Day: September 29, 2022

Categories : Diseases, Syndromes and Conditions Environmental EffectsTags : Leave a comment

Lassa Virus Endemic Area may Grow in Coming Decades

On By ModernMedia
Pictured are projections of the ecological niche suitability for Lassa virus based on climate models and other data. Credit: Scripps Research and University of Brussels

Analysing decades of environmental data associated with Lassa virus outbreaks, researchers projected that areas hospitable to Lassa virus spread may extend from West Africa into Central and East Africa in the next several decades. With this expansion and expected African population growth, the human population living in the areas where the virus should theoretically be able to circulate may rise by more than 600 million.

“Our analysis shows how climate, land use, and population changes in the next 50 years could dramatically increase the risk of Lassa fever in Africa,” says first author Raphaëlle Klitting, PhD, a postdoctoral researcher at Scripps Research during the study, which is published in Nature Communications.

Lassa virus is a zoonotic pathogen found in the Natal multimammate rat (Mastomys natalensis), most likely transmitted to humans via its droppings. While an estimated 80% of infections are mild or asymptomatic, the remaining cases are more severe, with signs and symptoms that can include haemorrhaging from the mouth and gut, hypotension, and potentially permanent hearing loss. Mortality rate in hospitalised patients can be up to 80%.

An estimated several hundred thousand infections occur each year, chiefly in Nigeria and several other West African countries. So far there is no approved vaccine or highly effective drug treatment.

Although the primary animal reservoir for Lassa virus is known, the virus spreads in only a subset of the areas where the animal is found. Thus, it is possible that environmental factors also help determine whether and where significant viral transmission can occur. In the study, the researchers developed an ‘ecological niche’ model of Lassa virus transmission, using environmental data at sites of known spread.

Combining the model with projections of climate and land-use changes in Africa in the next several decades, as well as the known range of the Natal multimammate rat, the researchers estimated the areas of Africa that could support Lassa virus transmission currently, and in the years 2030, 2050, and 2070. The projected current areas corresponded well to known endemic areas in West Africa, but the estimates for future decades suggested a vast expansion within and beyond West Africa.

“We found that several regions will likely become ecologically suitable for virus spread in Central Africa, including in Cameroon and the Democratic Republic of the Congo, and even in East Africa, in Uganda,” Klitting said.

Currently Africa’s population is undergoing rapid growth; the researchers therefore considered projections of this population growth for the areas of current and potential future Lassa virus circulation. They found that the number of people potentially exposed to the virus could increase from about 92 million today to 453 million by 2050, and 700 million by 2070 – an increase of over 600%.

More hopefully, the researchers examined the dynamics of the spread of Lassa virus using data on sequenced viral genomes sampled at various locations in West Africa and found that virus dispersal appeared to be slow. They concluded that, unless transmission dynamics change drastically in the new location where the virus circulates, the virus’s spread into new ecologically suitable areas in the coming decades may also be slow.

The authors say that the findings should inform African public health policies, for example, by encouraging officials to add Lassa virus to lists of viruses under epidemiologic surveillance in parts of Central and East Africa.

“With the ongoing climate change and increasing impact of human activities on the environment, further comprehensive studies of the ecology and spread of zoonotic and vector-borne diseases are needed to anticipate possible future changes in their distribution as well as their impact on public health,” said senior author Simon Dellicour, PhD, of the University of Brussels.

Source: Scripps Research Institute

Categories : Obstetrics & GynaecologyTags : Leave a comment

Trial Finds Linzagolix Safe and Effective for Uterine Fibroids

On By ModernMedia
Photo by Sora Shimazaki on Pexels

A new, safer drug has been developed that could revolutionise the way clinicians treat some of the most common gynaecologic diseases including fibroids and endometriosis. A clinical trial published in the Lancet found that linzagolix, an oral drug that hinders oestrogen production, is an effective and customisable treatment for fibroids. Not only does linzagolix ease symptoms but also shrinks the fibroids themselves.

Professor Hugh S. Taylor, MD, co-author of the paper, said: “No treatments to date for fibroid growth are something I would ever want my patients to take for a prolonged period of time, as they did not treat the underlying cause of the problem. This is an extremely well tolerated class of drugs that can control fibroid growth. We’ve never had anything like that before.”

The suffering and inconvenience caused by uterine fibroids can have a serious impact on quality of life. “This can be an impediment to getting a good night’s sleep and being socially active, and it can even affect job performance,” said Prof Taylor.

As fibroids grow larger, they may begin putting pressure on other organs, resulting in a range of unpleasant symptoms including diarrhoea or constipation and frequent urination. Fibroids can also lead to difficulty in getting pregnant and increased risk of miscarriage. They are more common and aggressive in black patients.

Most drugs commonly used for uterine fibroids, including birth control pills, do not treat the fibroids themselves and just lighten or stop periods. And more aggressive drugs, although they treat the root of the problem are “overkill” Prof Taylor said. For example, leuprolide is an injectable drug that puts patients into a menopausal state by initially overstimulating hormonal receptors, which eventually shuts them down and completely blocks oestrogen production. Although the treatment addresses the fibroids, it also can initially exacerbate symptoms and cause harsh side effects. In more extreme cases, patients may opt for hysterectomy.

Promising clinical trial results

Linzagolix is an oral medication that works similarly to leuprolide by hindering hormone production. However, unlike its predecessor, it works by directly blocking the receptors instead of overstimulating them. The drug is also titratable, allowing reduction of oestrogen production without initiating menopause.

The new drug may however cause menopause symptoms such as hot flashes, with hormonal add-back therapy an option for mitigating these symptoms. For some patients, however, including patients with obesity, hypertension, or diabetes, this therapy has risks and may not be a suitable option. These conditions also tend to be more prevalent in Black patients. In this group, a lower dose of linzagolix without add-back therapy might be preferable.

To test the effectiveness of the drug, Prof Taylor’s team ran two large prospective, randomised, double-blind, placebo-controlled clinical trials known as PRIMROSE 1 and PRIMROSE 2. The studies enrolled patients suffering from substantial bleeding who were randomised to placebo or one of several different doses of the drug: 100mg alone, 100 mg with add-back therapy, 200mg alone, or 200mg with add-back therapy. Patients were followed for one year. The researchers considered the therapy successful if the patient’s bleeding was reduced by half and also stayed in what is considered the normal range.

Patients in all four treatment groups experienced a significant reduction in menstrual bleeding. The 200 mg with add-back therapy group worked with “amazing efficacy,” said Prof Taylor: the clinical trials showed a 75.5% response rate in PRIMROSE 1 and a 93.9% rate in PRIMROSE 2. Even the lower dose of the drug still showed promising results. There were greater than 60% response rates in both trials for the 100mg group with add-back therapy, and the 100mg group without add-back showed better than 50% response rates.

“What is interesting and unique about our trials, that has not been done with other drugs in this class, is that we used a low dose with or without hormones,” said Prof Taylor. “This is a great option for patients who experience severe menopause symptoms from the high dose or have a medical problem where they can’t tolerate hormonal add-back therapy.”

Changing the treatment of gynaecologic disease

Linzagolix is one of several in this new class of drugs in development for the treatment for common gynaecologic diseases. Prof Taylor was also involved in the 2017 clinical trial for elagolix, a medication designed to suppress endometriosis that has recently become available for patients.

Linzagolix has so far been approved in Europe. Taylor says drugs in this class will radically change how clinicians treat fibroids, and he hopes linzagolix will lead to a reduction in future hysterectomies once it becomes available.

“A good medical therapy is finally here for fibroids, and I predict that what was a very common operation will dramatically decrease within the next few years,” he says. “Reducing the need for hysterectomy is very important for patients who don’t want to undergo a major surgery, especially for younger people who may still want to preserve the potential of having children in the future.”

Source: Yale University

Categories : Mental Health Metabolic DisordersTags : Leave a comment

Genes and Environment Bridge Depression and Endocrine-metabolic Disorders

On By ModernMedia
Photo by Engin Akyurt on Pexels

While endocrine-metabolic disorders and depression are known to co-occur, genetic and environmental factors are known to underlie both. In a study examining the link, published in the American Journal of Psychiatry, analysis revealed the balance of genetic and environmental influences underlying the co-occurrence of depression for a range of endocrine-metabolic disorders.

It is known that there is elevated co-occurrence between endocrine-metabolic disorders and depression, but the relationship between them is still not well understood.

Familial aggregation

The authors identified 2.2 million individuals born in Sweden between 1973 and 1996, as well as their full and half siblings, and followed them up to age 40. A number of medical conditions were studied; depression and various endocrine-metabolic disorders, including three autoimmune diseases (autoimmune hypothyroidism, Graves’ disease, and type 1 diabetes) and three non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome).

Individuals with endocrine-metabolic disorders had 1.4 to 3.5 times the risk of depression compared to people without these diagnoses. Full and half siblings of these individuals also showed some elevated risk for depression, suggesting that genetic and/or environmental risk factors shared between family members play a role in the co-occurrence of these mental and physical disorders.

Genetic and environmental contributions

By comparing pairs of full sibling (who share about half of their genes) to pairs of half siblings (who share about a quarter of their genes), it was possible to calculate the relative contribution of genetic and environmental factors to the co-occurrence of depression and various endocrine-metabolic disorders. 

The results were a mix of these possibilities; the overlap between depression and non-autoimmune conditions was mainly explained by shared genetic influences, while environmental factors were predominantly involved in the association between depression and autoimmune disorders, particularly type 1 diabetes.

This indicates that the link between depression and different endocrine-metabolic disorders may be driven by different mechanisms. For example, shared biological mechanisms, such as immuno-inflammatory and metabolic dysregulations, may underlie the co-occurrence of depression and type 2 diabetes, obesity, and polycystic ovarian syndrome. In contrast, the absence of shared genetics in the association between type 1 diabetes and depression may reflect the existence of environmental factors influencing the risk of both conditions and/or a direct link between these conditions through mediating factors – eg, biological and psychosocial mechanisms connected to type 1 diabetes, including inflammation, cerebral damage, as well as stress of this lifelong condition that is often diagnosed early in life and that requires a complex management regime for both patients and their families.

“Our results underscore that clinicians should be aware of increased risks of depression in individuals with endocrine-metabolic disorders, and vice versa, and be vigilant for shared symptoms. This study also provides a useful foundation for future research aimed at identifying and targeting the biological mechanisms and modifiable risk factors underlying the co-presentation of endocrine-metabolic disorders and depression”, said Marica Leone, first author for the study.

Source: Karolinska Institutet

Categories : Diet and NutritionTags : Leave a comment

Guar Gum Limits Inflammation and Delays MS-like Symptoms

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Guar gum is a common additive in foods such as gummy sweets, but a healthier alternative should be found for its inflammation-limiting benefits. Photo by Amit Lahav on Unsplash

Guar gum is derived from guar beans, and is a common food additive and dietary fibre. Surprisingly, limited inflammation and delayed the onset of multiple sclerosis (MS) symptoms in mice, according to new research published in Cell Reports.

“The rapid increase of autoimmune and inflammatory disorders in industrialised countries in the last few decades indicates dietary choices are one environmental factor contributing to incidence,” said Dr Lisa Osborne, senior study researcher on the study.

“Dietary fibres are potent modulators of immune responses and can control inflammation in multiple diseases, but they’re a very biochemically diverse family. Our study gives us a clearer window into the potential of several sources of fibre in maintaining immune health.”

Dr Osborne and colleagues exposed groups of mice to a variety of diets: a control diet with 5% cellulose fibre, a no-fibre diet, or diets enriched (30%) with fibre in either resistant starch, inulin, pectin, or guar gum. Guar gum was the only fibre type that significantly limited the MS-like symptoms. 

Guar gum (guaran) is extracted from guar beans, and is often used as an additive to thicken and stabilise food and animal feed, and in industrial applications.

“Guar beans aren’t that common in western diets, and the gum isn’t used at these high levels as an additive in the west,” says Naomi Fettig, first author on the study and a PhD student with the Department of Microbiology and Immunology at UBC.

“Experts have consistently been saying fibre is good for you – and a variety of fibre sources is important to immune health – but there hasn’t been very much critical work into identifying how the body responds to different fibre types. It’s fascinating that this particular source has such an impact.”

In the US and Canada, the average daily intake of fibre is 15g – current recommendations are 30g, with no regard to specific fibre type. “Incorporating guar beans might be challenging to achieve at the doses we gave to mice,” says Dr Osborne. “But a guar gum derivative, partially hydrolysed guar gum, is commercially available as a prebiotic.”

After the gum is broken down by the gut microbiota of mice, the resulting molecules appeared to reduce the activity and proliferation of a type of CD4+ T cells, Th1 cells, which have a key role in triggering the autoimmune response, which can lead to MS-like symptoms in mice. The effects of fibre on Th1 cells remained largely unknown prior to this study, and these findings suggest that the biochemical differences in fibre structures can influence diverse immune pathways.  

Dr Osborne and her lab now want to explore the potential benefits in humans – including developing a more detailed understanding of the molecular picture, which might help design therapeutics that offer the benefits of such high guar gum diets in a more practical form.

Source: University of British Columbia

Categories : Exercise GenderTags : Leave a comment

Male and Female Running Speeds are Closer in Shorter Sprints

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Man and woman about to sprint
Source: Andrea Piacquadio on Pexels

Conventional wisdom holds that men run 10–12% faster than women regardless of the distance raced. But new research published in the Journal of Applied Physiology suggests that the performance gap narrows at shorter sprint distances.

Speed over short distances is determined by different factors – specifically, the magnitude of the ground forces athletes can apply in relation to their body mass. Muscular force to body mass ratios are greater in smaller individuals.

PhD candidate Emily McClelland, working with Peter Weyand, the Director of SMU’s Locomotor Performance Lab, quantified sex performance differences using data from sanctioned international athletic competitions such as the Olympics and World Championships. An accomplished athlete, McClelland has always had a natural interest in the scientific basis of human performance. The researchers hypothesised that these data would reveal smaller male-female performance differences at shorter distances.

The understanding of comparative strength, speed and endurance capabilities of male and female athletes has been a contentious issue for modern sport.  Yet, prior to the new SMU study, quantitative understanding of sex performance differences for short sprint events had received little attention. McClelland’s background, male-female differences in force/mass capabilities, and existing data trends led her to hypothesise that sex differences in sprint running performance might be relatively small and increase with distance.

Her analysis of race data from sanctioned international competitions between 2003 and 2018 supported her initial hypothesis. These data revealed that the difference between male and female performance time increased with event distance from 8.6% to 11% from shortest to longest sprint events (60 to 400m). Additionally, within-race analysis of each 10-meter segment of the 100m event revealed a more pronounced pattern across distance: sex differences rose from 5.6% for the first segment to 14.2% in the last segment.

Why then are women potentially less disadvantaged versus men at shorter sprint distances?

Unlike other running species like horses and dogs, there is significant variation in body size between human males and females. Holding all other factors equal, body size differences result in muscular force to body mass ratios that are greater in relatively smaller individuals.  Since sprinting velocities are directly dependent on the mass-specific forces runners can apply during the foot-to-ground contact phase of the stride, greater force/mass ratios of smaller individuals provide a theoretical relative advantage. A female runner’s shorter legs may confer the advantage of more steps and pushing cycles per unit time during the acceleration phase of a race. These factors offset male advantages (longer legs and greater muscularity) that become more influential over longer distances.

Source: Southern Methodist University