Categories : Ageing Skeletal SystemTags :

Osteoporosis in Men is Often Overlooked

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Osteoporosis in men is often overlooked by health care professionals, found the authors of a review published in The Lancet Diabetes and Endocrinology. There is a desperate need for raising awareness of the condition in men to help improve outcomes for patients, the authors said.

Women are generally at higher risk of developing osteoporosis, as their bone density declines more rapidly than men at an earlier age, especially post-menopause. In most populations, men have larger and stronger bone and joint surfaces, so they can be overlooked when diagnosing the condition.

Reviewing available data on the condition in men, researchers found that they are generally diagnosed later, comply with treatment less and present to hospital in older ages than women. With fatality rates from hospitalisations with fragility fractures, like a broken hip, being higher than women.

The review’s author, Dr Tatiane Vilaca, said: “Generally diagnosis of osteoporosis happens when a patient presents at hospital with some kind of fragility fracture in older age, for example falling from standing height, and breaking a hip, wrist or spine.

“Research suggests men hospitalised with hip fractures tend to be older than women, which could be because the condition develops more slowly in men. As older people are usually slightly frailer, with poorer states of overall health, this could explain the slightly higher levels of disability and mortality associated in men with osteoporosis who are hospitalised following a fracture.”

The review found that although there is a lack of research about which treatment options are most effective in men, diagnosis and treatment options are effective.

The team believe further research specifically tailored to osteoporosis in male patients will help improve current diagnosis systems, helping clinicians with earlier diagnosis, and a focus on education for patients will support compliance with drug treatment programs, all improving outcomes for men living with osteoporosis.

Dr. Richard Eastell, Professor of Bone Metabolism at the Department of Oncology and Metabolism, said: “As women make up larger numbers of people living with osteoporosis, the data we have on the progression of the condition in men is currently not as robust. This updated review shows that further studies of male patients could help improve current diagnosis systems, as well as resources for the education of primary care clinicians and the general public on the early warning signs of osteoporosis in men.”

Dr. Vilaca added: “Despite the current gap in knowledge, men can still easily be screened for osteoporosis at their general practitioner surgery.

“Anyone with a family history of osteoporosis, broken bones, or fractures, those with acute back pain or a loss of height should be encouraged to have a check-up.

“These are all early warning signs of the condition in both men and women, and early preventative treatment is the best way to ensure a slower disease progression and longer, healthier life without a fracture.”

Source: University of Sheffield

Categories : GastrointestinalTags :

Using Ablation Therapy to Treat Stomach Disorders

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Photo by Andrea Piacquadio on Pexels

Researchers have shown that ablation therapy, often used to correct an abnormally beating heart, could be used to correct disorders of the stomach such as ‘stomach dysrhythmias’. They outline the results of their work in AJP Gastrointestinal and Liver Physiology.

In normal circumstances the stomach is coordinated by underlying bioelectrical ‘slow wave’ activity, which coordinates the contraction of the muscles that mix and move contents into and through the gastrointestinal (GI) tract.  When these electrical slow waves don’t work as they should, described as ‘stomach dysrhythmias’, it can lead to severe GI disorders and symptoms of nausea, vomiting, pain and bloating, and is often untreatable.

When dysrhythmic activity occurs in the heart it results in atrial fibrillation, which is often treated with ablation therapy in which tissues are precisely ‘burnt’ to control the naturally occurring electricity in the heart. Dr Tim Angeli-Gordon and PhD student Zahra Aghababaie of the ABI have shown that the technique could also be applied to control the naturally occurring bioelectrical “slow wave” activity in the stomach.

With last year’s publication of the team’s initial research using ablation in the stomach, they demonstrated that it was possible to use the technique to block the electrical activation of the stomach in localised regions. “The more recent paper builds on that foundational work and is an important advance because we have now shown that we can eliminate abnormal electrical activation with ablation, and also that the normal electrical activation of the stomach can be restored after ablation,” said Dr Angeli-Gordon. “Although these studies were done in our pre-clinical lab, they demonstrate the powerful potential of ablation in the stomach which may now be able to be translated as a therapy for patients suffering from gastrointestinal disorders.”

Source: EurekAlert!

Categories : AddictionTags :

Single Pathway Controls Drug Withdrawal-induced Anxiety

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Depression, young man
Source: Andrew Neel on Unsplash

New research published today in Cell Reports finds that drug withdrawal-induced anxiety and return to drug seeking behaviours are controlled by a single pathway in the brain and are centred on dopamine cells, which are normally associated with reward behaviours.

Addiction occurs in phases: the initial drug exposures are rewarding, and then repeated administration leads to tolerance or sensitisation to the drug’s effects, with withdrawal leading to anxiety and a negative affective state, which, in turn, contributes to a return to drug taking or seeking.

“In order to prevent relapse among drug users, specifically cocaine users, we need to understand the factors in the brain that contribute to drug seeking behaviours and the vulnerability to relapse,” said Kevin Beier, PhD, assistant professor of physiology and biophysics from the University of California, Irvine. “In this study, we identified a brain circuit that is responsible for drug withdrawal-induced anxiety as well as relapse-related behaviour, along with the identification of a potential target for therapeutic interventions.”

The negative affective state induced by drug withdrawal is a critical factor in the relapse of drug users.

“Both the drug withdrawal-induced anxiety and reinstatement of drug seeking are controlled by a single pathway centred around dopamine cells in the ventral midbrain,” explained Dr Beier. “That a single pathway controls both sets of behavioural changes may help to explain many addiction-related behavioural phenomena. Importantly, it links them both directly to dopamine, which is more typically linked to reward-related behaviours.”

While midbrain dopamine circuits are central to motivated behaviours, just how experience modifies these circuits to facilitate subsequent behavioural adaptations is not well understood. This study demonstrates the selective role of a ventral tegmental area dopamine projection to the amygdala for cocaine induced anxiety, but not for cocaine reward or sensitisation. Silencing this projection prevents development of anxiety during protracted withdrawal after cocaine use.

According to the National Center for Drug Abuse Statistics, there are roughly 70 000 drug overdoses each year in the United States. In 2017, nearly one in five drug overdose deaths was cocaine-related, with the highest rate of cocaine-related overdoses and deaths occurring among non-Hispanic black populations. Between 2012 and 2018, the rate of cocaine-related overdose deaths increased from 1.4 to 4.5%. The American Addiction Centers state recent drug relapse statistics show that more than 85% of individuals relapse and return to drug use within a year following treatment.

Source: University of California – Irvine

Categories : VaccinesTags :

BCG Vaccine Activates Immune System in Newborns

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Syringe
Source: Raghavendra V Konkathi on Unsplash

In the century since it was first used in humans, the Bacille Calmette-Guérin (BCG) vaccine against tuberculosis has become one of the world’s most widely used vaccines. Administered in countries with endemic TB, it has surprisingly been found to protect newborns and young infants against multiple bacterial and viral infections unrelated to TB. Some evidence even suggests that it can reduce severity of COVID. Now, a new study in Cell Reports sheds light on the mechanisms behind its extra protective effects.

Surprisingly little is known about how BCG exerts its many side benefits. To better understand its mechanism of action, researchers collected and comprehensively profile blood samples from newborns vaccinated with BCG, using a powerful ‘big data’ approach analysing lipid and metabolite biomarkers.

Their study found that the BCG vaccine induces specific changes in metabolites and lipids that correlate with innate immune system responses. The findings provide clues toward making other vaccines more effective in vulnerable populations with distinct immune systems, such as newborns.

First author Dr Joann Diray Arce and her colleagues started off with blood samples from low-birthweight newborns in Guinea Bissau who were enrolled in a randomised clinical trial to receive BCG either at birth or after a delay of six weeks. Blood samples were taken at four weeks for both groups (after BCG was given to the first group, and before it was given to the second group).

The researchers comprehensively profiled the impact of BCG immunisation on the newborns’ blood plasma. They found that BCG vaccines given at birth changed metabolite and lipid profiles in newborns’ blood plasma in a pattern distinct from those in the delayed-vaccine group. The changes were associated with changes in cytokine production, a key feature of innate immunity.

The researchers had parallel findings when they tested BCG in cord blood samples from a cohort of Boston newborns and samples from a separate study of newborns in The Gambia and Papua New Guinea.

“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said Dr Arce. “We studied three different BCG formulations and showed that they converge on similar pathways of interest. Reshaping of the metabolome by BCG may contribute to the molecular mechanisms of a newborn’s immune response.”

“A growing number of studies show that BCG vaccine protects against unrelated infections,” said Ofer Levy, MD, PhD, the study’s senior investigator. “It’s critical that we learn from BCG to better understand how to protect newborns. BCG is an ‘old school’ vaccine – it’s made from a live, weakened germ – but live vaccines like BCG seem to activate the immune system in a very different way in early life, providing broad protection against a range of bacterial and viral infections. There’s much work ahead to better understand that and use that information to build better vaccines for infants.”

Source: Boston Children’s Hospital via News-Medical.Net

Categories : COVID Medical Research & TechnologyTags :

Natural Facial Asymmetry Affects Mask Fit

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In research published in Physics of Fluids, researchers used computer modelling investigate mask fit and found that face shape, especially natural facial asymmetry, influences the most ideal fit. The findings suggested that double masking with improperly fitted masks may not greatly improve mask efficiency and produces a false sense of security.

Using more layers results in a less porous face covering, leading to more flow forced out the sides, top, and bottom of masks with a less secure fit. Double layers increase filtering efficiency only with good mask fit, however they could also lead to difficulties in breathing.

The researchers modelled a moderate cough jet from a mouth of an adult male wearing a cloth mask over the nose and mouth with elastic bands wrapped around the ears. They calculated the maximum volume flow rates through the front of mask and peripheral gaps at different material porosity levels.

To create a more realistic 3D face shape and size, the researchers used head scan data for 100 adult male and 100 adult female heads.

Their model showed how the slight asymmetry typical in all facial structures can affect proper mask fitting. For example, a mask can have a tighter fit on the left side of the face than on the right side.

“Facial asymmetry is almost imperceivable to the eye but is made obvious by the cough flow through the mask,” explained co-author Tomas Solano, from Florida State University. “For this particular case, the only unfiltered leakage observed is through the top. However, for different face shapes, leakage through the bottom and sides of the mask is also possible.”

Producing individually customised ‘designer masks’ is not practical at large scales. Still, better masks can be designed for different populations by revealing general differences between male and female or child versus elderly facial structures and the associated air flow through masks.

Source: American Institute of Physics

Categories : Respiratory DiseasesTags :

WHO Announces Guidance Updates to Treatment of Drug-resistant TB

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The World Health Organization (WHO) Global Tuberculosis Programme has announced upcoming updates to the guidance on the treatment of drug-resistant tuberculosis (DR-TB). These updates are announced in a Rapid Communication and include shorter novel 6-month all-oral regimens for the treatment of multidrug- and rifampicin-resistant TB (MDR/RR-TB), with or without additional resistance to fluoroquinolones (pre-XDR-TB), and also an alternative 9-month all-oral regimen for the treatment of MDR/RR-TB.

The Rapid Communication is released ahead of updated WHO consolidated guidelines to come later in the year which will inform national programmes and stakeholders.

Dr Tereza Kasaeva, Director of WHO’s Global TB Programme said: “We now have more and much better treatment options for people with drug-resistant TB thanks to research generating new evidence. This is major progress compared to what was available even a few years ago, and will be of great benefit for people struggling with TB and drug-resistant TB, resulting in better outcomes, saving lives and reducing suffering.”

All patients with MDR/RR-TB, including those with additional resistance to fluoroquinolones, stand to benefit from effective all-oral treatment regimens, either shorter or longer, implemented under programmatic conditions.

The summary of the updates are as follows:

The 6-month BPaLM regimen, comprising bedaquiline, pretomanid, linezolid (600 mg) and moxifloxacin, may be used programmatically in place of 9-month or longer (>18 months) regimens, in patients (aged ≥ 15 years) with MDR/RR-TB who have not had previous exposure to bedaquiline, pretomanid and linezolid (defined as > 1 month exposure). This regimen may be used without moxifloxacin (BPaL) in the case of documented resistance to fluoroquinolones (in patients with pre-XDR-TB). Drug susceptibility testing (DST) to fluoroquinolones is strongly encouraged, but DST should not delay treatment initiation.

The 9-month, all-oral, bedaquiline-containing regimens are preferred over the longer (>18 months) regimen in adults and children with MDR/RR-TB, without previous exposure to second-line treatment (including bedaquiline), without fluoroquinolone resistance and with no extensive pulmonary TB disease or severe extrapulmonary TB. In these regimens, 2 months of linezolid (600 mg) can be used as an alternative to 4 months of ethionamide. Access to rapid DST for ruling out fluoroquinolone resistance is required before starting a patient on one of these regimens.

Patients with extensive forms of DR-TB (eg XDR-TB4) or those who are not eligible for or have failed shorter treatment regimens will benefit from an individualised longer regimen designed using the priority grouping of medicines recommended in current WHO guidelines.6

Decisions on appropriate regimens should be made according to clinical judgement and patient preference, considering results of DST, patient treatment history, risk of adverse events, and severity and site of the disease.

All treatment should be delivered under WHO-recommended standards, including patient-centred care and support, informed consent where necessary, principles of good clinical practice, active drug safety monitoring and management, and regular monitoring of patients and of drug resistance to assess regimen effectiveness.

The full details of the regimens included in the review are available in the Rapid Communication.

Source: World Health Organization

Categories : Environmental Effects PaediatricsTags :

PFAS and Phthalates Linked to Reduced Bone Density in Teen Boys

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Per- and polyfluoroalkyl substances (PFAS) and phthalates (two types of endocrine-disrupting chemicals) may be associated with lower areal bone mineral density (aBMD) in teenage boys, according to a new study published in the Journal of Clinical Endocrinology and Metabolism.

Endocrine disrupting chemicals (EDCs) and potential EDCs are mostly man-made found in various materials. By interfering with the body’s endocrine system, endocrine disruptors produce adverse developmental, reproductive, neurological, and immune effects in humans, abnormal growth patterns and neurodevelopmental delays in children. These include per- and polyfluoroalkyl substances (PFAS) are used in non-stick pots and pans, clothing and food packaging, and are increasingly being found in US water supplies. Phthalates are used in medical devices, personal care products, food processing and children’s toys.

“Adolescence is an important time when our bodies build up bone. Almost all US children and adolescents are exposed to PFAS and phthalates, but few studies have looked at how these chemicals could be impacting our bone health,” said Abby F. Fleisch, MD, MPH, of the Maine Medical Center Research Institute and Maine Medical Center. “Our research found an association between certain PFAS and phthalates and reduced bone mineral density in adolescent males. Because bone accrual primarily occurs during adolescence, if replicated, this finding may have implications for lifelong bone health.”

The researchers accessed data on urine and blood samples from 453 boys and 395 girls from the National Health and Nutrition Examination Survey (NHANES). Participants were on average 15.1 years old, and found that higher levels of PFAS and phthalates may be associated with lower aBMD in adolescent males. The same effect was not found in girls; rather a slight increase in aBMD was observed for certain PFAS and phthalates.

The researchers noted that bone mineral density tracks across a lifetime, so if the same results are seen in longitudinal cohorts, this finding may have implications for lifelong skeletal health.

Source: The Endocrine Society

Categories : COVIDTags :

Omicron Sub-lineages are Evolving Increased Immune Escape Potential

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SARS-CoV-2 lineages. Credit: Professor Ryan Gregory, University of Guelph

A paper published May 1 on the medRxiv preprint server on two new sub-lineages of Omicron, BA.4 and BA.5, reported evidence that they may escape immunity conferred by previous BA.1 infection. The study’s authors suggest that this immune escape potential may drive another wave of infections.

In recent weeks, the BA.4 and BA.5 variants have been detected circulating in South Africa, and are close descendants of the Omicron BA.2 lineage.

Researchers isolated live BA.4 and BA.5 viruses and tested their ability to evade infection to 24 participants who had been infected with BA.1 but unvaccinated and 15 vaccinated participants with breakthrough BA.1 infection.

In unvaccinated individuals, FRNT50, the inverse of the dilution for 50% neutralisation, declined from 275 for BA.1 to 36 for BA.4 and 37 for BA.5, a 7.6 and 7.5-fold drop, respectively. In vaccinated BA.1 breakthroughs, FRNT50 declined from 507 for BA.1 to 158 for BA.4 (3.2-fold) and 198 for BA.5 (2.6-fold). Absolute BA.4 and BA.5 neutralisation levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants.

The observed escape of BA.4 and BA.5 from immunity elicited by BA.1 was more moderate than of BA.1 against previous immunity, the researchers found. The researchers warned that the low absolute neutralisation levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection. They suggest that, based on neutralisation escape, BA.4 and BA.5 have potential to result in a new infection wave.

Experts warn however that even these sub-lineages are unlikely to be the last, with plenty of potential remaining for new mutations.

Professor of evolutionary biology T. Ryan Gregory at the University of Guelph, Canada, laid out in a series of tweets that these new sub-lineages are not the final “Pokemon” evolution of SARS-CoV-2. He warned that with all of the replication that is still going on, the virus is still mutating rapidly, especially around the Spike protein, and thus is capable of producing new variants.

Alpha and Delta, which drove two major waves around the world with high levels of mortality, did not give rise to Omicron, but now the variants of concern are increasingly emerging from within the Omicron clade. Prof Gregory noted that a growing number of variants are being seen with transmission or immune escape advantages.

“Sorry to say it, but this pandemic isn’t over,” he concluded.

Categories : Cardiovascular Disease ExerciseTags :

Cutting Down on Sedentary Time Reduces Cardiovascular Risk

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Feet in sports shoes
Source: Pixabay

Cutting down daily sedentary time can have a positive effect on the risk factors of cardiovascular disease and type 2 diabetes in as little as three months, according to a study published in the Journal of Science and Medicine in Sport. The study findings suggest that simply one hour less sitting daily and increasing light physical activity can help in the prevention of these diseases.

Regular exercise is well known to be beneficial in weight management and prevention of chronic diseases. However, many adults do not meet the weekly recommendation of 2.5 hours of moderate-intensity exercise, and the majority of the day is typically spent sitting.

In an intervention study, researchers investigated whether health benefits can be achieved by reducing daily sedentary time during a three-month intervention period. The research participants were sedentary and physically inactive working-age adults with an increased risk of type 2 diabetes and cardiovascular diseases.

The researchers compared two groups: the intervention group was guided to reduce their sitting time by one hour per day by increasing standing and light-intensity physical activity, while the control group was instructed to maintain their usual habits and sedentary lifestyle.

“What makes our research design unique is that sedentary time and physical activity of both groups were measured with accelerometers throughout the entire three-month period, whereas in earlier studies activity has typically been measured only for a few days at the beginning and end of the study period. This makes it possible to receive more information on the actual behaviour changes over a longer time period,” explained  Doctoral Candidate Taru Garthwaite from the University of Turku in Finland.

The intervention group reduced sedentary time by 50 minutes per day on average, mainly by increasing the amount of light- and moderate-intensity physical activity. Over the three-month period, the researchers observed benefits in health outcomes related to blood sugar regulation, insulin sensitivity and liver health in the intervention group.

“It is an encouraging thought that health benefits can be achieved by reducing the time spent sitting and increasing the amount of even light-intensity physical activity. For many, this may be an easier starting point than increasing actual exercise,” said Garthwaite.

People who do not meet the weekly physical activity recommendations atre the most likely to benefit the most from replacing sedentary time with light physical activity. However, reducing sedentary time is probably not enough in itself to prevent diseases if the person has several risk factors of diabetes and cardiovascular diseases.

Garthwaite stressed the encouraging nature of the findings: “Reducing the time spent sitting might still slow down the development of these diseases, but greater benefits can of course be gained by increasing the amount or intensity of physical activity in addition to sitting less.”

The researchers next aim to study how changes in daily activity and sedentary time affect energy metabolism and body composition in addition to the risk factors of diabetes and cardiovascular diseases over a six-month study period.

Source: University of Turku

Categories : AntibioticsTags :

Fungal Microbiota May Explain Antibiotics’ Long Term Effects in Infants

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Gut microbiome. Credit: Darryl Leja, NIH

In infants treated with antibiotics, fungal gut microbiota are more abundant and diverse compared with the control group even six weeks following the start of the antibiotic course, according to a study published in the Journal of Fungi. The study’s authors suggest that reduced competition from gut bacteria being killed by antibiotics left more space for fungi to multiply.

“The results of our research strongly indicate that bacteria in the gut regulate the fungal microbiota and keep it under control. When bacteria are disrupted by antibiotics, fungi, Candida in particular, have the chance to reproduce,” explained PhD student Rebecka Ventin-Holmberg from the University of Helsinki.

A new key finding in the study was that the changes in the fungal gut microbiota, together with the bacterial microbiota, may be partly responsible for the long-term adverse effects of antibiotics on human health.

Antibiotics are the most commonly prescribed drugs for infants, causing changes in the gut microbiota at its most important developmental stage. These changes are more long-term compared to those in adults.

“Antibiotics can have adverse effects on both the bacterial and the fungal microbiota, which can result in, for example, antibiotic-associated diarrhoea,” Ventin-Holmberg said.

“In addition, antibiotics increase the risk of developing chronic inflammatory diseases, such as inflammatory bowel disease (IBD), and they have been found also to have a link to overweight,” she added.

These long-term effects are thought to be caused, at least in part, by an imbalance in the gut microbiota.

This study involved infants with a respiratory syncytial virus (RSV) infection who had never previously received antibiotics. While some of the children were given antibiotics due to complications, others received no antibiotic therapy throughout the study.

“Investigating the effects of antibiotics is important for the development of techniques that can be used to avoid chronic inflammatory diseases and other disruptions to the gut microbiota in the future,” Ventin-Holmberg emphasised.

While there have been many studies on the effect of antibiotics on bacterial microbiota, there has been a lack of studies on fungal microbiota. This study’s findings indicate that fungal microbiota may also have a role in the long-term effects of imbalance in the gut microbiota.

“Consequently, future research should focus on all micro-organisms in the gut together to better understand their interconnections and to obtain a better overview of the microbiome as a whole,” Ventin-Holmberg noted.

Source: University of Helsinki