Pain reflects the informational value of nociceptive inputs.

Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pain's learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock.

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels.

Despite recent therapeutic advances, achieving optimal glycaemic control remains a challenge in managing Type 2 Diabetes (T2D). Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have emerged as effective treatments by promoting urinary glucose excretion. However, the full scope of their mechanisms extends beyond glycaemic control.

A rapid review of differences in cerebrospinal neurofilament light levels in clinical subtypes of progressive multiple sclerosis.

Background: Multiple sclerosis (MS) is divided into three clinical phenotypes: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). It is unknown to what extent SPMS and PPMS pathophysiology share inflammatory or neurodegenerative pathological processes. Cerebrospinal (CSF) neurofilament light (NfL) has been broadly studied in different MS phenotypes and is a candidate biomarker for comparing MS subtypes.

The effect of electron backscatter and charge build up in media on beam current transformer signal for ultra-high dose rate (FLASH) electron beam monitoring.

Beam current transformers (BCT) are promising detectors for real-time beam monitoring in ultra-high dose rate (UHDR) electron radiotherapy. However, previous studies have reported a significant sensitivity of the BCT signal to changes in source-to-surface distance (SSD), field size, and phantom material which have until now been attributed to the fluctuating levels of electrons backscattered within the BCT. The purpose of this study is to evaluate this hypothesis, with the goal of understanding and mitigating the variations in BCT signal due to changes in irradiation conditions.

The journey from bench to bedside-it takes a science village.

I was fortunate enough to start my career at what was the dawn of modern-day molecular biology and to apply it to an important health problem. While my early work focused on fundamental science, the desire to understand human disease better and to find practical applications for research discoveries resulted, over the following decades, in creating a stream of translational research directed specifically toward epithelial cancers. This could only have been possible through multiple collaborations.

Do we intervene less and slower in the epilepsy monitoring unit for psychogenic seizures?

Purpose: Individuals with psychogenic non-epileptic seizures (PNES) can be stigmatized in healthcare settings. We aimed to compare intervention rate (IR), intervention time (IT), and adverse event (AE) rate between PNES and epileptic seizures (ES) in the epilepsy monitoring unit (EMU).

Methods: We used a prospective database of consecutive admissions to our centre's EMU between August 2021 and September 2022.

Impact of a carrageenan gel on viral load of genital human papillomavirus infections in sexually active women: Findings from the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) trial.

Previous research has shown that women's use of a carrageenan gel reduces the risk of acquiring genital human papillomavirus (HPV) infections but does not help to clear existing ones. Although gel use may not result in complete clearance, it may decrease the viral load of HPV infections. We tested this hypothesis in the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) randomized controlled trial.

School- and intervention-related factors associated with institutionalization of health promotion interventions in elementary schools.

Introduction: Long-term availability of health-promoting interventions (HPIs) in school settings can translate into health benefits for children. However, little is known about factors associated with HPI institutionalization in schools. In this study, we identified correlates of the institutionalization of HPIs offered in elementary schools in Quebec, Canada.

Evaluation of interleukin-1 and interleukin-6 receptor antagonists in a murine model of acute lung injury.

The acute exudative phase of acute respiratory distress syndrome (ARDS), a severe form of respiratory failure, is characterized by alveolar damage, pulmonary oedema, and an exacerbated inflammatory response. There is no effective treatment for this condition, but based on the major contribution of inflammation, anti-inflammatory strategies have been evaluated in animal models and clinical trials, with conflicting results. In COVID-19 ARDS patients, interleukin (IL)-1 and IL-6 receptor antagonists (IL-1Ra and IL-6Ra, kineret and tocilizumab, respectively) have shown some efficacy.

Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

Background: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients.

Methods: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass.

Impact of Depressive Symptom Severity on Buprenorphine/Naloxone and Methadone Outcomes in People With Prescription-Type Opioid Use Disorder: Results From a Pragmatic Randomized Controlled Trial.

Objective: To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD).

Method: We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback.

Mediating effect of craving on the impact of buprenorphine/naloxone and methadone treatment on opioid use: Results from a randomized controlled trial.

Background: The relationship between opioid craving and opioid use is unclear. We sought to determine to what extent craving mediated the relationship between opioid agonist therapy and changes in opioid use.

Methods: Data came from a pragmatic, 24-week, pan-Canadian, multi-centric, open-label, randomized controlled trial comparing flexible buprenorphine/naloxone take-home doses to standard supervised methadone models of care for the treatment of prescription-type opioid use disorder.

A senescence restriction point acting on chromatin integrates oncogenic signals.

We identify a senescence restriction point (SeRP) as a critical event for cells to commit to senescence. The SeRP integrates the intensity and duration of oncogenic stress, keeps a memory of previous stresses, and combines oncogenic signals acting on different pathways by modulating chromatin accessibility. Chromatin regions opened upon commitment to senescence are enriched in nucleolar-associated domains, which are gene-poor regions enriched in repeated sequences.

Brachytherapy on-a-chip: a clinically-relevant approach for radiotherapy testing in 3d biology.

We describe the first microfluidic device for testing of brachytherapy (BT), with applications in translational cancer research. Our PDMS-made BT-on-chip system allows highly precise manual insertion of clinical BT seeds, reliable dose calculation using standard clinically-used TG-43 formalism and easy culture of naturally hypoxic spheroids in less than 3 days, thereby increasing the translational potential of the device. As the BT-on-chip platform is designed to be versatile, we showcase three different gold-standard post-irradiation bioassays and recapitulate, for the first time on-chip, key clinical observations such as dose rate effect and hypoxia-induced radioresistance.

14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation.

We previously established the scaffold protein 14-3-3ζ as a critical regulator of adipogenesis and adiposity, but the temporal specificity of its action during adipocyte differentiation remains unclear. To decipher if 14-3-3ζ exerts its regulatory functions on mature adipocytes or on adipose precursor cells (APCs), we generated 14-3-3ζKO and 14-3-3ζKO mouse models. Our findings revealed a pivotal role for 14-3-3ζ in APC differentiation in a sex-dependent manner, whereby male and female 14-3-3ζKO mice display impaired or potentiated weight gain, respectively, as well as fat mass.

Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis.

Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs.

Simultaneous multiple cervical vessel dissection manifested as pulsatile tinnitus.

A previously healthy 43-year-old woman with Wallenberg syndrome, stemming from a left vertebral artery dissection and resulting in a left lateral medulla oblongata infarct, was later diagnosed with simultaneous bi-carotid and right V3 dissection. Seven days post-admission, she experienced sudden right-sided pulsatile tinnitus and exhibited a right-sided carotid murmur. High-resolution vessel wall MR imaging confirmed the new dissections.

A phase IIb randomized placebo-controlled trial testing the effect of MAG-EPA long-chain omega-3 fatty acid dietary supplement on prostate cancer proliferation.

Background: High prostate eicosapentaenoic fatty acid (EPA) levels were associated with a significant reduction of upgrading to grade group (GG) ≥ 2 prostate cancer in men under active surveillance. We aimed to evaluate the effect of MAG-EPA long-chain omega-3 fatty acid dietary supplement on prostate cancer proliferation.

Methods: A phase II double-blind randomized placebo-controlled trial was conducted in 130 men diagnosed with GG ≥ 2 prostate cancer and undergoing radical prostatectomy between 2015-2017 (Clinicaltrials.

Disease-associated astrocyte epigenetic memory promotes CNS pathology.

Disease-associated astrocyte subsets contribute to the pathology of neurologic diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis. However, little is known about the stability of these astrocyte subsets and their ability to integrate past stimulation events. Here we report the identification of an epigenetically controlled memory astrocyte subset that exhibits exacerbated pro-inflammatory responses upon rechallenge.

Decline in Mobility and Balance in Persons With Post-COVID-19 Condition.

Objectives: Post-COVID-19 condition (PCC) may impact mobility and balance and affect physical function. The objectives of the study were to estimate the prevalence of decline in balance and mobility in individuals with PCC; explore the association between comorbidities and sociodemographic characteristics with decline in balance and mobility; and evaluate correlations between decline in mobility and balance with change in performance of usual activities, personal care, and global health perception.

Methods: The design was a cross-sectional study of persons with a COVID-19 diagnosis that was confirmed at least 3 months before the study.

Antithrombotic Management and Outcomes of Anterior ST-Elevation Myocardial Infarction With New-Onset Wall Motion Abnormalities in Men and Women.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown.

Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded.

Pathophysiology of Myocardial Infarction With Nonobstructive Coronary Artery Disease: A Contemporary Systematic Review.

Background: Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is defined as acute myocardial infarction (AMI) with angiographically nonobstructive coronary artery disease. MINOCA represents 6% of all AMI cases and is associated with increased mortality and morbidity. However, the wide array of pathophysiological factors and causes associated with MINOCA presents a diagnostic conundrum.