Treatment with antibiotics is a major risk factor for infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to growth and competition between the microbiota and for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to infection in 12 different microbial communities cultivated from healthy individuals.
View Article and Find Full Text PDFMembers of the casein kinase 1 (CK1) family have emerged as key regulators of cellular signaling and as potential drug targets. Functional annotation of the 7 human isoforms would benefit from isoform-selective inhibitors, allowing studies on the role of these enzymes in normal physiology and disease pathogenesis. However, due to significant sequence homology within the catalytic domain, isoform selectivity is difficult to achieve with conventional small molecules.
View Article and Find Full Text PDFMicrobiol Resour Announc
August 2024
Bacteriophage Curie is a podovirus that infects . The Curie genome spans 16,810 bp, has 90 bp terminal inverted repeats, and includes 23 protein-coding genes. Its genome architecture resembles phage PineapplePizza and other phi29-like phages.
View Article and Find Full Text PDFHistamine is an important biogenic amine known to impact a variety of patho-physiological processes ranging from allergic reactions, gut-mediated anti-inflammatory responses, and neurotransmitter activity. Histamine is found both endogenously within specialized host cells and exogenously in microbes. Exogenous histamine is produced through the decarboxylation of the amino acid L-histidine by bacterial-derived histidine decarboxylase enzymes.
View Article and Find Full Text PDFClin Child Fam Psychol Rev
September 2024
Considerable attention has been devoted to the concept of flexible emotion regulation, which de-emphasizes the importance of any specific regulatory strategy in favor of the flexible deployment of strategies in response to specific situational challenges. The bulk of research in this area has been conducted on adult samples. Research on emotion regulation flexibility (ERF) in youth has been documented in only a limited number of studies and using various definitions.
View Article and Find Full Text PDFST-segment elevation myocardial infarction (STEMI) is a significant source of morbidity and mortality. Despite guideline-driven management and increased awareness of social determinants of health, there are persistent disparities in diagnosis, management, and outcomes. The coronavirus disease 2019 (COVID-19) pandemic has greatly affected emergency department visitation, conditions and throughput.
View Article and Find Full Text PDFThe quorum-sensing system links metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of HO, a crucial host defense against . We now report that protection by surprisingly extends beyond post-exponential growth to the exit from stationary phase when the system is no longer turned on. Thus, can be considered a constitutive protective factor.
View Article and Find Full Text PDFBackground And Objectives: Children undergoing airway management during general anesthesia may experience airway complications resulting in a rare but life-threatening situation known as "Can't Intubate, Can't Oxygenate". This situation requires immediate recognition, advanced airway management, and ultimately emergency front-of-neck access. The absence of standardized procedures, lack of readily available equipment, inadequate knowledge, and training often lead to failed emergency front-of-neck access, resulting in catastrophic outcomes.
View Article and Find Full Text PDFCoastal elevation data are essential for a wide variety of applications, such as coastal management, flood modelling, and adaptation planning. Low-lying coastal areas (found below 10 m +Mean Sea Level (MSL)) are at risk of future extreme water levels, subsidence and changing extreme weather patterns. However, current freely available elevation datasets are not sufficiently accurate to model these risks.
View Article and Find Full Text PDFIntroduction: The Department of Defense is reforming the military health system where surgeries are increasingly referred from military treatment facilities (MTFs) with direct care to higher-volume civilian hospitals under purchased care. This shift may have implications on the quality and cost of care for TRICARE beneficiaries. This study examined the impact of care source and surgical volume on perioperative outcomes and cost of total hip arthroplasties (THAs) and total knee arthroplasties (TKAs).
View Article and Find Full Text PDFBacteriophages (phages) are the most abundant biological entities on Earth, exerting a significant influence on the dissemination of bacterial virulence, pathogenicity, and antimicrobial resistance. Temperate phages integrate into the bacterial chromosome in a dormant state through intricate regulatory mechanisms. These mechanisms repress lytic genes while facilitating the expression of integrase and the CI master repressor.
View Article and Find Full Text PDFLantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome-derived commensals produce lantibiotics to impair pathogens' colonization and promote healthy microbiomes.
View Article and Find Full Text PDFNewly discovered liver lesions have a broad differential ranging from malignancy to infection. While tissue biopsy is the gold standard diagnostic modality, imaging can also aid in diagnosis. Hepatocellular carcinoma (HCC) can be diagnosed via imaging alone; however, masses suspicious for infection ultimately require biopsy and culture.
View Article and Find Full Text PDFStaphylococcus aureus is a clinically important bacterial pathogen that has become resistant to treatment with most routinely used antibiotics. Alternative strategies, such as vaccination and phage therapy, are therefore actively being investigated to prevent or combat staphylococcal infections. Vaccination requires that vaccine targets are expressed at sufficient quantities during infection so that they can be targeted by the host's immune system.
View Article and Find Full Text PDFIn Canada, individuals found not criminally responsible on account of mental disorder (NCR) fall under the supervision of a jurisdictional review board (RB) per the Criminal Code. Limited research has examined whether RB decisions balance the needs of public safety with social reintegration as intended by federal legislation. To fill this gap, the present study determined whether forensic decisional outcomes in one provincial RB system accounted for information relevant to violence risk.
View Article and Find Full Text PDFBackground: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.
View Article and Find Full Text PDFInterest in the communication between the gastrointestinal tract and central nervous system, known as the gut-brain axis, has prompted the development of quantitative analytical platforms to analyze microbe- and host-derived signals. This protocol enables investigations into connections between microbial colonization and intestinal and brain neurotransmitters and contains strategies for the comprehensive evaluation of metabolites in in vitro (organoids) and in vivo mouse model systems. Here we present an optimized workflow that includes procedures for preparing these gut-brain axis model systems: (stage 1) growth of microbes in defined media; (stage 2) microinjection of intestinal organoids; and (stage 3) generation of animal models including germ-free (no microbes), specific-pathogen-free (complete gut microbiota) and specific-pathogen-free re-conventionalized (germ-free mice associated with a complete gut microbiota from a specific-pathogen-free mouse), and Bifidobacterium dentium and Bacteroides ovatus mono-associated mice (germ-free mice colonized with a single gut microbe).
View Article and Find Full Text PDFBackground: 3-phenyllactic acid (PLA) is produced by both intestinal bacteria and the human host. PLA exists in its D- and L- chiral forms. It modulates human immune functions, thereby acting as a mediator of bacterial-host interactions.
View Article and Find Full Text PDFRes Child Adolesc Psychopathol
December 2023
The present study elucidates heterogeneity in post-traumatic stress symptoms (PTSS) across adolescence in a sample of youth who have experienced myriad types and combinations of potentially traumatic events (PTEs), including substantiated physical abuse, sexual abuse, neglect and/or at least one other self-reported PTE. A machine learning technique was used to assess a multivariate set of variables (e.g.
View Article and Find Full Text PDFMultiple sclerosis (MS) is an incurable autoimmune disease known to cause widespread demyelinating lesions in the central nervous system (CNS) and a host of debilitating symptoms in patients. The development of MS is believed to be driven by the breakdown of the blood brain barrier, subsequent infiltration by CD4 and CD8 T cells, and widespread CNS inflammation and demyelination. Disease modifying therapies (DMTs) profoundly disrupt these processes and therefore compose an essential component of disease management.
View Article and Find Full Text PDFInfluenza A virus (IAV) assembly at the plasma membrane is orchestrated by at least five viral components, including hemagglutinin (HA), neuraminidase (NA), matrix (M1), the ion channel M2, and viral ribonucleoprotein (vRNP) complexes, although particle formation is observed with expression of only HA and/or NA. While these five viral components are expressed efficiently in primary human monocyte-derived macrophages (MDMs) upon IAV infection, this cell type does not support efficient HA-M2 association and IAV particle assembly at the plasma membrane. Both defects are specific to MDMs and can be reversed upon disruption of F-actin.
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