Investigating the pathogenicity of the recessive p.A251T variant in monogenic diabetes using iPSC-derived beta-like cells.

Monogenic diabetes, formerly called Maturity-Onset Diabetes of the Young (MODY), involves single-gene mutations, typically with dominant inheritance, and has been associated with variants in 14 genes. Among these, mutations are the most common, and their diagnosis allows the use of alternative therapies, including sulfonylureas. In an earlier study, we described a variant displaying recessive transmission, p.

Surgical vs Transcatheter Treatment in Patients With Coronary Artery Disease and Severe Aortic Stenosis.

Background: Severe aortic stenosis (AS) coexists with coronary artery disease (CAD) in approximately 50% of patients. The preferred treatment is combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG). However, transcatheter aortic valve replacement (TAVR) along with percutaneous coronary intervention (PCI) has emerged as a viable alternative.

Comparison of Pathologic Tumor Necrosis of Conventional Versus Ultrahypofractionated Preoperative Radiation Therapy in Localized Extremity Soft Tissue Sarcoma and Its Correlation With Clinical Outcomes.

Purpose: We aimed to determine if ultrahypofractionated radiation therapy (UHYPO-RT) delivering 6 Gy x 5 fractions yields similar tumor necrosis compared with conventional radiation therapy (CONV-RT) with 2 Gy x 25 fractions in soft tissue sarcoma. The clinical significance of tumor necrosis on loco-regional recurrence-free survival (LRFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed.

Methods And Materials: Patients with localized soft tissue sarcoma treated with CONV-RT or UHYPO-RT followed by surgery were included.

Combined portal and hepatic vein embolisation in perihilar cholangiocarcinoma.

Background: Major hepatectomy in perihilar cholangiocarcinoma (pCCA) patients with a small future liver remnant (FLR) risks posthepatectomy liver failure (PHLF). This study examines combined portal and hepatic vein embolisation (PVE/HVE) to increase preoperative FLR volume and potentially decrease PHLF rates.

Methods: In this retrospective, multicentre, observational study, data was collected from centres affiliated with the DRAGON Trials Collaborative and the EuroLVD registry.

The cellular and molecular properties of capsule surrounding silicone implants in humans vary uniquely according to the tissue type adjacent to the implant.

The foreign body reaction (FBR) to biomaterials results in fibrous encapsulation. Excessive capsule fibrosis (capsular contracture) is a major challenge to the long-term stability of implants. Clinical data suggests that the tissue type in contact with silicone breast implants alters susceptibility to developing capsular contracture; however, the tissue-specific inflammatory and fibrotic characteristics of capsule have not been well characterized at the cellular and molecular level.

Proteomics Impact on Cell Biology to Resolve Cell Structure and Function.

The acceleration of advances in proteomics has enabled integration with imaging at the EM and light microscopy levels, cryo-EM of protein structures, and artificial intelligence with proteins comprehensively and accurately resolved for cell structures at nanometer to subnanometer resolution. Proteomics continues to outpace experimentally based structural imaging, but their ultimate integration is a path toward the goal of a compendium of all proteins to understand mechanistically cell structure and function.

Effect of statin use for the primary prevention of cardiovascular disease among older adults: a cautionary tale concerning target trials emulation.

Objectives: Evidence concerning the effect of statins in primary prevention of cardiovascular disease (CVD) among older adults is lacking. Using Quebec population-wide administrative data, we emulated a hypothetical randomized trial including older adults >65 years on April 1, 2013, with no CVD history and no statin use in the previous year.

Study Design And Setting: We included individuals who initiated statins and classified them as exposed if they were using statin at least 3 months after initiation and nonexposed otherwise.

N-glycosylation mediated folding and quality control in serine proteases of the hepsin family.

N-linked glycans are specifically attached to asparagine residues in a N-X-S/T motif of secretory pathway glycoproteins. N-glycosylation of newly synthesized glycoproteins directs their folding via the lectin chaperones calnexin and calreticulin that are associated with protein-folding enzymes and glycosidases of the endoplasmic reticulum (ER). Misfolded glycoproteins are retained in the ER by the same lectin chaperones.

Effect of Focal vs Extended Irreversible Electroporation for the Ablation of Localized Low- or Intermediate-Risk Prostate Cancer on Early Oncological Control: A Randomized Clinical Trial.

Importance: Focal ablative irreversible electroporation (IRE) is a therapy that treats only the area of the tumor with the aim of achieving oncological control while reducing treatment-related functional detriment.

Objective: To evaluate the effect of focal vs extended IRE on early oncological control for patients with localized low- and intermediate-risk prostate cancer.

Design, Setting, And Participants: In this randomized clinical trial conducted at 5 centers in Europe, men with localized low- to intermediate-risk prostate cancer were randomized to receive either focal or extended IRE ablation.

A Multicenter, Randomized, Single-blind, 2-Arm Intervention Study Evaluating the Adverse Events and Quality of Life After Irreversible Electroporation for the Ablation of Localized Low-intermediate Risk Prostate Cancer.

Purpose: Our goal was to evaluate the effect of focal vs extended irreversible electroporation on side effects, patient-reported quality of life, and early oncologic control for localized low-intermediate risk prostate cancer patients.

Materials And Methods: Men with localized low-intermediate risk prostate cancer were randomized to receive focal or extended irreversible electroporation ablation. Quality of life was measured by International Index of Erectile Function, Expanded Prostate Cancer Index Composite questionnaire, and International Prostate Symptom Score.

Spatial modeling of ambient concentrations of volatile organic compounds in Montreal, Canada.

Unlabelled: Volatile organic compounds (VOCs) are components of the complex mixture of air pollutants within cities and can cause various adverse health effects. Therefore, it is necessary to understand their spatial distribution for exposure assessment in epidemiological studies.

Objectives: The objective was to model measured concentrations of five VOCs within the city of Montreal, Canada, developing spatial prediction models that can be used in health studies.

Formulation and exploration of novel, intramuscular pressure based, muscle activation strategies in a spine model.

Optimization models are often devised to assess spinal stability via estimating individual muscle forces. However, neglecting muscles' fluidic behavior remains an approximation due to the role of muscle pressure in force transmission. The purpose of this study was to leverage a validated Finite Element (FE) model of the spine, inclusive of Intra-Muscular Pressure (IMP), to explore muscle activation strategies towards maintaining equilibrium spinal stability.

The Psychological Impact of COVID-19 on Arthroplasty Surgeons.

Background: After the COVID-19 pandemic declaration in March 2020, all the elective total joint replacement surgeries in Canada were abruptly canceled for an indefinite period of time. The principal objective of this study was to determine the prevalence of psychological morbidity experienced by arthroplasty surgeons during the peak of the first wave of the COVID-19 pandemic. Secondary objectives included characterizing influential variables affecting the surgeon's well-being and suggesting directives for improvement.

Ecological studies of COVID-19 and air pollution: How useful are they?

Background: Results from ecological studies have suggested that air pollution increases the risk of developing and dying from COVID-19. Drawing causal inferences from the measures of association reported in ecological studies is fraught with challenges given biases arising from an outcome whose ascertainment is incomplete, varies by region, time, and across sociodemographic characteristics, and cannot account for clustering or within-area heterogeneity. Through a series of analyses, we illustrate the dangers of using ecological studies to assess whether ambient air pollution increases the risk of dying from, or transmitting, COVID-19.

The association between the incidence of post-menopausal breast cancer and residential greenness.

Background: There is little data as to whether exposure to residential greenness is associated with the incidence of breast cancer. Lack of physical activity and obesity are two of the accepted risk factors for postmenopausal breast cancer and living near green areas may contribute to an active lifestyle and maintaining a normal body mass index and, consequently, residential greenness may be associated with lower incidence rates.

Objectives: The objective of this study was to determine whether there was an association between past exposure to residential greenness and the incidence of invasive postmenopausal breast cancer among Canadian women living in Montreal, Quebec, in the mid-2000s.

Household determinants of biocontaminant exposures in Canadian homes.

Exposure to biocontaminants, such as dust mites, animal dander, bacteria, and mold, is associated with a range of health effects. This study identified household characteristics associated with indoor biocontaminant loadings in four Canadian cities. Floor dust was collected in 290 Canadian homes in Edmonton, Halifax, Montreal, and Windsor.

Inter-rater reliability of occupational exposure assessment in a case-control study of female breast cancer.

The objective of this paper was to estimate the inter-rater reliability of expert assessments of occupational exposures. An inter-rater reliability sub-study was conducted within a population-based case-control study of postmenopausal breast cancer. Detailed information on lifetime occupational histories was obtained from participants and two industrial hygienists assigned exposures to 185 jobs using a checklist of 293 agents.

Modeling High-Grade Serous Ovarian Carcinoma Using a Combination of Fallopian Tube Electroporation and CRISPR-Cas9-Mediated Genome Editing.

Ovarian cancer is the most lethal gynecologic cancer to date. High-grade serous ovarian carcinoma (HGSOC) accounts for most ovarian cancer cases, and it is most frequently diagnosed at advanced stages. Here, we developed a novel strategy to generate somatic ovarian cancer mouse models using a combination of electroporation and CRISPR-Cas9-mediated genome editing.

Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review.

Purpose Of Review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing -induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS).

Relationship Between Genetic Risk and Age of Diagnosis in Systemic Lupus Erythematosus.

Objective: Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis.

Methods: Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip.