This study focuses on the development of single dose vaccines based on biodegradable polyanhydride microspheres that have the unique capability to modulate the immune response mechanism. The polymer system employed consists of copolymers of 1,6-bis(p-carboxyphenoxy)hexane and sebacic acid. Two copolymer formulations that have been shown to provide extended release kinetics and protein stability were investigated. Using tetanus toxoid (TT) as a model antigen, in vivo studies in C3H/HeOuJ mice demonstrated that the encapsulation procedure preserves the immunogenicity of the TT. The polymer itself exhibited an adjuvant effect, enhancing the immune response to a small dose of TT. The microspheres provided a prolonged exposure to TT sufficient to induce both a primary and a secondary immune response (i.e., high antibody titers) with high-avidity antibody production, without requiring an additional administration. Antigen-specific proliferation 28 weeks after a single immunization indicated that immunization with the polyanhydride microspheres generated long-lived memory cells and plasma cells (antibody-secreting B cells) that generally do not occur without maturation signals from T helper cells. Furthermore, by altering the vaccine formulation, the overall strength of the T helper type 2 immune response was selectively diminished, resulting in a balanced immune response, without reducing the overall titer. This result is striking, considering free TT induces a T helper type 2 immune response, and has important implications for developing vaccines to intracellular pathogens. The ability to selectively tune the immune response without the administration of additional cytokines or noxious adjuvants is a unique feature of this delivery vehicle that may make it an excellent candidate for vaccine development.

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Excessive intake of saturated fatty acids and/or linoleic acid favors the induction of an array of lipid mediators and cytokines enhancing inflammatory responses. Conversely, dietary supplementation with (n-3) fatty acids or vitamin D ameliorates inflammation and autoimmune diseases. Although it was well accepted that conjugated linoleic acid (CLA) prevented diseases with a common inflammatory pathogenesis (i.e., cancer and atherosclerosis), no studies were available on the roles of CLA in mucosal inflammation. The present study was designed to investigate the anti-inflammatory actions and molecular mechanisms underlying the regulation of colonic health by CLA. We hypothesized that colonic inflammation can be ameliorated by dietary CLA supplementation. To test this hypothesis, inflammation of the colonic mucosa was triggered by challenging pigs fed either soybean oil-supplemented or CLA-supplemented diets with an enteric bacterial pathogen (i.e., Brachyspira hyodysenteriae). Immunoregulatory cytokines and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression were assayed in colonic lymph nodes and colon of pigs. Colonic mucosal lesions and lymphocyte subset distribution were evaluated by histology and immunohistochemistry. Supplementation of CLA in the diet before the induction of colitis decreased mucosal damage; maintained cytokine profiles (i.e., interferon-gamma and interleukin-10) and lymphocyte subset distributions (i.e., CD4+ and CD8+), resembling those of noninfected pigs; enhanced colonic expression of PPAR-gamma; and attenuated growth failure. Therefore, CLA fed preventively before the onset of enteric disease attenuated inflammatory lesion development and growth failure.

Background Hookahs (e.g., water pipes) are increasingly being used in the U.S. and elsewhere. Despite the popularity of hookah bars, there is a paucity of research assessing the health effects of hookah smoke, and although New York City (NYC) bans indoor tobacco smoking, hookah lounges claim that they only use herbal products without tobacco and are exempt. This study investigated levels of multiple indices of air pollution in the indoor air of hookah bars in NYC. Methods Air samples were collected in 8 hookah bars in NYC during the summer and fall of 2013. Along with venue characteristics, real-time measurements of fine particulate matter (PM2.5), black carbon (BC), and carbon monoxide (CO), and integrated samples of total gravimetric PM, elemental carbon (EC), organic carbon (OC), and nicotine were collected in 1–2 hour sessions. Results Overall, levels of indoor air pollution increased with increasing numbers of active hookahs smoked. The mean (SD) real time PM2.5 level was 1179.9 (939.4) µg/m3, whereas the filter-based total PM mean was 691.3 (592.6) µg/m3. The mean real time BC level was 4.1 (2.3) µg/m3, OC was 237.9 (112.3) µg/m3, and CO was 32 (16) ppm. Airborne nicotine was present in all studied hookah bars (4.2 (1.5) µg/m3). Conclusions These results demonstrate that despite the ban on smoking tobacco products, at the very least, some NYC hookah bars are serving tobacco-based hookahs, and have elevated concentrations of indoor air pollutants and toxicants that may present significant health threat to visitors and employees. Therefore, there is an urgent need for better air quality monitoring in such establishments and policies to combat this emerging public health threat.

A parallel screening method has been developed to rapidly evaluate discrete library substrates of biomaterials using cell-based assays. The biomaterials used in these studies were surface-erodible polyanhydrides based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) that have been previously studied as carriers for drugs, proteins, and vaccines. Linearly varying compositional libraries of 25 different polyanhydride random copolymers (based on CPH:SA and CPTEG:CPH) were designed, fabricated, and synthesized using discrete (organic solvent-resistant) multi-sample substrates created using a novel rapid prototyping method. The combinatorial libraries were characterized at high throughput using infrared microscopy and validated using 1H NMR and size exclusion chromatography. The discrete libraries were rapidly screened for biocompatibility using standard SP2/0 myeloma, CHO and L929 fibroblasts, and J774 macrophage cell lines. At a concentration of 2.8 mg/mL, there was no appreciable cytotoxic effect on any of the four cell lines evaluated by any of the CPH:SA or CPTEG:CPH compositions. Furthermore, the activation of J774 macrophages was evaluated by incubating the cells with the polyanhydride libraries and quantifying the secreted cytokines (IL-6, IL-10, IL-12, and TNFalpha). The results indicated that copolymer compositions containing at least 50% CPH induced elevated amounts of TNFalpha. In summary, the results indicated that the methodologies described herein are amenable to the high throughput analysis of synthesized biomaterials and will facilitate the rapid and rational design of materials for use in biomedical applications.

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Quantification and standardization of concepts like risk and vulnerability are increasingly being used in high-stakes, client-facing social services, also presenting the potential for data-driven tools for decision-making in this context. These trends necessitate an understanding of the role of quantitative data in the work of street-level decision-makers in social services. We present a qualitative study of existing data practices and perceptions of potential data-driven tools in housing allocation, engaging the perspective of service providers and policymakers in homeless services in a large urban county in the United States. Our findings highlight participants' concerns around centering clients' choices and ensuring integrity in a resource-constrained, high-stakes context. We also highlight differences between the perspectives of policymakers and service providers on standardization and fairness in the decision-making process. We discuss how use of and policies around data in social services need to consider the importance of the relationships that client-facing service providers have with other workers in the organization, with their work, and with clients.

Summary The spirochaete Brachyspira hyodysenteriae causes swine dysentery, a severe colitis characterized by mucosal enlargement as a result of crypt elongation and epithelial necrosis. Most efforts to understand the pathogenesis of this disease have focused on the aetiological agent and its virulence factors. However, the host immune response has been considered an important factor in disease development. Previous research has shown that B. hyodysenteriae induces systemic CD4+ and γδ T‐cell responses after intramuscular immunization. Here, we have evaluated changes in the CD4+ and γδ T‐cell composition and distribution the different compartments of the colonic mucosa of pigs challenged with B. hyodysenteriae. We report that, in infected pigs, γδ T cells were significantly depleted from the epithelial layer, although their numbers were maintained in the lamina propria. In addition, CD4+ T cells aggregated in clusters located in the lamina propria and submucosa. Ex vivo analyses of CD4+ T‐cell responses to B. hyodysenteriae antigens correlated with the changes in the mucosal CD4+ T‐cell distribution observed in infected pigs; CD4+ T cells recovered from peripheral blood and colonic lymph nodes of infected pigs proliferated to B. hyodysenteriae antigens, whereas no differences were found in the γδ T‐cell responses between challenged and control groups. In addition, colonic lymph node CD4+ T cells had a predominant memory/activated phenotype. These results indicate that infection with B. hyodysenteriae induces a mucosal CD4+ T‐cell response and points to CD4+ T cells being important contributors to the immunopathogenesis of swine dysentery.