A systematic review and meta-analysis of interventions to delabel low-risk penicillin allergies with consideration for sex and gender.

Aims: Sex and gender may influence penicillin allergy label (PAL) prevalence and outcomes. This review evaluates the effectiveness and safety of direct delabelling (DD) and oral challenge (OC) for low-risk patients and examines sex and gender differences in reporting and outcomes.

Methods: We searched PubMed, Database of Abstracts of Reviews and Effects, ClinicalTrials.

STEMIN and YAP5SA, the future of heart repair?

This review outlines some of the many approaches taken over a decade or more to repair damaged hearts. We showcase the recent breakthroughs in organ regeneration elicited by reprogramming factors OCT3/4, SOX2, KLF4, and C-MYC (OKSM). Transient OKSM transgene expression rejuvenated senescent organs in mice.

Comprehensive stable-isotope tracing of glucose and amino acids identifies metabolic by-products and their sources in CHO cell culture.

Mammalian cell culture processes are widely utilized for biotherapeutics production, disease diagnostics, and biosensors, and hence, should be optimized to support robust cell growth and viability. However, toxic by-products accumulate in cultures due to inefficiencies in metabolic activities and nutrient utilization. In this study, we applied comprehensive C stable-isotope tracing of amino acids and glucose to two Immunoglobulin G (IgG) producing Chinese Hamster Ovary (CHO) cell lines to identify secreted by-products and trace their origins.

Lysophosphatidic Acid Signaling in the Gastrointestinal System.

The intestinal epithelium undergoes continuous homeostatic renewal to conduct the digestion and absorption of nutrients. At the same time, the intestinal epithelial barrier separates the host from the intestinal lumen, preventing systemic infection from enteric pathogens. To maintain homeostasis and epithelial functionality, stem cells, which reside in the base of intestinal crypts, generate progenitor cells that ultimately differentiate to produce an array of secretory and absorptive cells.

Highly Soluble β-Glucan Fiber Modulates Mechanisms of Blood Glucose Regulation and Intestinal Permeability.

β-glucans found in cereal grains have been previously demonstrated to improve blood glucose control; however, current understanding points to their high viscosity as the primary mechanism of action. In this work, we present a novel, highly soluble, low-viscosity β-glucan fiber (HS-BG fiber) and a preclinical dataset that demonstrates its impact on two mechanisms related to the prevention of hyperglycemia. Our results show that HS-BG inhibits the activity of two key proteins involved in glucose metabolism, the α-glucosidase enzyme and the SGLT1 transporter, thereby having the potential to slow starch digestion and subsequent glucose uptake.

Retrospective evaluation of shock index and mortality in dogs with head trauma (2015-2020): 86 cases.

Objective: To assess the relationship between shock index (SI) and mortality in dogs with head trauma (HT). A secondary objective was to compare SI with the animal trauma triage (ATT) score and Modified Glasgow Coma Scale (MCGS) score in HT cases. A tertiary aim was to assess if SI is predictive of survival to discharge or improvement in presenting neurologic signs.

Increased Generalization, Stronger Acquisition, or Reduced Extinction? Investigation of the Mechanisms Underlying the Acquisition-in-Multiple-Contexts Effect.

Prior research has demonstrated that conducting acquisition in multiple contexts results in more responding to the point that it can even nullify the benefit of subsequent extinction in multiple contexts on reducing renewal of excitatory responding. The underlying mechanism to explain why this happens has not been systematically examined. Using self-reported expectancy of the outcome, the current study investigates three mechanisms that potentially explain why acquisition in multiple contexts results in more responding-greater generalization, stronger acquisition learning, or slower extinction learning.

LPA-Dependent signaling regulates regeneration of the intestinal epithelium following irradiation.

Lysophosphatidic acid (LPA) is a bioactive lipid molecule that regulates a wide array of cellular functions, including proliferation, differentiation, and survival, via activation of cognate receptors. The LPA receptor is highly expressed in the intestinal epithelium, but its function in restoring intestinal epithelial integrity following injury has not been examined. Here, we use a radiation-induced injury model to study the role of LPA in regulating intestinal epithelial regeneration.

AKAP12 Upregulation Associates With PDE8A to Accelerate Cardiac Dysfunction.

Background: In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3',5'-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases).

The origin recognition complex requires chromatin tethering by a hypervariable intrinsically disordered region that is functionally conserved from sponge to man.

The first step toward eukaryotic genome duplication is loading of the replicative helicase onto chromatin. This 'licensing' step initiates with the recruitment of the origin recognition complex (ORC) to chromatin, which is thought to occur via ORC's ATP-dependent DNA binding and encirclement activity. However, we have previously shown that ATP binding is dispensable for the chromatin recruitment of fly ORC, raising the question of how metazoan ORC binds chromosomes.

Predicting school uptake of The Daily Mile in Northern Ireland- a data linkage study with School Census Data and Multiple Deprivation Measures.

Background: Participating in physical activity benefits health, yet a majority of children remain inactive. The Daily Mile™ (TDM) originated in Scotland in 2012 with the aim of increasing primary school children's physical fitness. Despite being a practically feasible and popular initiative, it remains unclear the extent to which schools implement TDM, and whether TDM core principles are adhered to (i.

Protein intrinsically disordered regions have a non-random, modular architecture.

Motivation: Protein sequences can be broadly categorized into two classes: those which adopt stable secondary structure and fold into a domain (i.e. globular proteins), and those that do not.

Neurological injury following peripheral nerve blocks: a narrative review of estimates of risks and the influence of ultrasound guidance.

Background: Peripheral nerve injury or post-block neurological dysfunction (PBND) are uncommon but a recognized complications of peripheral nerve blocks (PNB). A broad range of its incidence is noted in the literature and hence a critical appraisal of its occurrence is needed.

Objective: In this review, we wanted to know the pooled estimates of PBND and further, determine its pooled estimates following various PNB over time.

The experience of maternal mental distress in The Gambia: A qualitative study identifying idioms of distress, perceptions of contributing factors and the supporting role of existing cultural practices.

Maternal mental health problems are experienced frequently in the perinatal period and can be up to twice as common in women from low- and middle-income countries. The terms used to describe mental illness symptoms and the factors that contribute to developing these symptoms are affected by culture and context. Based on 14 focus group discussions held with pregnant women, health professionals and cultural leaders, this qualitative study aimed to understand women's experiences of mental distress during the perinatal period in The Gambia.

Mapping sleep's oscillatory events as a biomarker of Alzheimer's disease.

Introduction: Memory-associated neural circuits produce oscillatory events including theta bursts (TBs), sleep spindles (SPs), and slow waves (SWs) in sleep electroencephalography (EEG). Changes in the "coupling" of these events may indicate early Alzheimer's disease (AD) pathogenesis.

Methods: We analyzed 205 aging adults using single-channel sleep EEG, cerebrospinal fluid (CSF) AD biomarkers, and Clinical Dementia Rating® (CDR®) scale.

Expression of antenatal symptoms of common mental disorders in The Gambia and the UK: a cross-sectional comparison study.

Objectives: It is important to be able to detect symptoms of common mental disorders (CMDs) in pregnant women. However, the expression of these disorders can differ across cultures and depend on the specific scale used. This study aimed to (a) compare Gambian pregnant women's responses to the Edinburgh Postnatal Depression Scale (EPDS) and Self-reporting Questionnaire (SRQ-20) and (b) compare responses to the EPDS in pregnant women in The Gambia and UK.

Astrogliosis, neuritic microstructure, and sex effects: GFAP is an indicator of neuritic orientation in women.

Background: Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life.

A Novel Mouse Model to Analyze Non-Genomic ERα Physiological Actions.

Nongenomic effects of estrogen receptor α (ERα) signaling have been described for decades. Several distinct animal models have been generated previously to analyze the nongenomic ERα signaling (eg, membrane-only ER, and ERαC451A). However, the mechanisms and physiological processes resulting solely from nongenomic signaling are still poorly understood.

Peripartum mental health and the role of the pharmacist: A scoping review.

Background: The global prevalence of peripartum mental illness is 20%, though estimates have increased since the start of the COVID-19 pandemic. Chronic illnesses affect one in five pregnancies and may be associated with higher rates of peripartum mental illness. Though pharmacists are well-positioned to facilitate appropriate and timely care of co-occurring mental and physical health conditions during this period, little is understood regarding their potential roles.

Chemical inhibitors of hexokinase-2 enzyme reduce lactate accumulation, alter glycosylation processing, and produce altered glycoforms in CHO cell cultures.

Chinese hamster ovary (CHO) cells, predominant hosts for recombinant biotherapeutics production, generate lactate as a major glycolysis by-product. High lactate levels adversely impact cell growth and productivity. The goal of this study was to reduce lactate in CHO cell cultures by adding chemical inhibitors to hexokinase-2 (HK2), the enzyme catalyzing the conversion of glucose to glucose 6-phosphate, and examine their impact on lactate accumulation, cell growth, protein titers, and N-glycosylation.

A Small Molecule That In Vitro Neutralizes Infection of SARS-CoV-2 and Its Most Infectious Variants, Delta, and Omicron.

The COVID-19 pandemic has underscored the urgent need to develop highly potent and safe medications that are complementary to the role of vaccines. Specifically, it has exhibited the need for orally bioavailable broad-spectrum antivirals that are able to be quickly deployed against newly emerging viral pathogens. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and its variants Delta and Omicron are still a major threat to patients of all ages.