Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons.

Huntington's Disease (HD) is caused by a CAG repeat expansion in the gene encoding Huntingtin (HTT . While normal HTT function appears impacted by the mutation, the specific pathways unique to CAG repeat expansion versus loss of normal function are unclear. To understand the impact of the CAG repeat expansion, we evaluated biological signatures of HTT knockout ( KO) versus those that occur from the CAG repeat expansion by applying multi-omics, live cell imaging, survival analysis and a novel feature-based pipeline to study cortical neurons (eCNs) derived from an isogenic human embryonic stem cell series (RUES2).

Enhanced fluorescence lifetime imaging microscopy denoising via principal component analysis.

Fluorescence Lifetime Imaging Microscopy (FLIM) quantifies the autofluorescence lifetime to measure cellular metabolism, therapeutic efficacy, and disease progression. These dynamic processes are intrinsically heterogeneous, increasing the complexity of the signal analysis. Often noise reduction strategies that combine thresholding and non-selective data smoothing filters are applied.

A Double-Gene Metabarcoding Approach for the Authentication of Shrimp Surimi-Based Products.

Background/objectives: Shrimp surimi-based products (SSPs) are composed of minced shrimp meat and are highly susceptible to food fraud as fish surimi. This study employed a double-gene metabarcoding approach to authenticate SSPs sold on Chinese e-commerce platforms.

Methods: 16S rRNA and 12S rRNA genes were amplified and sequenced from 24 SSPs.

16S rRNA metabarcoding applied to the microbiome of insect products (novel food): a comparative analysis of three reference databases.

The 16S rRNA metabarcoding, based on Next-Generation Sequencing (NGS), is used to assess microbial biodiversity in various matrices, including food. The process involves a "dry-lab" phase where NGS data are processed through bioinformatic pipelines, which finally rely on taxonomic unit assignment against reference databases to assign them at order, genus, and species levels. Today, several public genomic reference databases are available for the taxonomic assignment of the 16S rRNA sequences.

Novel Cyclohexyl Amido Acid Antagonists of Lysophosphatidic Acid Type 1 Receptor for the Treatment of Pulmonary Fibrosis.

Lysophosphatidic acid (LPA) is a phospholipid activating different biological functions by binding to G protein-coupled receptors (LPA). Among these, the role of the LPA receptor in modulating fibrotic processes is well-known, making it a therapeutic target for pulmonary fibrosis and other fibrotic disorders. Herein we report the search for a new class of LPA antagonists for the oral treatment of idiopathic pulmonary fibrosis with a focus on hepatobiliary safety.

Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST.

Ergothioneine (EGT) is a diet-derived, atypical amino acid that accumulates to high levels in human tissues. Reduced EGT levels have been linked to age-related disorders, including neurodegenerative and cardiovascular diseases, while EGT supplementation is protective in a broad range of disease and aging models. Despite these promising data, the direct and physiologically relevant molecular target of EGT has remained elusive.

Exploring Gender Differences in the Effects of Diet and Physical Activity on Metabolic Parameters.

Background: Gender differences in metabolic response to lifestyle interventions remain poorly explored. This study aimed to evaluate the impact of a six-month Mediterranean diet (MD) intervention combined with regular physical activity on metabolic parameters in overweight adults.

Methods: A prospective cohort study was conducted in an obesity clinic in Rome, Italy, involving overweight adults (BMI ≥ 25 kg/m) motivated to improve their lifestyle.

Microbiological Analysis Conducted on Raw Milk Collected During Official Sampling in Liguria (North-West Italy) over a Ten-Year Period (2014-2023).

Milk has been consumed by humans for thousands of years for its nutritional properties. In recent years, raw milk demand has increased, valued for its authenticity and connection to local traditions. In Italy, the sale of raw milk is allowed exclusively through direct sale from the producing farm to the final consumer, either at the producing farm itself or through vending machines.

Assessing the Effects of Immune Checkpoint Inhibitors on Bone Utilizing Machine Learning-assisted Opportunistic Quantitative Computed Tomography.

Immune checkpoint inhibitors (ICI) are widely used in cancer treatment, yet their impact on bone health remains unclear. This study aimed to perform a retrospective cohort study utilizing routine computed tomography (CT) scans from patients with melanoma to perform opportunistic quantitative CT (QCT) analysis to investigate the effects of ICI treatment on skeletal health, including volumetric bone mineral density (vBMD) measurements and osteoarthritis (OA) parameters. A previously established machine-learning assisted opportunistic QCT pipeline was used to estimate lumbar spine vBMD from baseline and 12-month follow-up CT scans in patients with melanoma treated with ICI therapy and those not treated with ICI therapy.

COVID-19 Pandemic Impact on the Birth Weight of Children Born in a Brazilian Metropolis.

Objective: To assess the birth weight of newborns whose mothers gave birth during the COVID-19 pandemic.

Methods: A cross-sectional study based on data collected from medical records and through postnatal interviews to assess maternal and neonatal health outcomes (n = 470) during the pandemic. All participants were assisted in three Brazilian public hospitals in 2020.

Exploring the impact of health literacy on pregnant women from ethnic minority groups: A scoping review.

Objective: Health Inequalities refer to disparities in healthcare access and outcomes based on social determinants of health. These inequalities disproportionately affect Black, Asian, Minority Ethnic (BAME) groups, particularly pregnant women, who face increased risks and limited access to care due to low health literacy. Maternal mortality rates for BAME women can be up to four times higher than for white women.

Assessing the knowledge, attitudes and practices of healthcare staff and students regarding disposal of unwantead medications: a systematic review.

Objectives: We sought to review studies that examine healthcare professionals' and students' knowledge, attitudes and practices (KAP) regarding medication disposal. We also explore recommendations and barriers related to appropriate medication disposal.

Design: A systematic review was conducted that adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Bradyarrhythmias in patients with embolic stroke of undetermined source: a tight relationship with atrial cardiomyopathy.

Background: Implantable loop recorders (ILRs) have been shown to significantly improve the detection of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS). The incidence and characterization of bradyarrhythmias in this subset of patients is still unknown.

Methods: All consecutive patients who received ILRs, after an ESUS, between March 2015 and December 2022 in our Center were retrospectively enrolled and analyzed.

Left atrial volumetric/mechanical coupling index and atrial fibrillation in the embolic stroke of undetermined source.

Introduction: Nowadays, no clear predictors of atrial fibrillation in patients with embolic stroke of undetermined source (ESUS) are known. Some echocardiographic parameters have been proposed as potential predictors of atrial fibrillation in patients with ESUS. The ratio between left atrial volume and tissue Doppler (TDI) a' provides the left atrial volumetric/mechanical coupling index (LACI) and represents a feasible surrogate for left atrial function, and might be useful to identify atrial fibrillation in this subset of patients.

Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes.

Arrayed CRISPR libraries extend the scope of gene-perturbation screens to non-selectable cell phenotypes. However, library generation requires assembling thousands of vectors expressing single-guide RNAs (sgRNAs). Here, by leveraging massively parallel plasmid-cloning methodology, we show that arrayed libraries can be constructed for the genome-wide ablation (19,936 plasmids) of human protein-coding genes and for their activation and epigenetic silencing (22,442 plasmids), with each plasmid encoding an array of four non-overlapping sgRNAs designed to tolerate most human DNA polymorphisms.

An Overview of a Re-Emerging Disease in Italy: Bovine Tuberculosis Outbreaks in Cattle from MTBC-Free Territories.

Bovine tuberculosis (bTB) is a zoonotic disease with consequences for public health as well as the economy. In the EU, compulsory eradication programmes have been applied, and most territories in Italy have been reported as disease-free (FTs). However, outbreaks (OBs), i.

Empowering Thai community pharmacists in combating antimicrobial resistance: Qualitative insight and sentiment analysis.

Background: Antimicrobial resistance (AMR) is increasing globally and poses a significant public health challenge. Community pharmacists, especially in primary care settings, play a pivotal role in mitigating the irrational use of antibiotics, a key driver of AMR.

Objectives: This study aims to explore qualitative insights from community pharmacists regarding antibiotic supply and usage, analyze sentiments related to AMR, and highlight the crucial role of community pharmacists in AMR stewardship at the primary care/community level.

Scoping review of enablers and challenges of implementing pharmacogenomics testing in the primary care settings.

Introduction: Pharmacogenomic testing (PGx) plays a crucial role in improving patient medication safety, yet ethical concerns and limitations impede its clinical implementation in the primary care settings.

Aims: To systematically review the current state of PGx in the primary care settings and determine the enablers and challenges of its implementation.

Design: A scoping review was carried out by adhering to Arksey and O'Malley's 6-stage methodological framework and the 2020 Joanna Briggs Institute and Levac DATA SOURCES: Cochrane Library, EMBASE, Global Health, MEDLINE and PubMed were searched up to 17 July 2023.

Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2.

Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson's disease (PD), with 10-30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity.

Antibacterial mechanism of atmospheric cold plasma against Pseudomonas fluorescens and Pseudomonas putida and its preservation application on in-packaged red shrimp paste.

This study aimed to investigate the antibacterial mechanism of atmospheric cold plasma (ACP) against Pseudomonas fluorescens and Pseudomonas putida and its preservation effect on red shrimp paste. A reactive species (RS) assay showed that O, HO, and total nitric oxide were generated after ACP treatment, which possessed great potential for antibacterial and food preservation. In vitro antibacterial results showed that excess RS inhibited bacterial activity through cell membrane damage.

Right ventricular-pulmonary artery coupling in patients undergoing cardiac resynchronization therapy.

Introduction: The ratio between tricuspid annular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (PASP) has been shown to be a reliable, non-invasive surrogate of the right ventricular-pulmonary artery (RV-PA) coupling. The present study analysed the association between TAPSE/PASP and response to cardiac resynchronization therapy (CRT) and the prognostic role of RV-PA in patients undergoing CRT implantation. The primary endpoints were: the association between baseline TAPSE/PASP and CRT response/cardiovascular and all-cause death.

Polypharmacy in primary care: A population-based retrospective cohort study of electronic health records.

Background: Polypharmacy, prescription of multiple medications to a patient, is a major challenge for health systems. There have been no peer-reviewed studies of polypharmacy prevalence and medication cost at a population level in England.

Aims: To determine prevalence and medication cost of polypharmacy, by patient characteristics.