Iron Chelation Prevents Age-Related Skeletal Muscle Sarcopenia in Klotho Gene Mutant Mice, a Genetic Model of Aging.

Background: A decline in skeletal muscle mass and function known as skeletal muscle sarcopenia is an inevitable consequence of aging. Sarcopenia is a major cause of decreased muscle strength, physical frailty and increased muscle fatigability, contributing significantly to an increased risk of physical disability and functional dependence among the elderly. There remains a significant need for a novel therapy that can improve sarcopenia and related problems in aging.

Integrating Model-Informed Drug Development With AI: A Synergistic Approach to Accelerating Pharmaceutical Innovation.

The pharmaceutical industry constantly strives to improve drug development processes to reduce costs, increase efficiencies, and enhance therapeutic outcomes for patients. Model-Informed Drug Development (MIDD) uses mathematical models to simulate intricate processes involved in drug absorption, distribution, metabolism, and excretion, as well as pharmacokinetics and pharmacodynamics. Artificial intelligence (AI), encompassing techniques such as machine learning, deep learning, and Generative AI, offers powerful tools and algorithms to efficiently identify meaningful patterns, correlations, and drug-target interactions from big data, enabling more accurate predictions and novel hypothesis generation.

Evaluation of Cartilage-Like Matrix Formation in a Nucleus Pulposus-Derived Cartilage Analog Scaffold.

The formation of fibrocartilage in microfracture (MFX) severely limits its long-term outlook. There is consensus in the scientific community that the placement of an appropriate scaffold in the MFX defect site can promote hyaline cartilage formation and improve therapeutic benefit. Accordingly, in this work, a novel natural biomaterial-the cartilage analog (CA)-which met criteria favorable for chondrogenesis, was evaluated in vitro to determine its candidacy as a potential MFX scaffold.

Safety, Tolerability, and Pharmacokinetics of NIM-1324 an Oral LANCL2 Agonist in a Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Trial.

NIM-1324 is an oral investigational new drug for autoimmune disease that targets the Lanthionine Synthetase C-like 2 (LANCL2) pathway. Through activation of LANCL2, NIM-1324 modulates CD4+ T cells to bias signaling and cellular metabolism toward increased immunoregulatory function while providing similar support to phagocytes. In primary human immune cells, NIM-1324 reduces type I interferon and inflammatory cytokine (IL-6, IL-8) production.

Chest wall lift for thoracoscopic lung lobectomy: Technique and results in two cats.

Objective: To report the technique and outcomes of utilizing chest wall lift to perform thoracoscopic surgery in two cats.

Study Design: Short case series.

Animals: Client-owned cats (n = 2).

A meta-analysis of eHealth interventions to promote physical activity in young, middle-aged, and late middle-aged adults with obesity or overweight.

The purpose of this study was to calculate the effects of recent eHealth interventions to promote physical activity in young, middle-aged, and late middle-aged adults with obesity or overweight. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. In the search, 3550 articles were identified, and 15 studies met all inclusion criteria.

Teaching experience, not surgical residency training, is the critical factor in optimizing student learning outcomes in performing ovariohysterectomy on a model.

Objective: To determine if surgical skills instructors' experience and qualifications influence students' learning of small animal ovariohysterectomy on a model (mOVH).

Sample Population: Second-year veterinary students (n = 105).

Methods: Students were randomized to three groups, taught by: (1) residency-trained surgeons with over 3 years' experience teaching mOVH, (2) general practitioners with over 3 years' experience teaching mOVH (GP >3), and (3) general practitioners with under 3 years' experience (GP <3).

Antepartum multidisciplinary approach improves postpartum pain scores in patients with opioid use disorder.

Objectives: Pregnancies affected by opioid use disorder (OUD) face difficulties with postpartum pain control. This study aims to determine if prenatal anesthesia consultation for patients on medication for opioid use disorder (MOUD) affects maternal postpartum pain control.

Methods: This is a retrospective cohort study of pregnant patients diagnosed on MOUD who received prenatal care and delivered at a single academic institution between January 2017 and July 2023.

New Insights Into Hepatic Impairment (HI) Trials.

Hepatic impairment (HI) trials are traditionally part of the clinical pharmacology development to assess the need for dose adaptation in people with impaired metabolic capacity due to their diseased liver. This review aimed at looking into the data from dedicated HI studies, cluster these data into various categories and connect the effect by HI with reported pharmacokinetics (PK) properties in order to identify patterns that may allow waiver, extrapolations, or adapted HI study designs. Based on a ratio ≥ 2 or ≤ 0.

WS/MHS PdTe/Si Mixed-Dimensional Heterojunction as Ultra-Broadband Photodetector for Health and Safety Monitoring.

Ultra-broadband photodetectors (UB-PDs) are essential in medical applications, public safety monitoring, and various other fields. However, developing UB-PDs covering multiple bands from ultraviolet to medium infrared remains a challenge due to material limitations. Here, a mixed-dimensional heterojunction composed of 2D WS/monodisperse hexagonal stacking (MHS) 3D PdTe particles on 3D Si is proposed, capable of detecting light from 365 to 9600 nm.

Comparative Evaluation of Chatbot Responses on Coronary Artery Disease.

Objective: Coronary artery disease (CAD) is the leading cause of morbidity and mortality globally. The growing interest in natural language processing chatbots (NLPCs) has driven their inevitable widespread adoption in healthcare. The purpose of this study was to evaluate the accuracy and reproducibility of responses provided by NLPCs, such as ChatGPT, Gemini, and Bing, to frequently asked questions about CAD.

Proximity-Ligation Metagenomic Sequence Analysis Reveals That the Antibiotic Resistome Makes Significant Transitions During Municipal Wastewater Treatment.

Shotgun and proximity-ligation metagenomic sequencing were used to generate thousands of metagenome assembled genomes (MAGs) from the untreated wastewater, activated sludge bioreactors, and anaerobic digesters from two full-scale municipal wastewater treatment facilities. Analysis of the antibiotic resistance genes (ARGs) in the pool of contigs from the shotgun metagenomic sequences revealed significantly different relative abundances and types of ARGs in the untreated wastewaster compared to the activated sludge bioreactors or the anaerobic digesters (p < 0.05).

Distinct Transmission of Left- and Right-Handed Magnon Modes in Compensated Ferrimagnet/Antiferromagnet Structures.

The chirality of magnons, exhibiting left- and right-handed polarizations analogous to the counterparts of spin-up and spin-down, has emerged as a promising paradigm for information processing. However, the potential of this paradigm is constrained by the controllable excitation and transmission of chiral magnons. Here, the magnon transmission is explored in the GdFeO/NiO/Pt structures.

Dasatinib and Quercetin Limit Gingival Senescence, Inflammation, and Bone Loss.

Cellular senescence has emerged as one of the central hallmarks of aging and drivers of chronic comorbidities, including periodontal diseases. Senescence can also occur in younger tissues and instigate metabolic alterations and dysfunction, culminating in accelerated aging and pathological consequences. Senotherapeutics, such as the combination of dasatinib and quercetin (DQ), are being increasingly used to improve the clinical outcomes of chronic disorders and promote a healthy life span through the reduction of senescent cell burden and senescence-associated secretory phenotype (SASP).

Cold Surface Waters of the Sub-Antarctic Pacific Ocean Support High Cyanophage Abundances and Infection Levels.

Cyanobacterial distributions are shaped by abiotic factors including temperature, light and nutrient availability as well as biotic factors such as grazing and viral infection. In this study, we investigated the abundances of T4-like and T7-like cyanophages and the extent of picocyanobacterial infection in the cold, high-nutrient-low-chlorophyll, sub-Antarctic waters of the southwest Pacific Ocean during austral spring. Synechococcus was the dominant picocyanobacterium, ranging from 4.

Analysis of healthcare utilization before the diagnosis of radiologically isolated syndrome.

Background: Previous studies have shown that people with multiple sclerosis (MS) had frequent healthcare visits up to 10 years before being diagnosed but with no information from magnetic resonance imaging (MRI) scans of the connection with the radiologically isolated syndrome (RIS).

Objective: To analyze healthcare use 3 years before the RIS diagnosis.

Methods: We examined healthcare usage before the first scan in RIS cases from 2010 to 2019.

Aggressive Digital Papillary Adenocarcinoma: A Meta-Analysis of the Presentation, Treatment, and Outcomes of a Rare Hand Tumor.

Background: Aggressive digital papillary adenocarcinoma (ADPA) is a rare skin adnexal tumor with a predilection for the hand. The presentation, treatment, and outcomes of ADPA remain poorly defined due to the scarcity of reports and low-level evidence of published findings.

Methods: We performed a meta-analysis following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines with the intent to provide hand surgeons a better understanding of the diagnosis and treatment of the disease.

Creation and validation of an extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) clinical risk scoring tool for select Enterobacterales in non-urinary isolates.

Background: Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) are increasing in the United States. Although many risk factor scoring tools exist, many are specific to bloodstream isolates and may not represent all patient populations. The purpose of this study was to create and validate an institution-specific scoring tool for select ESBL-E of non-urinary origin based on previously identified risk factors.

Progress in Tandem Mass Spectrometry Data Analysis for Nucleic Acids.

Mass spectrometry (MS) has become a critical tool in the characterization of covalently modified nucleic acids. Well-developed bottom-up approaches, where nucleic acids are digested with an endonuclease and the resulting oligonucleotides are separated before MS and MS/MS analysis, provide substantial insight into modified nucleotides in biological and synthetic nucleic. Top-down MS presents an alternative approach where the entire nucleic acid molecule is introduced to the mass spectrometer intact and then fragmented by MS/MS.

Activation of δ-opioid receptors blocks allodynia in a model of headache induced by PACAP.

Background And Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor.

Binuclear ruthenium complex linker length tunes DNA threading intercalation kinetics.

Binuclear ruthenium complexes have been investigated for potential DNA-targeted therapeutic and diagnostic applications. Studies of DNA threading intercalation, in which DNA base pairs must be broken for intercalation, have revealed means of optimizing a model binuclear ruthenium complex to obtain reversible DNA-ligand assemblies with the desired properties of high affinity and slow kinetics. Here, we used single-molecule force spectroscopy to study a binuclear ruthenium complex with a longer semi-rigid linker relative to the model complex.

Missense variants weakening a SOX9 phosphodegron linked to odontogenesis defects, scoliosis and other skeletal features.

SOX9 encodes an SRY-related transcription factor critical for chondrogenesis and sex determination among other processes. Loss-of-function variants cause campomelic dysplasia and Pierre Robin Sequence, while both gain- and loss-of-function variants cause disorders of sex development. SOX9 has also been linked to scoliosis and cancers, but variants are undetermined.

Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates.

mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.

Morbid obesity among Crohn's disease patients is on the rise and is associated with a higher rate of surgical complications after ileocolic resection.

Aim: Crohn's disease (CD) is regarded as a wasting disease, yet there is a growing population of CD patients with a body mass index (BMI) of 35 and above. The rate of postoperative complications is relatively high in CD patients but might be even higher in CD with morbid obesity (MO).

Methods: This was a retrospective study using a prospectively maintained database of all patients undergoing Ileocolic resection for CD between 2014 and 2021 in two referral centres, comparing postoperative complication rates according to BMI.