Mechanical Heart Valve Replacements have Better Long-term Survival

Artificial heart valve. Credit: Scientific Animations CC4.0

Patients aged between 50 to 70 years with a mechanical heart valve replacement had better long-term survival compared to those with a biological valve, new research led by the University of Bristol has found. The study is published in the European Journal of Cardio-Thoracic Surgery.

The last two decades have seen an increase in the use of biological over mechanical heart valve replacements. However, while short-term clinical outcomes are known to be the same, long-term outcomes are still under debate.

Existing guidelines support the use of mechanical valves made of synthetic materials in patients below the age of 50, while biological valves made of animal tissue are favoured for those above the age of 65 or 70. The guidelines leave the choice to the decision of surgeons and patients who are 50 to 70 years old.

The research team wanted to find out the clinical outcomes for patients aged between 50 to 70 years undergoing elective and urgent heart valve replacement at the Bristol Heart Institute (BHI) over a 27 year period [1996 to 2023].

The researchers also sought to investigate trends, early outcomes and long-term survival rates, the incidence of repeat valve interventions and patient prosthesis mismatch (PPM).

A total of 1708 (61% male) patients with an average age of 63 years were included with 1191 (69.7%) receiving a biological valve replacement.

The research found there were no short-term differences when comparing patients receiving biological and mechanical valves. However, patients who received mechanical valves had better long-term survival up to 13 years after having surgery. 

Patients with a size 19mm biological valve replacement (a fairly small valve commonly used in females) had the worse long-term survival. Patients with a size 21mm mechanical valve had better survival compared to both size 19 and 21mm biological valves.  The study confirmed that severe PPM is a significant risk factor for poor long-term survival.

Gianni Angelini, BHF Professor of Cardiac Surgery at the Bristol Medical School: Translational Health Sciences (THS), Director of the Bristol Heart Institute and corresponding author, said: “Our study has implications for decision-making in surgical heart valve replacements for patients aged between 50 and 70 years old. The evidence supporting better long-term survival in patients receiving a mechanical heart valve suggests the current trend favouring biological valves in this age bracket should be urgently reconsidered. The survival benefit is especially clear in smaller sized valves.”

The research team recommends the evaluation of the long-term benefits associated with mechanical valves, especially in smaller sizes, despite long-term blood thinners not being needed with biological valves.

Study limitations

The single-institution design, retrospective collection of data, and absence of randomisation make the study open to bias. The lack of echocardiographic information could potentially underestimate the incidence of structural valve failure. In terms of repeat valve interventions, only patients who underwent re-do surgical aortic valve replacement or valve in valve transcatheter aortic valve implantation (TAVI) at the BHI were included.

As the BHI is a supra-regional centre, it is very unlikely that many patients might have undergone reintervention in other institutions. The cause of  death (cardiovascular/non cardiovascular) was not available.

Source: University of Bristol

No Clear Government Plan Yet to Confront US Aid Cuts

Photo by Reynaldo #brigworkz Brigantty

By Ufrieda Ho

South Africa’s National Department of Health is still to outline a clear contingency plan as a United States (US) funding freeze puts lives at risk, spells job losses, and presents threats to keeping HIV and TB under control.

The ripple effects of US President Donald Trump’s 90-day freeze of funding on foreign aid programmes have hit South Africa hard. The damage is being counted at multiple levels – even as some limited funding flows are being restored.

For the country, the fallout has heightened civil society’s calls for a prompt, implementable plan to fill the gaps in care and services. Also needed, they say, is clarity on longer-term strategies for greater self-sufficiency in the country’s HIV responses as donor-funded models look increasingly precarious. Such an argument for increased independence in Africa and the global south was made by president of the South African Medical Research Council (SAMRC), Professor Ntobeko Ntusi, writing in the journal Nature.

South Africa should have been better prepared and not caught off guard to be left in the position it now finds itself in, some beneficiaries of US-funded projects told Spotlight. They were speaking on condition of anonymity, given the risk of public comments jeopardising their prospects of having their funding restored.

The immediate need is to ensure that the country’s overburdened and under-resourced public clinic system is able to absorb the tens of thousands of people living with HIV who will have to use public facilities. This is partly because the NGOs they have relied on have been forced to close shop – virtually overnight. Clinics catering to specific groups, such as men who have sex with men, have been particularly hard hit.

South Africa is the largest global recipient of President’s Emergency Plan for Aids Relief (PEPFAR) funds. These funds make its way to South Africa through the United States Agency for International Development (USAID) and the Centers for Disease Control and Prevention (CDC). Through PEPFAR, USAID has been funding and supporting local NGOs and our Department of Health for around two decades. According to USAID’s website, it invested $5.6 billion (roughly R100 billion at the current rand/dollar exchange rate) between 2004 and 2020 towards prevention and treatment of HIV and TB in South Africa.

Trump’s initial executive order, signed on 20 January, halted funding received via USAID. USAID is an agency of the US government that now falls under the State Department under the leadership of Secretary of State Marco Rubio. Since taking office, Trump has slated USAID as “corrupt” and run by “radical left lunatics”.

The Washington head offices of USAID were closed on Friday 7 February as per Trump’s orders and even as the 90-day review period had just got underway, signage on the building was being removed or taped over. Trump’s actions have now been challenged in courts with successful temporary blocks to his orders to place 2 200 USAID workers in the US on paid leave and to reinstate 500 US-based staff who were already placed on administrative leave from when the order was first signed. The situation is highly fluid and several court actions remain in progress.

Some limited relief

In South Africa, NGOs that received USAID funding remain largely in limbo. Although the United States mission in South Africa confirmed that some PEPFAR-funded services could continue in the country, it is subject to some relatively strict limitations and with no assurances of longer term support. As is clear from reporting by Bhekisisa, the process to get at least some funding to flow again to PEPFAR-supported projects is not straight forward.

There was some good news this week linked to PEPFAR-funding channelled through the CDC – a US federal agency under the Department of Health and Human Services. Following a court order, organisations getting these funds should for now be able to continue their work. However, the court process is far from over and the future prospects of NGOs that depend on CDC funds remains precarious.

Given these ongoing uncertainties and severe disruptions to cash flows, Spotlight understands that some large NGOs may have to close down, while others may have to drastically reduce their services. As reported by Spotlight and GroundUp, several NGOs have appealed to the private sector for assistance. As it stands, thousands of people employed or contracted by local NGOs face the loss of their jobs, cut-backs and deepening anxiety over income security. These people include community health workers, peer counsellors, patient navigators, community activists and advocates, support and administrative staff members, and contract workers who keep these organisations functioning.

At stake too are specialised services for so-called key populations such as sex workers, men who have sex with men, the LGBTQI+ community, and people who use drugs. Until recently, a focus on improving services for key populations was generally accepted, including by PEPFAR, to be the right strategy given the disproportionate risk of HIV infection in these groups. But under the Trump administration’s “anti-woke” agenda, it seems likely that many services aimed at key populations are set to be defunded.

A White House media note on 29 January made clear the US’s stance: “The previously announced 90-day pause and review of U.S. foreign aid is already paying dividends to our country and our people. We are rooting out waste. We are blocking woke programs. And we are exposing activities that run contrary to our national interests. None of this would be possible if these programs remained on autopilot.”

A timeline of the US aid cuts


20 January

90-day pause 

In an executive order, US President Donald Trump orders a 90-day pause in US foreign development for “assessment of programmatic efficiencies and consistency with United States foreign policy”. 

26 January

USAID funding paused 

US Secretary of State Marco Rubio pauses all US foreign assistance funded by or through the State Department and US Agency for International Development (USAID) for review. 

28 January

Waiver issued 

Subject to certain conditions, Rubio issues a waiver stating: “Implementers of existing life-saving humanitarian assistance programs should continue or resume work if they have stopped.” 

1 February

Waiver clarified 

The extent of the January 28 waiver is clarified in a memo from the US Department of State. 

5 February

Health portfolio committee briefing 

South Africa’s Health Minister Dr Aaron Motsoaledi briefs Parliament on the US funding cuts and their impact on healthcare services. 

7 February

South Africa singled out 

In an executive order applying only to South Africa, Trump orders that “the United States shall not provide aid or assistance to South Africa”. 

10 February

Waiver still applies 

The US mission in South Africa releases an FAQ in which they state that PEPFAR activities that fall under the limited waiver will resume despite the February 7 executive order. 

12 February

CDC grants reinstated 

The grants of NGOs receiving support through the CDC are reinstated following a court order issued in a US court. 


Crisis of fear, silence, and uncertainty

Spotlight understands that staff of affected NGOs have essentially been forbidden from speaking publicly about the 90-day funding freeze. Many declined to speak on the record to Spotlight, even anonymously – too afraid it might affect the decision on their funding after the 90-day review period.

According to an FAQ by the US mission in South Africa that was published on February 10, they have been communicating with the South African government, though it is not clear when this happened. Five days earlier on 5 February, Health Minister Dr Aaron Motsoaledi told Parliament’s Portfolio Committee that he had not had any official communication from the US government on the matter.

Figures from Motsoaledi’s presentation showed that in 2023/2024, PEPFAR funding to South Africa’s health department amounted to 17% of its spending on HIV. Funding totals R4.6 billion for staffing and R2.9 billion for running costs for NGOs. These NGOs include organisations working directly with people living with HIV, mobile units and youth organisations and programmes. PEPFAR focuses on the 27 districts in South Africa with the highest disease burden.

The health department did not respond to Spotlight’s questions on contingencies, or details of next steps to fill the funding gaps or how capacity and resources will be redirected to avert catastrophe. Motsoaledi did not give any of these details in his presentation to Parliament either.

What he did say was that since Trump’s executive order came into place, the health department had hosted a meeting with the provincial leads on HIV and TB; conducted assessments on the immediate impacts of the executive order; met with people living with HIV and engaged with SANAC to finalise a sustainability framework.

collective of activist organisations, including the Health Justice Initiative, SECTION27, the Cancer Alliance, Treatment Action Campaign, Sweat, PSAM and the African Alliance, have pressed the Department of Health to create an “urgent co-ordinated emergency plan” along with an increased budget to avert a looming disaster.

The activists highlighted that despite the announcement by the Trump administration that some NGOs could apply for a waiver, many have had no practical way to do so without ways to communicate with their USAID contacts. This as USAID employees were placed under a work stop order and were shut out of their offices and denied access to their work emails.

The appeal from the collective also extends to protecting the work of academic and clinical research in the fields of HIV, TB, and cervical cancer that will also be affected by the funding freeze. As Spotlight reported, around 28% of the South African Medical Research Council’s budget for 2025/2026 was set to come from the United States government.

An ‘unreal world’

Professor Linda-Gail Bekker, chief executive officer at the Desmond Tutu Health Foundation, said Trump’s actions put in jeopardy the goal to finally have epidemic control of HIV – and right at the final hurdles.

“We have made amazing progress. And thank you to PEPFAR that helped us to get this far, but the work is not over. For the US to pull out at this point is a massive loss of investment; it’s also regression. It’s like getting to the end of a book but having the last chapters torn out before you can read it,” said Bekker.

She said PEPFAR funding has made it possible to build a formidable cohort of lay and professional people trained and dedicated to their roles that supported public healthcare in the most critical ways.

“These are individuals who distribute antiretrovirals, distribute pre-exposure prophylaxis, find and trace individuals who’ve been lost to care. They take services into communities, to outside of the health facilities, and made the effort to go the last mile to find those individuals – that is how you close down the epidemic,” Bekker said.

Her caution too is that loosening a grip on HIV control means potential surges in tuberculosis. “HIV and TB track together all the time, and an HIV epidemic that is once again out of control, almost certainly means what will follow is a TB epidemic that is out of control,” Bekker said.

Trump has created an “unreal world”, said Dr Andy Gray of the University of KwaZulu-Natal, who has also worked with the World Health Organization (WHO) in various capacities over two decades. “People are being held to ransom; and people are scared.”

“We have always been used to the oscillation between the United States’ Republican and Democratic administrations; things may be a little uncomfortable or there may be some disruption, but not this ‘let’s burn down the house’ approach taken by the Trump administration,” he said.

“There is no consideration of human rights or for human beings anywhere in the world, including America,” he added, pointing out too that the CDC has for the first time in 60 years been instructed to cease publishing weekly mortality and morbidity data, despite a breakout of avian flu (H5) in the country.

For Gray, South Africa’s strategic health response in the wake of this crisis should be to shift from a donor-funded model. His concern, however, is that with a stretched South African purse and with competing priorities, the HIV response will slip down the list.

Gray said that better self-sufficiency comes from eliminating waste, investing in employing the right people in the right jobs as well as investing in efficient systems.

He added that National Treasury will have to redirect money for the interim shortfall left by the US funding freeze, and provinces will have to step up by getting their houses in order.

South Africa, he warned, should ready itself for the “worst case scenario” once the 90-day review period is up.

SANAC response

The South African National AIDS Council (SANAC) role is meant to bring together government, civil society and the private sector to create a collective response to HIV, TB and STIs in South Africa. But if there is a crisis strategy from the council, it has not yet been announced.

SANAC head of communications, Nelson Dlamini, said that they have been left in a position of not being able to engage publicly because they haven’t had any direct communication with PEPFAR’s and USAID representatives based in Pretoria.

“PEPFAR is a government-to-government agreement and there ought to be official communication with the government of South Africa so we know what this means for our working relationship, but nothing has been forthcoming,” said Dlamini. “SANAC is a co-ordinator so we have to still coordinate. We are engaging in the background with relevant structures but we can’t say we are doing X, Y, Z till we have a sit down with PEPFAR,” he said.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

A Short Course of Radiation Therapy for Endometrial Cancer Patients is Effective

Female reproductive system. Credit: Scientific Animations CC4.0 BY-SA

In a randomised clinical trial, researchers from Huntsman Cancer Institute at the University of Utah (the U) have found that short-course, higher dose vaginal brachytherapy for endometrial cancer had similar effectiveness to more frequent, lower dose sessions.

Gita Suneja, MD, MS, physician-scientist at Huntsman Cancer Institute and professor of radiation oncology at the U, is the first author of the SAVE trial report – which stands for, Short-Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared with Standard of Care.

“There isn’t high quality-data on optimal dose and schedule for brachytherapy treatments. Because of this, practice patterns really vary,” says Suneja. “The SAVE trial sought to try to lower the number of treatments that patients were receiving but maintain short-term quality of life and disease control.”

Endometrial cancer is a disease that begins in the lining of the uterus. The primary treatment for endometrial cancer is surgery, including the removal of the uterus, cervix, and upper vagina. Brachytherapy, a form of internal radiation, is used as a secondary treatment to prevent the cancer’s return. Patients receiving vaginal cuff brachytherapy are treated with internal radiation by way of an applicator in the vaginal cavity.

The SAVE trial compared two groups who received different treatment doses over a varying number of sessions. The control group received the standard treatment – between three to five appointments with lower doses. The experimental group received higher doses of radiation in just two sessions.

“The study outcomes will help improve cancer care for Huntsman Cancer Institute patients across the five states of the Mountain West.”

Gita Suneja, MD, MS

The researchers found similarly effective short-term outcomes and few acute toxicities for the patients in the experimental group.

David Gaffney, MD, PhD, FACR, FABS, FASTRO, physician-scientist at Huntsman Cancer Institute and professor of radiation oncology at the U, developed the idea for the SAVE study after seeing patient need. According to the American Cancer Society, endometrial cancer is the most common cancer of the female reproductive organs. Incidence is on the rise, as is the mortality rate.

“It is a big win when we can preserve good outcomes and make cancer care easier,” says Gaffney.

The results of the SAVE trial were published in JCO Oncology Advances.

Source: Huntsman Cancer Institute

Type 1 Diabetes: Hybrid Closed-loop and Open-loop Systems Compared

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People with type 1 diabetes require continuous insulin treatment and must regularly measure their glucose levels. With open-loop therapies*, insulin administration is manually controlled, while hybrid closed-loop systems* automatically regulate insulin delivery. A study with the involvement of the German Center for Diabetes Research showed that hybrid closed-loop systems offer improved long-term blood sugar values (HbA1c levels) and a lower risk of hypoglycaemic coma, but lead to a higher rate of diabetic ketoacidosis. The results were published in The Lancet Diabetes & Endocrinology.

Despite advances in insulin therapy, many people do not achieve their blood glucose targets and have a high risk of complications. Until now, the effect of insulin delivery in hybrid closed-loop systems on the risk of acute diabetes complications in people with type 1 diabetes has been unclear. Researchers have therefore now investigated whether the rates of severe hypoglycaemia and diabetic ketoacidosis are lower with hybrid closed-loop insulin therapy compared with sensor-augmented (open-loop) pump therapy.

Study with Nearly 14 000 Participants

In order to answer this question, the researchers, led by Professor Beate Karges, Faculty of Medicine at the RWTH Aachen, examined the data of nearly 14 000 participants. The study involved young people with type 1 diabetes from 250 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The participants were aged 2 to 20 years and had a type 1 diabetes duration of more than one year. They were identified from the Diabetes Prospective Follow-up Registry (DPV)**. The primary objectives of the study were to determine the rates of severe hypoglycaemia and ketoacidosis. Differences in HbA1c levels, time in the target range of 3.9 to 10.0mmol/L (70–180mg/dL), and fluctuations in blood sugar were also investigated. The data of 13 922 patients (51% male) were included in the analysis. Median age was 13.2 years; 7088 used a hybrid closed-loop system and 6834 used an open-loop system. The median observation time was 1.6 years.

Lower Rate of Hypoglycaemic Coma and More Ketoacidosis Events with Hybrid Closed-Loop Therapies

The results: People using hybrid closed-loop therapy had a significantly lower rate of rate of hypoglycaemic coma (0.62 per 100 patient-years) than those using open-loop therapy (0.91 per 100 patient-years). Furthermore, patients in the hybrid closed-loop group had a significantly lower HbA1c level (7.34% versus 7.50%). They had a higher percentage of time in the target glucose range of 3.9 to 10.0 mmol/L (64% versus 52% of the time). Their glycaemic variability was also lower (coefficient of variation of 35.4% versus 38.3%). There was no significant difference in the rate of severe hypoglycaemia.

However, individuals using a hybrid closed-loop system had a higher rate of ketoacidosis (1.74 events per 100 patient-years) than those using open-loop therapy (0.96 per 100 patient-years). The rate of ketoacidosis was particularly high in people with an HbA1c level of 8.5% or higher in the closed-loop therapy group (5.25 per 100 patient-years). In the comparison group, a rate of 1.53 events per 100 patient-years was observed.

Recommendation: Monitor Ketone Bodies Closely

Due to the higher risk of ketoacidosis, it is important to provide patients with targeted information and, in case of potential metabolic decompensation, to closely monitor ketone bodies in the blood or urine in order to prevent such adverse events, emphasize the authors of the study. 

Source: Deutsches Zentrum fuer Diabetesforschung DZD

Study Probes How to Predict Complications from Preeclampsia

Data from 8843 women diagnosed with preeclampsia during pregnancy showed that existing risk prediction models are most accurate only in the days after diagnosis

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The existing prediction models for severe complications of preeclampsia are most accurate only in the two days after hospital admission, with deteriorating performance over time, according to a new study published February 4th in the open-access journal PLOS Medicine by Henk Groen of University of Groningen, the Netherlands, and colleagues.

Preeclampsia is a potentially life-threatening condition that can occur during pregnancy; of women diagnosed with preeclampsia, 5-20% will develop severe complications. Two existing PIERS (Pre-eclampsia Integrated Estimate of RiSk) models, PIERS Machine Learning (PIERS-ML) and the logistic-regression-based fullPIERS, are designed to identify individuals at greatest or least risk of adverse maternal outcomes in the 48 hours following hospital admission for preeclampsia. However, both models are regularly used for ongoing assessment beyond the first 48 hours.

In the new study, researchers used data from 8843 women diagnosed with preeclampsia at a median gestational age of 36 weeks between 2003 and 2016. Data included PIERS-ML and fullPIERS assessments as well as health outcomes.

The study found that neither the PIERS-ML nor fullPIERS model maintained good performance over time for repeated risk stratification in women with preeclampsia. The PIERS-ML remained generally good at identifying the very high-risk and very-low risk groups over time, but performance of the larger high-risk and low-risk groups deteriorated significantly after 48 hours. The fullPIERS model underperformed compared to the PIERS-ML model.

“Since there are no better options, clinicians may still use these two models for ongoing assessments after the first admission with pre-eclampsia, but the predictions should be treated with increasing caution as the pregnancy progresses,” the authors say. More prediction models are needed that perform well over time, they add.

The authors add, “Pregnancy hypertension outcome prediction models were designed and validated for initial assessment of risks for mothers; this study shows that such ‘static’ models if used repeatedly over days yield increasingly inaccurate predictions.”

Provided by PLOS

Cystic Fibrosis Damages the Immune System Early on

Photo by Robina Weermeijer on Unsplash

Despite new medication, cystic fibrosis often leads to permanent lung damage. Working with an international team, researchers from the Technical University of Munich (TUM) have discovered that the disease causes changes in the immune system early in life, presumably even in newborns. These changes lead to frequent inflammation and are not affected by drugs targeting the altered mucus production.

Cystic fibrosis is caused by hereditary genetic mutations that impair or halt the production of the CFTR protein. The respiratory tract is most severely affected. There, the mucus becomes so viscous that pathogens like bacteria cannot be removed by coughing. The result is often a deadly cycle of infection and inflammation.

In recent years, doctors have started using so-called CFTR modulator therapies to enhance the protein’s function. This reduces mucus formation and significantly improves the quality of life for those affected. However, clinical studies show that airway inflammation continues to occur frequently. In older patients, the decline in lung function seems unstoppable.

Current research aims to uncover additional processes in cystic fibrosis. “We specifically looked at how the immune system behaves in cystic fibrosis before the cycle of infection and inflammation begins,” said Prof. Nikolai Klymiuk from TUM. He is part of the international team that recently published a study on cystic fibrosis in Science Translational Medicine.

Immature immune cells in blood samples from children

The researchers found that in blood samples from children with cystic fibrosis and biological material from pigs with the same genetic defect, certain cells of the innate immune system are immature. This makes them less effective at fighting bacteria. Pigs with cystic fibrosis also showed an increased number and significantly altered composition of immune cells in the lungs at birth. The strong resemblance between the immune systems of pigs and humans suggests that this finding likely applies to human patients as well.

‘Emergency program’ responsible?

According to the authors, one possible explanation for the changes in the immune system could be a kind of “emergency program”. The program stimulates the body to produce a large number of immune cells particularly quickly or over a longer period of time. One consequence is the formation of immature immune cells, which could contribute to the fatal cycle of infections and inflammation in cystic fibrosis: Although immune cells are present in the lungs, they are ineffective and cause damage to the lung tissue without preventing infections in the long term.

Since immune cells generally produce only very small amounts of CFTR, the research team believes that the influence of cystic fibrosis on the immune system is indirect. This could explain why defective immune reactions cannot be treated well with novel CFTR modulator therapies.

Changes not a result of frequent infections

“We don’t yet know exactly why the immune cells in cystic fibrosis show such changes,” says Nikolai Klymiuk, Professor of Cardiovascular Translation in Large Animal Models. “However, we can show that these occur early in life. They then persist in the further course of life.” According to Klymiuk, although altered immune cells were known from blood samples of adults with cystic fibrosis, they were seen as a consequence of the numerous infections.

“To enable people with cystic fibrosis to live without symptoms, we probably need to tackle the disease on several levels,” said Klymiuk. “We hope our work will help us better understand the causes of the defective immune system and correct them in the future”

Source: Technical University of Munich (TUM)

Researchers Discover New Strength-boosting Mechanism in Androgens

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Researchers at Leipzig University’s Faculty of Medicine and Shandong University in China have discovered a new mechanism that is used by a key androgen essential for muscle and bone function. The findings could lead to the development of new drugs with fewer side effects, for use in applications such as strengthening the muscles of immobile patients. The researchers have published their findings in the prestigious journal Cell.

The most powerful of the androgens is called 5α-dihydrotestosterone (5α-DHT). Among other things, it is essential for bone and muscle function and for the development of secondary male sexual characteristics during puberty. As a driver of bone and muscle formation, 5α-DHT increases bone mineral density and promotes skeletal muscle growth to increase muscle strength. 

In this international study, the scientists were able to show that one of the adhesion G protein- coupled receptors – GPR133 – is activated by the androgenic steroid hormone 5α-DHT.

“This activation can, among other things, increase the contractile force of skeletal muscles, and our study also uses a newly developed, potent activator of this receptor to specifically trigger this effect,” says Professor Ines Liebscher, Professor of Signal Transduction at Leipzig University and co-leader of the study.

Increasing muscle strength with the chance of significantly fewer negative effects of androgens

Activation of GPR133 by the novel agonist AP503 increases muscle strength without triggering a specific negative effect that is otherwise observed when androgens are administered. For example, increased and prolonged exposure to testosterone can promote the development of prostate cancer, as evidenced by tissue changes in the prostate in mice after only two weeks of androgen administration. This side effect has not yet been observed with AP503.

In addition, the current study uses structural biology methods to elucidate the molecular basis of the interaction between the steroid hormone, the substance AP503 and GPR133. This will allow the activator to be specifically optimised and further developed into a new therapeutic agent. This could lead to the development of new muscle-strengthening drugs with a lower side-effect profile.

This publication is the result of a long-standing and successful collaboration between the Rudolf Schönheimer Institute of Biochemistry and the research group of Professor Jin-Peng Sun at Shandong University in China. The researchers are currently working on several follow-up studies to further investigate the use of AP503 in disease processes and the role of GPR133 in the organism. Here the data were analysed in animal models. Further studies are needed to investigate the applicability of the findings to humans.

Source: Universität Leipzig

Born to Heal: Why Babies Recover, but Adults scar, After Heart Damage

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Newborns with heart complications can rely on their newly developed immune systems to regenerate cardiac tissues, but adults aren’t so lucky. After a heart attack, most adults struggle to regenerate healthy heart tissue, leading to scar-tissue buildup and, often, heart failure.

A new Northwestern Medicine study in experimental animals reveals a critical difference in how macrophages help repair the heart in newborns versus adults after a heart attack. The study highlights a fundamental difference in how the immune system drives healing based on age.

The study appears in the journal Immunity.

“Understanding why newborns can regenerate their hearts while adults cannot will open the door to developing treatments that could ‘reprogram’ adult macrophages,” said first and co-corresponding author Connor Lantz, lead scientist of the bioinformatics core at the Comprehensive Transplant Center at Northwestern University Feinberg School of Medicine.

In newborns, macrophages perform a process called efferocytosis, which recognizes and eats dying cells. This process triggers the production of a bioactive lipid called thromboxane, signaling nearby heart muscle cells to divide, and allowing the heart to regenerate damaged heart muscle, the study found. In adults, macrophages produce much less thromboxane, leading to a weaker repair signal.

“By mimicking the effects of thromboxane, we might one day improve tissue repair after a heart attack in adults,” Lantz said.

How the study worked

The study examined how the immune system responds to heart injury in mice of different ages, including newborn mice (one day old) and adult mice (eight weeks old). The researchers found the ability of macrophages to engulf dying cells was enhanced in newborn mice due to increased expression of MerTK, a receptor that recognizes dying cells. Therefore, when the scientists blocked this key receptor, newborn mice lost their ability to regenerate their hearts, resembling adult hearts after a heart attack.

Engulfment of dying cells by newborn macrophages triggered a chemical chain reaction that produced a molecule called thromboxane A2, which unexpectedly stimulated heart muscle cells to multiply and repair the damage, the study found. Additionally, nearby muscle heart cells in newborns are primed to respond to thromboxane A2, leading them to change their metabolism to support their growth and healing. But in adults, this process did not work the same way – after an injury, their macrophages did not produce enough thromboxane A2, limiting their ability to regenerate heart tissue.

Source: Northwestern University

Empathy for Other Peoples’ Pain Peaks in Young Adulthood

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Empathy responses to others in pain peak in young adulthood according to a new study led by Kent’s School of Psychology. Psychologists have discovered that young adults are especially sensitive to social pain, such as situations of embarrassment, grief and sadness, and empathise more strongly with others experiencing social pain than adolescents or older adults do.

Empathy is a critical component of social interaction that enables individuals to understand and share the emotions of others.

The research, published in the journal Social Cognitive and Affective Neuroscience, explored how empathy responses differ between adolescents (10-19 years old), young adults (20-40 years old) and older adults (60+ years old), by recording brain activity while participants viewed photographs of people in physically or socially painful situations. Findings showed that brain responses to painful situations increased from adolescence to young and older adulthood. This demonstrates that empathy responses develop throughout the lifespan as social experience and exposure to different social and pain-related situations increases.

While the research showed that people’s brain empathy responses get stronger as they age, the increased brain activity in older adults comes alongside reduced ratings of pain for others. Professor Heather Ferguson, lead researcher on the paper and Professor of Psychology at Kent, suggests that this is because older adults are less good at expressing empathy for others compared to young adults.

Professor Ferguson said: ‘This study provides valuable insights into the complex nature of empathic responses to others in pain. Empathy responses to others in pain peak in young adulthood, as seen in their behavioural ratings of pain intensity felt by others. However, the brain becomes increasingly reactive to seeing others in pain as we age, which suggests that older adults experienced empathy at the time of viewing the photographs of pain – but were less accurate later at rating the intensity of this pain.’

Source: University of Kent

Myth busted: Healthy Habits Take Longer than 21 Days to Set in

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Forming a healthy habit can take longer than you expect. In the first systematic review of its kind, University of South Australia researchers found that new habits can begin forming within about two months (median of 59-66 days) but can take up to 335 days to establish.

It’s an important finding that could inform health interventions to promote healthy behaviours and prevent chronic disease.

Many conditions, including type 2 diabetes, heart disease, lung diseases and stroke, can be prevented by changing unhealthy habits or lifestyle factors. University of South Australia researcher, Dr Ben Singh, says that contrary to popular belief, healthy habits take far longer than three weeks to lock down.

“Adopting healthy habits is essential for long-term well-being but forming these habits – and breaking unhealthy ones – can be challenging,” Dr Singh says.

“At the beginning of the year, many of us are setting goals and making plans for the months ahead –things like being more active, cutting back on sugar, or making healthier food choices – but while common wisdom suggests that it takes just 21 days to form such habits, these claims are not evidence-based.

“In our research, we’ve found that habit formation starts within around two months, but there is significant variability, with formation times ranging from four days to nearly a year.

“So, it’s important for people who are hoping to make healthier habits not to give up at that mythical three-week mark.”

The study of more than 2600 participants also found that certain factors can influence successful habit formation.

“When trying to establish a new healthy habit, success can be influenced by a range of things including how frequently we undertake the new activity, the timing of the practice, and whether we enjoy it or not,” Dr Singh says.

“If you add a new practice to your morning routine, the data shows that you’re more likely to achieve it. You’re also more likely to stick to a new habit if you enjoy it.

“Planning and intending to complete a new behaviour can also help solidify a new habit, so make sure you continue to make time to include your new healthy habits into your everyday activities. This could be as easy as laying out your gym clothes the night before a morning walk or having a healthy lunch ready to go in the fridge.

“Tailoring habit-building strategies into our day and making plans on how we can achieve them, will put you in a position for success.”

While more research is needed, researchers say that these findings can guide public health initiatives and personalised programs that support sustained and healthy behaviour change.

Source: University of South Australia