Functional differences between rodent and human PD-1 linked to evolutionary divergence.

Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2.

Prevalence of and Risk Factors for Hearing Impairment in Craniofacial Microsomia.

Background: While ear anomalies and hearing impairment are common in patients with craniofacial microsomia (CFM), their prevalence, characteristics, and relationship to speech-language development remain unclear.

Purpose: This study analyzed the prevalence and risk factors for hearing impairment in patients with CFM.

Study Design, Setting, Sample: This retrospective cohort study included patients with unilateral or bilateral CFM from a single center between January 1980 and July 2023 who had evidence of a hearing assessment at <18 years.

Environmentally sustainable opportunities for health systems: Metered-dose inhaler prescribing, dispensing, use and waste at a tertiary academic centre.

Background: The Canadian health sector's carbon footprint is among the highest in the world and is responsible for 4.6% of Canada's total greenhouse gas emissions, a quarter of which is linked to pharmaceuticals, with metered-dose inhalers (MDIs) contributing disproportionally high amounts.

Objectives: To describe MDI prescribing, dispensing, use and waste patterns at a Canadian tertiary care academic hospital.

Evolutionary fingerprint in rodent PD1 confers weakened activity and enhanced tumor immunity compared to human PD1.

Mechanistic understanding of the immune checkpoint receptor PD1 is largely based on mouse models, but human and mouse PD1 orthologs exhibit only 59.6% identity in amino acid sequences. Here we show that human PD1 is more inhibitory than mouse PD1 due to stronger interactions with the ligands PDL1 and PDL2 and with the effector phosphatase Shp2.

Community-engaged research: Bringing the science of developmental psychopathology into the real world.

The science of developmental psychopathology has made outstanding progress over the past 40 years in understanding adaptive and maladaptive developmental processes across the life span. Yet most of this work has been researcher driven with little involvement of community partners in the research process, limiting the potential public health significance of our work. To continue to advance the field we must move beyond the physical and conceptual walls of our research laboratories and into the real world.

MAP kinase kinase 1 (MEK1) within extracellular vesicles inhibits tumour growth by promoting anti-tumour immunity.

Extracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized.

Individualized pretest risk estimates to guide treatment decisions in patients with clinical high risk for psychotic disorders.

Introduction: Clinical high risk for psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness.

Sex-specific loss of mitochondrial membrane integrity in the auditory brainstem of a mouse model of Fragile X syndrome.

Sound sensitivity is one of the most common sensory complaints for people with autism spectrum disorders (ASDs). How and why sounds are perceived as overwhelming by affected people is unknown. To process sound information properly, the brain requires high activity and fast processing, as seen in areas like the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem.

Factors associated with the use of benzodiazepine and opioid prescription drug in the student population: a cross-sectional study.

The misuse of benzodiazepines and opioid medications is frequent in students. To improve our understanding of this behavior, we aimed to identify factors associated with separate and concomitant use of these substances. Anonymous self-reported questionnaires were e-mailed to students enrolled at a French university between March and July 2021, covering: sociodemographic characteristics, academics, psychoactive substance use, ADHD symptomatology (adulthood and childhood), and psychiatric/psychological or addiction follow-up.

Pathways to care in youth and young adults at clinical high risk for psychosis in Switzerland: Current situation and clinical implementation of the PsyYoung project.

Aim: We aim to give an insight into the current situation in Switzerland concerning the pathways to care of young people with clinical high risk of psychosis. In a second step we propose a procedure of optimizing pathways to care developed within the project PsyYoung.

Methods: A qualitative survey derived and adapted from Kotlicka-Antczak et al.

Environmentally sustainable opportunities for health systems: metered-dose inhaler prescribing, dispensing, usage, and waste at The Ottawa Hospital.

Background: The carbon footprint of Canada's health sector is among the worst in the world, responsible for 4·6% of Canada's total greenhouse gas emissions. A quarter of emissions from Canada's health sector are linked to pharmaceuticals, including metered dose inhalers (MDIs). MDIs use propellants, such as hydrofluorocarbons, which act as greenhouse gas emissions and contribute to the health-care sector's overall carbon footprint.

Velopharyngeal dysfunction and speech-related characteristics in craniofacial microsomia: a retrospective analysis of 223 patients.

This study aimed to document the prevalence, severity, and risk factors of velopharyngeal dysfunction (VPD) in craniofacial microsomia (CFM) and to analyse differences in VPD-related speech characteristics between CFM patients without cleft lip and/or palate (CL/P), CFM patients with CL/P, and CL/P patients without CFM (control). A total of 223 patients with CFM were included, of whom 59 had a CL/P. Thirty-four CFM patients had VPD, including 20 with a CL/P.

Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500).

ATR is a key kinase in the DNA-damage response (DDR) that is synthetic lethal with several other DDR proteins, making it an attractive target for the treatment of genetically selected solid tumors. Herein we describe the discovery of a novel ATR inhibitor guided by a pharmacophore model to position a key hydrogen bond. Optimization was driven by potency and selectivity over the related kinase mTOR, resulting in the identification of camonsertib (RP-3500) with high potency and excellent ADME properties.

Cristae shaping and dynamics in mitochondrial function.

Mitochondria are multifunctional organelles of key importance for cell homeostasis. The outer mitochondrial membrane (OMM) envelops the organelle, and the inner mitochondrial membrane (IMM) is folded into invaginations called cristae. As cristae composition and functions depend on the cell type and stress conditions, they recently started to be considered as a dynamic compartment.

Velopharyngeal insufficiency, speech, and language impairment in craniofacial microsomia: a scoping review.

This review provides a comprehensive overview of the literature on velopharyngeal insufficiency, associated anomalies, and speech/language impairment in patients with craniofacial microsomia (CFM). A systematic search of the literature was conducted to identify records on VPI and speech impairment in CFM from their inception until September 2022 within the databases Embase, PubMed, MEDLINE, Ovid, CINAHL EBSCO, Web of Science, Cochrane, and Google Scholar. Seventeen articles were included, analysing 1,253 patients.

Could psychostimulant drug use among university students be related to ADHD symptoms? A preliminary study.

We aimed to explore if psychostimulant use among student could be linked to attention deficit-hyperactivity disorder (ADHD) symptoms using a self-administered questionnaire sent by email to French students in 2021. Participants were asked about their psychostimulant use and the presence of ADHD symptoms using the Wender Utah Rating Scale and the Adult Self-Report Scale. Among the 4431 respondents, the prevalence of psychostimulant use was concerning and significantly associated with ADHD symptoms.

Alfalfa weevils (Coleoptera: Curculionidae) in the western United States are resistant to multiple type II pyrethroid insecticides.

The alfalfa weevil (Hypera postica Gyllenhal (Coleoptera: Curculionidae)), a key pest of alfalfa (Medicago sativa L. (Fabales: Fabacae)) across the US, has developed resistance to pyrethroids lambda-cyhalothrin and zeta-cypermethrin in at least 6 western US states. Unfortunately, 6 pyrethroid active ingredients represent most commercial insecticides registered for alfalfa weevil control in forage alfalfa systems.

An overview of the use of psychoactive substances among students at the University of Lille during the COVID-19 health crisis: Results of the PETRA study.

Objectives: Students represent a population at risk for substance abuse. That risk may have been exacerbated by the COVID-19 pandemic. We aimed to describe substance abuse among students and to compare consumption according to the university field.

Comparison of Tympanostomy Tubes Under Local Anesthesia Versus General Anesthesia for Children.

Objective: Tympanostomy tube insertion (TTI) is typically accomplished under general anesthesia (GA) in the operating room. We aimed to compare pain between GA and local anesthesia (LA) in surgically naïve children undergoing TTI. Secondary objectives examined patient's quality of life (QoL) and parent's satisfaction.

Emotional Impact of Medication-Related Patient Safety Incidents on Canadian Hospital Pharmacists: A Mixed-Methods Study.

Background: Patient safety incidents are the third leading cause of death in Canada. These occurrences have negative effects on patients and on the well-being of health care professionals. They also lead to financial burdens on the health care system.

Improving Pathways to Care for Patients at High Psychosis Risk in Switzerland: PsyYoung Study Protocol.

Aims: Psychotic disorders are one of the main causes of chronic disability in young people. An at-risk mental state (ARMS) is represented by subclinical symptoms that precede the first episode of psychosis (FEP). The PsyYoung project aims to optimize the detection of an ARMS while reducing unnecessary psychiatric treatments.

The Effect of Cued-Speech (CS) Perception on Auditory Processing in Typically Hearing (TH) Individuals Who Are Either Naïve or Experienced CS Producers.

Cued Speech (CS) is a communication system that uses manual gestures to facilitate lipreading. In this study, we investigated how CS information interacts with natural speech using Event-Related Potential (ERP) analyses in French-speaking, typically hearing adults (TH) who were either naïve or experienced CS producers. The audiovisual (AV) presentation of lipreading information elicited an amplitude attenuation of the entire N1 and P2 complex in both groups, accompanied by N1 latency facilitation in the group of CS producers.

Evaluation of Research Diagnostic Criteria in Craniofacial Microsomia.

Characteristics of patients with craniofacial microsomia (CFM) vary in type and severity. The diagnosis is based on phenotypical assessment and no consensus on standardized clinical diagnostic criteria is available. The use of diagnostic criteria could improve research and communication among patients and healthcare professionals.

Dual receptor T cells mediate effective antitumor immune responses via increased recognition of tumor antigens.

Background: Discovery that ~16% of T cells naturally co-express two T-cell receptor (TCR) clonotypes prompts examining the role of dual TCR cells in immune functions.

Methods: Using TCRα-reporter transgenic mice, enabling unambiguous identification of single-TCR and dual-TCR cells, we tested the role of dual TCR cells in antitumor immune responses against immune-responsive syngeneic 6727 sarcoma and immune-resistant B16F10 melanoma.

Results: Dual TCR cells were specifically increased among tumor-infiltrating lymphocytes (TILs) in both models, indicating selective advantage in antitumor responses.

cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8 T cell function and anti-tumor immunity.

B7 ligands (CD80 and CD86), expressed by professional antigen-presenting cells (APCs), activate the main co-stimulatory receptor CD28 on T cells in trans. However, in peripheral tissues, APCs expressing B7 ligands are relatively scarce. This raises the questions of whether and how CD28 co-stimulation occurs in peripheral tissues.