Month: January 2021

Large Study Casts Doubt on “Fat but Fit”

New Spanish research casts doubt on the “fat but fit” paradox, where it is thought that physical fitness is enough to eliminate cardiovascular disease (CVD) risk.

Overweight and obesity is a worldwide problem that is greatly contributing to the burden of noncommunicable diseases, including CVD. A high body mass index (BMI) is strongly associated with CVD risk factors, such as hypercholesterolaemia, hypertension and diabetes. The cardiovascular complications arising from overweight and obesity are driven by processes such as inflammation, insulin resistance, endothelial dysfunction, coronary calcification. Some evidence suggested that physical activity was cardioprotective, partly or completely eliminating the CVD risk from disease – the “fat but fit” paradox.

A recent meta-analysis showed that cardiovascular fitness was a better predictor of cardiovascular disease over overweight/obesity, suggesting that perhaps public health programmes should emphasise fitness over control of body weight. To this end, the researchers sought to confirm if the “fat but fit” paradox was real.

The researchers gathered data from workers’ health insurance, with participants aged 18-64 grouped into normal weight, overweight and obesity by BMI, and into regularly active ( >150 min moderate physical activity or equivalent per week), insufficiently active (less than regularly active) and inactive (no physical activity at all). They were further separated by age, sex, smoking status and residential address.

Approximately 42%, 41%, and 18% of participants had normal weight, overweight, or obesity, respectively; 63.5%, 12.3%, and 24.2% were inactive, insufficiently active, and regularly active; and 30%, 15%, and 3% had hypercholesterolaemia, hypertension, and diabetes.

However, the protective effect of physical activity was far less than the excess risk from overweight/obesity. So much so that even regularly active obese participants had two to five-fold risk increases over their inactive but normal weight peers in the risk factors.

The protective effect of physical activity in overweight/obesity remains controversial. Shortcomings of the study were that they did not control for diet, and only accounted for self-reported leisure time activities. However, the large study size, with over 500 000 participants, should put paid to the theory that a physically active lifestyle can completely eliminate the deleterious effects of overweight/obesity.

The researchers concluded that, “weight loss per se should remain a primary target for health policies aimed at reducing CVD risk in people with overweight/obesity.”

Journal article source: European Journal of Protective Cardiology

Journal information: Pedro L Valenzuela, et al., Joint association of physical activity and body mass index with cardiovascular risk: a nationwide population-based cross-sectional study, European Journal of Preventive Cardiology, 2021;, zwaa151, https://doi.org/10.1093/eurjpc/zwaa151

LSD Shown to Heighten Sociability in Mice

Scientists at McGill University have discovered that mice micro-dosed with LSD have an increased level of sociability, pointing to a mechanism by which the drug can influence behaviour at these low concentrations.

Lysergic acid diethylamide (LSD) was discovered by accident while developing stimulants, and was first used to study psychotic states. There was initially great interest in and use of LSD for psychiatric treatment, but the harmful and lasting side-effects resulted in it steadily being outlawed. However, recent anecdotal evidence of individuals self-administering micro-doses of LSD to improve cognitive functioning have helped spur renewed interest in the famous drug.To investigate the ways LSD might be working on the brain, the McGill University researchers dosed mice with low levels of LSD over seven days, and observed a measurable increase in sociability.

This is useful as a main outcome of the study is a mechanism that describes the increased feelings of empathy and awareness that users of LSD describe.

Co-lead author Prof Nahum Sonenberg at McGill University, world renowned expert in the molecular biology of diseases, explained: “The fact that LSD binds the 5-HT2A receptor was previously known. The novelty of this research is to have identified that the prosocial effects of LSD activate the 5-HT2 receptors, which in-turn activate the excitatory synapses of the AMPA receptor as well as the protein complex mTORC1, which has been demonstrated to be dysregulated in diseases with social deficits such as autism spectrum disorder.

“Their next research goal is treating mutant mice with behavioural deficits mimicking human psychological pathologies, and to find out if micro-dosed LSD or some derivative could be a safe and effective therapeutic option.

“Social interaction is a fundamental characteristic of human behaviour,” noted co-lead author Dr Gabriella Gobbi, Professor in the Department of Psychiatry at McGill and psychiatrist at the McGill University Health Centre. “These hallucinogenic compounds, which, at low doses, are able to increase sociability may help to better understand the pharmacology and neurobiology of social behavior and, ultimately, to develop and discover novel and safer drugs for mental disorders.”

Source: Medical Xpress

Journal information: Danilo De Gregorio et al, Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2020705118

Black American Children Have Higher Rates of Shellfish and Fish Allergies

A study from Rush University Medical Center in the US has shown that black children in that country are more likely to have allergies to fish and shellfish than white children.

Some 8% of children in the US suffer from food allergies, which can result in signs and symptoms such as hives, breathing and digestive problems or anaphylaxis, sometimes severe enough to be life-threatening.

Lead author Dr Mahboobeh Mahdavinia at Rush University Medical Center, explained: “Food allergy is a common condition in the U.S., and we know from our previous research that there are important differences between African-American and white children with food allergy, but there is so much we need to know to be able to help our patients from minority groups.”

The study found that the black children were more likely to have an allergy to shellfish and fin fish, and also higher odds of having a wheat allergy, compared to the white children. The researchers believe the reason for this is environmental and socioeconomic: in the US, black children are more likely to be exposed to cockroaches than white children due to the increased probability of living in more socioeconomically deprived areas.

Tropomyosin, a protein found in two common household allergens, dust mite and cockroaches, share 80% of amino acid sequencing with shellfish. Some 72-98% of individuals allergic to prawns have an immunoglobin E response to tropomyosin. It has also been found in fin fish. Although the exact mechanism by which the allergy is established is not known, it provides evidence as to the importance of reducing the exposure of black children to cockroaches.

The study also showed that shellfish allergy was associated with increased asthma risk in black children. “This information can help us care for not only a child’s food allergy, but all of their allergic diseases, including asthma, allergic rhinitis and atopic dermatitis,” said co-author Susan Fox, PA-C, MMS, an allergy and immunology physician assistant at Rush University Medical Center.

The increased risk of asthma combined with food allergies can prove a lethal combination for children. “A major concern is that there is a higher prevalence of asthma in African-American children with food allergies when compared with white children with food allergies. Approximately 70% of fatal food anaphylaxis is accompanied by asthma. African-American children are at a two- to threefold risk of fatal anaphylaxis compared to white children,” Dr Mahdavinia said. “By knowing this information, it can identify [our] most at risk patients.

“We need to conduct further research to identify food allergies and food sensitivities among all races and ethnicities so we can develop culturally-sensitive and effective educational programs to improve food allergy outcomes for all children,” Dr Mahdavinia concluded.

Source: News-Medical.Net

Sceptical South Africans Want More Vaccine Info

Professor Carin Runciman, Director of the Centre for Social Change at UJ, has said that most people who are sceptical about COVID vaccines simply want more information. 

An online survey of 10 000 South African adults conducted with the Human Sciences Research Council showed that 67% were likely to take the vaccine if it were offered to them. Runciman said that many of the participants had indicated that they wanted more information before they could decide to take it.

Government and scientists came for criticism recently for giving mixed messages about vaccines, which are a few days away from their first rollout in South Africa. With the first million doses arriving in SA from the end of January, an ambitious target of 31 000 vaccinations a day has been announced, though with few firm details. The majority (70%) of the vaccines are to be AstraZeneca, although given their delays in supplying the EU and the bloc’s subsequent restrictions on vaccine exports, that may impact on SA’s vaccination programme.

Opinions also differed according to age and race. In a very strange result, those with higher levels of education were less likely to want to take a vaccine than those with a lower level. Age and race also played a factor, although no explanation was offered for the discrepancy. “Black African adults were more likely to want to take the vaccine – 69% for black African adults, 55% for white adults – those who [are] older are more likely to want to take the vaccine compared to those that are younger. Those that have a less than matric education are much more likely to want to take the vaccine than those with a tertiary education.”

Source: Eyewitness News

New Study Has Good and Bad News on TIAs

There is both good and news on transient ischaemic attacks (TIAs) from a more than six-decade long study: TIAs are indeed harbingers of strokes, but also the incidence of post-TIA strokes has been falling over the decades.

A TIA is defined as a passing episode of neurologic dysfunction due to the focal brain, spinal cord, or retinal ischaemia, without acute infarction or tissue injury. The results were derived from the Framingham Heart Study had 14 059 participants and ran for over six decades, allowing for a more-complete picture of strokes that happen after a TIA. Of the participants, 435 had a TIA; these were compared against a second group of 2175 participants who did not have a TIA.

Even after accounting for other risk factors such as hypertension or diabetes, people who had experienced a TIA had a 4.5 to five times greater chance of a stroke. Study lead author Vasileios-Arsenios Lioutas, MD, said that the results show a need for intensive follow-up of TIA : “According to our findings, people continue to have a high risk of stroke for a sustained time after they’ve had a TIA. Therefore, one shouldn’t think that the high-risk period is just in the first 90 days after the attack and then one can relax. It seems these patients should be followed closely over time, keeping in mind that they are at risk for stroke and paying close attention to controlling their cardiovascular risk factors.”

The 66 years of study data was broken into three epochs. One- and five-year risks of post-TIA stroke in the 2000-2017 epoch were 7.6% and 16.1%, compared to 23.9% and 35.5% during the earliest epoch, from 1948 to 1985.

Sudha Seshadri, MD, professor of neurology at The University of Texas Health Science Center at San Antonio, said: “We examined 66 years of follow-up from Framingham participants, which allowed us to study trends over time. We can see that starting in the very early years of the Framingham study, the 1950s, moving on to the most recent times, the risk of subsequent stroke went down a lot.”

Source: News-Medical.Net

Journal information: Lioutas, V-A., et al. (2021) Incidence of Transient Ischemic Attack and Association With Long-term Risk of Stroke. JAMA.doi.org/10.1001/jama.2020.25071.

Mystery Protein is an Immune System Component

A protein called ITIH4, the function of which was largely a mystery, has been shown to a as a protease inhibitor, and a component of the innate immune system.

The discovery was made by Professor Steffen Thiel and PhD student Rasmus Pihl at Aarhus University, with the help of a mass spectrometry team led by Professor Jan J Enghild.

Proteases are enzymes which cleave other proteins, and usually occur in cascade networks where proteases cleave each other in a chain reaction. One example of this is blood clotting.

There is also the complement system in the body, which is responsible for eliminating pathogens, and cancerous or dying cells. Immunoglobin G (IgG) and M (IgM) antibodies activate complement proteins which work with them, hence the name “complement”. This system of enzymes is kept in check by protease inhibitors.

The researchers wanted to find out which other proteins in our blood the “MASP” proteases from the complement cascade interact with. They found to their surprise that two MASP proteases formed a strong complex with the ITIH4 protein, about which very little is known, especially its function.

“I was highly surprised when I saw the first data from our partners, showing that ITIH4 could form a complex with the MASP-1 and MASP-2 enzymes. At Biomedicine, we have been studying these two proteases for 25 years, and ITIH4 has simply never been on the radar. But it made good sense, as proteins similar to ITIH4 act as inhibitors of other proteases,” said Rasmus Pihl.

It was also discovered that when ITIH4 formed a complex with MASP-1 and MASP-2, they could still cleave small proteins, but when ITIH4 inhibited them, they could not cleave large proteins.The researchers discovered that ITIH4 performs an inhibitory enzyme function similar to that of one discovered in the 1980s called AM2, but it accomplished it in a new, entirely different manner.

“There is very little knowledge about ITIH4, but it is known that under various pathological conditions, the protein can be cleaved. Our results show that such a cleavage is absolutely necessary for the way ITIH4 can function as an enzyme inhibitor,” Professor Steffen Thiel explained.

Their colleague Gregers R Andersen added: “By using cryo-electron microscopy, we now try to understand in detail how ITIH4 inhibits MASP-1 and MASP-2 via this new inhibition mechanism. We already know that when ITIH4 is cleaved, it forms a complex with both MASP-1 and another ITIH4 molecule. We are very excited to see how it takes place.”

Source: Medical Xpress

Journal information: Rasmus Pihl et al, ITIH4 acts as a protease inhibitor by a novel inhibitory mechanism, Science Advances (2021). DOI: 10.1126/sciadv.aba7381

Happier Memories in Teens Linked to Less Alcohol and Marijuana Use

A study of teenage American students has found that happy childhood memories, along with a positive view of the present and outlook for the future are associated with reduced alcohol use, binge drinking and marijuana use. 

Researchers say that action is needed because COVID restrictions have left teenagers isolated and vulnerable. Quarantining results in anxiety, stress and feelings of loneliness in children and adolescents, and the closure of schools has also taken away mental health support systems which some teenagers may rely on.

John Mark Froiland of Purdue University said: “School often seems a source of stress and anxiety to students. This puts them at greater risk of not participating in lessons, getting lower grades and of substance misuse. Many teenagers also aren’t engaging with online learning during Covid or have lower engagement levels.

“But they’re more likely to be enthusiastic learners and not use drink and drugs if teachers take time to build more positive relationships with them. They can help students see that everything they’re learning is truly valuable. Parents have a role to play too.”

The study was based on questionnaires completed by 1961 student participants in San Francisco, of which 53% were female. The researchers examined how happy the students believed their childhood was, how happy they were currently and how optimistic they were about their futures.

In addition, they looked at alcohol and marijuana use over the past 30 days and binge use, as well as academic grades, behaviour during lessons and motivation.

Positive attitudes towards the past, present and future was associated with lower alcohol use, binge drinking and marijuana use, while the reverse was true for negative attitudes.

An optimistic outlook increased the likelihood that they would be motivated and focus on learning. Other findings included drinking being associated with marijuana use, and that girls had better behavioural engagement than boys.

Source: News-Medical.Net

Journal information: Froiland, J.M., et al. (2020) Positive and negative time attitudes, intrinsic motivation, behavioral engagement and substance use among urban adolescents. Addiction Research & Theory. doi.org/10.1080/16066359.2020.1857740.

Blood Vessels Self-Reinforce After Aneurysms

Immediately following an aneurysm, blood vessels reinforce themselves by adapting collagen fibres to spread out the load, a study has found. 

An aneurysm is an abnormal bulge in the artery wall that can form in brain arteries. Brain aneurysms that rupture are fatal in nearly 50% of cases. In a rabbit model, the researchers used cutting-edge high-resolution microscopes to observe changes within the aneurysm, and observed that new collagen fibres laid down to deal with the strain and existing ones were re-oriented. Blood vessels had already been known to be able to reform and restructure over time, but this kind of primary restructuring is the first time that it has been observed, happening immediately after an event.  Instead of forming along the same direction, the blood vessels adapt to the different directions the new loads are in. 

Professor Anne Robertson at the University of Pittsburgh’s Swanson School of Engineering explained: “Imagine stretching a rubber tube in a single direction so that it only needs to be reinforced for loads in that direction. However, in an aneurysm, the forces change to be more like those in a spherical balloon, with forces pulling in multiple directions, making it more vulnerable to bursting. Our study found that blood vessels are capable of adapting after an aneurysm forms. They can restructure their collagen fibers in multiple directions instead of just one, making it better able to handle the new loads without rupturing.

“The first restructuring phase involves putting down a layer collagen fibres in two directions to deal with the new load, and the second phase involves re-orienting existing layers to adjust to these two directions, explained Chao Sang, who was a primary investigator on this research as part of his doctoral dissertation.

“The long-term restructuring is akin to a scar forming after a cut has healed, while this first phase that we observed can be thought of as having a role similar to clotting immediately after the cut–the body’s first response to protect itself,” added Robertson, who has a secondary appointment in the Swanson School’s Department of Bioengineering. “Now that we know about this first phase, we can begin to investigate how to promote it in patients with aneurysms, and how factors like age and preexisting conditions affect this ability and may place a patient at higher risk for aneurysm rupture

Source: News-Medical.Net

Journal information: Sang, C., et al. (2020) Adaptive Remodeling in the Elastase-Induced Rabbit Aneurysms. Experimental Mechanics. doi.org/10.1007/s11340-020-00671-9.

Breast Cancer in Mice Inhibited by Restricted Feeding Times

Restricting calorie intake to an eight-hour window coinciding with physical activity reduced breast cancer risk in female mouse models.

Researchers from University of California San Diego School of Medicine, Moores Cancer Center and Veterans Affairs San Diego Healthcare System (VASDSH) found that the restricted feeding times, which are kind of circadian rhythm-linked intermittent fasting, enhanced metabolic health and tumour circadian rhythms in female mice with obesity-driven postmenopausal breast cancer. Breast cancer is the second most common cancer in US women, after skin cancer.

“Previous research has shown that obesity increases the risk of a variety of cancers by negatively affecting how the body reacts to insulin levels and changing circadian rhythms,” explained senior author Nicholas Webster, PhD. professor at UC San Diego School of Medicine and senior research career scientist at VASDSH. “We were able to increase insulin sensitivity, reduce hyperinsulinemia, restore circadian rhythms and reduce tumor growth by simply modifying when and for how long mice had access to food.”

Female mouse models mimicking postmenopausal hormone conditions were used to investigate if time-restricted feeding of obese mice affected the tumour growth and development, and reduced metastasis to the lungs. The mice were split into three groups, one with constant access to food, one with access for eight hours at night when they have the greatest activity, and the last was fed an unrestricted low-fat diet.

Obesity and menopause disrupt the circadian rhythm, with increased risk of insulin resistance and thereby chronic diseases such as cancer. A number of cancers are known to be associated with insulin resistance, such as breast cancer and pancreatic cancer. High insulin levels in obese mice drive tumour growth. Artificially increasing insulin levels has been shown to accelerate tumour growth whilst lowering them is similar to the effect of limiting eating.
Manasi Das, PhD, postdoctoral fellow in the Webster lab and first author, said: “Time-restricted eating has a positive effect on metabolic health and does not trigger the hunger and irritability that is associated with long-term fasting or calorie restriction. Through its beneficial metabolic effects, time-restricted eating may also provide an inexpensive, easy to adopt, but effective strategy to prevent and inhibit breast cancer without requiring a change in diet or physical activity.”

Webster believes that time-restricting eating warrants further investigations as it may present a way to reduce breast cancer risk, or that of cancer in general.

“The increase in risk of breast cancer is particularly high in women who are overweight and have been through menopause. For this reason, doctors may advise women to adopt weight loss strategies to prevent tumor growth,” said Das. “Our data suggests that a person may benefit from simply timing their meals differently to prevent breast cancer rather than changing what they eat.”

Source: Medical Xpress

Journal information: Manasi Das et al. Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models, Nature Communications (2021). DOI: 10.1038/s41467-020-20743-7

EU to Restrict AstraZeneca Exports to Tackle Vaccine Shortage

In response to AstraZeneca’s COVID vaccine production and delays, the European Union has warned that it will tighten exports of the company’s vaccine to countries outside its borders.

EU Health Commissioner Stella Kyriakides warned it would “take any action required to protect its citizens”, adding that she had requested detailed delivery schedules and a meeting next week with the company. She added that “in the future, all companies producing vaccines against Covid-19 in the EU will have to provide early notification whenever they want to export vaccines to third countries”.

The vaccine, developed by Oxford University and the British-Swedish company AstraZeneca, is still yet to be approved in the EU but should receive it by the end of January, with distribution set to start on the 15th of February. The EU has been suffering from a number of vaccination programme setbacks, including a previous announcement last week from Pfizer that its own deliveries were being delayed in order to upgrade manufacturing capabilities at a plant in Belgium, provoking ire amongst EU politicians. Italy’s PM has resigned over handling of the pandemic.

The EU had signed a deal in August to secure 300 million doses from AstraZeneca, with an option for another 100 million. Last week, AstraZeneca had announced a slowdown in delivery due to “reduced yields at a manufacturing site within our European supply chain”. The problem is thought to be from a manufacturing plant also in Belgium, which is run by an AstraZeneca partner firm. The exact size of the shortfall is not known but some believe it to be a drop of 31 million doses, or 60% of those meant to be delivered by the end of the quarter.

Where this leaves low and middle-income countries counting on the Oxford/AstraZeneca vaccines is unclear, but it certainly will add to mounting tension between countries seeking vaccines for their populations amidst the spread of more contagious COVID variants. President Cyril Ramaphosa warned in an address to the World Economic Forum that vaccine nationalism was a growing concern and threat to global recovery. The African Union’s vaccine task team has thus far managed to secure only 270 million doses.

Source: BBC News