Month: August 2024

The Arms and Torso of Human Males Evolved to Throw a Punch

Photo by Hermes Rivera on Unsplash

In the animal kingdom, males develop specialised weapons such as deer antlers for competition when winning a fight is critical. Humans do too, according to new research from the University of Utah. Males’ upper bodies are built for more powerful punches than females’, says the study, published in the Journal of Experimental Biology, suggesting that fighting may have long been a part of our evolutionary history.

“In mammals in general,” says professor David Carrier of the School of Biological Sciences, “the difference between males and females is often greatest in the structures that are used as weapons.”

Assembling evidence

For years, Carrier has been exploring the hypothesis that generations of interpersonal male-male aggression long in the past have shaped structures in human bodies to specialise for success in fighting. Past work has shown that the proportions of the hand aren’t just for manual dexterity- they also protect the hand when it’s formed into a fist. Other studies looked at the strength of the bones of the face (as a likely target of a punch) and how our heels, planted on the ground, can confer additional upper body power.

“One of the predictions that comes out of those,” Carrier says, “is if we are specialised for punching, you might expect males to be particularly strong in the muscles that are associated with throwing a punch.”

Jeremy Morris, then a doctoral student and now an assistant professor at Wofford College, designed an experiment with Carrier, doctoral student Jenna Link and associate professor James C. Martin to explore the sexual dimorphism, or physical differences between men and women, of punching strength. It’s already known that males’ upper bodies, on average, have 75% more muscle mass and 90% more strength than females’. But it’s not known why.

“The general approach to understanding why sexual dimorphism evolves,” Morris says, “is to measure the actual differences in the muscles or the skeletons of males and females of a given species, and then look at the behaviours that might be driving those differences.”

Cranking through a punch

To avoid potential hand injury from a using punching bag, the researchers instead rigged up a hand crank that would mimic the motions of a punch. They also measured participants’ strength in pulling a line forward over their head, akin to the motion of throwing a spear. This tested an alternative hypothesis that males’ upper body strength may have developed for the purpose of throwing or spear hunting.

Twenty men and 19 women participated. “We had them fill out an activity questionnaire,” Morris says, “and they had to score in the ‘active’ range. So, we weren’t getting couch potatoes, we were getting people that were very fit and active.”

But even with roughly uniform levels of fitness, the males’ average power during a punching motion was 162% greater than females’, with the least-powerful man still stronger than the most powerful woman. Such a distinction between genders, Carrier says, develops with time and with purpose.

“It evolves slowly,” he says, “and this is a dramatic example of sexual dimorphism that’s consistent with males becoming more specialised for fighting, and males fighting in a particular way, which is throwing punches.”

They didn’t find the same magnitude of difference in overhead pulling strength, lending additional weight to the conclusion that males’ upper body strength is specialised for punching rather than throwing weapons.

Breaking a legacy of violence

It’s an uncomfortable thought to consider that men may be designed for fighting. That doesn’t mean, however, that men today are destined to live their ancestor’s violent lives.

“Human nature is also characterized by avoiding violence and finding ways to be cooperative and work together, to have empathy, to care for each other, right?” Carrier says. “There are two sides to who we are as a species. If our goal is to minimise all forms of violence in the future, then understanding our tendencies and what our nature really is, is going to help.”

Source: University of Utah

Each Gram of Sugar Dropped from a Diet Slows Biological Aging

Photo by Sharon Mccutcheon on Unsplash

Researchers at UC San Francisco have found a link between following a diet that is rich in vitamins and minerals, especially one without much added sugar, and having a younger biological age at the cellular level.

They looked at how three different measures of healthy eating affected an “epigenetic clock” – a biochemical test that can approximate both health and lifespan – and found that the better people ate, the younger their cells looked. Even when people ate healthy diets, each gram of added sugar they consumed was associated with an increase in their epigenetic age.

“The diets we examined align with existing recommendations for preventing disease and promoting health, and they highlight the potency of antioxidant and anti-inflammatory nutrients in particular,” said Dorothy Chiu, PhD, a postdoctoral scholar at the UCSF Osher Center for Integrative Health and first author of the study, appearing in JAMA Network Open. “From a lifestyle medicine standpoint, it is empowering to see how heeding these recommendations may promote a younger cellular age relative to chronological age.”

The study is one of the first to show a link between added sugar and epigenetic aging, and the first to examine this link in a heterogenous group of women – both Black and white – in midlife. Most studies on the topic have involved older white participants.

The study helps deepen our understanding of why sugar is so detrimental to health, said study co-senior author Elissa Epel, PhD, a UCSF professor in the Department of Psychiatry and Behavioral Sciences.

“We knew that high levels of added sugars are linked to worsened metabolic health and early disease, possibly more than any other dietary factor,” Epel said. “Now we know that accelerated epigenetic aging is underlying this relationship, and this is likely one of many ways that excessive sugar intake limits healthy longevity.”

Women in the study reported consuming an average of 61.5 grams of added sugar per day, though the range was large: from 2.7 to 316 grams of added sugar daily. A bar of milk chocolate has about 25 grams of added sugar, while a can of cola has about 39 grams. The US Food and Drug Administration recommends adults consume no more than 50 grams of added sugar per day.

A nutrient-based approach

For the cross-sectional study, researchers analysed food records from 342 Black and white women with a mean age of 39 years from Northern California. Then, they compared their diets with epigenetic clock measures, which were derived from saliva samples.

Researchers scored the women’s diets to see how they compared to a Mediterranean-style diet rich in anti-inflammatory and antioxidant foods and then to a diet linked to lower risk for chronic disease.

Finally, they scored the women’s diets against a measure they created called the “Epigenetic Nutrient Index (ENI),” which is based on nutrients (not foods) that have been linked to anti-oxidative or anti-inflammatory processes and DNA maintenance and repair. These include Vitamins A, C, B12 and E, folate, selenium, magnesium, dietary fibre and isoflavones.

Adherence to any of the diets was significantly associated with lower epigenetic age, with the Mediterranean diet having the strongest association.

The researchers examined sugar intake separately and found that consuming foods with added sugar was associated with accelerated biological aging, even in the presence of an otherwise healthy diet.

“Given that epigenetic patterns appear to be reversible, it may be that eliminating 10 grams of added sugar per day is akin to turning back the biological clock by 2.4 months, if sustained over time,” said co-senior author Barbara Laraia, PhD, RD, a UC Berkeley professor in the Food, Nutrition and Population Health program. “Focusing on foods that are high in key nutrients and low in added sugars may be a new way to help motivate people to eat well for longevity.”

Source: University of California San Francisco

Transforming South Africa’s Healthcare Sector: The Essential Role of Leadership

Dr Ali Hamdulay

By Dr Ali Hamdulay – CEO, Metropolitan Health Corporate

South Africa’s healthcare sector, a sophisticated and ever-changing industry, is central to the health and prosperity of our communities. Its effective operation, however, hinges on the strength and direction of its leadership.

Leadership, given the broad healthcare landscape, is far from a singular role; it’s a complex undertaking that requires comprehensive understanding of the wide medical ambit, the regulatory environment, compassion, and a forward-thinking mindset. Leaders are the primary builders of healthcare infrastructure, moulding it to encourage innovation, prioritise patient-focused care, and maintain the highest ethical standards.

Attracting and retaining skilled healthcare workers is a critical role that leadership in South Africa’s healthcare landscape must play. This includes attracting and retaining a diverse range of healthcare professionals such as doctors, nurses, and specialists. Leaders are responsible for creating a conducive work environment that not only draws in skilled workers but also motivates them to stay and thrive. Furthermore, leaders are advocates for healthcare workers, ensuring they have the necessary resources and support to carry out their roles effectively.

The rise of technology has ushered in substantial shifts in the healthcare sector. From telemedicine and AI diagnostics to electronic health records, technology has revolutionised how we provide care. Integrating these innovations into the healthcare system, though, is a challenging task that demands visionary leadership.

Leaders must understand these technologies, evaluate their potential advantages and risks, and oversee their implementation in a manner that enhances patient care without jeopardising privacy and security. Teams must also be equipped with the necessary skills to adapt to these changes and effectively implement new procedures.

A pivotal role of a healthcare leader is to champion health equity. Despite progress in healthcare, disparities in access and outcomes remain. Leaders play a crucial role in creating pathways to eradicate these disparities and to ensure that everyone, irrespective of their background, has access to quality healthcare. This involves understanding the social determinants of health, implementing policies that promote equity, and establishing an inclusive and respectful culture within the healthcare environment.

This cannot be done without support.

Leadership isn’t solely about leading; it’s also about inspiring others to lead. By exemplifying excellence and integrity, leaders can inspire their teams to aspire to the same standards. They can cultivate a culture of continuous learning and improvement, encouraging everyone to contribute their ideas and expertise.

A resilient healthcare system is anchored by robust leadership. It requires a mix of knowledge, skills and attitudes, a thorough understanding of the healthcare landscape, the ability to make critical decisions, the vision to embrace innovation, the empathy to advocate for health equity, and the charisma to inspire others.

We must elevate both individual and group thinking within our operating environments if we are to make meaningful progress in establishing a healthcare sector that prioritises access and quality. This approach contributes to a resilient healthcare workforce—one that can adapt to the dynamic landscape and is essential for the sector’s long-term viability and the overall health of South Africa’s population. By embracing this combination of collective and individual thinking, we propel the sector forward across businesses, the healthcare industry, and the nation as a whole.

Navigating the intricacies of the healthcare sector, particularly in the dawn of South Africa’s Government of National Unity, underscores the critical role of strong and reliable leadership. This fresh political landscape brings with it a wave of optimism. It has the potential to catalyse transformative change in our healthcare sector, from policy reforms and resource reallocation to the introduction of initiatives aimed at enhancing healthcare quality.

In our journey towards a more equitable and efficient healthcare system in South Africa, the focus on public-private partnerships must remain steadfast. These partnerships are instrumental in leveraging the strengths of both sectors to deliver better healthcare outcomes. They foster innovation, improve service delivery, and enhance accessibility, making them a crucial component of a robust healthcare system.

During this era of change, leadership is our compass guiding us towards quality access to healthcare for all. The role of leadership in ensuring progress and maintaining stability cannot be overstated. It is the driving force behind a healthcare sector that truly serves its people.

The future of South Africa’s healthcare sector is promising, but it requires the collective effort of all stakeholders. As a business, we recognise the critical role of nurturing our emerging leaders through mentoring and coaching. Our partnerships ensure continuity and preserve the essential skill and knowledge base of our healthcare workforce. These partnerships are key in establishing a healthcare system that is accessible to all and provides quality care.

As we commemorate Nelson Mandela Day, let us honour his unwavering commitment to justice, equality, and compassion. Our responsibility lies not only in the present but also in shaping a legacy for future generations. Let us build a healthcare system that echoes Mandela’s vision—a system that ensures access for all and equips our leaders to carry forth their roles with purpose and resilience.

Body Appreciation Varies Across Cultures

Body appreciation levels are associated with internalisation of thin ideals and with sociocultural pressure, which vary by culture and age

Photo by I Yunmai on Unsplash

People from different cultures show both similarities and differences in how body appreciation, sociocultural pressure, and internalisation of thin ideals vary, according to a study published July 31, 2024 in the open-access journal PLOS ONE by Louise Hanson from Durham University, UK, and colleagues.

Body image is a multifaceted and complex phenomenon encapsulating how we think, behave, and feel about our body. To date, most body image research has focused on young, White, Western women, and has focused on negative rather than positive body image.

By contrast, Hanson and colleagues examined body appreciation, encapsulating positive thoughts and feelings regarding one’s own body. They also included participants not only from Western countries (ie, Australia, Canada, United Kingdom, United States of America), but also China and Nigeria. A final sample of 1186 women completed the questionnaires and were included in the analysis.

The results did not reveal significant difference in body satisfaction between women of different ages, but there was significant variation between cultures. Black Nigerian women had the highest body appreciation, followed by Eastern Asian Chinese women, with White Western women reporting lowest body appreciation. The findings suggest that ethnicity and culture are important influences on body appreciation and might act as protective factors that promote positive body image.

High internalisation of the thin ideal, and high perceived pressure about appearance from family, peers, and the media, were associated with lower body appreciation. Internalisation varied by age in some cultures: older White Western and Black Nigerian women reported lower thin-ideal internalisation than younger women, but Chinese women experienced the same thin-ideal internalisation across the lifespan.

For women from all cultures, older women reported lower perceived sociocultural pressure than younger women. White Western women experienced more perceived pressure from the media than Black Nigerian and Chinese women, but Chinese women reported the most pressure from peers. The results also showed that Black Nigerian women reported the lowest sociocultural pressure overall, and that Chinese women reported the most pressure.

The authors suggest that future studies should include more women in older age groups to obtain a fully representative picture of women’s body appreciation across the lifespan. In addition, further development of measurement tools is necessary for future research in cross-cultural contexts. According to the authors, the results of the current study could be used to target positive body image interventions to each culture. Further research may be required to develop effective interventions for each group.

The authors add: “We found that body appreciation was relatively stable across all ages and sociocultural pressure was evident in all cultures. However, the extent to which this pressure was experienced and where it came from differed across cultures.”

Provided by PLOS

Zero HIV Infections in Trial of New Twice-yearly Prophylaxis

Photo by Miguel Á. Padriñán

Finalised data published in the New England Journal of Medicine, has confirmed the stunning results of a trial in which a twice-yearly dose of lenacapavir completely prevented HIV infection in a group of adolescent girls and women in South Africa and Uganda.

A major challenge with HIV prophylaxis with cisgender women is adherence and persistence with daily oral regimens. The twice-yearly subcutaneous injection of lenacapavir helps to circumvent these problems by offering extended protection.

Based on the initial results announced by Gilead Sciences on the 20th of June, the PURPOSE 1 phase 3 clinical trial met its key efficacy endpoints of superiority of twice-yearly lenacapavir to once-daily oral (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) and background HIV incidence. Given the strength of these results, the blinded phase of the trial was halted and open-label lenacapavir was offered to all participants.

The double-blind, randomised, controlled trial recruited 5338 participants who were initially HIV-negative. They were randomised 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral F/TDF (active control); all participants also received the alternate subcutaneous or oral placebo. They compared the efficacy of lenacapavir and F/TAF with F/TDF against the estimated background incidence of HIV infection.

Among the 2134 participants in the lenacapavir group, there were 0 infections (0 per 100 person-years). Meanwhile in the F/TAF group, there were 39 infections among 2136 participants (2.02 per 100 person-years) and 16 infections among the F/TDF group’s 1068 participants (1.69 per 100 person-years).

HIV incidence with lenacapavir was significantly lower than background HIV incidence and than HIV incidence with F/TDF. HIV incidence with F/TAF did not differ significantly from background HIV incidence, and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF.

The researchers did note that adherence to F/TAF and F/TDF was low. While no safety concerns were found, injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions.

US Fast-Tracks a Promising New Therapy for Metastatic Prostate Cancer

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

The US Food and Drug Administration (FDA) has granted Fast Track designation for SYNC-T SV-102 therapy for the treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC). SV-102 is part of Syncromune Inc.’s SYNC-T platform, an in situ personalised therapy that uses a combination multi-target approach to cancer treatment, aiming to improve outcomes and quality of life for patients.

The Fast Track designation was granted based on the potential of SYNC-T SV-102 therapy to address the significant unmet need in treating patients with mCRPC. This advanced form of prostate cancer affects over 40 000 men in the US alone and is associated with a very poor prognosis. The Fast Track process is designed to facilitate the development and expedite the review of therapies that treat serious conditions and fulfil an unmet medical need, with the goal of getting important new treatments to patients sooner. Fast Track designation provides Syncromune with several key benefits, including more frequent FDA interactions, eligibility for accelerated approval, and priority review.

“The Fast-Track designation for SYNC-T SV-102 therapy signifies another step forward in bringing our potentially groundbreaking therapy to patients who need it most,” said Eamonn Hobbs, Chief Executive Officer and co-founder of Syncromune. “This accomplishment builds upon the foundation of positive Phase 1 clinical data and recent IND clearance.”

Syncromune’s lead candidate, SYNC-T SV-102, is a platform therapy that combines an in situ vaccine via partial oncolysis of a tumour followed by intratumoural infusion of the SV-102 fixed-dose multi-target biologic drug into the lysed tumour. This combination is designed to provide both immune stimulation and block immune suppression to activate and proliferate T cells to elicit a systemic anti-tumour response. Interim data from a Phase 1 study of SV-102 in males with mCRPC demonstrated an overall response rate of 85% with a favourable safety profile and tolerability. The Fast-Track designation comes on the heels of clearance of the company’s investigational new drug (IND) application, with studies expected to begin in the US this year.

Charles Link, M.D., Executive Chairman of Syncromune added, “We believe that Fast-Track designation for SYNC-T SV-102 will significantly aid our development goals for this therapy for men with difficult to treat prostate cancer. We look forward to initiating trials at multiple US sites later this year to expand our efforts to develop the SYNC-T SV-102 Therapy.”

Source: Syncromune

Study Uncovers Connections Between Obesity and Heart Failure at the Cellular Level

Right side heart failure. Credit: Scientific Animations CC4.0

A new small study led by Johns Hopkins Medicine researchers recently published in the journal Nature Cardiovascular Research has revealed the impact of obesity on muscle structure in patients having a form of heart failure called heart failure with a preserved ejection fraction (HFpEF). They observed swollen mitochondria, lipid droplets and tattered muscle fibre bundles, all independent of diabetes status.

According to the Journal of Cardiac Failure, HFpEF represents more than half of all heart failure world-wide. Originally, this form of heart disease was associated with hypertension and along with this, excess muscle growth (hypertrophy) to help counter the pressures. Over the past two decades, HFpEF is occurring more often in patients with severe obesity and diabetes according to the Journal of the American College of Cardiology. However, there are still very few effective HFpEF therapies, and a challenge in developing therapies has been the lack of studies in human heart tissue to determine exactly what is abnormal. As hospitalisation and death rates in HFpEF patients are quite high, (30–40% over 5 years), understanding its underlying causes is critical.  

“HFpEF is a complex syndrome, involving abnormalities in many different organs”, says lead investigator David Kass, MD, Professor of Medicine at the Johns Hopkins University School of Medicine. “We call it heart failure (HF) because its symptoms are similar to those found in patients with hearts that are weak. However, with HFpEF, heart contraction seems fine, yet heart failure symptoms still exist. While many prior efforts to treat HFpEF using standard HF drugs have not worked, success has since come from drugs used to treat diabetes and obesity.”

More specifically, the drug used to treat diabetes, known as an SGLT2 inhibitor (sodium glucose transporter 2 inhibitor) is currently the only evidence-based drug for HFpEF that has improved not only its symptoms but also reduced long-term rehospitalisation rates and endpoints of mortality. The weight loss drug GLP1-receptor agonist has been tested and found to improve symptoms in patients with HFpEF, and ongoing studies are determining if a similar hard end-point (mortality reduction, hospitalisation for HF reduction) are also possible outcomes. As such, these drugs have already been shown to be effective not only in diabetes where they started, but also in HFpEF.

To perform the study, the research team obtained a small piece of muscle tissue from 25 patients who had been diagnosed with varying degrees of HFpEF caused by diabetes and obesity and compared them to heart tissue from 14 organ donors whose hearts were considered to be normal. They examined the muscle using an electron microscope that shows muscle structure at a very high magnification.  

Mariam Meddeb, MD, MS, cardiovascular disease specialist at the Johns Hopkins University School of Medicine, who conducted the study says that a scanning electron micrograph “provides a very clear picture inside the muscle cell, what we call ultrastructure, such as mitochondria that are the energy power plants, and sarcomeres (unit of muscle fibre) that generate force”.

The researchers found notable ultrastructural abnormalities were particularly present in tissue of the most obese patients who had HEpEF, which had mitochondria that were swollen, pale, and disrupted, had many fat droplets, and their sarcomeres appeared tattered. These abnormalities were not related to whether the patient had diabetes, and were less prominent in patients who were less obese.

“These results will help those trying to develop animal models of HFpEF, since they show what one wants to generate at this microscopic level,” notes Dr Kass. “It also raises the key question of whether reducing obesity, as is now being done with several drug therapies, will reverse these ultrastructural abnormalities, and in turn improve HFpEF outcome.”  

Source: John Hopkins Medicine

Climate Anomalies may Play a Major Role in Driving Cholera Pandemics

Global climate change could create more opportunities for rise and spread of new cholera strains

Scanning electron micrograph image of cholera bacteria.

New research suggests that an El Niño event may have aided the establishment and spread of a novel cholera strain during an early 20th-century pandemic, supporting the idea that climate anomalies could create opportunities for the emergence of new cholera strains. Xavier Rodo of Instituto de Salud Global de Barcelona, Spain, and colleagues present these findings in the open-access journal PLOS Neglected Tropical Diseases.

Since 1961, more than 1 million people worldwide have died in an ongoing cholera pandemic, the seventh cholera pandemic to have occurred since 1817. The drivers of past cholera pandemics have been unclear, but one hypothesis holds that anomalous climate conditions may act synergistically with genetic changes of Vibrio cholerae—the bacterium that causes the disease—to facilitate the spread and dominance of new strains.

To help clarify potential links between climate and cholera, Rodo and colleagues applied a variety of statistical and computational tools to historical records of climate conditions and cholera deaths in various regions of former British India during the sixth cholera pandemic, which lasted from 1899 to 1923. They also compared past conditions with climate and cholera data for the ongoing pandemic.

This analysis revealed that anomalous patterns of cholera deaths from 1904 to 1907 occurred alongside out-of-the-ordinary seasonal temperatures and rainfall levels associated with an El Niño event; the timing of these occurrences correlates with the establishment of a new invasive strain during the sixth pandemic. In addition, these historical climate conditions show similarities to strong El Niño events that have been associated with cholera strain changes during the ongoing pandemic.

These findings support the possibility that anomalous climate events could help facilitate the establishment and spread of new cholera strains.

The researchers then explored future possibilities for climate-facilitated emergence of new cholera strains using standard climate prediction models. They found that climate change-driven increases in climate variability and extremes could boost the chances of emergence of novel strains through the end of the current century.

Meanwhile, to deepen understanding of this deadly disease, the scientists call for further research focused on the interplay of cholera evolution and climate anomalies.

Dr Rodó and co-author Dr Mercedes Pascual summarise: “Variation in climate conditions or the evolutionary change of a pathogen can be important drivers of major epidemics and pandemics. But these two drivers are typically considered separately in studies seeking to explain the emergence of unusually large outbreaks…here, we present indirect evidence that the two can act together to synergistically underlie the establishment and widespread transmission of a new strain.”

Provided by PLOS

Surprising Finding in Glioblastomas: Islands of Potent Immune Cells in Bone Marrow

Photo by Anna Shvets

Researchers from Germany have made a surprising discovery about the aggressive, lethal glioblastomas: in the vicinity of glioblastomas, they found islands of highly potent immune cells in the neighbouring bone marrow of the skull, which play a central role in defending against cancer. The new data may open up prospects for innovative therapies. On the other hand, they cast a shadow over conventional strategies.

“What we have found is surprising and fundamentally new,” says Björn Scheffler, German Cancer Consortium (DKTK) researcher at the Essen site. Until now, the body’s own defences have always been thought of as a holistic system that sends its troops to different parts of the body as required. “However,” says Scheffler, “our data show that highly potent immune cells gather in regional bone marrow niches close to the tumour and organise the defence from there. At least this is the case with glioblastomas.”

Immune system on site

Based on new findings from animal experiments, the Essen team took tissue samples from the bone marrow near the tumor in the skull from untreated patients with glioblastoma. “However, the methods for this first had to be established,” reports first author Celia Dobersalske, emphasizing the fact that the new research results were obtained from human tissue samples.

The researchers hit the bull’s eye in their search: Bone marrow niches in close proximity to the glioblastoma appear to be the reservoir from which the anti-tumour defence is recruited. Apart from active lymphoid stem cells that develop into immune cells, the researchers also found mature cytotoxic T lymphocytes (CD8 cells) in the bone marrow close to the tumour. “These are highly effective immune cells that play a central role in the defence against cancer,” adds Celia Dobersalske. They can recognize and destroy malignant cells.

The CD8 cells in the bone marrow near the tumour had an increased number of receptors on their surface, which control the proliferation of mature T lymphocytes. In line with this, descendants of the same cell clones – one clone originates from one and the same cell – were detected both in the bone marrow and in the tumour tissue. This is clear evidence that the immune cells gathered on site are fighting the glioblastoma. “And they are successful – at least for a while,” says Björn Scheffler. “We were able to show that the course of the disease correlates with the activity of the local CD8 cells.”

Valuable immune cells destroyed?

This finding not only turns conventional ideas about how the immune system works on their head. The treatment concepts for glioblastoma must also be reconsidered in light of the new data. “Until now, we hadn’t even considered the skullcap in our considerations. How could we, since there was no evidence that highly potent immune cells could be hiding there,” says senior author Scheffler.

“When we opened the skull, we may have destroyed important immune cells in the process,” confirms Ulrich Sure, Director of the Department of Neurosurgery and member of the Essen research team. “In view of the new findings, we find ourselves in a dilemma: we have to gain access to the tumour in order to remove it and also to be able to confirm the diagnosis. There is currently no other way than through the skull. But we are thinking about how we can minimise damage to the local bone marrow in the future.”

On the other hand, the discovery of the local immune system opens up opportunities for innovative therapies. In particular, so-called checkpoint inhibitors are coming back into play. These are immunotherapeutic agents that aim to boost the body’s own cancer defenses. However, checkpoint inhibitors tested to date have shown little effect on glioblastomas.

“Various explanations have been suggested as an explanation, but perhaps we also need to rethink things in this respect,” says Björn Scheffler. “We now know that highly potent immune cells are indeed present on site. We were able to prove that they are fit to fight tumours, but they are not capable of destroying the tumour on their own. This is where we can start. One challenge will be to deliver drugs in sufficient concentration to the regional bone marrow niches at the right time. If we succeed, we may have a chance of controlling the growth of glioblastomas and improving our patients’ chances of survival.”

Source: German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

‘Push to Failure’ Works for Bigger Muscles, but not Strength

Photo by Jonathan Borba on Unsplash

When performing resistance training such as lifting weights, there’s a lot of interest in how close you push yourself to failure – the point where you can’t do another rep – and how it affects your results. While research has looked at this concept in different ways, to date, no meta-analysis has explored the pattern (ie, linear or non-linear) of how the distance from failure (measured by repetitions in reserve) affects changes in muscle strength and size.

As such, it’s still unclear how close to failure one needs to go to maximise muscle growth and strength.

Researchers from Florida Atlantic University and collaborators analyzed how training close to failure or not impacts muscle growth and strength. The study primarily looked at how training close to failure affects muscle growth in the main muscles used in an exercise. For example, if an individual was doing leg presses, the focus was on how training close to failure affects the quadriceps.

Researchers estimated the number of repetitions in reserve, which means how many more reps you could have done before reaching failure. They collected data from 55 various studies and ran detailed statistical analyses to see how different reps in reserve levels affected strength and muscle growth.

Results of the study, published in the journal Sports Medicine, found that how close you train to failure doesn’t have a clear impact on strength gains. Whether you stop far from failure or very close to it, your strength improvement appears to be similar. On the other hand, muscle size (hypertrophy) does seem to benefit from training closer to failure. The closer you are to failure when you stop your sets, the more muscle growth you tend to see.

“If you’re aiming for muscle growth, training closer to failure might be more effective. In other words, it doesn’t matter if you adjust training volume by changing sets or reps; the relationship between how close you train to failure and muscle growth remains the same,” said Michael C. Zourdos, Ph.D., senior author and professor and chair of the Department of Exercise Science and Health Promotion within FAU’s Charles E. Schmidt College of Science. “For strength, how close you push to failure doesn’t seem to matter as much.”

The researchers suggest that individuals who aim to build muscle should work within a desired range of 0-5 reps short of failure for optimized muscle growth or while minimizing injury risk. For strength training, they suggest individuals should work toward heavier loads instead of pushing their muscles to failure. As such, they recommend that to train to gain strength, individuals should stop about 3-5 reps short of failure without applying additional physical strain on the body.

“Training closer to failure enhances the accuracy of self-reported repetitions in reserve,” said Zac P. Robinson, Ph.D., first author and a Ph.D. graduate of FAU’s Department of Exercise Science and Health Promotion. “When people estimate how many reps they have left, this perception influences the weights they choose. If the estimation is off, they might use lighter weights than needed, which could limit strength gains. On the flip side, our meta-analysis shows that training closer to failure also leads to greater muscle growth. So, for the average individual, training close to failure may be the best option – as it seems to improve the accuracy of our perception of effort as well as gains in muscle size.”

Findings help underscore the difficulties of training close to failure, which can be tough and harder to recover from, potentially impacting long-term performance negatively. In addition, the researchers say that training closer to failure might better simulate the conditions and experiences of a maximal strength test, commonly used in strength training programs, rehabilitation and athletic performance assessments to gauge an individual’s strength capabilities and track progress over time. 

“As the load increases, motor patterns change, which means performing sets closer to failure can more closely mimic the demands of max strength assessments,” said Zourdos. “This approach aligns with the principle of specificity by exposing you to similar motor patterns and psychological challenges. Moreover, training near failure may also improve psychological factors like visualisation, which are important for achieving maximal strength.”

Results from the study could help guide future research and provide valuable insights for trainers on how proximity to failure affects muscle growth and strength. However, researchers say the exact numerical relationship between training close to failure and strength gain remains unclear and future studies should be deliberately designed to explore the continuous nature of the effects in larger samples. 

Source: Florida Atlantic University