The association between gout and subsequent cardiovascular events: a retrospective cohort study with 132,000 using propensity score matching in primary care outpatients in Germany.

Background: Both the risk of developing heart disease and the course of the disease are determined in particular by comorbidities. In this context, gout has recently been identified as an important factor in influencing the development of cardiovascular events such as heart failure or coronary artery disease.

Methods: This retrospective cohort study compared the incidence of angina pectoris (AP) (ICD-10: I20), myocardial infarction (MI) (ICD-10: I21, I22), chronic coronary heart disease (CHD) (ICD-10: I25), atrial fibrillation (AF), and heart failure (HF) as a function of gout in Germany in a large collective of 66,000 gout patients in comparison to 66,000 individuals without gout between using propensity score matching (1:1) from January 2005 to December 2020.

Autoantigen-specific CD4 T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases.

Pro-inflammatory autoantigen-specific CD4 T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced.

In vivo biocompatibility of a new hydrophobic coated Al/AlO nanowire surface on stents.

Background: Intima proliferation and in-stent restenosis is a challenging situation in interventional treatment of small vessel obstruction. Al/AlO nanowires have been shown to accelerate vascular endothelial cell proliferation and migration in vitro, while suppressing vascular smooth muscle cell growth. Moreover, surface modification of Al/AlO nanowires with poly[bis(2,2,2-trifluoromethoxy)phosphazene (PTFEP) coating enables further advantages such as reduced platelet adhesion.

Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the K channel TALK-2.

Two-pore domain K (K) channel activity was previously thought to be controlled primarily via a selectivity filter (SF) gate. However, recent crystal structures of TASK-1 and TASK-2 revealed a lower gate at the cytoplasmic pore entrance. Here, we report functional evidence of such a lower gate in the K channel K2P17.

Gynecomastia and Its Management In Boys With Partial Androgen Insensitivity Syndrome.

Introduction: Partial androgen insensitivity syndrome (PAIS) is a rare condition that is reported to be commonly associated with gynecomastia in males.

Objectives: To assess the management of gynecomastia in male PAIS.

Materials And Methods: Retrospective review of males with PAIS over the age of 10 years in the I-DSD registry.

In vivo endocultivation of CAD/CAM hybrid scaffolds in the omentum majus in miniature pigs.

Purpose: Correction of bony mandibular defects is a challenge in oral and maxillofacial surgery due to aesthetic and functional requirements. This study investigated the potential of a novel hybrid scaffold for bone regeneration and degradation assessment of the ceramic within the omentum majus over 6 months and the extent to which rhBMP-2 as a growth factor, alone or combined with a hydrogel, affects regeneration.

Materials And Methods: In this animal study, 10 Göttingen minipigs each had one scaffold implanted in the greater omentum.

Hepatitis B vaccine responders show higher frequencies of CD8 effector memory and central memory T cells compared to non-responders.

Hepatitis B (HB) infection is a major global health problem. There is limited knowledge about HB vaccination-induced immune memory responses. We compared the frequency of CD8 memory T cell subsets between responders (RSs) and non-responders (NRs) to HB vaccination.

Network medicine-based epistasis detection in complex diseases: ready for quantum computing.

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs) (1-3). Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs.

GOLD-Grade Specific Disease Characterization and Phenotyping of COPD Using Quantitative Computed Tomography in the Nationwide COSYCONET Multicenter Trial in Germany.

Introduction: The aim of this study was to apply quantitative computed tomography (QCT) for GOLD-grade specific disease characterization and phenotyping of air-trapping, emphysema, and airway abnormalities in patients with chronic obstructive pulmonary disease (COPD) from a nationwide cohort study.

Methods: As part of the COSYCONET multicenter study, standardized CT in ex- and inspiration, lung function assessment (FEV1/FVC), and clinical scores (BODE index) were prospectively acquired in 525 patients (192 women, 327 men, aged 65.7 ± 8.

The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis.

Background: Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota.

Methods: In a prospective, longitudinal study, we included pediatric (N = 30) and adult (N = 30) patients with newly or previously (>1 year) diagnosed UC.

Effect of a single pill concept on clinical and pharmacoeconomic outcomes in cardiovascular diseases.

Aims: Our study aimed to assess whether a single pill concept (SPC) is superior to a multi-pill concept (MPC) in reducing cardiovascular (CV) events, all-cause death, and costs in CV patients.

Method And Results: Anonymized medical claims data covering 2012-2018, including patients with hypertension, dyslipidaemia, and CV diseases who started a drug therapy either as SPC or identical MPC were analysed after 1:1-propensity score matching. Hospitalizations with predefined CV events, all-cause mortality, and costs were studied in 25 311 patients with SPC and 25 311 patients with MPC using incidence rate ratios (IRRs) and non-parametric tests for continuous variables.

The microRNA expression in crypt-top and crypt-bottom colonic epithelial cell populations demonstrates cell-type specificity and correlates with endoscopic activity in ulcerative colitis.

Background And Aims: Colonic epithelial barrier dysfunction is one of the early events in ulcerative colitis (UC) and microRNAs (miRNAs) participate in its regulation. However, cell type-specific miRNome during UC is still unknown. Thus, we aimed to explore miRNA expression patterns in colon tissue and epithelial cells at active and quiescent UC.

A Novel 3/4-Fused Indole Scaffold through Acid-Catalyzed Cascade Reaction.

3,4-bridged indoles are underrepresented among the vast number of indoles described in the literature. Attempts to access 3,4-macrocyclized indoles led to the unexpected formation of a novel tetracyclic indole through intramolecular acid-catalyzed ring contraction. The herein-established one-step synthetic route provides an excellent medicinal chemistry platform for the construction of screening libraries covering a unique chemical space of indoles.

Manual toothbrushing techniques for plaque removal and the prevention of gingivitis-A systematic review with network meta-analysis.

Background: The meaning of the toothbrushing technique for the effectivity of toothbrushing in terms of plaque removal and parameters of gingivitis is unknown. This systematic review and network meta-analysis (NMA) aimed to synthesize evidence from randomized controlled trials (RCTs).

Methods: We searched MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials, and the Web of Science for RCTs that compared any self-applied manual toothbrushing technique to any other technique or control and assessed plaque after toothbrushing and gingivitis.

Simultaneous Inference of Multiple Binary Endpoints in Biomedical Research: Small Sample Properties of Multiple Marginal Models and a Resampling Approach.

In biomedical research, the simultaneous inference of multiple binary endpoints may be of interest. In such cases, an appropriate multiplicity adjustment is required that controls the family-wise error rate, which represents the probability of making incorrect test decisions. In this paper, we investigate two approaches that perform single-step -value adjustments that also take into account the possible correlation between endpoints.

Individualized Physiotherapy of Upper Body Functional Movement Disorder - Two Illustrative Cases.

Background: Information on specialist physiotherapeutic treatment for functional movement disorders is scarce. Previous studies focussed on functional gait disorders and availability of descriptions of the practical application especially for other body regions is very limited.

Cases: We present two illustrative cases, demonstrating the key elements of physiotherapy for the treatment of functional movement disorders beyond gait difficulties.

The Role of Nrf2 in the Regulation of Mitochondrial Function and Ferroptosis in Pancreatic Cancer.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) represents the master regulator of the cellular antioxidant response and plays a critical role in tumorigenesis. This includes a preventive effect of Nrf2 on cell death through ferroptosis, which represents an essential mechanism of therapy resistance in malignant tumors, such as pancreatic ductal adenocarcinoma (PDAC) as one of the most aggressive and still incurable tumors. Addressing this issue, we provide an overview on Nrf2 mediated antioxidant response with particular emphasis on its effect on mitochondria as the organelle responsible for the execution of ferroptosis.

Intergenic risk variant rs56258221 skews the fate of naive CD4 T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease of unknown pathogenesis, with a high risk to develop cirrhosis and malignancies. Functional dysregulation of T cells and association with genetic polymorphisms in T cell-related genes were previously reported for PSC. Here, we genotyped a representative PSC cohort for several disease-associated risk loci and identified rs56258221 (BACH2/MIR4464) to correlate with not only the peripheral blood T cell immunophenotype but also the functional capacities of naive CD4 T (CD4 T) cells in people with PSC.