Association between extracellular DNA levels, markers of inflammation and left ventricular mass index in children with chronic kidney disease.

Chronic kidney disease (CKD) is associated with chronic low-grade inflammation, but the primary factors triggering this inflammation remain unclear. Extracellular or cell-free DNA (exDNA) originates from virtually all tissues, being released during cell death, and stimulates the innate immune system. Our study was designed as an observational, cross-sectional cohort study of children with CKD (both before and after kidney transplantation) and controls to analyze associations between exDNA, markers of inflammation, and cardiovascular health.

Expression Levels of MUC5AC and MUC5B in Airway Goblet Cells Are Associated with Traits of COPD and Progression of Chronic Airflow Limitation.

Mucins 5AC (MUC5AC) and 5B (MUC5B) are the major mucins providing the organizing framework for the airway's mucus gel. We retrieved bronchial mucosal biopsies and bronchial wash (BW) samples through bronchoscopy from patients with chronic obstructive pulmonary disease ( = 38), healthy never-smokers ( = 40), and smokers with normal lung function ( = 40). The expression of MUC5AC and MUC5B was assessed immunohistochemically.

Anti-gene oligonucleotide clamps invade dsDNA and downregulate expression.

Anti-gene oligonucleotides belong to a group of therapeutic compounds, which, in contrast to antisense oligonucleotides, bind to DNA. Clamp anti-gene oligonucleotides bind through a double-stranded invasion mechanism. With two arms connected by a linker, they hybridize to one of the DNA strands forming Watson-Crick and Hoogsteen hydrogen bonds.

Plasmon-Enhanced Fluorescence of Single Extracellular Vesicles Captured in Arrayed Aluminum Nanoholes.

Extracellular vesicles (EVs) are nanoparticles encapsulated with a lipid bilayer, and they constitute an excellent source of biomarkers for multiple diseases. However, the heterogeneity in their molecular compositions constitutes a major challenge for their recognition and profiling, thereby limiting their application as an effective biomarker. A single-EV analysis technique is crucial to both the discovery and the detection of EV subpopulations that carry disease-specific signatures.

Kidney Function Decline After COVID-19 Infection.

Importance: COVID-19 infection has been associated with acute kidney injury. However, its possible association with long-term kidney function is not well understood.

Objective: To investigate whether kidney function decline accelerated after COVID-19 compared with after other respiratory tract infections.

Clinical importance of patient-reported outcome measures in severe asthma: results from U-BIOPRED.

Rationale: Knowledge about the clinical importance of patient-reported outcome measures (PROMs) in severe asthma is limited.

Objectives: To assess whether and to what extent asthma exacerbations affect changes in PROMS over time and asthma-specific PROMs can predict exacerbations in adult patients with severe asthma in usual care.

Methods: Data of 421 patients with severe asthma (62% female; mean age 51.

Distinct Tissue-Dependent Composition and Gene Expression of Human Fetal Innate Lymphoid Cells.

The human fetal immune system starts to develop in the first trimester and likely plays a crucial role in fetal development and maternal-fetal tolerance. Innate lymphoid cells (ILCs) are the earliest lymphoid cells to arise in the human fetus. ILCs consist of natural killer (NK) cells, ILC1s, ILC2s, and ILC3s that all share a common lymphoid origin.

Epigenetic suppression of creatine kinase B in adipocytes links endoplasmic reticulum stress to obesity-associated inflammation.

In white adipose tissue, disturbed creatine metabolism through reduced creatine kinase B (CKB) transcription contributes to obesity-related inflammation. However, the mechanisms regulating CKB expression in human white adipocytes remain unclear. By screening conditions perturbed in obesity, we identified endoplasmic reticulum (ER) stress as a key suppressor of CKB transcription across multiple cell types.

Development and External Validation of a Combined Clinical-Radiomic Model for Predicting Insufficient Hypertrophy of the Future Liver Remnant following Portal Vein Embolization.

Objectives: This study aimed to develop and externally validate a model for predicting insufficient future liver remnant (FLR) hypertrophy after portal vein embolization (PVE) based on clinical factors and radiomics of pretreatment computed tomography (CT) PATIENTS AND METHODS: Clinical information and CT scans of 241 consecutive patients from three Swedish centers were retrospectively collected. One center (120 patients) was applied for model development, and the other two (59 and 62 patients) as test cohorts. Logistic regression analysis was adopted for clinical model development.

Emerging mutation in SARS-CoV-2 facilitates escape from NK cell recognition and associates with enhanced viral fitness.

In addition to adaptive immunity, natural killer (NK) cells of the innate immune system contribute to the control of viral infections. The HLA-E-restricted SARS-CoV-2 Nsp13232-240 epitope VMPLSAPTL renders infected cells susceptible to NK cells by preventing binding to the inhibitory receptor NKG2A. Here, we report that a recently emerged methionine to isoleucine substitution at position 2 (pM2I) of Nsp13232-240 impairs binding of the mutated epitope to HLA-E and diminishes HLA-E/peptide complex stability.

Exploring the Anxiolytic Potential of NPY by a Dipeptidyl Peptidase-IV Inhibitor in an Animal Model of PTSD.

Background: The regulatory neuropeptide Y (NPY) is implicated in anxiety and post-traumatic stress disorder (PTSD)-related behaviors. NPY exerts its effects through 5 receptor subtypes, with Y1 and Y2 receptors being predominantly expressed in the rat brain. Activation of Y1 by full-length NPY1-36 induces anxiolytic effects, whereas Y2 binds truncated peptides, eliciting region-specific anxiogenic responses.

Longitudinal changes in regional fat and muscle composition and cardiometabolic biomarkers over 5 years of hormone therapy in transgender individuals.

Background: Longitudinal studies investigating hormone therapy in transgender individuals are rare and often limited to 1- to 2-year follow-up periods.

Objectives And Methods: We examined changes in body composition, muscle volumes, and fat distribution as well as muscle strength, arterial stiffness, and cardiometabolic biomarkers in both transgender men (TM; n = 17, age 25 ± 5 years) and transgender women (TW; n = 16, age 28 ± 5 years) at baseline and after 1 and 5-6 years of hormone therapy in a longitudinal prospective cohort design. Whole-body and regional fat and muscle volumes were analyzed using magnetic resonance imaging, and blood samples were taken.

Clinical spectrum of primary hemophagocytic lymphohistiocytosis: experience of reference centers in Central and Southeast Anatolia.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease, with a high mortality if left untreated. In addition, the disease has unique diagnostic challenges. Therefore, despite the existing guidelines on management, current clinical practice data is informative on the course and outcome.

Impaired branched-chain amino acid (BCAA) catabolism during adipocyte differentiation decreases glycolytic flux.

Dysregulated branched-chain amino acid (BCAA) metabolism has emerged as a key metabolic feature associated with the obese insulin-resistant state, and adipose BCAA catabolism is decreased in this context. BCAA catabolism is upregulated early in adipogenesis, but the impact of suppressing this pathway on the broader metabolic functions of the resultant adipocyte remains unclear. Here, we use CRISPR/Cas9 to decrease BCKDHA in 3T3-L1 and human pre-adipocytes, and ACAD8 in 3T3-L1 pre-adipocytes to induce a deficiency in BCAA catabolism through differentiation.

A genome-wide association study in Swedish colorectal cancer patients with gastric- and prostate cancer in relatives.

Background: A complex inheritance has been suggested in families with colorectal-, gastric- and prostate cancer. Therefore, we conducted a genome-wide association study (GWAS) in colorectal cancer patients, who's relatives had prostate-, and/or gastric cancer.

Methods: The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden.

Assessing Pharmacokinetics and Safety of Therapeutic Alpha-1-Microglobulin in First-in-Human Kidney Transplantation: A Noncomparative Open-Label Multiple-Dose Phase 1b Study.

Background: RMC-035 is a modified version of alpha-1-microglobulin, an endogenous protein developed as a renoprotective agent. Its intended use is to reduce the risk of irreversible loss of kidney function in cardiac surgery patients and to reduce delayed graft function in kidney transplant recipients. This first-in-human study aimed to evaluate the pharmacokinetics and safety of RMC-035 in kidney transplant recipients.

Augmented glycerosomes as a promising approach against fungal ear infection: Optimization and microbiological, and assessments.

In the current study, voriconazole (VCZ) augmented glycerosomes were optimized for topical otomycosis management according to a 2 factorial design, employing a thin film hydration method. By optimizing Glycerol volume, limonene: VCZ ratio and Span® 60: soybean phosphatidyl choline (PC) ratio, glycerosomes with maximum percentage entrapment efficiency (%EE) and zeta potential (ZP) and minimum vesicle size (VS) and polydispersity index (PDI) were to be obtained. An optimal augmented glycerosomal formula (OAG) that contained 10 mg VCZ, 150 mg PC, and 3 mL glycerol, comprising 2.

Weight Changes Are Linked to Adipose Tissue Genes in Overweight Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18-40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care.

Long-term effects of pelvic floor training in male chronic pelvic pain, correlation between subjective and objective outcomes: a study protocol for a randomised controlled trial.

Introduction: Chronic primary pelvic pain syndrome (CPPPS) is a condition characterised by pain in the pelvic area together with lower urinary tract symptoms. Pathophysiology remains largely unclear. Common treatment modalities show unsatisfactory results.