Mitochondrial Ca2+-coupled generation of reactive oxygen species, peroxynitrite formation, and endothelial dysfunction in Cantú syndrome.

Cantú syndrome is a multisystem disorder caused by gain-of-function (GOF) mutations in KCNJ8 and ABCC9, the genes encoding the pore-forming inward rectifier Kir6.1 and regulatory sulfonylurea receptor SUR2B subunits, respectively, of vascular ATP-sensitive K+ (KATP) channels. In this study, we investigated changes in the vascular endothelium in mice in which Cantú syndrome-associated Kcnj8 or Abcc9 mutations were knocked in to the endogenous loci.

Multi-drug resistance pattern and genome-wide SNP detection in levofloxacin-resistant uropathogenic Escherichia coli strains.

Objectives: Antibiotic treatment is extremely stressful for bacteria and has profound effects on their viability. Such administration induces physiological changes in bacterial cells, with considerable impact on their genome structure that induces mutations throughout the entire genome. This study investigated drug resistance profiles and structural changes in the entire genome of uropathogenic Escherichia coli (UPEC) strains isolated from six adapted clones that had evolved under laboratory conditions.

Impaired intracellular Ca signaling contributes to age-related cerebral small vessel disease in mutant mice.

Humans and mice with mutations in and manifest hallmarks of cerebral small vessel disease (cSVD). Mice with a missense mutation in at amino acid 1344 () exhibit age-dependent intracerebral hemorrhages (ICHs) and brain lesions. Here, we report that this pathology was associated with the loss of myogenic vasoconstriction, an intrinsic vascular response essential for the autoregulation of cerebral blood flow.

PI3K block restores age-dependent neurovascular coupling defects associated with cerebral small vessel disease.

Unlabelled: Neurovascular coupling (NVC), a vital physiological process that rapidly and precisely directs localized blood flow to the most active regions of the brain, is accomplished in part by the vast network of cerebral capillaries acting as a sensory web capable of detecting increases in neuronal activity and orchestrating the dilation of upstream parenchymal arterioles. Here, we report a mutant mouse model of cerebral small vessel disease (cSVD) with age-dependent defects in capillary-to-arteriole dilation, functional hyperemia in the brain, and memory. The fundamental defect in aged mutant animals was the depletion of the minor membrane phospholipid phosphatidylinositol 4,5 bisphosphate (PIP ) in brain capillary endothelial cells, leading to the loss of inwardly rectifier K (Kir2.

Faulty TRPM4 channels underlie age-dependent cerebral vascular dysfunction in Gould syndrome.

Gould syndrome is a rare multisystem disorder resulting from autosomal dominant mutations in the collagen-encoding genes and Human patients and mutant mice display brain pathology that typifies cerebral small vessel diseases (cSVDs), including white matter hyperintensities, dilated perivascular spaces, lacunar infarcts, microbleeds, and spontaneous intracerebral hemorrhage. The underlying pathogenic mechanisms are unknown. Using the mouse model, we found that vasoconstriction in response to internal pressure-the vascular myogenic response-is blunted in cerebral arteries from middle-aged (12 mo old) but not young adult (3 mo old) animals, revealing age-dependent cerebral vascular dysfunction.

In Vitro Probiotic Characterization and Safety Assessment of Lactic Acid Bacteria Isolated from Raw Milk of Japanese-Saanen Goat ().

Two novel probiotic strains of lactic acid bacteria were successfully isolated from the raw milk of dairy Japanese-Saanen goats. Selection criteria for positive candidates were grown on de Man-Rogosa-Sharpe or M17 selective medium at 30, 35, or 42 °C anaerobically, and characterized based on Gram reaction, catalase test, and tolerance to low pH and bile salts. Among the 101 isolated positive candidates, two strains, YM2-1 and YM2-3, were selected and identified as using 16S rDNA sequence similarity.

Prognostic Impact of Ectopic Fat Deposition within Psoas Muscle in Stage IV Gastric Cancer Patients Undergoing Systemic Chemotherapy.

In this study, we focused on the fat ratio within psoas muscle (FRPM) and sought to clarify the impact of FRPM on overall survival (OS) in stage IV gastric cancer (GC) patients undergoing systemic chemotherapy ( = 79, median age = 69 years, 59 males). The median FRPM was 1.67 %.

A Prospective Study Regarding the Efficacy and Safety of the BNT162b2 Vaccine in Patients With Solid Malignancies Undergoing Systemic Chemotherapy.

Background/aim: To prospectively evaluate the efficacy and safety of the BNT162b2 vaccine in solid cancer patients undergoing systemic chemotherapy (n=63).

Patients And Methods: COVID-19 anti-spike protein antibody levels were measured before the first BNT162b2 vaccination, just before the second BNT162b2 vaccination, one month after the second BNT162b2 vaccination, and 3 months after the second BNT162b2 vaccination. Anti-spike protein antibody seropositivity was set at ≥0.

Postoperative Analgesia Management Evaluation in the Postanesthesia Unit: An Exploratory Analysis Based on Patient and Surgery Characteristics.

Purpose: Several methods have been proposed for postoperative pain management, including administration of opioid analgesics, epidural analgesia, and perineural and infiltrative techniques; however, data are lacking on the relationship between pain intensity, patients' age and gender, and surgery duration.

Design: Prospective, observational, single-center study.

Methods: The study included patients greater than or equal to 18 years old who underwent surgery with different anesthesia types, grouped according to the American Society of Anesthesiologists' physical status classification score.

A Scoping Review on the Status of Female Breast Cancer in Asia with a Special Focus on Nepal.

This study aimed to provide updated evidence on the status of female breast cancer and cancer treatment facilities in Asia, with a special focus on Nepal. This review used search phrases that included, breast neoplasm or cancer, health status, epidemiology, breast cancer survivors, cancer care facilities, Asia, Nepal. Researchers examined databases from January 2011 to December 2020 (PubMed, PMC, Google Scholar, and the reference lists of included papers).

The Relevance in the Neutrophil to Lymphocyte Ratio and the SARC-F Score in Gastrointestinal Diseases.

We sought to clarify the relevance in the neutrophil to lymphocyte ratio (NLR) and the SARC-F score in patients with gastrointestinal diseases (G-Ds, n = 672, median age = 73 years). Univariate and multivariate analysis for the SARC-F score were performed. Advanced malignancy was identified in 162 patients (24.

Prevalence of Shiga toxin-producing Escherichia coli in Yezo sika deer (Cervus nippon yesoensis) in the Tokachi sub-prefecture of Hokkaido, Japan.

In food hygiene, the surveillance of foodborne pathogens in wild animals is indispensable because we cannot control hygienic status of them. Yezo sika deer (Cervus nippon yesoensis), which are found only on the island of Hokkaido, Japan, are the most common game animal in the country. In this study, we analyzed the incidence of Shiga toxin-producing Escherichia coli (STEC) in Yezo sika deer hunted in the Tokachi sub-prefecture, which is one of the densest zones for the sub-species.

STIM1-dependent peripheral coupling governs the contractility of vascular smooth muscle cells.

Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate the membrane potential and contractility of vascular smooth muscle cells (VSMCs). The mechanisms responsible for these membrane interactions are poorly understood. In many cells, STIM1 (stromal interaction molecule 1), a single-transmembrane-domain protein that resides in the endoplasmic reticulum (ER), transiently moves to ER-PM junctions in response to depletion of ER Ca stores and initiates store-operated Ca entry (SOCE).

Nitric Oxide Signals Through IRAG to Inhibit TRPM4 Channels and Dilate Cerebral Arteries.

Unlabelled: Nitric oxide (NO) relaxes vascular smooth muscle cells (SMCs) and dilates blood vessels by increasing intracellular levels of cyclic guanosine monophosphate (cGMP), which stimulates the activity of cGMP-dependent protein kinase (PKG). However, the vasodilator mechanisms downstream of PKG remain incompletely understood. Here, we found that transient receptor potential melastatin 4 (TRPM4) cation channels, which are activated by Ca released from the sarcoplasmic reticulum (SR) through inositol triphosphate receptors (IPRs) under native conditions, are essential for SMC membrane depolarization and vasoconstriction.

Brain endothelial cell TRPA1 channels initiate neurovascular coupling.

Cerebral blood flow is dynamically regulated by neurovascular coupling to meet the dynamic metabolic demands of the brain. We hypothesized that TRPA1 channels in capillary endothelial cells are stimulated by neuronal activity and instigate a propagating retrograde signal that dilates upstream parenchymal arterioles to initiate functional hyperemia. We find that activation of TRPA1 in capillary beds and post-arteriole transitional segments with mural cell coverage initiates retrograde signals that dilate upstream arterioles.

The intracellular Ca release channel TRPML1 regulates lower urinary tract smooth muscle contractility.

TRPML1 (transient receptor potential mucolipin 1) is a Ca-permeable, nonselective cation channel that is predominantly localized to the membranes of late endosomes and lysosomes (LELs). Intracellular release of Ca through TRPML1 is thought to be pivotal for maintenance of intravesicular acidic pH as well as the maturation, fusion, and trafficking of LELs. Interestingly, genetic ablation of TRPML1 in mice ( ) induces a hyperdistended/hypertrophic bladder phenotype.

Rapid Serotyping of Isolates Based on Single Nucleotide Polymorphism-Like Sequence Profiles of a Specific Gene.

Although serotyping is the most important method of identification of taxonomy in , conventional serotype determination with a complete set of antisera is time consuming and laborious. Recently, rapid serotyping procedures with polymerase chain reaction (PCR) have been developed. In this study, we established a novel PCR-based rapid serotyping method that employs a unique target gene.

Genomic Sequences of Uropathogenic Escherichia coli Strains with Various Fluoroquinolone Resistance Profiles.

The emergence of drug-resistant uropathogenic (UPEC) has hampered antibiotic therapy for urinary tract infections. To elucidate the resistance mechanisms of UPEC, we performed whole-genome sequencing of eight UPEC strains with different fluoroquinolone resistance levels. Here, we report our sequencing data, providing a valuable resource for understanding such mechanisms.

TRPML1 channels initiate Ca sparks in vascular smooth muscle cells.

TRPML1 (transient receptor potential mucolipin 1) is a Ca-permeable, nonselective cation channel localized to the membranes of endosomes and lysosomes and is not present or functional on the plasma membrane. Ca released from endosomes and lysosomes into the cytosol through TRPML1 channels is vital for trafficking, acidification, and other basic functions of these organelles. Here, we investigated the function of TRPML1 channels in fully differentiated contractile vascular smooth muscle cells (SMCs).

Fermentation Ability of Gut Microbiota of Wild Japanese Macaques in the Highland and Lowland Yakushima: In Vitro Fermentation Assay and Genetic Analyses.

Wild Japanese macaques (Macaca fuscata Blyth) living in the highland and lowland areas of Yakushima are known to have different diets, with highland individuals consuming more leaves. We aim to clarify whether and how these differences in diet are also reflected by gut microbial composition and fermentation ability. Therefore, we conduct an in vitro fermentation assay using fresh feces from macaques as inoculum and dry leaf powder of Eurya japonica Thunb.

Evaluation of the Integrated Health Information System (IHIS) in Public Hospitals in Cyprus Utilizing the DIPSA Framework.

Introduction: The Ministry of Health of the Republic of Cyprus has implemented an Integrated Health Information System (IHIS) in two hospitals. However, no evaluation of IHIS has been conducted to assess its safety, efficiency and effectiveness. The proper utilization of IHIS is essential for the provision of quality healthcare services.

Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature.

Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (ATRs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the ATR blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone.

Nanoscale coupling of junctophilin-2 and ryanodine receptors regulates vascular smooth muscle cell contractility.

Junctophilin proteins maintain close contacts between the endoplasmic/sarcoplasmic reticulum (ER/SR) and the plasma membrane in many types of cells, as typified by junctophilin-2 (JPH2), which is necessary for the formation of the cardiac dyad. Here, we report that JPH2 is the most abundant junctophilin isotype in native smooth muscle cells (SMCs) isolated from cerebral arteries and that acute knockdown diminishes the area of sites of interaction between the SR and plasma membrane. Superresolution microscopy revealed nanometer-scale colocalization of JPH2 clusters with type 2 ryanodine receptor (RyR2) clusters near the cell surface.