VX-770, C-A1, and Increased Intracellular cAMP Have Distinct Acute Impacts upon CFTR Activity.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that is dysfunctional in individuals with cystic fibrosis (CF). The permeability of CFTR can be experimentally manipulated though different mechanisms, including activation via inducing the phosphorylation of residues in the regulatory domain as well as altering the gating/open probability of the channel. Phosphorylation/activation of the channel is achieved by exposure to compounds that increase intracellular cAMP, with forskolin and IBMX commonly used for this purpose.

Prognostic Significance of Lymph Node Ratio in Intrahepatic and Extrahepatic Cholangiocarcinomas.

. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC.

Food Security and Cardio-Metabolic Risk in Individuals with Metabolic Syndrome.

This study assessed the association of food security with potential cardio-metabolic risk factors among persons with metabolic syndrome (MetS). Data were derived from the baseline data of a randomized controlled lifestyle intervention trial for individuals with MetS. Household food security, fruit and vegetable intake, perceived food environment, and perceived stress were collected using validated questionnaires.

Supporting Holistic Health and Gestational Diabetes Mellitus Risk Reduction Among Young Native Females Prior to Pregnancy: A Qualitative Exploration.

AI/AN communities are disproportionately impacted by food insecurity and gestational diabetes mellitus (GDM). Decreasing the risk of GDM can interrupt the intergenerational cycle of diabetes in AI/AN families, and can decrease diabetes-related health disparities. The goal of this study was to explore ways of supporting holistic health and reducing the risk of GDM among young American Indian and Alaska Native (AI/AN) females prior to pregnancy.

Enlightening Nursing Care: A Protocol for a Multicenter Observational Study Measuring Nursing Work in Hospital Settings.

: Rising costs and demands for improved quality of care present complex challenges for existing healthcare systems. The strain on healthcare resources is exacerbated by the increasing complexity of patient conditions. The Diagnosis-Related Group (DRG) system classifies inpatients according to clinical and treatment criteria, controls healthcare expenditures, and ensures the sustainability of procedures.

A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome.

Background: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

Design: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

Methods: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment.

Longitudinal phage-bacteria dynamics in the early life gut microbiome.

Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Detection of selected vector-borne pathogens in domestic animals, ectoparasites, and their owners in a rural community in Southwest Guatemala.

Vector-borne pathogens, which are transmitted by blood-feeding arthropods to animals and people, are common in tropical regions where, combined with economic factors, can cause significant public health burden. A community-level study was undertaken in southwestern Guatemala to assess the presence of vector-borne pathogens in blood samples from humans (n = 98), their animals (n = 90), and ectoparasites (n = 83) over a period of 2 weeks. Human capillary blood was collected from participant's index finger, and animal venous blood (chickens, pigs, dogs, and cats) was collected from the jugular or cephalic veins at the enrollment period of a concurrent study.

Physiologic Pulmonary Phenotyping of Infants Born Preterm and Post-Discharge Respiratory Morbidity.

Objectives: To determine whether airway and parenchymal function identifies subgroups of infants born preterm according to the predominant pulmonary pathophysiology, and whether these subgroups have different risks for respiratory disease during infancy.

Study Design: We prospectively enrolled a cohort of 125 infants born preterm with planned clinical follow-up after NICU discharge. The study included monthly questionnaires for wheeze and visits to a physician or care provider for any respiratory illness.

Phospho-flow cytometry assays for diagnostic use - A discussion of assay utility and assay development and validation challenges.

Detection of changes in phosphorylation of cell signaling molecules using flow cytometry is termed "phosphoflow" or "phospho-flow cytometry". Phosphoflow has wide application for basic research into the mechanics of cell signaling, for evaluating aberrant signaling in cancerous cells and tissues, for studying efficacy or off-target effects during drug and vaccine development, and for functional assessment of pathogenic variants of genes that are known to play a role in development or function of the immune system. Phosphoflow has not been widely adopted in clinical laboratories owing to the challenges with developing and validating robust assays consistent with clinical laboratory regulatory standards.

Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist Devices: A MOMENTUM 3 Trial Analysis.

Background: The benefit of implantable cardioverter-defibrillators (ICD) and cardiovascular resynchronization therapy (CRT-D) in patients supported with a HeartMate 3 left ventricular assist device (LVAD) remains uncertain.

Methods: An analysis of the MOMENTUM 3 randomized clinical trial and the first 1000 patients in the Continued Access Protocol trial. Patients were divided into three groups based on the presence of ICD and/or CRT-D: No device (n=153, 11%), ICD only (n=699, 50.

Mixed Methods RCT comparing quality of life for pregnant women with type 1 diabetes using Hybrid Closed-Loop (HCL) to Sensor-Augmented Pump Therapy (SAPT).

Objectives: Type 1 diabetes (T1D) in pregnancy is challenging. This study explores how assisted hybrid closed-loop (HCL) therapy versus sensor-augmented pump therapy (SAPT) impacts quality of life (QoL) in pregnancy.

Methods: We interviewed 22 of 24 participants randomized to HCL therapy or SAPT in the Pregnancy Intervention with a Closed-Loop System study.

Managing home oxygen and nasogastric feeds post-NICU discharge: PCP practices and perspectives.

Objective: NICU graduates are frequently technology dependent including home oxygen, pulse oximetry, and/or nasogastric (NG) feedings. Primary care provider (PCP) perceptions, practices, and barriers to managing these infants are not well described, especially at altitude. We sought to 1) describe PCP comfort and 2) determine practices and barriers in managing this technology at higher altitude.

BabyFM: Towards accurate 3D baby facial models using spectral decomposition and asymmetry swapping.

In this paper, we present the first publicly available 3D statistical facial shape model of babies, the Baby Face Model (BabyFM). Constructing a model of the facial geometry of babies entails specific challenges, such as occlusions, extreme and uncontrollable expressions, and data shortage. We address these challenges by proposing (1) a non-template dependent method that jointly estimates a 3D facial baby-specific template and the point-to-point correspondences; (2) a novel method to establish correspondences based on the spectral decomposition of the Laplace Beltrami Operator, which provides a more robust theoretical foundation than state-of-the-art methods; and (3) an asymmetry-swapping strategy to alleviate the shortage of large scale datasets by decoupling the identity-related and the asymmetry-related shape deformation fields.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258.

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status.

One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Association of chronic kidney disease with acute clinical outcomes and hospitalization costs of cancer resection.

Purpose: Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been noted to face increased cancer incidence. Yet, the impact of concomitant renal dysfunction on acute outcomes following elective surgery for cancer remains to be elucidated.

Methods: All adult hospitalizations entailing elective resection for lung, esophageal, gastric, pancreatic, hepatic, or colon cancer were identified in the 2016-2020 National Inpatient Sample.

Anesthesia Trauma Guidelines: A Systematic Review of Global Accessibility and Quality.

This systematic review describes the available clinical practice guidelines (CPGs) for the anesthetic management of trauma and appraises the accessibility and quality of these resources. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was conducted across 8 databases (MEDLINE, Embase, Web of Science, CABI Digital Library, Global Index Medicus, SciELO, Google Scholar, and National Institute for Health and Care Excellence) for guidelines from 2010 to 2023.

Cognitive Outcomes and Delirium After Cardiac Neurodevelopmental Program Implementation for Children With Congenital Heart Disease.

Importance: A recent advisory from the American Heart Association delineated the potential benefits of developmental care for hospitalized children with congenital heart disease (CHD) and a critical gap in research evaluating the association of such inpatient programs with neurodevelopmental outcomes.

Objective: To investigate associations between the Cardiac Inpatient Neurodevelopmental Care Optimization (CINCO) program interventions, delirium, and neurodevelopment in young children (newborn through age 2 years) hospitalized with CHD.

Design, Setting, And Participants: This cohort study used quality improvement data from inpatient cardiac units at a tertiary care children's hospital in the US.

Quantitative evaluation of placental microvascular blood flow and microstructure in fetal growth restriction with IVIM MRI.

Background: Intravoxel incoherent motion (IVIM) MRI uses diffusion-weighted (DW) MRI acquisitions to evaluate the microvascular and cellular environments of tissue. Due to these properties, IVIM has been increasingly utilized to evaluate abnormal placentation.

Objective: Our primary objective was to compare IVIM parameters in the placenta of patients with fetal growth restriction and appropriate for gestational age controls across gestational ages.

The efficiency of venturi versus peristaltic based phacoemulsification in femtosecond laser cataract surgery: Venturi vs peristaltic based phacoemulsification for cataract.

Purpose: To compare the efficiency of peristaltic vs venturi vacuum platforms when applied to the femtosecond treated cataract.

Setting: Outpatient Eye Center, Mercy Health System, Springfield, MO, USA.

Design: This is a prospective randomized controlled trial of 111 patients with moderate nuclear sclerosis scheduled for bilateral routine laser cataract surgery (clinicaltrials.