Variants in the AGBL5 gene are responsible for autosomal recessive Retinitis pigmentosa with hearing loss.

The AGBL5 gene encodes for the Cytoplasmic Carboxypeptidase 5 (CCP5), an α-tubulin deglutamylase that cleaves the γ-carboxyl-linked branching point of glutamylated tubulin. To date, pathogenic variants in AGBL5 have been associated only with isolated retinitis pigmentosa (RP). Hearing loss has not been reported in AGBL5-caused retinal disease.

GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment.

Here we conduct a study involving 12 individuals with retinal dystrophy, neurological impairment, and skeletal abnormalities, with special focus on GPATCH11, a lesser-known G-patch domain-containing protein, regulator of RNA metabolism. To elucidate its role, we study fibroblasts from unaffected individuals and patients carrying the recurring c.328+1 G > T mutation, which specifically removes the main part of the G-patch domain while preserving the other domains.

Retinal oxygen metabolic function in choroideremia and retinitis pigmentosa.

Purpose: To measure the retinal oxygen metabolic function with retinal oximetry (RO) in patients with choroideremia (CHM) and compare these findings with retinitis pigmentosa (RP) patients and controls.

Methods: Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.

Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

Purpose: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis.

Methods: We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015.

Bi-allelic variants in COQ8B, a gene involved in the biosynthesis of coenzyme Q10, lead to non-syndromic retinitis pigmentosa.

Retinitis pigmentosa (RP) is a Mendelian disease characterized by gradual loss of vision, due to the progressive degeneration of retinal cells. Genetically, it is highly heterogeneous, with pathogenic variants identified in more than 100 genes so far. Following a large-scale sequencing screening, we identified five individuals (four families) with recessive and non-syndromic RP, carrying as well bi-allelic DNA changes in COQ8B, a gene involved in the biosynthesis of coenzyme Q10.

Whole-Exome Analysis for Polish Caucasian Patients with Retinal Dystrophies and the Creation of a Reference Genomic Database for the Polish Population.

We present the results of the first study of a large cohort of patients with inherited retinal dystrophies (IRD) performed for the Polish population using whole-exome sequencing (WES) in the years 2016-2019. Moreover, to facilitate such diagnostic analyses and enable future application of gene therapy and genome editing for IRD patients, a Polish genomic reference database (POLGENOM) was created based on whole-genome sequences of healthy Polish Caucasian nonagenarians and centenarians. The newly constructed database served as a control, providing a comparison for variant frequencies in the Polish population.

Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression.

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.

Negotiating Safety: Facilitation of Return to Work for Individuals Employed in High-Risk Occupations.

Purpose: Return-to-work (RTW) after absence due to a mental illness is a largely understudied area, especially in industries already struggling with retention like those posing unique and high risks for public or personal safety (i.e., pilots, police officers, and health professionals), otherwise known as safety-sensitive sectors.

Detection of elusive DNA copy-number variations in hereditary disease and cancer through the use of noncoding and off-target sequencing reads.

Copy-number variants (CNVs) play a substantial role in the molecular pathogenesis of hereditary disease and cancer, as well as in normal human interindividual variation. However, they are still rather difficult to identify in mainstream sequencing projects, especially involving exome sequencing, because they often occur in DNA regions that are not targeted for analysis. To overcome this problem, we developed OFF-PEAK, a user-friendly CNV detection tool that builds on a denoising approach and the use of "off-target" DNA reads, which are usually discarded by sequencing pipelines.

GNB1-Related Rod-Cone Dystrophy: A Case Report.

Introduction: The (guanine nucleotide-binding protein, β1) gene encodes for the ubiquitous β1 subunit of heterotrimeric G proteins, which are associated with G-protein-coupled receptors (GPCRs). mutations cause a neurodevelopmental disorder characterized by a broad clinical spectrum. A novel variant has recently been confirmed in a case of rod-cone dystrophy.

Loss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration.

Purpose: Inherited retinal diseases (IRDs) are a group of monogenic conditions that can lead to progressive blindness. Their missing heritability is still considerable, due in part to the presence of disease genes that await molecular identification. The purpose of this work was to identify novel genetic associations with IRDs.

Genetic profile of syndromic retinitis pigmentosa in Portugal.

Purpose: Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal.

Navigating interprofessional boundaries: Midwifery students in Canada.

The literature on professional socialization focuses on how students adopt and internalize professional identities and values, and assumes that boundary work is essential to learning how best to practice their profession. However, a focus on boundary work in the context of midwifery training - which is embedded in the gendered and hierarchical landscape of maternity care - is lacking. Thus, this article examines how Canadian student-midwives learn to navigate and negotiate interprofessional boundaries.

Rearrangement of thiazolidine derivatives - a synthesis of a chiral fused oxathiane-γ-lactam bicyclic system.

Reaction of L-cysteine with carbonyl compounds leads to thiazolidine derivatives which undergo a stereoselective conversion to two types of chiral bicyclic products bearing two or three stereogenic centers, including the first fused oxathiane-γ-lactam system.

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common inherited retinal disease (IRD) and is characterized by photoreceptor degeneration and progressive vision loss. We report 4 patients presenting with RP from 3 unrelated families with variants in TBC1D32, which to date has never been associated with an IRD. To validate TBC1D32 as a putative RP causative gene, we combined Xenopus in vivo approaches and human induced pluripotent stem cell-derived (iPSC-derived) retinal models.

Benefits of Treadmill Training for Patients with Down Syndrome: A Systematic Review.

Background: The objective of this study was to evaluate the effectiveness of various results of treadmill training in children and adults with Down syndrome (DS).

Methods: To provide an overview of this effectiveness, we conducted a systematic literature review of studies in which participants with DS from all age groups received treadmill training, alone or combined with physiotherapy. We also looked for comparisons with control groups of patients with DS who did not undergo treadmill training.

Novel inhibitors of HSV-1 protease effective in vitro and in vivo.

Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with acyclovir is sufficient to manage the disease progression. However, the emergence of ACV-resistant strains drives the need for new therapeutics and molecular targets.

The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis.

Inherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease.

The diversity and utility of arylthiazoline and aryloxazoline siderophores: challenges of total synthesis.

Siderophores are unique ferric ion chelators produced and secreted by some organisms like bacteria, fungi and plants under iron deficiency conditions. These molecules possess immense affinity and specificity for Fe and other metal ions, which attracts great interest due to the numerous possibilities of application, including antibiotics delivery to resistant bacteria strains. Total synthesis of siderophores is a must since the compounds are present in natural sources at extremely small concentrations.

Multidisciplinary team directed analysis of whole genome sequencing reveals pathogenic non-coding variants in molecularly undiagnosed inherited retinal dystrophies.

The purpose of this paper is to identify likely pathogenic non-coding variants in inherited retinal dystrophy (IRD) genes, using genome sequencing (GS). Patients with IRD were recruited to the study and underwent comprehensive ophthalmological evaluation and GS. The results of GS were investigated through virtual gene panel analysis, and plausible pathogenic variants and clinical phenotype evaluated by the multidisciplinary team (MDT) discussion.

Chiral sulfonamides with various N-heterocyclic and aromatic units - Synthesis and antiviral activity evaluation.

Chiral sulfonamides with aromatic fragments are important chemical building blocks found widely in many natural products, catalysts, and molecules of biological importance. In this report, we describe the efficient synthesis of a series of chiral sulfonamides which, in addition to the aromatic part (phenyl, biphenyl, and dansyl units), possess N-heterocyclic systems. The described compounds were obtained by nucleophilic substitution of chiral N-heterocyclic amines and commercially available aromatic sulfonyl chlorides under mild conditions.

Application of Polyamines and Amino Acid Derivatives Based on 2-Azabicycloalkane Backbone in Enantioselective Aldol Reaction.

Carbon-carbon bond forming reactions, such as aldol reaction and condensation, belong to extremely desired transformations as manifested by >25,000 entries in SciFinder. Their stereoselective variant requires the use of an appropriate catalyst with a strictly defined structure. Hence, chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested in a stereoselective aldol reaction between cyclic/acyclic ketone and -nitrobenzaldehyde both in organic and aqueous media.