[Influencing fracture healing by specific osteoporosis medications].

Background: Osteoporosis is a widespread disease defined by a reduction in bone mass and structure, thereby increasing the risk of fragility fractures. Treatment typically involves specific medications, which either inhibit bone resorption (antiresorptive) or stimulate bone formation (anabolic) and may potentially influence the healing of osteoporotic fractures. On the other hand, metabolic disorders, immune system dysfunctions or circulatory problems can impair fracture healing.

Clinical Practice Guideline: The Diagnosis and Treatment of Osteoporosis.

Background: Osteoporosis is a common disease that affects approximately 6 million people in Germany alone. Osteoporotic fractures impair the quality of life and may make independent living impossible. Recommendations on the diagnosis and treatment of osteoporosis are indispensable for the effective care of this large group of patients.

Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries.

Study Question: Does endometriosis affect the mental health of women using oral contraceptives?

Summary Answer: Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small.

What Is Known Already: Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear.

Study Design, Size, Duration: A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia.

Neuropsychiatric manifestations following chimeric antigen receptor T cell therapy for cancer: a systematic review of clinical outcomes and management strategies.

Background: Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative modality in the treatment of patients with cancer. However, it is increasingly evident that this therapeutic approach is not without its challenges. The unique nature of CAR-T cells as living drugs introduces a distinct set of side effects.

Predicting the risk of intensive care unit admission in patients with COVID-19 presenting in the emergency room: Development and evaluation of the CROSS score.

Background: Existing risk evaluation tools underperform in predicting intensive care unit (ICU) admission for patients with the Coronavirus Disease 2019 (COVID-19). This study aimed to develop and evaluate an accurate and calculator-free clinical tool for predicting ICU admission at emergency room (ER) presentation.

Methods: Data from patients with COVID-19 in a nationwide German cohort (March 2020-January 2023) were analyzed.

Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model.

Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture.

Blood and urinary cytokine balance and renal outcomes at orthopaedic surgery.

Background: In patients undergoing orthopaedic trauma surgery, acute kidney injury (AKI) can develop post-operatively and is a major cause of increased mortality and hospital stay time. Development of AKI is associated with three main processes: inflammation, ischaemia-reperfusion injury (IRI) and hypoperfusion. In this study, we investigated whether ratios of urine and blood anti-inflammatory biomarkers and biomarkers of hypoperfusion, IRI and inflammation are elevated in patients who develop post-trauma orthopaedic surgery acute kidney injury (PTOS-AKI).

Klebsiella pneumoniae Glycoconjugate Vaccine Leads Based on Semi-Synthetic O1 and O2ac Antigens.

Klebsiella pneumoniae (KP) is a common opportunistic pathogen that emerged as a new critical threat to human health, due to its hypervirulence and widespread resistance against many antibiotics, including carbapenems. Alternative intervention strategies such as vaccines are not available. Cell-surface lipopolysaccharides (LPS) and capsular polysaccharides (CPS) are attractive targets for vaccine development.

Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease.

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

Impact of dopamine deficiency and REM sleep behavior disorder on cognition in early neuronal synuclein disease with hyposmia.

Objectives: To determine the impact of dopamine deficiency and isolated REM sleep behavior disorder (iRBD) on cognitive performance in early neuronal alpha-synuclein disease (NSD) with hyposmia.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) developed by applying regression-based internal norms derived from a robust healthy control (HC) group. Performance was examined for participants with hyposmia classified as NSD-Integrated Staging System (NSD-ISS) Stage 2, either Stage 2A (CSF alpha-synuclein seed amplification assay [SAA]+, SPECT dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix.

Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM), and receptor-mediated endocytosis.

Diagnostic Use of Genome Sequencing in Patients With 11p15.5 Imprinting Disorder Features: A Pilot Study.

To assess the suitability of genome sequencing (GS) as the second step in the diagnostics of patients with the features of 11p15.5-associated imprinting disorders (ImpDis: Silver-Russell syndrome [SRS], Beckwith-Wiedemann syndrome [BWS]), we performed short-read GS in patients negatively tested for imprinting disturbances. Obtaining a genetic diagnosis for patients with the features of these syndromes is challenging due to the clinical and molecular heterogeneity and overlap, and many patients remain undiagnosed after the currently suggested stepwise diagnostic workup.

Label-free single-cell RNA multiplexing leveraging genetic variability.

Single cell RNA sequencing has provided unprecedented insights into the molecular cues and cellular heterogeneity underlying human disease. However, the high costs and complexity of single cell methods remain a major obstacle for generating large-scale human cohorts. Here, we compare current state-of-the-art single cell multiplexing technologies, and provide a widely applicable demultiplexing method, SoupLadle, that enables simple, yet robust high-throughput multiplexing leveraging genetic variability of patients.

Factors Associated With Emergency Medical Clinicians Leaving EMS.

Objectives: Many United States (U.S.) communities face challenges with Emergency Medical Services (EMS) workforce turnover.

The Importance of Diagnostics in the Treatment of Urinary Tract Infections in the United Kingdom.

Current diagnosis of urinary tract infections (UTIs) in the UK initially relies on self-reported patient symptoms with no point-of-care test robust enough to accurately identify the causative pathogen and inform on antibiotic susceptibility. In serious UTI cases, standard urine culture is regarded as the gold standard for diagnosis and involves direct isolation, culture and antibiotic susceptibility testing of pathogens. These methods are not suitable in initial UTI diagnosis and treatment because of the time taken to conduct these analyses (≥3 days).

Not Just 9-1-1: The Expanded Work Environment of United States Emergency Medical Service Clinicians.

Introduction: Recently, there have been annual increases in emergency medical service (EMS) demand with concurrent clinician shortages. Understanding the diverse number of EMS clinicians available for emergent roles is vital for planning and resource management. Our study aims to understand the roles and environments of US EMS clinicians.

Evidence of Magnetic Reconnection in Ganymede's Wake Region From Juno.

Magnetic reconnection has been commonly reported between the solar wind IMF and the magnetic field of Earth and other planets. A similar phenomenon is expected between Jupiter's magnetosphere and Ganymede's mini magnetosphere inside the Jovian magnetosphere. This article is the first report of a reconnection event in the tail region of Ganymede.

Digital Health Interventions for Informal Family Caregivers of People With First-Episode Psychosis: Systematic Review on User Experience and Effectiveness.

Background: First-episode psychosis (FEP) imposes a substantial burden not only on the individual affected but also on their families. Given that FEP usually occurs during adolescence, families overtake a big part of informal care. Early family interventions, especially psychoeducation, are crucial for informal family caregivers to best support the recovery of their loved one with FEP and to reduce the risk of a psychotic relapse as much as possible, but also to avoid chronic stress within the family due to the burden of care.

Microbial melatonin metabolism in the human intestine as a therapeutic target for dysbiosis and rhythm disorders.

Melatonin (MT) (N-acetyl-5-methoxytryptamine) is an indoleamine recognized primarily for its crucial role in regulating sleep through circadian rhythm modulation in humans and animals. Beyond its association with the pineal gland, it is synthesized in various tissues, functioning as a hormone, tissue factor, autocoid, paracoid, and antioxidant, impacting multiple organ systems, including the gut-brain axis. However, the mechanisms of extra-pineal MT production and its role in microbiota-host interactions remain less understood.

Inceptor binds to and directs insulin towards lysosomal degradation in β cells.

Blunted first-phase insulin secretion and insulin deficiency are indicators of β cell dysfunction and diabetes manifestation. Therefore, insights into molecular mechanisms that regulate insulin homeostasis might provide entry sites to replenish insulin content and restore β cell function. Here, we identify the insulin inhibitory receptor (inceptor; encoded by the gene IIR/ELAPOR1) as an insulin-binding receptor that regulates insulin stores by lysosomal degradation.

Causal inference concepts can guide research into the effects of climate on infectious diseases.

A pressing question resulting from global warming is how climate change will affect infectious diseases. Answering this question requires research into the effects of weather on the population dynamics of transmission and infection; elucidating these effects, however, has proved difficult due to the challenges of assessing causality from the predominantly observational data available in epidemiological research. Here we show how concepts from causal inference-the sub-field of statistics aiming at inferring causality from data-can guide that research.

Mortality in a Clostridium sordellii Case Series.

Introduction: Clostridium sordellii (C sordellii) is a gram positive, anaerobic bacterium that causes severe, often fatal infections. Classically, C sordellii infection is described as a high mortality process for women of childbearing age. We examined C sordellii infections in our hospital to determine if there have been any changes in prevalence, treatment, or outcome.