Category: Diseases, Syndromes and Conditions

Categories : COVID Diseases, Syndromes and ConditionsTags :

Vigorous Exercise and Talking Produce Similar Levels of Aerosols

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Old man jogging
Photo by Barbra Olsen on Pexels

Vigorous exercise produces a similar level of aerosol particles as speaking, but high-intensity exercise produces more, according to new research published in Communications Medicine. This is the first study to measure exhaled aerosols generated during exercise, to help inform the risk of airborne viral transmission of SARS-CoV-2 for gyms and indoor physical training.

Inhalation of infectious aerosol is considered to be the main route of SARS-CoV-2 transmission. In this study, researchers performed a series of experiments to measure the size and concentration of exhaled particles (up to 20µm diameter) which are generated in our respiratory tracts and breathed out, during vigorous and high-intensity exercise.

Using a cardiopulmonary exercise test, 25 healthy participants (13 male, 12 female) with a range of athletic abilities were recruited to undertake four different activities (breathing at rest, speaking at normal conversational volume, vigorous exercise and high-intensity exercise) on a cycle ergometer. Airflow and particles emitted were measured by particle counter. Experiments were carried out in an orthopaedic operating theatre — an environment with ‘zero aerosol background’, letting the researchers to unambiguously identify the aerosols generated by the participants.

The results showed that the size of airborne particles emitted during vigorous exercise was consistent with those emitted while breathing at rest. However, the rate of aerosol mass exhaled during vigorous exercise was found to be similar to speaking at a conversational volume.

Jonathan Reid, scientific lead on the paper, said: “COVID has profoundly impacted sports and exercise, and this study provides a comprehensive analysis of the mass emission rates of aerosol that can potentially carry infectious virus produced from an individual during exercise. Our research has shown that the likely amount of virus that someone can exhale in small aerosol particles when exercising is comparable to when someone speaks at a conversational volume.  The most effective way to reduce risk is to ensure spaces are appropriately ventilated to reduce the risk of airborne transmission.”

Source: University of Bristol

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An Oral Drug for Sleep Apnoea

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Sleeping man
Photo by Mert Kahveci on Unsplash

A new study published in the American Journal of Respiratory and Critical Care Medicine has tested a sleep apnoea treatment using a drug that inhibits carbonic anhydrase – an enzyme that balances carbonic acid and carbon dioxide in the body. The treatment reduced breathing pauses by more than 20 per hour for patients given the drug.

Several drugs with carbonic anhydrase (CA) inhibitory properties are already available on the market, and used for treatment of glaucoma, epilepsy and other disorders.

Previous research has not systematically tested whether CA inhibitors also might be used to treat obstructive sleep apnoea. A total of 59 patients with moderate or severe sleep apnoea completed the four-week trial, and were randomised to two groups receiving either 400 or 200 mg of the CA inhibitor, and a control group that received placebo.

The results show that, overall, the treatment reduced the number of breathing pauses and promoted oxygenation during the night. A few patients experienced side effects, such as headache and breathlessness, which were more common in those receiving the highest dose.

The study results together with established safety data of the drug sulthiame provide support for continued research on CA inhibition as a new potential treatment for obstructive sleep apnoea.

“Among the patients who received the higher dosage of the drug, the number of breathing pauses decreased by approximately 20 per hour. For just over a third of patients in the study, only half of their breathing pauses were left, and in one in five the number fell by at least 60 percent,” said first authpr Professor Jan Hedner.

The fact that several approved drugs in the CA inhibitor category are available on the market makes fast-tracking development of an approved drug for sleep apnoea practicable. The drug used in this clinical trial was sulthiame, which is sometimes used to treat epilepsy in children.

Current treatment for a patient with sleep apnoea is either an oral appliance therapy or a CPAP (Continuous Positive Airway Pressure) mask. Both help to maintain airway patency during sleep.

“These therapy options take time to get used to and, since they frequently are perceived as intrusive or bulky. Insufficient user time is therefore common. If we develop an effective drug, it will therefore make life easier for many patients and, in the long run, potentially also save more lives,” said senior author Ludger Grote.

Source: University of Gothenburg

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Zika Can Mutate to Increase its Infectivity

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Mosquito, a malaria parasite vector
Photo by Егор Камелев on Unsplash

Researchers have found that Zika virus has the potential to mutate and increase its infectivity, potentially breaking through pre-existing immunity.

“The world should monitor the emergence of this Zika virus variant,” said LJI Professor Sujan Shresta, PhD, who co-led the La Jolla Institute for Immunology (LJI) study which is published in Cell Reports.

A mosquito-borne virus, symptoms of Zika infection are usually mild in adults. However, in a developing foetus, infection can cause birth defects such as microcephaly.

Zika virus and dengue virus occur together in a number of countries. Both viruses are a mosquito-borne flavivirus, sharing biological similarity:  similar enough that prior dengue exposure can offer immune protection against Zika.

“In areas where Zika is prevalent, a vast majority of people have already been exposed to dengue virus and have both T cells and antibodies that cross-react,” said Prof Shresta.

Unfortunately, both viruses share the trait of rapid mutation. “Dengue and Zika are RNA viruses, which means they can change their genome,” she further explained. “When there are so many mosquitoes and so many human hosts, these viruses are constantly moving back and forth and evolving.”

To study Zika’s fast-paced evolution, the researchers simulated infection cycles that repeatedly switched back and forth between mosquito cells and mice. This painted a picture of how Zika virus naturally evolves as it encounters more hosts.

The LJI team found that an easy change of a single amino acid allows the virus to make more copies of itself — and help infections take hold more easily. This mutation (called NS2B I39V/I39T mutation) boosts viral replication in both mice and mosquitoes – and also in human cells.

“This single mutation is sufficient to enhance Zika virus virulence,” commented study first author Jose Angel Regla-Nava, PhD. “A high replication rate in either a mosquito or human host could increase viral transmission or pathogenicity – and cause a new outbreak.”

Prof Shresta added, “The Zika variant that we identified had evolved to the point where the cross-protective immunity afforded by prior dengue infection was no longer effective in mice. Unfortunately for us, if this variant becomes prevalent, we may have the same issues in real life.”

To help prepare for this variant, Dr Shresta’s laboratory is already looking at ways to tailor Zika vaccines and treatments that counteract this dangerous mutation.

“We want to understand at what point in the viral life cycle this mutation makes a difference,” said Dr Shresta.

Source: La Jolla Institute for Immunology

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Cycling Can Improve Mobility in Myotonic Dystrophy

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Photo by Jeremias Radny on Unsplash

Regular cycling can greatly improve mobility in patients with myotonic dystrophy (MD), an inherited genetic disease that causes muscle degeneration, according to research published in The Journal of Clinical Investigation. Professor Mark Tarnopolsky, senior author of the study, said that cycling for 35 minutes three times a week for 12 weeks led to a 32% increase in overall fitness in people with MD.

The participants also saw a 1.6-kilogram increase in their muscle mass and a two percent reduction of body fat. They were also able to walk an extra 47 metres in six minutes, when tested by researchers at the end of the 12-week trial.

The research team recruited 11 patients with MD to examine how effective cycling was in restoring and maintaining their physical health. Researchers also studied the underlying molecular mechanisms through which exercise strengthens the skeletal muscles, which can be severely weakened by MD.

“Exercise really is medicine – we just need to get the message out,” said Prof Tarnopolsky. “Myotonic dystrophy is a progressive condition that will impair your mobility and can put you in a wheelchair. There is no cure for it and only regular exercise helps you achieve better function.”

Prof Tarnopolsky said that some patients with MD are even advised by their doctors not to exercise, for fear of making their condition worse, but that is now proven false. 

Prior studies with mouse models showed a range of similar physiological benefits from regular exercise, the researchers said. MD is the most commonly diagnosed type of muscular dystrophy in adults, and the second most prevalent of all muscular dystrophies, noted Prof Tarnopolsky.

MD’s main symptoms include severe skeletal muscle atrophy, general muscle weakness, reduced lung capacity and impaired heart function. Other symptoms may include cataracts, endocrine disorders including diabetes and gastro-intestinal disorders. 

“MD itself is really a form of accelerated ageing,” said Prof Tarnopolsky.

Source: McMaster University

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Kisspeptin Might Be a New Treatment for Fatty Liver Disease

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The Hershey’s Kisses after which the hormone is named. Photo by Aaron Burden on Unsplash

Kisspeptin, a hormone named for the iconic Hershey’s ‘Kisses’ might be developed as a treatment for non-alcoholic fatty liver disease (NAFLD), according to a new study appearing in the Journal of Clinical Investigation. The hormone also serves to regulate puberty and fertility in humans. 

Globally, non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease that affects children and adults and is linked to the rise in obesity and Type 2 diabetes. Largely without symptoms in the early stages, NAFLD begins with the accumulation of fat in the liver, leading to ‘fatty liver’. With disease progression, inflammation sets in, resulting in non-alcoholic steatohepatitis (NASH). This is followed by fibrosis and cirrhosis, and a subset of NASH patients with cirrhosis will also develop liver cancer. There are presently no approved therapeutics to treat NASH.

Study lead investigator, Moshmi Bhattacharya, an associate professor at Rutgers University, has spent over 15 years studying kisspeptin in health and disease. Kisspeptin, encoded by the KISS1 gene, was discovered in a city called Hershey, and named for the iconic Hershey chocolate ‘kisses’. As well as playing key roles in pubertal development and maintaining reproductive function, kisspeptin has also been linked to appetite and, coincidentally given its name, sexual attraction.

In the study, mice fed on a high-fat, high-sugar ‘Western’ diet to induce obesity and NAFLD, were protected from the development of fatty liver, NASH and fibrosis when given kisspeptin. Kisspeptin works by binding its receptor, a protein called KISS1R, which, when deleted from liver cells, prevents kisspeptin from functioning, leading mice on Western diets to develop fatty liver. These experiments uncover a powerful relationship between kisspeptin and the reduction of liver fat and fibrosis.
“This work shows the kisspeptin receptor signaling pathway has a potential therapeutic role in NAFLD,” said co-author, Professor Vinod K Rustgi. “It does this by protecting against the development of fat in the liver and reducing inflammation and fibrosis. As such, it has the potential to favorably impact the health and lives of millions of patients around the globe.”

Source: Rutgers University

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More Evidence Linking Erectile Dysfunction Drugs to Eye Conditions

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Photo by Mike Dorner on Unsplash

The risk of developing one of three serious eye conditions increases by 85 percent for regular users of common erectile dysfunction (ED) medications such as the phosphodiesterase 5 (PDE5) inhibitors, sildenafil, tadalafil, vardenafil and avanafil, according to new research.

Previously, two of the three conditions had been linked to ED medications only by anecdotal case studies. Now, these links have been confirmed for the first time by a large, epidemiological study, which appears in JAMA Ophthalmology.

“These are rare conditions, and the risk of developing one remains very low for any individual user. However, the sheer number of prescriptions dispensed each month in the US – about 20 million – means that a significant number of people could be impacted,” said first author Dr Mahyar Etminan. “Regular users of these drugs who find any changes in their vision should take it seriously and seek medical attention.”

The researchers analysed health insurance claim records of 213 000 men in the US without a history of these eye problems in the year before they became regular users of ED medications.

They followed the records to see how many men developed one or more of the three conditions, and how that rate compared to men who didn’t use the medications. After accounting for conditions associated with eye problems, such as hypertension, diabetes and coronary artery disease, they found the increased risk for each to be as follows:

A key limitation was that the study could only show correlation between eye conditions and use of these drugs, and could not prove causation. However, possible explanations can be found in the way ED medications function.

“These medications address erectile dysfunction by improving blood flow, but we know that they can also hinder blood flow in other parts of the body,” explained Dr Etminan. “So although our study doesn’t prove cause-and-effect, there is a mechanism by which these medications could conceivably lead to these problems. The totality of the evidence points toward a strong link.”

The potential risk of SRD and RVO is not covered in the information currently provided to patients along with their ED medications, unlike the ION risk which has been demonstrated by previous research.

Dr Etminan hopes his team’s work will change that. Patients who are unaware of all potential side effects might not seek help in time to avoid serious visual consequences.

Source: University of British Columbia

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Community-acquired Antimicrobial Resistant UTIs can be More Deadly

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Pseudomonas
Scanning Electron Micrograph of Pseudomonas aeruginosa. Credit: CDC/Janice Carr.

A study from Australia’s scientific organisation CSIRO has revealed that antimicrobial resistant (AMR) bacteria in urinary tract infections are more lethal, especially Enterobacteriaceae. The findings are published online in Open Forum Infectious Diseases.

Antimicrobial resistance (AMR) bacteria can be passed between humans: through hospital transmission and community transmission. While hospital acquired resistance is well researched, there are few studies focusing on the burden of community transmission.

To address this, the study analysed data from 21 268 patients across 134 Queensland hospitals who acquired their infections in the community. The researchers found that patients were almost two and a half (2.43) times more likely to die from community acquired drug-resistant UTIs caused by Pseudomonas aeruginosa and more than three (3.28) times more likely to die from community acquired drug-resistant blood stream infections caused by Enterobacteriaceae than those with drug-sensitive infections. The high prevalence of UTIs make them a major contributor to antibiotic use, said CSIRO research scientist, Dr Teresa Wozniak.

“Our study found patients who contracted drug-resistant UTIs in the community were more than twice as likely to die from the infection in hospital than those without resistant bacteria,” Dr Wozniak said. “Without effective antibiotics, many standard medical procedures and life-saving surgeries will becoming increasingly life-threatening. “Tracking the burden of drug-resistant infections in the community is critical to understanding how far antimicrobial resistance is spreading and how best to mitigate it.”

The study’s findings will provide further guidance for managing AMR in the community, such as developing AMR stewardship programs that draw on data from the population being treated.

CEO of CSIRO’s Australian e-Health Research Centre, Dr David Hansen, said the magnitude of the AMR problem needs to be understood to mitigate it. “Tracking community resistance is difficult because it involves not just one pathogen or disease but multiple strains of bacteria,” Dr Hansen said. “Until now we haven’t been using the best data to support decision making in our fight against AMR. Data on community acquired resistance is an important contribution to solving the puzzle. “Digital health has an important role in using big data sets to describe patterns of disease and drive important population health outcomes.”

Source: CSIRO

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Caffeine May Help with Cognitive Symptoms of ADHD

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Coffee cup and beans
Photo by Mike Kenneally on Unsplash

Researchers in Spain have found that caffeine may be beneficial in alleviating cognitive symptoms of ADHD, such as improving attention span and retention capacity. Their findings, published in Nutrients, may provide a less controversial addition to the therapeutic arsenal for this disorder.

Attention deficit hyperactivity disorder (ADHD) diagnoses have increased exponentially over the last 20 years. It is currently estimated that this disorder affects between 2% and 5% of children in Spain, an average of one or two children per classroom, and up to 4% of the adult population.

Despite these high incidence rates, controversy surrounds the treatment of this pathology and the therapeutic approach to it. This varies widely depending on each patient, the symptoms they present and their intensity. For this reason, experts are continuing to investigate different components and substances that may be capable of providing new treatment opportunities for patients diagnosed with ADHD.

A team of experts at the Universitat Oberta de Catalunya (UOC) has investigated caffeine to alleviate some of the symptoms of ADHD, given the controversy surrounding the use of some medicines derived from methylphenidate, among others. Their systematic review of animal studies concludes that a prescribed consumption of caffeine can increase attention and retention capacity in adolescents and adults with ADHD.

“The therapeutic arsenal for alleviating ADHD is limited, and there is a certain degree of controversy around the use of some types of medications and stimulants, especially during childhood and adolescence. That’s why it’s useful to study the efficacy of other substances, such as caffeine,” explained Javier Vázquez, one of the paper’s main authors.

This is the first systematic review with results linking caffeine consumption in different animal models of ADHD with an increased attention span, improved concentration, learning benefits, and improvements in some types of memory.

“This substance improves these types of cognitive procedures, and increases capacity and flexibility in both spatial attention and selective attention, as well as in working memory and short-term memory,” emphasised Vazquez, who added that controlled treatment with this substance “doesn’t alter blood pressure, and doesn’t lead to an increase or reduction in body weight.”

The researchers point out that while possibly effective for cognitive symptoms, the results are unclear for other characteristic symptoms of ADHD, such as hyperactivity and impulsivity. “The results are very positive, but we must be much more careful when prescribing a caffeine-based medical treatment for these symptoms. In diagnoses in which the problem is purely attentional, caffeine may be an appropriate therapy, but if there’s a symptomatological presence of hyperactivity or impulsivity, we must be more cautious,” said Vasquez.

However, the results show that caffeine has a clear benefit in ADHD’s cognitive symptoms. “Our results reinforce the hypothesis that the cognitive effects of caffeine found in animal models can be translated and applied in the treatment of ADHD in people, especially at young ages such as adolescence,” the authors concluded.

“We want to emphasise that we aren’t against medication for ADHD, but we’re open to investigating all possible alternatives for improving this type of disorder, and for being able to use caffeine from a therapeutic point of view with all the appropriate medical supervision, a prescribed treatment and follow-up,” said Vázquez.

Source: Universitat Oberta de Catalunya (UOC)

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New Hope for Alopecia Treatment with JAK Inhibitor Baricitinib

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Before and after images for participants who received 36 weeks of treatment for alopecia areata with baricitinib. Credit: Yale University

Results from a new study in three patients with alopecia areata treated with a Janus kinase (JAK) inhibitor, baricitinib, were able to regrow hair. The study is based on Phase III clinical trials using baricitinib – a drug commonly used for arthritis – to treat alopecia areata, a skin disease characterised by loss of hair from the scalp and sometimes eyebrows and eyelashes.

“This is so exciting, because the data clearly show how effective baricitinib is,” said Dr. Brett King, an associate professor of dermatology at the Yale School of Medicine and lead author of the new study, published in the New England Journal of Medicine. “These large, controlled trials tell us that we can alleviate some of the suffering from this awful disease.”

Alopecia areata is an autoimmune disorder in which the body’s immune system attacks hair follicles, and which typically occurs in people under the age of 40. At present there is no FDA-approved treatment for the disease.

To test the drug, the researchers conducted two large, randomised trials involving a total of 1 200 people. The participants were adults with severe alopecia areata, who had lost at least half of their scalp hair.

For 36 weeks, participants were randomised to either a daily dose of either 4mg of baricitinib, 2mg of baricitinib, or a placebo. One-third of the patients who received the larger dose grew hair back.

According to the researchers, baricitinib works by disrupting the communication of immune cells involved in harming hair follicles. Baricitinib and other JAK inhibitors are routinely used to treat autoimmune forms of joint disease.

“Alopecia areata is a crazy journey, marked by chaos, confusion, and profound sadness for many who suffer from it,” King said. “It will be incredible to have a medicine to help people emerge on the other side, normalcy restored, recognizable again to themselves and those around them.”

Over the past decade, A/Prof King has developed methods for using JAK inhibitors to treat a variety of skin diseases — including eczema, vitiligo, granuloma annulare, sarcoidosis, and erosive lichen planus.

A/Prof King noted that the clinical trials involving baricitinib are ongoing, allowing researchers to assess the long-term effectiveness and safety of the treatment.

Source: Yale University

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Why Some Infections Can Be so Persistent

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C. difficile bacteria. Source: CDC

University of Utah researchers have discovered a novel mechanism that infectious bacteria use to rapidly adapt to environmental stress, which could help explain why certain types of common infections such as sepsis can be so persistent.

The mechanism, described in the journal Nucleic Acids Research, alters the precision with which the bacteria make the proteins that carry out most of the work in cells. These changes may improve the bacteria’s chance for survival.

“Understanding how pathogens survive stressful situations can reveal new targets for development of anti-microbial drugs and vaccines,” said the study’s senior author, Professor Matthew Mulvey.

Adapt or die
Bacteria infecting a host are exposed to stresses such as acidity or antibiotics. If even one of the bacteria’s key pathways for survival is crippled, the entire population could die off.

However, bacteria can adapt, an ability that relies on a slight twist to basic principles of biology.

Traditionally, each gene is thought to carry instructions for making a single kind of protein. A molecule called transfer RNA (tRNA) then uses these instructions to oversee protein production in the cell. In times of stress, though, random changes to the tNRA-mediated process can be an especially quick way to alter a cell’s array of proteins. This can generate useful new proteins that help the organism to thrive.

“There is a growing appreciation that a little bit of noise in the system can be good,” Prof Mulvey said.

Shifting expectations
A graduate student in the lab happened to stumbled onto a bacterial enzyme, MiaA, which turned out to be both sensitive to environmental stress and key to regulating protein expression. In one experiment, he created a version of an especially pathogenic bacteria that lacked the gene that encodes MiaA.

“Every kind of stress we exposed the MiaA-deficient strain to seemed to cause problems,” said the study’s co-first author Matthew Blango, PhD, who is now a junior research group leader at the Leibniz Institute for Natural Product Research and Infection Biology in Jena, Germany. “So, we really thought that this protein might be playing an important role in gene regulation.”

Bacteria lacking MiaA did not thrive and did not cause urinary tract infections or sepsis in mice. This same effect also occurred with bacteria manipulated into expressing too much MiaA. “There appears to be a Goldilocks zone, where just the right amount of MiaA allows the optimal stress response,” Dr Blango said.

Seeing how badly things went when MiaA levels were out of balance, Brittany Fleming, PhD, the study’s co-first author, investigated further. She discovered that knocking out MiaA caused random ‘frameshifting’ – an error where tRNA delivers three-letter genetic codes to be translated into proteins that are off by one letter. For example, a genetic code of “CAT CAT GTA” might read as “ATC ATG TA…” when frameshifted. In the bacteria, the result of such a shift was impaired production of important proteins and production of unexpected proteins.

Another co-first author, graduate student Alexis Rousek, showed that changing levels of MiaA could alter the availability of key metabolites that feed into other important stress response pathways within the bacteria. These findings implicate MiaA as a key player within a web of pathways that can impact pathogen stress resistance

Prof Mulvey says his lab’s next step is learning how environmental stress alters MiaA levels within bacteria.

The implications for this research may extend beyond infection control. Humans express a version of MiaA that is linked to certain cancers and metabolic diseases. “What we learned about how MiaA works is likely to be relevant to research on cancer and other non-infectious human diseases,” Mulvey said.

Source: University of Utah