Month: October 2024

Categories : Neurodegenerative DiseasesTags :

Epstein-Barr Virus: How does a Common Infection Trick the Immune System into Attacking the Brain in People with MS?

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An electron micrograph showing three Epstein-Barr virus (EBV) particles colourised red-orange. Credit: NIAID

Olivia Thomas, Karolinska Institutet; Graham Taylor, University of Birmingham, and Jill Brooks, University of Birmingham

Almost 3 million people worldwide have multiple sclerosis (MS) – an autoimmune disease caused by the immune system mistakenly attacking the brain and central nervous system.

While treatments for MS have improved over the years, there’s still no cure. This is largely because researchers still don’t fully understand what goes wrong in the immune system to cause MS. But our latest research has revealed new insights into the way certain immune cells behave in people with MS. This discovery brings us closer to understanding why some people get MS – and may also be a crucial step in developing better treatments and even cures.

Although the causes of MS aren’t fully understood, we know that genetics, lifestyle and environment factors can all influence MS risk. But the biggest risk factor for developing MS appears to be a common virus called Epstein-Barr virus (EBV).

EBV typically infects people during childhood without causing any symptoms – so most early infections go unnoticed. But if the infection occurs during adolescence, it may cause glandular fever (infectious mononucleosis) which, although debilitating in the short-term, usually has no long-term effects.

Most viral infections are rapidly cleared by the body’s immune system, but EBV is cleverer than most viruses. Although the immune system controls the infection, it is unable to completely eradicate the virus as it hides inside a type of immune cell called a B cell (which normally produce antibodies that bind to and destroy invading viruses or bacteria). Once you’re infected with EBV you carry it for life – although for most people this causes no problems.

By adulthood about 95% of people are infected with EBV, but in people with MS nearly 100% are infected. Large epidemiological studies have shown that EBV infection increases the risk of developing MS over 30-fold. For people who have had glandular fever the risk is even higher. Research has also shown that in people with MS, EBV infection occurs before the very earliest stages of disease.

Many researchers now believe being infected with EBV is more than a risk factor in MS – it’s essential.

But how does EBV cause MS – and why does a common virus only cause MS in a few people? Several theories are currently being investigated.

One theory is that in some people the immune cells activated by EBV mistakenly attack parts of the brain and central nervous system. This process, called molecular mimicry, also occurs in other autoimmune diseases, such as Guillain-Barré syndrome. This could explain why drugs which prevent immune cells from entering the brain are shown to dramatically improve MS symptoms.

Research into EBV molecular mimicry in MS has mainly focused on the viral protein EBNA1. Without EBNA1 EBV cannot live in B cells, and MS patients have higher levels of antibodies towards EBNA1.

But EBV makes over 80 different proteins during its life cycle. In our latest work we investigated immune responses to these other viral proteins in people with MS.

Altered immunity

We compared the immune responses of 31 people with MS, 33 healthy people and 11 people who had recently recovered from glandular fever. We wanted to see if each group reacted to EBV infections differently.

We found that antibodies targeting EBNA1 and another viral protein called VCA were higher in people with MS compared to the other groups. People with MS were also more likely to have antibodies targeting several other viral proteins. This suggests EBV antibodies are more altered in MS than previously thought – but it isn’t certain whether these antibodies are fighting infection or if they have a role in MS disease.

Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID

Antibodies aren’t the full story. Previous research has suggested another type of immune cell, called a T cell, may also play an important role as they’re found in high numbers in MS brain lesions. As such, we wanted to understand whether T cells which fight EBV were different in people with MS.

By analysing blood samples we found that, although EBV T cell numbers were similar in MS and healthy people, these cells behaved differently in people with MS. T cells from people with MS produced slightly higher amounts of an inflammatory substance called interleukin-2. The body normally produces this substance in response to injury or infection, but too much interleukin-2 can cause chronic disease.

We also looked at molecular mimicry, wondering whether EBV T-cells mistakenly target brain proteins rather than fighting the virus.

Surprisingly, we found that in both people with MS and healthy people, their EBV T cells reacted to multiple proteins found in the brain. Notably, most people had EBV T cells that targeted a protein called myelin oligodendrocyte glycoprotein, or Mog, which surrounds the nerves.

Looking at one person with MS in more detail, we found individual T cells that directly recognised both EBNA1 and Mog. This means that, rather than just fighting infection, some EBV T cells could also target nerve cells in the brain.

This widespread misdirection between EBV T cells and the brain goes some way to suggest how infection with this common virus can lead to MS. But its presence in healthy people is slightly confusing. One possible explanation could be that EBV T cells are better able to cross the blood-brain barrier (a tight-knit lining of cells that protect the brain) in people with MS. This idea is something we’re keen to explore in future research.

While there’s still much we don’t know about these misdirected EBV T cells in the brain, our latest findings provide fresh evidence for researchers and hopefully will lead to the development of new, targeted treatments for MS.

Olivia Thomas, Assistant Professor, Department of Clinical Neuroscience, Karolinska Institutet; Graham Taylor, Associate Professor in Viral and Tumour Immunology, University of Birmingham, and Jill Brooks, Research Fellow, Institute of Cancer and Genomic Sciences, University of Birmingham

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Expert Opinion Medical IndustryTags :

Opinion Piece: Prioritising Healthcare Access for All Employees Makes Sound Business Sense

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By Reo Botes, Managing Executive at Essential Employee Benefits

22 October 2024

South African businesses operate in an environment in which many employees, particularly those in lower income segments, struggle to afford basic healthcare services. Healthcare benefits like medical aid are simply not affordable for the majority of the workforce, even if they are subsidised, which exacerbates the existing dichotomy. Addressing this issue should be a strategic imperative as well as a matter of ethical compliance and social responsibility.

While executives play a crucial role in setting strategy, many layers of employees are operationally required to fulfil said strategy. Keeping all layers of employees healthy by promoting access to quality healthcare, boosts both sustainability and competitiveness. We dare not wait for the National Health Insurance (NHI) to come into effect to solve this challenge; we have a responsibility to make private healthcare more accessible, and one way that companies can do this is by incorporating affordable health insurance products into their employee benefits basket.

A legacy of inequality

The legacy of apartheid has left an indelible mark on South Africa’s socio-economic landscape. This is reflected in the persistent inequality that permeates many facets of life, including significant disparities between rural and urban areas, as well as access to healthcare. Decades later, private healthcare remains predominantly accessible to the wealthy, while the majority of South Africans are left to rely on an overburdened public health system.

Medical aid has been the traditional path to affordably accessing private healthcare, but the premiums remain out of reach for the lower income earners, even if companies subsidise the cost. The lower-cost medical aid options have struggled to get off the ground, and the effective rollout of the NHI will take many years to come to fruition. Since most people cannot afford medical aid and cannot rely on universal access to public healthcare, there needs to be another option that will enable them to access healthcare affordably. Making health insurance benefits available with options that suit different income segments will not only help to address this issue, but it will also benefit businesses as well.

A healthy workforce just makes business sense

From a legal standpoint, South African companies are bound by the Labour Relations Act and the Occupational Health and Safety Act (OHSA), both of which mandate the provision of a safe and healthy working environment. While these regulations primarily focus on workplace safety, the concept of a healthy workplace extends beyond physical safety to encompass the overall well-being of employees. Ethical governance demands that companies do more than the bare minimum required by law; it requires a proactive approach to employee welfare.

Beyond ethical and compliance concerns, having a healthy workforce is simply good for business. Healthy employees are more likely to be engaged, motivated, and productive, which in turn contributes to the overall success of the business. Moreover, a company that invests in the health of its workforce is likely to see a return on investment (ROI) through reduced turnover, lower absenteeism, and higher employee satisfaction.

By offering health insurance benefits that are tailored to the needs of employees across different income brackets, companies can demonstrate a genuine commitment to their employees’ well-being. This not only fosters trust and loyalty among the workforce but also enhances the company’s reputation as an employer of choice.

Health insurance for all, not just for executives

Photo by Emmanuel Ikwuegbe on Unsplash

Budget constraints are often cited as a major barrier when it comes to subsidising healthcare costs, but health insurance products aimed at lower income segments are a fraction of the cost of the more comprehensive medical aid products offered to executive tiers, and the cost-benefit ratio of providing greater access to healthcare services can be profound. When employees have access to health insurance, they can seek medical attention promptly, reducing the likelihood of prolonged illness and absenteeism, which in turn are detrimental to business.

Even if businesses, particularly small and medium-sized enterprises, cannot afford to subsidise health insurance products, they can still offer access to them as part of employee benefits. Companies can negotiate group rates for health insurance on behalf of their employees, making it more affordable than taking out a policy on their own and thus reducing the cost without the need to subsidise. Aligning health insurance benefits with employee needs and income levels ensures that the cover is both relevant and accessible and supports long-term business goals by promoting a healthier, more resilient employee base.

Change comes from the top

Human Resources (HR) and executive leadership play a pivotal role in the implementation of inclusive health insurance benefits. While executives are responsible for setting the overall strategy, it is the HR teams that must operationalise these strategies and ensure they are effectively communicated and implemented across the organisation. This includes understanding the diverse needs of the workforce, negotiating with insurance providers, and designing benefits packages that are both affordable and impactful.

By integrating health insurance into the broader employee value proposition, companies can enhance their appeal to top talent, including high performers in lower income brackets. A comprehensive benefits package that includes health insurance is a key differentiator in a competitive job market, helping companies attract and retain skilled workers who are critical to executing business strategies.

Inclusivity drives resilience

Ultimately, the provision of health insurance benefits for all employees is about building a strong foundation for business success. A healthy, happy, and productive workforce is essential for any company looking to achieve long-term sustainability and growth. By taking care of their employees’ health, companies are not only doing the right thing from an ethical standpoint but are also making a smart business decision that will pay dividends in terms of productivity, employee retention, and overall organisational resilience.

South African companies must recognise the importance of inclusive health insurance benefits as a critical component of their business strategy. Addressing the historical inequalities in healthcare access, meeting legal and ethical obligations, and investing in the health and well-being of all employees are essential steps towards building a more equitable and prosperous future for both businesses and their workforce. Businesses can play a pivotal role as the country continues to grapple with the challenges of inequality and healthcare access.

Categories : AgeingTags :

Ground-breaking Identification of Key Enzyme in Aging Cells

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Photo by National Cancer Institute on Unsplash

A team at Kumamoto University has made a ground-breaking discovery in the field of aging and inflammation. The research focuses on “cellular senescence,” a process where cells stop dividing and enter a state associated with chronic inflammation and aging. This cellular state, known as the senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and disease, such as dementia, diabetes, and atherosclerosis.

The researchers found that ATP-citrate lyase (ACLY), an enzyme involved in converting citrate to acetyl-CoA, plays a critical role in activating SASP. This discovery was made using advanced sequencing and bioinformatics analyses on human fibroblasts, a type of cell found throughout the body. They demonstrated that blocking ACLY activity, either genetically or with inhibitors, significantly reduced the expression of inflammation-related genes in aging cells. This suggests that ACLY is a crucial factor in maintaining the pro-inflammatory environment in aged tissues.

Furthermore, the study revealed that ACLY-derived acetyl-CoA modifies histones, proteins that DNA wraps around, allowing the chromatin reader BRD4 to activate inflammatory genes. By targeting the ACLY-BRD4 pathway, the researchers were able to suppress inflammation responses in aged mice, highlighting the potential of ACLY inhibitors in controlling chronic inflammation while maintaining healthy aging.

This discovery opens new avenues for developing treatments that specifically target the harmful aspects of aging cells without removing them, offering a promising strategy for managing aging and age-related diseases. The research provides a stepping stone toward therapies that can control cellular aging, promoting longer, healthier lives.

Categories : Metabolic Disorders Respiratory DiseasesTags :

TB Alters Liver Metabolism and could Promote Diabetes, Study Shows

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Tuberculosis bacteria. Credit: CDC

Scientists from the University of Leicester have discovered that tuberculosis disrupts glucose metabolism in the body. The findings, which have now been published in PLoSPathogens complement the understanding that diabetes worsens the symptoms of tuberculosis. Importantly, they now say, undiagnosed tuberculosis could be pushing vulnerable patients towards metabolic disease such as diabetes.

Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide, killing over 4,000 people every day. Prevention through the development of improved vaccines remains a priority for the World Health Organisation. Currently only one vaccine exists for TB and this is predominantly given to infants and young children to help protect them from severe forms of infection. 

Scientists at the University are researching tuberculosis in the hope of creating improved vaccines and are specifically looking at ways in which undiagnosed and subclinical infection can impact health. This new discovery, they say, could pave the way to define the molecular pathways by which the immune response changes liver metabolism, thereby allowing for the creation of targeted interventions. 

Professor Andrea Cooper from the University’s Leicester Tuberculosis Research Group (LTBRG), is among the authors on the paper.

She said: “Our paper changes the focus from diabetes making TB worse to the possibility that late diagnosis of TB can contribute to disruption of glucose metabolism, insulin resistance and therefore can promote progress towards diabetes in those that are susceptible. 

“As diabetes compromises drug treatment, our paper also supports the idea that metabolic screening should be involved in any drug or vaccine trials.”

The study first used laboratory models of pulmonary TB to examine the changes happening within the liver during the early stages of infection. It found that an immune response was triggered within the liver cells and glucose metabolism was altered. 

First author Dr Mrinal Das then reanalysed published metabolic data from humans, where he found that liver glucose metabolism was also disrupted when people progressed to TB from latent infection.

Professor Cooper added: “Our future aim is to define the molecular pathways by which the immune response is changing liver metabolism, allowing us to potentially create targeted interventions.

 “We will also be investigating how latent TB (which is infection with the bacterial agent of TB without significant symptoms) might be impacting metabolic health in humans.” 

Source: University of Leicester

Categories : Gender Obstetrics & GynaecologyTags :

Boy or Girl? This Genetic Mutation Increases Odds of Having a Daughter

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Source: Pixabay CC0

Each year, roughly the same numbers of boys and girls are born. But in individual families, some couples have four or more daughters and no sons, and some have all male children and no female children, points out University of Michigan evolutionary geneticist Jianzhi Zhang. This has led some scientists to question whether this skewed sex ratio is a result of the genes of the parents.

Now, Zhang and U-M doctoral student Siliang Song have detected a human genetic variant that influences the sex ratio of children. Additionally, they found that many hidden genetic variants of sex ratio may exist in human populations. Their results are published in the Proceedings of the Royal Society B: Biological Sciences.

“Scientists have been pondering and researching a genetic basis for sex ratio for decades, yet no unambiguous evidence for a genetic variation that alters the human sex ratio from an approximately 50:50 ratio has been found,” said Zhang, professor of ecology and evolutionary biology.

Zhang says this has led some scientists to think that the human sex ratio is not subject to mutation.

“But this scenario seems unlikely, because almost all human characteristics are subject to mutation and genetic variation,” he said. “Instead, we think genetic variation of sex ratio is too difficult to detect because sex ratio is not measured precisely.”

That is, each person typically has a very small number of children, which can lead to large errors in the estimation of the true sex ratio of a person’s children. For example, if a person only has one child, the estimated sex ratio would be either zero (if it’s a girl) or 1 (if it’s a boy) even if the true sex ratio is 0.5.

To detect genetic influence on sex ratio, the researchers realised they needed a much larger sample than in all previous studies. They turned to the UK Biobank, a biomedical database that contains the genetic and phenotypic information of about 500 000 British participants.

Analysing this data, the researchers identified a single nucleotide change named rs144724107 that is associated with a 10% increase in the probability of giving birth to a girl as opposed to a boy. But this nucleotide change is rare among the UK Biobank participants: About 0.5% of the participants carry this change. The nucleotide change is located near a gene named ADAMTS14, which is a member of the ADAMTS gene family known to be involved in spermatogenesis and fertilisation. The researchers also note that their discovery has not yet been confirmed in other samples.

The researchers also identified two genes, called RLF and KIF20B, that may also influence the sex ratio.

The study’s findings align with a theory in evolutionary biology called Fisher’s principle, which states that natural selection favours the genetic variant that increases the births of the rare sex. That is, if fewer males than females are born in a population, natural selection favours genetic variants that increase the number of males born, and vice versa. As a result, this selection yields a more or less even sex ratio in the population

“For Fisher’s principle to work, there must be mutations that influence the sex ratio,” Zhang said. “The fact that no genetic variation on human sex ratio had been identified has led some scientists to question the applicability of Fisher’s principle in humans.

“Our study shows that in fact, human data are consistent with Fisher’s principle and the reason no genetic variants of sex ratio had been discovered was the imprecision of the measure of a person’s offspring sex ratio.”

Next, the researchers hope to verify their findings in other samples – not an easy task, Zhang says, because of the large sample size requirement and the rareness of the identified genetic variant.

Source: University of Michigan

Categories : Environmental EffectsTags :

The More Chemicals, the More their Neurotoxic Effects Add Up

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Photo by Louis Reed on Unsplash

Chemicals are omnipresent today: they enter our bodies through food, air or the skin. But how do these complex mixtures of chemicals affect our health? In a study published in the journal Science, a research team from the Helmholtz Centre for Environmental Research (UFZ) has shown that chemicals that occur in complex mixtures and in concentration ratios as found in humans act together. Even if the concentrations of the individual substances were each below the effect threshold, the chemicals in the mixture showed a cumulative neurotoxic effect.

For their investigations, they used blood samples from pregnant women from the LiNA mother-child study (lifestyle and environmental factors and their influence on the newborn allergy risk), which has been running at the UFZ since 2006. 

In our everyday lives, we are exposed to a wide variety of chemicals that are distributed and accumulate in our bodies. These are highly complex mixtures that can affect bodily functions and our health,” says Prof Beate Escher, Head of the UFZ Department of Cell Toxicology and Professor at the University of Tübingen. “It is known from environmental and water studies that the effects of chemicals add up when they occur in low concentrations in complex mixtures. Whether this is also the case in the human body has not yet been sufficiently investigated – this is precisely where our study comes in.” 

The extensive research work was based on over 600 blood samples from pregnant women from the Leipzig mother-child cohort LiNA, which has been coordinated by the UFZ since 2006. The researchers first analysed the individual mixtures of chemicals present in these samples.

“We wanted to find out which chemicals were contained in the blood plasma and in what concentrations. We used a two-step extraction process to isolate as diverse chemical mixtures as possible,” says Georg Braun, postdoctoral researcher in Beate Escher’s working group and first author of the study. “Using mass spectrometry analyses, we searched for 1000 different chemicals that we knew could occur in the environment, could potentially be ingested by humans and could be relevant for adverse human health effects. Of these, we were able to quantify around 300 chemicals in several plasma samples.” This provided the researchers with information on the composition and concentration ratios of the chemical mixtures present in the 600 individual plasma samples. 

The researchers used a prediction model to calculate the neurotoxic effects of the chemical mixtures. To test the predictions of the mixture effects experimentally, they used an established cellular bioassay based on human cells that indicates neurotoxic effects.

“We analysed individual chemicals as well as around 80 different, self-produced chemical mixtures in realistic concentration ratios. The extracts of the plasma samples were also tested,” says Georg Braun. The results were clear. “The laboratory experiments confirmed the predictions from the model: the effects of the chemicals add up in complex mixtures,” says environmental toxicologist Beate Escher. “Even if the individual concentrations of neurotoxic chemicals are so low that they are each below the effect threshold, there is still an effect on nerve-like cells in complex mixtures with many other chemicals.”

But what exactly do these results mean? “With our study, we were able to prove for the first time that what is known about the effects of chemical mixtures in the environment also applies to humans,” says Escher. “It is therefore imperative that we rethink risk assessment. Indicator substances alone are far from sufficient. In future, we must learn to think in terms of mixtures.” UFZ environmental immunologist and head of the LiNA study Dr Gunda Herberth adds: “It is becoming increasingly clear that many diseases such as allergies, immune system disorders, obesity or the development of the nervous system are linked to exposure to chemicals in the womb or in early childhood.” 

The test method presented in this study – the extraction of chemical mixtures from human samples and their characterisation using chemical analysis combined with cell-based biotest systems – opens up new possibilities for researching the effects of complex chemical mixtures on human health. In future research projects, the scientists want to refine their test method and investigate the effects of chemical mixtures on other health-relevant endpoints such as immunotoxicity. In addition, they would like to uncover possible links between chemical exposure and the development of developmental disorders in children. 

Source: Helmholtz Centre for Environmental Research – UFZ

Categories : Diet and Nutrition PaediatricsTags :

Raising Happy Eaters: Unlocking the Secrets of Childhood Appetite

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Photo by Vanessa Loring on Pexels

The foundation for healthy eating behaviour starts in infancy. Young children learn to regulate their appetite through a combination of biological, psychological, and sociological factors. In a new paper published in Social Science & Medicine, researchers at the University of Illinois Urbana-Champaign propose a model that explores these factors and their interactions, providing guidelines for better understanding childhood appetite self-regulation.

“When we talk about obesity, the common advice is often to just eat less and exercise more. That’s a simplistic recommendation, which almost makes it seem like an individual’s willpower solely determines their approach to food,” said lead author Sehyun Ju, a doctoral student in the Department of Human Development and Family Studies, part of the College of Agricultural, Consumer and Environmental Sciences at Illinois. 

Appetite self-regulation is related to general self-regulation, but it specifically concerns an individual’s ability to regulate food intake, which affects healthy development and obesity risk. Children are born with a capacity to regulate appetite based on hunger and satiety signals, but with increased exposure to environmental factors, their eating is increasingly guided by psychological reasoning and motivations. Therefore, it is important to take a developmental perspective to trace changes in eating behaviours over time, Ju stated.

Ju and her colleagues provide a comprehensive framework based on the biopsychosocial pathways model, which outlines three interacting categories: Biological factors, including sensory experience, physiological hunger and satiety signals, brain-gut interaction, and the influence of the gut microbiome; psychological factors, including emotional self-regulation, cognitive control, stress regulation, and reward processing; and social factors, such as parental behaviour and feeding practices, culture, geographic location, and food insecurity.

The researchers combine this framework with temperamental theory to explore how the pathways are modified by individual temperament.

Children react differently to stimuli based on their psychological and emotional make up, Ju explained. For example, openness to novelty and positive anticipation can affect whether a child is willing to try new foods. If a parent pressures their child to eat, it could be counter-productive for a child with heightened sensitivity to negative affect, causing the child to consume less.

The model also takes children’s developmental stages into account. Infants have basic appetite regulation based on physiological cues. They gradually become more susceptible to external influences and by age 3-5, children begin to exhibit greater self-control and emotional regulation.

“By analysing the pathways outlined in our model, we can better understand the combined influences of multiple factors on children’s appetite self-regulation and their motivations to approach food,” Ju said. “For example, the presence of palatable food may not generate similar responses in everyone. Children could approach food as a reward, for pleasure-seeking, or to regulate emotions. The underlying motivations can be diverse, and they are influenced by external factors as well as temperamental characteristics.”

Socio-environmental influences include parent-child interactions around food, as well as non-food-related caregiver practices that can impact the child’s emotional regulation. The household food environment, cultural value of food intake, and food availability are also important factors, the researchers stated.

“If we understand the differential susceptibility to various factors, we can identify and modify the environmental influences that are particularly obesogenic based on children’s temperamental characteristics. Then we will be able to provide more refined approaches to support children’s healthy eating behaviour,” Ju explained.

Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences

Categories : CancerTags :

Healthy Diet may Help Keep Low Grade Prostate Cancer from Progressing

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Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

In a peer-reviewed study believed to be the first of its kind published, a research team led by Johns Hopkins Medicine provides scientific evidence that a healthy diet may reduce the chance of low risk prostate cancer progressing to a more aggressive state in men undergoing active surveillance – a clinical option in which men with lower risk cancer are carefully monitored for progression in lieu of treatments that could have undesired side effects or complications.

The findings are reported in the journal JAMA Oncology.

“Many men diagnosed with low grade prostate cancer are interested in changes they can make to reduce the risk of their tumour becoming more aggressive, and the role of diet and nutrition is one of the most commonly asked questions,” says study co-senior author Bruce Trock, PhD, a professor of urology, epidemiology and oncology at the Johns Hopkins University School of Medicine, and director of the Brady Urological Institute’s epidemiology division. “These men are motivated to make changes that may improve their prognosis, which is why we began collecting data on their diets, lifestyles and exposures 20 years ago. Hopefully, these latest findings will enable us to develop some concrete steps they can take to reduce the risk of cancer progression.”

When a patient is found after a biopsy to have developed prostate cancer, the sampled cells are assigned to a grade group based on comparison normal prostate tissue. Grade groups range from 1 to 5, with grade group 1 indicating indolent cancer cells that don’t look very different than normal tissue and do not metastasise. At the other end of the scale, grade group 5 indicates cancer cells that are quite abnormal in appearance, and can grow and metastasise if untreated

During active surveillance, biopsies are performed at regular intervals to see if prostate cancer should be move it to a higher grade group. Called grade reclassification, this often leads to a recommendation for treatment. It also is a common way for researchers to evaluate the effectiveness of therapies and lifestyle modifications.

“While there have been previous research studies looking at diet and its relationship to prostate cancer, we believe that ours is the first to provide statistically significant evidence that a healthy diet is associated with a reduction in risk of prostate cancer progressing to a higher grade group, as shown by a reduction in the percentage of men on active surveillance experiencing grade reclassifications over time,” says study co-senior author Christian Pavlovich, MD, a professor in urologic oncology at the Johns Hopkins University School of Medicine and director of the Brady Urological Institute’s prostate cancer active surveillance program.

In the newly published study, the researchers prospectively evaluated the histories of 886 men (median age at diagnosis: 66) diagnosed with grade group 1 prostate cancer from January 2005 to February 2017, all of whom were in the Johns Hopkins Medicine active surveillance program and whom, at the time of enrolment, completed a validated food frequency survey regarding their usual dietary patterns. Of the participants, 55 were Black (6.2%), 803 (90.6%) were white and 28 (3.2%) identified as other races and ethnicities.

Based on their responses to the questionnaire, a Healthy Eating Index (HEI) score was calculated for each patient. The HEI ranges from 0 to 100.

“The HEI is a validated measure of overall diet quality, quantifying how well an individual’s dietary pattern adheres to the recommendations of the U.S. Department of Agriculture’s Dietary Guidelines for Americans,” says study lead author Zhuo Tony Su, MD. “We looked at each patient’s HEI score – as calculated from their dietary information recorded at enrolment in our active surveillance programme – and assessed whether men with a higher quality diet were less likely to experience grade reclassification in the years afterward.”

Su says the researchers also evaluated the patients using an energy-adjusted HEI (E-HEI) score that takes into account a person’s daily caloric intake.

Along with those two metrics, Su says, the researchers calculated scores for each study participant using the Dietary Inflammatory Index (DII) and the energy-adjusted DII (E-DII).

“The DII and E-DII scores assess the inflammatory or anti-inflammatory potential of any diet, so higher scores indicate a diet that may cause more inflammation, which in turn, may contribute to the development and progression of prostate cancer,” says Su. “We evaluated whether higher inflammatory potential was associated with increased risk of grade reclassification.”

By a follow-up assessment at 6.5 years after diagnosis, 187 men (21%) had been reclassified as grade group 2 or greater, of whom 55 (6%) had extreme grade reclassification to grade group 3 or greater.

“When our team looked at the HEI and E-HEI scores in relation to the grade reclassification rates, we found a statistically significant inverse association between adherence to a high quality diet – as indicated by high HEI and E-HEI scores – and the risk of grade reclassification during active surveillance,” says Trock. “In other words, the higher the HEI and E-HEI scores, the more reduced the risk that a low grade prostate cancer had progressed to a higher grade disease that mandated curative treatment.”

Pavlovich says for patients adhering to a high quality diet, every increase of 12.5 points in the HEI score was associated with an approximately 15% reduction in reclassification to grade group 2 or greater, and a 30% reduction in reclassification to grade group 3 or greater.

The researchers say their findings also indicate that lower inflammation potential is among several possible risk lowering mechanisms as a result of a higher quality diet. However, they did not find an association between grade reclassification and baseline DII/E-DII scores.

“This lack of association with DII/E-DII may indicate that inflammation plays a role in driving the progression from a healthy prostate to one with cancer,” says Trock. “Whereas, in men who already have prostate cancer, the more subtle biological change from a lower to higher grade may reflect other mechanisms potentially influenced by diet.”

The researchers report several limitations in their study, including diet data based on patient self-reporting, results subject to potential nonresponse bias (bias occurring when respondents and nonrespondents differ in ways that impact the research, making the sample population less representative of the whole population) and not accounting for dietary changes over time. Additionally, they say the study population, consisting predominantly of white men with grade group 1 disease at diagnosis, may not be generalisable to all patients.

“Our findings-to-date should be helpful for the counselling of men who choose to pursue active surveillance and are motivated to modify their behaviours, including quality of diet,” says Pavlovich. “However, to truly validate the association between higher quality diet and reduced risk of prostate cancer progression, future studies with more diverse populations are needed.”

Source: John Hopkins Medicine

Categories : Cardiovascular DiseaseTags :

New Guideline: Preventing a First Stroke may be Possible

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Updated clinical recommendations, including lifestyle changes, prevention strategies and treatment options, to reduce the risk of a first stroke outlined in a new guideline from the American Stroke Association

Credit: American Heart Association

Healthy lifestyle behaviours, such as good nutrition, smoking cessation and being physically active, along with routine health screenings and managing risk factors for cardiovascular disease and stroke with medication, can help prevent individuals from having a first stroke. Screening for stroke risk and educating people on how to lower their chances of having a stroke ideally begin with their primary care professional and include evidence-based recommendations, according to a new clinical guideline from the American Stroke Association, and published in the journal Stroke.

“The most effective way to reduce the occurrence of a stroke and stroke-related death is to prevent the first stroke – referred to as primary prevention,” said Chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, professor and vice chair of research in the department of neurology at Wake Forest University School of Medicine. “Some populations have an elevated risk of stroke, whether it be due to genetics, lifestyle, biological factors and/or social determinants of health, and in some cases, people do not receive appropriate screening to identify their risk.”

The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 version and is a resource for clinicians in implementing a variety of prevention strategies for individuals with no prior history of stroke. The new guideline provides evidence-based recommendations for strategies to support brain health and prevent stroke throughout a person’s lifespan by improving healthy lifestyle behaviours and getting preventive care.

“This guideline is important because new discoveries have been made since the last update 10 years ago. Understanding which people are at increased risk of a first stroke and providing support to preserve heart and brain health can help prevent a first stroke,” said Bushnell. 

Key stroke prevention recommendations include regular health screenings, identifying risk factors, lifestyle interventions and medications, when indicated.

Identifying and managing risk factors

Unidentified and unmanaged cardiovascular disease risk factors can cause damage to arteries, the brain and the heart years before cardiovascular disease and stroke occur. Primary care health professionals should promote brain health for patients through stroke prevention education, screenings and addressing risk factors from birth to old age.

Modifiable risk factors for stroke, such as high blood pressure, overweight and obesity, elevated cholesterol and elevated blood sugar, can be identified with physical exams and blood tests. These conditions should be addressed with healthy lifestyle and behavioural changes and may include medications for select patients. Antihypertensive medications to reduce blood pressure and statin medications to lower cholesterol can help to reduce the risk of first stroke in adults with increased cardiovascular disease risk and those receiving CVD care. A new recommendation is consideration of glucagon-like protein-1 (GLP-1) receptor agonist medications, which are FDA-approved to reduce the risk of cardiovascular disease in people with overweight or obesity and/or Type 2 diabetes.

Healthy lifestyle behaviours

The most common, treatable lifestyle behaviours that can help reduce stroke risk are detailed in the Association’s Life’s Essential 8 cardiovascular health metrics. They include healthy nutrition, regular physical activity, avoiding tobacco, healthy sleep and weight, controlling cholesterol, and managing blood pressure and blood sugar. The guideline recommends that adults with no prior cardiovascular disease, as well as those with increased risk, follow a Mediterranean dietary pattern. Mediterranean dietary programs have been shown to reduce the risk of stroke, especially when supplemented with nuts and olive oil.

Physical activity is also essential for stroke risk reduction and overall heart health. Physical activity can help to improve important health measures such as blood pressure, cholesterol, inflammatory markers, insulin resistance, endothelial function and weight. The guideline urges health care professionals to routinely screen patients for sedentary behaviour, a confirmed risk factor for stroke, and counsel them to engage in regular physical activity. The Association reinforces the U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion’s recommendation that adults get at least 150 minutes per week of moderate-intensity aerobic activity or 75 minutes per week of vigorous aerobic activity, or a combination of both, preferably spread throughout the week.  

Health equity and stroke risk

New to the guideline is an emphasis on social determinants of health and the impact they have on stroke risk. Social determinants of health are non-medical factors, including education, economic stability, access to care, discrimination, structural racism and neighborhood factors (such as the lack of walkability, lower availability of healthy food and fewer health resources), that contribute to inequities in care and influence overall health. Health care professionals should ensure patient education is available for various educational and language levels, and advocate for their patients by choosing treatments and medications that are effective and affordable.

Health care professionals are also encouraged to connect patients to resources that help address health-related social needs such as food and housing insecurity, refer them to programs that support healthy lifestyle changes and direct them to support programs that may help defray health care costs including medication expenses.

New sex- and gender-specific recommendations

The guideline also includes some new gender- and sex-specific recommendations for women. Health professionals should screen for conditions that can increase a woman’s risk of stroke, including use of oral contraceptives, high blood pressure during pregnancy, other pregnancy complications such as premature birth, endometriosis, premature ovarian failure and early onset menopause. Treatment of elevated blood pressure during pregnancy and within six weeks of delivery is recommended to reduce the risk of maternal intracerebral haemorrhage.

Transgender women and gender-diverse individuals taking oestrogens for gender affirmation may also be at an increased risk of stroke. Evaluation and modification of any existing risk factors are needed to reduce the risk of stroke for these individuals.

“Implementing the recommendations in this guideline would make it possible to significantly reduce the risk of people having a first stroke. Most strategies that we recommend for preventing stroke will also help reduce the risk of dementia, another serious health condition related to vascular issues in the brain,” said Bushnell.

The writing group notes that writing recommendations focused on preventing a first stroke was challenging. There are limitations to some of the evidence that informed the guideline, including that many clinical trials enrolled adults who have already had a cardiovascular event that may include a stroke. The writing group also identified knowledge gaps to help inform topics for future research.

The guideline highlights the need for risk assessment in primary stroke prevention and includes the use of risk prediction tools to estimate risk for atherosclerotic cardiovascular disease so that patients receive timely prevention and treatment strategies. The Association has recently developed a new Predicting Risk of Cardiovascular Disease Events (PREVENT) risk calculator as a screening tool that can help inform preventive treatment decisions. The PREVENT calculator can estimate 10-year and 30-year stroke and heart disease risk in individuals starting at age 30 – a decade earlier than the Pooled Cohort Equations, another CVD risk calculator.

According to the American Stroke Association, learning the warning signs of stroke and preventative measures are the best way to avoid strokes and keep them from happening again. The abbreviation F.A.S.T. – for face drooping, arm weakness, speech difficulty, time to call 911 – is a useful tool to recognise the warning signs of stroke and when to call for help.

This guideline was prepared by the volunteer writing group on behalf of the American Stroke Association and is endorsed by the Preventive Cardiovascular Nurses Association and the Society for Vascular Surgery. The American College of Obstetricians and Gynecologists supports the clinical value of this document as an educational tool.

Since 1990, the American Stroke Association has translated scientific evidence into clinical practice guidelines with recommendations to improve cerebrovascular health. The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 “Guidelines for the Primary Prevention of Stroke.” This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke. The Association supports the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts.

Source: American Heart Association

Categories : AgeingTags :

Who will Live to 100?

On By ModernMedia
Photo by Ravi Patel on Unsplash

Those who wish to live to 100 cannot rely on chance. Instead, it is essential to keep biomarkers associated with ageing and disease in check. By the age of 60, it may already be too late.

Text by: Maja Lundbäck, first published in Medical Science No 3 2024

Swedes are increasingly living to older ages. Thirty years ago, 85-90- year-olds were rare, but now the majority reach that age ‒ and two percent even get to see 100 candles on their birthday cake.

“Centenarians are the age group that is increasing the most now,” says Karin Modig, Associate Professor at the Institute of Environmental Medicine at Karolinska Institutet, who researches ageing and health.

In a study published in the journal GeroScience, she and her colleagues show that it is possible to predict who has the greatest chance of becoming very old already during early ageing. The study is based on approximately 44 000 Swedes who underwent health examinations between 1985 and 1996, aged between 64 and 99. Of these, 1224 individuals lived to 100.

“The results suggest that becoming very old is not solely a matter of chance; it also seems to be linked to lifestyle,” says Karin Modig.

Known biomarkers 

By looking at known biomarkers previously associated with ageing and disease, the researchers found that the centenarians had better health than their peers already in their 60s. All but two of twelve biomarkers examined could be linked to increased chances of reaching 100 years. Low iron levels reduce the chance, as does low total cholesterol, which can be a marker of disease processes in the body.

Four of the biomarkers stood out as particularly important: creatinine levels, which indicate kidneys health, were almost always normal at age 60 in those who lived to 100. The same was true for liver markers and uric acid levels, a marker for inflammatory processes. Individuals with the lowest uric acid levels had a four percent chance of living to 100, while those with the highest levels had a 1.5 percent chance. Blood sugar levels were also rarely above 6.5mmol/litrw.

The results suggest that it may be possible to increase one’s chances of living to 100 by changing your lifestyle, she believes.

“At the same time, life is not about living according to an algorithm; everyone must find their own balance between risk factors and health factors,’ she says.

Source: Karolinska Institutet