Portrait of Montréal healthcare workers infected with SARS-CoV-2 during the first wave of the pandemic: a cross-sectional study.

OBJECTIVES: During the first wave of COVID-19 in Québec, healthcare workers (HCWs) represented 25% of the cases in Montréal. A study was conducted to describe SARS-CoV-2-infected HCWs in Montréal, and certain workplace and household characteristics. Secondary objectives included estimating the associations between having had access to personal protective equipment (PPE) and training, and following self-isolation recommendations, and certain sociodemographic and workplace characteristics. METHODS: A cross-sectional study was conducted, based on a stratified random sample, among Montréal HCWs who tested positive for SARS-CoV-2 between March and July 2020. A total of 370 participants answered a telephone-administered questionnaire. Descriptive statistics were conducted, followed by log binomial regressions to estimate the associations. RESULTS: Study participants were mostly female (74%), born outside of Canada (65%), and identified as Black, Indigenous, and People of Colour (BIPOC; 63%). In terms of healthcare positions, most were orderlies (40%) or registered nurses (20%). Half (52%) of the participants reported having had insufficient access to PPE and 30% reported having received no training related to SARS-CoV-2 infection prevention, with large proportions being BIPOC women. Working evening or night shifts decreased chances of having had sufficient access to PPE (OR 0.50; 0.30-0.83). CONCLUSION: This study describes the profile of the HCWs who were infected during the first wave of the pandemic in Montréal. Recommendations include collecting comprehensive sociodemographic data on SARS-CoV-2 infections and ensuring equitable access to infection prevention and control training and PPE during health crises, particularly those at highest risk of exposure.

RéSUMé: OBJECTIFS: Lors de la première vague de la COVID-19 au Québec, les travailleurs de la santé (TS) représentaient 25 % des cas à Montréal. Une étude a été menée pour décrire les TS infectés par le SRAS-CoV-2 à Montréal, ainsi que certaines caractéristiques liées au travail et au ménage. Les objectifs secondaires visaient à estimer les associations entre le fait d'avoir eu accès à un équipement de protection individuelle (EPI) et à une formation, ainsi que la capacité de suivre les recommandations d'auto-isolement et différentes caractéristiques sociodémographiques et du lieu de travail. MéTHODOLOGIE: Une étude transversale a été menée, sur la base d'un échantillon aléatoire stratifié, parmi les TS de Montréal qui ont été testés positifs pour le SRAS-CoV-2 entre mars et juillet 2020. Un total de 370 participants a répondu à un questionnaire administré par téléphone. Des statistiques descriptives ont été réalisées, suivies de régressions log binomiales pour estimer les associations. RéSULTATS: Les participants étaient en majorité des femmes (74 %), nés à l'extérieur du Canada (65 %) et s'identifiaient comme des personnes Noires, des Autochtones et des personnes de couleur (BIPOC; 63 %). En termes d'emploi dans le système de santé, 40 % étaient des préposés aux bénéficiaires et 20 % des infirmières cliniciennes. La moitié (52 %) des participants ont déclaré ne pas avoir eu un accès suffisant à l'EPI et 30 % ont déclaré n'avoir reçu aucune formation liée à la prévention des infections SRAS-CoV-2, une grande partie d'entre eux étant des femmes BIPOC. Le fait de travailler le soir ou la nuit diminuait les chances d'avoir un accès suffisant aux EPI (OR 0,50; 0,30­0,83). CONCLUSION: Cette étude décrit le profil des travailleurs de santé qui ont été infectés lors de la première vague de la pandémie à Montréal. Les recommandations comprennent la collecte de données sociodémographiques complètes et de s'assurer de fournir de l'EPI et des formations en prévention et contrôle des infections pendant les crises sanitaires, en particulier pour les personnes les plus à risque d'exposition.

Factors Associated with Complicated Grief Following a Railway Tragedy.

On July 6, 2013, a train with 72 crude oil tank cars derailed in the heart of Lac-Mégantic, a small municipality of 6,000 inhabitants located in Québec (Canada). This tragedy killed 47 people. Technological disasters are rarely studied in bereavement research, and train derailments even less. The goal of this article is to increase our understanding of the bereavement consequences of technological disasters. Specifically, we aim to identify the factors that lead to the experience complicated grief and distinguish from the protective factors. A representative population-based survey was conducted among 268 bereaved people, three and a half years after the train accident. Of these, 71 people (26.5%) experienced complicated grief. People with complicated grief (CG) differ significantly from those without CG in terms of psychological health, perception of physical health, alcohol use and medication, as well as social and professional relationships. Hierarchical logistic regression analysis identified four predictive factors for CG: level of exposure to the disaster, having a negative perception of the event, as well as having a paid job and low-income increase the risk of CG. The importance of having health and social practitioners pay attention to these factors of CG are discussed along with future directions for research.

Why urban communities from low-income and middle-income countries participate in public and global health research: protocol for a scoping review.

INTRODUCTION: As the number of people living in cities increases worldwide, particularly in low-income and middle-income countries (LMICs), urban health is a growing priority of public and global health. Rapid unplanned urbanisation in LMICs has exacerbated inequalities, putting the urban poor at increased risk of ill health due to difficult living conditions in cities. Collaboration with communities in research is a key strategy for addressing the challenges they face. The objective of this scoping review is, therefore, to identify factors that influence the participation of urban communities from LMICs in public and global health research. METHODS AND ANALYSIS: We will develop a search strategy with a health librarian to explore the following databases: MEDLINE, Embase, Web of Science, Cochrane, Global Health and CINAHL. We will use MeSH terms and keywords exploring the concepts of 'low-income and middle-income countries', 'community participation in research' and 'urban settings' to look at empirical research conducted in English or French. There will be no restriction in terms of dates of publication. Two independent reviewers will screen and select studies, first based on titles and abstracts, and then on full text. Two reviewers will extract data. We will summarise the results using tables and fuzzy cognitive mapping. ETHICS AND DISSEMINATION: This scoping review is part of a larger project to be approved by the University of Montréal's Research Ethics Committee for Science and Health in Montréal (Canada), and the Institutional Review Board of the James P Grant School of Public Health at BRAC University in Dhaka (Bangladesh). Results from the review will contribute to a participatory process seeking to combine scientific evidence with experiential knowledge of stakeholders in Dhaka to understand how to better collaborate with communities for research. The review could contribute to a shift toward research that is more inclusive and beneficial for communities.

Perspectives on COVID-19 Vaccination and Vaccine Passports in a Diverse Urban Adolescent Population: A Youth Participatory Mixed Methods Study.

PURPOSE: Disparities in youth COVID-19 vaccine acceptance and uptake have been documented in several countries, yet few studies have explored the attitudes and perceptions underlying vaccine-related decision-making among adolescent populations with unique sociocultural, environmental, and/or structural contexts that may influence vaccine uptake. METHODS: This study used data from surveys and semistructured interviews collected between January and March 2022 as part of an ongoing community-based research project in two ethnoculturally diverse, lower income neighborhoods of Montreal, Canada. Youth researchers designed and conducted interviews with unvaccinated adolescents, and thematic analysis was employed to explore attitudes and perceptions underlying vaccine-related decisions and opinions about vaccine passports. Survey data were used to describe sociodemographic and psychological determinants of COVID-19 vaccination. RESULTS: Among 315 survey participants aged 14-17 years, most (74%) were fully vaccinated against COVID-19. Prevalence ranged from 57% among Black adolescents to 91% among South and/or Southeast Asian adolescents (34% difference, 95% confidence interval: 20-49). Qualitative and quantitative findings highlighted several misconceptions about the safety, effectiveness, and necessity of COVID-19 vaccines and adolescents' desire for trusted sources of information to address their concerns. Vaccine passports likely increased uptake, yet adolescents were strongly resistant to the policy, and for some, it may have fueled distrust of government and scientific institutions. DISCUSSION: Strategies that increase the trustworthiness of institutions and foster genuine partnership with underserved youth may improve vaccine confidence and help ensure an effective, proequity recovery from COVID-19.

Barriers to family planning through structural health vulnerabilities: findings from case studies from rural Uganda.

The burden of maternal mortality in sub-Saharan Africa is the highest in the world. As high fertility rates present an increased risk to women's health, programmes and services have been put in place to increase access to family planning. Several studies have identified sociocultural factors as limiting access to family planning, including male resistance and women's low decision-making power. However, these studies have often used a behavioural approach that anchors barriers to access in women's attitudes or motivations. In 2019, a qualitative evaluation of a family planning programme using a behavioural approach was conducted in rural Uganda, focusing on women's attitudes and unmet needs. With hindsight, we realised that our evaluation was insufficient to adequately capture barriers that extend beyond women's motivations. This paper shares three case studies that we analysed using a structural health vulnerabilities approach. Our analysis highlights political, economic, social and cultural structures that can impede access to family planning. Using a structural health vulnerabilities approach, we identify structural barriers which have their roots in the local realities women face and propose context-specific structural recommendations. Finally, we contrast our initial results with findings the case studies presented to highlight the relevance of taking structural vulnerabilities into account in future family planning programme evaluation and women's sexual and reproductive health studies.

Psychological, Physical and Behavioral Health of Adults, 3 Years After Exposure to a Train Derailment.

In July 2013, a train derailment profoundly disrupted the tranquility of the population of Lac-Mégantic for months and even years. In 2016, we conducted a representative population-based survey among 387 people from Lac-Mégantic and 413 from other municipalities with the aim to document psychological and physical health of adults exposed to the disaster. This article examines differences between 3 groups of respondents: those who were highly, moderately or not exposed to the train accident. Khi Square analyses, odds ratios and logistic regressions were used to examine differences between the 3 groups of respondents (high, moderate and no exposure). Results show that the level of exposure to this technological disaster is strongly associated with psychological suffering, post-traumatic growth, physical heath, drinking patterns, and use of prescribed and non-prescribed drugs. We can explain these results by the nature and cause of the event as well as its consequences.

Understanding malnutrition management through a socioecological lens: Evaluation of a community-based child malnutrition program in rural Uganda.

In Uganda, almost half of children under 5 years old suffer from undernutrition. Undernutrition, a common form of malnutrition in children, encompasses stunting, wasting and underweight. The causes of child undernutrition are complex, suggesting that interventions to tackle malnutrition must be multifaceted. Furthermore, limited access to healthcare for vulnerable populations restricts the potential of hospital-based strategies. Community-based management of acute malnutrition (CMAM), which includes nutritional counselling, ready-to-use therapeutic foods and the outpatient management of malnutrition by caregivers, is recognised as an effective approach for children's recovery. However, evaluations of CMAM programs are largely based on biomedical and behavioural health models, failing to incorporate structural factors that influence malnutrition management. The objective of this evaluation was to understand the factors influencing malnutrition management in a CMAM program in rural Uganda, using the socioecological model to assess the multilevel determinants of outpatient malnutrition management. This evaluation used qualitative methods to identify factors related to caregivers, healthcare providers and societal structures that influence children's outpatient care. Data were collected at a community health clinic in 2019 through observations and interviews with caregivers of malnourished children. We observed 14 caregiver-provider encounters and interviewed 15 caregivers to examine factors hindering outpatient malnutrition management. Data were thematically analysed informed by the socioecological model. Findings showed that caregivers had a limited understanding of malnutrition. Counselling offered to caregivers was inconsistent and insufficient. Poverty and gender inequality limited caregivers' access to healthcare and their ability to care for their children. Factors at the caregiver and healthcare levels interacted with societal factors to shape malnutrition management. Results suggest that CMAM programs would benefit from providing holistic interventions to tackle the structural barriers to children's care. Using a socioecological approach to program evaluation could help move beyond individual determinants to address the social dynamics shaping malnutrition management in low- and middle-income countries.

Using human-centred design to tackle COVID-19 vaccine hesitancy for children and youth: a protocol for a mixed-methods study in Montreal, Canada.

INTRODUCTION: To successfully combat COVID-19 vaccine hesitancy and increase uptake, research has demonstrated that interventions are most effective when tailored to meet local needs through active engagement and co-development with communities. This mixed-methods project uses a human-centred design (HCD) approach to understand local perspectives of COVID-19 vaccine hesitancy and develop strategies to enhance vaccine confidence for children and adolescents. METHODS AND ANALYSIS: Project ECHO (Étude Communautaire sur l'Hésitation vaccinale contre la COVID-19) combines population-based surveys of parents and adolescents with community-based participatory action research to design and pilot strategies to enhance COVID-19 vaccine confidence in two underserved and ethnoculturally diverse neighbourhoods of Montreal, Canada. Two surveys conducted 6 months apart through primary and secondary schools are used to monitor vaccine acceptance and its social determinants among children and youth. Analyses of survey data include descriptive and inferential statistical approaches. Community-led design teams of parents and youth from the two participating neighbourhoods, supported by academic researchers, design thinking experts and community partners, use an HCD approach to: (1) gather data to understand COVID-19 vaccine decision-making among parents and youth in their community and frame a design challenge (inspiration phase); (2) develop an intervention to address the design challenge (ideation phase) and (3) pilot the intervention (implementation phase). Strategies to evaluate the community-led interventions will be co-developed during the implementation phase. ETHICS AND DISSEMINATION: This study has been approved by the research ethics boards of the Sainte-Justine University Hospital Centre and the University of Montreal. Community design teams will be involved in the dissemination of findings and the design of knowledge translation initiatives that foster dialogue related to COVID-19 vaccination for children and adolescents among community, school and public health stakeholders. Findings will be disseminated through peer-reviewed publications, conference presentations, community forums, policy briefs, and social media content.

Evaluation of a youth-led participatory action research to address adolescent sexual and reproductive health and rights issues in Senegal.

Participatory approaches are increasingly popular in public health, but remain little used to address adolescent health issues. However, adolescent participation in research has enormous potential for identifying solutions to health issues that concern them. In Senegal, a youth-led participatory action research (YPAR) project was implemented in four communities where teams of adolescents were trained to conduct a research project and identify solutions to address adolescent sexual and reproductive health and rights (ASRHR) issues. This article presents the results of the project evaluation, which aimed to explore the potential of YPAR to address ASRHR issues and inform future YPAR projects. Observations and interviews were carried out during results dissemination meetings in each of the communities. The evaluation of the project demonstrated the potential of YPAR to identify relevant solutions, while promoting positive and meaningful adolescent participation. Despite some difficulties, such as community resistance, the youth researchers were able to successfully complete their research project, while developing their confidence and self-esteem. The adolescents were convinced that they could act as agents of positive social change. This project has shown that it is possible and relevant to involve adolescents in research projects, and that this approach has significant potential in global health.

Early school-age family meal characteristics matter for the later development of boys and girls.

Objective: Sharing a meal together offers an innovative approach to study the family environment. How often families eat together may not capture the distinct experience for sons and daughters. Instead, studying family meal characteristics might be more enlightening. This study aims to examine the prospective associations between family meal environment quality at age 6 years and later well-being at age 12 years in 734 boys and 758 girls. Method: Participants are from the Quebec Longitudinal Study of Child Development birth cohort. When children were aged 6 years, parents reported on their family meal environment experience. At age 12 years, child outcomes included parent-reported healthy lifestyle habits, teacher-reported academic achievement, and self-reported social adjustment. The relationship between early family meal environment quality and later child outcomes were analyzed using multivariate linear regressions. Results: For girls, better family meal environment quality at age 6 years predicted an earlier bedtime, a lower consumption of soft drinks and sweet snacks, more classroom engagement, and fewer behavior problems at age 12 years. For boys, better family meal environment quality at age 6 years predicted an earlier bedtime and less anxiety and more prosocial behaviour at age 12 years. These significant relationships were adjusted for a multitude of child/family characteristics. Conclusion: From a population-health perspective, our findings suggest that family meals represent a cost-efficient, effective protective factor that likely has long-term influences on bio-psycho-social development. Information campaigns that promote family meals as a health intervention could optimize the well-being of boys and girls.

Seroprevalence of SARS-CoV-2 Antibodies Among Children in School and Day Care in Montreal, Canada.

Importance: Quebec prioritized in-person learning after the first wave of the COVID-19 pandemic, with school closures being implemented temporarily in selected schools or in hot-spot areas. Quebec's decision to keep most schools open was controversial, especially in Montreal, which was the epicenter of Canada's first and second waves; therefore, understanding the extent to which children were infected with SARS-CoV-2 provides important information for decisions about school closures. Objective: To estimate the seroprevalence of SARS-CoV-2 antibodies in children and teenagers in 4 neighborhoods of Montreal, Canada. Design, Setting, and Participants: This cohort study (the Enfants et COVID-19: Étude de séroprévalence [EnCORE] study) enrolled a convenience sample of children aged 2 to 17 years between October 22, 2020, and March 22, 2021, in Montreal, Canada. Exposures: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: The main outcome was seroprevalence of SARS-CoV-2 antibodies, collected using dried blood spots (DBSs) and analyzed with a research-based enzyme-linked immunosorbent assay (ELISA). Parents also completed an online questionnaire that included questions on self-reported COVID-19 symptoms and tests, along with sociodemographic questions. Results: This study included 1632 participants who provided a DBS sample from 30 day cares, 22 primary schools, and 11 secondary schools. The mean (SD) age of the children who provided a DBS sample was 9.0 (4.4) years; 801 (49%) were female individuals, with 354 participants (22%) from day cares, 725 (44%) from primary schools, and 553 (34%) from secondary schools. Most parents had at least a bachelor's degree (1228 [75%]), and 210 (13%) self-identified as being a racial or ethnic minority. The mean seroprevalence was 5.8% (95% CI, 4.6%-7.0%) but increased over time from 3.2% (95% CI, 0.7%-5.8%) in October to November 2020 to 8.4% (95% CI, 4.4%-12.4%) in March to April 2021. Of the 95 children with positive SARS-CoV-2 antibody results, 78 (82%) were not tested or tested negative with reverse transcription-polymerase chain reaction (RT-PCR) testing, and all experienced mild (49 [52%]) or no clinical symptoms (46 [48%]). The children of parents who self-identified as belonging to a racial and ethnic minority group were more likely to be seropositive compared with children of White parents (adjusted seroprevalence ratio, 1.9; 95% CI, 1.1-2.6). Conclusions and Relevance: These results provide a benchmark of the seroprevalence status in Canadian children. The findings suggest that there was more transmission occurring in children compared with what was being detected by RT-PCR, although children experienced few or mild symptoms. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.

Seroprevalence of anti-SARS-CoV-2 antibodies among school and daycare children and personnel: protocol for a cohort study in Montreal, Canada.

INTRODUCTION: Further evidence is needed to understand the contribution of schools and daycares for the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Étude de séroprévalence (EnCORE) study will estimate the seroprevalence and seroconversion of SARS-CoV-2 among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and sociodemographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes. METHODS AND ANALYSIS: This study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children aged 2-17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot, at baseline (October 2020-March 2021) and follow-up (May-June 2021). Questionnaires include sociodemographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts and health and lifestyle information. Logistic regression using generalised estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering. ETHICS AND DISSEMINATION: This study was approved by the research ethics boards of the Université de Montréal (CERSES) and the Centre Hospitalier Universitaire Sainte-Justine. Results will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares and will be made available to study participants and their families, school and public health decision-makers and the research community.

Childhood exercise as medicine: Extracurricular sport diminishes subsequent ADHD symptoms.

Extracurricular sport has been a valued educational investment to promote both physical and mental health in children and adolescents. Few longitudinal studies have tested whether extracurricular sport is associated with inattentive/hyperactive symptoms. Using a prospective-longitudinal birth cohort of 758 girls and 733 boys, we examined the prospective relationship between consistent middle childhood participation in extracurricular sport and subsequent ADHD symptoms. We hypothesized that engaging in extracurricular sport will promote reductions in symptoms. As a predictor, mothers reported on whether the child participated in sport or organized physical activities with a coach/instructor at ages 6, 7, 8, and 10 years. Developmental trajectories of the sport predictor, from ages 6 to 10 years, were generated using longitudinal latent class analysis. At age 12 years, sixth grade teachers reported on child ADHD symptom outcomes observed in the school setting over the last 6 months. ADHD symptoms were linearly regressed on trajectories of participation in organized sport in boys and girls, while controlling for pre-existing child and family characteristics. For girls, consistent participation in organized sport significantly predicted lower subsequent ADHD symptoms, compared with girls with low-inconsistent participation (unstandardized B = 0.07, p ≤ .05, 95% CI, 0.01-0.14). Early sustained middle childhood involvement in organized sport seems beneficial for the subsequent behavioral development of girls but no associations were found for boys. Middle childhood participation in structured venues that demand physical skill and effort with a coach or instructor may thus represent a valuable policy strategy to promote this aspect of behavioral development for girls.

Medium-Term Effects of a Train Derailment on the Physical and Psychological Health of Men.

In July 2013, the derailment of a train caused the death of 47 people and the destruction of Lac-Mégantic's downtown area (Canada). Three years after this event, a population survey was conducted among a representative sample of 800 adults, including 282 men. Several significant differences were observed among respondents of a survey based on their level of exposure to this tragedy, including their physical (changes in physical health) and psychological health (post-traumatic stress disorder, mood and anxiety disorders, psychological distress, signs of depression, consultation of social workers and psychologists) as well as their use of prescribed (anxiolytics and antidepressants) and nonprescribed drugs. Such results can be explained by the nature, magnitude, and cause of the event.

Seniors Who Experienced the Lac-Mégantic Train Derailment Tragedy: What Are the Consequences on Physical and Mental Health?

Introduction: In July 2013, a train derailment caused the death of 47 people and destroyed the downtown area in the city of Lac-Mégantic (Quebec, Canada). This tragedy had several impacts on this small community. Method: Three years after this disaster, we used a representative population-based survey conducted among 800 adults (including 265 seniors aged 65 or above) to assess the physical and mental health of seniors. Results: Several differences were observed in seniors' physical and mental health based on their level of exposure to the tragedy. Nearly half of seniors highly exposed to the train derailment (41.7%) believe that their health has deteriorated in the past 3 years. The majority of seniors highly exposed to the train derailment (68.7%) also show symptoms of posttraumatic stress disorders. Seniors highly or moderately exposed to the tragedy were also more likely to have found positive changes in their personal and social life as compared with nonexposed seniors. Discussion: A technological disaster such as a train derailment still had negative impacts on seniors' physical and mental health 3 years later. Conclusion: Public health authorities must tailor prevention and promotion programs to restore health and well-being in this population.

CD47 fusion protein targets CD172a+ cells in Crohn's disease and dampens the production of IL-1ß and TNF.

In mice, the transfer of CD172a(+) (SIRP-α) dendritic cells (DCs) elicits T cell-driven colitis, whereas treatment with CD47-Fc protein, a CD172a-binding agent, confers protection. The aim of this study was to elucidate the nature and functional properties of human CD172a(+) DCs in chronic intestinal inflammation. Here, we show that CD172a(+)CD11c(+) cells accumulate in the mesenteric lymph nodes (mLNs) and inflamed intestinal mucosa in patients with Crohn's disease (CD). These cells are distinct from resident DCs and may coexpress markers typically associated with monocyte-derived inflammatory DCs such as CD14 and/or DC-SIGN, E-Cadherin, and/or CX3CR1. Spontaneous IL-1ß and TNF production by HLA-DR(+) cells in CD tissues is restricted to those expressing CD172a. An avidity-improved CD47 fusion protein (CD47-Var1) suppresses the release of a wide array of inflammatory cytokines by CD172a(+) cells, which may include HLA-DR(-)CD172a(+) neutrophils, in inflamed colonic explant cultures and impairs the ability of HLA-DR(+)CD172a(+) cells to activate memory Th17 but not Th1 responses in mLNs. In conclusion, targeting CD172a(+) cells may represent novel therapeutic perspectives for patients with CD.

CD47(low) status on CD4 effectors is necessary for the contraction/resolution of the immune response in humans and mice.

How do effector CD4 T cells escape cell death during the contraction of the immune response (IR) remain largely unknown. CD47, through interactions with thrombospondin-1 (TSP-1) and SIRP-α, is implicated in cell death and phagocytosis of malignant cells. Here, we reported a reduction in SIRP-α-Fc binding to effector memory T cells (T(EM)) and in vitro TCR-activated human CD4 T cells that was linked to TSP-1/CD47-induced cell death. The reduced SIRP-α-Fc binding (CD47(low) status) was not detected when CD4 T cells were stained with two anti-CD47 mAbs, which recognize distinct epitopes. In contrast, increased SIRP-α-Fc binding (CD47(high) status) marked central memory T cells (T(CM)) as well as activated CD4 T cells exposed to IL-2, and correlated with resistance to TSP-1/CD47-mediated killing. Auto-aggressive CD4 effectors, which accumulated in lymph nodes and at mucosal sites of patients with Crohn's disease, displayed a CD47(high) status despite a high level of TSP-1 release in colonic tissues. In mice, CD47 (CD47(low) status) was required on antigen (Ag)-specific CD4 effectors for the contraction of the IR in vivo, as significantly lower numbers of Ag-specific CD47(+/+)CD4 T cells were recovered when compared to Ag-specific CD47(-/-) CD4 T cells. In conclusion, we demonstrate that a transient change in the status of CD47, i.e. from CD47(high) to CD47(low), on CD4 effectors regulates the decision-making process that leads to CD47-mediated cell death and contraction of the IR while maintenance of a CD47(high) status on tissue-destructive CD4 effectors prevents the resolution of the inflammatory response.

L-Carnitine and intestinal inflammation.

The intestinal barrier is one of the most dynamic surfaces of the body. It is here where a single layer of epithelial cells mediates the intricate encounters that occur between the host's immune system and a multitude of potential threats present in the intestinal lumen. Several key factors play an important role in the final outcome of this interaction, including the state of oxidative stress, the level of activation of the immune cells, and the integrity of the epithelial barrier. This chapter describes the main evidence demonstrating the impact that l-carnitine has on each of these factors. These findings, combined with the demonstrated safety profile of l-carnitine, underscore the potential therapeutic value of l-carnitine supplementation in humans suffering from intestinal inflammation and highlight the functional data supporting an association between Crohn's disease and mutations in the l-carnitine transporter genes.

Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele. CONCLUSION: The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.