Previous studies have indicated that group B streptococcus (GBS), a frequent human pathogen, potently induces the release of interleukin-1 (IL-1), an important mediator of inflammatory responses. Since little is known about the role of this cytokine in GBS disease, we analyzed the outcome of infection in IL-1-deficient mice. These animals were markedly sensitive to GBS infection, with most of them dying under challenge conditions that caused no deaths in wild-type control mice. Lethality was due to the inability of the IL-1-deficient mice to control local GBS replication and dissemination to target organs, such as the brain and the kidneys. Moreover, in a model of inflammation induced by the intraperitoneal injection of killed GBS, a lack of IL-1 was associated with selective impairment in the production of the neutrophil chemokines CXCL1 and CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood neutrophil counts and impaired neutrophil recruitment to the brain and kidneys were also observed during GBS infection in IL-1-deficient mice concomitantly with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the hypersusceptibility to GBS infection observed in the immune-deficient animals was recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our data identify a cytokine circuit that involves IL-1-induced production of CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites. Moreover, our data point to an essential role of these cells in controlling the progression and outcome of GBS disease.
Background: Well-informed interventions are needed if school-based health promotion is to be effective. Among other aims, the Iranian Health Promoting School (IHPS) program that was launched in 2011, has an important aim of promoting dietary behaviors of adolescents. The present study, therefore, aimed to investigate the factors affecting unhealthy snacking of adolescents and provide evidence for a more effective IHPS program. Methods: In a cross-sectional study design, 1320 students from 40 schools in Kerman city were selected using a proportional stratified random sampling method. A modified qualitative Food Frequency Questionnaire (FFQ) was used to gather data about unhealthy snacking behavior. Data about intrapersonal and environmental factors were obtained using a validated and reliable questionnaire. A mixed-effects negative-binomial regression model was used to analyze the data. Results: Taste and sensory perception (prevalence rate ratio [PRR]=1.18; 95% CI: 1.09-1.27), being a male (PRR=1.20; 95% CI: 1.05-1.38) and lower nutritional knowledge (PRR=0.96; 95% CI: 0.91-0.99) were associated with higher weekly unhealthy snaking. Perceived self-efficacy (PRR=0.95; 95% CI: 0.91-1.00) negatively influenced the frequency of unhealthy snaking, with this approaching significance (P<.06). In case of environmental factors, high socio-economic status (SES) level (PRR=1.45; 95% CI: 1.26-1.67), single-parent family (PRR=1.14; 95% CI: 1.01-1.30), more social norms pressure (PRR=1.08; 95% CI: 1.01-1.17), pocket money allowance (PRR=1.21; 95% CI: 1.09-1.34), easy accessibility (PRR=1.06; 95% CI:1.01-1.11), and less perceived parental control (PRR=0.96; 95% CI: 0.92-0.99) all had a role in higher consumption of unhealthy snacks. Interestingly, larger school size was associated with less unhealthy snacking (PRR=0.79; 95% CI: 0.68-0.92). Conclusion: Unhealthy snacking behavior is influenced by individual, socio-cultural and physical-environmental influences, namely by factors relating to poor parenting practices, high SES level, family characteristics, improper social norms pressure, and less knowledge and self-efficacy of students. This evidence can be used to inform a more evidencebased IHPS program through focusing on supportive strategies at the home, school, and local community levels.
Natural killer (NK) cells are thought to develop from common lymphoid progenitors in the bone marrow. However, immature thymocytes also retain NK potential. Currently, the contribution of the thymus-dependent pathway in normal steady-state NK-cell development is unknown. Here, we show that TCRgamma genes are rearranged in approximately 5% of neonatal and 1% of adult mouse splenic NK cells, and similar levels are detected in NK cells from TCRbeta,delta double-knockout mice, excluding the possibility of T-cell contamination. NK-cell TCRgamma gene rearrangement is thymus dependent because this rearrangement is undetectable in nude mouse NK cells. These results change the current view of NK-cell development and show that a subset of NK cells develops from immature thymocytes that have rearranged TCRgamma genes.
This study used a locally designed and validated questionnaire to describe the distribution of food and nutrition literacy (FNLIT) in a cross-sectional sample of 803 students aged 10-12 years from elementary schools in Tehran city, Iran. Logistic regression was used to assess the extent to which various independent covariates were associated with low FNLIT. The data were used to identify significant differences using a range of social and cultural variables relevant to the context of school students in Iran. The results of the study showed that although the total FNLIT level was good, this headline finding masked important differences in the sub-domains. More than half of the children (69%) had high levels of FNLIT in the cognitive domain, but in the skills domain, very few (3%) scored highly. The study also identified some associations between the total FNLIT and its subscales and sociodemographic variables including gender, parent's education and age, birth order. These results highlighted groups within the school population who were at higher risk of having lower FNLIT levels. They also indicate that girls feel more able to exert choice and control over food and nutrition decisions than boys are but may be less able to do so in practice. Overall, these results are a general reminder to schools of the different learning needs of children from different family backgrounds. The article highlights the need for continuous improvement in the health education curriculum of schools in Iran, particularly highlighting the importance of giving greater attention to the development of practical food and nutrition skills alongside more traditional food and nutrition knowledge. Additional studies (with long-term follow-up) are needed to more fully assess and understand the predictors of FNLIT.
c Murine Toll-like receptor 13 (TLR13), an endosomal receptor that is not present in humans, is activated by an unmethylated motif present in the large ribosomal subunit of bacterial RNA (23S rRNA). Little is known, however, of the impact of TLR13 on antibacterial host defenses. Here we examined the role of this receptor in the context of infection induced by the model pathogen group B streptococcus (GBS). To this end, we used bacterial strains masked from TLR13 recognition by virtue of constitutive expression of the ErmC methyltransferase, which results in dimethylation of the 23S rRNA motif at a critical adenine residue. We found that TLR13-mediated rRNA recognition was required for optimal induction of tumor necrosis factor alpha and nitrous oxide in dendritic cell and macrophage cultures stimulated with heat-killed bacteria or purified bacterial RNA. However, TLR13-dependent recognition was redundant when live bacteria were used as a stimulus. Moreover, masking bacterial rRNA from TLR13 recognition did not increase the ability of GBS to avoid host defenses and replicate in vivo. In contrast, increased susceptibility to infection was observed under conditions in which signaling by all endosomal TLRs was abolished, i.e., in mice with a loss-of-function mutation in the chaperone protein UNC93B1. Our data lend support to the conclusion that TLR13 participates in GBS recognition, although blockade of the function of this receptor can be compensated for by other endosomal TLRs. Lack of selective pressure by bacterial infections might explain the evolutionary loss of TLR13 in humans. However, further studies using different bacterial species are needed to prove this hypothesis.
Previous studies have shown that the pro-inflammatory cytokine IL-1β has a crucial role in host defenses against group B streptococcus (GBS), a frequent human pathogen, by recruiting neutrophils to infection sites. We examined here the cell types and mechanisms involved in IL-1β production during infection. Using a GBS-induced peritonitis model in mice, we first found that a large proportion of exudate cells contain intracellular IL-1β by immunofluorescence. Of the IL-1β positive cells, 82 and 7% were neutrophils and macrophages, respectively, suggesting that the former cell type might significantly contribute to IL-1β production. Accordingly, depletion of neutrophils with anti-Ly6G antibodies resulted in a significant reduction in the levels of IL-1β, but not of TNF-α or IL-6. We next found that neutrophils are capable of releasing mature IL-1β and TNF-α directly in response to in vitro stimulation with GBS. The production of pro-IL-1β and TNF-α in these cells required the Toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B1, which is involved in mobilization of a subfamily of TLRs to the endosomes. Moreover, pro-IL-1β processing and IL-1β release was triggered by GBS hemolysin and required components of the canonical inflammasome, including caspase-1, ASC and NLRP3. Collectively our findings indicate that neutrophils make a significant contribution to IL-1β production during GBS infection, thereby amplifying their own recruitment. These cells directly recognize GBS by means of endosomal TLRs and cytosolic sensors, leading to activation of the caspase-1 inflammasome.
To mark the 25th anniversary of the Ottawa Charter, this paper will discuss what remains to be achieved in strengthening community actions as an integral part of health promotion practice. To do this, the paper discusses four key elements for the future of health promotion programmes: (1) engage communities to share priorities; (2) build community capacity; (3) mechanisms for flexible and transparent funding; and (4) being creative in order to expand or replicate successful local initiatives. The paper uses a number of international case study examples of how these key elements can be achieved in health promotion programmes. A major challenge for the future is how health promotion agencies can develop and maintain the trust of communities, especially socially marginalized communities in society. The paper concludes by identifying a number of short and longer term challenges to achieve these goals and offers a way forward for a brighter future direction of health promotion practice.
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