Categories : Cardiovascular DiseaseTags :

New Approach to Address Cardiac Disease in Rheumatoid Arthritis

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A new approach to address cardiac disease in rheumatoid arthritis (RA) patients has been developed.

Currently patients suffering from RA are also particularly susceptible to diastolic dysfunction, a type of cardiac deficiency which may lead to heart failure, resulting in a higher mortality rate among such patients.
To address this unmet clinical need, researchers from Queen Mary’s William Harvey Research Institute (WHRI) responded by developing an experimental model of cardiomyopathy in inflammatory arthritis.

After several attempts, the researchers finally hit upon the right model by characterising experimental animals with arthritis. The animals developed cardiac diastolic dysfunction, recapitulating the symptoms presented by RA patients. Diastolic dysfunction means the heart is able to contract as normal but unable to dilate properly, ultimately leading to heart failure over time.

Professor Mauro Perretti, lead study author and Professor of Immunopharmacology at Queen Mary University of London said, “As is often the case, the description of a valid model of disease can open new vistas on pathogenic mechanisms as well as on novel therapeutic approaches. At present, the cardiomyopathy of patients affected by rheumatoid arthritis is not treated, and on top of this, current anti-rheumatic drugs (eg biologics or steroids) may even worsen it. As such there is an urgent therapeutic need to intervene and treat, if not cure, the cardiomyopathy of patients affected by rheumatoid arthritis.”

“The broad area of cardiac inflammation is largely unexplored. At the WHRI we have several groups addressing experimental and translational work on several syndromes of the heart. Thus, there is work on myocarditis, on diabetes-induced cardiomyopathy and now with this study, the cardiomyopathy of inflammatory arthritis. The WHRI at Queen Mary University of London is a place of excellence to study cardiac inflammation in all its multiple faces, thanks also to our partnership with the Barts Heart Centre at Barts Health NHS Trust.”

The study was published in PNAS.

Source: EurekAlert!

Categories : ImmunologyTags :

How Vitamin A Enters into Gut Immune Cells

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Researchers have reported in Science how vitamin A enters immune cells in the intestines – findings that could offer insight to treat digestive diseases and perhaps help improve the efficacy of certain vaccines.

“Now that we know more about this important aspect of immune function, we may eventually be able to manipulate how vitamin A is delivered to the immune system for disease treatment or prevention,” said Lora Hooper, PhD, Chair of Immunology at UT Southwestern, Howard Hughes Medical Institute Investigator.

Vitamin A is a fat-soluble nutrient which is converted to retinol and then to retinoic acid before it is used. It is important for every tissue in the body, said Dr. Hooper, Professor of Immunology, Microbiology, and in the Center for the Genetics of Host Defense at UT Southwestern. It is particularly crucial for the adaptive immune system, a subset of the broader immune system that reacts to specific pathogens based on immunological memory, the type formed by exposure to disease or vaccines.

Although researchers knew that some intestinal immune cells called myeloid cells can convert retinol to retinoic acid, how they acquire retinol to perform this task was a mystery, said Dr. Hooper, whose lab investigates how resident intestinal bacteria influence the biology of humans and other mammalian hosts.

Lead author Ye-Ji Bang, PhD, a postdoctoral fellow in the Hooper Lab, and colleagues focused on serum amyloid A proteins, a family of retinol-binding proteins that some organs produce during infections. They used biochemical techniques to determine which cell surface proteins they attached to, and identified LDL receptor-related protein 1 (LRP1).

Drs. Bang, Hooper, Herz, and colleagues showed that LRP1 was present on intestinal myeloid cells, where it seemed to be transferring retinol inside. When the researchers deleted the gene for this receptor in mice, preventing their myeloid cells from taking up the vitamin A derivative, the adaptive immune system in their gut virtually disappeared, said Dr Hooper. T and B cells and the molecule immunoglobulin A, critical components of adaptive immunity, were significantly reduced. Researchers then compared the response to Salmonella infection between mice with LRP1 and those without. Those without the receptor quickly succumbed to the infection.

The findings suggest that LRP1 is what conveys retinol into myeloid cells. If a way could be developed to inhibit this process, explained Dr Hooper, it could calm down the immune response in inflammatory diseases that affect the intestines, such as inflammatory bowel disease and Crohn’s disease. Alternatively, boosting LRP1 activity could boost immune activity, making oral vaccines more effective.

Source: UT Southwestern Medical Center

Categories : Diseases, Syndromes and ConditionsTags :

Discovery of Cell Type Linked to Skin Conditions

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Researchers have found a cell type in human skin that contributes to inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO). Their study findings were published in the Journal of Experimental Medicine. The team hails from A*STAR’s Singapore Immunology Network (SIgN).

Chronic inflammatory skin diseases such as AD and PSO are characterised by the presence of an activated T cell subtype which secretes pro-inflammatory cytokines in the skin. This immune dysregulation mediated by T cells is central to the pathogenesis of a wide range of inflammatory skin diseases. Thus, understanding the factors modulating T cell priming and activation in healthy and diseased skin is key to developing effective treatments for these diseases.

Recently, a single-cell RNA sequencing (RNA-seq) approach has been used to analyse immune cells in human skin, including dendritic cells (DCs) and macrophages, which are cells that can T cell activation. To tease out the role of DCs and macrophages in chronic inflammatory skin diseases, the team used a combination of complex approaches to yield an unbiased profile/ landscape of DCs and macrophages, and to describe their distinct molecular signatures and proportions in skin lesions of AD and PSO patients.

The researchers found an increase in the proportion of CD14+ DC3s in PSO lesional skin, where they were one of the major cell types co-expressing IL1B and IL23A, two cytokines essential for PSO pathogenesis. This finding suggests that targeting CD14+ DC3 might represent a novel therapeutic option in the treatment of PSO, and demonstrates the potential for the single-cell myeloid cell landscape database to provide important insights into skin biology in health and disease.

Last author Dr Florent Ginhoux, Senior Principal Investigator, SIgN said: “The findings from this study are significant as it will allow the design of new strategies to target or modulate myeloid cell populations for better health outcomes for patients of atopic dermatitis and psoriasis.”

“The roles of antigen-presenting cells in the development of inflammatory skin diseases remain unclear. This study clearly revealed the functions of each antigen-presenting cell subset, which is very informative and valuable to understand the pathogenesis of atopic dermatitis and psoriasis. We expect that this study will lead to the design of new treatment for refractory inflammatory skin diseases.” said Prof Kenji Kabashima, Adjunct Principal Investigator from SIgN and SRIS.

Source: EurekAlert!

Categories : Diet and Nutrition Mental HealthTags :

Fruit and Vegetable Consumption Directly Increases Happiness

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Fruit and vegetable consumption and exercise can directly increase levels of self-reported happiness, according to findings from a new study.

Public health campaigns encourage healthier diets and exercise by virtue of the well-studied link between lifestyle and wellbeing, and will benefit from new findings published by the Journal of Happiness Studies showing that there is also a positive causation from lifestyle to life satisfaction.

This research is the first to identify the causation of happiness, the consumption of fruit and vegetables and exercising are related, rather than generalising a correlation. The researchers, Dr Adelina Gschwandtner (Kent’s School of Economics), Dr Sarah Jewell and Professor Uma Kambhampati (both from the University of Reading’s School of Economics), used an instrumental variable approach to filter out any effect from happiness to lifestyle. This approach revealed that it is the effect of fruit and vegetables and exercising that makes people happy and not the other way round.

The findings show individuals’ ability to delay gratification and apply self-control plays a major role in influencing lifestyle decisions, which in turn has a positive impact on wellbeing. The research also shows that men appear to exercise more, and women eat more fruit and vegetables.

Dr Gschwandtner said: ‘Behavioural nudges that help the planning self to reinforce long-term objectives are likely to be especially helpful in maintaining a healthy lifestyle. If a better lifestyle not only makes us healthier but also happier, then it is a clear win-win situation.’

Professor Kambhampati said: ‘There has been a bigger shift in recent years for healthier lifestyle choices. To establish that eating more fruit and vegetables and exercising can increase happiness as well as offer health benefits is a major development. This may also prove useful for policy campaigns around environment and sustainability.’

Source: University of Kent

Categories : Cardiovascular DiseaseTags :

Strong Adherence to Stroke Medication is Crucial

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A new study emphasises the importance of survivors of first-time stroke or transient ischaemic attack (TIA) to take medications on an ongoing basis, highlighting long-term associations with survival.

Stroke is the second leading risk of death worldwide, with In 2016, the average lifetime risk of stroke after 25 for the global population was 24.9%. Nearly half of all survivors of stroke are expected to experience a recurrent cardiovascular event within 10 years. Specific medications help to prevent this long-term risk, but adherence to these agents is often suboptimal among patients.

The study, published in Stroke, demonstrates the importance of medication adherence after stroke to maximise survival, even for patients with near-perfect adherence. These findings are in support of targeted initiatives to maximise medication adherence after stroke/TIA, such as implementation of medication reminder systems, mobile health technologies, increased follow-up by clinicians or complex behaviour change programs.

Drawing from Australian databases, the study enrolled 8363 adult patients who survived a first stroke or TIA between July 2010 and June 2014, with follow-up for a further three years. For patients with one-year adherence above 60%, each 10% improvement in adherence was associated with a 13-15% reduction in mortality risk. These results suggest that aiming for an arbitrary adherence target of 80% may be inappropriate as maximal survival benefits were observed closer to 100% adherence.

The study’s lead author, Associate Professor Monique Kilkenny, said continued use of secondary prevention medications can be improved with several factors: provision of medication on hospital discharge, regular contact with a primary care physician, and specialist physician contact.

“These findings represent important implications for practice by highlighting the value of efforts to improve medication adherence post-stroke/TIA, even among patients with near-perfect adherence,” said Associate Professor Kilkenny.

“Our findings provide evidence in support of targeted initiatives to maximise medication adherence after stroke/TIA and there is considerable scope for further interventions to improve medication adherence.”

Source: Monash University

Categories : COVIDTags :

COVID Variants Evolving to Improved Airborne Transmission

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A new study found that people infected with SARS-CoV-2 shed significant numbers of virus particles in their breath – and those infected with the Alpha variant put 43 to 100 times more virus into the air than people infected with the original strains. 

The researchers also found that loose-fitting cloth and surgical masks reduced the amount of virus that gets into the air around infected people by about half. The study was published in Clinical Infectious Diseases.

“Our latest study provides further evidence of the importance of airborne transmission,” said Dr Don Milton, Professor, Environmental Health, University of Maryland School of Public Health. “We know that the Delta variant circulating now is even more contagious than the Alpha variant. Our research indicates that the variants just keep getting better at traveling through the air, so we must provide better ventilation and wear tight-fitting masks, in addition to vaccination, to help stop spread of the virus.”

The numbers of airborne virus particles coming from infections with the Alpha variant (the dominant strain circulating at the time this study was conducted) was much more (18 times more) than could be explained by the increased amounts of virus picked up in nasal swabs and saliva. 
Doctoral student Jianyu Lai, a lead author of the study, explained: “We already knew that virus in saliva and nasal swabs was increased in Alpha variant infections. Virus from the nose and mouth might be transmitted by sprays of large droplets up close to an infected person. But, our study shows that the virus in exhaled aerosols is increasing even more.” These major increases in airborne virus from Alpha infections occurred before the arrival of the Delta variant, suggesting that the virus is evolving to have improved airborne transmission.

To test the efficacy of masks in reducing transmission, the researchers measured how much SARS-CoV-2 is exhaled into the air with and without wearing a cloth or surgical mask. They found that face coverings significantly reduced virus-laden particles in the air around the person with COVID by about 50%.

Co-author Dr Jennifer German said, “The take-home messages from this paper are that the coronavirus can be in your exhaled breath, is getting better at being in your exhaled breath, and using a mask reduces the chance of you breathing it on others.” This means that a layered approach to control measures (including improved ventilation, increased filtration, UV air sanitation, and tight-fitting masks, in addition to vaccination) is critical to protect people in public-facing jobs and indoor spaces.

Source: University of Maryland

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

New Drug Targets for Memory Loss

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Researchers have identified specific drug targets within memory-encoding neural circuits, opening up possibilities for new treatments of a range of brain disorders.

Memory loss is a main feature of a number of neurological and psychiatric disorders including Alzheimer’s disease and schizophrenia. Presently, there are few, very limited memory loss treatments and the search for safe and effective drug therapies has, until now, borne little fruit.

The research was done in collaboration with colleagues at the international biopharmaceutical company Sosei Heptares. The findings, published in Nature Communications, identify specific receptors for the neurotransmitter acetylcholine that re-route information flowing through memory circuits in the hippocampus. Acetylcholine is released in the brain during learning and is critical for the acquisition of new memories. Until now, the only effective treatment for the symptoms of cognitive or memory impairment seen in diseases such as Alzheimer’s is using drugs that broadly boost acetylcholine. However, this leads to multiple adverse side effects. The discovery of specific receptor targets that have the potential to provide the positive effects whilst avoiding the negative ones is promising.

Lead author Professor Jack Mellor from the University of Bristol’s Center for Synaptic Plasticity, said: “These findings are about the fundamental processes that occur in the brain during the encoding of memory and how they may be regulated by brain state or drugs targeting specific receptor proteins. In the long-term, the discovery of these specific targets opens up avenues and opportunities for the development of new treatments for the symptoms of Alzheimer’s disease and other conditions with prominent cognitive impairments. The academic-industry partnership is important for these discoveries and we hope to continue working together on these projects.”

Dr Miles Congreve, Chief Scientific Officer at Sosei Heptares, added: “These important studies have helped us to design and select new, exquisitely targeted therapeutic agents that mimic the effects of acetylcholine at specific muscarinic receptors, without triggering the unwanted side effects of earlier and less-well targeted treatments. This approach has the exciting potential to improve memory and cognitive function in patients with Alzheimer’s and other neurological diseases.”

“It is fascinating how the brain prioritises different bits of information, working out what is important to encode in memory and what can be discarded. We know there must be mechanisms to pull out the things that are important to us but we know very little about how these processes work. Our future program of work aims to reveal how the brain does this using acetylcholine in tandem with other neurotransmitters such as dopamine, serotonin and noradrenaline,” said Professor Mellor.

Source: University of Bristol

Categories : COVID Obstetrics & GynaecologyTags :

Menstrual Changes After COVID Vaccinations

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In an article in the BMJ, authors argue that menstrual changes after COVID vaccination are plausible and should be investigated. 

Listed common side effects of COVID vaccination include a sore arm, fever, fatigue, and myalgia. However, changes to periods and unexpected vaginal bleeding are not listed, and primary care clinicians and those in the reproductive health field are seeing more and more people who have experienced these events shortly after vaccination.

More than 30 000 reports of these events had been made to the UK;s surveillance scheme for adverse drug reactions by 2 September 2021, across all COVID vaccines currently offered.

Most post-vaccination changes to periods return to normal, and there is no evidence that COVID vaccination adversely affects fertility. In clinical trials, there were similar rates for unintended pregnancies in vaccinated and unvaccinated groups. In fertility clinics, fertility measures and pregnancy rates are similar in vaccinated and unvaccinated patients. The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) says that there are few reported that 

Menstrual changes have been reported after both mRNA and adenovirus vectored COVID vaccines, suggesting that, if there is a connection, it is likely to be a result of the immune response to vaccination rather than a specific vaccine component. Human papillomavirus (HPV) vaccinations have also been associated with menstrual changes. Indeed, the menstrual cycle can be affected by immune activation from various stimuli, including viral infection: one study found about a quarter of menstruating women with COVID experienced menstrual disruption.

Biologically plausible mechanisms linking immune stimulation with menstrual changes include immunological influences on the hormones driving the menstrual cycle or effects mediated by immune cells in the lining of the uterus, which are involved in the cyclical build-up and breakdown of this tissue. Research may also help understand the mechanism.

Though the period changes are short lived, there is need for adequate research. Vaccine hesitancy among young women is largely driven by false claims that COVID vaccines could harm their chances of future pregnancy. Failing to thoroughly investigate reports of menstrual changes after vaccination is likely to fuel these fears. If a link between vaccination and menstrual changes is confirmed, this information will allow people to plan for potentially altered cycles. Clear and trusted information is particularly important for those who rely on being able to predict their menstrual cycles to either achieve or avoid pregnancy.

In terms of management, the Royal College of Obstetricians and Gynaecologists and the MHRA recommend that anyone reporting a change in periods persisting over several cycles, or new vaginal bleeding after the menopause, should be managed according to the usual clinical guidelines for these conditions.

The authors conclude by stating there is an important lesson in that the effects of medical interventions on menstruation should not be an afterthought in future research. In clinical trials, participants are unlikely to report changes to periods unless specifically asked, so in future trials, information about menstrual cycles and other vaginal bleeding should be actively solicited.

Source: The BMJ

Categories : VaccinesTags :

Attenuated Virus Confers Broader Flu Protection

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A mouse study using both attenuated and inactivated forms of influenza has helped explain why people vaccinated with the inactivated virus still occasionally end up contracting the illness. The finding should help researchers develop vaccines that offer broad protection against viruses.

Influenza is a major global health burden, with the World Health Organization estimating that it causes one billion cases annually. Each year, vaccines are developed that offer some protection against infection. But the influenza virus is a moving target that is constantly mutating, and so vaccines can lose their effectiveness as a season progresses.

Influenza vaccines commonly come in two forms: inactivated vaccines (including component vaccines) and live attenuated vaccines. Live vaccines confer broader protection against variants than inactivated vaccines, but side effects such as fevers and headaches are more common. A result they have yet to be approved in some countries. Live vaccines induce the production of broadly reactive antibodies, but until now, scientists didn’t know why.

In a recent study, Masato Kubo of the RIKEN Center for Integrative Medical Sciences and his co-workers have discovered two processes that live vaccines induce in mice that together account for their broader protection.

They found that, like the virus itself, the live vaccine virus causes the virus to replicate deep in the lungs, which in turn induces a structural change in the virus haemagglutinin, a mushroom-shaped protein on the surface of the virus involved in infecting cells. This structural change exposes previously hidden regions of antigens that the immune system can recognise.

Next, germinal cells are activated by interleukin 4 (IL-4), a cytokine heavily involved in regulating antibody production. IL-4 is derived from special T cells known as follicular helper T cells. This activation causes a minor population of B cells to proliferate and it is these B cells that are responsible for generating broadly protective antibodies.

The role of IL-4 in inducing the broad immune response came as a surprise. “Until now there had been no direct evidence to show the importance of IL-4,” says Kubo. “That was one of the surprises of this study for me.”

“We believe both processes are needed for generating broadly active antibodies: viral duplication in the lungs and expansion of the minor population of B cells,” says Kubo. “These two processes mostly likely occur when a person is infected by the influenza virus itself.”

The team now plans to see if there are similar mechanisms for other viruses such as SARS-CoV-2.

Source: RIKEN

Categories : UncategorizedTags :

Nelson Mandela Bay Area Hit by Rabies Outbreak

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An outbreak of rabies has hit the Nelson Mandela Bay metro, with a nine-year-old Gqeberha boy being its first victim so far.

The Nelson Mandela Bay Metropolitan Municipality (NMBMM) issued a warning calling on residents to be vigilant and to take their domestic pets for rabies vaccinations, following the death of a boy last weekend who was bitten by a dog. Health-e News received confirmation from NMBMM that the nine-year-old boy died at the Dora Nginza Hospital on Friday last week.

“We have learnt with sadness of the passing of the boy from Motherwell, who died due to rabies. We have the family in our prayers,” said Acting Mayor Luxolo Namette.

The municipality’s health services directorate deputy director Dr Patrick Nodwele said vaccinating domestic pets can be the most effective way of preventing rabies transmission to humans.

“The boy passed at Dora Nginza Hospital where it was established that he had been bitten by a dog. Our health officials, together with the Department of Agrarian Reform, have been busy these last couple months vaccinating dogs and cats in an effort to curb the virus as we know that rabies is a vaccine-preventable disease and post-bite vaccinations save lives,” Dr Nodwele told Health-e News.

Rabies causes viral encephalitis which kills up to 70 000 people a year around the world. Infected animal saliva transmits viral encephalitis to humans. Rabies is one of the oldest known diseases in history with cases dating back to 4000 years ago. For most of human history, a bite from a rabid animal was uniformly fatal. In the past, people were so scared of rabies that after being bitten by a potentially rabid animal, many would commit suicide. 

Rabies cases rose significantly over August and September, he added, which is why they are calling on residents to take their domestic pets for vaccinations. The outbreak is spread throughout the entire Nelson Mandela metro region and Nodwele said that 61 rabies specimens submitted for testing all came back positive.

So far 5254 dogs and 438 cats have been vaccinated across the metro. The municipality from time to time issues a domestic pets vaccination schedule, and is calling on residents to observe the schedule so that they bring their animals for vaccination. A vaccination and community education programme is also being run.

Dr Nodwele said the incubation period of rabies is two to three months, though with factors such as bite location and viral load, it can also vary from one week to a year.

“Initial symptoms include a fever and pain, and unusual or unexplained tingling, pricking or burning sensations at the wound site. As the virus spreads through the body to the central nervous system, progressive and fatal inflammation of the brain and spinal cord develops,” Dr Nodwele explained.

Source: Health-e News