Long-term deposition of inhaled antigen in lung resident CD11b-CD11c+ cells

In this study we report the characterization of a population of lung resident CD11b(-)CD11c(+) cells that are able to take up inhaled antigen and retain it for extended periods of time. Ovalbumin conjugated to fluorescein-isothiocyanate (FITC-OVA) administered intranasally to mice was taken up by two main populations of cells in the lung, a migratory CD11c(+)CD11b(+) population consisting of dendritic cells (DC), which rapidly transported antigen to the draining lymph node (LN), and a resident CD11b(-)CD11c(+) population that retained engulfed antigen without apparently degrading it for up to 8 wk after administration. The FITC(+)CD11b(-)CD11c(+) cells did not migrate to draining LN at a detectable rate, and did not up-regulate expression of costimulatory molecules in response to LPS treatment. FITC(+)CD11b(-)CD11c(+) cells were found in the lung and bronchoalveolar lavage fluid, and their distribution was compatible with macrophages. Although FITC(+)CD11b(-)CD11c(+) cells expressed the DC marker DEC205 and other molecules associated with antigen-presenting cell function, they did not induce proliferation of antigen-specific CD4(+) T cells in vitro or acute cytokine production by activated CD4(+) T cells in vivo. Thus, FITC(+)CD11b(-)CD11c(+) cells appear to represent an intermediate cell type sharing properties with DC and macrophages. These cells may have a role in modulating the responses of lung resident T cells to inhaled antigens.     

G-protein-coupled receptor expression, function, and signaling in macrophages

G-protein-coupled receptors (GPCRs) are widely targeted in drug discovery. As macrophages are key cellular mediators of acute and chronic inflammation, we review here the role of GPCRs in regulating macrophage function, with a focus on contribution to disease pathology and potential therapeutic applications. Within this analysis, we highlight novel GPCRs with a macrophage-restricted expression profile, which provide avenues for further exploration. We also review an emerging literature, which documents novel roles for GPCR signaling components in GPCR-independent signaling in macrophages. In particular, we examine the crosstalk between GPCR and TLR signaling pathways and highlight GPCR signaling molecules which are likely to have uncharacterized functions in this cell lineage.     

FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis

The survival of long-lived plasma cells, which produce most serum immunoglobulin, is central to humoral immunity. We found here that the inhibitory Fc receptor FcgammaRIIb was expressed on plasma cells and controlled their persistence in the bone marrow. Crosslinking FcgammaRIIb induced apoptosis of plasma cells, which we propose contributes to the control of their homeostasis and suggests a method for therapeutic deletion. Plasma cells from mice prone to systemic lupus erythematosus did not express FcgammaRIIb and were protected from apoptosis. Human plasmablasts expressed FcgammaRIIb and were killed by crosslinking, as were FcgammaRIIb-expressing myeloma cells. Our results suggest that FcgammaRIIb controls bone marrow plasma cell persistence and that defects in it may contribute to autoantibody production.     

Addressing Gaps in Cardiopulmonary Resuscitation Education: Training Middle School Students in Hands‐Only Cardiopulmonary Resuscitation

BACKGROUND

Training middle school students to perform hands‐only cardiopulmonary resuscitation (HOCPR) is a potential method to increase overall rates of bystander cardiopulmonary resuscitation (CPR). We aimed to examine the feasibility of teaching this population CPR using teacher‐implemented education sessions guided by American Heart Association (AHA) training kits and resources.

METHODS

We conducted a national HOCPR training campaign in middle schools during the 2014‐2015 school year. Participating schools utilized AHA CPR training kits to train seventh and eighth grade students. We assessed pretest/posttest knowledge and comfort in performing HOCPR.

RESULTS

We recruited 1131 schools and trained approximately 334,610 students in HOCPR. The average pretest score on knowledge questions was 50% and the average posttest score was 84%. Most students (76%) felt comfortable performing HOCPR after the education session. Overall, 98% of teachers said they would continue to implement CPR training in the future.

CONCLUSIONS

Large‐scale, teacher‐implemented CPR education sessions in the middle school setting are a successful approach to increase middle school student's knowledge and comfort in performing HOCPR and to increase overall bystander CPR rates.

     

Impacts of a School‐Wide,Peer‐Led Approach to Sexuality Education: A Matched Comparison Group Design

BACKGROUND

Teen Prevention Education Program (PEP) is a school‐wide, peer‐led comprehensive sexuality education program currently implemented in more than 50 schools across 2 states. Many teen pregnancy prevention researchers and practitioners view peer‐led programs as a promising approach for reducing teen pregnancy and associated sexual risk behaviors. However, prior research on the effectiveness of these programs indicates mixed results.

METHODS

We randomly assigned schools to implement Teen PEP immediately (intervention group) or on a delayed schedule (comparison group) and used propensity score matching to improve the comparability of the study groups. We surveyed students at baseline and about 6 months after the program ended.

RESULTS

Teen PEP did not significantly impact rates of sexual activity or unprotected sex; however, the program led to improvements in exposure to information about sexual health topics and knowledge of preventing pregnancy and transmission of sexually transmitted infections.

CONCLUSIONS

Teen PEP succeeded in accomplishing some of its most proximal goals, increasing students' access to information and knowledge. However, we found little evidence that the program affects sexual risk‐taking within 6 months of its conclusion. Future research will examine the program's longer‐term impacts on sexual risk behaviors.

     

Thinking with care infrastructures: people,devices and the home in home blood pressure monitoring

The growing consumer market in health monitoring devices means that technologies that were once the preserve of the clinic are moving into spaces such as homes and workplaces. We consider how one such device, blood pressure monitors, comes to be integrated into everyday life. We pursue the concept of ‘care infrastructure’, drawing on recent scholarship in STS and medical sociology, to illuminate the work and range of people, things and spaces involved in self‐monitoring. Drawing on a UK study involving observations and interviews with 31 people who have used a consumer blood pressure monitor, we apply the concept beyond chronic illness, to practices involving consumer devices – and develop a critical account of its value. We conclude that the care infrastructure concept is useful to highlight the socio‐material arrangements involved in self‐monitoring, showing that even for ostensibly personal devices, monitoring may be a shared practice that expresses care for self and for others. The concept also helps draw attention to links between different objects and spaces that are integral to the practice, beyond the device alone. Care infrastructure draws attention to the material, but ensures that analytic attention engages with both material and social elements of practice and their connections.     

Informing school sex education using the stages of change construct: sexual behaviour and attitudes towards sexual activity and condom use of children aged 13-16 in England

A survey of 3820 school children in England aged 13-16 years examined sexual activity using the Transtheoretical Model (TTM) Stages of Change. A quarter (26%) of teens were sexually experienced, 44.8 per cent did not use contraception and 48.9 per cent did not use condoms, every time. Past history of condom and contraceptive use, and partner willingness to use condoms were the best predictors of being in Action or Maintenance stage for condom use. Of virgins, 19.82 per cent were in Contemplation or Preparation stages for intercourse, and 85.4 per cent would use condoms every time. Sex education should be tailored to Stage, and signposting to sexual health and contraception services.     

Typing and subtyping of Clostridium difficile isolates by using multiple-locus variable-number tandem-repeat analysis

Using the genomic sequence of Clostridium difficile strain 630, we developed multiple-locus variable-number tandem-repeat analysis (MLVA) with automated fragment analysis and multicolored capillary electrophoresis as a typing method for C. difficile. All reference strains, representing 31 serogroups, 25 toxinotypes, and 7 known subtypes of PCR ribotype 001, could be discriminated from each other. Application of MLVA to 28 isolates from 7 outbreaks due to the emerging hypervirulent PCR ribotype 027-pulsed-field gel electrophoresis type NAP1 resulted in recognition of 13 clusters. Additionally, 29 toxin A-negative, toxin B-positive isolates belonging to PCR ribotype 017 from eight different countries revealed eight country-specific clusters. MLVA is a highly discriminatory genotyping method and a new tool for subtyping of newly emerging variants of C. difficile.