes. Nonetheless, the study's authors believe their findings "indicate that limiting the intake of processed meat should be encouraged."

GENEVA, LAUSANNE, 31 March 2021: Cocaine is a highly addictive substance that, in the long term, can have adverse effects on health and wellbeing. There are around 18 million cocaine users globally, according to a UN report. Understanding how cocaine modifies brain networks could reveal potential targets for therapies to treat addiction and other neuropsychological disorders.

A new study published today in the journal Frontiers in Synaptic Neuroscience by a team of researchers from the University of Lausanne and the Wyss Center for Bio and Neuroengineering reveals that during cocaine withdrawal, neurons in a brain area associated with depression connect to neurons embedded in an anti-reward system.

When we receive a reward, neurons fire in the brain's ventral tegmental area (VTA) - a region of the brain that produces dopamine. Dopamine is a chemical messenger that creates feelings of joy or pleasure. It spreads throughout the brain, motivating us to repeat our actions and achieve the feeling of pleasure again, a central facet of addictive behavior.
When we miss out on a reward, or stop taking an addictive drug, the lateral habenula - a brain area linked to depression - becomes hyperactive and sends signals to the VTA that results in depressive symptoms.

What researchers did not know, until now, is exactly where the neurons from the lateral habenula extend into the VTA and what they connect to during withdrawal from cocaine. Through a series of experiments, the team discovered that, in mice, the neurons from the lateral habenula synapse mostly to neurons in the VTA that do not produce dopamine, creating a connection to an anti-reward system that may be key in driving adverse behavior.

Manuel Mameli, PhD, Associate Professor in the Department of Fundamental Neuroscience, University of Lausanne said: "We wanted to understand why individuals experience depression when they stop taking a substance like cocaine. We knew that cocaine withdrawal induces changes to brain circuits linked to depression and reward, but our results have now taken us a step further and show that there is a reorganization of brain circuits that drive negative behavior."

The team combined their expertise in sample preparation and advanced microscopy to capture 3D images of entire intact mouse brains. They used viral 'tags' to make the neurons fluoresce, then created completely transparent samples by removing lipids, before imaging with the Wyss Center's custom-built lightsheet microscope. With data analytics and visualization tools, they identified the 3D morphology of specific neurons to understand their anatomical distribution inside the brain.

Stephane Pages, PhD, Scientific Coordinator at the Wyss Center and Senior Research Associate at the University of Geneva said: "The beauty of lightsheet imaging is being able to see which neurons connect to each other in the brain. Our microscope and data analytics capabilities pinpointed the specific neuronal connections between the two major brain areas implicated in drug withdrawal."

The results of the study also show that neurons in the anti-reward circuits not only project to the VTA but also from there into other parts of the brain resulting in a cascade of 'anti-reward' information into areas responsible for decision making and motivation, amongst others. The next step is to dissect the functionality of these non-dopamine, anti-reward, circuits to better understand how they influence behavior.

DALLAS, March 31, 2021 -- Following a routine of regular physical activity combined with a diet including fruits, vegetables and other healthy foods may be key to middle-aged adults achieving optimal cardiometabolic health later in life, according to new research using data from the Framingham Heart Study published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

Cardiometabolic health risk factors include the metabolic syndrome, a cluster of disorders such as excess fat around the waist, insulin resistance and high blood pressure. Presence of the metabolic syndrome may increase the risk of developing heart disease, stroke and Type 2 diabetes.

Researchers noted it has been unclear whether adherence to both the U.S. Department of Health and Human Services' 2018 Physical Activity Guidelines for Americans and their 2015-2020 Dietary Guidelines for Americans - as opposed to only one of the two - in midlife confers the most favorable cardiometabolic health outcomes later in life. The physical activity guidelines recommend that adults achieve at least 150 minutes of moderate or 75 minutes of vigorous physical activity per week, such as walking or swimming. The dietary guidelines, which were updated in January 2021, offer suggestions for healthy eating patterns, nutritional targets and dietary limits.

In an analysis of data from participants of the Framingham Heart Study, which began more than 70 years ago in Framingham, Massachusetts, investigators examined data from 2,379 adults ages 18 and older and their adherence to the two guidelines. They observed that meeting a combination of the two recommendations during midlife was associated with lower odds of metabolic syndrome and developing serious health conditions as participants aged in their senior years in 2016-2019 examinations.

"Health care professionals could use these findings to further promote and emphasize to their patients the benefits of a healthy diet and a regular exercise schedule to avoid the development of numerous chronic health conditions in the present and in later life," said corresponding author Vanessa Xanthakis, Ph.D., FAHA, assistant professor of medicine and biostatistics in the Section of Preventive Medicine and Epidemiology at Boston University School of Medicine in Boston. "The earlier people make these lifestyle changes, the more likely they will be to lower their risk of cardiovascular-associated diseases later in life."

Study participants were selected from the third generation of the Framingham Heart Study. Participants (average age 47, 54% women) were examined between 2008 and 2011. Researchers evaluated physical activity using a specialized device known as an omnidirectional accelerometer. The device, which tracks sedentary and physical activity, was worn on the participant's hip for eight days. Researchers also collected dietary information from food frequency questionnaires to measure the kinds and levels of food and nutrients consumed.

In this investigation, researchers observed that among all participants, 28% met recommendations of both the physical activity and dietary guidelines, while 47% achieved the recommendations in only one of the guidelines. Researchers also observed that:

participants who followed the physical activity recommendations alone had 51% lower odds of metabolic syndrome;

participants who adhered to the dietary guidelines alone had 33% lower odds; and

participants who followed both guidelines had 65% lower odds of developing metabolic syndrome.

"It is noteworthy that we observed a dose-response association of adherence to diet and physical activity guidelines with risk of cardiometabolic disease later in life," Xanthakis said. "Participants who met the physical activity guidelines had progressively lower risk of cardiometabolic disease as they increased adherence to the dietary guidelines."

All study participants were white adults, therefore, the findings cannot be generalized to people in other racial or ethnic groups. Additional studies with a multiethnic participant sample are needed, researchers said.

More research is needed on the environmental impact of sunscreen on the world's coral reefs, scientists at the University of York say.

The concerns over the number of cases of cancer as a result of overexposure to UV solar radiation, has led to extensive production and use of skin protection products. The chemical compounds used in these products, however, can enter the environment at the points of manufacture as well as through use by the consumer.

It is already understood that UV-filter compounds have toxic effects on marine organisms, but research in this area is limited and does not take into account certain variables, such as differences in environmental conditions.

Dr Brett Sallach, from the University of York's Department of Environment and Geography, said: "Given the declining status of coral reef ecosystems and the many stressors they already face, it is important to identify the potential occurrence and toxicological risks associated with UV-filter exposure to reef ecosystems.

"Our research aimed to identify what research was out there and what gaps we had in our knowledge. Importantly we needed to understand what areas could be considered priority for future attention in order to understand the impacts of these products, and hopefully prevent any further damage to the environment.

"Undoubtedly products that can help protect against the harmful effects of UV radiation on human health are hugely important, and therefore we need reliable and extensive evidence to suggest any changes or scaling back of these products."

Researchers consulted with experts and industry representatives within the field of marine UV-filter exposure to understand the limitations of current research and what areas needed urgent attention.

They found that the majority of research on UV-filter compounds focuses on freshwater organisms and ecosystems, and that environmental conditions can either increase or decrease the response to toxic elements, making the true risk of the compounds difficult to establish.

This research does not translate easily to the unique ecology of coral reefs, and therefore long-term environmental monitoring would be needed in tropical and subtropical climates to understand the toxic effects here.

Yasmine Watkins, who led the work as part of her Masters degree in the Department of Environment and Geography, said: "We make four recommendations for priority research areas going forward, based on our consultation with experts. We need more work in the area of understanding UV-filter toxicity under different climate conditions, and long-term study into exposure and recovery of coral reefs.

"We also need to know realistic exposure to these compounds and how long they exist in the marine environment, to determine what the 'safe' limits are."

Researchers aim to highlight these priority areas to better inform regulators and policy makers to improve conservation and management of coral reefs, whilst ensuring that human health can continue to be protected by UV-filter products.

A*STAR's Institute of Bioengineering and Nanotechnology (IBN) has teamed up with Singapore Institute of Advanced Medicine Holdings Pte Ltd (SIAMH) to establish the first of its kind in-vitro patient-derived 3D organoid models of Nasopharyngeal Cancer (NPC).

The study was published in Frontiers in Oncology on 23 February 2021. It is the first direct experimental evidence to predict optimal Radiation Treatment (RT) boost dose required to cause sufficient damage to recurrent hypoxic (low oxygen level) NPC tumour cells, which can be further used to develop dose-painting algorithms in clinical practice.

Two patient-derived xenograft (PDX) lines were used to further establish in-vitro 3D models of hypoxic radioresistant NPC for the first time. This collaboration helps to fine-tune radiation treatment, lower the chances of recurrence of NPC and reduce the mortality rate.

Nasopharyngeal carcinoma is endemic in east and southeast Asia, where 95% of the cases are invariably associated with Epstein-Barr virus (EBV) infection. More than 50% of the patients present with locally advanced and distant metastasis during initial diagnosis, and the 5-year survival rate reduces to between 50% to 70%. The disease is most prevalent in Brunei, Maldives, Indonesia, and Singapore.

The current treatment for NPC includes Radiation Treatment. There are recurrent cases that occur due to insufficient radiation. This poses a clinical challenge to the oncologists. Usually, radiotherapy is used as a re-treatment on inoperable advanced recurrent cases. This results in patients having complications during treatment and the 5-year survival rate will be reduced further. With no relevant in-vitro models to study NPC except the C666-1 cell-line which was established in late 1990's, the lack of disease-specific in-vitro models of NPC has further hindered the development of personalised therapeutic options.

IBN and SIAMH collaborated with the Singapore General Hospital and The Hong Kong University of Science and Technology to create the new in-vitro hypoxic 3D organoid models. These mimicked the hypoxic radioresistant sub-volumes of recurrent NPC, and were found to closely resemble NPC patient tumours.

By using novel patient-derived 3D models, IBN and SIAMH were able to determine experimentally on the radiobiological parameters which provide a better guide in radiation dosing, such that hypoxic radioresistant NPC cells could be eliminated, thus reducing the chances of tumour recurrences.

The study has demonstrated that radiation dose escalation by about 1.4 folds to the hypoxic radioresistant areas in the tumour would further improve the outcome of the treatment. Delivering high dose radiation - in a smaller number of fractions (hypofractionated radiotherapy) may be the way to treat hypoxic radioresistant NPCs. This could reduce long-term side effects, mortality rates due to recurrence, and improve patients' quality of life.

Dr Lucky Sasidharan, Postdoctoral Fellow at A*STAR's IBN and first author of the Frontiers in Oncology paper said, "These insights may help to develop personalised radiotherapy regimens and dose painting algorithms which could save time and lives through the prevention of re-irradiation or re-treatment."

Dr Djeng Shih Kien, Chairman and CEO of SIAMH said, "We are indeed very happy to work with IBN and contribute towards the findings of escalating dose and fractionation of radiotherapy in the treatment of hypoxic radioresistant Nasopharyngeal carcinoma.

The use of in-vitro 3D organoid models of patient-derived xenografts for the first time opens up unlimited opportunities for further research with proton beams when it is available towards the end of 2021.

SIAMH's Proton Therapy Centre is a member of the FlashForwardTM Consortium and it will be extremely exciting to study the effects of Flash Therapy on hypoxic radioresistant 3D models of NPC."

IBN is planning to work with experts at the Proton Therapy Centre located in Biopolis on this study for evaluating the effects and benefit of utilising Proton therapy and Ultra-High Dose Rate (FLASH) Radiotherapy for the treatment of NPC. These new platforms would also add the advantage of delivering very high radiation doses in sub-seconds with high precision targeting on just the areas of the tumours -and sparing the surrounding normal tissues. IBN and SIAMH have been collaborating since 2019 to explore how to better tackle NPC.

Researchers from Loyola Marymount University, San Diego State University, Indian Institute of Management, and Iowa State University published a new paper in the Journal of Marketing that examines how effective marketplace participation by subsistence consumers requires knowledge and skills that relate to what, how, and why to participate.

The study, forthcoming in the Journal of Marketing, is titled "Marketplace Literacy as a Pathway to a Better World: Evidence from Field Experiments in Low-Access Subsistence Marketplaces" and is authored by Madhu Viswanathan, Nita Umashankar, Arun Sreekumar, and Ashley Goreczny.

Success for marketers looking to emerging markets for growth is inextricably linked to the wellbeing of the hundreds of millions of subsistence consumers and microentrepreneurs who face poor infrastructure, material resource constraints, and low literacy. Such markets are some of the fastest growing in the world, with nearly $5 trillion of consumption spending annually. As a result, many multinational companies (e.g., Proctor & Gamble, Nokia, Unilever) market products to subsistence consumers.

Unique to subsistence marketplaces is that micro-entrepreneurship serves as a primary source of livelihood, and consumers' purchasing power depends on their microenterprise success. A primary disconnect between marketers' engagement in such markets and subsistence consumers' demand for their products, however, is the latter's inability to participate in marketplaces effectively and beneficially.

Beneficial marketplace participation involves consumers making optimal decisions and generating income by creating value for others through micro-entrepreneurship. With low marketplace participation and suboptimal decision making, firms may sell substandard products rather than high-quality and valuable products. Moreover, firms might not partner with local entrepreneurs, which is an important strategy for market entry in emerging markets.

Viswanathan explains that "Our research demonstrates that subsistence consumers' effective and beneficial marketplace participation requires not only material resources, such as access to capital, but also marketplace literacy--the knowledge and skills that enable marketplace participation both as a consumer and as an entrepreneur." Umashankar adds that "Marketplace literacy causes an increase in psychological wellbeing and consumer outcomes related to wellbeing like consumer confidence and decision-making ability, especially for subsistence consumers with lower marketplace access. It also causes an increase in entrepreneurial outcomes related to wellbeing, such as starting a microenterprise, for those with higher marketplace access."

The research provides insights for public policy makers, development efforts, and companies' corporate social responsibility initiatives. First, subsistence consumers play a significant role in mainstream marketing research since they represent a sizable proportion of consumers globally and function in extreme conditions that challenge the theories developed for resource-rich consumers and markets. Second, marketplace literacy offers a pathway to a better world for subsistence consumers. This pathway is fundamentally about literacy in a marketing domain, which encompasses buyers, sellers, and their interactions. Third, marketplace access is an important contextual factor that should be considered when exploring marketing phenomena across income levels. Fourth, marketplace literacy is a critical form of literacy, in addition to consumer and financial literacy, that should be cultivated. Fifth, marketplace literacy interventions should be implemented to help subsistence consumers overcome their lack of marketplace access and allow them to engage in entrepreneurship.

Even brief programs (4 to 12 hours) with rudimentary methods can aid the development of marketplace literacy and generate substantive outcomes. Such programs can be customized for different audiences (e.g., women vs. men) and occupations (farmers vs. artists) and can have their causal impact assessed. Lessons can be reinforced through short clips on web-based smartphone applications (e.g., WhatsApp, which has widespread adoption, even in rural areas of developing economies) or through text messages.

Given that multinational firms engage in corporate social responsibility initiatives to build stakeholder engagement, policymakers should hold marketers accountable for playing a central role in engendering marketplace literacy. This can be achieved through consumer and entrepreneur protection agencies, subsidies, and metrics that reward firms adhering to such standards. Sreekumar says that "We recommend that the United Nations include marketplace literacy explicitly in its sustainable development goals to build consumer and entrepreneurial knowledge and skills."

Chestnut Hill, Mass. (3/31/21) -- Spinach, a cost-efficient and environmentally friendly scaffold, provided an edible platform upon which a team of researchers led by a Boston College engineer has grown meat cells, an advance that may accelerate the development of cultured meat, according to a new report in the advance online edition of the journal Food BioScience.

Stripped of all but its veiny skeleton, the circulatory network of a spinach leaf successfully served as an edible substrate upon which the researchers grew bovine animal protein, said Boston College Professor of Engineering Glenn Gaudette, the lead author of the new study. The results may help increase the production of cellular agriculture products to meet rising demand and reduce environmental costs.

"Cellular agriculture has the potential to produce meat that replicates the structure of traditionally grown meat while minimizing the land and water requirements," said Gaudette, the inaugural chair of BC's new Engineering Department. "We demonstrate that decellularizing spinach leaves can be used as an edible scaffold to grow bovine muscle cells as they develop into meat."

Earlier advances by Gaudette in this area garnered worldwide attention. In 2017, Gaudette and a multi-university team showed that human heart tissue could be cultivated on a spinach leaf scaffold, which was chosen because it offered a natural circulatory system that is nearly impossible to replicate with available scientific tools and techniques.

"In our previous work, we demonstrated that spinach leaves could be used to create heart muscle patches," said Gaudette. "Instead of using spinach to regrow replacement human parts, this latest project demonstrates that we can use spinach to grow meat."

Gaudette said the team, which included Worcester Polytechnic Institute graduate students Jordan Jones and Alex Rebello, removed the plant cells from the spinach leaf and used the remaining vascular framework to grow isolated cow precursor meat cells. The cells remained viable for up to 14 days and differentiated into muscle mass.

"We need environmentally and ethically friendly ways to grow meat in order to feed the growing population," said Gaudette, whose research is supported by New Harvest. "We set out to see if we can use an edible scaffold to accomplish this. Muscle cells are anchorage dependent, meaning they need to grab on to something in order to grow. In the lab, we can use plastic tissue culture plates, but plastic is not edible."

The researchers point out that the successful results will lead to further characterization of the materials and scientific processes to better understand how to meet consumer demand and gauge how large-scale production could be accomplished in accordance with health and safety guidelines.

"We need to scale this up by growing more cells on the leaves to create a thicker steak," said Guadette. "In addition, we are looking at other vegetables and other animal and fish cells."

LA JOLLA, CA--The faster-spreading B.1.1.7 variant of SARS-CoV-2 first detected in the United Kingdom, the coronavirus that causes COVID-19, is quickly on its way to becoming the dominant variant of the virus in the United States, according to a study from scientists at Scripps Research and the COVID-19 test maker Helix.

The findings, which appear today in Cell, suggest that future COVID-19 case numbers and mortality rates in the United States will be higher than would have been otherwise. The analysis suggests that the variant, which has been detectable in an increasing proportion of SARS-CoV-2 samples, is 40-50 percent more transmissible than SARS-CoV-2 lineages that were previously dominant. Other studies have found evidence that the B.1.1.7 variant may be about 50 percent more likely to cause fatal COVID-19.

"B.1.1.7 rapidly became the dominant SARS-CoV-2 variant in the U.K. and other countries after its emergence late last year, and the U.S. is now on a similar trajectory," says study co-senior author Kristian Andersen, PhD, a professor in the Department of Immunology and Microbiology at Scripps Research and director of Infectious Disease Genomics at the Scripps Research Translational Research Institute. "We need immediate and decisive action to minimize COVID-19 morbidity and mortality."

In addition to Andersen, the other senior author was William Lee, PhD, vice president of science at Helix, which provides PCR-based COVID-19 testing to organizations across the United States. The study was also authored by Nicole Washington, PhD, associate director of research at Helix, and Karthik Gangavarapu of the Andersen Lab.

"B.1.1.7 has a doubling rate of a little over a week and an increased transmission rate of 40-50 percent, which means it could have a meaningful impact on public health," says Lee. "It is critical that we continue to monitor the spread of this and other emerging variants, but our current level of surveillance is inadequate and lags behind that of other countries. We need a more comprehensive national SARS-CoV-2 genomics surveillance program to address this."

The B.1.1.7 variant emerged in southern England last year and has since become the dominant variant in the U.K. In December, Andersen's team at Scripps Research with colleagues at University of California, San Diego confirmed the first evidence of the variant in California.

A pattern of dominance

The B.1.1.7 variant contains several mutations, including several in the gene that encodes the viral spike protein. These mutations increase the spike's ability to bind to the ACE2 receptor on human cells. Although there is no evidence yet that the B.1.1.7 variant can evade COVID-19 vaccines, public health officials fear its relatively high rate of spread will significantly worsen the pandemic before vaccines can end it.

Standard swab tests for the coronavirus check for distinctive genetic sequences at three sites on the viral genome; the B.1.1.7 variant, due to its mutations, shows up as positive for two of those sites, but negative for the third site, which is within the virus's spike gene.

The new analysis of roughly 500,000 Helix test results since July 2020 revealed that this two-of-three pattern, known as S-gene target failure, or SGTF, became consistently evident at a low frequency (0.2 percent) in mid-October. By the third week of February, it had risen to a frequency of 10.6 percent and was detected in patients from 25 different U.S. states and territories.

The SGTF pattern can occur with other SARS-CoV-2 variants that have spike gene mutations, but the researchers found by sequencing every SGTF sample they had from December through February, 662 of the 986 samples (67 percent) contained the B.1.1.7 variant. This suggests that the SGTF pattern on the swab tests can provide a quick albeit rough indication of B.1.1.7 prevalence.

Variant entered the country many times

The analysis also indicated that B.1.1.7 since December has accounted for a rapidly rising proportion of SGTF results--for example, reaching about 95 percent in California by mid-January. In addition to the 659 B.1.1.7 cases they detected via the SGTF method the researchers found three other cases of the B.1.1.7 variant among samples gathered as part of unbiased SARS-CoV-2 genomic surveillance efforts in California.

The 662 instances of B.1.1.7 sequenced in the study were from samples gathered in 10 U.S. states, although the researchers note that other testing labs covering a total of 33 U.S. states and territories have by now reported to the CDC at least one B.1.1.7 case.

The researchers' family tree-type analysis of the detected B.1.1.7 sequences show the variant has been introduced to the U.S. multiple times since at least late November 2020, especially in California and Florida, and in periods coinciding with increased travel, including Thanksgiving week.

The scientists also found that the variant, on the whole, appears to be spreading 40-50 percent faster than the variants of SARS-CoV-2 that previously dominated. They estimated that by the first week of February 2021, B.1.1.7 made up about 4.3 percent of COVID-19 cases in the U.S., including 4.2 percent of cases in California and about 11.5 percent of cases in Florida.