Tag: 2/3/23

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Pseudomonas Aeruginosa Locks out Immune Cells

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Pseudomonas
Scanning Electron Micrograph of Pseudomonas aeruginosa. Credit: CDC/Janice Carr

Pseudomonas aeruginosa bacteria are a common menace in hospital wards, causing life-threatening infections, and are often resistant to antibiotics. Researchers have discovered a mechanism that likely contributes to the severity of P. aeruginosa infections, which could also be a target for future treatments. The results were recently appeared in the journal EMBO Reports.

Many bacterial species use sugar-binding molecules called lectins to attach to and invade host cells. Lectins can also influence the immune response to bacterial infections. However, these functions have hardly been researched so far. A research consortium led by Prof Dr Winfried Römer at the University of Freiburg and Prof Dr Christopher G. Mueller at the CNRS/University of Strasbourg has investigated the effect of the lectin LecB from P. aeruginosa on the immune system. It found that isolated LecB can render immune cells ineffective: The cells are then no longer able to migrate through the body and trigger an immune response. The administration of a substance directed against LecB prevented this effect and led to the immune cells being able to move unhindered again.

LecB blockades immune cells

As soon as they perceive an infection, cells of the innate immune system migrate to a nearby lymph node, where they activate T and B cells, triggering a targeted immune response. LecB, according to the current study, prevents this migration. “We assume that LecB not only acts on the immune cells themselves in this process, but also has an unexpected effect on the cells lining the inside of the blood and lymph vessels,” Römer explains. “When LecB binds to these cells, it triggers extensive changes in them.” Indeed, the researchers observed that important structural molecules were relocated to the interior of the cells and degraded. At the same time, the cell skeleton became more rigid. “The cell layer thus becomes an impenetrable barrier for the immune cells,” Römer said.

An effective agent against LecB

Can this effect be prevented? To find out, the researchers tested a specific LecB inhibitor that resembles the sugar building blocks to which LecB otherwise binds. “The inhibitor prevented the changes in the cells, and T-cell activation was possible again,” Mueller said. The inhibitor was developed by Prof Dr Alexander Titz, who conducts research at the Helmholtz Institute for Pharmaceutical Research Saarland and Saarland University.

Further studies are needed to determine how clinically relevant the inhibition of the immune system by LecB is to the spread of P. aeruginosa infection and whether the LecB inhibitor has potential for therapeutic application. “The current results provide further evidence that lectins are a useful target for the development of new therapies, especially for antibiotic-resistant pathogens such as P. aeruginosa,” the authors conclude.

Source: University of Freiburg

Categories : Ageing Diet and NutritionTags :

Vitamin D Supplements may Ward off Dementia

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Vitamin D pills
Photo by Michele Blackwell on Unsplash

Taking vitamin D supplements may help ward off dementia, according to a new, large-scale study published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring.

Canadian and UK researchers explored the relationship between vitamin D supplementation and dementia in more than 12 388 participants of the US National Alzheimer’s Coordinating Center, who had a mean age of 71 and were dementia-free when they signed up.

The team found that taking vitamin D was associated with living dementia-free for longer, and they also found 40% fewer dementia diagnoses in the group who took supplements.

Of the group, 2696 participants progressed to dementia over ten years; amongst them, 2017 (75%) had no exposure to vitamin D throughout all visits prior to dementia diagnosis, and 679 (25%) had baseline exposure.

Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: “We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline.”

While Vitamin D was effective in all groups, the team found that effects were significantly greater in females, compared to males. Similarly, effects were greater in people with normal cognition, compared to those who reported signs of mild cognitive impairment – changes to cognition which have been linked to a higher risk of dementia.

The effects of vitamin D were also significantly greater in people who did not carry the APOEe4 gene, known to present a higher risk for Alzheimer’s dementia, compared to non-carriers. The authors suggest that people who carry the APOEe4 gene absorb vitamin D better from their intestine, which might reduce the vitamin D supplementation effect. However, no blood levels were drawn to test this hypothesis.

Previous research has found that low levels of vitamin D are linked to higher dementia risk. Vitamin D is involved in the clearance of amyloid in the brain, the accumulation of which is one of the hallmarks of Alzheimer’s disease. Studies have also found that vitamin D may provide help to protect the brain against build-up of tau, another protein involved in the development of dementia.

Co-author Dr Byron Creese, at the University of Exeter, said: “Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected. The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case. The ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo and examining changes in memory and thinking tests over time.”

Source: University of Exeter

Categories : Cardiovascular Disease GenderTags :

Gender Affirming Hormone Therapy Linked to Greatly Increased Cardiovascular Risk

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Source: CC0

People undergoing hormone replacement therapy (HRT) for gender dysphoria have a greatly increased risk of serious cardiac events, according to a study presented at the American College of Cardiology annual meeting. Compared to people with gender dysphoria not taking HRT, those taking HRTY saw a seven-fold risk increase for ischaemic stroke, and risk increases for myocardial infarction and pulmonary embolism.

People with gender dysphoria may use HRT as part of gender affirmation therapy to transition to a different gender than their biological sex at birth. HRT for this purpose is rapidly increasing, especially among teens and young adults.

Previous research on hormone-modulating medications has primarily focused on younger women using hormone-based birth control or on older women following a hysterectomy or during menopause. In these populations, long-term HRT has been associated with an increased risk of breast cancer, stroke and blood clots.

Researchers retrospectively examined rates of cardiovascular events in over 21 000 people with gender dysphoria from a national database of hospital records, of whom 1675 had used HRT. Typically, people assigned male at birth receive oestrogen and people assigned female at birth receive testosterone. Overall results found hormone replacements were associated with higher rates of cardiac events, mostly related to dangerous blood clots, but were not associated with higher rates of death.

Compared with hospitalised patients with gender dysphoria who had never used HRT, those taking gender affirmation HRT had higher rates for a range of in-hospital cardiovascular events:

  • ST-elevation myocardial infarction (OR 5.90, 95% CI 1.07-32.42)
  • Ischaemic cerebrovascular accident (OR 7.15, 95% CI 2.74-18.67)
  • Non-ST-elevation myocardial infarction (OR 3.30, 95% CI 1.20-9.04)
  • Pulmonary embolism (OR 4.92, 95% CI 2.08-11.62)

“It’s all about risks and benefits. Starting transitioning is a big part of a person’s life and helping them feel more themselves, but hormone replacement therapy also has a lot of side effects – it’s not a risk-free endeavour,” said Ibrahim Ahmed, MD, a third-year resident at Mercy Catholic Medical Center in Darby, Pennsylvania and the study’s lead author.

HRT was not associated with any increase in deaths, incident atrial fibrillation, diabetes, hypertension, haemorrhagic stroke, or heart failure.

Both oestrogen and testosterone are known to increase the clotting activity of blood, which could explain the increase in clotting-related cardiovascular events, researchers said. Those taking hormone replacement therapy also had higher rates of substance use disorder and hypothyroidism.

“Looking at a person’s medical and family history should definitely be part of the screening protocol before they even start hormone replacement therapy,” Ahmed said. “It is also important that people considering this therapy are made aware of all the risks.”

One limitation of the study is that it only accounted for whether individuals had ever used any type of hormone replacement therapy. To better inform clinical decisions, researchers said it would be helpful to assess whether the duration of treatment, the age at which it is initiated or the type of hormone therapy used affects the risks.

“I’m curious to see if the method of administration alters the outcomes,” Ahmed said. “Is one way of giving hormone replacement therapy better or associated with a lower risk of cardiovascular outcomes? If so, then that should be the focus for how we give these patients their hormone replacement therapy going forward.”

In addition to considering ways to mitigate potential cardiovascular risks before starting hormone replacement therapy for individual patients, researchers said it will be important to continue to study potential long-term cardiovascular and other health effects of gender affirmation therapies as the use of these therapies become more common.

Source: American College of Cardiology

Categories : Paediatrics Respiratory DiseasesTags :

Improving Diagnosis of Chronic Lung, Ear and Sinus Infections in Young Children

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Young girl sneezing
Photo by Andrea Piacquadio on Unsplash

An international Task Force has recommended a method to help diagnose preschool age children with Primary Ciliary Dyskinesia (PCD), a rare, inherited condition that leads to chronic lung, ear and sinus infections. The Task Force’s findings were published in the European Respiratory Journal.

Children with PCD have a problem with mucus build-up, which leads to inflammation in the airways and infections in the lungs, nose, sinuses and ears. Most people with PCD have symptoms from birth or early childhood. But some children with PCD may not be diagnosed until much later.

Currently, a commonly used diagnostic test for PCD is measuring the nitric oxide (nNO) in the nose using a chemiluminescent analyser. This involves holding a sampling tube at the nostril, whilst the patient either holds their breath, or breathes out through their mouth against a resistance – but for young children such controlled breathing isn’t always practical. Furthermore, chemiluminescence analysers are extremely expensive, not portable, and not available in most countries.

Jane Lucas, Professor of Paediatric Respiratory Medicine at University of South Hampton, led an international Task Force to review existing studies and literature to establish whether there were more effective and accessible methods of diagnosis for PCD in younger children.

The task force concluded that although holding the breath or breathing against a resistor whilst using a chemiluminescence analyser was more reliable in older children and adults, adequate measurements could be achieved by measuring nasal nitric oxide whilst a pre-school child breathes normally and should be the standard way when diagnosing PCD in children under the age of five.

The Task Force also suggested that although chemiluminescence analysers are more reliable, the relatively inexpensive electrochemical devices have a role in healthcare systems with limited resources. They also recognised that the portability of electrochemical devices may be useful in countries where patients live long distances from a specialist centre, enabling the specialist to travel to the patient.

“We know that the earlier we can diagnose a condition, the better the chances are of implementing the best treatment plan for the patient,” Professor Lucas said. “But current guidelines and technical standards focus on nNO measurements in older, cooperative children using technology that is not widely available.

“Pre-schoolers often need different methods to be employed when measuring nNO, methods that are less invasive and adaptable. Without guidelines for younger children, and electrochemical analysers there is huge variability in how people take the measurements and interpret them.

“This paper is the first step towards standardising sampling, analysis, and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups including preschool-age children. We hope this will promote earlier diagnosis of PCD, and a standardised approach to interpreting and reporting results.”

The task force also recommends that future research is needed to ensure the technical standard is kept up to date.

Source: University of Southampton

Categories : Obstetrics & Gynaecology PaediatricsTags :

Elective Induced Labour Associated with Lower Grades at Age 12

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Photo by Mary Taylor on Pexels

According to a new study published in Acta Obstetricia et Gynecologica Scandinavica, in women with uncomplicated pregnancies, elective induction of labour at any point between 37 and 41 weeks was consistently associated with those children having lower scholasti performance at age 12.

Investigators analysed data for 266 684 children born between 37 and 42 weeks from uncomplicated pregnancies in white women in the Netherlands. Scholastic performance scores at age 12 years were lower in those from pregnancies with induced labour at 37–41 weeks compared with those with uninduced labour. At 42 weeks, there was no significant difference in scholastic performance between these groups.

The proportion of children who reached higher secondary school level was significantly lower after induction of labour at each gestational week from 38–41 weeks. For example, at 38 weeks, rates were 48% versus 54% in induced versus uninduced. (In the Dutch education system, when children reach the end of primary school, around 12 years of age, they are divided over four different levels of secondary education according to their intellectual ability. All children in the last year of regular primary education take a test to guide the choice of level of secondary education.)

“Of course, if there is an indication to induce delivery before 41 weeks, there is little doubt we should do this. But if the reason is purely elective, it is reasonable to be cautious of these subtle adverse effects,” said Wessel Ganzevoort, MD, PhD, senior investigator and maternal foetal medicine specialist at Amsterdam UMC.

Source: Wiley