Gpr83 expression is not required for the maintenance of intestinal immune homeostasis and regulation of T-cell-dependent colitis

Regulatory T (TR) cells are integral to the maintenance of intestinal homeostasis, where an intricate balance between tolerance and immunity must be maintained. Recently, studies have focused on the identification of molecules involved in the function and/or development of TR cells. One such molecule, the G-protein coupled receptor Gpr83, has been identified through gene expression analysis as being overexpressed within thymic and peripheral naturally arising regulatory T (nTR) cell populations. The aim of this study was to further define the characteristics of Gpr83 expression and to investigate the role of Gpr83 in TR-cell development and function through the generation and analysis of Gpr83-deficient mice. Following activation, naïve CD4+ T cells induce Gpr83 expression in a transforming growth factor (TGF)-β dependent manner. Rather than being a general marker of activation, Gpr83 expression could only be detected in cells also expressing forkhead/winged helix transcription factor (Foxp3), further supporting the association of Gpr83 with the regulatory cell phenotype. Mice deficient in Gpr83 expression developed normally and did not display signs of inflammatory disease. Thymic nTR-cell development was unaffected by a lack of Gpr83 expression and peripheral nTR-cell homeostasis was normal when compared with that of wild-type mice. Gpr83 expression was dispensable for the regulatory activity of nTR cells as Gpr83-deficient nTR cells could suppress the development of disease in a T-cell transfer model of colitis. These results suggest a redundant role for Gpr83 in the function of TR cells in this model of disease. Further studies are required to determine the role of Gpr83 in TR-cell biology

Anaemia, iron status and vitamin A deficiency among adolescent refugees in Kenya and Nepal

AbstractObjectiveTo investigate the prevalence of anaemia (haemoglobin 8.3 μg ml−1) and vitamin A deficiency (serum retinol < 0.7 μmoll−1) in adolescent refugees.DesignCross-sectional surveys.SettingKakuma refugee camp in Kenya and seven refugee camps in Nepal.SubjectsAdolescent refugee residents in these camps.ResultsAnaemia was present in 46% (95% confidence interval (CI): 42–51) of adolescents in Kenya and in 24% (95% CI: 20–28) of adolescents in Nepal. The sensitivity of palmar pallor in detecting anaemia was 21%. In addition, 43% (95% CI: 36–50) and 53% (95% CI: 46–61) of adolescents in Kenya and Nepal, respectively, had iron deficiency. In both surveys, anaemia occurred more commonly among adolescents with iron deficiency. Vitamin A deficiency was found in 15% (95% CI: 10–20) of adolescents in Kenya and 30% (95% CI: 24–37) of adolescents in Nepal. Night blindness was not more common in adolescents with vitamin A deficiency than in those without vitamin A deficiency. In Kenya, one of the seven adolescents with Bitot's spots had vitamin A deficiency.ConclusionsAnaemia, iron deficiency and vitamin A deficiency are common among adolescents in refugee populations. Such adolescents need to increase intakes of these nutrients; however, the lack of routine access makes programmes targeting adolescents difficult. Adolescent refugees should be considered for assessment along with other at-risk groups in displaced populations

Posttraumatic Stress in Women after the September 11 Terrorist Attacks in New York City

Background: Women have been shown to be at higher risk than men of developing posttraumatic stress disorder (PTSD) after traumatic events. Women in New York City were more likely than men to have probable PTSD 5–8 weeks after the September 11, 2001, terrorist attacks on the World Trade Center. We explored the factors that could explain the higher prevalence of probable PTSD among women in the aftermath of the attacks. Methods: Data from a telephone survey of a randomly selected group of residents of Manhattan living south of 110th street, conducted 5–8 weeks after September 11, were used in these analyses. The survey assessed demographic information, lifetime experience of traumatic events, life stressors, social support, event exposure variables, perievent panic attacks, postevent concerns, and probable PTSD related to the attacks. We determined the contribution of key covariates that could explain the gender-probable PTSD relation through stratified analyses and manual stepwise logistic regression model building. Results: Among 988 respondents, women were two times more likely than men to report symptoms consistent with probable PTSD after the September 11 attacks. When adjusted for potential confounders, the association between gender and probable PTSD diminished from OR 5 2.2 (95% confidence interval [CI] 1.3–3.6) to OR 5 1.2 (95% CI 0.7–2.2). Conclusions: These results suggest that specific behavioral and biographic factors (including previous traumatic experiences and psychological disorders, social responsibilities, and perievent emotional reactions) explained most of the excess burden of probable PTSD among women after a disaster. Isolating the characteristics that place women at greater risk for probable PTSD after disasters can inform public health prevention strategies and spur further research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40341/2/Pulcino_Posttraumatic Stress in WOmen after_2003.pd

La recherche en santé mondiale : recueil de cas

Version anglaise disponible dans la Bibliothèque numérique du CRDI : Global health research : caseboo

Decoding information in the human hippocampus: a user's guide

Multi-voxel pattern analysis (MVPA), or 'decoding', of fMRI activity has gained popularity in the neuroimaging community in recent years. MVPA differs from standard fMRI analyses by focusing on whether information relating to specific stimuli is encoded in patterns of activity across multiple voxels. If a stimulus can be predicted, or decoded, solely from the pattern of fMRI activity, it must mean there is information about that stimulus represented in the brain region where the pattern across voxels was identified. This ability to examine the representation of information relating to specific stimuli (e.g., memories) in particular brain areas makes MVPA an especially suitable method for investigating memory representations in brain structures such as the hippocampus. This approach could open up new opportunities to examine hippocampal representations in terms of their content, and how they might change over time, with aging, and pathology. Here we consider published MVPA studies that specifically focused on the hippocampus, and use them to illustrate the kinds of novel questions that can be addressed using MVPA. We then discuss some of the conceptual and methodological challenges that can arise when implementing MVPA in this context. Overall, we hope to highlight the potential utility of MVPA, when appropriately deployed, and provide some initial guidance to those considering MVPA as a means to investigate the hippocampus

The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081

The human enteropathogen, Yersinia enterocolitica, is a significant link in the range of Yersinia pathologies extending from mild gastroenteritis to bubonic plague. Comparison at the genomic level is a key step in our understanding of the genetic basis for this pathogenicity spectrum. Here we report the genome of Y. enterocolitica strain 8081 (serotype 0:8; biotype 1B) and extensive microarray data relating to the genetic diversity of the Y. enterocolitica species. Our analysis reveals that the genome of Y. enterocolitica strain 8081 is a patchwork of horizontally acquired genetic loci, including a plasticity zone of 199 kb containing an extraordinarily high density of virulence genes. Microarray analysis has provided insights into species-specific Y. enterocolitica gene functions and the intraspecies differences between the high, low, and nonpathogenic Y. enterocolitica biotypes. Through comparative genome sequence analysis we provide new information on the evolution of the Yersinia. We identify numerous loci that represent ancestral clusters of genes potentially important in enteric survival and pathogenesis, which have been lost or are in the process of being lost, in the other sequenced Yersinia lineages. Our analysis also highlights large metabolic operons in Y. enterocolitica that are absent in the related enteropathogen, Yersinia pseudotuberculosis, indicating major differences in niche and nutrients used within the mammalian gut. These include clusters directing, the production of hydrogenases, tetrathionate respiration, cobalamin synthesis, and propanediol utilisation. Along with ancestral gene clusters, the genome of Y. enterocolitica has revealed species-specific and enteropathogen-specific loci. This has provided important insights into the pathology of this bacterium and, more broadly, into the evolution of the genus. Moreover, wider investigations looking at the patterns of gene loss and gain in the Yersinia have highlighted common themes in the genome evolution of other human enteropathogens

Validation of self-reported post-treatment mammography surveillance among breast cancer survivors by electronic medical record extraction method

Little is known about validity of self-reported mammography surveillance among breast cancer survivors. Most studies have focused on accuracy among healthy, average-risk populations and none have assessed validity by electronic medical record (EMR) extraction method. To assess validity of survivor-reported mammography post-active treatment care, we surveyed all survivors diagnosed 2004–2009 in an academic hospital cancer registry (n = 1441). We used electronic query and manual review to extract EMR data. Concordance, sensitivity, specificity, positive predictive value, and report-to-records ratio were calculated by comparing survivors' self-reports to data from each extraction method. We also assessed average difference in months between mammography dates by source and correlates of concordance. Agreement between the two EMR extraction methods was high (concordance 0.90; kappa 0.70), with electronic query identifying more mammograms. Sensitivity was excellent (0.99) regardless of extraction method; concordance and positive predictive value were good; however, specificity was poor (manual review 0.20, electronic query 0.31). Report-to-records ratios were both over 1 suggesting over-reporting. We observed slight forward telescoping for survivors reporting mammograms 7–12 months prior to survey date. Higher educational attainment and less time since mammogram receipt were associated with greater concordance. Accuracy of survivors' self-reported mammograms was generally high with slight forward telescoping among those recalling their mammograms between 7 and 12 months prior to the survey date. Results are encouraging for clinicians and practitioners relying on survivor reports for surveillance care delivery and as a screening tool for inclusion in interventions promoting adherence to surveillance guidelines

Temperate infection in a virus–host system previously known for virulent dynamics

The blooming cosmopolitan coccolithophore Emiliania huxleyi and its viruses (EhVs) are a model for density-dependent virulent dynamics. EhVs commonly exhibit rapid viral reproduction and drive host death in high-density laboratory cultures and mesocosms that simulate blooms. Here we show that this system exhibits physiology-dependent temperate dynamics at environmentally relevant E. huxleyi host densities rather than virulent dynamics, with viruses switching from a long-term non-lethal temperate phase in healthy hosts to a lethal lytic stage as host cells become physiologically stressed. Using this system as a model for temperate infection dynamics, we present a template to diagnose temperate infection in other virus–host systems by integrating experimental, theoretical, and environmental approaches. Finding temperate dynamics in such an established virulent host–virus model system indicates that temperateness may be more pervasive than previously considered, and that the role of viruses in bloom formation and decline may be governed by host physiology rather than by host–virus densities