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Student perceptions of novel and traditional anatomy teaching tools in sport and exercise science
Anatomy teaching is considered a cornerstone of Sport and Exercise Science programmes, however has a wide array of teaching tools to consider. The present study has compared student perceptions of traditional anatomy teaching tools (cadaveric prosections, plastic models, electronic resources and printed resources) and novel teaching tools (ultrasound, muscle elastics and muscle modelling). 28 students from a Sport and Exercise Science cohort completed a student perception of anatomy teaching tools questionnaire. Students ranked cadaveric prosections, muscle modelling and muscle elastics as their top 3 tools, while cadaveric prosections were consistently rated significantly higher than printed resources and plastic models in students’ perception of achieving learning outcomes (P
Using Randomized Controlled Trials in the Sports Medicine and Performance Environment: Is It Time to Reconsider and Think Outside the Methodological Box?
SYNOPSIS: Randomized controlled trials (RCTs) are ubiquitous in medicine and have facilitated great strides in clinical care. However, when applied in sport, RCTs have limitations that hinder implementing effective interventions in the real-world clinical setting. Pragmatic clinical trials offer some solutions. Yet due to the competitive, high-pressure nature of sport at the individual, team, and governing body level, RCTs are likely infeasible in certain sport settings. The small number of athletes at the elite team level, along with the potential financial consequences of randomizing at the individual athlete and team level, also restricts study power and feasibility, limiting conclusions. Consequently, researchers may need to "think outside the box" and consider other research methodology, to help improve athlete care. In this Viewpoint, we detail alternative study designs that can help solve real-world problems in sports medicine and performance, while maintaining robust research standards and accounting for the challenges that RCTs pose. We also provide practical examples of alternative designs. J Orthop Sports Phys Ther 2023;53(6):1-4. Epub: 18 April 2023. doi:10.2519/jospt.2023.11824.
Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.
IMPORTANCE: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. OBJECTIVE: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONS: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURES: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. CONCLUSIONS AND RELEVANCE: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.
Immune responses in pancreatic cancer may be restricted by prevalence of activated regulatory T-cells, dysfunctional CD8+ T-cells, and senescent T-cells
<jats:title>Abstract</jats:title><jats:p>Pancreatic cancer has the worst prognosis of any human malignancy and lymphocytes appear to be a major prognostic marker of the disease. There is a need to better characterise T-cells of pancreatic cancer in order to identify novel therapeutic strategies. In this study, a multi-parameter analysis of human pancreatic cancer cases revealed three novel characteristics of T-cells. Using a T-cell focused CyTOF panel, we analysed approximately 32,000 T-cells in eight patients. Our observations show a regulatory T-cell population was characterized by a highly immunosuppressive state with high TIGIT and ICOS expression, and the CD8 T-cells were either senescent or exhausted but with lower PD1 levels. These data suggest that the microenvironment of pancreatic cancer is extremely suppressive and could be a major driver of poor prognosis. These findings have been subsequently validated in a large pancreatic cancer single-cell RNA sequencing dataset using 13,000 T cells. This work identifies potential therapeutic targets and avenues that should be further investigated through rational design of clinical trials.</jats:p>
Role of Gynecologic Findings in Interstitial Cystitis/Bladder Pain Syndrome: A Consensus.
ObjectiveTo evaluate the role of gynecologic findings in Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) by reviewing current international guidelines and identifying relevant gynecologic co-morbidities.MethodsThis consensus statement was developed through a systematic four-phase process: (1) comprehensive literature review across PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science databases (inception-January 2025) using predefined search terms related to IC/BPS and gynecologic conditions; (2) assembly of a 6-member multidisciplinary expert panel including urologists, urogynecologists, gynecologists and pain specialists; (3) consensus development via modified Delphi technique comprising several electronic rating rounds and a face-to-face meeting, with consensus defined as ≥ 80% agreement; and (4) manuscript preparation with iterative review.ResultsA number of associated gynecologic disorders may overlap with IC/BPS, our consensus committee identified five main co-morbid disorders: Endometriosis/Adenomyosis, Genito-Pelvic Pain Penetration Disorder/Sexual Dysfunction, Overactive Pelvic Floor Muscles, Hormone- Associated Genitourinary Changes, Vulvodynia/Vestibulodynia.ConclusionWhile not exhaustive, this consensus highlights the most prevalent gynecologic co-morbidities supported by current literature. Clinical evaluation should prioritize a detailed medical history and pelvic examination to identify these overlapping conditions. Future directions include developing a multidisciplinary diagnostic and treatment algorithm to guide clinicians-including urologists, gynecologists, urogynecologists, physical therapists-in comprehensive IC/BPS care.
Mucosal signatures of pathogenic T cells in HLA-B*27+ anterior uveitis and axial spondyloarthritis.
HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint and eye inflammation, respectively. Gastrointestinal inflammation has been suggested as a trigger of axSpA. We recently identified a bacterial peptide (YeiH) that can be presented by HLA-B*27 to expanded public T cell receptors in the joint in axSpA and the eye in B27AAU. While YeiH is present in enteric microbiota and pathogens, additional evidence that pathogenic T cells in HLA-B*27-associated autoimmunity may have had a prior antigenic encounter within the gastrointestinal tract remains lacking. Here, we analyzed ocular, synovial, and blood T cells in B27AAU and axSpA, showing that YeiH-specific CD8+ T cells express a mucosal gene set and surface proteins consistent with intestinal differentiation, including CD161, integrin α4β7, and CCR6. In addition, we found an expansion of YeiH-specific CD8+ T cells in axSpA and B27AAU blood compared with that from individuals acting as healthy controls, whereas influenza-specific CD8+ T cells were equivalent across groups. Finally, we demonstrated the dispensability of TRBV9 for antigen recognition. Collectively, our data suggest that, in HLA-B27-associated autoimmunity, early antigen exposure and differentiation of pathogenic CD8+ T cells may occur in enteric organs.
Autoimmunity in inflammatory bowel disease: a holobiont perspective.
Adaptive immunity towards self-antigens (autoimmunity) and intestinal commensal microbiota is a key feature of inflammatory bowel disease (IBD). Considering mucosal adaptive immunity from a holobiont perspective, where the host and its microbiome form a single physiological unit, emphasises the challenge of avoiding damaging responses to self-antigen and symbiotic microbial communities in the gut while protecting against potential pathogens. Intestinal tolerance mechanisms prevent maladaptive T and B cell responses to microbial, environmental, and self-antigens, which drive inflammation. We discuss the spectrum of antimicrobial and autoantibody responses and highlight mechanisms by which common IBD-associated adaptive immune responses contribute to disease.
Effects of temporarily suspending low-dose methotrexate treatment for 2 weeks after SARS-CoV-2 vaccine booster on vaccine response in immunosuppressed adults with inflammatory conditions: protocol for a multicentre randomised controlled trial and nested mechanistic substudy (Vaccine Response On/Off Methotrexate (VROOM) study)
This article consists of a citation of a published article describing research funded by the Efficacy and Mechanism Evaluation programme under project number NIHR134607, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1136/bmjopen-2022-062599 Introduction It is unknown if a temporary break in long-term immune-suppressive treatment after vaccination against COVID-19 improves vaccine response. The objective of this study was to evaluate if a 2-week interruption in low-dose weekly methotrexate treatment after SARS-CoV-2 vaccine boosters enhances the immune response compared with continuing treatment in adults with autoimmune inflammatory conditions. Methods and analysis An open-label, pragmatic, prospective, parallel group, randomised controlled superiority trial with internal feasibility assessment and nested mechanistic substudy will be conducted in rheumatology and dermatology clinics in approximately 25 UK hospitals. The sample size is 560, randomised 1:1 to intervention and usual care arms. The main outcome measure is anti-spike receptor-binding domain (RBD) antibody level, collected at prebooster (baseline), 4 weeks (primary outcome) and 12 weeks (secondary outcome) post booster vaccination. Other secondary outcome measures are patient global assessments of disease activity, disease flares and their treatment, EuroQol 5- dimention 5-level (EQ-5D-5L), self-reported adherence with advice to interrupt or continue methotrexate, neutralising antibody titre against SARS-CoV-2 (mechanistic substudy) and oral methotrexate biochemical adherence (mechanistic substudy). Analysis of B-cell memory and T-cell responses at baseline and weeks 4 and 12 will be investigated subject to obtaining additional funding. The principal analysis will be performed on the groups as randomised (ie, intention to treat). The difference between the study arms in anti-spike RBD antibody level will be estimated using mixed effects model, allowing for repeated measures clustered within participants. The models will be adjusted for randomisation factors and prior SARS-CoV-2 infection status. Ethics and dissemination This study was approved by the Leeds West Research Ethics Committee and Health Research Authority (REC reference: 21/HRA/3483, IRAS 303827). Participants will be required to give written informed consent before taking part in the trial. Dissemination will be via peer review publications, newsletters and conferences. Results will be communicated to policymakers. Trial registration number ISRCTN11442263. Funding This publication was funded by the Efficacy and Mechanism Evaluation programme as a part of award number NIHR134607. This article reports on one component of the research award Vaccine Response On/Off Methotrexate (VROOM): does temporarily suspending methotrexate treatment for two weeks enhance COVID-19 vaccine response? A randomised controlled trial. For more information about this research please view the award page [https://fundingawards.nihr.ac.uk/award/NIHR134607] DOI https://doi.org/10.1136/bmjopen-2022-062599
Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial
This article consists of a citation of a published article describing research funded by the Efficacy and Mechanism Evaluation programme under project number NIHR134607, and is provided as as part of the complete record of research outputs for this project. The original publication is available at: https://doi.org/10.1016/S2665-9913(23)00298-9 Summary Background Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227-29 056) in the suspend methotrexate group and 12 326 U/mL (10 538-14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59-2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding National Institute for Health and Care Research. Funding This publication was funded by the Efficacy and Mechanism Evaluation programme as a part of award number NIHR134607. This article reports on one component of the research award Vaccine Response On/Off Methotrexate (VROOM): does temporarily suspending methotrexate treatment for two weeks enhance COVID-19 vaccine response? A randomised controlled trial. For more information about this research please view the award page [https://fundingawards.nihr.ac.uk/award/NIHR134607] DOI https://doi.org/10.1016/S2665-9913(23)00298-9
Exploring nutritional supplement use for countering respiratory tract infections through an X (formerly Twitter)-based survey
Background: Respiratory tract infections are a common health issue, driving interest in preventive strategies like nutritional supplements, while evidence on their usage and effectiveness remains limited. In this context, social media platforms, particularly X (formerly Twitter), provide a unique opportunity to gather large-scale public health-related data. Objectives: In this study, we aimed to survey participants’ uses and opinions on nutritional supplements in prevention or treatment of respiratory tract infections, by using X. Methods: A survey was conducted between 1st and 15th December 2022. A single open-ended question “Which are the best dietary supplements to counteract respiratory infections?“ was asked. One week after the start of the survey, a poll was posted to get more relevant information and boost the survey's reach. Total endorsements were calculated for each tweet posted as the total sum of replies, retweets, and likes. Results: The open-ended question received a total of 118 retweets, 39 quotes, and 371 likes, while the poll received 56 retweets, 13 quotes, and 67 likes. A total of 495 replies, 2,251 retweets, 5,118 likes, and 148 quotes were received for the question and its related tweets. Vitamin D (1,607 endorsements), zinc (1,347 endorsements), vitamin C (803 endorsements), magnesium (694 endorsements), and honey (661 endorsements) were the nutritional supplements that received most endorsements. Conclusion: Various foods, drinks, and natural ingredients have been suggested as potentially helpful for counteracting respiratory infections. Approximately half of respondents indicated using such supplements for themselves. The result of this study supports the idea that the X platform can be used as an effective survey tool to study global health-related behaviours and trends.
Harnessing the neuroprotective effect of oral administration of benfotiamine in MPTP induced Parkinson's disease in rats.
The study was performed to evaluate the neuroprotective effects of Benfotiamine (BFT) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in rats. The rats were given daily doses of BFT (100 mg/kg, 200 mg/kg) through oral administration for 42 days. The rats were given a single bilateral dosage of MPTP (0.1 mg/nostril) intranasally once before the drug treatment to induce PD. On day 42, the animals were subjected to various behavioral paradigms. Post-treatment with BFT for 42 days significantly improved the motor and nonmotor fluctuations of MPTP. The results demonstrated that treatment with BFT ameliorated MPTP-induced disorders in behavior, body balance, and dopamine levels in the mid-brain. Among the post-treated groups, a high dose of BFT was the most effective treatment. Mean values are indicated in ±SEM, n = 5***(p
Mucoepidermoid carcinoma of the bronchus: is conservative surgery always justified?
A case of mucoepidermoid carcinoma of the bronchus in a 7-year-old boy is reported. The patient underwent right pneumonectomy. Histologically, the tumor was a low-grade muco-epidermoid carcinoma arising from the bronchus with lymph node metastasis in the drainage area. Presence of lymph node metastasis in this low-grade tumor suggests the possibility of early progression of disease in what has until now been considered a very slow growing tumor. Aggressive surgery may be necessary in these situations.
A linear ontogeny accounts for the development of naive, memory, and tumor-infiltrating regulatory T cells in mice.
Regulatory T cells (Treg cells) are critical regulators of adaptive immunity and the pathophysiology of antitumoral immunity. Treg cells are both generated during thymic development and induced from peripheral conventional T cells. How these distinct pathways contribute to the homeostasis of circulating Treg cells in health and disease remains unclear. We addressed this question using multiple fate-mapping mouse systems and modeling. Naive and effector/memory (EM) Treg cells exhibit distinct dynamics but are both continuously replenished by de novo generation throughout life. The predominant precursors of circulating EM Treg cells are naive thymic Treg cells and not conventional T cells, a process driven by self rather than foreign antigen recognition. Using the same fate reporters and three tumor models, we demonstrate that infiltrating Treg cells specifically derive from preexisting EM Treg cells. In summary, we define a linear ontogeny of Treg cells from the thymus to EM, driven by self-antigen recognition, that then gives rise to tumor-infiltrating Treg cells.
Multidisciplinary evidence-based consensus statements on salvage surgery for recurrent head and neck cancer (International Centre for Recurrent head and neck Cancer).
BACKGROUND: Recurrent head and neck squamous cell carcinomas (rHNSCC) are an understudied subgroup, lacking high quality evidence and thus gold standard management recommendations, resulting in significant variations in practice. The aim of this project was to deliver a national multi-disciplinary expert consensus on patients with rHNSCC managed by curative salvage surgery. METHODS: The AGREEII protocol guided the Delphi process. Best practice statements were developed after literature review on the perioperative management and surgical salvage of major rHNSCC subsites. Members of the International centre for Recurrent head and neck cancer (IREC) network, and other UK based professional stakeholder organisations were invited into an online Delphi study. Participants voted upon statements over three rounds, with items modified in response to vote thresholds and comments. RESULTS: Twenty-eight experts participated including 11 otolaryngologists, 7 oncologists, 9 oral and maxillofacial surgeons, and 1 speech and language therapist. Consensus was achieved on 73 statements, with 29 (39.7%) achieving unanimous (threshold: 100%) and 25 (34.2%) (threshold >90%) agreement. CONCLUSIONS: Salvage surgery for rHNSCC are challenging cases that require intensive multidisciplinary input to achieve cure while balancing impact on function and quality-of-life. In this article, we provide a large series of statements based on UK-wide expert consensus, that will guide clinicians through the complex intra- and perioperative management of patients undergoing surgical salvage.
Asparagine availability controls germinal center B cell homeostasis.
The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2. Conditional deletion of Asns in B cells impaired survival and proliferation in low Asn conditions. Removal of environmental Asn by asparaginase or dietary restriction compromised the GC reaction, impairing affinity maturation and the humoral response to influenza infection. Furthermore, metabolic adaptation to the absence of Asn required ASNS, and oxidative phosphorylation, mitochondrial homeostasis, and synthesis of nucleotides were particularly sensitive to Asn deprivation. These findings demonstrate that Asn metabolism acts as a key regulator of B cell function and GC homeostasis.