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Monday, April 29, 2024
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In a living systematic review and meta-analysis in The BMJ, scientists from the United Kingdom, along with international collaborators, continue to collate and analyze emerging evidence of how COVID-19 affects women and their babies during and shortly after pregnancy.

In the latest update, the team confirms that pregnant women attending or admitted to the hospital from whatever cause continue to be at a greater risk of severe COVID-19 than nonpregnant women of similar ages.

Preexisting diabetes, chronic hypertension, asthma, smoking, gestational diabetes, preeclampsia, being aged 35 years or over, and having a body mass index (BMI) of 30 or above were all associated with greater odds of severe COVID-19 and requiring admission to the intensive care unit (ICU).

Nonwhite ethnicity was linked with a greater likelihood of ICU admission, but not necessarily with severe COVID-19.

Meanwhile, babies of mothers with COVID-19 were more likely to require admission to the neonatal intensive care unit (NICU). The authors note that this could be due to hospital policies for observation and quarantine of babies in contact with COVID-19.

Dr. John Allotey, the study’s first author and a lecturer in epidemiology and women’s health at the World Health Organization (WHO) Collaborating Centre for Global Women’s Health at the University of Birmingham in the U.K., comments: “Pregnant women should be considered a high risk group, particularly those identified to have risk factors, for severe COVID-19 based on our findings.”

“Mothers should also be reassured that the risks to their babies are very low,” he continues.

Reviewing the evidence

The research team started work on the review in April 2020. For its first iteration, they collated data from available publications between December 2019 and June 2020.

Each week, the researchers looked for newly published data, which they aimed to review every 2–4 months. For the recent update, they added new studies published up until October 2020.

The review now includes data from 192 studies and 29 different countries. Of these studies, 115 were new editions to the latest update.

Overall, the data show that 10% of pregnant women who are either admitted to the hospital or visiting the hospital receive a positive SARS-CoV-2 test.

Pregnant women are more likely than nonpregnant women to have an asymptomatic SARS-CoV-2 infection.

However, the reason for this may lie in the strategy for testing.

Pregnant people routinely undergo COVID-19 testing when they attend hospital appointments, while nonpregnant individuals most likely have a test when they experience symptoms.

“[The] true prevalence of [COVID-19] in pregnancy is likely to be lower than the current estimate if all pregnant women, including those not attending the hospital, are included,” the authors comment in the paper.

While the risk of severe COVID-19 was greater for pregnant women than for nonpregnant women overall, there were specific risk factors that the team identified.

These include age, BMI, preexisting conditions, as well as conditions developed during pregnancy.

The researchers found that pregnant women or those who had recently given birth were more likely to die if they had COVID-19 than those who were the same age but not pregnant. In addition, the rates of premature birth and stillbirth were higher for women with the disease.

However, the team caveat that the premature births are likely to be the result of medical decisions to induce early delivery in those with COVID-19 as the number of spontaneous preterm births was the same as baseline levels. The number of stillbirths across all of the studies included in the review was very small (9 out of 5,794 women with COVID-19).

More data needed

One further issue that this review found is that women who were of nonwhite ethnicity were more likely to require admission to the ICU for COVID-19 treatment.

There was a link between nonwhite ethnicity and a greater likelihood of ICU admission, based on four studies covering 31,456 individuals. Four smaller studies covering 2,263 women suggested that nonwhite ethnicity may result in having a 6% lower chance of severe disease. However, this figure could vary between 43% less likely and 57% more likely.

Other studies have previously found disparities in maternal outcomes between people of different ethnicities.

“The observed disparity could be attributed to associated comorbidities, socioeconomic characteristics, and factors related to access to and quality of care in the preconception, pregnancy, and postpartum periods,” the review’s authors write in their discussion. “The multifaceted contributors to ethnic disparities need to be investigated to reduce mortality and morbidity related to both [COVID-19] and pregnancy.”

The team highlights several limitations of their review, including the fact that the studies included in the analysis did not use the same methods to collect and gather data. This is an issue that all systematic reviews face.

Senior study author Professor Shakila Thangaratinam, who is the Co-Director of the WHO Collaborating Centre for Global Women’s Health, comments on the team’s finding:

“In the current situation, where evidence is rapidly produced, our living systematic review — underpinned by robust methods and continually updated at regular intervals — is crucial to address important research questions and to shape healthcare policy and clinical decision-making.”

“Pregnant women and healthcare professionals will need to take into account the additional risks faced by pregnant women with COVID-19 in making decisions, such as taking-up of vaccines if offered to prevent COVID-19 and plan management in pregnancy.” – Prof. Shakila Thangaratinam

The Centers for Disease Control and Prevention (CDC) additionally state that “[a]lthough the overall risk of severe illness is low, pregnant people are at an increased risk for severe illness from COVID-19 when compared to nonpregnant people.”

They advise nonpharmaceutical interventions, such as mask wearing, physical distancing, avoiding crowds, and limiting contact with people who may have been exposed to the SARS-CoV-2 virus to reduce the risk of developing COVID-19.

The CDC also suggest having a COVID-19 vaccine when it is available to pregnant people and speaking with a healthcare professional about any questions or concerns.

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Humans first drank caffeinated tea more than 4,000 years ago in China. Since then, it has become one of the most popular drinks worldwide, second only to water.

Both green and black teas are brewed from the leaves of the same shrub, Camellia sinensis, but green tea, which is made from unfermented leaves, contains more antioxidants.

Oxidation during the fermentation process of black tea reduces its antioxidant levels.

Several studies have found that green tea inhibits the formation of cancers, lowers high blood pressure, and reduces the risk of heart disease.

However, the molecular mechanism responsible for the effect on blood pressure has been unclear until now.

Scientists at the University of California, Irvine (UCI) and the University of Copenhagen, in Denmark, have found that antioxidants in tea open ion channels and can relax the muscles that line blood vessels.

They report their findings in the journal Cellular Physiology & Biochemistry.

Preventable risk factor

The discovery could guide the design of more effective antihypertensive drugs, which could potentially improve the health of millions of people around the world.

According to the National Heart, Lung, and Blood Institute, controlling or lowering high blood pressure can help prevent chronic kidney disease, heart attacks, heart failure, and possibly dementia.

The Centers for Disease Control and Prevention (CDC) report that almost half of all adults in the United States have hypertension. It estimates that in 2018, the condition played a role in the deaths of nearly half a million people in the country.

The World Health Organization (WHO), meanwhile, estimate that more than 1 billion people worldwide have hypertension.

The new study first shows that two antioxidants in tea, known as catechins, open a protein channel in the membranes of the smooth muscle cells that line blood vessels. This allows positively charged potassium ions to leave the cells.

Channels in nerve and muscle cells maintain voltages across their membranes by allowing negative and positive ions to pass in and out in a controlled way. They are “voltage-gated,” which means that they respond to changes in this voltage by opening or closing.

The researchers found that the catechins in green tea activate a particular type of potassium ion channel, called KCNQ5.

Previous work by some of the same scientists suggests that this protein channel may underlie the antihypertensive effects of several plants used as folk medicines for millennia.

Voltage sensor

For the new study, the researchers used computer modeling and mutated versions of the channel protein to show that the two catechins bind to a section that senses voltage changes.

“This binding allows the channel to open much more easily and earlier in the cellular excitation process,” explains senior study author Prof. Geoffrey Abbott, of the Department of Physiology & Biophysics at the UCI School of Medicine.

In theory, this should make the muscle cells less “excitable” and therefore less likely to contract. They should instead relax, dilating the blood vessel and reducing blood pressure.

To test this theory, Prof. Abbott’s co-authors at the University of Copenhagen measured changes in tension in the walls of arteries from rats. Their findings confirmed that the two catechins from tea relax and dilate arteries by activating the KCNQ5 ion channel.

Milky tea

The authors are confident that adding a dash of milk to black tea does not reduce its antihypertensive effects.

Milky tea, applied directly to cells in the lab, failed to activate their KCNQ5 channels. But this is likely not the case when a person drinks it.

Prof. Abbott explains:

“We don’t believe this means one needs to avoid milk when drinking tea to take advantage of the beneficial properties of tea. We are confident that the environment in the human stomach will separate the catechins from the proteins and other molecules in milk that would otherwise block [the] catechins’ beneficial effects.”

The scientists also discovered that warming green tea to 35°C increased the activation of KCNQ5.

However, lovers of iced tea need not be concerned.

“Regardless of whether tea is consumed iced or hot, this temperature is achieved after tea is drunk, as human body temperature is about 37°C,” says Prof. Abbott. “Thus, simply by drinking tea, we activate its beneficial, antihypertensive properties.”

Electrical activity in the brain

KCNQ5 also exists in the membranes of nerves in the brain, where it helps regulate electrical activity and signal transmission.

People with a disorder called epileptic encephalopathy have a version of the channel protein that does not respond effectively to voltage changes, which leads to frequent seizures.

The study authors point out that catechins can cross the blood-brain barrier, which prevents larger molecules, including some drugs, from entering the brain.

In theory, drugs modeled on catechin molecules could, therefore, help correct the cause of epileptic encephalopathy.

“Discovery of their ability to activate KCNQ5 may suggest a future mechanism to fix broken KCNQ5 channels to ameliorate brain excitability disorders stemming from their dysfunction,” the researchers conclude.

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Globally, heart disease is the number one cause of death. It is responsible for 17.9 million deaths each year.

According to the Centers for Disease Control and Prevention (CDC), in the United States, one person dies every 36 seconds from cardiovascular disease. Heart disease accounts for 1 in 4 deaths in the U.S.

As February is American Heart Month, today, we will tackle some persistent myths about heart disease.

1. Young people do not need to worry about heart disease

It is true that heart disease is more likely to affect people over the age of 65, but 4–10% of heart attacks occur in people under the age of 45 years, mainly in men. In addition, it is how we live our lives as children, adolescents, and adults that lays the groundwork for heart health as we age.

For instance, eating a diet that is high in trans and saturated fats or smoking tobacco slowly increases the risk of heart disease as we age. Changes to lifestyle today build the foundation for a healthier heart in later life.

In the U.S. as a whole, heart disease mortality has slowly dropped since the 1970s, although the trend seems to be slowing. However, in some regions, rates have increased.

One study that investigated heart disease mortality in different age groups in the U.S. found that “over 50% of counties [experienced] increases in heart disease mortality from 2010 through 2015 among adults aged 35–64 years.”

2. People should avoid exercise if they have heart disease

This is a myth. Exercise helps strengthen the heart muscle and improve blood flow around the body.

In August 2020, the European Society of Cardiology published guidelines on exercise in patients with cardiovascular disease. Prof. Sanjay Sharma, who was involved in creating the guidelines, explains:

“The chance of exercise triggering a cardiac arrest or heart attack is extremely low.” However, he also adds a note of caution: “People who are completely inactive and those with advanced heart disease should consult their doctor before taking up sports.”

3. I take cholesterol-lowering drugs, so I can eat whatever I like

Some drugs, such as statins, reduce the level of cholesterol in the blood. However, this does not mean that a person who is taking statins can consume foods containing saturated fats with abandon.

Cholesterol is either consumed in the food that you eat or produced in the liver. Statins block an enzyme in the liver that is necessary for producing cholesterol, reducing overall blood cholesterol levels. However, this means that ingested cholesterol can still make it into the blood.

In short, statins may just be able to override the adverse effects of a poor diet, but a poor diet will increase risk of other independent risk factors for heart disease, such as obesity, hypertension, and diabetes.

4. Heart disease runs in my family, so there is nothing I can do to stop it

If close family members have experienced heart disease, it could mean that you have an increased risk. However, it is not set in stone, and there are a number of ways to reduce the risk, even for people with a genetic susceptibility.

These include eating a healthful diet, stopping smoking, managing blood pressure, and exercising regularly.

It is also worth noting that if heart disease runs in the family, it may not be a sign of genetic susceptibility. Families tend to share lifestyle factors, such as diet and exercise habits, both of which can impact the risk of heart disease.

5. Vitamins can prevent heart disease

Although most vitamins, taken at the recommended doses, are unlikely to be bad for heart health, there is no evidence that taking any vitamin supplements can reduce the risk of heart disease. And they certainly cannot replace a healthful diet and regular exercise.

For instance, a systematic review and meta-analysis looked for associations between multivitamin and mineral supplements and a number of cardiovascular outcomes, including coronary heart disease and stroke.

The analysis, published in 2018, took data from 18 existing studies, including 2,019,862 participants.

The authors concluded that multivitamin and mineral “supplementation does not improve cardiovascular outcomes in the general population.”

According to Victoria Taylor, the nutrition lead at the British Heart Foundation: “There are no shortcuts when it comes to nutrition — supplements are not a replacement for healthy food. You might be prescribed a vitamin or mineral supplement by a health professional for other reasons, but we do not recommend people take multivitamins to help prevent heart and circulatory diseases.”

6. I have smoked for years, there is no point stopping now

This is a myth. Smoking tobacco is a major cause of heart disease. As soon as a person stops smoking, the health benefits begin. The National Institute on Aging write:

“It doesn’t matter how old you are or how long you’ve been smoking, quitting smoking at any time improves your health. When you quit, you are likely to add years to your life, breathe more easily, have more energy, and save money.”

They also explain that you will lower the risk of heart attack and stroke and have better circulation.

7. Heart disease only really affects men

This is a myth, as heart disease is the leading cause of death in both men and women. In 2017 in the U.S., 24.2% of men and 21.8% of women died from heart disease.

However, when strokes, which have similar risk factors, are added in, the figures are even more similar between men and women: 28.7% of men and 28% of women died from heart disease or stroke.

It is a common misconception that only men are affected by heart disease. It is true that men tend to develop cardiovascular disease at an earlier age than women and have a greater risk of coronary heart disease. However, women have a higher risk of stroke.

One paper explains, “Although the incidence of [cardiovascular disease] in women is usually lower than in men, women have a higher mortality and worse prognosis after acute cardiovascular events.”

8. Cardiac arrest and heart attack are the same

Heart attacks and cardiac arrests are not the same thing. A heart attack is a circulation problem. It occurs when the coronary artery, which carries oxygenated blood to the muscles of the heart, becomes blocked.

A cardiac arrest is an “electrical problem,” where the heart stops pumping blood around the body effectively. Cardiac arrests are often caused by a heart attack.

During a heart attack, an individual is likely to be conscious. During a cardiac arrest, they are almost always unconscious. Both are a medical emergency.

9. Coughing during a heart attack can save your life

According to some sources, coughing vigorously during a heart attack — so-called cough CPR — can save your life.

This is an internet distortion of a paper published over 40 years ago, which showed that patients who had a cardiac arrest during arteriography in hospital and who coughed every 1–3 seconds stayed conscious for an additional 39 seconds.

There is no evidence that this technique works in the community for heart attacks that are not induced by medical procedures.

According to Christopher Allen, a senior cardiac nurse:

“The absolute priority when you think you or someone else is having a heart attack is to call [the emergency services]. This way, paramedics can assess and aid you, and you’ll get to hospital as fast as possible. There is no medical evidence to support ‘cough CPR.’”

10. People with heart disease should avoid eating all fat

A person with cardiovascular disease certainly should reduce their intake of saturated fats — which are found in foods such as butter, biscuits, bacon, and sausages — and partially hydrogenated and trans fats, which are found in foods such as baked goods, frozen pizzas, and microwave popcorn.

However, unsaturated fats can provide benefits. For instance, there is some evidence that omega-3, which is a polyunsaturated fat, might protect heart health.

The American Heart Association recommend “that all adults eat fish (particularly fatty fish) at least 2 times a week. Fish is a good source of protein and is low in saturated fat. Fish, especially oily species like mackerel, lake trout, herring, sardines, albacore tuna, and salmon, provide significant amounts of the two kinds of omega-3 fatty acids shown to be cardioprotective, [eicosapentaenoic acid] and [docosahexaenoic acid].”

They also recommend eating plant-derived omega-3 fatty acids. These can be found in tofu and other forms of soybeans; walnuts, flaxseeds, and their oils; and canola oil.

The take-home

Heart disease is common, but it is not inevitable. There are lifestyle changes that we can all implement to reduce the risk of developing cardiovascular problems, whatever our age.

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For many decades, nutritionists have recommended a balanced diet to provide the body with the proper nutrients to stay healthy. The core components of this diet include vegetables, fruits, grains, proteins, and dairy.

A recent study by researchers at the Harvard T. H. Chan School of Public Health in Boston, MA, provides further evidence for current dietary guidelines and expands on them, finding that consuming at least 2 fruit and 3 vegetable servings on a daily basis may lower the risk of both disease-related death and death from all causes.

The study appears in Circulation, a scientific journal of the American Heart Association (AHA).

Current dietary guidelines

“While groups like the American Heart Association recommend 4–5 servings each of fruits and vegetables daily, consumers likely get inconsistent messages about […] the recommended amount and which foods to include and avoid,” says Dr. Dong D. Wang, M.D., Sc.D., an epidemiologist and nutritionist at Harvard Medical School and lead author of the study.

The Department of Health and Human Services and the Department of Agriculture published their recommendations in the form of the 2020–2025 Dietary Guidelines for Americans.

According to this set of guidelines, half of the plate for every meal should contain fruits and vegetables.

However, the guidelines also note that more than 80% of people in the United States do not meet this recommendation and should aim to increase their consumption of nutrient-dense foods.

Participant dietary information

The researchers collected self-reported dietary information from two large cohort studies: the Nurses’ Health Study (NHS) and the Health Professionals’ Follow-up Study (HPFS).

The NHS cohort included registered female nurses between the ages of 30 and 55 years, while the HPFS cohort included males aged 40–75 years with occupations in the health profession. These studies included follow-ups with the participants every 2–4 years to accumulate dietary information over a span of approximately 30 years.

The researchers excluded participants with baseline heart disease, cancer, or diabetes, leaving them with data from 66,719 females and 42,016 males.

They also incorporated data from an additional 26 studies involving a total of 1.9 million participants, which examined the relationship between fruit and vegetable intake and death rates.

The high participant numbers and continuous longitudinal assessments provided the team with an extensive collection of data for analysis.

However, it is important to note that the criteria of the two cohorts — occupation and corresponding education — suggest a similar socioeconomic status across the participants, who may have been more likely than other members of the population to have access to a healthy diet. The study does not address the realities and effects of food insecurity.

Nutritional values of fruits and vegetables lower risk of death

The study outcomes showed that an increased intake of fruits and vegetables is associated with a lower risk of death, including death due to cancer, heart disease, or respiratory disease.

Additionally, the researchers saw the lowest risk of death at a threshold of a combined 5 servings, beyond which there was no apparent benefit on risk.

These results point to the nutritional value of these foods. For example, higher consumption of fruits and vegetables increases the intake of potassium and antioxidant activity, which link to lower blood pressure and improved lung function, respectively.

As the data are fully self-reported, there may be discrepancies between the actual and reported intakes. Participants with higher intake, in particular, may have tended to overestimate how many servings they consumed.

This margin of error may blur the defined threshold of 5 servings, so the study authors acknowledge that slightly higher servings (up to 10) could also lead to lowered risk.

This study also expands beyond current guidelines by differentiating among specific groups of fruits and vegetables.

The researchers observed trends with a lowered risk of death for leafy greens and foods rich in vitamin C and beta carotene. Fruits and vegetables that fall into these categories include spinach, kale, carrots, and citrus fruits.

Conversely, they did not identify any trends for fruit juices or starchy vegetables, such as potatoes and peas. One possible reason for the latter is the prominence of canned foods. The canning process may deprive starchy vegetables of their antioxidant properties.

Compared with whole fruits, the fluid form of juices may cause a more rapid elevation of blood glucose and insulin levels, which can increase the risk of disease.

In contrast to the existing guidelines, which include canned foods and juices among the recommended foods and drinks, this study calls for further research on the effects of these items on health.

Continued support for ‘5-a-day’ serving recommendation

Rather than being an interventional study, in which researchers directly implement variables and analyze the effects, this study was observational. As a result, it is not possible to conclude that the trends present in this study indicate a causal relationship.

Regardless, there is plentiful evidence that highlights the benefits of a balanced diet containing plenty of fruits and vegetables. The present conclusions also correspond to findings from similar observational studies on the associations between fruit and vegetable intake and disease.

The findings of this study conform to the overall current dietary guidelines to eat at least 5 servings of fruits and vegetables a day. Additionally, it provides further insight into the specificities and benefits of fruit and vegetable intake.

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Around 1 million people in the United States and 10 million people worldwide have Parkinson’s. It is the second most common neurodegenerative disorder after Alzheimer’s disease.

Parkinson’s disease is a progressive brain disorder that affects dopamine-producing neurons. It causes tremors, muscular stiffness or rigidity, and slowness of movement, among other symptoms.

Loss and degeneration of dopamine-producing neurons in a specific region of the brain called the substantia nigra causes the movement-related, or “motor,” symptoms that can characterize Parkinson’s.

There is no cure for Parkinson’s disease, though several drug treatments can help alleviate the symptoms. The most commonly prescribed medication for this purpose is levodopa (Sinemet), which replenishes dopamine levels.

“Currently, there is no preventive medicine for Parkinson’s disease,” notes Dr. Akiko Kojima-Yuasa, an associate professor at the Graduate School of Human Life Science at Osaka City University, in Japan, “we only have coping treatments.”

One cause of cell loss in the substantia nigra is oxidative stress. This led Dr. Kojima-Yuasa and colleagues to investigate whether sesaminol, a powerful antioxidant, could prevent nerve cell death in a model of Parkinson’s.

Sesaminol is found in abundance in sesame seed husks, which are a waste product from the industrial extraction of sesame oil.

Oxidative damage

The researchers used a toxic chemical called 6-hydroxydopamine to model the oxidative damage that occurs in Parkinson’s.

When they applied the chemical to human nerve cells growing in lab cultures, the concentration of damaging reactive oxygen species increased, and the cells began to die off.

Adding sesaminol to the cultures significantly reduced the concentration of reactive oxygen species and prevented cell death. Sesaminol appeared to shield the cells from oxidative damage by increasing their production of two protective proteins: Nrf2 and NQO1.

Next, the researchers turned to a standard animal model of Parkinson’s disease, which involves dosing mice with the neurotoxin rotenone.

The toxin reduces dopamine production in the animals’ brains. This impairs their motor abilities and reduces their gut motility, which are both classic symptoms of Parkinson’s in humans. In fact, people with the disease might experience constipation decades before difficulties with movement become apparent.

Mice that ate a diet containing sesaminol for 36 days had higher dopamine levels and performed better on a standard test of motor abilities than control-group mice that ate a normal diet. The gut motility of the mice in the test group was also normal.

In addition, the mice that ate sesaminol had lower levels of alpha-synuclein in their substantia nigras. Alpha-synuclein is a protein that clumps together to form larger structures called Lewy bodies, which are a characteristic feature of neurodegeneration in Parkinson’s.

The research has been published in the journal Heliyon.

Preventive treatment?

In their paper, the scientists conclude:

“Notably, the protective effect was observed with the feeding of a small amount of sesaminol. These results show that sesaminol is very suitable for use as a preventive treatment of [Parkinson’s disease]. Further detailed elucidation of the mechanism of action will be necessary for practical application.” Dr. Kojima-Yuasa and her team are keen to start clinical trials of the extract.

The authors suggest that sesaminol may be able to cross the blood-brain barrier in humans. This barrier prevents pathogens and large molecules from entering the brain. Further investigation, however, is needed to support the findings.

Overall, it is worth keeping in mind that results of studies in cell cultures and animal models do not always reflect what happens in the human body.

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Research is currently underway to determine whether it is possible to repurpose existing medications to prevent or treat COVID-19.

To guide healthcare professionals through this ever-evolving wave of new evidence, the World Health Organization (WHO) is creating a ‘living’ guideline outlining the most complete, accurate, up-to-date information on COVID-19 management.

This guideline also offers patients the chance to consider their best treatment options. The WHO have called it a ‘living’ guideline because they will continuously update it to reflect new knowledge.

To create this living guideline, experts, doctors, patients, and methodologists from around the world are assessing existing studies to produce a set of universal recommendations.

On March 1, 2020, the panel released the first installment of the living WHO guideline on drugs to prevent COVID-19 in the British Medical Journal.

In this first installment, the panel evaluates whether hydroxychloroquine can help prevent COVID-19.

These findings could focus research efforts on more effective, safer treatment and prevention options for COVID-19. It could also discourage doctors and patients from using a medication that is likely to do more harm than good.

Why focus on hydroxychloroquine?

Scientists developed hydroxychloroquine in 1946 to reduce the risk of getting malaria and help treat it. Today, doctors use the drug to treat several autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus.

Some early in vitro studies suggested that hydroxychloroquine may help reduce the risk of developing COVID-19 in several ways.

Hydroxychloroquine raises the pH inside of endosomes, a group of organelles inside cells that regulate the exchange of proteins and lipids. This may make it difficult for SARS-CoV-2 to fuse with cell membranes.

Some studies have also shown that hydroxychloroquine appears to block the release of SARS-CoV-2 viral particles from infected cells.

Once viruses enter cells, they take over the cell’s machinery to reproduce its own genetic material, ribonucleic acid (RNA). The cell typically releases these new viral particles with help from late-stage or mature endosomes.

Hydroxychloroquine appears to prevent the transport of new viral particles into these special endosomes, preventing their release.

But scientists have not confirmed most of these findings in humans, only in cells from organisms.

In one study, hydroxychloroquine had some antiviral effect in African green monkey kidney cells, but not in cell models from the lining of human airways.

Another study using macaque monkeys also concluded that hydroxychloroquine was not effective in preventing infection with SARS-CoV-2.

A few early studies, including small human studies without a control group, suggested that hydroxychloroquine could treat patients with COVID-19.

The FDA issued an emergency use authorization in March 2020 that allowed healthcare professionals to use hydroxychloroquine in teens and adults hospitalized for COVID-19 who weigh more than 110 pounds.

And doctors in many hospitals starting using hydroxychloroquine routinely in COVID-19 patients.

But even at the time of its issuing, the FDA noted that a person should only use the drug when a healthcare professional feels the possible benefits outweigh the risks.

That is because hydroxychloroquine carries substantial health risks, including:

  • serious heart rhythm problems
  • anemia
  • low blood sugar
  • damage to the tissues in the inner eye that may cause a vision problem
  • worsening of neurological problems or seizures
  • drug interactions, such as with some beta-blockers, antidepressants, antipsychotics, and methadone

Dangers outweigh potential health benefits

By mid-June, the FDA formally revoked this emergency issue, claiming the potential benefits of the drug in cases of COVID-19 did not outweigh existing and potential health risks.

There were reports of serious cardiac side effects and other adverse effects at the doses doctors used for treating people hospitalized with Covid-19.

Hydroxychloroquine typically has few severe side effects when used to treat conditions such as rheumatoid arthritis and systemic lupus erythematosus.

Possible reasons why the drug is more toxic in people with COVID-19 include:

  • people hospitalized with COVID-19 received higher doses of the drug
  • the cardiac inflammation caused by COVID-19 may have increased the cardiac side effects of the drug
  • interaction with other medications, such as azithromycin, exacerbated the risk of potentially lethal cardiac rhythm abnormalities

A few days later, the National Institute of Health (NIH) halted its clinical trial evaluating the efficacy and safety of using hydroxychloroquine in adults hospitalized for COVID-19.

Creating a ‘living guideline’

To create the living WHO guideline, collaborators from the MAGIC Evidence Ecosystem Foundation first analyzed six randomized, controlled trials. The six trials included 6,059 participants with or without exposure to COVID-19.

Making GRADE the Irresistible Choice (MAGIC) is a non-profit foundation that creates reliable, evidence-based digital tools to share guidelines with healthcare professionals and patients.

The acronym GRADE stands for Grading of Recommendations, Assessment, Development and Evaluations. It describes a popular framework for assessing and sharing summaries of scientific evidence that help guide clinical recommendations.

The WHO panel reviewed the MAGIC team’s findings to determine the accuracy of the findings and form their recommendations for the guideline.

Researchers often describe how confident they are in study findings by defining the level of certainty of the evidence supporting it. Typically, the more positive research to support an idea, the higher the certainty of the evidence and the more likely it is to be true in the real world.

In the new review of trials testing hydroxychloroquine for preventing COVID-19, the team found high certainty evidence indicating hydroxychloroquine has no significant impact on the risk of COVID-19 death or hospital admission.

The WHO panel also found moderate certainty evidence that the drug does not significantly impact the risk of developing COVID-19.

The panel concludes that using hydroxychloroquine may increase the risk of experiencing side effects severe enough to stop taking the drug when compared with a placebo.

People in the trials taking hydroxychloroquine had many more minor side effects, such as diarrhea and headaches, than those in the placebo group (56% vs. 6%). However, only marginally more people had side effects serious enough to stop taking the drug compared with a placebo.

Reconsidering priorities and resources

Based on these findings, the panel recommends that researchers shift their priority and resources to explore other medications.

This new guideline could help uncover more effective COVID-19 therapies by focusing research efforts and funding on prevention and treatment options with more promising results.

It may also bust the widespread myths and misconceptions that led to some people accessing or taking hydroxychloroquine to prevent or treat COVID-19 without medical advice.

And this is good news given the long-list of adverse side effects associated with taking hydroxychloroquine unnecessarily.

It could also be very good news for people with autoimmune diseases, such as lupus, who need the medication to stay healthy and who have been facing drug shortages.

The panel encourages researchers, doctors, and patients to check back for more information as they include new recommendations within the existing published document.

This review is a good reminder that drugs showing promise in the laboratory and in initial observational, non-randomized human studies may not deliver the hoped-for results in well-conducted randomized trials.

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Mental health conditions can cause changes in thinking, emotions, behavior, or all of these, impairing interpersonal relationships and daily functioning. They can be temporary or chronic.

Approximately 26% of adults in the United States will experience a mental health condition within a given year, with close to 9.5% having a serious condition, such as major depression or bipolar disorder.

Although pharmacologic and psychosocial treatment options for psychiatric illnesses can be safe and effective, there are cases in which the treatments may cause significant adverse effects in some individuals, potentially leading to discontinuation. In addition, some illnesses are treatment-resistant.

One possible reason why current standard-of-care treatments have varying efficacy is that they do not target the disruption to neural circuits that researchers have associated with mental illness.

Researchers can use functional MRI (fMRI), a noninvasive neuroimaging tool that measures brain activity through changes in cerebral blood flow, to comprehend the neurobiological changes accompanying psychiatric illness.

In the new study, the researchers used rtfMRI-NF, which incorporates biofeedback, to teach the participants how to control their own brain neural activity instantaneously while in a scanner. Biofeedback is a treatment that healthcare professionals sometimes use to control involuntary bodily processes.

Novel treatment method

Although some studies using rtfMRI-NF experimentally to treat a wide range of mental illnesses have demonstrated benefits, rtfMRI-NF is costly, and it requires extensive setup for real-time analysis.

Researchers at the University of Rochester Medical Center in New York conducted a meta-analysis of 17 relevant studies to determine the effectiveness of rtfMRI-NF in modulating brain activity and behavioral outcomes.

They have published their findings in Neuroscience & Biobehavioral Reviews.

Study co-author Dr. David Dodell-Feder, an assistant professor at both the Department of Psychology in the School of Arts and Sciences at the University of Rochester and the Department of Neuroscience at the University’s Medical Center, comments on the objectives of the review:

“Ultimately, we want people to be able to take what they learn in the scanner during the training sessions to use in their day-to-day life. If they can do that, it shows that the neurofeedback is meaningful, that they are taking something away from it, and that they can now apply that experience — even without neurofeedback.”

The meta-analysis evaluated whether rtfMRI-NF led to voluntary control of brain activity during training, whether the effects persisted after training (in the absence of neurofeedback), and whether treatment resulted in improved outcomes.

The studies that the team analyzed included 410 participants, of whom 234 received rtfMRI-NF. The study participants were 34 years old, on average, and there were almost equal numbers of males and females. About 53% of the participants took psychotropic medications.

The studies included participants with diagnoses such as:

  • depressive disorders
  • schizophrenia and other psychotic disorders
  • neurodevelopmental disorders
  • substance-related and addictive disorders
  • trauma and stressor-related disorders
  • anxiety disorders

The study participants completed an average of two sessions with a total regulation time of about 24 minutes across sessions. Most studies compared active neurofeedback with a sham feedback control group.

The area of the brain targeted most often as the source of the neurofeedback signal was the amygdala. The amygdala is part of the brain’s limbic system, and it is responsible for processing strong emotions, such as fear and pleasure.

Additionally, most studies provided explicit instructions for regulating the neural signal, measured the percent signal-change that a task triggered, provided continuous neurofeedback, and included a transfer task to measure whether the participant could perform the previously learned regulation during the period of no neurofeedback.

Some positive results

The meta-analysis found that rtfMRI-NF produced a moderate effect on the brain activity of targeted regions during training and a large effect after training in the absence of neurofeedback.

However, rtfMRI-NF demonstrated only a small effect on symptoms and cognitive impairment.

Emily Dudek, lead author and a clinical research coordinator at the Brain Injury Research Center of Mount Sinai in New York City, comments on the results:

“We believe this provides relatively strong evidence that volitional control over neural processes that are specifically targeted during training is possible. This volitional control was also present in contexts in which no feedback was provided,” she notes.

The possibility of publication bias — the influence of nonpublished studies that failed to find an effect — that the team detected during analyses may further decrease the measured effect of rtfMRI-NF on symptoms.

Limitations of the meta-analysis include small study sample sizes leading to potential underpowering and decreased validity of results.

Further research involving adequately powered, high quality studies is necessary to elucidate specifically how and for whom rtfMRI-NF demonstrates effectiveness to optimize potential clinical benefits. Future studies may be crucial to proving the clinical utility of rtfMRI-NF outside a research setting.

Prof. Dodell-Feder, Dr. J. Steven Lamberti, from the Department of Psychiatry at the University of Rochester Medical Center, and a graduate student team have set out to conduct a rtfMRI-NF research study aiming to teach people with schizophrenia to self-regulate areas of the brain responsible for social information processing.

The trial is ongoing, and, hopefully, the results of the study will provide some much-needed answers.

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Researchers have found that aerobic exercise may reduce cognitive decline in people with Alzheimer’s disease.

The research, published as a pilot study in the Journal of Alzheimer’s Disease, supports aerobic exercise as an intervention for people with this condition and lays the ground for future, larger studies to corroborate the initial findings.

Alzheimer’s treatments

According to the National Institute on Aging (NIA), Alzheimer’s disease is an irreversible and progressive neurological disorder.

At its mildest, it can affect a person’s ability to think or remember things. Moderate forms of the condition can affect a person’s brain areas and impair language, reasoning, sensory processing, and conscious thought.

When the disease progresses to become severe, it can stop a person from performing basic, everyday tasks and recognizing or communicating with friends or family.

According to the NIA, researchers estimate Alzheimer’s disease affects over 5.5 million people in the United States. It typically first appears in people in their mid-60s.

The Alzheimer’s Association highlight that there is no known cure for the condition, with treatments instead focusing on easing the symptoms of the disease or slowing its progression.

While various drugs are available in the treatment of Alzheimer’s disease, there is an emerging body of evidence suggesting that aerobic exercise may also be effective in reducing the progression of the disease.

However, as the authors of the present study note, randomized controlled trials that have put this to the test have produced inconsistent findings.

To begin to resolve this problem in existing research, the present authors devised a randomized controlled trial to act as a pilot study.

This study examined whether a group of older adults with Alzheimer’s disease would have less cognitive decline following 6 months of aerobic exercise compared with the expected level of cognitive decline they would experience if the disease progressed naturally.

Pilot study

The study involved 96 participants aged 66 years or older with Alzheimer’s disease.

Researchers randomly split these participants into two groups. One group of 64 people took part in supervised cycling exercise classes three times a week for 6 months.

The remaining 32 participants took part in supervised stretching and range of motion exercise classes, which the scientists matched to the cycling group in terms of the regularity of the classes and their length of time, but at low intensity. This latter group also acted as a control.

Researchers continually monitored participants’ heart rates in both groups. The team also supported the cycling group to achieve 50–75% heart rate reserve while helping the control group maintain less than 20% heart rate reserve.

In addition, the scientists measured participants’ cognition at the beginning of the intervention, as well as at months 3, 6, 9, and 12.

Exercise reduced cognitive decline

The researchers found that both the cycling group and the stretching or range of motion group scored significantly better than would have been predicted if they had continued with treatment as normal.

The researchers used the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, a scaling system where a greater number reflects worse cognition.

According to this scale, after 6 months, the cycling group scored 1.0±4.6, and the control group 0.1±4.1. This compares with a score of 3.2±6.3, which would be in line with expectations given the natural progression of Alzheimer’s disease.

According to Prof. Fang Yu, Edson Chair in Dementia Translational Nursing Science at the Arizona State University Edson College of Nursing and Health Innovation, and corresponding author of the study, “our primary finding indicates that a 6-month aerobic exercise intervention significantly reduced cognitive decline in comparison to the natural course of changes for Alzheimer’s dementia.”

“However, we did not find a superior effect of aerobic exercise to stretching, which is likely due to the pilot nature of our trial. We do not have the statistical power to detect between-group differences, there was a substantial social interaction effect in the stretching group, and many stretching participants did aerobic exercise on their own.”

As a consequence, scientists need to conduct further research to corroborate these initial encouraging findings.

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The research found small but significant decreases in the risk of SARS-CoV-2 infection among females — but not males — who took multivitamins, vitamin D, omega-3 fatty acids, or probiotics.

Researchers at King’s College London, in the United Kingdom, analyzed data from 1.4 million users of the COVID Symptom Study app in the U.K., the United States, and Sweden. The participants answered questions about their regular use of dietary supplements.

The app users also reported results from COVID-19 tests and whether they had experienced symptoms of the illness.

“Our research is an observational study and not a clinical trial, so we can’t make strong recommendations based on the data we have,” cautions senior researcher Dr. Cristina Menni, of the School of Life Course Sciences, at King’s.

“Until we have further evidence about the role of supplements from randomized controlled trials, we recommend following the [National Health Service] guidelines on vitamin usage as part of a healthy, balanced diet,” she adds.

The study, which has not yet been peer-reviewed, has been uploaded to the preprint server MedRxiv.

Female immune defenses

The researchers were surprised to find that only females appeared to benefit from taking the four supplements in question.

They cite, however, several studies that have found that females have more robust immune systems, which may mean that their immune defenses get more of a boost from supplements.

Alternately, females may be more likely to wear masks or wash their hands than males, which could increase the apparent protective effects of taking supplements.

“These are interesting results, but due to the way the study has been conducted, these data absolutely cannot tell us that taking such supplements ‘protects’ against infection [resulting in] COVID-19,” says Naveed Sattar, a professor of metabolic medicine at the University of Glasgow, in the U.K., who was not involved in the research.

“It may be that by being more health-conscious, some women are less likely to become infected, so that it’s the behaviors that explain these results, not the supplements,” he hypothesizes.

Seif Shaheen, a professor of respiratory epidemiology at Queen Mary University of London, adds that the researchers had not accounted for factors such as income and educational attainment in their analysis.

“A major concern is that these findings may be confounded by socioeconomic status, given that individuals of higher status are more likely to take supplements and are also less likely to become infected with SARS-CoV-2,” he cautions.

The results in detail

Out of 327,720 users of the app in the U.K. who had each had a polymerase chain reaction or serology test for SARS-CoV-2, 175,652 reported having used supplements regularly since the beginning of the pandemic. The study sample was predominantly female, at 66.8%.

In total, 10,508, or 6.0%, of the supplement users had tested positive for the novel coronavirus, while 13,013, or 6.6%, of the nonusers had received positive results.

After the researchers had adjusted for other factors that could contribute to COVID-19 risk, they found that four supplements were associated with reduced risk.

Taking probiotics, multivitamins, omega-3 fatty acids, or vitamin D was associated with a 14%, 13%, 12%, and 9% lower risk of COVID-19.

Taking vitamin C, zinc, or garlic supplements was not associated with any reduced risk.

When the researchers broke down the numbers by sex, they found reduced risk associated with probiotics, multivitamins, omega-3 fatty acids, and vitamin D in females only.

After analyzing data from app users in the U.S. and Sweden, the researchers found similar associations between supplement use and confirmed SARS-CoV-2 infections.

Among the 993,365 regular users of the app worldwide who had not undergone testing, 126,556 had reported a loss of smell or taste. This suggests that they likely had COVID-19.

When the researchers analyzed data from these individuals, they found a small but significant reduction in risk among both males and females who regularly took omega-3 fatty acids, multivitamins, vitamin D, or probiotics.

Vitamin D uncertainties

During the ongoing pandemic, vitamin D has attracted a lot of media attention following the publication of studies suggesting that it may have a protective effect. The evidence to date has been mixed and inconclusive, however.

Two clinical trials underway may provide more clarity — one run by the Queen Mary University of London and the other by the Angers University Hospital, in France.

Meanwhile, the researchers behind the present study acknowledge several limitations. For example, all the participants were “self-selected.” They chose to download and use the app and so may not be representative of the general population.

In addition, the information that they provided may be inaccurate. For example, they may have started taking supplements after developing symptoms.

The authors emphasize that, as an observational study, their research cannot provide definitive proof that taking any supplement reduces the risk of COVID-19.

They conclude:

“Large randomized controlled trials of selected supplements testing their protective effects and also possible adverse effects on disease severity are required before any evidence-based recommendations can be made. We eagerly await the result of ongoing trials, including [those investigating] vitamin D and COVID risk.”

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New research into the plant-based sweetener stevia indicates that the sugar substitute may have negative implications for gut health.

People use sugar substitutes as a way to reduce their sugar intake. Excess sugar consumption can cause weight gain, lead to diabetes, and contribute to inflammation in the body.

For this reason, researchers have worked to find the perfect replacement that tastes like real sugar and is safe to consume.

Scientists have considered stevia a safe sugar alternative for years, but a new study raises the question of whether it can be harmful to gut health.

What is stevia?

Sugar replacements come in handy for many people, including individuals with diabetes who need to control their blood sugar and those trying to reduce their calorie intake to reach or maintain a moderate weight.

Various substitutes are available. These include several artificial sweeteners, such as sucralose, aspartame, and saccharin, and the sugar alcohols xylitol and erythritol.

Some people use plant-based options to replace sugar, and stevia is one such sweetener that is widely available.

People have used the plant stevia as a sweetener for hundreds of years. People originally discovered the plant in Brazil and Paraguay and now grow it all over the world.

Stevia is up to 300 times sweeter than table sugar, so only a very small amount is necessary to achieve a sweetening effect.

Some people prefer plant-derived stevia over artificial sweeteners that manufacturers create in a lab.

Moreover, stevia is a zero-calorie substitute, whereas other artificial sweeteners may have a few calories. Another benefit to stevia is that it has a glycemic index of less than 1, so it does not raise blood sugar the way a few alternatives do.

Some sugar substitutes are also safer than others. Studies have linked other substitutes, such as sucralose and saccharin, with tumor growth in mice, although these effects are not confirmed. Research on stevia, on the other hand, had not previously uncovered any serious negative health implications.

Importance of gut health

Although people generally understand the importance of maintaining a moderate weight and engaging in best practices for heart health, they sometimes overlook gut health.

According to Dr. Elizabeth Hohmann of the Infectious Diseases Division at Harvard-affiliated Massachusetts General Hospital, “This is a new frontier of medicine, and many are looking at the gut microbiota as an additional organ system.”

Hohmann goes on to say, “It’s most important to the health of our gastrointestinal system, but may have even more far-reaching effects on our well-being.”

The digestive system is home to various types of bacteria. Some of these bacteria help keep the body healthy. Maintaining a healthy and balanced gut is important in many ways.

Some gut bacteria can prevent inflammation, protect against certain types of cancer, and reduce symptoms associated with rheumatoid arthritis.

There are various ways to maintain a healthy gut, one of which is to avoid the overuse of antibiotics. Antibiotics can affect the good bacteria living in the gut.

Avoiding foods that can harm gut health, such as processed foods and red meat, is also important. People can take probiotics, eat foods high in fiber, and eat fermented foods, such as yogurt or kombucha, to promote good gut health.

Stevia research results

While experts typically view stevia as a safe sugar replacement, the latest research indicates that it may have some drawbacks.

Researchers from Ben-Gurion University of the Negev (BGU) in Beersheba, Israel, focused on stevia in a study that recently featured in Molecules. Their findings suggest that stevia can have a negative effect on gut health.

The research team studied two forms of stevia: the commercialized herb supplement and purified stevia extract. They looked at how the different forms of stevia affect bacterial communication.

The gut has quorum sensing (QS) pathways. These pathways enable bacteria molecules to communicate with each other, which is important in terms of microbial regulation.

The team found that the stevia herb supplement had an “inhibitory effect on bacterial communication.” The purified stevia extract showed “a molecular interaction and possible interruption of [some forms of] bacterial communication.”

While the study shows that stevia may contribute to an unbalanced gut, neither form of stevia showed evidence of killing bacteria in the gut.

Lead researcher Dr. Karina Golberg, who is part of the BGU Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, commented on the findings:

“This is an initial study that indicates that more research is warranted before the food industry replaces sugar and artificial sweeteners with stevia and its extracts.”

The researchers plan to study stevia more closely and use their findings to shape guidelines for stevia intake.

“With reference to the effects identified in our study and the growing consumption of stevia, we urge that more studies be conducted to help further elucidate the effects of these sweeteners and to adjust the highest daily doses recommended today,” the study authors write.

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