Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease.

Pathogenic variants in NOTCH1 are associated with non-syndromic congenital heart disease (CHD) and Adams-Oliver syndrome (AOS). The clinical presentation of individuals with damaging NOTCH1 variants is characterized by variable expressivity and incomplete penetrance; however, data on systematic phenotypic characterization are limited. We report the genotype and phenotype of a cohort of 33 individuals (20 females, 13 males; median age 23.

Identification of determinants of lipid and ion transport in TMEM16/anoctamin proteins through a Bayesian statistical analysis.

The TMEM16/Anoctamin protein family (TMEM16x) is composed of members with different functions; some members form Ca-activated chloride channels, while others are lipid scramblases or combine the two functions. TMEM16x proteins are typically activated in response to agonist-induced rises of intracellular Ca; thus, they couple Ca-signalling with cell electrical activity or plasmalemmal lipid homeostasis. The structural domains underlying these functions are not fully defined.

Challenges experienced by genetic counselors while they provided counseling about mosaic embryos.

Objective: To survey genetic counselors (GCs) who have counseled about mosaic embryos regarding the challenges they faced in counseling this patient population and assess their need for more resources to support their practice.

Design: Self-administered online survey.

Setting: Academic university.

In Silico and In Vitro Evaluation of the Mechanism of Action of Three VX809-Based Hybrid Derivatives as Correctors of the F508del CFTR Protein.

Cystic fibrosis (CF), the most common autosomal recessive fatal genetic disease in the Caucasian population, is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel that regulates salt and water transport across a variety of secretory epithelia. Deletion of phenylalanine at position 508, F508del, the most common CF-causing mutation, destabilises the CFTR protein, causing folding and trafficking defects that lead to a dramatic reduction in its functional expression. Small molecules called correctors have been developed to rescue processing-defective F508del CFTR.

α-Casein-Loaded Proteo-liposomes as Potential Inhibitors in Amyloid Fibrillogenesis: Effects on a Model of Alzheimer's Disease.

According to the amyloid hypothesis, in the early phases of Alzheimer's disease (AD), small soluble prefibrillar aggregates of the amyloid β-peptide (Aβ) interact with neuronal membranes, causing neural impairment. Such highly reactive and toxic species form spontaneously and transiently in the amyloid building pathway. A therapeutic strategy consists of the recruitment of these intermediates, thus preventing aberrant interaction with membrane components (lipids and receptors), which in turn may trigger a cascade of cellular disequilibria.

Drug-resistant focal epilepsy in a girl with SETD5-related intellectual disability.

None.

Short-pulsed Q-switched fiber laser using graphene oxide quantum dots based as saturable absorber.

In this work, we report the experimental study of a Q-switched optical fiber laser based on graphene oxide quantum dots (GOQDs) as saturable absorber (SA). GOQDs are fabricated by carbonization and exfoliation electrospun polyacrylonitrile (PAN) fibers. The results of Fourier Transform Infrared Spectroscopy (FTIR) showed bands caused by the CHs and C[bond, double bond]O groups associated with the GOQDs.

Elexacaftor Mediates the Rescue of F508del CFTR Functional Expression Interacting with MSD2.

Cystic fibrosis (CF) is one of the most frequent lethal autosomal recessive diseases affecting the Caucasian population. It is caused by loss of function variants of the cystic fibrosis transmembrane conductance regulator (CFTR), a membrane protein located on the apical side of epithelial cells. The most prevalent CF-causing mutation, the deletion of phenylalanine at position 508 (F508del), is characterized by folding and trafficking defects, resulting in the decreased functional expression of the protein on the plasma membrane.

Perinatal Outcome following the Suspension of Intrapartum Oxygen Treatment.

Objective: This study aimed to evaluate whether the suspension of intrapartum maternal oxygen supplementation for nonreassuring fetal heart rate is associated with adverse perinatal outcomes.

Study Design: A retrospective cohort study, including all individuals that underwent labor in a single tertiary medical center. On April 16, 2020, the routine use of intrapartum oxygen for category II and III fetal heart rate tracings was suspended.

Remotely Delivered Cardiac Rehabilitation Exercise for Coronary Heart Disease: Nonrandomized Feasibility Study.

Background: Exercise-based cardiac rehabilitation (CR) is recommended for coronary heart disease (CHD). However, poor uptake of and poor adherence to CR exercise programs have been reported globally. Delivering CR exercise classes remotely may remove some of the barriers associated with traditional hospital- or center-based CR.

Cost-effectiveness of cladribine tablets and dimethyl fumarate in the treatment of relapsing remitting multiple sclerosis in Spain.

To analyze the cost-effectiveness of treatment of relapsing remitting multiple sclerosis (RRMS) with cladribine tablets (CladT) and dimethyl fumarate (DMF) from the perspective of the Spanish National Health System (NHS). A probabilistic Markov model (second-order Monte Carlo simulation) with a 10-year time horizon and annual Markov cycles was performed. CladT was the dominant treatment, with lower costs (-74,741 € [95% CI: -67,247; -85,661 €]) and greater effectiveness (0.

Modulator Combination Improves In Vitro the Microrheological Properties of the Airway Surface Liquid of Cystic Fibrosis Airway Epithelia.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a plasma membrane protein expressed on the apical surface of secretory epithelia of the airways. In the airways, defective or absent function of the CFTR protein determines abnormalities of chloride and bicarbonate secretion and, in general, of the transepithelial homeostasis that lead to alterations of airway surface liquid (ASL) composition and properties. The reduction of ASL volume impairs ciliary beating with the consequent accumulation of a sticky mucus.

Piezo buffers mechanical stress via modulation of intracellular Ca handling in the heart.

Throughout its lifetime the heart is buffeted continuously by dynamic mechanical forces resulting from contraction of the heart muscle itself and fluctuations in haemodynamic load and pressure. These forces are in flux on a beat-by-beat basis, resulting from changes in posture, physical activity or emotional state, and over longer timescales due to altered physiology (e.g.

Investigating the needs and concerns of older adults with multimorbidity and their healthcare professionals for conceivable digital psychotherapeutic interventions.

Multimorbidity, defined as the concurrent experience of more than one chronic health condition in an individual, affects ∼65% of people over 65 and 85% of those over 85 years old with 30% of those also experiencing mental health concerns. This can lead to reduced quality of life and functioning as well as poorer outcomes in terms of condition management, adherence to treatment, and ultimately disease prognosis and progression. Digital health interventions offer a viable means of condition self-management, as well as psychological support, particularly for those who may have difficulty accessing in-person services.

Efficacy of a Digital Acceptance and Commitment Therapy Intervention for the Improvement of Self-management Behaviors and Psychological Flexibility in Adults With Cardiac Disease: Protocol for a Single Case Experimental Design.

Background: Research indicates that the management of distress levels in those with cardiac disease is not only important for improving quality of life and functioning but also critical for condition management; adherence to treatment; and, ultimately, disease prognosis and progression. Acceptance and commitment therapy (ACT) has consistently demonstrated positive long-term outcomes across a wide array of conditions, including chronic illness. However, most empirical investigations conducted to date have also involved in-person therapy, which can be difficult to access, particularly for those dealing with the demands of chronic disease.

The VRAC blocker DCPIB directly gates the BK channels and increases intracellular Ca in melanoma and pancreatic duct adenocarcinoma cell lines.

Background And Purpose: The volume regulated anion channel (VRAC) is known to be involved in different aspects of cancer cell behaviour and response to therapies. For this reason, we investigated the effect of DCPIB, a presumably specific blocker of VRAC, in two types of cancer: pancreatic duct adenocarcinoma (PDAC) and melanoma.

Experimental Approach: We used patch-clamp electrophysiology, supported by Ca imaging, gene expression analysis, docking simulation and mutagenesis.

Small Angle X-ray Scattering Sensing Membrane Composition: The Role of Sphingolipids in Membrane-Amyloid β-Peptide Interaction.

The early impairments appearing in Alzheimer's disease are related to neuronal membrane damage. Both aberrant Aβ species and specific membrane components play a role in promoting aggregation, deposition, and signaling dysfunction. Ganglioside GM1, present with cholesterol and sphingomyelin in lipid rafts, preferentially interacts with the Aβ peptide.

Accuracy of Wrist-Worn Photoplethysmography Devices at Measuring Heart Rate in the Laboratory and During Free-Living Activities.

This study compared heart rate (HR) measurements taken from two wrist-worn devices; the Empatica E4 and the Apple Watch Series 5, to that taken from a Polar H10 chest strap. Ten healthy adult volunteers took part in a laboratory validation study and performed a treadmill exercise protocol. A single-subject validity study was also conducted to evaluate the accuracy of continuous HR measurements obtained during free-living activities.

Quantifying Steps During a Timed Up and Go Test Using a Wearable Sensor System: A Laboratory-Based Validation Study in Healthy Young and Older Volunteers.

Mobility is an important factor in maintaining health and independence in an aging population. Facilitating community-dwelling older adults to independently identify signs of functional decline could help reduce disability and frailty development. Step-count from a body-worn sensor system was compared with a criterion measure in healthy young (n = 10) and healthy older adults (n = 10) during a Timed Up and Go test under different conditions.

NBD2 Is Required for the Rescue of Mutant F508del CFTR by a Thiazole-Based Molecule: A Class II Corrector for the Multi-Drug Therapy of Cystic Fibrosis.

Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) protein, an anion channel that regulates epithelial surface fluid secretion. The deletion of phenylalanine at position 508 (F508del) is the most common CFTR mutation. F508del CFTR is characterized by folding and trafficking defects, resulting in decreased functional expression of the protein on the plasma membrane.

Delivering Cardiac Rehabilitation Exercise Virtually Using a Digital Health Platform (ECME-CR): Protocol for a Pilot Trial.

Background: Exercise-based cardiac rehabilitation is recognized as a core component of cardiovascular disease management and has been shown to reduce all-cause and cardiovascular mortality and reduce the risk of hospital readmission following a cardiac event. However, despite this, the uptake of and long-term adherence to cardiac rehabilitation exercise is poor. Delivering cardiac rehabilitation exercise virtually (ie, allowing patients to participate from their own homes) may be an alternative approach that could enhance uptake and increase adherence.

The Application of Bicarbonate Recovers the Chemical-Physical Properties of Airway Surface Liquid in Cystic Fibrosis Epithelia Models.

Cystic fibrosis (CF) is a genetic disease associated with the defective function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that causes obstructive disease and chronic bacterial infections in airway epithelia. Deletion of phenylalanine at position 508, p.F508del, the most frequent mutation among CF patients, causes a folding and traffic defect, resulting in a dramatic reduction in the CFTR expression.

The different anion transport capability of prodiginine- and tambjamine-like molecules.

Prodiginines and tambjamines are anion-selective ionophores capable of facilitating the transport of anions across the plasma membrane in mammalian cells. One of the potential applications of these anionophores is the possibility of employing them as a substitutive therapy for pathologies involving anion channels, as in cystic fibrosis. We have studied the interaction of a large anion as gluconate with three prodiginine- and two tambjamine-like compounds.

Successful vaginal delivery after external cephalic version (ECV): does time interval from ECV to delivery make a difference? A multicenter study.

Purpose: The risk of cesarean delivery after a successful external cephalic version for breech presentation is higher as compared with fetuses in cephalic presentation. However, the role of the time interval between version attempt to delivery on the risk for cesarean delivery is unclear. We aimed to study the effect of the time interval from a successful external cephalic version to delivery on the risk for cesarean delivery and assess factors associated with cesarean delivery after a successful version.

Correctors modify the bicarbonate permeability of F508del-CFTR.

One of the most common mutations in Cystic Fibrosis (CF) patients is the deletion of the amino acid phenylalanine at position 508. This mutation causes both the protein trafficking defect and an early degradation. Over time, small molecules, called correctors, capable of increasing the amount of mutated channel in the plasma membrane and causing an increase in its transport activity have been developed.