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Arrhythmogenic cardiomyopathy (AC) is an incurable genetic disease, whose pathogenesis is poorly understood. AZD4573 AC is characterized by arrhythmia, fibrosis, and cardiodilation that may lead to sudden cardiac death or heart failure. To elucidate AC pathogenesis and to design possible treatment strategies of AC, multiple murine models have been established. Among them, mice carrying desmoglein 2 mutations are particularly valuable given the identification of desmoglein 2 mutations in human AC and the detection of desmoglein 2 auto-antibodies in AC patients. Using two mouse strains producing either a mutant desmoglein 2 or lacking desmoglein 2 in cardiomyocytes, we test the hypothesis that inflammation is a major component of disease pathogenesis. We show that multifocal cardiomyocyte necrosis initiates a neutrophil-dominated inflammatory response, which also involves macrophages and T cells. Increased expression of Ccl2/Ccr2, Ccl3/Ccr5, and Cxcl5/Cxcr2 mRNA reflects the observed immune cell recruitment. During the ensuing acute disease phase, Mmp12+ and Spp1+ macrophages and T cells accumulate in scars, which mature from cell- to collagen-rich. The expression of Cx3cl1/Cx3cr1, Ccl2/Ccr2, and Cxcl10/Cxcr3 dominates this disease phase. We furthermore find that during chronic disease progression macrophages and T cells persist within mature scars and are present in expanding interstitial fibrosis. Ccl12 and Cx3cl1 are predominant chemokines in this disease phase. Together, our observations provide strong evidence that specific immune cell populations and chemokine expression profiles modulate inflammatory and repair processes throughout AC progression.Introduction Women with ST-elevation myocardial infarction (STEMI) present with different symptoms compared to men. This can result in delays in diagnosis and in the timely treatment of women. The aim of this study is to examine these differences, including the short- and long-term mortality in women and men. Methods This quality registry study included all patients with STEMI who received primary percutaneous coronary intervention in 2015 or 2016 in Amsterdam and the surrounding region. Results Three PCI centres and the Emergency Medical Service in Amsterdam participated. In total, 558 men (71%) and 229 women (29%) were included. Women were on average 7 years older than men (68 vs 61 years, p less then 0.001), and suffered more often from hypertension (46% vs 34%, p = 0.002) and monovascular disease (69% vs 57%, p = 0.002). A higher percentage of men were current smokers (41% vs 49%, p = 0.043). Patient delay, system delay and overall ischaemic times were similar in both women and men (medians 51, 94 and 157 min, respectively). Initiation of treatment was achieved within 90 min after STEMI diagnosis in 85% of patients (87% in women, 85% in men). Thirty-day and 1‑year mortality adjusted hazard ratio for women versus men was 1.60 (95% CI 0.9-3.0) and 1.24 (95% CI 0.8-2.0), respectively. Discussion Recognition of cardiac complaints remains challenging for patients. In the Amsterdam region, time delays and mortality were not significantly different between men and women presenting with STEMI. These results are in contrast to findings in similar registries. This suggests that implementation of current knowledge and national campaigns are effective in increasing awareness of the signs and symptoms suggestive of myocardial infarction.Priority setting in health research can assist stakeholders to identify research and policies that have the greatest potential for benefits to public health. Priority setting has been utilized by researchers to identify barriers, facilitators, and recommendations for future public health research. This commentary describes how a priority-setting approach was used as part of a workshop activity on the school nutrition environment in Ontario, Canada, to facilitate brainstorming, sorting, and rating of concepts related to the school nutrition environment. This work demonstrates an interesting and concrete case of priority setting, of interest for various planning activities (both programming and research), particularly those around school-based healthy eating programs or a related research agenda.Objectives In Quebec, three pneumococcal conjugate vaccines (PCV) were used sequentially starting in December 2004. The objective of the study was to investigate the association between exposure to different PCV regimens and hospitalizations for lower respiratory tract infection (LRTI). Methods Records with a main diagnosis of LRTI in children born in 2000-2012 and observed up to their second birthday were extracted from the provincial hospital administrative database. Main vaccine regimen in different birth cohorts was derived from the Quebec City Immunization Registry. Hospital admission risk was analyzed by Poisson regression models adjusting for age, season of birth, ambient air temperature, circulation of respiratory viruses, and the weekly hospital admission rate for all other causes excluding LRTI to control for temporal changes in hospital admission practices. Results In univariate analyses, hospitalizations for LRTI, pneumonia, and bronchiolitis were less frequent in cohorts exposed to PCVs than in unvaccinated cohorts with no difference between PCV regimens. For pneumonia, the difference in cumulative incidence was 16% (13%; 18%). In multivariate analyses, exposure to any PCV schedule was associated with a lower although statistically non-significant hospitalization risk for pneumonia as compared with unvaccinated cohorts. Again, differences between PCV regimens were minimal. Conclusions Interpretation of results of this ecological study should be made with care as many factors could influence hospitalizations for respiratory infection in young children. Results are compatible with a modest effect of PCVs in reducing hospitalizations for pneumonia in children. No substantial differences between various PCV schedules were observed.Objectives HIV pre-exposure prophylaxis (PrEP) is a proven tool for HIV prevention, but PrEP use in Ontario, Canada, and the effects of recent policies are unknown. We estimated the number and characteristics of PrEP users in Ontario and evaluated the impacts of policy changes between July 2015 and June 2018. Methods We obtained tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) dispensation data for Ontario from IQVIA, and applied an algorithm to identify use for PrEP. We report prevalent PrEP use for the second quarter of 2018 according to age, sex, region, prescriber specialty, and payer type, and generate "PrEP-to-need ratios" (PNR) by dividing these numbers by the estimated numbers of new HIV diagnoses. We used interventional autoregressive integrated moving average models to examine the impact of three policy changes on PrEP use Health Canada approval (February 2016), availability of generic TDF/FTC and partial public drug coverage (September 2017), and public drug coverage for individuals aged less then 25 years (January 2018).
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