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Pre-Participation Examination (PPE) is recommended in many countries prior to or during the practice of competitive sports. The dedicated exploration of psychological complaints and illnesses in the sense of a psychiatric basic assessment within the PPE is not yet the rule. The implementation of a Psychiatric Basic Assessment (PBA) in the PPE is proposed and presented in terms of content. Abnormal findings in the PBA, crises, emergencies as well as conspicuous changes in behaviour should lead to further sports psychiatric evaluation (SPE) by child, adolescent and adult psychiatrists and psychotherapists qualified for this purpose.The goal is to use diagnostic and procedural standards to identify risks to mental health, stress, and already manifest illnesses in a timely manner and to provide qualified, specialized medical or psychiatric treatment. The diagnostic standards are intended to promote research and the benefits are to be verified by studies.Key Words: Psychiatric Basic Assessment (PBA), Sports Psychiatric Evaluation (SPE), Mental Health, Mental Disorders, Pre-Participation Examination (PPE)

Objectives Spondyloarthritis ( Sp A) is one of the most frequently observed inflammatory joint diseases in HIV-1-seropositive patients. T-cells were described frequently as one of the major driving forces in SpA, therefore we tried to look for T-cell aberrancies in our HIV-positive patients with SpA. Methods A total of 1098 files for HIV-positive patients who attended the HIV out-patient clinic of the Department of Clinical Immunology and Rheumatology at the Medical University Hanover for at least one visit between January 2004 and December 2010 were screened for the presence of a diagnosis of Sp A. A cross-sectional study was conducted to investigate aberrancies in T-cell homeostasis induced by HIV-1 in these subjects. Results The prevalence of Sp A in the HIV-positive patients was 1.6% (18 of 1098). Interestingly, the percentage of patients with Sp A who were human leucocyte antigen ( HLA)- B27 negative in our HIV-positive cohort was 80%. Despite combination antiretroviral therapy (c ART) and viral suppression, an incomplete immune recovery of T-cell naïve/memory distribution and turnover, as identified by intracellular Ki-67 expression, was observed in HIV-positive patients with Sp A. Conclusions Independent of HLA- B27 status and despite c ART, HIV-positive patients can develop Sp A and exhibit an increased T-cell turnover rate. [ABSTRACT FROM AUTHOR]

Objectives The diagnosis of extrapulmonary tuberculous infections and nontuberculous mycobacterial ( NTM) infections is difficult because the symptoms are nonspecific and suitable specimens for bacterial culture are often not available. Recent publications reported the existence of autoantibodies in tuberculous infections. We screened for specific autoantibodies in mycobacterial infections. Methods We screened four in 29 patients with active mycobacterial infections and different controls using protein array technology. We could identify autoantibodies against ubiquitin-fold modifier-conjugating enzyme 1 ( Ufc1) and pleckstrin homology domain containing, family G (with Rho Gef domain) member 2 ( Plekhg2) in all four patients. Subsequently, we designed enzyme-linked immunosorbent assays ( ELISAs) for the detection of autoantibodies binding to Ufc1 and Plekhg2. Results Autoantibodies binding to Ufc1 and Plekhg2 were found in 19 of 29 patients (66%) with active mycobacterial infections. In comparison, we found these autoantibodies in one of 31 patients (3%) with successfully treated mycobacterial infections, in three of 40 (8%) HIV-infected patients not receiving combination antiretorviral therapy ( cART) and in six of 134 (5%) blood donors. Interestingly, six of eight (75%) patients with HIV-associated B-cell non-Hodgkin lymphoma ( B- NHL) at the onset of disease had autoantibodies against Ufc1 and Plekhg2, but none of nine (0%) patients after treatment of HIV-associated B- NHL, none of seven patients with non- HIV-associated B- NHL and 11 of 115 (10%) patients with other malignant diseases had autoantibodies against both proteins. Conclusions In view of the high frequency of these autoantibodies, we postulate that they might be of potential use for additional diagnostics for mycobacterial infections, and further studies may shed light on the pathomechanisms of these two autoantibodies. [ABSTRACT FROM AUTHOR]

Introduction: Interprofessional learning is a critical pre-requisite for future interprofessional work. Structural adaptations in education offer possibilities to introduce new concepts. Rheumatic and musculoskeletal diseases (RMD) are both prevented and treated by physicians and physiotherapists but the development of interprofessional roles is seldom part of curricula.Project description: A complex, longitudinal interprofessional educational approach for future doctors and physiotherapists was designed and implanted at various stages (anatomy, physical examination, pathology, therapy). Most segments of the RMD curriculum are now based on interprofessional classes. Student satisfaction with learning is continually and comparatively evaluated. Learning success is assessed with practical and written exams.Results: Interprofessional teaching was first introduced in 2013 for 420 first-year and 360 fourth-year medical students, along with 40 first- and third-year physiotherapy majors. The satisfaction with teaching and learning is high and distinctly above average for all teaching areas (satisfaction RMD rated as 2.4; average for all is 3.3). The percentage of those who pass the final exam is 94%. 100% of the students surveyed support the continuation of this interprofessional unit.Conclusion: Interprofessional teaching of RMD can be successfully implemented for future physicians and physiotherapists at different learning levels.

Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons. While much of this cell type selectivity may be driven by intrinsic differences among the neuron subpopulations, neuron-extrinsic mechanisms such as the selective malfunction of glial support cells may also play a role. Recently, we identified a population of Schwann cells (SCs) expressing Adamtsl1 , Cldn14 , and Pmp2 (a.k.a. PMP2+ SCs) that preferentially myelinate large-caliber motor axons. PMP2+ SCs are decreased in both ALS model mice and ALS patient nerves. Thus, PMP2+ SC dysfunction could contribute to motor-selective neuropathies. We engineered a tamoxifen-inducible Pmp2-CreERT2 mouse and expressed diphtheria toxin in PMP2+ SCs to assess the consequences of ablating this SC subtype in male and female mice. Loss of PMP2+ SCs led to significant loss of large-caliber motor axons with concomitant behavioral, electrophysiological, and ultrastructural defects. Subsequent withdrawal of tamoxifen restored both PMP2+ SCs and large-caliber motor axons and improved behavioral and electrophysiological readouts. Together, our findings highlight that the survival of large-caliber motor axons relies on PMP2+ SCs, demonstrating that malfunction of a specific SC subtype can lead to selective neuronal vulnerability. Significance Statement A hallmark of neurodegenerative disease is the differential vulnerability of neuron subtypes. While differences between neurons explain some differential sensitivity of neuronal subtypes, neuron-extrinsic mechanisms likely also contribute to selective neuronal vulnerability. Building on the recent identification of genetically distinct subtypes of myelinating Schwann cells, we test the hypothesis that Schwann cell subtypes support distinct classes of peripheral axons. To examine this, we ablated the PMP2+ subclass of myelinating Schwann cells and found preferential loss of large-caliber motor axons. These findings demonstrate that disrupting a specific SC subtype results in selective axonal vulnerability, highlighting the importance of considering neuron-extrinsic mechanisms when dissecting selective neuronal vulnerability in neurodegenerative disorders., (Copyright © 2025 the authors.)

Modulation of immune tone at mucosal surfaces is critical to maintain homeostasis while facilitating the handling of emerging threats. One dynamic component of immune modulation is the phagocytosis and clearance of apoptotic bodies known as efferocytosis that inhibits inflammation by promoting its resolution. Here, we evaluated the effects of apoptotic body phagocytosis by intestinal epithelial stem and progenitor cells (ISCs). Unexpectedly, instead of immunomodulation through efferocytosis, this process elevated local immune system activity. To achieve this result, ISCs actively engaged apoptotic bodies in a unique fashion, leading to their engulfment and ultimate delivery to lysosomes for processing. We found that ISCs were capable of actively recruiting inert material such as apoptotic bodies by using actin-based intrinsic biomechanical processes. Uptake of apoptotic bodies was facilitated by complement factor C3 produced by apoptotic bodies themselves. ISCs in turn generated signals heightening T cell activity that was driven in part by ISC-generated TNF. Taken together, uptake of apoptotic bodies by ISCs produced a local inflammatory alert to specific immune cells. This altered paradigm for the response to phagocytosed apoptotic bodies fits the needs of active mucosal surfaces and demonstrates that efferocytosis as currently defined is not a universal response of all cell types.

Enhancers are critical for regulating tissue-specific gene expression, and genetic variants within enhancer regions have been suggested to contribute to various cancer-related processes, including therapeutic resistance. However, the precise mechanisms remain elusive. Using a well-defined drug-gene pair, we identified an enhancer region for dihydropyrimidine dehydrogenase (DPD, DPYD gene) expression that is relevant to the metabolism of the anti-cancer drug 5-fluorouracil (5-FU). Using reporter systems, CRISPR genome-edited cell models, and human liver specimens, we demonstrated in vitro and vivo that genotype status for the common germline variant (rs4294451; 27% global minor allele frequency) located within this novel enhancer controls DPYD transcription and alters resistance to 5-FU. The variant genotype increases recruitment of the transcription factor CEBPB to the enhancer and alters the level of direct interactions between the enhancer and DPYD promoter. Our data provide insight into the regulatory mechanisms controlling sensitivity and resistance to 5-FU., Competing Interests: TZ, AA, HH, KB, AE, RS, BB, ZT, ZW, DS, RD, CL No competing interests declared, FI Currently an AbbVie employee and receives stocks from the company, SO Reports current research support from Processa Pharmaceuticals, Inc, which are outside of the conduct of this study. Has previously served as an independent consultant for Processa Pharmaceuticals, Inc, in matters not related to this study, (© 2024, Zhang et al.)

Objectives: Early diagnosis of inflammatory arthritis is critical to prevent joint damage and functional incapacities. However, the discrepancy between recommendations of early diagnosis and reality is remarkable. The Rheuma-VOR study aimed to improve the time to diagnosis of patients with early arthritis by coordinating cooperation between primary care physicians, specialists and patients in Germany., Methods: This prospective non-randomised multicentre study involved 2340 primary care physicians, 72 rheumatologists, 4 university hospitals and 4 rheumatology centres in 4 German Federal States. The two coprimary endpoints (time to diagnosis and screening performance of primary care physicians) were evaluated for early versus late implementation phase. Additionally, time to diagnosis and secondary endpoints (decrease of disease activity, increase in quality of life and overall well-being, improvement of fatigue, depression, functional ability, and work ability, reduction in drug and medical costs and hospitalisation) were compared with a reference cohort of the German Rheumatism Research Centre (DRFZ) reflecting standard care., Results: A total of 7049 patients were enrolled in the coordination centres and 1537 patients were diagnosed with a rheumatic disease and consented to further participation. A follow-up consultation after 1 year was realised in 592 patients. The time to diagnosis endpoint and the secondary endpoints were met. In addition, the calculation of cost-effectiveness shows that Rheuma-VOR has a dominant cost-benefit ratio compared with standard care., Discussion: Rheuma-VOR has shown an improvement in rheumatological care, patient-reported outcome parameters and cost savings by coordinating the cooperation of primary care physicians, rheumatologists and patients, in a nationwide approach., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Differential gene expression in bulk transcriptomics data can reflect change of transcript abundance within a cell type and/or change in the proportions of cell types. Expression deconvolution methods can help differentiate these scenarios. BEDwARS is a Bayesian deconvolution method designed to address differences between reference signatures of cell types and corresponding true signatures underlying bulk transcriptomic profiles. BEDwARS is more robust to noisy reference signatures and outperforms leading in-class methods for estimating cell type proportions and signatures. Application of BEDwARS to dihydropyridine dehydrogenase deficiency identified the possible involvement of ciliopathy and impaired translational control in the etiology of the disorder., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating disease. Failure to remyelinate successfully is common in MS lesions, often with consequent neuronal/axonal damage. CNS myelin is normally produced by oligodendroglial cells. Remyelination by Schwann cells (SchC) has been reported in spinal cord demyelination, in which SchCs are in close proximity to CNS myelin. We identified an MS cerebral lesion that was remyelinated by SchCs. This prompted us to query the extent of SchC remyelination in the brain and spinal cords of additional autopsied MS specimens. CNS tissues were obtained from the autopsies of 14 MS cases. Remyelinated lesions were identified by Luxol fast blue-periodic-acid Schiff and solochrome cyanine staining. Deparaffinized sections containing remyelinated lesions were stained with anti-glial fibrillary acid protein to identify reactive astrocytes. Glycoprotein P zero (P0) is a protein exclusive to peripheral but not CNS myelin. Areas of SchC remyelination were identified by staining with anti-P0. Myelinated regions in the index case cerebral lesion were confirmed to be of SchC origin using anti-P0 staining. Subsequently, 64 MS lesions from 14 autopsied MS cases were examined, and 23 lesions in 6 cases showed remyelination by SchCs. Lesions from the cerebrum, brainstem, and spinal cord were examined in each case. When present, SchC remyelination was most commonly located adjacent to the venules and associated with a lower surrounding density of glial fibrillary acid protein + reactive astrocytes than areas of only oligodendroglial cell remyelination. The difference was significant only for spinal cord and brainstem lesions but not for lesions located in the brain. In conclusion, we demonstrated SchC remyelination in the cerebrum, brainstem, and spinal cord of 6 autopsied MS cases. To our knowledge, this is the first report of supratentorial SchC remyelination in MS., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Sleep loss is associated with cognitive decline in the aging population and is a risk factor for Alzheimer's disease (AD). Considering the crucial role of immunomodulating genes such as that encoding the triggering receptor expressed on myeloid cells type 2 (TREM2) in removing pathogenic amyloid-β (Aβ) plaques and regulating neurodegeneration in the brain, our aim was to investigate whether and how sleep loss influences microglial function in mice. We chronically sleep-deprived wild-type mice and the 5xFAD mouse model of cerebral amyloidosis, expressing either the humanized TREM2 common variant, the loss-of-function R47H AD-associated risk variant, or without TREM2 expression. Sleep deprivation not only enhanced TREM2-dependent Aβ plaque deposition compared with 5xFAD mice with normal sleeping patterns but also induced microglial reactivity that was independent of the presence of parenchymal Aβ plaques. We investigated lysosomal morphology using transmission electron microscopy and found abnormalities particularly in mice without Aβ plaques and also observed lysosomal maturation impairments in a TREM2-dependent manner in both microglia and neurons, suggesting that changes in sleep modified neuro-immune cross-talk. Unbiased transcriptome and proteome profiling provided mechanistic insights into functional pathways triggered by sleep deprivation that were unique to TREM2 and Aβ pathology and that converged on metabolic dyshomeostasis. Our findings highlight that sleep deprivation directly affects microglial reactivity, for which TREM2 is required, by altering the metabolic ability to cope with the energy demands of prolonged wakefulness, leading to further Aβ deposition, and underlines the importance of sleep modulation as a promising future therapeutic approach.

Aims: We examined major protein components of Schwann cells (SCs) and myelin in normal and diseased human peripheral nerves., Methods: We evaluated distributions of neural cell adhesion molecule (NCAM), P0 protein (P0) and myelin basic protein (MBP) in frozen sections of 98 sural nerves., Results: Non-myelinating SC in normal adults contained NCAM, but not P0 or MBP. With chronic axon loss, SC without associated axons (Büngner band cells) often co-stained for both NCAM and P0. Onion bulb cells also co-stained for both P0 and NCAM. Infants had many SC with MBP but no P0. All myelin sheaths contained P0. Myelin around large, and some intermediate-sized, axons co-stained for both MBP and P0. Myelin on other intermediate-sized axons had P0, but no MBP. Regenerated axons often had sheaths with MBP, P0 and some NCAM. During active axon degeneration, myelin ovoids often co-stained for MBP, P0 and NCAM. Demyelinating neuropathy patterns included SC (NCAM) loss, and myelin with abnormally distributed, or reduced, P0., Conclusions: Peripheral nerve SC and myelin have varied molecular phenotypes, related to age, axon size and nerve pathology. In normal adult peripheral nerve, myelin has two different patterns of molecular composition. MBP is mostly absent from myelin around a population of intermediate-sized axons, whereas P0 is present in myelin around all axons. Denervated SCs have a molecular signature that differs from normal SC types. With acute denervation, SCs may stain for both NCAM and MBP. Chronically denervated SCs often stain for both NCAM and P0., (© 2023 British Neuropathological Society.)