The solute carrier family 26 member 9 modifies rapidly progressing cystic fibrosis associated with homozygous F508del CFTR mutation.

Background And Aims: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations to the CF transmembrane conductance regulator (CFTR). Symptoms and severity of the disease can be quite variable suggesting modifier genes play an important role.

Materials And Methods: Exome sequencing was performed on six individuals carrying homozygous deltaF508 for CFTR genotype but present with rapidly progressing CF (RPCF).

Predicting Time to Return to Cannabis Use After a Cessation Attempt: Impact of Cumulated Exposure to Nicotine-Containing Products.

Cannabis is frequently co-used with tobacco/nicotine products, especially among young adults. Little is known about the effects of this co-use on cannabis cessation outcomes. Within a sample of young adults using cannabis frequently (current use of ≥5 days/week in the past 3 months), this study aimed to (a) document sources of exposure to tobacco/nicotine products, whether used simultaneously with cannabis or on different occasions, (b) examine if the level of cumulated exposure to tobacco/nicotine (self-reported or from biochemical testing) could predict time to cannabis lapse during a cannabis abstinence period, and (c) explore the relationship between nicotine/tobacco exposure and time to cannabis lapse according to tobacco cigarette smoking status.

Molecular Changes Implicate Angiogenesis and Arterial Remodeling in Systemic Sclerosis-Associated and Idiopathic Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a common complication of systemic sclerosis (SSc) and a leading cause of mortality among patients with this disease. PH can also occur as an idiopathic condition (idiopathic pulmonary arterial hypertension). Investigation of transcriptomic alterations in vascular populations is critical to elucidating cellular mechanisms underlying pathobiology of SSc-associated and idiopathic PH.

CRISPR Dependency Screens in Primary Hematopoietic Stem Cells Identify KDM3B as a Genotype-specific Vulnerability in IDH2- and TET2-mutant Cells.

Clonal hematopoiesis (CH) is a common premalignant state in the blood and confers an increased risk of blood cancers and all-cause mortality. Identification of therapeutic targets in CH has been hindered by the lack of an ex vivo platform amenable for studying primary hematopoietic stem and progenitor cells (HSPCs). Here, we utilize an ex vivo co-culture system of HSPCs with bone marrow endothelial cells to perform CRISPR/Cas9 screens in mutant HSPCs.

Impact of Insurance Type on Access to Pediatric Surgical Care.

Background: This study aimed to measure the impact of insurance type on access to pediatric surgical care, clinical and surgical scheduling decisions, provider-driven cancelations, and missed care opportunities (MCOs). We hypothesize that patients with public health insurance experience longer scheduling delays and more frequently canceled surgical appointments compared with patients with private health insurance.

Methods: This retrospective study reviewed the demographics and clinical characteristics of patients who underwent a surgical procedure within the plastic and oral surgery department at our institution in 2019.

The Connection Between Anatomical Substrate and Clinical Severity in Fetal Ebstein Anomaly.

Ebstein anomaly (EA) is a rare congenital heart defect characterized by abnormal development of the tricuspid valve (TV) and right ventricular myocardium. This study documents 2 dramatic cases of fetal EA characterized by hydrops and cardiomegaly, leading to intrauterine or early neonatal death. These clinical outcomes were associated with morphological abnormalities including severe tricuspid regurgitation, unguarded TV orifice, pulmonary atresia, and flattened right ventricular myocardium.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

Background & Aims: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers.

Methods: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project.

Implementing Entrustable Professional Activities in Pediatric Fellowships: Facilitating the Process.

Background And Objectives: Entrustable professional activities (EPAs) will be used for initial certification by the American Board of Pediatrics by 2028. Less than half of pediatric fellowships currently use EPAs for assessment, yet all will need to adopt them. Our objectives were to identify facilitators and barriers to the implementation of EPAs to assess pediatric fellows and to determine fellowship program directors' (FPD) perceptions of EPAs and Milestones.

Sleeve Gastrectomy is Associated with Longitudinal Improvements in Lung Function and Patient-Reported Respiratory Outcomes.

Purpose: Obesity exerts negative effects on pulmonary function through proven mechanical and biochemical pathways. Multiple studies have suggested that bariatric surgery can improve lung function. However, the timing of these effects on lung function and its association with patient reported outcomes is not known.

Dysregulation of platelet serotonin, 14-3-3, and GPIX in sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has abnormalities in the neurotransmitter, serotonin (5-hydroxytryptamine [5-HT]) and the adaptor molecule, 14-3-3 pathways in regions of the brain involved in gasping, response to hypoxia, and arousal. To evaluate our hypothesis that SIDS is, at least in part, a multi-organ dysregulation of 5-HT, we examined whether blood platelets, which have 5-HT and 14-3-3 signaling pathways similar to brain neurons, are abnormal in SIDS.

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series.

Background: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population.

The Asthma Risk Gene, , Promotes Mitochondrial DNA-induced Expression.

Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen in asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), the most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine whether and how GSDMB regulates mtDNA-activated cGAS-STING pathway and subsequent induction in human airway epithelial cells.

The Burden of Pelvic Pain Associated With Endometriosis Among Women in Selected European Countries and the United States: A Restricted Systematic Review.

Objective: To evaluate the burden of endometriosis-associated pelvic pain (EAPP) on health-related quality of life (HRQoL) among women living in similar socio-economic conditions.

Data Sources: Searches were performed in PubMed and Embase on September 26, 2022. The review was performed in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P) and was registered on PROSPERO (ID: CRD42023370363).

Sensory transduction in auditory hair cells-PIEZOs can't touch this.

In this Viewpoint, Holt, Fettiplace, and Müller weigh the evidence supporting a role for PIEZO and TMC channels in mechanosensory transduction in inner ear hair cells.

Intervention for critical aortic stenosis in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare genetic premature aging disease that is historically fatal in teenage years, secondary to severe accelerated atherosclerosis. The only approved treatment is the farnesyltransferase inhibitor lonafarnib, which improves vascular structure and function, extending average untreated lifespan of 14.5 years by 4.

A modifiable valve-sparing pediatric cardiac dissection technique promotes specimen longevity and optimizes advanced image analysis postpathological examination.

This paper illustrates a valve-sparing cardiac dissection technique that keeps the atrioventricular and semilunar valves and other important cardiac structures intact. The technique minimizes disruption in heart specimens, so they remain suitable for teaching, demonstration, and further research. When performed following the perfusion-distension method of fixation, as our group previously described, this technique could optimize the preservation of heart specimens for teaching and digital archiving postdissection.