Day: September 11, 2024

Concussions in Amateur Sport not Linked to Long-term Cognitive Effects

Photo by Olga Guryanova on Unsplash

The impact of concussion while playing sport is different in those who don’t play professionally, says new research.

Sports-related concussions (SRC) may not be associated with long-term cognitive risks for non-professional athletes, a study led by a UNSW medical researcher suggests. In fact, study participants who had experienced an SRC had better cognitive performance in some areas than those who had never suffered a concussion, pointing to potential protective effects of sports participation.

Published in the Journal of Neurology, Neurosurgery and Psychiatry, the research reveals that individuals who reported experiencing any SRC during their lifetime had a marginally better cognitive performance than those who reported no concussions.

The study, a collaboration between researchers at UNSW Sydney, the University of Oxford, the University of Exeter and Harvard University, analysed data from more than 15 000 participants from the UK-based PROTECT study of 50- to 90-year-olds. This ongoing research aims to understand brain ageing and cognitive decline.

“Our findings suggest that there is something about playing sport, even though a person may experience concussion, that may be beneficial for long-term cognitive outcomes,” says lead author Dr Matt Lennon MD, PhD, at UNSW Medicine & Health.

“While it may be that those who play sports have had access to better education and more resources, we controlled for these factors in the analysis, so that doesn’t explain the result. We hypothesise that there may be physical, social and long-term behavioural effects of sport that may make for healthier adults in late-life,” said Dr Lennon.

Largest study of long-term effects of sports concussions

The study is the largest to date examining the long-term cognitive effects of SRC. Researchers collected lifetime concussion histories from 15 214 participants using the Brain Injury Screening Questionnaire. Among them, 6227 (39.5%) reported at least one concussion and 510 (3.2%) at least one moderate-severe concussion. On average, participants reported suffering their last head injury an average of 29 years prior to the study and their first head injury an average of 39 years earlier.

Researchers then compared cognitive function among individuals with 0, 1, 2 and 3+ SRCs and 0, 1, 2 and 3+ non-sports-related concussions (nSRCs)  (i.e. from falls, car accidents, assaults and other causes). The SRC group showed 4.5 percentile rank better working memory than those who hadn’t experienced an SRC, and 7.9% better reasoning capacity than those without concussions.

Those with one SRC also had better verbal reasoning and attention compared to those with no SRC.

Conversely, participants with 3+ nSRCs – so things like accident and assaults – had worse processing speed and attention, and a declining trajectory of verbal reasoning with age.

“This study suggests that there could be long term benefits from sport which could outweigh any negative effects of concussions, which could have important implications for policy decisions around contact sport participation. It may also be that non-sports related head injuries lead to greater brain damage than sports-related concussions,” said senior author Professor Vanessa Raymont from the University of Oxford and Oxford Health NHS Foundation Trust.

The researchers say the study had some limitations.

“The retrospective design of the study, with elderly participants often recalling details of events over three decades in the past, may have affected the reporting of head injuries, even though we used a well-validated head injury screening tool,” said Prof. Raymont.

Study implications

The study looked at mid-to-late-life people who experienced SRC years earlier, whereas most other studies on SRC focus on younger athletes in the immediate period after their head injuries, where cognitive effects are most salient.

“While these results do not indicate the safety of any sport in particular, they do indicate that overall sports may have greater beneficial effects for long-term cognitive health than the damage it causes, even in those who have experienced concussion,” said Dr Lennon.

“This finding should not be overstated – the beneficial effects were small and in people who had two or more sports-related concussions there was no longer any benefit to concussion. Additionally, this study does not apply to concussions in professional athletes whose head injuries tend to be more frequent, debilitating and severe.”

Anne Corbett, Professor at Exeter University and the lead investigator of the PROTECT study, said: “What we see emerging is a completely different profile of brain health outcomes for people who have concussions as a result of sport compared to those that are not related to sport. Concussions that occur during sport do not lead to brain health concerns whereas other concussion types do, especially when people experience multiple concussions. In fact, people who take part in sport seem to have better brain health regardless of whether they have had a concussion whilst taking part or not.”

Source: University of New South Wales

Common Skin Fungus Malassezia may Invade Tissue, Causing Breast Cancer

Photo by National Cancer Institute on Unsplash

A common skin fungus, Malassezia globosa may invade deep tissues through the skin or by other means, then cause tumour growth, according to a new study. The study results appear in mBio, an open access journal of the American Society for Microbiology.

“It is important to take care of skin not only for beauty, but also for health,” said corresponding study author Qi-Ming Wang, PhD, a professor in the School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Hebei, China. “As a factor promoting tumour growth, intertumoural microorganisms need to be paid more attention.” 

Recently, an increasing number of studies have shown a relationship between fungus and cancer. In the new study, Wang and colleagues subjected mouse breast cancer cells to tumour transplantation and then injected the M. globosa into the mammary gland fat pad. At the end of the experiment, they collected the tumour tissue to measure the tumour size and observe the content of intertumoral M. globosa. The researchers discovered that M. globosa colonises in breast fat pads leading to tumour growth. As a lipophilic yeast, the breast fat pad may provide an external source of lipids for the development of M. globosa, said the researchers. They also found that the pro-inflammatory cytokine interleukin (IL)-17a/macrophage axis plays a key role in mechanisms involved in M. globosa-induced breast cancer acceleration from the tumour immune microenvironment perspective.

“Although still controversial, the relationship between microbes and cancer is gaining attention. The imbalance of the microflora in the tumour may lead to disorder in the tumour microenvironment,” Wang said. “For example, Helicobacter pylori emerged as a potential cause of gastric cancer. In addition, Fusobacterium nucleatum has been identified as a potential colorectal cancer biomarker in stool and is predominantly found in the tumour microenvironment. Bacteria or fungi may play a direct (eg, toxins) or indirect (eg, inhibition of anti-tumoural immune responses) role in the tumorigenesis pathways of many of these risk factors. The imbalance of microbial homeostasis in tumours has a certain significance for cancer diagnosis, treatment and prognosis.” 

According to Wang, although the researchers found that M. globosa can promote the growth of tumours, the related transmission route is still unclear. 

Source: American Society for Microbiology

Scars of Destroyed Brain Tumours are Fertile Grounds for Recurrence

Types of tumour cells. Credit: Scientific Animations CC4.0

A Ludwig Cancer Research study has discovered that recurrent tumours of the aggressive brain cancer glioblastoma multiforme (GBM) grow out of the fibrous scars of malignant predecessors destroyed by interventions such as radiotherapy, surgery and immunotherapy.

Led by Ludwig Lausanne’s Johanna Joyce, Spencer Watson and alumnus Anoek Zomer and published in the current issue of Cancer Cell, the study describes how these scars enable the regrowth of tumours and identifies drug targets to sabotage their malignant support. It also demonstrates the efficacy of such combination therapies in preclinical trials using mouse models of GBM.

“We’ve identified fibrotic scarring as a key source of GBM resurgence following therapy, showing how it creates a protective niche for the regrowth of the tumor,” said Joyce. “Our findings suggest that blocking the process of scarring in the brain by adding anti-fibrosis agents to current treatment strategies could help prevent glioblastoma from recurring and improve the outcomes of therapy.”

There is a great need for such interventions. GBM is the most common and aggressive form of brain cancer in adults. Despite considerable effort to develop effective therapies for the cancer, the average life expectancy of patients remains around 14 months following diagnosis.

The origins of the current study date back to 2016, when the Joyce lab reported in the journal Science its examination in mouse models of strategies to overcome resistance to a promising immunotherapy for the treatment of GBM. That experimental therapy, which inhibits signalling by the colony stimulating factor-1 receptor (CSF-1R) and currently in clinical trials, targets immune cells known as macrophages and their brain-resident versions, microglia, both of which are manipulated by GBM cells to support tumour growth and survival.

The Joyce lab has demonstrated that CSF-1R inhibition reprograms these immune cells into an anti-tumour state and so induces significant tumour regression. Yet, as the Science study showed, about half the mice show relapse following an initial response to the therapy. “What was most remarkable about that observation was that every single time a brain tumour recurred following immunotherapy, it regrew right next to a scar that had formed at the original site of a tumour,” said Joyce.

In the current study, Joyce, Watson, Zomer and their colleagues examined tumour samples obtained from patients undergoing GBM therapy and showed that fibrotic scarring occurs following therapy in humans as well – and that it is similarly associated with tumour recurrence. They also showed that the fibrotic scarring occurs in response to not only immunotherapy but also following the surgical and radiological removal of tumours.

To explore how fibrosis contributes to relapse, the researchers applied an integrated suite of advanced technologies to analyze the cellular and molecular geography of the scars and the microenvironment of resurgent tumors.

These technologies include the analysis of global gene expression in individual cells, the comprehensive analysis of proteins in the tissues as well a workflow and AI-powered suite of analytical methods for the spatial analysis of tissues named hyperplexed immunofluorescence imaging (HIFI). Recently developed by Watson and colleagues in the Joyce lab, HIFI permits the simultaneous visualisation of multiple molecular markers in and around cells across broad cross-sections of tissues, enabling the generation of granular maps of the tumour microenvironment.

“Applied together, these advanced methods allowed us to see exactly how fibrotic scars form,” said Watson. “They revealed that the fibrosis serves as a kind of protective cocoon for residual cancer cells and pushes them into a dormant state in which they are largely resistant to therapy. We found that it also shields them from surveillance and elimination by the immune system.”

Integrated analyses of the tissue microenvironment following therapy revealed that the descendants of cells associated with tumor-feeding blood vessels become functionally altered to resemble fibroblasts—fiber-producing cells commonly involved in wound-healing. These perivascular-derived fibroblast-like (PDFL) cells fan out across the region previously occupied by the regressing tumor, where they mediate the generation of fibrotic scars. These cells, the researchers found, are especially activated by neuroinflammation and immune factors known as cytokines, most notably one called transforming growth factor-β (TGF-β).

“To see if targeting fibrotic scarring could improve therapeutic outcomes for GBM, we devised a treatment regimen using existing drugs to block TGF-β signaling and suppress neuroinflammation in combination with CSF-1R inhibition and evaluated it in preclinical trials using mouse models of GBM,” said Joyce. “We also timed these additional treatments to coincide with the period of maximal PDFL activation identified by our studies. Our results show that the drug combination inhibited fibrotic scarring, diminished the numbers of surviving tumor cells and extended the survival of treated mice compared to controls.”

The researchers suggest that approaches to limit fibrotic scarring could significantly improve outcomes for GBM patients receiving surgical, radiation or macrophage-targeting therapies. Additional research, they note, will likely yield even better drug targets for such combination therapies.

Source: Ludwig Institute for Cancer Research

Does Cognitive Behavioural Therapy Benefit Cancer Survivors?

Photo by Tima Miroshnichenko on Pexels

A recent analysis of all relevant published studies reveals clear benefits of Cognitive Behavioural Therapy (CBT) for improving mental health and quality of life in cancer survivors. The findings, which are published in Cancer Medicine, extend CBT’s effects beyond what has long been known in the general population.

For the analysis, investigators uncovered 132 clinical trials comparing CBT with controls, including standard therapy, waitlist control, or active/alternative therapy.

Across the trials, CBT moderately improved mental health and quality of life in people with past or current cancer, regardless of cancer type. It seemed to have stronger effects in younger individuals. In-person CBT also appeared more effective than delivering CBT through technology such as web-based videoconference platforms.

“In addition to confirming the general benefit of CBT for individuals with cancer, this study unveiled important nuances of how CBT can be most effective and for which populations. This has major clinical implications for supportive oncology providers,” said corresponding author Anao Zhang, PhD, of the University of Michigan.

Source: Wiley

Can Being More Flexible Help People to Live Longer?

Photo by Mikhail Nilov: https://www.pexels.com/photo/a-couple-doing-yoga-at-home-7500701/

Flexibility exercises are often included in the exercise regimens of athletes and exercisers. New research in the Scandinavian Journal of Medicine & Science in Sports suggests that levels of flexibility may affect survival in middle-aged individuals.

After analysing data on 3,139 people (66% men) aged 46–65 years, investigators obtained a body flexibility score, termed Flexindex. This score was derived from a combination of the passive range of motion in 20 movements (each scored 0–4) involving 7 different joints, resulting in a score range of 0–80.

Flexindex was 35% higher in women compared with men. During an average follow-up of 12.9 years, 302 individuals (9.6%) comprising 224 men and 78 women died. Flexindex exhibited an inverse relationship with mortality risk and was nearly 10% higher for survivors compared with non-survivors in both men and women.

After taking age, body mass index, and health status into account, men and women with a low Flexindex had a 1.87- and 4.78-times higher risk of dying, respectively, than those with a high Flexindex.

“Being aerobically fit and strong and having good balance have been previously associated with low mortality. We were able to show that reduced body flexibility is also related to poor survival in middle-aged men and women,” said corresponding author Claudio Gil S. Araújo, MD, PhD, of the Exercise Medicine Clinic – CLINIMEX, in Rio de Janeiro, Brazil.

He added that as flexibility tends to decrease with aging, it may be worth paying more attention to flexibility exercises and routinely including assessments of body flexibility as part of all health-related physical fitness evaluations.

Source: Wiley