Diversity-oriented synthesis of second generation guanidinium-rich transporters toward cell-selective penetration.

Cell-penetrating peptides (CPPs) hold significant promise for intracellular delivery of various cargo molecules such as therapeutics. However, the lack of selectivity remains a critical challenge and limits the clinical application of CPPs. Using an automated peptide synthesizer, we generated a diversity-oriented library of 256 peptidomimetics containing four modified peptoid guanidine-bearing monomers incorporated alternatively with four α-amino acids.

Mental health, psychosocial functioning, and health-related quality of life of children and adolescents with bladder exstrophy, cloacal exstrophy, and epispadias: A scoping review.

Background: The exstrophy-epispadias complex (EEC) is a spectrum of rare congenital defects affecting the genitourinary system that includes epispadias, bladder exstrophy, and cloacal exstrophy. EEC patients may require several surgeries throughout their lifetime and experience a number of difficulties that may impact their quality of life (QoL), mental health, and psychosocial functioning.

Objective: The purpose of this scoping review is to systematically map existing literature that explores the mental health, psychosocial functioning, and QoL of children and adolescents with EEC.

A GeSe switch-only-memory technology through polarized atomic distribution.

Ovonic threshold switching (OTS) materials that are frequently used with a resistor (1S1R) in memory devices have been found to show controllable and reversible memory properties, which could enable new memory architectures. Here, we examine the impact of composition on the polarity-dependent memory properties of GeSe OTS materials and reveal that an increase in Se content results in a higher set voltage threshold (V), a lower reset current (I), and a higher set energy. Specifically, GeSe demonstrates two distinct V of 5.

G protein selectivity profile of GPR56/ADGRG1 and its effect on downstream effectors.

GPR56, an adhesion G-protein coupled receptor (aGPCRs) with constitutive and ligand-promoted activity, is involved in many physiological and pathological processes. Whether the receptor's constitutive or ligand-promoted activation occur through the same molecular mechanism, and whether different activation modes lead to functional selectivity between G proteins is unknown. Here we show that GPR56 constitutively activates both G12 and G13.

G protein selectivity profile of GPR56/ADGRG1 and its effect on downstream effectors.

GPR56, an adhesion G-protein coupled receptor (aGPCRs) with constitutive and ligand-promoted activity, is involved in many physiological and pathological processes. Whether the receptor's constitutive or ligand-promoted activation occur through the same molecular mechanism, and whether different activation modes lead to functional selectivity between G proteins is unknown. Here we show that GPR56 constitutively activates both G12 and G13.

Targeting fatty acid oxidation enhances response to HER2-targeted therapy.

Metabolic reprogramming, a hallmark of tumorigenesis, involves alterations in glucose and fatty acid metabolism. Here, we investigate the role of Carnitine palmitoyl transferase 1a (Cpt1a), a key enzyme in long-chain fatty acid (LCFA) oxidation, in ErbB2-driven breast cancers. In ErbB2+ breast cancer models, ablation of Cpt1a delays tumor onset, growth, and metastasis.

Does Examination Table Paper Use Mitigate the Risk of Disease Transmission in a Family Medicine Clinic?

Reducing examination table paper (ETP) use may help curb carbon emissions from health care. Six participants applied Glo Germ (DMA International) to their hands before a common physical examination (abdominal, cardiorespiratory, hip and knee) both with and without ETP. After each exam, UV light was shined on the exam table and photographs were taken.

Incidence and predictors of delays in starting fellowship training in urology.

Introduction: The completion of residency and start of fellowship training marks a critical transition for urologists in the pursuit of subspeciality training. Most graduating urology residents are under contract until June 30, and most fellowships are scheduled to begin on July 1. There has been no investigation into the practical implications of fellowship delays in urology from a trainee perspective.

Disorder-Induced Magnetotransport Anomalies in Amorphous and Textured CoSi Semimetal Thin Films.

In recent times the chiral semimetal cobalt monosilicide (CoSi) has emerged as a prototypical, nearly ideal topological conductor hosting giant, topologically protected Fermi arcs. Exotic topological quantum properties have already been identified in CoSi bulk single crystals. However, CoSi is also known for being prone to intrinsic disorder and inhomogeneities, which, despite topological protection, risk jeopardizing its topological transport features.

Long-Term outcomes of cecostomy tube insertion for patients with bowel dysfunction: A retrospective review.

Background: Constipation is common in the pediatric population and in severe forms it can lead to debilitating fecal incontinence which has a significant impact on quality of life. Cecostomy tube insertion is a procedural option for cases refractory to medical management, however there is limited data investigating the long-term success and complication rate.

Methods: A retrospective review was performed evaluating patients at our centre undergoing cecostomy tube (CT) insertion between 2002 and 2018.

Primary Cilium Identifies a Quiescent Cell Population in the Human Intestinal Crypt.

Primary cilia are sensory antennae located at the cell surface which mediate a variety of extracellular signals involved in development, tissue homeostasis, stem cells and cancer. Primary cilia are found in an extensive array of vertebrae cells but can only be generated when cells become quiescent. The small intestinal epithelium is a rapidly self-renewing tissue organized into a functional unit called the crypt-villus axis, containing progenitor and differentiated cells, respectively.

Characterization of PGua, a Guanidinium-Rich Peptoid that Delivers IgGs to the Cytosol via Macropinocytosis.

To investigate the structure-cellular penetration relationship of guanidinium-rich transporters (GRTs), we previously designed PGua, a five-amino acid peptoid containing a conformationally restricted pattern of eight guanidines, which showed high cell-penetrating abilities and low cell toxicity. Herein, we characterized the cellular uptake selectivity, internalization pathway, and intracellular distribution of PGua, as well as its capacity to deliver cargo. PGua exhibits higher penetration efficiency in HeLa cells than in six other cell lines (A549, Caco-2, fibroblast, HEK293, Mia-PaCa2, and MCF7) and is mainly internalized by clathrin-mediated endocytosis and macropinocytosis.

Mepitel Film for the Prevention of Acute Radiation Dermatitis in Breast Cancer: A Randomized Multicenter Open-Label Phase III Trial.

Purpose: Radiation dermatitis (RD) is common in patients undergoing breast radiotherapy. Mepitel film (MF) can reduce RD, but the results from two randomized controlled trials are conflicting. We aimed to conduct a confirmatory randomized controlled trial in patients at risk of RD.

Renal outcomes of children born with posterior urethral valves at a tertiary center: A 15-year retrospective review.

Introduction: Posterior urethral valves (PUVs) is a congenital condition in which an obstruction in the urethra prevents drainage of urine from the bladder in males, with up to 60% of children diagnosed developing chronic kidney disease (CKD). The primary aim of this study was to identify novel factors that may predict development of CKD and end-stage real disease (ESRD ) in children with PUVs to potentially address modifiable factors and delay progression. The secondary aim was to compare rates of catheterization and incontinence between our patients and other case series to provide information to parents about long-term bladder outcomes.

Characterizing patients with multiple same-sided ureteric stones.

Purpose: Patients presenting with multiple same-sided ureteric stones (MSSUS) are a unique population with nuanced prognostic and treatment considerations, which have yet to be characterized in the literature. Therefore, our purpose was to examine outcomes of patients with MSSUS vs those with single ureteric stones (SUS).

Methods: A retrospective review of prospectively collected patients included adults (> 18yo) with [Formula: see text] 2 ipsilateral ureteral stones without prior treatment for their current stone burden.

Participation and Functional Independence in Adults With Recessive Spastic Ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a progressive disorder where upper and lower extremities motor performances may bring participation restriction. To document participation in adults with ARSAC and explore associations with motor performances. Twenty-eight participants took part in the study.

Direct Transition from Ultrathin Orthorhombic Dinickel Silicides to Epitaxial Nickel Disilicide Revealed by In Situ Synthesis and Analysis.

Understanding phase transitions of ultrathin metal silicides is crucial for the development of nanoscale silicon devices. Here, the phase transition of ultrathin (3.6 nm) Ni silicides on Si(100) substrates is investigated using an in situ synthesis and characterization approach, supplemented with ex situ transmission electron microscopy and nano-beam electron diffraction.

Geomechanical characterization of a heterogenous rock mass using geological and laboratory test results: a case study of the Niobec Mine, Quebec (Canada).

Abstract: To conduct a successful geomechanical characterization of rock masses, an appropriate interpretation of lithological heterogeneity should be attained by considering both the geological and geomechanical data. In order to clarify the reliability and applicability of geological surveys for rock mechanics purposes, a geomechanical characterization study is conducted on the heterogeneous rock mass of Niobec Mine (Quebec, Canada), by considering the characteristics of its various identified lithological units. The results of previous field and laboratory test campaigns were used to quantify the variability associated to intact rock geomechanical parameters for the different present lithological units.

Artificial Rearing of Atlantic Salmon Juveniles for Supportive Breeding Programs Induces Long-Term Effects on Gut Microbiota after Stocking.

In supportive breeding programs for wild salmon populations, stocked parr experience higher mortality rates than wild ones. Among other aspects of phenotype, the gut microbiota of artificially raised parr differs from that of wild parr before stocking. Early steps of microbiota ontogeny are tightly dependent upon environmental conditions, both of which exert long-term effects on host physiology.

Peptides Derived from Growth Factors to Treat Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease.

Assessment of muscular strength and functional capacity in the juvenile and adult myotonic dystrophy type 1 population: a 3-year follow-up study.

Introduction: Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic, and autosomal dominant disease. Muscle wasting and weakness have been associated with impaired functional capacity and restricted social participation in affected individuals. The disease's presentation is very heterogenous and its progression is still under-documented.