Improving Understanding of Fexofenadine Pharmacokinetics to Assess Pgp Phenotypic Activity in Older Adult Patients Using Population Pharmacokinetic Modeling.

Background And Objective: Fexofenadine is commonly used as a probe substrate to assess P-glycoprotein (Pgp) activity. While its use in healthy volunteers is well documented, data in older adult and polymorbid patients are lacking. Age- and disease-related physiological changes are expected to affect the pharmacokinetics of fexofenadine.

Monitoring Excavation-Induced Deformation of a Secant Pile Wall Using Distributed Fiber Optic Sensors.

This paper investigates the use of the BOTDA (Brillouin Optical Time-Domain Analysis) technology to monitor a large-scale bored pile wall in the field. Distributed fiber optic sensors (DFOSs) were deployed to measure internal temperature and strain changes during cement grouting, hardening, and excavation-induced deformation of a secant pile wall. The study details the geological conditions and DFOS installation process.

Urolithin A Modulates PER2 Degradation via SIRT1 and Enhances the Amplitude of Circadian Clocks in Human Senescent Cells.

Background/objectives: Circadian clocks are endogenous systems that regulate numerous biological, physiological, and behavioral events in living organisms. Aging attenuates the precision and robustness of circadian clocks, leading to prolonged and dampened circadian gene oscillation rhythms and amplitudes. This study investigated the effects of food-derived polyphenols such as ellagic acid and its metabolites (urolithin A, B, and C) on the aging clock at the cellular level using senescent human fibroblast cells, TIG-3 cells.

Biomarkers of Extracellular Matrix Fragments in Patients with Psoriasis.

Blood-based extracellular matrix (ECM) fragments have been identified as potential pharmacologic biomarkers in spondyloarthritis and diagnostic biomarkers in psoriatic arthritis and psoriasis vulgaris. This study aimed to explore whether ECM fragments can differentiate patients with psoriasis from healthy controls (HC) and determine their potential as biomarkers for response to treatment in psoriasis. The study population included 59 patients with moderate to severe psoriasis, not receiving systemic anti-psoriatic treatment at inclusion, and 52 HC matched by age, sex, and BMI.

Knowing is Half the Battle: The Factors Leading to Efficient Recruitment of Representative Samples in Schizophrenia Research.

Background And Objectives: Drug development in schizophrenia is limited by the differential scaling of the active treatment and placebo arms of a study, such that, as the number of sites increases, the magnitude of placebo response disproportionately increases. The objective of this article was to identify factors conducive to efficient recruitment as a step towards trial designs allowing recruitment of more participants per site, leading to reduced variability, and potentially a smaller placebo effect.

Patients And Methods: Using the information of 554 individuals, we calculated the percentage of individuals who were screened, consented, and retained in our research, along with rationale for nonconsent.

Integrated analysis of miRNAs and mRNAs in thousands of single cells.

The simultaneous sequencing of multiple types of biomolecules can facilitate understanding various forms of regulation occurring in cells. Cosequencing of miRNA and mRNA at single-cell resolution is challenging, and to date, only a few such studies (examining a quite limited number of cells) have been reported. Here, we developed a parallel single-cell small RNA and mRNA coprofiling method (PSCSR-seq V2) that enables miRNA and mRNA coexpression analysis in many cells.

Aptamer-conjugated gold nanoparticles enable oligonucleotide delivery into muscle stem cells to promote regeneration of dystrophic muscles.

Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic delivery of microRNA-206 to MuSCs, thereby promoting muscle regeneration and improving muscle functionality, in a mouse model of Duchenne Muscular Dystrophy.

Cardiovascular MRI-derived Right Atrial Strain for Improved Risk Stratification in Patients with Severe Aortic Stenosis.

Purpose To assess the prognostic implications of cardiac MRI-derived imaging markers in individuals with severe aortic stenosis (AS). Materials and Methods This prospective study (German Clinical Trials Register, DRKS00024479) enrolled individuals with severe AS who underwent cardiac MRI before transcatheter aortic valve replacement (TAVR) from January 2017 to March 2022. Image analyses included myocardial volumes, cardiac MRI feature tracking-derived left atrial (LA) and right atrial (RA) as well as left ventricular (LV) and right ventricular (RV) strain, myocardial T1 mapping, and late gadolinium enhancement analyses.

Predicting cell morphological responses to perturbations using generative modeling.

Advancements in high-throughput screenings enable the exploration of rich phenotypic readouts through high-content microscopy, expediting the development of phenotype-based drug discovery. However, analyzing large and complex high-content imaging screenings remains challenging due to incomplete sampling of perturbations and the presence of technical variations between experiments. To tackle these shortcomings, we present IMage Perturbation Autoencoder (IMPA), a generative style-transfer model predicting morphological changes of perturbations across genetic and chemical interventions.

Targeting N-Myc in neuroblastoma with selective Aurora kinase A degraders.

The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.

Neoadjuvant radiochemotherapy in patients with high-risk locally advanced cervical cancer-results of a clinical series.

Purpose: Neoadjuvant radiochemotherapy (NARCT) is an established standard of care in various tumor entities, promoting high response rates at commonly lower toxicities as compared to adjuvant approaches. This retrospective analysis was designed to investigate NARCT in early-stage high-risk cervical cancer.

Methods: Forty patients with early-stage high-risk cervical cancer (i.

All Suture Biceps Tenodesis Has Greater Biomechanical Strength Than Metal Button Fixation.

Purpose: To evaluate the maximal load to failure, cyclic displacement, stiffness, and modes of failure of onlay subpectoral biceps tenodesis with an intramedullary unicortical metal button (MB) versus an inlay, all-suture Caspari-Weber (CW) technique.

Methods: Sixteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either CW or MB using a high-strength suture (N = 16; 8 male, 8 female, mean age = 82.5 years, range 62-99 years).

US-Guided Thermal Ablation for Secondary Hyperparathyroidism: A Prospective Multicenter Study.

Background Interest in microwave ablation (MWA) and radiofrequency ablation (RFA) use for treating secondary hyperparathyroidism (SHPT) is rising; however, ablation outcomes in patients with SHPT are not well characterized. Purpose To assess the response of parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase (ALP) levels to US-guided parathyroid MWA and RFA and the safety of these treatments in participants with SHPT. Materials and Methods This prospective multicenter cohort study, conducted from September 2017 to March 2022, included participants with SHPT.

Gout and Hyperuricemia: A Narrative Review of Their Comorbidities and Clinical Implications.

Gout is the most common form of inflammatory arthritis, caused by the deposition of monosodium urate crystals in the joints due to elevated serum uric acid levels. Its prevalence and associated healthcare burden have been rising in recent decades, a trend expected to continue. It is crucial to recognize that gout and hyperuricemia are not merely causes of painful joint flares, but systemic metabolic disorders linked to a broad spectrum of comorbidities such as cardiovascular diseases, chronic kidney disease, diabetes, insulin resistance, steatotic liver disease, osteoarthritis, and respiratory and eye diseases.

Nutrition-Focused Quality Improvement Programs in Pediatric Care.

Nutrition is fundamental to a child's growth and development. However, nutritional health is often compromised by acute and chronic conditions and treatments that can commonly result in malnutrition. Malnutrition encompasses undernutrition and overnutrition and may be exacerbated by food insecurity.

Pharmacotherapy from Pre-COVID to Post-COVID: Longitudinal Trends and Predictive Indicators for Long COVID Symptoms.

Background/objectives: A significant number of COVID-19 cases experience persistent symptoms after the acute infection phase, a condition known as long COVID or post-acute sequelae of COVID-19. Approved prevention and treatment options for long COVID are currently lacking. Given the heterogeneous nature of long COVID, a personalized medicine approach is essential for effective disease management.

Efficacy of Fruit Extract in Hangover Mitigation: Double-Blind Randomized Clinical Evaluation.

The fruit of Thunb. (HD) is renowned for its medicinal properties and is rich in bioactive compounds, traditionally used in East Asian medicine as a natural antidote for alcohol intoxication. A randomized, double-blind, crossover, placebo (PLA)-controlled clinical trial was conducted to compare the effects of beverages containing 0.

Clinical Evaluation of Extract Combinations for Effective Hangover Relief in Humans.

Alcohol consumption is associated with both short- and long-term adverse effects, including hangover symptoms. The objective of this study was to examine the potential benefits of traditional beverages containing a combination of extract (HD) with either extract (HDPB) or glutathione yeast extract (HDGB) in abbreviating alcohol intoxication and mitigating hangover symptoms. A total of 25 participants between the ages of 19 and 40 who had previously experienced a hangover were evaluated in a randomized, double-blind, crossover, placebo (PLA)-controlled clinical trial.

Inheritance of Imaging Parameters of Arrhythmic Risk in Mitral Valve Prolapse: A Pedigree Study.

Background: A subset of patients with mitral valve prolapse (MVP), a highly heritable condition, experience sudden cardiac arrest (SCA) or sudden cardiac death (SCD). However, the inheritance of phenotypic imaging features of arrhythmic MVP remains unknown.

Methods: We recruited 23 MVP probands, including 9 with SCA/SCD and 14 with frequent/complex ventricular ectopy.

Comparative Analysis of Injury and Illness Rates Among Team USA Athletes at the Tokyo 2020 Summer Olympic and Paralympic Games.

Background: Previous research has reported higher rates of both injury and illness among Paralympic athletes compared with Olympic athletes during the Winter Olympic and Paralympic Games, but no studies have directly compared injury and illness incidence between Olympic and Paralympic athletes competing in a Summer Games.

Purpose: To compare injury and illness rates between Olympic and Paralympic Team USA athletes competing in the Tokyo 2020 Olympic and Paralympic Games.

Study Design: Descriptive epidemiology study.

Trends in Obesity Prevalence Among Adults With Hypertension in the United States, 2001 to 2023.

Background: Obesity is a factor contributing to the occurrence of hypertension and a risk factor for adverse outcomes in populations with hypertension. The changes in the prevalence of obesity in populations with hypertension remain unclear. Investigating the changes in the prevalence of obesity in populations with hypertension can provide information for the treatment and management of hypertension.

Protocol for capturing a full transcriptome from single preimplantation embryos using So-Smart-seq.

Strand-optimized Smart-seq (So-Smart-seq) can capture a comprehensive transcriptome from low-input samples. This technique detects both polyadenylated and non-polyadenylated RNAs, inclusive of repetitive RNAs, while excluding highly abundant ribosomal RNAs. So-Smart-seq preserves strand information and minimizes 5' to 3' coverage bias.

Home Urine Dipstick Screening for Bladder and Kidney Cancer in High-Risk Populations in England: A Microsimulation Study of Long-Term Impact and Cost-Effectiveness.

Background: Testing high-risk populations for non-visible haematuria may enable earlier detection of bladder cancer, potentially decreasing mortality. This research aimed to assess the cost-effectiveness of urine dipstick screening for bladder cancer in high-risk populations in England.

Methods:  A microsimulation model developed in R software was calibrated to national incidence data by age, sex and stage, and validated against mortality data.