Factors associated with diabetes mellitus and hypertension among adults in the northern rural area, Afghanistan.

Afghanistan has an increasing trend of mortality due to non-communicable diseases but most studies were conducted in urban areas. This study aimed to assess the prevalence and factors associated with diabetes mellitus and hypertension in a rural area in Afghanistan. A cross-sectional study was conducted from September to October 2019 including 373 people who were 18-79 years old and lived in Andkhoy District, Afghanistan.

Potentiating CD20 monoclonal antibody therapy by targeting complement C3 fragment covalently deposited on lymphoma cells.

Monoclonal antibodies (mAbs) improve survival of patients with mature B-cell malignancies. Fcγ-receptor dependent effector mechanisms kill tumor cells but can promote antigen loss through trogocytosis, contributing to treatment failures. Cell-bound mAbs trigger the complement cascade to deposit C3 activation fragments and lyse cells.

A new pipeline SPICE identifies novel JUN-IKZF1 composite elements.

Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partners and DNA motif spacing preferences. Using SPICE, we successfully identified known composite elements, such as AP1-IRF composite elements (AICEs) and STAT5 tetramers, and also uncovered several novel binding partners, including JUN-IKZF1 composite elements.

The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup.

Endonuclease G promotes hepatic mitochondrial respiration by selectively increasing mitochondrial tRNA production.

Mitochondrial endonuclease G (EndoG) contributes to chromosomal degradation when it is released from mitochondria during apoptosis. It is presumed to also have a mitochondrial function because EndoG deficiency causes mitochondrial dysfunction. However, the mechanism by which EndoG regulates mitochondrial function is not known.

Association of Mycobacterium tuberculosis aerosolization and HIV coinfection in the index case with T cell responses in household contacts.

Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in Mtb antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve Mtb infection detection among exposed household contacts (HHCs) and are associated with index case Mtb aerosolization (i.

Effects of seven days' fasting on physical performance and metabolic adaptation during exercise in humans.

Humans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.

Modeling predicts facile release of nitrite but not nitric oxide from the thionitrate CHSNO with relevance to nitroglycerin bioactivation.

Nitroglycerin is a potent vasodilator in clinical use since the late 1800s. It functions as a prodrug that is bioactivated by formation of an enzyme-based thionitrate, E-Cys-NO. This intermediate reportedly decomposes to release NO and NO but their relative yields remain controversial.

Orthologs of and impact sleep in mice.

Model organisms such as are powerful tools to study the genetic basis of sleep. Previously, we identified the genes and using selective breeding for long and short sleep duration in an outbred population of . is a transcription factor that is part of the epidermal growth factor receptor signaling pathway, while is involved in proline and arginine metabolism.

Generation of induced pluripotent stem cell lines TRNDi037-A and TRNDi038-A from two patients with Alagille syndrome carrying heterozygous JAG1 mutations.

Human induced pluripotent stem cell (iPSC) lines TRNDi037-A and TRNDi038-A were generated from the lymphoblastoid cell lines (LCL) of two patients with different heterozygous JAG1 variants resulting in Alagille syndrome (ALGS). ALGS is a rare genetic disease of haploinsufficiency that affects the formation of the bile duct, in addition to other symptoms. These ALGS iPSC lines can be used to model ALGS and aid in the identification of therapeutics to treat patients with ALGS.

Obesity modulates NK-cell activity via LDL & DUSP1 signaling for Populations with Adverse Social Determinants.

African American (AA) women are disproportionally affected by obesity and hyperlipidemia, particularly in the setting of adverse social determinants of health (aSDoH) contributing to health disparities. Obesity, hyperlipidemia, and aSDoH appear to impair Natural Killer cells (NKs). As potential common underlying mechanisms are largely unknown, we sought to investigate common signaling pathways involved in NK dysfunction related to obesity and hyperlipidemia in AA women from under-resourced neighborhoods.

A deficiency screen identifies genomic regions critical for sperm head-tail connection.

The Sperm Neck provides a stable connection between the sperm head and tail, which is critical for fertility in species with flagellated sperm. Within the Sperm Neck, the Head-Tail Coupling Apparatus serves as the critical link between the nucleus (head) and the axoneme (tail) via the centriole. To identify regions of the Drosophila melanogaster genome that contain genetic elements that influence Head-Tail Coupling Apparatus formation, we undertook a 2 part screen using the Drosophila Deficiency kit.

An analysis of the structural changes of the oxygen evolving complex of Photosystem II in the S and S states revealed by serial femtosecond crystallography.

Photosystem II (PSII) is a unique natural catalyst that converts solar energy into chemical energy using earth abundant elements in water at physiological pH. Understanding the reaction mechanism will aid the design of biomimetic artificial catalysts for efficient solar energy conversion. The MnOCa cluster cycles through five increasingly oxidized intermediates before oxidizing two water molecules into O and releasing protons to the lumen and electrons to drive PSII reactions.

Unveiling Tissue-Specific RNA Landscapes in Mouse Organs During Fasting and Feeding Using Nanopore Direct RNA Sequencing.

Understanding tissue-specific RNA landscapes is essential for uncovering the functional mechanisms of key organs in mammals. However, current knowledge remains limited, as short-read RNA sequencing-the predominant method for assessing gene expression-depends on incomplete gene annotations and struggles to resolve the diverse transcripts produced by genes. To address these limitations, an integrative approach combining nanopore direct RNA sequencing (DRS), ATAC-Seq, and short-read RNA-seq is used.

Genomic Landscape of Thrombosis Recurrence Risk Across Venous Thromboembolism Subtypes.

Venous thromboembolism (VT) is a frequent (annual incidence of 1 to 2 per 1,000) and potentially life-threatening (case-fatality rate up to 10%) disease. VT is associated with serious short-term and long-term complications including a recurrence rate of approximately 20% within five years. Anticoagulant therapy, the mainstay of VT treatment, drastically reduces the risk of early VT recurrence, but it exposes patients to a substantial risk of bleeding.

Oxidation of CaMKIIα cysteines inhibits autonomous activation induced by phosphorylation.

Ca/calmodulin-dependent protein kinase II α (CaMKIIα) "autonomous" activation induced by Thr286 phosphorylation has a crucial role in synaptic plasticity. Previous studies showed that in Alzheimer's disease brain, CaMKIIα autophosphorylation at Thr286 is reduced while the level of cysteine-oxidized CAMKIIα is elevated. We performed tryptic mapping of the oxidized CaMKIIα and discovered the formation of a disulfide between the N-terminal Cys6 and the regulatory domain Cys280.

Epidemiology and Outcomes of Antibiotic De-escalation in Patients with Suspected Sepsis in US Hospitals.

Background: Little is known about the frequency, hospital-level variation, predictors, and clinical outcomes of antibiotic de-escalation in suspected sepsis.

Methods: We retrospectively analyzed all adults admitted to 236 US hospitals between 2017-2021 with suspected sepsis (defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration) who were initially treated with ≥2 days of anti-MRSA and anti-pseudomonal antibiotics but had no resistant organisms requiring these agents identified through hospital day 4. De-escalation was defined as stopping anti-MRSA and anti-pseudomonal antibiotics or switching to narrower antibiotics by day 4.

Effectiveness of electronic medical record-based strategies for death and hospital admission endpoint capture in pragmatic clinical trials.

Objective: Event capture in clinical trials is resource-intensive, and electronic medical records (EMRs) offer a potential solution. This study develops algorithms for EMR-based death and hospitalization capture and compares them with traditional event capture methods.

Materials And Methods: We compared the effectiveness of EMR-based event capture and site-captured events adjudicated by a clinical endpoint committee in the multi-center INfluenza Vaccine to Effectively Stop cardio Thoracic Events and Decompensated heart failure (INVESTED) trial for participants from the Veterans Affairs healthcare system.

Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease.

Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or -thalassemia.

Multicamera simultaneous total internal reflection and interference reflection microscopy.

Interference Reflection Microscopy (IRM) is an optical technique that relies on the interference between the reflected light from an incident beam as it passes through materials of different refractive indices. This technique has been successfully used to image microtubules, biologically important biofilaments with a diameter of 25 nm. However, it is often desirable to image both the microtubule and microtubule interacting proteins simultaneously.

Role of STING Deficiency in Amelioration of Mouse Models of Lupus and Atherosclerosis.

Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome characterized by autoreactive responses to nucleic acids, dysregulation of the type I interferon (IFN-I) pathway, and accelerated atherosclerosis. The stimulator of IFN genes (STING), a cytosolic DNA sensor, has pathogenic implications in various inflammatory diseases. However, its specific role in SLE pathogenesis, particularly in tissue damage, remains unclear.