Implication de la lipide phosphatase SHIP1 dans les voies de signalisation du CD32a dans le neutrophile humain

Tableau d'honneur de la Faculté des études supérieures et postdoctorales, 2005-2006Le neutrophile est spécialisé dans la chimiotaxie et la phagocytose. Ces deux phénomènes sont accompagnés d'une accumulation de phosphatidylinositol(3,4,5)triphosphate. Ce dernier est formé par les phosphatidylinositols 3-kinases. Leur activation et la formation de phosphatidylinositol(3,4,5)triphosphate sont bien caractérisés dans le neutrophile. La régulation du niveau de phosphatidylinositol(3,4,5)triphosphate par les lipide phosphatases est peu étudiée. Nous avons examiné le rôle des lipide phosphatases SHIP1 et PTEN suite à la stimulation du CD32a, un FcyR, dans la régulation du niveau de phosphatidylinositol(3,4,5)triphosphate. Ce dernier augmente suite à la stimulation du CD32a. La localisation cellulaire et la phosphorylation de SHIP1, mais pas de PTEN, sont modifiées en réponse à la stimulation du CD32a. Ces événements seraient dépendants des Src kinases. Par contre, ils seraient indépendants de l'activation des phosphatidylinositol 3-kinases. SHIP1, et non PTEN, pourrait donc être impliquée dans la régulation du phosphatidylinositol(3,4,5)triphosphate formé suite à la stimulation du CD32a dans le neutrophile humain

Stressed and distressed: how is the COVID-19 pandemic associated with sexual frequency, sexual satisfaction, and relationship satisfaction?

Background: The Canadian government’s response to the ongoing COVID-19 pandemic included the implementation of several restrictive measures since March 2020. These actions sought to decrease social contact and increase physical distancing, including that within universities. Such constraints were required to impede the transmission of the virus; however, concerns remain about their impact on the sexual and intimate relationships of university employees and students. Aim: This study examined the associations between COVID-19–related stress and sexual frequency, sexual satisfaction, and relationship satisfaction, also testing the mediating role of psychological distress. Methods: The models were tested with Canadian data collected from university employees and students in 2 phases: the first wave in April-May 2020 (T1; n = 2754) and the second wave in November-December 2021 (T2; n = 1430), 18 months afterward. Participants completed self-report questionnaires online. Path analyses were performed to test the associations of the mediation models. Outcomes: The principal outcomes included psychological distress determined via the Patient Health Questionnaire–4, relationship satisfaction measured via the Dyadic Adjustment Scale, and sexual satisfaction and sexual frequency ascertained through a single item each. Results: Overall, COVID-19–related stress was associated with higher psychological distress, which in turn was related to lower sexual frequency, sexual satisfaction, and relationship satisfaction. Similar results were obtained with T1 and T2 data, indicating the mediating effect of psychological distress. Clinical implications: These findings increase scholarly comprehension of the negative associations between stress/distress and sexual and romantic relationships. Sexuality and close relationships are vital to the quality of human life; thus, targeted interventions should be developed to reduce COVID-19–related stress and its impact on sexual and romantic relationships to mitigate the long-term influences of this unique global challenge. Strengths & Limitations: To our knowledge, this study is the first to use a large sample size and replicate findings in 2 waves. Nonetheless, it is limited by the use of cross-sectional data. Longitudinal studies with the same participants are mandated to better understand the evolution of these outcomes. Conclusion: COVID-19–related stress and psychological distress were found among participating university students and employees and were associated with lower sexual satisfaction, sexual frequency, and intimate relationship satisfaction. These results were observed at the early onset of the pandemic and 18 months afterward, suggesting that the stress generated by the pandemic were not mere reactions to the onset of the pandemic but persisted over time

A value-based comparison of the management of ambulatory respiratory diseases in walk-in clinics, primary care practices, and emergency departments : protocol for a multicenter prospective cohort study

Background: In Canada, 30%-60% of patients presenting to emergency departments are ambulatory. This category has been labeled as a source of emergency department overuse. Acting on the presumption that primary care practices and walk-in clinics offer equivalent care at a lower cost, governments have invested massively in improving access to these alternative settings in the hope that patients would present there instead when possible, thereby reducing the load on emergency departments. Data in support of this approach remain scarce and equivocal. Objective: The aim of this study is to compare the value of care received in emergency departments, walk-in clinics, and primary care practices by ambulatory patients with upper respiratory tract infection, sinusitis, otitis media, tonsillitis, pharyngitis, bronchitis, influenza-like illness, pneumonia, acute asthma, or acute exacerbation of chronic obstructive pulmonary disease. Methods: A multicenter prospective cohort study will be performed in Ontario and Québec. In phase 1, a time-driven activity-based costing method will be applied at each of the 15 study sites. This method uses time as a cost driver to allocate direct costs (eg, medication), consumable expenditures (eg, needles), overhead costs (eg, building maintenance), and physician charges to patient care. Thus, the cost of a care episode will be proportional to the time spent receiving the care. At the end of this phase, a list of care process costs will be generated and used to calculate the cost of each consultation during phase 2, in which a prospective cohort of patients will be monitored to compare the care received in each setting. Patients aged 18 years and older, ambulatory throughout the care episode, and discharged to home with one of the aforementioned targeted diagnoses will be considered. The estimated sample size is 1485 patients. The 3 types of care settings will be compared on the basis of primary outcomes in terms of the proportion of return visits to any site 3 and 7 days after the initial visit and the mean cost of care. The secondary outcomes measured will include scores on patient-reported outcome and experience measures and mean costs borne wholly by patients. We will use multilevel generalized linear models to compare the care settings and an overlap weights approach to adjust for confounding factors related to age, sex, gender, ethnicity, comorbidities, registration with a family physician, socioeconomic status, and severity of illness. Results: Phase 1 will begin in 2021 and phase 2, in 2023. The results will be available in 2025. Conclusions: The end point of our program will be for deciders, patients, and care providers to be able to determine the most appropriate care setting for the management of ambulatory emergency respiratory conditions, based on the quality and cost of care associated with each alternative

The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release

The myeloid inhibitory C-type lectin receptor CLEC12A limits neutrophil activation, pro-inflammatory pathways and disease in mouse models of inflammatory arthritis by a molecular mechanism that remains poorly understood. We addressed how CLEC12A-mediated inhibitory signaling counteracts activating signaling by cross-linking CLEC12A in human neutrophils. CLEC12A cross-linking induced its translocation to flotillin-rich membrane domains where its ITIM was phosphorylated in a Src-dependent manner. Phosphoproteomic analysis identified candidate signaling molecules regulated by CLEC12A that include MAPKs, phosphoinositol kinases and members of the JAK-STAT pathway. Stimulating neutrophils with uric acid crystals, the etiological agent of gout, drove the hyperphosphorylation of p38 and Akt. Ultimately, one of the pathways through which CLEC12A regulates uric acid crystal-stimulated release of IL-8 by neutrophils is through a p38/PI3K-Akt signaling pathway. In summary this work defines early molecular events that underpin CLEC12A signaling in human neutrophils to modulate cytokine synthesis. Targeting this pathway could be useful therapeutically to dampen inflammation

Pornography Use and Sexual Health among Same-Sex and Mixed-Sex Couples: An Event-Level Dyadic Analysis

A large number of partnered individuals regularly use or are in a relationship with someone who uses pornography. However, knowledge concerning the association between pornography use and partnered sexual health—sexual satisfaction, distress, and function—is fragmentary. The current study used an event-level dyadic design to examine the associations between pornography use and sexual satisfaction, distress, and function on days when partnered sexual activity occurred. A convenience sample of 217 couples (Mage = 30.2; SD = 8.3; 72 same-sex couples) completed a short survey on days of sexual activity with their partner, over a 35-day period. Self-report measures included questions about today’s pornography use and masturbation as well as sexual satisfaction, distress, and function. Using pornography on days of partnered sexual activity was reported by half of the couples. An individual’s solitary pornography use on days of partnered sexual activity was related to their partner’s higher sexual distress and, for women’s use only, to their own higher quality of lubrication, compared to sex days without solitary pornography use. There was no evidence of an association between pornography use on sex days, whether alone or with the partner, and all other aspects of sexual health including sexual satisfaction. Our findings capture the complexity of the associations between pornography and sexual health. Men and women’s pornography use may create idealized fantasies around appearance and performance, which may lead the partner to feel distressed about their sex life. Women’s pornography use might facilitate their sexual responsiveness during partnered sexual activity