: Cognitive impairments are one of the most common and disabling symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here, we address the possibility of a specific cognitive profile inherent to ME/CFS. Due to the occurrence of cognitive deficits, fatigue, and pain in both pathologies, multiple sclerosis (MS) is a relevant comparison model.
View Article and Find Full Text PDFThe detection of skeletal remains using human remain detection dogs (HRD) is often reported anecdotally by handlers to be a challenge. Limited studies have been conducted to determine the volatile organic compounds (VOCs) emitted from bones, particularly when there is limited organic matter remaining. This study aimed to determine the VOCs emitted from dry, weathered bones and examine the detection performance of HRD dogs on these bones when used as training aids.
View Article and Find Full Text PDFCognitive biases have been studied in relation to schizophrenia and psychosis for over 50 years. Yet, the quality of the evidence linking cognitive biases and psychosis is not entirely clear. This umbrella-review examines the quality of the evidence and summarizes the effect sizes of the reasoning and interpretation cognitive biases studied in relation to psychotic characteristics (psychotic disorders, psychotic symptoms, psychotic-like experiences or psychosis risk).
View Article and Find Full Text PDFObjectives: HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data.
Methods: We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs.
Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab).
View Article and Find Full Text PDFBackground & Aims: Delayed diagnosis of inflammatory bowel disease (IBD) leads to prolonged symptoms and worse long-term outcomes. We sought to evaluate whether race, ethnicity, disease type, and social factors are associated with delayed diagnosis of pediatric IBD.
Methods: We performed a cross-sectional study of newly diagnosed pediatric patients with IBD at 22 United States sites from 2019 to 2022.
Gene therapy based on the CRISPR/Cas9 system has emerged as a promising strategy for treating the monogenic fragile skin disorder recessive dystrophic epidermolysis bullosa (RDEB). With this approach problematic wounds could be grafted with gene edited, patient-specific skin equivalents. Precise gene editing using homology-directed repair (HDR) is the ultimate goal, however low efficiencies have hindered progress.
View Article and Find Full Text PDFClin Gastroenterol Hepatol
October 2024
Single particle analysis from cryogenic transmission electron microscopy (cryo-EM) is particularly attractive for complexes for which structure prediction remains intractable, such as antibody-antigen complexes. Here we obtain the detailed structure of a particularly difficult complex between human epidermal growth factor receptor 2 (HER2) and the antigen-binding fragments from two distinct therapeutic antibodies binding to distant parts of the flexible HER2, pertuzumab and trastuzumab (HTP). We highlight the strengths and limitations of current data processing software in dealing with various kinds of heterogeneities, particularly continuous conformational heterogeneity, and in describing the motions that can be extracted from our dataset.
View Article and Find Full Text PDFMonoclonal antibodies (mAbs) are biotherapeutics that have achieved outstanding success in treating many life-threatening and chronic diseases. The recognition of an antigen is mediated by the fragment antigen binding (Fab) regions composed by four different disulfide bridge-linked immunoglobulin domains. NMR is a powerful method to assess the integrity, the structure and interaction of Fabs, but site specific analysis has been so far hampered by the size of the Fabs and the lack of approaches to produce isotopically labeled samples.
View Article and Find Full Text PDFTaiwan J Ophthalmol
January 2023
We describe a case of exogenous cryptococcal endophthalmitis without central nervous system (CNS) involvement or systemic infection in an immunocompetent patient. An 82-year-old male with hypertension, hyperlipidemia, type 2 diabetes mellitus, and primary open-angle glaucoma with a history of left eye trabeculectomy presented with 3 months of worsening left eye pain and redness. Vitreous cultures resulted as , prompting treatment with intravitreal amphotericin and further investigation.
View Article and Find Full Text PDFThe humoral response mediated by alloantibodies directed against donor HLA molecules (DSAs) is one of the main causes of graft loss in kidney transplantation. Understanding the pathophysiology leading to humoral kidney rejection as the development of therapeutic tools is therefore a main objective in the field of solid organ transplantation and necessitate adapted experimental models. Among the immunosuppressive agents used in renal transplantation, belatacept, a fusion protein targeting T costimulatory molecules has shown its ability to prevent more efficiently the secretion of DSA by different mechanisms including a direct action on plasma cells but also on B lymphocytes and follicular helper T lymphocytes (Tfh) cooperation.
View Article and Find Full Text PDFDuring a time of rapid urban growth and development, it is becoming ever more important to monitor the carbon fluxes of our cities. Unlike Canada's commercially managed forests that have a long history of inventory and modelling tools, there is both a lack of coordinated data and considerable uncertainty on assessment procedures for urban forest carbon. Nonetheless, independent studies have been carried out across Canada.
View Article and Find Full Text PDFColon cancer is the third most common malignancy in Canada. Computed tomography colonography (CTC) provides a creditable and validated option for colon screening and assessment of known pathology in patients for whom conventional colonoscopy is contraindicated or where patients self-select to use imaging as their primary modality for initial colonic assessment. This updated guideline aims to provide a toolkit for both experienced imagers (and technologists) and for those considering launching this examination in their practice.
View Article and Find Full Text PDFCardiorenal syndromes type 1 and 2 are complex disorders in which cardiac dysfunction leads to kidney dysfunction. However, the mechanisms remain incompletely explained, during pulmonary hypertension in particular. The objective of this study is to develop an original preclinical model of cardiorenal syndrome secondary to a pulmonary hypertension in piglets.
View Article and Find Full Text PDFGenome editing using the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) gene-editing system (CRISPR-Cas) is a valuable tool for fundamental and applied research applications. Significant improvements in editing efficacy have advanced genome editing strategies into phase 3 human clinical trials. However, recent studies suggest that our understanding of editing outcomes has lagged behind the developments made in generating the edits themselves.
View Article and Find Full Text PDFIntermittent fasting is becoming more popular as health benefits are described in recent literature. Various forms of fasting exist, one of them involving a zero-calorie diet and drinking only water. However, the safety of water-only fasting is still not well established.
View Article and Find Full Text PDFOffering an inferior and rarely chosen third (decoy) option to decision makers choosing between two options has a paradoxical effect: It increases the choice share of the option most similar to the decoy. This attraction effect is robust when options are numeric but rarely occurs in humans when options are visual, even though it occurs in animals. Building on psychophysics, we examined two types of visual attributes: quantitative and qualitative.
View Article and Find Full Text PDFIntroduction: Virtual Reality technology helps in creating virtual environments for evaluation of visual performance of low vision individuals with holistic experience. The purpose of this study was to develop a virtual reality (VR) platform for the objective assessment of functional vision in patients with low vision in two categories, central and peripheral vision loss .
Materials And Methods: Focus group discussions (FGD) were organized to understand the difficulties faced on a day to day basis by patients with low vision.
Background: Cognitive biases are recognized as important treatment targets for reducing symptoms associated with severe mental disorders. Although cognitive biases have been linked to symptoms in most studies, few studies have looked at such biases transdiagnostically. The Cognitive Bias Questionnaire for psychosis (CBQp) is a self-reported questionnaire that assesses cognitive biases amongst individuals with a psychotic disorder, as well as individuals with other severe mental disorders.
View Article and Find Full Text PDFThe process of human decomposition is driven by biological decomposers, mainly bacteria, vertebrates, and invertebrate scavengers. When vertebrate scavengers have access to a body, they can considerably accelerate decomposition through consumption of soft tissue and dispersal of skeletal elements. Presently, there are limited data available on vertebrate scavenging activity in Canada, particularly in densely populated provinces such as Ontario.
View Article and Find Full Text PDFAm J Ophthalmol Case Rep
September 2022
Purpose: To describe a case of late post-surgical sympathetic ophthalmia documented with multimodal imaging.
Observations: A 74-year-old male presented to the urgent care of the New York Eye and Ear Infirmary with blurry vision and discomfort in his left eye for three weeks. His vision was 20/50, with intraocular pressure of 13 mmHg, and slit lamp examination was significant for conjunctival congestion, 1+ anterior segment cell and flare, and diffuse keratic precipitates.
Background And Objectives: After two doses of mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients on dialysis show a defective humoral response, but a third dose could increase anti-SARS-CoV-2 spike IgG titers. Responses could be different in virus-naive and SARS-CoV-2-recovered patients on dialysis. However, characterization of memory B cell response after three doses is lacking.
View Article and Find Full Text PDFBackground: A small subset of cases of inflammatory bowel disease (IBD) occurs as a result of single gene defects, and typically occurs in young or very young pediatric patients, referred to as "monogenic very-early onset IBD (VEO-IBD)". The gene variants leading to monogenic VEO-IBD are often associated with primary immunodeficiency syndromes.
Case Report: A six year-old girl presented to our gastroenterology clinic with LRBA deficiency with a heterozygous mutation at c.