Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis.

Introduction: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness.

Methods: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]).

Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry.

Introduction: We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy.

Methods: Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics.

SHIP1 therapeutic target enablement: Identification and evaluation of inhibitors for the treatment of late-onset Alzheimer's disease.

Introduction: The risk of developing Alzheimer's disease is associated with genes involved in microglial function. Inositol polyphosphate-5-phosphatase (), which encodes Src homology 2 (SH2) domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1), is a risk gene expressed in microglia. Because SHIP1 binds receptor immunoreceptor tyrosine-based inhibitory motifs (ITIMs), competes with kinases, and converts PI(3,4,5)P to PI(3,4)P, it is a negative regulator of microglia function.

Challenges and Future Directions in Redo Aortic Valve Reintervention After Transcatheter Aortic Valve Replacement Failure.

Transcatheter aortic valve replacement (TAVR) is increasingly being performed in younger and lower surgical risk patients. Reintervention for failed transcatheter heart valves will likely increase in the future as younger patients are expected to outlive the initial bioprosthesis. While redo-TAVR has emerged as an attractive and less invasive alternative to surgical explantation (TAVR-explant) to treat transcatheter heart valve failure, it may not be feasible in all patients due to the risk of coronary obstruction and impaired coronary access.

Variability of temperature measurements recorded by a wearable device by biological sex.

Background: Females have been historically excluded from biomedical research due in part to the documented presumption that results with male subjects will generalize effectively to females. This has been justified in part by the assumption that ovarian rhythms will increase the overall variance of pooled random samples. But not all variance in samples is random.

Clonal haematopoiesis, ageing and kidney disease.

Clonal haematopoiesis of indeterminate potential (CHIP) is a preclinical condition wherein a sizeable proportion of an individual's circulating blood cells are derived from a single mutated haematopoietic stem cell. CHIP occurs frequently with ageing - more than 10% of individuals over 65 years of age are affected - and is associated with an increased risk of disease across several organ systems and premature death. Emerging evidence suggests that CHIP has a role in kidney health, including associations with predisposition to acute kidney injury, impaired recovery from acute kidney injury and kidney function decline, both in the general population and among those with chronic kidney disease.

Multicenter evaluation of the BIOFIRE Joint Infection Panel for the detection of bacteria, yeast, and AMR genes in synovial fluid samples.

The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes.

Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines.

metaGOflow: a workflow for the analysis of marine Genomic Observatories shotgun metagenomics data.

Background: Genomic Observatories (GOs) are sites of long-term scientific study that undertake regular assessments of the genomic biodiversity. The European Marine Omics Biodiversity Observation Network (EMO BON) is a network of GOs that conduct regular biological community samplings to generate environmental and metagenomic data of microbial communities from designated marine stations around Europe. The development of an effective workflow is essential for the analysis of the EMO BON metagenomic data in a timely and reproducible manner.

Therapeutic Drug Monitoring in Children and Adolescents: Findings on Fluoxetine from the TDM-VIGIL Trial.

Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial ("TDM-VIGIL"), a transdiagnostic sample of children and adolescents ( = 138; mean age, 15; range, 7-18 years; 24.

Home-based exergaming to treat gait and balance disorders in patients with Parkinson's disease: A phase II randomized controlled trial.

Background: Exergaming has been proposed to improve gait and balance disorders in Parkinson's disease (PD) patients. We aimed to assess the efficacy of a home-based, tailored, exergaming training system designed for PD patients with dopa-resistant gait and/or balance disorders in a controlled randomized trial.

Methods: We recruited PD patients with dopa-resistant gait and/or balance disorders.

Cardiac Metastasis from Prostate Cancer: A Case Study Underlying the Crucial Role of the PSMA PET/CT.

Prostate cancer still represents one of the most frequent cancers and causes of death worldwide, despite the huge therapeutic advances in the last decades. The introduction into clinical practice of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has significantly improved diagnostic capacity, allowing for the identification of lesions previously undetectable. The case we are presenting is about a 90-year-old man affected by metastatic prostate cancer and treated with hormonal therapies.

Transcriptomic and proteomic assessment of tocilizumab response in a randomized controlled trial of patients hospitalized with COVID-19.

High interleukin (IL)-6 levels are associated with greater COVID-19 severity. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways modified by tocilizumab in peripheral blood samples from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19.

Comparative Performance of Contrast-enhanced Mammography, Abbreviated Breast MRI, and Standard Breast MRI for Breast Cancer Screening.

Background Contrast-enhanced mammography (CEM) and abbreviated breast MRI (ABMRI) are emerging alternatives to standard MRI for supplemental breast cancer screening. Purpose To compare the diagnostic performance of CEM, ABMRI, and standard MRI. Materials and Methods This single-institution, prospective, blinded reader study included female participants referred for breast MRI from January 2018 to June 2021.

Topical Probiotic Formulation Promotes Rapid Healing in Dog Keratinocyte Cells: A Promising Approach for Wound Management.

The use of probiotics has gained increasing attention as a strategy for wound healing to decrease microbial resistance to disinfectants and antibiotics. This study aimed to investigate the potential of a non-medicinal topical cocktail of probiotic bacteria (CPB) in promoting wound healing in dogs using in vitro scratch assay. Canine Progenitors Epidermal Keratinocytes (CPEK) were exposed to a prototype product formulated with CPB (PPP), non-formulated CPB, and the vehicle.

Long-term low-dose tolvaptan efficacy and safety in SIADH.

Purpose: Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is usually 15 mg/day, but recent clinical experience suggests a lower starting dose (<15 mg/day) to reduce the risk of sodium overcorrection. However, long-term low-dose efficacy and safety has not been explored, so far.

Safety and Effectiveness of Carbon Dioxide Removal CO2RESET Device in Critically Ill Patients.

Background: In this retrospective study, we report the effectiveness and safety of a dedicated extracorporeal carbon dioxide removal (ECCOR) device in critically ill patients.

Methods: Adult patients on mechanical ventilation due to acute respiratory distress syndrome (ARDS) or decompensated chronic obstructive pulmonary disease (dCOPD), who were treated with a dedicated ECCOR device (CO2RESET, Eurosets, Medolla, Italy) in case of hypercapnic acidemia, were included. Repeated measurements of CO removal (VCO) at baseline and 1, 12, and 24 h after the initiation of therapy were recorded.

The human milk component -inositol promotes neuronal connectivity.

Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar -inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain.

Surgical Treatment of Spinal Deformities in Pediatric Orthopedic Patients.

Scoliosis and Scheuermann's disease are common spinal deformities that affect a substantial population, particularly adolescents, often impacting their quality of life. This comprehensive review aims to present a detailed understanding of these conditions, their diagnosis, and various treatment strategies. Through an extensive exploration of current literature, the review discusses the etiology of these spinal deformities and the use of diagnostic tools such as X-rays and MRI.