The impact of obstructive sleep apnoea on post-operative outcomes.

Background: Unrecognised obstructive sleep apnoea (OSA) has been associated with adverse cardiorespiratory perioperative outcomes. However, with changing anaesthetic and perioperative management, there is ongoing uncertainty about the importance of OSA as a risk factor for post-operative complications.

Methods: A cohort study involving subjects undergoing elective surgery was conducted.

GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18.

Neutrophils are critical for host defense against fungi. However, the short life span and lack of genetic tractability of primary human neutrophils has limited analysis of neutrophil-fungal interactions. Human induced pluripotent stem cell (iPSC)-derived neutrophils (iNeutrophils) are a genetically tractable alternative to primary human neutrophils.

Peptide macrocyclisation intramolecular interception of visible-light-mediated desulfurisation.

Synthetic methods that enable the macrocyclisation of peptides facilitate the development of effective therapeutic and diagnostic tools. Herein we report a peptide cyclisation strategy based on intramolecular interception of visible-light-mediated cysteine desulfurisation. This method allows cyclisation of unprotected peptides in an aqueous solution the installation of a hydrocarbon linkage.

Loss of filamentous actin, tight junction protein expression, and paracellular barrier integrity in frataxin-deficient human brain microvascular endothelial cells-implications for blood-brain barrier physiology in Friedreich's ataxia.

Friedreich's Ataxia (FRDA) is the most prevalent inherited ataxia. FRDA results from loss of Frataxin (FXN), an essential mitochondrial iron trafficking protein. FRDA starts with an early burst of neurodegeneration of the dorsal root ganglion and cerebellar dentate nuclei, followed by progressive brain iron accumulation in the latter.

Frataxin-deficient human brain microvascular endothelial cells lose polymerized actin and are paracellularly permeable -implications for blood-brain barrier integrity in Friedreich's Ataxia.

Background: Friedreich's Ataxia (FRDA) is the most prevalent inherited ataxia; the disease results from loss of Frataxin, an essential mitochondrial iron trafficking protein. FRDA presents as neurodegeneration of the dorsal root ganglion and cerebellar dentate nuclei, followed by brain iron accumulation in the latter. End stage disease includes cardiac fibrosis that contributes to hypertrophic cardiomyopathy.

Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C-C Bond Formation.

The site-selective modification of peptides and proteins facilitates the preparation of targeted therapeutic agents and tools to interrogate biochemical pathways. Among the numerous bioconjugation techniques developed to install groups of interest, those that generate C(sp )-C(sp ) bonds are significantly underrepresented despite affording proteolytically stable, biogenic linkages. Herein, a visible-light-mediated reaction is described that enables the site-selective modification of peptides and proteins via desulfurative C(sp )-C(sp ) bond formation.

Lack of Association Between Sex Hormones, MDSCs, LDGs and pDCs in Males and Females With Systemic Lupus Erythematosus.

Plasmacytoid dendritic cells (pDCs) and low-density granulocytes (LDGs) are interferon-alpha producing cells that create a pro-inflammatory response in Systemic Lupus Erythematosus (SLE) leading to auto antibody production and organ damage. Both pDCs and LDGs have been shown to be dysfunctional in patients with active SLE. Myeloid-derived suppressor cells (MDSCs) have the capacity to control T and B cell activation and differentiation, and have recently been identified as cells of interest in SLE as well.

Calcium and the Ca-ATPase SPCA1 modulate plasma membrane abundance of ZIP8 and ZIP14 to regulate Mn(II) uptake in brain microvascular endothelial cells.

Manganese (II) accumulation in human brain microvascular endothelial cells is mediated by the metal-ion transporters ZRT IRT-like protein 8 (ZIP8) and ZRT IRT-like protein 14 (ZIP14). The plasma membrane occupancy of ZIP14, in particular, is increased in cells treated with Mn, lipopolysaccharide, or IL-6, but the mechanism of this regulation has not been elucidated. The calcium-transporting type 2C member 1 ATPase, SPCA1, is a Golgi-localized Ca-uptake transporter thought to support Golgi uptake of Mn also.

X-linked sideroblastic anaemia in a female fetus: a case report and a literature review.

Background: X-linked sideroblastic anaemia (XLSA) is commonly due to mutations in the ALAS2 gene and predominantly affects hemizygous males. Heterozygous female carriers of the ALAS2 gene mutation are often asymptomatic or only mildly anaemic. XLSA is usually characterized by microcytic erythrocytes (reduced mean corpuscular volume (MCV)) and hypochromia, along with increased red cell distribution width.

Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts.

Background: Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (arts, mmunodeficiency, ymphoedema and anogenital ysplasia), have previously depended on a single case report.

Site-Selective Installation of N -Modified Sidechains into Peptide and Protein Scaffolds via Visible-Light-Mediated Desulfurative C-C Bond Formation.

Post-translational modifications (PTMs) enhance the repertoire of protein function and mediate or influence the activity of many cellular processes. The preparation of site-specifically and homogeneously modified proteins, to apply as tools to understand the biological role of PTMs, is a challenging task. Herein, we describe a visible-light-mediated desulfurative C(sp )-C(sp ) bond forming reaction that enables the site-selective installation of N -modified sidechains into peptides and proteins of interest.

Disruption of the Pseudomonas aeruginosa Tat system perturbs PQS-dependent quorum sensing and biofilm maturation through lack of the Rieske cytochrome bc1 sub-unit.

Extracellular DNA (eDNA) is a major constituent of the extracellular matrix of Pseudomonas aeruginosa biofilms and its release is regulated via pseudomonas quinolone signal (PQS) dependent quorum sensing (QS). By screening a P. aeruginosa transposon library to identify factors required for DNA release, mutants with insertions in the twin-arginine translocation (Tat) pathway were identified as exhibiting reduced eDNA release, and defective biofilm architecture with enhanced susceptibility to tobramycin.

Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis.

Diazophosphonates, readily prepared from α-ketophosphonates by oxidation of the corresponding hydrazones in batch or in flow, are useful partners in 1,3-dipolar cycloaddition reactions to alkynes to give N-H pyrazoles, including the first intramolecular examples of such a process. The phosphoryl group imbues a number of desirable properties into the diazo 1,3-dipole. The electron-withdrawing nature of the phosphoryl stabilizes the diazo compound making it easier to handle, whilst the ability of the phosphoryl group to migrate readily in a [1,5]-sigmatropic rearrangement enables its transfer from C to N to aromatize the initial cycloadduct, and hence its facile removal from the final pyrazole product.

PSENEN Mutation in Coexistent Hidradenitis Suppurativa and Dowling-Degos Disease.

Hidradenitis suppurativa is a chronic relapsing disease with multiple abscesses, nodules, and scars in the apocrine bearing areas. Dowling-Degos is a rare autosomal dominant genodermatosis characterized by multiple hyperpigmented macules or papules in reticulate pattern, affecting mainly the flexures. We report a case of coexisting hidradenitis suppurativa and Dowling-Degos disease in a 31-year-old male in whom mutation analysis revealed a splice site mutation c.

Perioperative diabetes management of adult patients with diabetes: a best practice implementation project.

Objectives: The objectives of this project were to conduct a retrospective healthcare records audit to determine the current compliance with evidence-based criteria regarding perioperative management of patients with diabetes; to identify barriers and facilitators to achieve compliance and develop strategies to address areas of non-compliance, and to implement evidence-based best practice recommendations for perioperative diabetic management and to assess the effectiveness of these strategies in improving compliance of perioperative diabetic management across five participating clinical areas in a large tertiary referral hospital.

Introduction: Type 2 diabetes is a frequent co-morbidity among inpatients. It affects up to 20% of the general surgical population.

Molecular Defects in Friedreich's Ataxia: Convergence of Oxidative Stress and Cytoskeletal Abnormalities.

Friedreich's ataxia (FRDA) is a multi-faceted disease characterized by progressive sensory-motor loss, neurodegeneration, brain iron accumulation, and eventual death by hypertrophic cardiomyopathy. FRDA follows loss of frataxin (FXN), a mitochondrial chaperone protein required for incorporation of iron into iron-sulfur cluster and heme precursors. After the discovery of the molecular basis of FRDA in 1996, over two decades of research have been dedicated to understanding the temporal manifestations of disease both at the whole body and molecular level.

Site-Selective Modification of Peptides and Proteins via Interception of Free-Radical-Mediated Dechalcogenation.

The development of site-selective chemistry targeting the canonical amino acids enables the controlled installation of desired functionalities into native peptides and proteins. Such techniques facilitate the development of polypeptide conjugates to advance therapeutics, diagnostics, and fundamental science. We report a versatile and selective method to functionalize peptides and proteins through free-radical-mediated dechalcogenation.

Sickle cell disease in Sri Lanka: clinical and molecular basis and the unanswered questions about disease severity.

Background: Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this "rare" group of patients.

Results: All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle β-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016-March 2019. The majority of patients were of Sinhalese ethnicity (n = 52, 86.

The Effect of the Food Matrix on the In Vitro Bio-Accessibility and IgE Reactivity of Peanut Allergens.

Scope: Factors such as food processing, the food matrix, and antacid medication may affect the bio-accessibility of proteins in the gastrointestinal tract and hence their allergenic activity. However, at present they are poorly understood.

Methods And Results: Roasted peanut flour was incorporated into either a chocolate dessert or cookie matrix and bio-accessibility were assessed using an in vitro digestion system comprising a model chew and simulated gastric and duodenal digestion.

The solute carriers ZIP8 and ZIP14 regulate manganese accumulation in brain microvascular endothelial cells and control brain manganese levels.

Manganese supports numerous neuronal functions but in excess is neurotoxic. Consequently, regulation of manganese flux at the blood-brain barrier (BBB) is critical to brain homeostasis. However, the molecular pathways supporting the transcellular trafficking of divalent manganese ions within the microvascular capillary endothelial cells (BMVECs) that constitute the BBB have not been examined.