Year: 2021

Categories : Metabolic DisordersTags :

Hair Loss Tied to High-fat Diets or Genetic Obesity

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A mouse study by Japanese researchers found that high-fat diets or genetically induced obesity can cause loss of hair follicles.

Obesity is linked to the development of numerous diseases in humans, such as heart disease and diabetes. However, it’s not fully clear how body organs specifically deteriorate and lose functionality from chronic obesity. Using mice, researchers from Tokyo Medical and Dental University (TMDU) examined how a high-fat diet or genetically induced obesity can affect hair thinning and loss. The findings, published in Nature, indicated that obesity can lead to depletion of hair follicle stem cells (HFSCs) by inducing certain inflammatory signals, blocking hair follicle regeneration and ultimately resulting in loss of hair follicles.

HFSCs normally renew themselves every hair follicle cycle. With progressing age, HFSCs fail to renew themselves leading to fewer HFSCs and therefore hair thinning. Although overweight people have a higher risk of male pattern balding, whether obesity accelerates hair thinning, how it does this and the molecular mechanisms behind it have remained largely a mystery. The TMDU group aimed to address those questions and identified some of the mechanisms.

Explaining the study, study lead author Hironobu Morinaga said: “High-fat diet feeding accelerates hair thinning by depleting HFSCs that replenish mature cells that grow hair, especially in old mice. We compared the gene expression in HFSCs between HFD-fed mice and standard diet-fed mice and traced the fate of those HFSCs after their activation.

“We found that those HFSCs in HFD-fed obesed mice change their fate into the skin surface corneocytes or sebocytes that secrete sebum upon their activation. Those mice show faster hair loss and smaller hair follicles along with depletion of HFSCs.

“Even with HFD feeding in four consecutive days, HFSCs show increased oxidative stress and the signs of epidermal differentiation.”

“The gene expression in HFSCs from the high-fat–fed mice indicated the activation of inflammatory cytokine signaling within HFSCs,” said senior author Emi Nishimura. “The inflammatory signals in HFSCs strikingly repress the Sonic hedgehog signaling that plays a crucial role in hair follicle regeneration in HFSCs.

However, the researchers noted that activating the Sonic hedgehog signaling pathway in this process can rescue the depletion of HFSCs. “This could prevent the hair loss brought on by the high-fat diet,” said Nishimura.

This study shines a light on cellular and tissue dysfunction from a high-fat diet or genetically induced obesity, and could lead to prevention and treatment of hair thinning along with greater understanding of obesity-related diseases.

Source: Tokyo Medical and Dental University

Categories : Cardiovascular DiseaseTags :

A Year of Exercise Reverses Heart Failure Signs

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In a small study, a year of exercise training helped to maintain or increase the youthful elasticity of the heart muscle among people in late middle age showing early signs of heart failure.

Published in Circulation, the research reinforces the notion that “exercise is medicine,” an important shift in approach, according to the researchers.

The study focused on heart failure with preserved ejection fraction, which is characterised by stiffening of the heart muscle and high pressures inside the heart during exercise. Once established, the condition is largely untreatable and causes fatigue, excess fluid in the lungs and legs, and shortness of breath.

“It is considered by some to be one of the most important virtually untreatable diseases in cardiovascular medicine,” said senior author Dr Benjamin Levine,  professor of internal medicine at UT Southwestern and director of the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Dallas. “So, of course, if there are no therapies, then the most important thing to do is to figure out how to prevent it from happening in the first place.”

In previous studies, prolonged exercise training was shown to improve heart elasticity in younger people, but was ineffective for heart stiffness in people 65 and older. The researchers decided to see if committed exercise could improve heart stiffness in healthy, sedentary men and women ages 45 to 64.

The study recruited 31 participants who showed some thickening of the heart muscle and an increase in blood biomarkers associated with heart failure, even though they had no other symptoms such as shortness of breath.

Eleven were randomly assigned to a control group and prescribed a program of yoga, balance and strength training three times a week. The rest were assigned to an individually tailored exercise regimen that gradually ramped up until the participants were doing intensive aerobic interval training for at least 30 minutes at least twice a week, plus two to three moderate-intensity training sessions and one to two strength training sessions each week. 

After one year, the group assigned vigorous exercise training showed a physiologically and statistically significant improvement in measures of cardiac stiffness and cardiorespiratory fitness, compared to no change in the control group.

The results suggest late middle age may be a “sweet spot” for using exercise to prevent heart failure with preserved ejection fraction, before the heart gets too stiff, Prof Levine said. He compared the heart muscle to an elastic band: a new one stretches easily and snaps right back.

“That’s a youthful cardiovascular system,” he said. “Now, stick it in a drawer and come back 30 years later—it doesn’t stretch, and it doesn’t snap back. And that’s one of the things that happens to the circulation, both the heart and the blood vessels as we age, particularly with sedentary aging.”

However, the study cannot determine if the participants will still go on to develop heart failure. This question will have to be addressed by larger studies. Furthermore, it is difficult for people to adhere to an exercise program, and the intensive intervention studied may be difficult and expensive to replicate on a large scale.

Source: American Heart Association

Categories : COVIDTags :

Stockpiling Could Cause 241 Million Vaccine Doses to be Wasted

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Analytics company Airfinity estimates the G7 and EU will have an excess of 1 billion vaccine doses by the end of 2021, of which 10% are expected to expire. 

When factoring the time taken to distribute and administer the doses in Lower Income Countries (LICs) and Lower Middle Income Countries (LMICs), the proportion rises. Many of these countries will refuse vaccines that don’t have at least a two month shelf life. Taking into account this two month shelf, 241 million doses could be wasted by the end of 2021, amounting to a quarter of the G7 and EU surplus stock. 

The available vaccines in the G7 and EU, together with already purchased doses and COVAX deliveries, are sufficient for LICs and LMICs to vaccinate 70% of their populations by May 2022. Airfinity estimates that total global COVID cases are likely to exceed 400 million by mid-2022 and immediately redistributing vaccines could potentially avert nearly 1 million deaths from the virus in that time frame. 

“Currently doses tend to get shared in low volumes, at short notice, and with shorter than ideal expiry dates – making it a huge logistical lift to allocate and deliver these to countries able to absorb them,” says Aurélia Nguyen, managing director of the COVAX facility.

Vaccine manufacturers are now making 1.5bn doses every month.

“They’re producing a huge number of doses. It has scaled up immensely over the last three or four months,” Dr Matt Linley, lead researcher at Airfinity, told BBC News.

“I don’t think it was necessarily rich countries being greedy, it’s more that they didn’t know which vaccines would work,” says Dr Linley. “So they had to purchase several of them.”

Airfinity hopes to show governments that there are enough vaccines to fulfil their needs, and thanks to this secure supply they can donate without stockpiling.

“They don’t want to be caught off guard,” said Agathe Demarais. “It’s also about domestic political pressure because part of the electorate would probably be very unhappy to see vaccines being donated, if there is a feeling that they’re still needed at home.”

Co-founder and CEO of Airfinity, Rasmus Bech Hansen said: “The world has witnessed two extraordinary scientific achievements in the pandemic: The fast development of highly effective vaccines and the unprecedented scale up of production.For the world to get the full benefit of this, our data shows, we need a third equally unprecedented achievement: A large scale, rapid, globally coordinated, science driven vaccination campaign.” 

Source: Airfinity

Categories : COVIDTags :

Now Iodine is the In-thing for COVID

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A dangerous new trend has emerged on social media, which involves a new COVID ‘cure’ by gargling the widely used antiseptic, povidone-iodine (PVP).

This trend has been sparked by an online video in Thai which has been widely shared on social media, featuring someone who claims to be a doctor. However this has been debunked. The trend is also cause for concern as the PVP may accidentally be swallowed. 

PVP, also sold under the name Betadine, is used for disinfection in surgical procedures and wound treatment. Gargling with 0.5% PVP has been shown to reduce the symptoms of sore throat associated with COVID, but has not been adequately shown to relieve any other symptoms.  
The immediate side effects of ingesting any PVP antiseptic include nausea, vomiting, general weakness, and diarrhoea. In severe cases, PVP ingestion can result in acute renal failure, cardiovascular collapse, liver function impairment, shortness of breath, low blood pressure, and even death.

In one study, researchers assessed the usage of 0.5% povidone-iodine mouthwash in patients as a way of reducing viral load during dental procedures, reducing possible exposure of healthcare workers. However, there is no evidence beyond in vitro testing that it actually reduces viral load in the throat. 

An official statement on the Betadine website reads as follows: “Betadine® Antiseptic First Aid products have not been approved to treat coronavirus. Products should only be used to help prevent infection in minor cuts, scrapes and burns. Betadine Antiseptic products have not been demonstrated to be effective for the treatment or prevention of COVID-19 or any other viruses.”

Source: Newsweek

Categories : CancerTags :

Cancer Follow-up Care Needs Improvement

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With greater long-term cancer survival, previous standards of cancer follow-up care and support may no longer meet current needs.

The side-effects of anticancer medicines and impacts of the illness itself that sometimes persist after the end of treatment can hinder  a return to normal life after beating cancer. A study presented at the ESMO Congress 2021 showed that a significant proportion of survivors continue to suffer from burdensome symptoms for several years and reveal widespread dissatisfaction with the assistance provided.

Prof Dorothy Keefe, CEO of Australia’s national cancer agency, Cancer Australia, chair of the congress’s supportive and palliative care track, not involved in the study, underlined its importance in a context where survivorship research has lagged behind research on cancer treatment. “This is probably due to the increase in survival rates itself lagging behind the introduction of new therapies, but also to a lack of prioritisation compared to the need to develop a cure,” Keefe said, and highlighted the scale of the issue today: “We now have millions of cancer survivors in Australia, hundreds of millions around the world – and an ever-increasing number who could potentially have long-term side-effects.”

One of the most common symptoms experienced by patients and survivors alike is cancer-related fatigue (CRF), a persistent sense of exhaustion, not alleviated by sleep or rest and significantly interferes with the person’s usual functioning. The FiX study initially evaluated the patterns, severity and management of CRF among 2508 patients with 15 different types of cancer two years after the discovery of their illness. In a follow-up survey, 36 potential long-term problems, completed by participants around four years after diagnosis, almost 40% of survivors continued to report fatigue that they rated as a moderate or severe burden. As well as fatigue, over 40% of patients reported loss of physical capacity as a burden and over one third suffered from trouble sleeping, sexual problems, joint pains and anxiety.

Although there are recommendations for managing side-effects like CRF, study author Dr Martina Schmidt from the German Cancer Research Centre (DKFZ) in Heidelberg, Germany, drew attention to their lack of implementation and reported that more than one in three affected individuals in the study evaluated the support they were offered for fatigue as poor. “Despite increasing awareness of the effectiveness of mitigating measures like exercise to reduce fatigue, patients are still too often left alone to seek help for symptoms that cannot be directly addressed with medicines in the same way as something like pain, for which satisfaction with the support received was high in our study.”

Prof Keefe commented on the results, saying: “This research shows that a staggeringly high number of patients still suffer from significant health issues years after being declared disease-free. Their dissatisfaction with the care available is a wake-up call that we should be paying more attention to these individuals, trying to understand the mechanisms at play in order to identify interventions that could help them to better recover.”

According to Dr Schmidt, cancer follow-up care should therefore also incorporate more systematic screening for additional symptoms that can burden patients. “The first step should be to make sure that patients themselves are better informed about these potential issues early on, so they know that conditions like CRF are not only expected, but often manageable and that they should not wait for symptoms to disappear on their own,” she said.

Recognising that possible models of long-term support remain largely untested, Keefe further advocated that all patients should be provided with a survivorship care plan when they reach the end of their treatment. “Going forward, we need to develop these models of care in a way that minimises the burden on healthcare systems, implement them and research their impact so that we can come back in five years’ time and evaluate whether they have made a difference for cancer survivors,” she concluded.

Source: European Society for Medical Oncology

Categories : AllergiesTags :

New Allergen Pathway Discovery Could Yield New Meds

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Researchers have uncovered the mechanism by which the innate immune system is triggered by allergens, such as insects, mites, and fungi.

In Nature Immunology, researchers revealed new details about how the body’s “type 2 innate immune response” system works, which could yield a new medication for allergy control.

“Disrupting this allergen sensing pathway could provide a unique opportunity to counteract type 2 immunity and alleviate allergic inflammation,” said senior author Marc Rothenberg, MD, PhD, Director, Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center

In addition to Rothenberg, the research team included , Mark Rochman, PhD, Yrina Rochman, PhD, Julie Caldwell, PhD. Lydia Mack, MS, Jennifer Felton, PhD, Jeff Habel, PhD, Aleksey Porollo, PhD and Chandrashekhar Pasare, DVM, PhD.

Multiple allergens had been shown to induce a similar IL-33 response upon breaching the epithelial layer of mucosal membranes, a process which the researchers pinned down.

“This breakthrough was made possible by new insights into the role of ripoptosome signaling and caspases in allergic inflammation,” said Michael Brusilovsky, MMedSc, PhD, who was the first author of the study.

Specifically, the allergens trigger activity among an interlocked set of cell death-inducing signals called the ripoptosome. This signaling “platform” includes numerous components, but for allergic inflammatory reactions, the key player appears to be a molecular switch called caspase 8. The investigators named the pathway, “RipIL-33” as IL-33 is processed (ripped) by the ripoptosome.

How allergens are sensed has remained a mystery.

“The discovery of this surprising mechanism is the most important breakthrough in understanding how the innate immune system senses allergens to initiate a type 2 response and subsequent allergic inflammation,” said Pasare, one of the senior authors of the study.

In mice, inhibiting caspase 8 reduced the IL-33 response to allergens and limited bronchial inflammation in the lungs. Analysis revealed a similar process in humans/ 
“In the human allergic disease eosinophilic esophagitis (EoE), we found that ripoptosome activation markers and mature IL-33 levels dynamically correlated with the degree of esophageal eosinophilia and disease activity,” the study states.

The next steps include studying the RipIL-33 pathway in human allergic reaction and determining whether existing or new drugs could disrupt it.

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions UncategorizedTags :

Diabetes Drug Could Halve Glaucoma Risk

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GLP-1R agonists, a popular class of diabetes drugs, may also have a protective effect against glaucoma in diabetic patients, according to a new study published in the British Journal of Ophthalmology.

The researchers examined retrospective data of 1961 diabetic patients who were new users of this class of drugs and matched them to 4371 unexposed control subjects. After 150 days on average, 10 patients in the medicated group were newly diagnosed with glaucoma (0.5%) compared to 58 patients (1.3%) in the control group. These results indicate that GLP-1 receptor agonists could halve a diabetic patient’s risk of developing glaucoma.

The findings are supported by a Penn Medicine study from 2020, which found that GLP-1R agonists reduced neuroinflammation and prevented retinal ganglion cell death in mice. This class of drugs has also shown similarly protective effects against Alzheimer’s and Parkinson’s diseases in animal models, and clinical trials are underway to test the medications against neurodegenerative diseases in humans.

Glaucoma is the second leading cause of blindness worldwide, and people with diabetes are twice as likely to develop the condition.

“It was very encouraging to see that a popular diabetes medication could significantly reduce the risk of developing glaucoma, and our study suggests that these medications warrant further study in this patient population,” said Qi N. Cui, MD, PhD, with Brian VanderBeek, MD, MPH, both assistant professors of Ophthalmology at Penn.

Source: EurekAlert!

Categories : VaccinesTags :

Are Combination COVID Vaccines the Wave of the Future?

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An article in MedPage Today examines the potential for combination COVID vaccines.

Novavax and Moderna have recently announced the development of combination vaccines that would protect not only against COVID, but also against influenza. In the case of Moderna, they are testing a combination vaccine that also includes protection against respiratory syncytial virus (RSV) — a viral illness for which no vaccine is currently available, which would be a major advancement Because COVID vaccines can be administered simultaneously with other vaccines, albeit in separate injections, the next step would be to co-formulate them in the same injection with other vaccinations.

Combination vaccines are extremely valuable for several reasons, chief among them is convenience. If, during one visit to a provider, a person can get multiple vaccinations, it ensures uptake of all those vaccines without the need to schedule multiple visits or use multiple injections. A single needle puncture is better than multiple punctures, even for those who are not needle phobic. As more vaccines are developed, combination vaccines become critical in getting doses into arms with the minimum number of injections.

Combination vaccines have been around for a long time, and are the mainstay of routine vaccination. Today, children receive several combination vaccinations including the well-known MMR (measles, mumps, rubella) and DTap (diphtheria, tetanus, acellular pertussis). These types of vaccines have a long history with DTP, the first combination vaccine used in humans, dating to the 1940s. Pentacel immunises against five different pathogens at once. Such convenience, especially with hard-to-reach populations, is invaluable. Adults also receive combination vaccinations, most prominently the Tdap (tetanus, diphtheria, acellular pertussis) boosters. Many physicians wish there were more combination vaccination products available because they have the potential to significantly increase vaccination rates.

It is of course necessary to determine that combination vaccines are safe and effective. Because they contain more antigen, reactions at injection sites might be more pronounced, fever might be slightly higher, and tolerability lower. To avoid the risk of febrile seizures, infants do not get the MMRV (measles, mumps, rubella, varicella) vaccine, instead getting varicella separately.
A combination vaccine’s components should not interfere with each other or blunt the immune response. This immune interference was a concern with vaccines combining Hib with DTap. For instance, vaccines with different storage conditions or delivery mechanisms (eg, subcutaneous vs intra-muscular; lipid nanoparticle encased) may not be the best candidates to combine. It is also important to combine vaccines that have compatible age or time-based schedules for administration.

As scientists explore a combination flu and COVID vaccine, they will be looking closely at all of these safety and efficacy considerations.

It’s important to emphasize, considering widespread disinformation from the anti-vaccine movement, that there is no “antigen overload” risk with combination vaccines. The human immune system is bombarded with antigens every day. We even become bacteremic, when we brush our teeth, or eat. The antigens contained in a combination vaccine are miniscule by comparison. In fact, the first ever vaccine, for smallpox, was packed with particles and impurities but was still incredibly efficacious and led to control and eventual elimination of one of humanity’s deadliest scourges.

It is likely to see individual attacks on COVID combination vaccines long before they are even available. We’ve previously seen such attacks on the MMR vaccine — these attacks became so pervasive that manufacturers started to produce the single vaccines again to placate people who were the victims of a concerted disinformation campaign. But we can learn from these past challenges. It will be important to fight disinformation about the COVID-19 combination vaccines early on, and encourage their uptake when they become available.

But one thing is certain: we should aim to make COVID vaccination convenient, normal, and easy. Proactively working on next generation vaccines that do this by combining with other vaccinations, altering the mode of delivery (eg, oral or nasal vaccines), or simplifying storage requirements are important tasks.

Source: MedPage Today

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 : Immune SystemTags :

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