Comparison of Widefield OCT Angiography Features Between Severe Non-Proliferative and Proliferative Diabetic Retinopathy.

Introduction: There is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR).

Methods: We conducted an observational longitudinal study from November 2022 to March 2023.

Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review.

Zellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, presenting difficulty in understanding individual prognosis and treatment effectiveness. The purpose of this study is to conduct a scoping review and meta-analysis of existing literature and a medical chart review to determine if characterization of clinical findings can predict severity in ZSD.

Clinical, neuroradiological, and molecular characterization of patients with atypical Zellweger spectrum disorder caused by PEX16 mutations: a case series.

Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD)-are primarily autosomal recessive disorders caused by mutations in any of 13 PEX genes involved in peroxisome assembly. Compared to other PEX-related disorders, some PEX16 defects are associated with an atypical phenotype consisting of spasticity, cerebellar dysfunction, preserved cognition, and prolonged survival. In this case series, medical records and brain MRIs from 7 patients with this PEX16 presentation were reviewed to further characterize this phenotype.

Improvements in Diabetic Neuropathy and Nephropathy After Bariatric Surgery: a Prospective Cohort Study.

Purpose: There are limited data on the impact of bariatric surgery on microvascular complications of type 2 diabetes (T2D), particularly diabetic neuropathy. We assessed microvascular complications (especially neuropathy) in obese patients with T2D before and 12 months after bariatric surgery.

Materials And Methods: This was a prospective observational cohort study.

Inaccuracies in epitope repertoire estimations when using Multi-Locus Allele-Level hla genotype imputation tools.

Background: Limited availability of allele-level HLA genotypes prompts their imputation from allele-group genotypes to estimate epitope mismatches. We evaluated the accuracy of epitope load and repertoire assignment when imputing allele-level HLA genotypes.

Methods: Analyses were conducted on 175 hematopoietic stem cell (HSC) donors from the Héma-Québec registry (HQR) and 57 HSC donor-recipient pairs from McGill University Health Centre (MUHC), Québec, Canada, genotyped for HLA-A, -B, -C, -DRB1 and -DQB1.

Performance of an allele-level multi-locus HLA genotype imputation tool in hematopoietic stem cell donors from Quebec.

Introduction: Donor-recipient HLA compatibility is an important determinant of transplant outcomes. Allele-group to allele-level imputations help assign HLA genotypes when allele-level genotypes are not available during donor selection.

Methods: We evaluated the performance of HaploStats, an allele-level multi-locus HLA genotype imputation tool from the National Marrow Donor Program, in a cross-sectional study including hematopoietic stem cell donors (HSCD) from Quebec, Canada.

Prophage Integrase Typing Is a Useful Indicator of Genomic Diversity in .

is a bacterial species that is a major cause of illness in humans and food-producing animals. exhibits considerable inter-serovar diversity, as evidenced by the large number of host adapted serovars that have been identified. The development of methods to assess genome diversity in will help to further define the limits of diversity in this foodborne pathogen.

A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer's disease.

Background: Clinical failures singularly targeting amyloid-β pathology indicate a critical need for alternative Alzheimer's disease (AD) therapeutic strategies. The mixed pathology reported in a large population of AD patients demands a multifunctional drug approach. Since activation of cAMP response element binding protein (CREB) plays a crucial role in synaptic strengthening and memory formation, we retooled a clinical drug with known neuroprotective and anti-inflammatory activity to activate CREB, and validated this novel multifunctional drug, NMZ, in 4 different mouse models of AD.

New Findings in Diabetic Maculopathy and Proliferative Disease by Swept-Source Optical Coherence Tomography Angiography.

Purpose: To describe the optical coherence tomography (OCT) angiography (OCTA) features of diabetic retinopathy.

Methods: Retrospective serial case reports were examined of patients who underwent routine clinical examination and OCTA with both DRI OCT Atlantis prototype and Triton Swept-Source OCT of the posterior pole and mid-periphery. When considered necessary, fluorescein fundus angiography (FFA) with OPTOS California wide-field imaging was performed.

The Insertion in Fingers Domain in Human Telomerase Can Mediate Enzyme Processivity and Telomerase Recruitment to Telomeres in a TPP1-Dependent Manner.

In most human cancer cells, cellular immortalization relies on the activation and recruitment of telomerase to telomeres. The telomere-binding protein TPP1 and the TEN domain of the telomerase catalytic subunit TERT regulate telomerase recruitment. TERT contains a unique domain, called the insertion in fingers domain (IFD), located within the conserved reverse transcriptase domain.

Characterization of Aldh2 (-/-) mice as an age-related model of cognitive impairment and Alzheimer's disease.

Background: The study of late-onset/age-related Alzheimer's disease (AD)(sporadic AD, 95% of AD cases) has been hampered by a paucity of animal models. Oxidative stress is considered a causative factor in late onset/age-related AD, and aldehyde dehydrogenase 2 (ALDH2) is important for the catabolism of toxic aldehydes associated with oxidative stress. One such toxic aldehyde, the lipid peroxidation product 4-hydroxynonenal (HNE), accumulates in AD brain and is associated with AD pathology.

Role of the lipid peroxidation product, 4-hydroxynonenal, in the development of nitrate tolerance.

Tolerance to nitrates such as nitroglycerin (GTN) is associated with oxidative stress, inactivation of aldehyde dehydrogenase 2 (ALDH2), and decreased GTN-induced cGMP accumulation and vasodilation. We hypothesized that GTN-induced inactivation of ALDH2 results in increased 4-hydroxy-2-nonenal (HNE) adduct formation of key proteins involved in GTN bioactivation, and, consequently, an attenuated vasodilator response to GTN (i.e.

In vivo imaging of cortical vitreous using 1050-nm swept-source deep range imaging optical coherence tomography.

Purpose: To image the cortical vitreous, determine the prevalence of the bursa premacularis and space of Martegiani, and measure the dimensions of the bursa using the new 1050-nm swept-source deep range imaging optical coherence tomography (DRI OCT-1 Atlantis).

Design: Retrospective cross-sectional study.

Methods: One hundred and nineteen consecutive patients (5-100 years) underwent an OCT scan using 1050-nm swept-source deep range imaging optical coherence tomography.

A translocation-defective telomerase with low levels of activity and processivity stabilizes short telomeres and confers immortalization.

Short, repetitive, G-rich telomeric sequences are synthesized by telomerase, a ribonucleoprotein consisting of telomerase reverse transcriptase (TERT) and an integrally associated RNA. Human TERT (hTERT) can repetitively reverse transcribe its RNA template, acting processively to add multiple telomeric repeats onto the same substrate. We investigated whether certain threshold levels of telomerase activity and processivity are required to maintain telomere function and immortalize human cells with limited lifespan.

Regulation of telomere length and homeostasis by telomerase enzyme processivity.

Telomerase is a ribonucleoprotein consisting of a catalytic subunit, the telomerase reverse transcriptase (TERT), and an integrally associated RNA that contains a template for the synthesis of short repetitive G-rich DNA sequences at the ends of telomeres. Telomerase can repetitively reverse transcribe its short RNA template, acting processively to add multiple telomeric repeats onto the same DNA substrate. The contribution of enzyme processivity to telomere length regulation in human cells is not well characterized.

Peripapillary choroidal neovascularisation in the context of ocular syphilis is sensitive to combination antibiotic and corticosteroid treatment.

Peripapillary choroidal neovascularisation (CNV) in the context of ocular syphilis is exceptional and little is known about its natural history and optimal therapeutic management. We report here a case of right eye peripapillary CNV with subretinal fluid encroaching on the fovea in a patient with mild bilateral ocular inflammation and cystoid macular oedema (CMO) in his contralateral eye. Extensive investigations revealed positive serology for active syphilitic infection.

Effect of overexpression of human aldehyde dehydrogenase 2 in LLC-PK1 cells on glyceryl trinitrate biotransformation and cGMP accumulation.

Background And Purpose: Recent studies suggest a primary role for aldehyde dehydrogenase 2 (ALDH2) in mediating the biotransformation of organic nitrates, such as glyceryl trinitrate (GTN), to the proximal activator of soluble guanylyl cyclase (sGC), resulting in increased cGMP accumulation and vasodilation. Our objective was to assess the role of ALDH2 in organic nitrate action using a cell culture model.

Experimental Approach: Porcine renal epithelial (LLC-PK1) cells possess an intact NO-sGC-cGMP signaling system, and can be used as a biochemical model of organic nitrate action.

Changes in aldehyde dehydrogenase 2 expression in rat blood vessels during glyceryl trinitrate tolerance development and reversal.

Background And Purpose: Recent studies have suggested an essential role for aldehyde dehydrogenase 2 (ALDH2) in the bioactivation of organic nitrates such as glyceryl trinitrate (GTN). In the present study, we utilized an in vivo GTN tolerance model to further investigate the role of ALDH2 in GTN bioactivation and tolerance.

Experimental Approach: We assessed changes in aortic ALDH activity, and in ALDH2 protein expression in various rat blood vessels (aorta, vena cava, femoral artery and femoral vein) during continuous GTN exposure (0.

Comparison of lectin binding of drusen, RPE, Bruch's membrane, and photoreceptors.

Purpose: Drusen are deposits located between the retinal pigment epithelium and Bruch's membrane in age-related maculopathy. They are believed to be photoreceptor byproducts that are incompletely metabolized by the retinal pigment epithelium. This study therefore compares the lectin histochemistry of drusen, photoreceptors, retinal pigment epithelium, and Bruch's membrane.