Medizin- & Sportwissenschaft-News: evidenzbasiert kuratiert

Publication date: Available online 7 October 2025Source: Physical Therapy in SportAuthor(s): Ebru TEKIN, Fatma UNVER

Publication date: November 2025Source: Physical Therapy in Sport, Volume 76Author(s): Séverine Abellaneda, Malgorzata Klass, Bruno Bonnechère, Joachim Van Cant

Publication date: November 2025Source: Physical Therapy in Sport, Volume 76Author(s): Anthony P. Sharp, Jonathon Neville, John B. Cronin

Publication date: November 2025Source: Physical Therapy in Sport, Volume 76Author(s): Anne Fältström, Martin Hägglund, Andreas Ivarsson, Joanna Kvist

Publication date: November 2025Source: Physical Therapy in Sport, Volume 76Author(s): Merve Karapınar, Hayley Powell Smitheman, Stephanie Grace Cone, Karin Grävare Silbernagel

Publication date: November 2025Source: Physical Therapy in Sport, Volume 76Author(s): Nigel Travers, Myles C. Murphy, Benedict M. Wand, Paul Kirwan, Mervyn Travers, James Debenham, William Gibson, Dana Hince

Objectives
Contact breast injury (CBI) and exercise-induced breast pain (EIBP) are common in adult female contact sports; however, incidence in adolescent players is unknown. The present study investigated the occurrence, mechanism and reporting behaviours of CBI and EIBP in under-18 international female rugby union.

Methods
A cross-sectional survey was distributed to players (n=110, 17.0±0.7 years) participating in the Women’s U18 Six Nations.

Results
Incidence of CBI and EIBP was 39% and 43%, respectively. Seventy-seven percent of players affected by CBI had experienced multiple incidents in the previous year. Activities associated with the highest severity of EIBP were running, jumping and tackling, with 27% reporting that breast pain inhibited their performance. Concerningly, 64% of players did not report CBI, and no injuries were reported to coaching/medical personnel. Notably, over half of players did not consciously adopt strategies to prevent CBI, which may be attributed to various bio-psycho-social mechanisms.

Conclusion
While there is a worryingly high incidence of CBI and EIBP in adolescent female international rugby players, reporting remains low, and there is a lack of uptake of support/protective strategies. Further research is warranted to investigate the effectiveness of female-specific protective equipment and educational programmes, aiming to improve breast health.

Background: Glioblastoma (GB) is a highly aggressive and treatment-resistant brain cancer with poor prognosis. Surgical resection followed by radiotherapy (RT) with the chemotherapeutic, temozolomide (TMZ), is the standard GB treatment; yet recurrence often occurs. GB is organized hierarchically with a small population of radiation-resistant glioma-initiating cells (GICs) that self-renew and drive tumor growth. Importantly, RT can induce a subset of cells from non-tumor-initiating into glioma-initiating cells (iGICs). Both GICs and iGICs contribute to tumor recurrence and therapy resistance. Thus, without effective elimination of non-tumorigenic GB and prevention or targeting of GICs, a cure is unlikely. The objective of this study is to identify small molecules that block RT-induced phenotypic conversion to occur. Method: We conducted a high-throughput screen of NCI Cancer Therapy Evaluation Program (CTEP) compounds with evidence for crossing the blood-brain-barrier. To identify stem-like or reprogramming of cells, we transduced GB cell lines representing each TCGA subtype to express a fluorescent reporter for proteasomal activity that distinguishes non-tumor-initiating cells from GICs. We tested CTEP agents at 10 different concentrations in combination with radiation. Results: Our results identified selumetinib as a candidate compound that effectively prevents radiation-induced phenotype conversion. Furthermore, in combination with radiation, selumetinib decreased stem cell maintenance in GICs with differential effects on viability in non-tumorigenic cells. Conclusion: Taken together, these findings suggest that repurposing FDA-approved compounds alongside current therapies may effectively target the cellular and molecular heterogeneity of GB. Furthermore, since these agents are already clinically approved, this approach can be rapidly implemented in the clinic.

During replication-coupled DNA interstrand cross-link (ICL) repair, fork reversal is thought to enable the Fanconi anemia (FA) pathway to resolve the ICL through nucleolytic incisions. Subsequent fork restoration then allows nascent DNA strand extension past the lesion. Although these fork remodeling events are crucial for ICL repair, their regulation remains poorly understood. Here, we use cell-free Xenopus egg extracts to investigate fork dynamics during ICL repair by the FA pathway. We find that the ataxia telangiectasia-mutated (ATM) kinase is activated concomitantly with fork reversal and promotes resection of the reversed fork intermediate. This resection depends on the coordinated activities of the EXO1 and DNA2 nucleases. Our data indicate that EXO1 initiates 5′ to 3′ resection of nascent lagging strands in the regressed arm, while DNA2 performs 5′ to 3′ resection of recessed lagging strands. We further show that the inhibition of protein phosphatase 2A (PP2A) during ICL repair results in ATM hyperactivation, reversed fork over-resection, and formation of aberrant end-joining products, indicating that PP2A counteracts ATM signaling to constrain reversed fork resection. Taken together, this work implicates reversed forks as substrates for ATM activation and reveals a phospho-regulatory circuit that governs reversed fork processing during ICL repair.

Patients with chronic kidney disease (CKD) face elevated fracture incidences, but mechanisms underlying CKD-related bone loss remain unclear. Using the adenine-induced chronic kidney injury (AdKI) murine model, we identified that AdKI induces dysregulated glucose metabolism in bones and kidneys via in vivo and ex vivo metabolic tracing. Ex vivo 13C-metabolic tracing of osteocyte-enriched femora revealed accelerated citrate production from [1,2-13C]-glucose and [U-13C]-glutamine in AdKI mice. These metabolic changes were observed together with increased circulating citrate and Slc13a5 overexpression in bones from AdKI mice. Thus, to explore the role of citrate in AdKI, we utilized mice harboring a loss of function mutation in the citrate importer SLC13A5 (Slc13a5R337*/R337*). Mutant mice displayed elevated osteocytic citrate production, and elevated circulating citrate, without significantly worsened AdKI-related bone loss. Coincident with this, Slc13a5R337*/R337* mutant mice were significantly protected from loss of kidney function with attenuated AdKI-induced nephrolithiasis. We also confirmed that Slc13a5 is highly expressed in cortical bone compared to the kidney, suggesting the effect of the mutation is mediated by SLC13A5’s function outside the kidney. Altogether, this study finds that accelerated osteocytic citrate production in CKD is associated with protection of kidney function, and modulation of citrate handling may be a site for therapeutic intervention in CKD.

Computational methodology has become ubiquitous in biomedical research with the rise of big data analysis and popularity of artificial intelligence and machine learning. However, undergraduate bioinformatics education has largely struggled to keep pace with the demand for bioinformatics skills, due to a combination of social and resource-based barriers. In this case study, we discuss the application and outcomes of Multi-Omic Data Analysis, a peer-to-peer learning-based undergraduate bioinformatics course offered by the Department of Quantitative and Computational Biology at the University of Southern California. Over eight semesters, a cohort of student instructors taught 2-3 weekly lectures to 107 undergraduate students in the Quantitative Biology Bachelor of Science degree program. Lectures covered a range of topics, including R and Python data analysis, scientific communication, and general research readiness as undergraduate students. We find that bioinformatics education courses structured around peer-to-peer learning have great potential to overcome many of the obstacles to comprehensive undergraduate bioinformatics education, and provide additional benefits related to student cohesion and community. We further discuss the longevity and feasibility of such courses, both specific to our program and in undergraduate universities at large.

The exploration-exploitation trade-off is ubiquitous in our everyday lives, and individuals display considerable variability in their preferred decision-making strategies. Most previous work pertaining to neural signatures of exploration is restricted to functional pathways. However, the specific contributions of cortical microarchitectures to high-level cognitive processes such as decision-making are as yet unknown. Here, we investigated the neuroanatomical foundations of inter-individual variability in decision-making strategies. To this end, 122 healthy participants completed a gamified multi-armed bandit paradigm aimed at teasing apart distinct exploration-exploitation decision strategies. We also collected whole-brain quantitative MRI maps indexing microstructural features of cortical myelination and iron content. Through computational modelling, we disentangled individual-specific exploration strategies, including value-free random exploration. Whole-brain regression analyses identified significant associations between value-free exploration and increased cortical myelination in right frontal brain areas with reported links to impulsivity. By elucidating the brain microstructural correlates of distinct exploration-exploitation strategies, we aimed to further our understanding of why individuals differ in their decision-making capabilities, and how decision-making may become aberrant in mental health conditions.

Cannabis use is linked to elevated psychosis risk, yet the neurobiological mechanisms that couple use to symptom expression remain unclear. Because glutamatergic dysregulation has been implicated in both cannabis effects and psychosis vulnerability, we examined whether brain glutamate relates to dimensional symptoms as a function of cannabis use across the psychosis spectrum. Seventy-nine participants–typically developing controls, clinical high-risk individuals, and patients with psychosis–completed dimensional clinical assessments, detailed cannabis surveys, urine toxicology, and ultra-high-field 7T 1HMRS quantification of anterior cingulate cortex (ACC) glutamate levels. Linear models assessed the main and interactive effects of ACC glutamate and cannabis use on positive and negative symptoms. Self-reported cannabis use showed strong concordance with urine toxicology. Cannabis use was associated with higher positive and negative symptoms. Independently, higher ACC glutamate predicted greater positive and negative symptoms. Notably, lower glutamate levels were associated with higher positive symptoms in cannabis users. Exploratory analyses suggested interactions for depressive and manic symptoms, indicating that glutamatergic abnormalities may amplify the overall severity of cannabis-related symptoms. Sensitivity analyses revealed lower ACC glutamate in psychosis patients–especially cannabis users–highlighting diagnostic group differences and reinforcing the link between cannabis exposure and glutamatergic dysfunction. These findings implicate ACC glutamatergic dysfunction as a transdiagnostic correlate of symptom burden, particularly in those with psychosis who are cannabis users. Glutamate-targeted interventions and longitudinal designs will be needed to examine causal pathways linking cannabis exposure to psychosis-relevant outcomes.

Astrocytes regulate the activity of nearby neurons so disruption of astrocyte calcium dynamics by traumatic brain injury (TBI) could have profound consequences for neural network activity in the brain. In this study, human induced pluripotent stem cell (hiPSC)-derived astrocytes were used in a two-dimensional (2D) in vitro stretch injury model to evaluate the effect of trauma on calcium dynamics, mitochondrial function, and the mechanosensitive ion channel Piezo1. Outcomes were assessed using live imaging, immunostaining, and RNA sequencing. Cell viability, mitochondrial membrane potential, and spontaneous calcium transients declined as injury severity increased. At moderate injury severity, the decreases in mitochondrial membrane potential and calcium dynamics were temporary. The spatial distribution of Piezo1 also changed temporarily after injury. RNA sequencing identified 196 genes that changed expression after injury, including downregulation of mitochondrial and oxidative metabolic processes and upregulation of cortical thinning pathways. These findings establish this model as a platform for investigating the cellular mechanisms of TBI and its influence on neurodegeneration. Keywords: Traumatic brain injury, hiPSC-derived astrocytes, calcium dynamics, mitochondrial dysfunction, Piezo1, RNA sequencing

The study of antigen-specific B cells has resulted in important advances in all fields of immunology, the development of experimentally and/or clinically useful antibodies, and as a starting point for rationally designed vaccine antigens. A key innovation allowing for widespread study of antigen-specific B cells was the development of fluorescent antigen probes for use with flow cytometry. Initially these studies were mostly focused upon B cells specific for a variety of model antigens, but over the past decade focus has shifted towards the study of B cells specific for antigens from pathogens such as SARS-CoV-2, HIV, and Influenza virus. Importantly however, these types of approaches have been used for hundreds of different antigens and could be used for thousands more. Unfortunately, studies of B cells specific for an antigen of interest are not easily searchable on current publication databases since these assays are often a small portion of a larger publication. To overcome this, we built a searchable database of studies analyzing antigen-specific B cells by flow cytometry using fluorescent antigen probes that is located at www.immunology.virginia.edu/Taylor/Bcell/Database.php. Using this database, we assessed the number of publications per year revealing rapid growth in the use of this approach in recent years. While much of this rapid growth was focused upon the assessment of B cells specific for SARS-CoV-2, HIV-1, or Influenza virus, studies assessing B cells specific for hundreds of different antigens derived from numerous microbes, animals, plants, or other sources can be found in the database. Combined, the antigen-specific B cell database was built to facilitate identification of studies assessing these cells and for analysis of the field as a whole.

Normative upper limb movements are produced by multiple redundant joints. While the reaching task is specified at the endpoint, such task objectives become implicit at the level of joints. A fundamental question is whether planning and control of joints is solely in the service of the endpoint or whether they also include joint trajectories. Using Spearmans correlation and zero crossings, we found differential kinematic signatures of control between shoulder and elbow joints in contrast to the wrist joint. However, the extent of control among joints was substantially diminished compared to the endpoint. Further, when such control measures were compared to the subspaces of inter-trial joint exploration, we found that online control at proximal joints, such as the shoulder and elbow, were significantly associated in regulating the task space, while control at the wrist (distal) joint was associated in regulating joint redundancy in null space. These results suggest that null space is not entirely uncontrolled as per the uncontrolled manifold hypothesis but selectively controlled by some distal joints. Additionally, across different directions, either the shoulder or the elbow contributed dominantly towards the movement of the endpoint while the other joint was lagging and that this strategy reflected in our kinematic measures of online and trajectory control. Taken together, this study shows how the selective implementation of a leading joint in task space and a lagging joint in null space can enable the control of multi-jointed movements and attenuate the problem of joint redundancy.

Opioid use disorder (OUD) remains a public health crisis in the United States. A key factor in continued use, relapse risk, and overdose is the severe withdrawal syndrome that accompanies abstinence. Observational studies suggest cannabis may improve outcomes for patients with OUD. Cannabidiol (CBD), a non-intoxicating compound found in cannabis, is being investigated as a potential treatment for OUD. This study investigated whether CBD alleviated withdrawal symptoms in a rat model of opioid dependence. Sprague Dawley rats (N = 100, 50% female) were administered escalating doses of morphine across 10 days (10-50 mg/kg, s.c., twice daily). Following abrupt discontinuation, withdrawal outcomes were evaluated across acute (38-hr) and protracted (up to day 7) timepoints. Rats were treated with pure CBD (10 or 30 mg/kg, p.o.) or vehicle (sesame oil; 1 mg/ml) daily, beginning 14-hrs after their final morphine or saline injection (n = 8-9 per sex/group). Withdrawal severity was assessed through physical measurements of body weight, food intake, and somatic signs (e.g., body shakes, diarrhea), and pain sensitivity, as well as measurements of anxiety-like behaviors in the protracted phase. Compared to non-dependent controls, morphine-dependent rats had decreased body weight and food intake, showed greater somatic signs, and had increased pain sensitivity that peaked in acute withdrawal (38-hr). Oral CBD did not affect physical symptoms of opioid withdrawal nor protracted anxiety-like behaviors. These data indicate that CBD alone may have limited effectiveness for treating opioid withdrawal. Reports of improved withdrawal symptoms after cannabis use may be attributed to other compounds in cannabis.

The lateral orbitofrontal cortex (OFC) is critical for flexibly adjusting choices when outcome values change. Anterior and posterior parts of the human lateral OFC differ in cytoarchitecture and connectivity, but whether these subregions make differential contributions to outcome-guided (i.e., goal-directed) behavior remains unclear. Outcome-guided behavior requires (a) representations of stimulus-outcome associations and (b) inferring the current value of options when making decisions. Here, we test whether these two functions are differentially supported by the posterior (pOFC) and anterior (aOFC) parts of the lateral OFC, using transcranial magnetic stimulation (TMS) to selectively disrupt activity in functional networks centered on the pOFC and aOFC during a two-day outcome devaluation task. Participants (n = 48) received pOFC or aOFC network-targeted TMS either on day 1 before learning associations between visual stimuli and sweet or savory food odors, or on day 2 before a meal that selectively devalued one of these outcomes, followed by a choice test. TMS targeting pOFC, but not aOFC, before the meal on day 2 disrupted outcome-guided behavior, as measured by choices of stimuli predicting non-sated rewards in the post-meal choice test. In contrast, TMS targeting aOFC, but not pOFC, before learning on day 1 similarly impaired behavior in the post-meal choice test on day 2. These findings demonstrate that anterior and posterior parts of the lateral OFC make distinct contributions to outcome-guided behavior by supporting learning of stimulus-outcome associations and inferring the current value of options, respectively.

The p75 neurotrophin receptor (p75NTR) contributes to the development of Alzheimer’s Disease (AD) pathology by enhancing amyloid precursor protein (APP) cleavage and amyloid plaque formation. However, the cell type-specific and temporal roles of p75NTR in AD progression remain unclear. Here, we report that conditional knock-in of functionally impaired p75NTR variants lacking the death domain ({Delta}DD) or transmembrane Cys259 (C259A) specifically in forebrain excitatory neurons of 5xFAD mice significantly attenuated multiple AD-associated pathologies, including amyloid plaque accumulation, gliosis, neurite dystrophy, as well as learning and memory deficits. Hippocampal amyloid plaque burden was reduced to levels comparable to those in whole-body knock-in mice. Strikingly, delaying introduction of p75NTR variants until advanced disease stages produced comparable beneficial effects, and rescued behavior performance in cognitively impaired animals. These findings suggest that blunting p75NTR function can have beneficial effects even during symptomatic stages of AD, offering a potential therapeutic approach complementary to passive vaccination.

Calcium (Ca2+) homeostasis is fundamental to neuronal physiology, including in the regulation of membrane excitability and synaptic transmission. Disruptions in the ion transporters regulating Ca2+ influx and efflux are clearly linked to seizure disorders and age-related neurodegenerative disease. Yet, the specific contributions of variants in genes encoding these transporters to neurological disease remain to be fully understood. Drosophila melanogaster has proven to be a powerful genetic model for uncovering such mechanisms, particularly through studies of mutants that display temperature-sensitive (TS) behavioral phenotypes. In a forward genetic screen, we identified a mutant line that exhibited TS convulsions along with progressive, age-dependent neurodegeneration. We mapped the mutation to Nckx30c, specifically within the transmembrane ion-binding region of this K+-dependent Na+/Ca2+ exchanger. Characterization of this mutant, together with a second Nckx30c allele, revealed TS convulsions, impaired locomotion, a markedly shortened lifespan, neurodegeneration with age, along with structural defects at larval and adult neuromuscular junctions (NMJs). Gene expression analysis confirmed that Nckx30c levels were reduced in heads of Nckx30c loss-of-function mutants. Tissue-specific manipulation revealed that knockdown of Nckx30c in neurons recapitulated the TS convulsions, locomotor defects, and shortened lifespan phenotypes. Drosophila Nckx30c is highly conserved and shares homology with mammalian SLC24A2, a solute carrier family 24 member whose neurological role is not yet fully elucidated. Our work establishes Nckx30c as an essential regulator of neuronal health and provides an in vivo framework for investigating the contribution of SLC24A2 to neuronal Ca2+ homeostasis, seizures and age-related neurodegeneration.