Genomic profiling at a single center cracks the code in inborn errors of immunity.

Inborn errors of immunity (IEI) entail a diverse group of disorders resulting from hereditary or de novo mutations in single genes, leading to immune dysregulation. This study explores the clinical utility of next-generation sequencing (NGS) techniques in diagnosing monogenic immune defects. Eight patients attending the immunodeficiency clinic and with unclassified antibody deficiency were included in the analysis.

The Value and Importance of a Professional Ethical Code for Medicines Development: IFAPP International Ethics Framework.

Pharmaceutical medicine professionals have to face many ethical problems during the entire life span of new medicines extending from animal studies to broad clinical practice. The primary aim of the general ethical principles governing research conducted in humans is to diminish the physical and psychological burdens of the participants in human drug studies but overlooks many additional social and ethical problems faced by medicine developers. These arise mainly at the interface connecting the profit-oriented pharmaceutical industry and the healthcare-centered medical profession cooperating in medicines development.

The paradoxical activity of BRAF inhibitors: potential use in wound healing.

The area of wound healing presents a promising field of interest for clinicians as well as the scientific community. A major concern for physicians is the rising number of elderly people suffering from diabetes, leprosy, tuberculosis and the associated chronic wounds. While traditional therapies target basic wound care, innovative strategies that accelerate wound healing are needed.

Effectiveness and safety of the use of sodium nitrite in patients with hypertension and pulmonary hypertension: a scoping review.

Evidence suggests that sodium nitrite may be effective in the treatment of hypertension and pulmonary hypertension. However, its use remains debated due to safety concerns. In response, a scoping review was conducted to map current knowledge on the efficacy and safety of sodium nitrite in patients with hypertension or pulmonary hypertension, addressing the question: What evidence supports the effectiveness and safety of using sodium nitrite in these patients? The databases MEDLINE (PubMed), EMBASE, Scopus, Web of Science, and LILACS were searched for clinical studies on hypertensive patients at any disease stage without restrictions on age, sex, ethnicity, publication date, or status.

Evidence for the anxiolytic- and antidepressant-like effects of three semi-synthetic derivatives of xylopic acid in mice.

Purpose: Major depressive disorder is one of the most common and burdensome psychiatric disorders worldwide. This study evaluated the anxiolytic- and antidepressant-like activity of three semi-synthetic derivatives of xylopic acid (XA) to identify the most promising derivative based on mechanism(s) of action, in vivo pharmacokinetics and in vitro cytotoxicity.

Methods: The anxiolytic potential and the involvement of GABAergic mechanisms were assessed in the elevated plus-maze and open field tests in mice.

Comprehensive Echocardiographic Protocol for Pigs with Emphasis on Diastolic Function: Advantages over MRI Assessment.

Swine are increasingly utilized in cardiovascular research due to their anatomical and physiological similarities to humans, particularly for studying diastolic dysfunction. While MRI offers excellent structural imaging, echocardiography provides superior real-time assessment of diastolic parameters. To address the lack of standardized methods and reduce variability across studies, we present a comprehensive guide for performing echocardiography in Yorkshire pigs, detailing anatomical considerations, equipment requirements, and technical approaches.

Restoring cefepime activity against multidrug-resistant KPC-producing by combination with boronic acid inhibitors, MB076 and S02030.

Foremost in the design of new β-lactamase inhibitors (BLIs) are the boronic acid transition state inhibitors (BATSIs). Two highly potent BATSIs being developed are S02030 and MB076 strategically designed to be active against cephalosporinases and carbapenemases, especially KPC. When combined with cefepime, S02030 and MB076 demonstrated potent antimicrobial activity against laboratory and clinical strains of expressing a variety of class A and class C β-lactamases, including and .

Temozolomide-Promoted MGMT Transcription Contributes to Chemoresistance by Activating the ERK Signalling Pathway in Malignant Melanoma.

Tumour cells possess a multitude of chemoresistance mechanisms, which could plausibly contribute to the ineffectiveness of chemotherapy. O-methylguanine-DNA methyltransferase (MGMT) is an important effector protein associated with Temozolomide (TMZ) resistance in various tumours. To some extent, the expression level of MGMT determines the sensitivity of cells to TMZ, but the mechanism of its expression regulation has not been fully elucidated.

Effects of Isoproterenol Administration in Dobutamine Stress Echocardiography.

Objective: This study evaluated the safety and efficacy of isoproterenol administration as an adjunct for achievement of target heart rate (HR) during dobutamine stress echocardiography (DSE).

Background: In DSE, optimal accuracy is achieved when a target HR of 85% of maximal predicted heart rate (MPHR) is attained. Although rarely studied, intravenous isoproterenol has been used as an adjunct therapy to dobutamine and atropine to increase chronotropic response during pharmacologic stress testing.

Aging and sex differences in salt sensitivity of blood pressure.

Salt sensitivity of blood pressure (SSBP) is a complex physiological trait characterized by changes in blood pressure in response to dietary salt intake. Aging introduces an additional layer of complexity to the pathophysiology of SSBP, with mitochondrial dysfunction, epigenetic modifications, and alterations in gut microbiota emerging as critical factors. Despite advancements in understanding these mechanisms, the processes driving increased salt sensitivity with age and their differential impacts across sexes remain unclear.

Neonatal Sevoflurane Exposure Exerts Sex-Specific Effects on Cognitive Function via C3- and TLR4-Related M1/M2 Microglial Cell Polarisation in Rats.

In this study, we aimed to explore the sex-specific effects and mechanisms of sevoflurane exposure on the neural development of pubertal rats on the basis of M1/M2 microglial cell polarisation and related signalling pathways. A total of 48 rat pups (24 males and 24 females) were assigned to the 0- or 2-h sevoflurane exposure group on the seventh day after birth. The Morris water maze (MWM) test was subsequently conducted on the 32nd to 38th days after birth.

A Natural Autophagy Activator Castanea crenata Flower Alleviates Skeletal Muscle Ageing.

Background: Sarcopenia, characterized by a gradual decline in skeletal muscle mass and function with age, significantly impacts both quality of life and mortality. Autophagy plays a crucial role in maintaining muscle health. There is growing interest in leveraging autophagy to mitigate muscle ageing effects.

Comparative dissection of transcriptional landscapes of human iPSC-NK differentiation and NK cell development.

Clinical and preclinical research has demonstrated that iPSC-derived NK (iNK) cells have a high therapeutic potential, yet poor understanding of the detailed process of their differentiation and their counterpart cell development has hindered therapeutic iNK cell production and engineering. Here we dissect the crucial differentiation of both fetal liver NK cells and iNK cells to enable the rational design of advanced iNK production protocols. We use a comparative analysis of single-cell RNA-seq (scRNA-seq) to pinpoint key factors lacking in the induced setting which we hypothesized would hinder iNK differentiation and/ or functionality.

A stumbling block in pancreatic cancer treatment: drug resistance signaling networks.

The primary node molecules in the cell signaling network in cancer tissues are maladjusted and mutated in comparison to normal tissues, which promotes the occurrence and progression of cancer. Pancreatic cancer (PC) is a highly fatal cancer with increasing incidence and low five-year survival rates. Currently, there are several therapies that target cell signaling networks in PC.

Sociodemographic and Clinical Determinants of the Quality of Life of Moroccan People With Multiple Sclerosis.

Background: The quality of life (QOL) of people with multiple sclerosis (MS) is considerably poorer than the QOL of people with other chronic diseases. QOL management should not be restricted to only clinical aspects but also factors modifying QOL. The aim of this study was to identify the sociodemographic and clinical determinants of QOL in people with MS.

Using Anal Cytology and Human Papillomavirus DNA and E6/E7 mRNA Detection to Optimize High-Resolution Anoscopy Referrals in Men Who Have Sex With Men With HIV.

Background: This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA).

Methods: This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing.

Defining and responding to the contextual drivers for implementation of antimicrobial stewardship in 14 neonatal units in South Africa.

Background: Research on the contextual drivers of antimicrobial stewardship (AMS) programme interventions in neonatal units is limited.

Methods: As part of a prospective mixed-methods multidisciplinary neonatal AMS (NeoAMS) interventional study in 14 South African hospitals, we applied a three-phased process to assess implementation barriers and contextual drivers experienced by participating health professionals. The study included: (Phase one; P1) a survey of pre-intervention barriers and enablers; (P2) written feedback during the study intervention phase; and (P3) semi-structured exit interviews.

First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors.

Background: Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach.

Comparison of Effect Sevoflurane-Based Anesthesia and Propofol-Based Anesthesia on the Early Postoperative Renal Function of Living Kidney Transplant Donors: A Randomized Controlled Trial.

Purpose: Living kidney transplantation is a common treatment for end-stage renal disease. The impact of anaesthetics on postoperative biomarkers of renal injury in living kidney transplant donors is not well understood.

Patients And Methods: 70 transplant donors who underwent kidney extraction were randomly assigned to following two groups: sevoflurane (S group) and propofol (P group).

Construction of an anaplastic thyroid cancer stratification signature to guide immune therapy selection and validation of the pivotal gene HLF through experiments.

Introduction: While most thyroid cancer patients have a favorable prognosis, anaplastic thyroid carcinoma (ATC) remains a particularly aggressive form with a median survival time of just five months. Conventional therapies offer limited benefits for this type of thyroid cancer. Our study aims to identify ATC patients who might bene t from immunotherapy.

From Atrial Small-conductance Calcium-activated Potassium Channels to New Antiarrhythmics.

Despite significant advances in its management, AF remains a major healthcare burden affecting millions of individuals. Rhythm control with antiarrhythmic drugs or catheter ablation has been shown to improve symptoms and outcomes in AF patients, but current treatment options have limited efficacy and/or significant side-effects. Novel mechanism-based approaches could potentially be more effective, enabling improved therapeutic strategies for managing AF.

The efficacy of resveratrol supplementation on inflammation and oxidative stress in type-2 diabetes mellitus patients: randomized double-blind placebo meta-analysis.

Background: The effects of resveratrol supplementation on inflammation and oxidative stress in patients with type 2 diabetes mellitus (T2DM) were controversial. A meta-analysis was performed to assess the changes in levels of inflammation and oxidative stress in patients with T2DM.

Methods: Relevant literatures before November 6, 2024 were screened through Web of Science,Embase,the Cochrane Library and other sources (ClinicalTrials, ProQuest Dissertations and Theses).

Knowledge, attitude, practices, and associated factors toward cervical cancer among female health sciences students of Addis Ababa University, Addis Ababa, Ethiopia.

Background: Cervical cancer is the most common cancer in women worldwide. Early screening and vaccination can prevent cervical cancer; however, the low levels of knowledge, attitude, and practice among the young can contribute to the high prevalence of cervical cancer.

Objective: This study aimed to assess the level of knowledge, attitude, and practice of cervical cancer and associated factors among female Health Sciences students of the College of Health Sciences at Addis Ababa University.

Trends and future predictions of chronic kidney disease due to diabetes mellitus type 2 attributable to dietary risks: insights based on GBD 2021 data.

Background: The 2021 Global Burden of Disease (GBD) study shows a continuous increase in the burden of chronic kidney disease due to diabetes mellitus type 2 (CKD-T2DM) from 1990 to 2021. This study examines the influence of dietary risk factors across various populations and socioeconomic groups.

Methods: Utilizing the 2021 GBD data, we analyzed age-standardized CKD-T2DM metrics-including mortality, disability-adjusted life years (DALY), and age-standardized rates (ASR)-stratified by age, gender, and region.

A gut instinct for childhood leukemia prevention: microbiome-targeting recommendations aimed at parents and caregivers.

Childhood leukemia accounts for 30% of all pediatric cancer cases with acute lymphoblastic leukemia (ALL) being the most common subtype. Involvement of the gut microbiome in ALL development has recently garnered interest due to an increasing recognition of the key contribution the microbiome plays in maintaining the immune system's homeostatic balance. Commensal gut microbiota provide a first line of defense against different pathogens and gut microbiome immaturity has been implicated in ALL pathogenesis.