Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis.

Mucosal-associated invariant T (MAIT) cells express semi-invariant T cell receptors (TCR) for recognizing bacterial and yeast antigens derived from riboflavin metabolites presented on the non-polymorphic MHC class I-related protein 1 (MR1). Neuroinflammation in multiple sclerosis (MS) is likely initiated by autoreactive T cells and perpetuated by infiltration of additional immune cells, but the precise role of MAIT cells in MS pathogenesis remains unknown. Here, we use experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, and find an accumulation of MAIT cells in the inflamed central nervous system (CNS) enriched for MAIT17 (RORγt) and MAIT1/17 (T-betRORγt) subsets with inflammatory and protective features.

Virtual clinical simulation as a paedagogical strategy in healthcare learning: Evidence and Gap Map protocol.

Introduction: Virtual clinical simulation involves creating and applying scenarios using technology like computers or virtual reality. This method provides a secure experiential learning environment, encouraging active student participation and stimulating clinical, critical and reflective thinking. This article outlines the development of the Evidence and Gap Map, which aims to identify, quantify and visually and interactively classify existing systematic reviews on the effectiveness of virtual clinical simulations in health professional training.

Metabolic Derangement of Essential Transition Metals and Potential Antioxidant Therapies.

Essential transition metals have key roles in oxygen transport, neurotransmitter synthesis, nucleic acid repair, cellular structure maintenance and stability, oxidative phosphorylation, and metabolism. The balance between metal deficiency and excess is typically ensured by several extracellular and intracellular mechanisms involved in uptake, distribution, and excretion. However, provoked by either intrinsic or extrinsic factors, excess iron, zinc, copper, or manganese can lead to cellular damage upon chronic or acute exposure, frequently attributed to oxidative stress.

Deadly excess copper.

Higher eukaryotes' life is impossible without copper redox activity and, literally, every breath we take biochemically demonstrates this. However, this dependence comes at a considerable price to ensure target-oriented copper action. Thereto its uptake, distribution but also excretion are executed by specialized proteins with high affinity for the transition metal.

Establishing a standing patient advisory board in family practice research: A qualitative evaluation from patients' and researchers' perspectives.

Introduction: Patient and public involvement is vital for high-quality research. Integrating patients' and providers' perspectives early in research enhances the feasibility and relevance of study results. Within our family practice-based research network ForN, we established a standing patient advisory board (PAB) to include patients with diverse conditions and experiences.

The neuropathobiology of multiple sclerosis.

Chronic low-grade inflammation and neuronal deregulation are two components of a smoldering disease activity that drives the progression of disability in people with multiple sclerosis (MS). Although several therapies exist to dampen the acute inflammation that drives MS relapses, therapeutic options to halt chronic disability progression are a major unmet clinical need. The development of such therapies is hindered by our limited understanding of the neuron-intrinsic determinants of resilience or vulnerability to inflammation.

Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis.

Background: Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which genes contribute to sex differences in autoimmune incidence.

Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation.

The deposition of islet amyloid polypeptide (hIAPP) fibrils is a hallmark of β-cell death in type II diabetes. In this study, we employ state-of-the-art MAS solid-state spectroscopy to investigate the previously elusive N-terminal region of hIAPP fibrils, uncovering both rigidity and heterogeneity. Comparative analysis between wild-type hIAPP and a disulfide-deficient variant (hIAPP) unveils shared fibril core structures yet strikingly distinct dynamics in the N-terminus.

Informational continuity of medication management in transitions of care: Qualitative interviews with stakeholders from the HYPERION-TransCare study.

Background: The transition of patients between inpatient and outpatient care can lead to adverse events and medication-related problems due to medication and communication errors, such as medication discontinuation, the frequency of (re-)hospitalizations, and increased morbidity and mortality. Older patients with multimorbidity and polypharmacy are particularly at high risk during transitions of care. Previous research highlighted the need for interventions to improve transitions of care in order to support information continuity, coordination, and communication.

The effect of measurement error on the positive predictive value of PSW methods for SLD identification: How buffer zones dispel the illusion of inaccuracy.

Patterns of Strengths and Weaknesses (PSW) methods are widely used for identifying specific learning disabilities (SLDs). Several researchers, however, have reported that the diagnostic accuracy of PSW methods is unacceptably low when strict thresholds were used to identify students with SLDs. We believe these findings give a misleading impression of the magnitude of the diagnostic errors that are likely to arise in PSW assessments.

Change of glucometabolic activity per PSMA expression predicts survival in mCRPC patients non-responding to PSMA radioligand therapy: introducing a novel dual imaging biomarker.

Purpose: The value of [F]fluorodeoxyglucose ([F]FDG) PET/CT in monitoring prostate-specific membrane antigen (PSMA) targeted radioligand therapy (RLT) is still unclear. The aim of this study was to identify appropriate prognostic dynamic parameters derived from baseline and follow-up [F]FDG and dual [F]FDG/[Ga]Ga-PSMA-11 PET/CT for monitoring early non-responding mCRPC patients undergoing PSMA-RLT.

Methods: Twenty-three mCRPC patients of a prospective registry (NCT04833517), who were treated with [Lu]Lu-PSMA-617 RLT and classified as early non-responders were included in this study.

Risk of abnormal uterine bleeding associated with high-affinity compared with low-affinity serotonin and norepinephrine reuptake inhibitors.

Background: Concerns have been raised about the potential association between selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) and the risk of abnormal uterine bleeding (AUB), which may be influenced by the affinity of SSRIs/SNRIs for serotonin transporter. Thus, we assessed whether SSRIs/SNRIs with high-affinity for serotonin transporter are associated with AUB compared to SSRIs/SNRIs with low-affinity in non-pregnant women.

Methods: Using the UK Clinical Practice Research Datalink, we identified a cohort of women aged 15-24 years, newly prescribed a high- or low-affinity SSRI/SNRI between 1990 and 2019.

MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration.

Neuroinflammation causes neuronal injury in multiple sclerosis (MS) and other neurological diseases. MicroRNAs (miRNAs) are important modulators of neuronal stress responses, but knowledge about their contribution to neuronal protection or damage during inflammation is limited. Here, we constructed a regulatory miRNA-mRNA network of inflamed motor neurons by leveraging cell type-specific miRNA and mRNA sequencing of mice undergoing experimental autoimmune encephalomyelitis (EAE).

Consistency checks to improve measurement with the Young Mania Rating Scale (YMRS).

Background: Mitigating rating inconsistency can improve measurement fidelity and detection of treatment response.

Methods: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that developed logical consistency (LC) checks for ratings of the Young Mania Rating Scale (YMRS), which is widely used in studies of mood and bipolar disorders. LC and statistical outlier-response pattern checks (SC) were applied to 63,228 YMRS administrations from 14 clinical trials evaluating treatments for bipolar disorder.

Calcium channel β3 subunit regulates ATP-dependent migration of dendritic cells.

Migratory dendritic cells (migDCs) continuously patrol tissues and are activated by injury and inflammation. Extracellular adenosine triphosphate (ATP) is released by damaged cells or actively secreted during inflammation and increases migDC motility. However, the underlying molecular mechanisms by which ATP accelerates migDC migration is not understood.

Implementation and evaluation of a complex intervention to improve information availability at the interface between inpatient and outpatient care in older patients with multimorbidity and polypharmacy (HYPERION-TransCare) - study protocol for a pilot and feasibility cluster-randomized controlled trial in general practice in Germany.

Background: Despite attempts to improve the cross-sectoral flow of information, difficulties remain in routine healthcare. The resulting negative impact on continuity of care is often associated with poor health outcomes, especially in older patients. Our intervention aims to increase information availability with respect to medications and health conditions at the interface between inpatient and outpatient care and to contribute towards improving the quality of care in older patients.

Portable RT-PCR and MinION Nanopore Sequencing as a Proof-of-Concept SARS-CoV-2 Biosurveillance in Wastewater.

In this study, wastewater samples collected from a participating sentinel site were initially screened for the presence or absence of SARS-CoV-2 RNA using portable RT-PCR, with positive samples sequenced using a handheld MinION nanopore sequencing device. Genomic biosurveillance of SARS-CoV-2 and its variants within wastewater has been established as an early warning system of infectious disease spread in a given catchment area, due to good correlation between spikes in viral levels detected in wastewater coincident with increases in COVID-19 incidence rates. Moreover, viral titers detected in a single wastewater sample are reflective of pre-symptomatic, asymptomatic, and post-symptomatic cases, making wastewater-based epidemiology (WBE) a cost-effective, non-invasive public health surveillance method complementary to clinical diagnostic testing.

Enhancing Partnerships of Institutions and Journals to Address Concerns About Research Misconduct: Recommendations From a Working Group of Institutional Research Integrity Officers and Journal Editors and Publishers.

Importance: Institutions and journals strive to promote and protect the integrity of the research record, and both groups are equally committed to ensuring the reliability of all published data.

Observations: Three US universities coordinated a series of virtual meetings from June 2021 to March 2022 for a working group composed of senior, experienced US research integrity officers (RIOs), journal editors, and publishing staff who are familiar with managing issues of research integrity and publication ethics. The goal of the working group was to improve the collaboration and transparency between institutions and journals to ensure that research misconduct and publication ethics are managed properly and efficiently.

[SaxoForN-a transregional primary care research network in Dresden and Frankfurt am Main : Design of a practice-based research infrastructure].

Establishing primary care research networks (PCRNs) makes it easier to conduct clinical trials and health services research in a general-practice setting. Since February 2020, the German Federal Ministry of Education and Research (BMBF) has sponsored the development of six PCRNs and a coordination unit throughout Germany, with the aim of setting up a sustainable outpatient research infrastructure to raise the quantity and quality of primary care.The present article describes the design of a PCRN in Dresden and Frankfurt am Main - SaxoForN - and explains its structure and how it operates.

Impact of COVID-19 on the Research Career Advancement of Health Equity Scholars from Diverse Backgrounds.

The COVID-19 pandemic has significantly taxed scientific research and seems to have exacerbated existing inequities within the research field, particularly for early-stage investigators (ESIs). This study examines the effects of the COVID-19 pandemic on traditionally underrepresented ESIs enrolled in an NIH-supported study evaluating the effectiveness of developmental networks, grant writing coaching, and mentoring on research career advancement. The survey consisted of 24 closed-ended (quantitative) and 4 open-ended questions (qualitative) linked to a participant's ability to meet grant submission deadlines, research and professional development disruptions, stress level, career transition level, self-efficacy and management of scholarly tasks, and familial responsibilities.

GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses.

G-protein coupled receptors (GPCR) regulate 3',5'-cyclic adenosine monophosphate (cAMP) levels in T cells. cAMP as ubiquitous second messenger is crucial for adequate physiology of T cells by mediating effector T cell (Teff) function as well as regulatory T cell (Treg)-mediated immunosuppression. Several GPCRs have been identified to be crucial for Teff and Treg function.

State-wide implementation of patient-reported outcome measures (PROMs) in specialized outpatient palliative care teams (ELSAH): A mixed-methods evaluation and implications for their sustainable use.

Background: Such patient-reported outcome measures (PROMs) and patient-centered outcome measures as the Integrated Palliative Care Outcome Scale (IPOS), Phase of Illness, and IPOS Views on Care (IPOS VoC), facilitate patient-centered care and help improve quality. To ensure sustainability, implementation and usage should be adapted according to setting. When settings involve several distinct teams that differ in terms of views and working practices, it is more difficult to integrate outcome measures into daily care.

Tipping points ahead? How laypeople respond to linear versus nonlinear climate change predictions.

We investigate whether communication strategies that portray climate change as a nonlinear phenomenon provoke increases in laypeople's climate change risk perceptions. In a high-powered, preregistered online experiment, participants were exposed to linear or nonlinear predictions of future temperature increases that would be expected if global greenhouse gas emissions were not reduced. We hypothesized that the type of climate change portrayal would impact perceptions of qualitative risk characteristics (catastrophic potential, controllability of consequences) which would, in turn, affect laypeople's holistic risk perceptions.