Long-lived cytokinetic bridges coordinate sister-cell elimination in mouse embryos.

Apoptosis is a key feature of preimplantation development, but whether it occurs in a cell-autonomous or coordinated manner was unknown. Here, we report that plasma membrane abscission, the final step of cell division, is profoundly delayed in early mouse embryos such that a cytokinetic bridge is maintained for the vast majority of the following interphase. Early embryos thus consist of many pairs of sister cells connected by stable cytokinetic bridges that allow them to share diffusible molecules.

Effect of Cariprazine on Outcomes in Older-aged and Younger-aged Patients with Bipolar I Disorder: A Post-hoc Analysis.

Objectives: To evaluate cariprazine in adults with older- and younger-age bipolar I disorder (OABD-I and YABD-I) and compare treatment effects between them.

Design And Setting: Pooled post-hoc analysis of studies in depressive or acute manic/mixed episodes associated with bipolar I disorder.

Participants: 475/1383 patients (34.

The PREPARE Study: Acceptability and Feasibility of a Telehealth Trimodal Prehabilitation Program for Women with Endometrial Neoplasia.

Patients with endometrial neoplasia (EN) often have multiple comorbidities and a higher surgical risk. Prehabilitation programs (PPs) combine various interventions to improve preoperative conditions and reduce impairment due to surgical stress. We conducted a pragmatic pilot study to evaluate the acceptability and feasibility of a trimodal telehealth PP (exercise, nutrition, and psychological support) for EN patients.

Rehabilitation Interventions for Fear Avoidance Beliefs and Behaviors in Sudden Onset Musculoskeletal Conditions: A Scoping Review.

Fear avoidance (FA) describes beliefs and behaviors related to avoiding movements or activities after a painful event. FA is a prevalent issue that limits the recovery outcomes and social reintegration of burn survivors. However, as current literature focuses on chronic conditions, understanding the impact and treatment of FA within sudden onset musculoskeletal (MSK) conditions, specifically in the burn survivor population, is lacking.

Attenuating hyperammonemia preserves protein synthesis and muscle mass via restoration of perturbed metabolic pathways in bile duct-ligated rats.

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD.

Characteristics of supervised injection site clients and factors associated with requiring overdose intervention, Montreal, Canada, 2018-2022.

Background: Supervised injection sites (SIS) offer a hygienic environment in which people can inject drugs under observation; as such, these harm reduction services have been on the forefront of the overdose epidemic. We sought to understand factors predictive of an overdose requiring an emergency response intervention at SIS in Montréal, Canada.

Methods: We used administrative data from all four Montréal SIS from 1 March 2018 - 31 October 2022 to first calculate the rate of onsite overdose requiring intervention (e.

Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood.

Methods: We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays.

Under-recognised neurocognitive deficits in adults and adolescents with tuberous sclerosis complex.

Background: Tuberous sclerosis complex (TSC) is a genetic disease characterised by the growth of benign tumours. The Tuberous sclerosis Associated Neuropsychiatric Disorders (TAND) Checklist is used to identify patient-reported neurocognitive deficits. Patients may, however, under-recognise mild cognitive impairment.

Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation.

Intratumoral heterogeneity (ITH) is spatial, phenotypic, or molecular differences within the same tumor that have important implications for accurate tumor classification and assessment of predictive biomarkers. The Canadian Ovarian Experimental Unified Resource (COEUR) has created a cohort of 437 FFPE tissue specimens from 108 tubo-ovarian high-grade serous carcinoma (HGSC) patients to quantify ITH across the anatomical sites and between primary and recurrence. We quantified the ITH of six clinically used immunohistochemical diagnostic and prognostic biomarkers (WT1, p53, p16, PR, CD8, and Ki67).

Nanoscale Viscometry Reveals an Inherent Mucus Defect in Cystic Fibrosis.

The abnormally viscous and thick mucus is a hallmark of cystic fibrosis (CF). How the mutated CF gene causes abnormal mucus remains an unanswered question of paramount interest. Mucus is produced by the hydration of gel-forming mucin macromolecules that are stored in intracellular granules prior to release.

Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.

Objective: Tuberous sclerosis complex (TSC) is a monogenetic disorder associated with sustained mechanistic target of rapamycin (mTOR) activation, leading to heterogeneous clinical manifestations. Epilepsy and renal angiomyolipoma are the most important causes of morbidity in adult people with TSC (pwTSC). mTOR is a key player in inflammation, which in turn could influence TSC-related clinical manifestations.

SMARCA4 regulates the NK-mediated killing of senescent cells.

Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells.

Thoracolumbar fascia ultrasound shear strain differs between low back pain and asymptomatic individuals: expanding the evidence.

Objectives: To compare thoracolumbar fascia (TLF) shear strain between individuals with and without nonspecific low back pain (NSLBP), investigate its correlation with symptoms, and assess a standardized massage technique's impact on TLF shear strain.

Methods: Participants were prospectively enrolled between February 2021 and June 2022. Pre- and post-intervention TLF ultrasound and pain/disability questionnaires were conducted.

Addressing evidence needs during health crises in the province of Quebec (Canada): a proposed action plan for rapid evidence synthesis.

Background: The COVID-19 pandemic necessitated the rapid availability of evidence to respond in a timely manner to the needs of practice settings and decision-makers in health and social services. Now that the pandemic is over, it is time to put in place actions to improve the capacity of systems to meet knowledge needs in a situation of crisis. The main objective of this project was thus to develop an action plan for the rapid syntheses of evidence in times of health crisis in Quebec (Canada).

Cemiplimab in recurrent cervical cancer: Final analysis of overall survival in the phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks.

Serum glial fibrillary acidic protein in acute stroke: feasibility to determine stroke-type, timeline and tissue-impact.

Background: Interest is emerging regarding the role of blood biomarkers in acute stroke. The aim of this pilot study was to determine the feasibility of biomarker acquisition in suspected acute stroke, using modern ultrasensitive immunoassay techniques, and explore their potential usefulness for stroke diagnosis and management.

Methods: In 62 patients with suspected acute stroke, blood samples were prospectively obtained upon arrival and prior to neuroimaging.

Novel Lipid Formulation Increases Absorption of Oral Cannabidiol (CBD).

: Cannabidiol (CBD) is an approved treatment for childhood epilepsies and a candidate treatment for several other CNS disorders. However, it has poor oral bioavailability. We investigated the effect of a novel lipid formulation on its absorption in humans and on its tissue distribution in mice.

Canagliflozin inhibits hedgehog interacting protein (Hhip) induction of tubulopathy in diabetic Akita mice.

Renal hedgehog interacting protein (Hhip) activates sodium-glucose cotransporter 2 (Sglt2) expression and promotes tubular senescence in murine diabetic kidney disease (DKD), yet its underlying mechanism(s) are poorly understood. Here we study the effect of the SGLT2 inhibitor, canagliflozin on tubulopathy (fibrosis and apoptosis) in Akita/Hhip-transgenic (Tg) mice with overexpression of Hhip in their renal proximal tubular cells (RPTCs) and its relevant mechanisms. The DKD-tubulopathy with pronounced Sglt2 expression was aggravated in the kidney of Akita/Hhip-Tg cf.

Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes.

The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Cortical hemodynamics of electrographic status epilepticus in the critically ill.

Objectives: The pathophysiological mechanisms of status epilepticus (SE) underlying potential brain injury remain largely unclear. This study aims to employ functional near-infrared spectroscopy (fNIRS) combined with video-electroencephalography (vEEG) to monitor brain hemodynamics continuously and non-invasively in critically ill adult patients experiencing electrographic SE. Our primary focus is to investigate neurovascular coupling and cerebrovascular changes associated with seizures, particularly during recurring and/or prolonged episodes.

Heterozygous UBR5 variants result in a neurodevelopmental syndrome with developmental delay, autism, and intellectual disability.

E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder.

Comparing the efficacy of intra-articular injection of Platelet Rich Plasma (PRP) with corticosteroids (CS) in patients with chronic zygapophyseal joint low back pain confirmed by double intra-articular diagnostic blocks: A triple-blinded randomized multicentric controlled trial with a 6-month follow-up.

Objective: To compare the safety and effectiveness in improving function and reducing pain of autologous PRP to corticosteroid (CS) zygapophyseal (Z-joint) intra-articular (IA) injections at six months for patients with chronic osteoarthritis Z-joint mediated low back pain (LBP).

Design: Prospective triple-blinded multicentric randomized controlled trial.

Methods: Fifty participants with radiological signs of Z-joint OA and chronic Z-joint mediated LBP confirmed by a ≥80 % pain improvement after two IA local anesthetic injections were randomized into PRP and CS groups, using a 1:1 ratio.

HPV vaccination and anal HPV infection in gay, bisexual, and other men who have sex with men.

Background: Gay, bisexual, and other men who have sex with men (gbMSM) have a higher risk of human papillomavirus (HPV) infection and related diseases and would benefit from preventive measures such as HPV vaccination. We assessed the association between HPV vaccination and anal HPV infection in HIV-negative gbMSM and gbMSM living with HIV from the Lubricant Investigation in Men to Inhibit Transmission of HPV Infection study.

Methods: Participants attended 7 visits over 12 months where they provided a nurse-collected anal sample and self-completed a questionnaire on risk factors and HPV vaccination.