Hit II

BACKGROUND: Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH. METHODS: Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019...

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache...

Delta opioid receptors hold potential as a target for neurological and psychiatric disorders, yet no delta opioid receptor agonist has proven efficacious in critical phase II clinical trials. The exact reasons for the failure to produce quality drug candidates for the delta opioid receptor is nuclear. However, it is known that certain delta opioid receptor agonists can induce seizures and exhibit tachyphylaxis. Several studies have suggested that those adverse effects are more prevalent in delta agonists that share the SNC80/BW373U86 chemotype...

We performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. The 3178 patients who met inclusion criteria were predominantly male (97%) and white (75%). Median age of diagnosis for Black patients was 63 years vs 69 years for the entire cohort ( p  < 0.001). However, patients in each race/ethnicity subgroup presented with similar rates of stage I/II and III/IV disease, IPI score, cell of origin and HIT status...

Salt stress significantly impacts the functions of the photosynthetic apparatus, with varying degrees of damage to its components. Photosystem II (PSII) is more sensitive to environmental stresses, including salinity, than photosystem I (PSI). This study investigated the effects of different salinity levels (0 to 200 mM NaCl) on the PSII complex in isolated thylakoid membranes from hydroponically grown pea ( Pisum sativum L.) and maize ( Zea mays L.) plants treated with NaCl for 5 days. The data revealed that salt stress inhibits the photochemical activity of PSII (H2 O → BQ), affecting the energy transfer between the pigment-protein complexes of PSII (as indicated by the fluorescence emission ratio F695 /F685 ), QA reoxidation, and the function of the oxygen-evolving complex (OEC)...

Chagas disease, or American trypanosomiasis, is a neglected tropical disease which is a top priority target of the World Health Organization. The disease, endemic mainly in Latin America, is caused by the protozoan Trypanosoma cruzi and has spread around the globe due to human migration. There are multiple transmission routes, including vectorial, congenital, oral, and iatrogenic. Less than 1% of patients have access to treatment, relying on two old redox-active drugs that show poor pharmacokinetics and severe adverse effects...

The advent of ultra-large libraries of drug-like compounds has significantly broadened the possibilities in structure-based virtual screening, accelerating the discovery and optimization of high-quality lead chemotypes for diverse clinical targets. Compared to traditional high-throughput screening, which is constrained to libraries of approximately one million compounds, the ultra-large virtual screening approach offers substantial advantages in both cost and time efficiency. By expanding the chemical space with compounds synthesized from easily accessible and reproducible reactions and utilizing a large, diverse set of building blocks, we can enhance both the diversity and quality of the discovered lead chemotypes...

BACKGROUND: Mendelian randomization (MR) studies are susceptible to metadata errors (e.g. incorrect specification of the effect allele column) and other analytical issues that can introduce substantial bias into analyses. We developed a quality control (QC) pipeline for the Fatty Acids in Cancer Mendelian Randomization Collaboration (FAMRC) that can be used to identify and correct for such errors. METHODS: We collated summary association statistics from fatty acid and cancer genome-wide association studies (GWAS) and subjected the collated data to a comprehensive QC pipeline...

Alzheimer's disease accounts for 60-70% of dementia cases. Current treatments are inadequate and there is a need to develop new approaches to drug discovery. Recently, in cancer, morphological profiling has been used in combination with high-throughput screening of small-molecule libraries in human cells in vitro . To test feasibility of this approach for Alzheimer's disease, we developed a cell morphology-based drug screen centred on the risk gene, SORL1 (which encodes the protein SORLA). Increased Alzheimer's disease risk has been repeatedly linked to variants in SORL1 , particularly those conferring loss or decreased expression of SORLA, and lower SORL1 levels are observed in post-mortem brain samples from individuals with Alzheimer's disease...

Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug response. Significant progress has been made in pMHCII presentation modeling due to the collection of large-scale pMHC mass spectrometry datasets (ligandomes) and advances in machine learning. Here, we develop graph-pMHC, a graph neural network approach to predict pMHCII presentation...

Despite many benefits, the extensive deployment of Health Information Technology (HIT) systems by healthcare organizations has encountered many challenges, particularly in the field of telemetry concerning patient monitoring and its operational workflow. These challenges can add more layers of complexity when an unplanned software security patching is performed, affecting patient monitoring and causing disruption in daily clinical operations. This study is a reflection on what happened associated with software security patching and why it happened through the lens of an incident report to develop potential preventive and corrective strategies using qualitative analyses-inductive and deductive approaches...

A remarkably high rate of post-transplant relapse in patients with TP53-mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non-HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non-HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion (p < ...

BACKGROUND: The Nonstructural Protein (NSP) 4B of Zika virus of 251 amino acids from (ZIKV/Human/POLG_ZIKVF) with accession number (A0A024B7W1), Induces the production of Endoplasmic Reticulum ER-derived membrane vesicles, which are the sites of viral replication. To understand the physical basis of how proteins fold in nature and to solve the challenge of protein structure prediction, Ab-initio and comparative modeling are crucial tools. RESULTS: The systematic in silico technique, ThreaDom, had only predicted one domain (4 - 190) of NSP4B...

Clostridioides difficile, a gram-positive anaerobic bacterium, is one of the most frequent causes of nosocomial infections. C. difficile infection (CDI) results in almost a half a million infections and approximately 30,000 deaths in the U.S. each year. Broad-spectrum antibacterial use is a strong risk factor for development of recurring CDI. There is a critical need for narrow-spectrum antibacterials with activity limited to C. difficile. The C. difficile enoyl-acyl carrier protein (ACP) reductase II enzyme (CdFabK), an essential and rate-limiting enzyme in the organism's fatty acid biosynthesis pathway (FAS-2), is an attractive target for narrow-spectrum CDI therapeutics as it is not present in many of the non-pathogenic gut organisms...

BACKGROUND: This study examined access to technology, internet usage, and online health information-seeking behaviors, in a racially diverse, lower-income population. METHODS: Data were obtained via a cross-sectional survey of low-income communities in Houston, Los Angeles, and New York between April and August 2023. Binary responses to the following online health information-seeking behaviors, internet and technology access, were examined: using the internet to (i) understand a medical diagnosis, (ii) fill a prescription, (iii) schedule a healthcare appointment, (iv) email communication with a healthcare provider, and (v) access electronic health records and medical notes...

Research on Alzheimer disease (AD) genetics has provided critical advances to the knowledge of AD pathophysiological mechanisms. The etiology of AD can be divided into monogenic (autosomal dominant inheritance) and complex (multifactorial determinism). In monogenic AD, recent advances mainly concern mutation-associated mechanisms, presymptomatic clinical studies, and the search for modifiers of ages of onset that are still ongoing. In complex AD, genetic factors can be further categorized into three classes: (i) the APOE-ɛ4 and ɛ2 common alleles that represent a category by themselves as they are both common and with a strong impact on AD risk; (ii) common variants with a modest effect, identified in genome-wide association studies (GWAS); and (iii) rare variants with a moderate-to-strong effect, identified in case-control sequencing studies...

BACKGROUND: Despite growing attention paid to health equity and efforts to promote gender mainstreaming-a global strategy to promote gender equality-how policymakers have 'institutionalized' this in their work is less clear. Therefore, this planned scoping review seeks to search the peer-reviewed and grey literature to compile evidence on the ways in which policymakers have routinely or systematically considered equity and/or gender in their work. METHODS: A scoping review will be undertaken by drawing on the PRISMA guidelines for Scoping Reviews (PRISMA-ScR)...

Antibiotics resistance by bacterial pathogens is a major concern to public health worldwide resulting in high health care costs and rising mortality. Subtractive proteomics prioritized D-alanyl-D-alanine carboxypeptidas (DacB) enzyme from Enterobacter cloacae ATCC 13047 as a potential candidate for drugs designing to block pathogen cell wall biosynthesis. Virtual screening of an antibacterial library against the target unraveled a hit compound (2-[(1-methylsulfonylpiperidin-3-yl)methyl]-6-(1H-pyrazol-4-yl) pyrazine) showing high affinity and stability with the target...

Multiple factors cause heart failure with preserved ejection fraction (HFpEF) and involve various systems. HFpEF prevalence is rapidly rising, and its prognosis remains poor after the first hospitalization. Adopting a more active lifestyle has been shown to provide beneficial clinical outcomes for HFpEF patients. Using a two-hit HFpEF murine model, we studied cardiac reverse remodelling (RR) after stopping the causing stress and introducing voluntary exercise (VE). We checked in 2-month-old male and female C57Bl6/J mice the heart's response to angiotensin II (AngII; 1...

BACKGROUND: Autoimmune diseases (ADs) may be complicated by sepsis when intensive care unit (ICU) admission. But repeated sepsis among AD patients has not been studied yet. The aim of this study is to investigate the impact of repeated in-ICU sepsis on the 1-year overall-cause mortality, septic shock and in-ICU death of AD patients. METHODS: Data of AD patients with sepsis retrieved from Medical Information Mart for Intensive Care IV (MIMIC-IV) database were divided into the single group and the repeated group according to the frequency of in-ICU sepsis...