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.

ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice.

α/β-hydrolase domain 6 (ABHD6) is a lipase linked to physiological functions affecting energy metabolism. Brain ABHD6 degrades 2-arachidonoylglycerol and thereby modifies cannabinoid receptor signalling. However, its functional role within mesoaccumbens circuitry critical for motivated behaviour and considerably modulated by endocannabinoids was unknown.

Is COVID-19 Still a Threat? An Expert Opinion Review on the Continued Healthcare Burden in Immunocompromised Individuals.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. The emergence of several variants during the pandemic has presented numerous challenges in preventing and managing this disease. The development of vaccines has played a pivotal role in controlling the pandemic, with a significant portion of the global population being vaccinated.

Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection in hospitalized COVID-19 patients.

Genome-wide association studies performed in patients with coronavirus disease 2019 (COVID-19) have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity. However, the underlying -regulatory genetic factors that contribute to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we used single-cell RNA-sequencing to quantify genetic contributions to -regulatory variation in 361,119 peripheral blood mononuclear cells across 63 COVID-19 patients during acute infection, 39 samples collected in the convalescent phase, and 106 healthy controls.

Integration of Non-invasive Screening for Cystic Fibrosis Related Liver Disease in the Regular Follow-Up for Cystic Fibrosis.

Background: The reported prevalence of cystic fibrosis (CF)-related liver disease (CFLD) reaches up to 40% in some cohorts. CFLD is the 3rd leading cause of mortality among patients with CF. The aims of this study were to evaluate the prevalence of CFLD in a cohort followed at a tertiary university center, to define the types of liver involvement, and to determine how non-invasive screening methods can be optimally integrated into clinical practice.

Exposure to renin-angiotensin system inhibitors before kidney transplantation is associated with a decreased risk of delayed graft function.

Introduction: Animal models suggest a protective role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs) in reducing renal and cardiac ischemia-reperfusion injury. Our aim was to determine the association between pre-transplant ACEi/ARBs use and the occurrence of delayed graft function (DGF) in patients who received a kidney transplantation from a deceased donor.

Methods: Consecutive recipients between 2008 and 2021 in 2 Canadian university-affiliated centers were included in this retrospective cohort study.

Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice.

Angiopoietin-like protein 8 (Angptl8), expressed in the liver and adipocytes, forms a complex with Angptl3 or Angptl4, which regulates lipoprotein lipase and triglyceride metabolism. However, the precise functions of adipocyte Angptl8 remain elusive. Here we report that adipocyte-specific inducible Angptl8-knockout (AT-A8-KO) male mice on normal diet showed minor phenotypic changes, but after a high-fat high fructose (HFHF) diet, exhibited decreased body weight gain and glycemia, elevated rectal temperature and early dark phase energy expenditure compared to the Cre controls.

Development of an organizational typology of interprofessional primary care teams in Quebec, Canada: A multivariate analysis.

Background: This study aimed to develop an organizational typology of Interprofessional Primary Care (IPC) teams in Quebec, Canada, by describing their organizational profiles and assessing the association between the characteristics of the populations served and the organizational profiles.

Methods: This cross-sectional study was carried out using a finite mixture model of the 2021 financial monitoring data from the Ministry of Health and Social Services of Quebec. The population consisted of all IPC teams in Quebec (N = 368).

Injectable, cryopreservable mesenchymal stromal cell-loaded microbeads for pro-angiogenic therapy:proof-of-concept.

Despite their recognized potential for ischemic tissue repair, the clinical use of human mesenchymal stromal cells (hMSC) is limited by the poor viability of cells after injection and the variability of their paracrine function. In this study, we show how the choice of biomaterial scaffolds and the addition of cell preconditioning treatment can address these limitations and establish a proof-of-concept for cryopreservable hMSC-loaded microbeads. Injectable microbeads in chitosan, chitosan-gelatin, and alginate were produced using stirred emulsification to obtain a similar volume moment mean diameter (D[4,3] ∼ 500 µm).