Polypharmacy in older patients with asthma: hidden risks and opportunities for improvement.

Introduction: Polypharmacy can be considered the norm in elderly patients, because older individuals experience an increasing number of concomitant respiratory and non-respiratory diseases other than asthma, carrying the risk of drug-to-drug-interactions and drug-to-comorbidities interactions. In this context, asthma in older adults, conventionally aging >65 years of age, cannot be adequately managed without considering their individual characteristics, as these challenge the traditional therapeutic algorithms/management strategies commonly applied to younger populations.

Areas Covered: The current article aims at addressing pitfalls and advantages of current pharmacological strategies in older individuals with asthma.

Cracking the Codes for Congenital Diarrhea and Enteropathies (CoDEs): A Case Report and Review.

Congenital diarrhea and enteropathies (CoDEs) condition is a rare cause of chronic diarrhea in infants that can be challenging to diagnose. This article discusses key signs to recognize in considering a CoDEs diagnosis and provides an overview of the diagnostic process. We report a late preterm twin infant with intractable watery diarrhea starting shortly after birth.

Exogenous estrogen partially rescues progesterone deficiency and autophagosome enlargement in mouse model with lysosomal storage disorder.

Objective: Female mice exhibit progressive progesterone (P4) deficiency, luteal cell degeneration, and premature embryo implantation failure at 5 months old. We attempted to rescue embryo implantation in non-virgin mice (5-6 months old) with exogenous P4 treatment on days 1.5 post-coitum (D1.

A Comparative Study of Auditory Processing and Working Memory Profiles in Young and Older Adults.

Purpose: This study aimed to profile and compare the auditory processing and working memory skills of young and older adults with near-normal hearing thresholds (up to 2000 Hz) and cognition. This was done to investigate the effect of aging on these skills despite exhibiting near-normal peripheral hearing in low frequencies and normal cognitive skills.

Method: Twenty-five young adults (18 to 35 years) and 35 older adults (56 to 79 years) were recruited for the study.

Delphi-driven consensus definition for mesenchymal stromal cells and clinical reporting guidelines for mesenchymal stromal cell-based therapeutics.

Background Aims: Despite promising results in pre-clinical studies, mesenchymal stromal cells (MSCs) face significant challenges in clinical translation. A scoping review by our group highlighted two key issues contributing to this gap: (i) lack of a clear and consensus definition for MSCs and (ii) under-reporting of critical parameters in MSC clinical studies. To address these issues, we conducted a modified Delphi study to establish and implement a consensus definition for MSCs and develop reporting guidelines for MSC clinical studies.

Cross-Generational Impact of Maternal Exposure to Low Level of PM2.5 on Kidney Health.

Introduction: Inhaled fine and ultrafine particulate matter may affect organs other than the lung, including the kidney. Recent studies have consistently shown the possibility of air pollution in highly polluted countries to be nephrotoxic. However, in countries like Australia, where air quality generally adheres to or remains below the WHO standards, the subtle yet consequential impacts of chronic exposure to seemingly safe levels of traffic PM2.

Focal segmental glomerulosclerosis (FSGS) in pregnancy: The case of a 27-year-old woman with nephrotic syndrome at 22 weeks of gestation.

Nephrotic syndrome (NS) in pregnancy has been associated with poor fetal outcomes. Focal segmental glomerulosclerosis (FSGS) is one of the common causes of NS and can be primary or secondary. However, there are few case reports of FSGS diagnosed in the peripartum period and the approaches to management.

Lifestyle Behaviors of Bronx Middle-School Students Enrolled in an Afterschool Program: Lessons Learned from the COVID-19 Shutdown.

A minority of American youth meet CDC lifestyle behavior recommendations. Children in the Bronx face barriers to healthy behaviors amplified by COVID-19. This research evaluated baseline behavior among distinct cohorts attending afterschool programming before and after the COVID-19 shutdown.

Recent advances in microfluidic chip technologies for applications as preclinical testing devices for the diagnosis and treatment of triple-negative breast cancers.

The leading cause of cancer-related death among female patients is breast cancer. Among all the types of breast cancer, triple-negative breast cancer (TNBC) is the most dangerous molecular subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. Since there is no particular therapeutic strategy for TNBC that has been shown to worsen the disease prognosis, 3D models are superior to 2D models as a predictive tool for drug discovery because they more accurately reflect the in vivo biological components of humans.

Timeliness of reperfusion in ST-segment elevation myocardial infarction and outcomes in Kerala, India: results of the TRUST outcomes registry.

Purpose: Transatlantic guidelines endorse quality metrics for timely reperfusion in patients with ST-elevation myocardial infarction (STEMI). Compliance in low- and middle-income countries (LMICs) is largely unknown.

Study Design: We prospectively evaluated 2928 STEMI patients in Kerala, India, across 16 PCI-capable hospitals who received reperfusion with either primary percutaneous coronary intervention (PPCI) or fibrinolysis.

Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration.

In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8 basaloid cells. IL11 is similarly expressed by KRT8 alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease.

Early and Late Microvascular Inflammation Have Differing Etiological Causes and Clinical Expression.

Background: Microvascular inflammation (MVI) is an important pathological feature of antibody-mediated rejection (AMR). How posttransplant time affects its clinicopathological expression is little understood.

Methods: This retrospective, single-center study screened 3398 kidney transplant biopsies and dichotomized 202 MVI ≥ 2 (Banff glomerulitis + peritubular capillaritis ≥ 2) samples by 9-mo median incidence time for comparison.

Differential diagnosis of suspected multiple sclerosis: global health considerations.

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe.

Reversible bonding in thermoplastic elastomer microfluidic platforms for harvestable 3D microvessel networks.

Transplantable ready-made microvessels have therapeutic potential for tissue regeneration and cell replacement therapy. Inspired by the natural rapid angiogenic sprouting of microvessels , engineered injectable 3D microvessel networks are created using thermoplastic elastomer (TPE) microfluidic devices. The TPE material used here is flexible, optically transparent, and can be robustly yet reversibly bonded to a variety of plastic substrates, making it a versatile choice for microfluidic device fabrication because it overcomes the weak self-adhesion properties and limited manufacturing options of poly(dimethylsiloxane) (PDMS).

Selective optogenetic inhibition of Gα or Gα signaling by minimal RGS domains disrupts circuit functionality and circuit formation.

Optogenetic techniques provide genetically targeted, spatially and temporally precise approaches to correlate cellular activities and physiological outcomes. In the nervous system, G protein-coupled receptors (GPCRs) have essential neuromodulatory functions through binding extracellular ligands to induce intracellular signaling cascades. In this work, we develop and validate an optogenetic tool that disrupts Gα signaling through membrane recruitment of a minimal regulator of G protein signaling (RGS) domain.

An approach - molecular docking analysis of flavonoids against GSK-3β and TNF-α targets in Alzheimer's disease.

Introduction: Drug development for Alzheimer's disease has one of the greatest failure rates of any therapeutic field and AD is still incurable. Glycogen synthase kinase-3β is a critical enzyme implicated in the pathogenesis of AD, particularly in the hyperphosphorylation of tau protein, which leads to the formation of neurofibrillary tangles. TNF-α also plays a significant role in the pathogenesis of Alzheimer's disease by promoting neuroinflammation, contributing to the formation of amyloid plaques and neurofibrillary tangles, impairing synaptic function, and disrupting the balance of neurotrophic factors.

Surgical Outcomes of Syndesmotic Fixation of Ankle Fractures Using Syndesmotic Screws Versus Suture Button Devices.

Introduction: Ankle fractures associated with disruption of the syndesmotic complex could potentially have poorer outcomes if missed or malreduced at the time of surgery. Favourable results have been reported for the suture button (SB) technique and may provide advantages over standard screw fixation of the syndesmosis, although this remains the gold standard method in many units.

Aim: To compare the outcomes of syndesmotic screws (SS) with SB fixation of the syndesmosis during ankle fracture fixation at a high-volume orthopaedic department of a Scotland trauma unit.

Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia.

Background: Progressive supranuclear palsy (PSP) is largely a sporadic disease with few reported familial cases. Genome-wide association studies (GWAS) in sporadic PSP in Caucasian populations have identified MAPT as the most commonly associated genetic risk locus with the strongest effect size. At present there are limited data on genetic factors associated with PSP in Asian populations.

TFE3 fusions direct an oncogenic transcriptional program that drives OXPHOS and unveils vulnerabilities in translocation renal cell carcinoma.

Translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic metabolism of most other renal cancers. This TFE3 fusion-driven OXPHOS program, together with heightened glutathione levels found in renal cancers, renders tRCCs sensitive to reductive stress - a metabolic stress state induced by an imbalance of reducing equivalents.

Etiology and Outcomes in Patients With Chronic Kidney Disease and Ascites.

Introduction Nephrogenic ascites is an uncommon disorder associated with grave prognosis. Studies on etiopathogenesis and outcomes are scarce. This study aimed to identify the etiologies of ascites in patients with chronic kidney disease (CKD) and estimate the proportion of nephrogenic ascites and the 90-day mortality.

Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).

Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS).

Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed.