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LD between nine functional CYP2A6 variants and top six overlapping associations between MEC & TRICL - among Whites and Overall MEC sample

List of 226 overlapping associations for CYP2A6 in the TRICL & MEC Studies

Metabolism of nicotine by cytochrome P450 2A6 (CYP2A6) is a suspected determinant of smoking dose and, consequently, lung cancer risk. We conducted a genome-wide association study (GWAS) of CYP2A6 activity, as measured by the urinary ratio of trans-3′-hydroxycotinine and its glucuronide conjugate over cotinine (total 3HCOT/COT), among 2,239 smokers in the Multiethnic Cohort (MEC) study. We identified 248 CYP2A6 variants associated with CYP2A6 activity (P < 5 × 10−8). CYP2A6 activity was correlated (r = 0.32; P < 0.0001) with total nicotine equivalents (a measure of nicotine uptake). When we examined the effect of these variants on lung cancer risk in the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium GWAS dataset (13,479 cases and 43,218 controls), we found that the vast majority of these individual effects were directionally consistent and associated with an increased lung cancer risk. Two hundred and twenty-six of the 248 variants associated with CYP2A6 activity in the MEC were available in TRICL. Of them, 81% had directionally consistent risk estimates, and six were globally significantly associated with lung cancer. When conditioning on nine known functional variants and two deletions, the top two SNPs (rs56113850 in MEC and rs35755165 in TRICL) remained significantly associated with CYP2A6 activity in MEC and lung cancer in TRICL. The present data support the hypothesis that a greater CYP2A6 activity causes smokers to smoke more extensively and be exposed to higher levels of carcinogens, resulting in an increased risk for lung cancer. Although the variants identified in these studies may be used as risk prediction markers, the exact causal variants remain to be identified. Cancer Res; 76(19); 5768–76. ©2016 AACR.

List of 251 globally significant associations (p < 5E-8) for CYP2A6 in the MEC Cohort

Descriptive Characteristics of TRICL participants

Results of the six overlapping globally significant associations (p < 5E-8) with lung cancer risk in TRICL and with CYP2A6 activtiy in MEC stratified by cell type.

Purpose The theft of drugs from healthcare facilities, also known as drug diversion, occurs frequently but is often undetected. This paper describes a research study to develop and test novel drug diversion detection methods. Improved diversion detection and reduction in diversion improves patient safety, limits harm to the person diverting, reduces the public health impact of substance use disorder, and mitigates significant liability risk to pharmacists and their organizations. Methods Ten acute care inpatient hospitals across 4 independent health systems extracted 2 datasets from various health information technology systems. Both datasets were consolidated, normalized, classified, and sampled to provide a harmonious dataset for analysis. Supervised machine learning methods were iteratively used on the initial sample dataset to train algorithms to classify medication movement transactions as involving a low or high risk of diversion. Thereafter, the resulting machine learning model classified the risk of diversion in a historical dataset capturing 8 to 24 months of history that included 27.9 million medication movement transactions by 19,037 nursing, 1,047 pharmacy, and 712 anesthesia clinicians and that included 22 known, blinded diversion cases to measure when the model would have detected the diversion compared to when the diversion was actually detected by existing methods. Results The machine learning model had 96.3% accuracy, 95.9% specificity, and 96.6% sensitivity in detecting transactions involving a high risk of diversion using the initial sample dataset. In subsequent testing using the much larger historical dataset, the analytics detected known diversion cases (n = 22) in blinded data faster than existing detection methods (a mean of 160 days and a median of 74 days faster; range, 7-579 days faster). Conclusion The study showed that (1) consolidated datasets and (2) supervised machine learning can detect known diversion cases faster than existing detection methods. Users of the technology also noted improved investigation efficiency.

Introduction A potential precision medicine approach to smoking cessation is tailoring pharmacotherapy to a biomarker known as the nicotine metabolite ratio (NMR). Little is known about the potential impact and acceptability of this approach for American Indian (AI) persons. Aims and Methods Tribal-academic collaboration was formed and during 2019–2020 AI adults who smoke(N = 54) were recruited to (1) examine correlations between NMR, dependence, and smoking exposure; (2) assess the extent to which pharmacotherapy preference aligned with NMR-informed recommendations; (3) explore acceptability of NMR-informed pharmacotherapy selection. Participants provided samples for assessment of salivary NMR and urinary total nicotine equivalents (TNE) and completed a questionnaire that assessed cigarettes per day (CPD), Fagerstrom Test for Cigarette Dependence (FTCD), pharmacotherapy preference, and perceptions of NMR-informed pharmacotherapy selection. Results Significant positive correlations were observed between NMR and FTCD (r = 0.29;p = .0383) and its abbreviated version Heaviness of Smoking Index (HIS) (r = 0.28;p =.0426). Post-hoc analyses suggest that relationships between dependence and NMR were driven by time to first cigarette. Nonsignificant, but directionally consistent, relationships were observed between NMR and CPD (r = 0.21; p =0.1436) and TNE (r = 0.24;p = .2906). Most participants preferred nicotine replacement therapy (71%) over varenicline (29%) and preference for pharmacotherapy matched NMR-based recommendations in 54% of participants. NMR-informed pharmacotherapy selection was supported by 62% of participants. Conclusion In a sample of AI adults who smoke, NMR was related to cigarette dependence and about one-half of participants’ pharmacotherapy preference matched their NMR-informed recommendation. There was lower acceptability of NMR-informed approach in this sample of AI adults than prior studies among white or black/African American people who smoke. Implications Relationships between NMR, dependence, and self-preference for pharmacotherapy suggest that NMR-informed pharmacotherapy selection may have potential for enhancing smoking quitting success in this Tribe. Lower acceptability of NMR-informed pharmacotherapy in this Tribe suggests that this approach may not be equitably utilized. Future work could include identifying community-driven solutions to mitigate precision medicine concerns.

Objectives Solar ultraviolet radiation (UVR) has major adverse effects on human health. While the mechanisms responsible for induction of UVR-induced inflammation are well-documented, the mediation of its resolution and longer-term adaptive homeostasis is unknown. Therefore, we examined the skin immune and lipid profile over time following UVR inflammation. Methods To investigate the self-resolving events of UVR inflammation in vivo, human skin was exposed to a single pro-inflammatory dose of UVR. Skin biopsies and suction blister fluid were taken at intervals up to 2 weeks post-UVR. The immune infiltrate was quantified by immunohistochemistry, and lipid mediators were profiled by liquid chromatography/mass spectrometry. Results We identified that cellular resolution events including switching of macrophage phenotype apply to human sunburn. However, UVR-induced inflammation in humans involves a post-resolution phase that differs from other experimental models. We demonstrate that 2 weeks after the initiating UVR stimulus, there is considerable immune activity with CD8+GATA3+ T cells maintained in human skin. Our results challenge the dogma of CD4+FOXP3+ T cells being the main effector CD4+ T-cell population following UVR, with CD4+GATA3+ T cells the dominant phenotype. Furthermore, lipid mediators are elevated 14 days post-UVR, demonstrating the skin lipid microenvironment does not revert to the tissue setting occurring prior to UVR exposure. Conclusion We have identified for the first time that CD4+GATA3+ and CD8+GATA3+ T-cell subpopulations are recruited to UVR-inflamed human skin, demonstrating discrepancies between the adaptive UVR response in mice and humans. Future strategies to abrogate UVR effects may target these T-cell subpopulations and also the persistent alteration of the lipid microenvironment post-UVR.

Foreword {#article-title-2} The ASHP Research and Education Foundation (“the Foundation”) is pleased to present the sixth edition of the annual Pharmacy Forecast . While the first 4 editions of the Pharmacy Forecast were published as standalone reports, the fifth edition of the Pharmacy

Diabetes mellitus (DM) during pregnancy can result in fetal overgrowth, likely due to placental dysfunction, which has health consequences for the infant. Here we test our prediction from previous work using a placental cell line that high glucose concentrations affect placental lipid metabolism. Placentas from women with type 1 (n = 13), type 2 (n = 6) or gestational (n = 12) DM, BMI-matched to mothers without DM (n = 18), were analysed for lipase and fatty acid transport proteins and fatty acid and triglyceride content. Explants from uncomplicated pregnancies (n = 6) cultured in physiological or high glucose were similarly analysed. High glucose levels did not alter placental lipase or transporter expression or the profile and abundance of fatty acids, but triglyceride levels were higher (p

Nutritional supplementation with fish oil or ω-3 (n-3) polyunsaturated fatty acids (PUFAs) has potential benefits for skin inflammation. Although the differential metabolism of the main n-3PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could lead to distinct activities, there are no clinical studies comparing their relative efficacy in human skin. Following a 10-wk oral supplementation of healthy volunteers and using mass spectrometry-based lipidomics, we found that n-3PUFA mainly affected the epidermal mediator lipidome. EPA was more efficient than DHA in reducing production of arachidonic acid–derived lipids, and both n-3PUFA lowered N-acyl ethanolamines. In UV radiation–challenged skin (3 times the minimum erythemal dose), EPA attenuated the production of proinflammatory lipids, whereas DHA abrogated the migration of Langerhans cells, as assessed by immunohistochemistry. Interestingly, n-3PUFA increased the infiltration of CD4+ and CD8+ T cells but did not alter the erythemal response, either the sunburn threshold or the resolution of erythema, as assessed by spectrophotometric hemoglobin index readings. As EPA and DHA differentially impact cutaneous inflammation through changes in the network of epidermal lipids and dendritic and infiltrating immune cells, they should be considered separately when designing interventions for cutaneous disease.—Kendall, A. C., Pilkington, S. M., Murphy, S. A., Del Carratore, F., Sunarwidhi, A. L., Kiezel-Tsugunova, M., Urquhart, P., Watson, R. E. B., Breitling, R., Rhodes, L. E., Nicolaou, A. Dynamics of the human skin mediator lipidome in response to dietary ω-3 fatty acid supplementation.

Two separate methods were used to prepare a tetra(4-carboxyphenyl)porphyrin (TCPP)-TiO2 composite. In method A TCPP was absorbed onto TiO2 in methanol at room temperature, whilst in method B TCPP was absorbed onto TiO2 in dimethylformamide (DMF) at reflux. Both composites exhibited the same physical and chemical characteristics as shown by FT-IR, SEM and UV–vis diffuse reflectance spectroscopy (DRS). The photocatalytic activity of both composites was then determined by HPLC monitoring of the photo-degradation of the pharmaceutical Famotidine under both visible and solar light irradiation. The recyclability of the composites was also examined by recovery of the composite post-reaction, although the absorbed TCPP was found to partially degrade, the recycled composite still exhibited catalytic behaviour. All reactions were monitored by HPLC which revealed that the photodegradation of Famotidine by the TCPP–TiO2 composites does not lead to complete mineralisation, but instead generates a range of intermediates/products. Investigation of these products by LC–MS–MS and DI–MS analysis found that one major degradation product was formed, the S-oxide of Famotidine. The TCPP–TiO2 composites were also screened in the photo-degradation of the pharmaceuticals tamsulosin and solifenacin using the optimised conditions developed for famotidine. However, the composites were found to be ineffective for the photo-catalytic degradation of these compounds, demonstrating that this class of composite are only effective for specific compounds.

The East India Company began to establish lending libraries for soldiers at its stations in India from about 1891 and, by the early 1830s, the majority of those responsible for the day-to-day operation of these institutions were keen to stress their beneficial effect upon the readers who frequented them. In a series of reports that were written at this time station chaplains and commanding officers emphasised that reading was having a positive effect upon the men's behaviour. What also emerges from these reports is evidence of a contemporary belief that the ‘setting’ in which reading took place determined the degree to which the activity was beneficial.

Britain enjoyed unparalleled overseas expansion in the years between 1780 and 1830, consolidating her rule over India and parts of Canada, and developing or adding greatly to her colonial possessions in Australia, South Africa, and the Caribbean.1 During this same period, "a new cultural and social phenomenon known as 'the rise of the reading public'" emerged, with readers avidly consuming the prose fiction that rolled off the nation's printing presses.2 That this prose fiction, in particular the novel, crucially facilitated the spread of empire has been persuasively argued by theorists and critics who suggest that the form worked in complex ways to prepare readers to imagine and, hence, "accommodate" Britain's imperial expansion. Works such as Robinson Crusoe (1719) and Mansfield Park (1814), it has been suggested, contributed to the naturalization of a sense of England's cultural and military power, and promoted notions of racial identity that made a British Empire seem both inevitable and necessary to the reading public. This is not to say that writers like Daniel Defoe or Jane Austen selfconsciously set out to promote imperial ideology in their writing, but rather that their works illuminated "the far from accidental convergence between . . . patterns of narrative authority constitutive of the novel on the one hand, and, on the other, a complex ideological configuration underlying the tendency to imperialism."3 Despite the attention that has been paid to the link between the novel and empire, critics have devoted strangely little effort to identifying the types of fiction that may have been read by actual soldiers or sailors, the British Empire's most immediate agents. They tend to take it for granted that the

This article reports a study of coauthor Laura Wright as she learned to teach secondary school grammar in four settings: university teacher education program, student teaching, her first job, and second job. Data for her university program came from Laura’s journals and projects from her course work. Data from student teaching and her first job included interviews and field notes from observations and interviews and self-reports by Laura of teaching conducted on other occasions. Information from her second job came from self-reports by Laura. The data were analyzed using a system that identified the pedagogical tools Laura employed and the attributions she made for learning how to use them. The data suggest that Laura sought to teach in ways that students found engaging, meaningful, enjoyable, and relevant. How she was able to make grammar instruction fit this goal varied according to the setting in which her instruction took place.

There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies.

e have witnessed recently the emergence of a new vision of reading assessment. That vision, created out of a disenchantment with standardized achievement tests, has been fueled by factors such as current research on language, literacy, and cognitive development (Chittenden 1987); a waning faith in behaviorism and the emergence of a new paradigm (Heshusius 1989); and an explicit recognition of the politicization of educational assessment (Shannon 1993). The drive to create statewide measures that were alternatives to standardized tests began somewhat tentatively with efforts in Illinois (Valencia and Pearson 1987) and Wisconsin (Wixson, Peters, Weber, and Roeber 1987). Although these early ventures still retained multiple choice questions, they introduced new elements, concepts such as the activation of schema in preparation for reading, the inclusion of some openended response questions, and an increase in the length of texts. Such elements have been advocated in the research and theoretical literature for some time; given that standardized testing permeates the educational culture of the United States, however, initial moves to “revision” reading assessment were quite significant. More recent efforts have moved toward making the text in reading assessments more like the reading of the real world and less like an artifact that exists nowhere else but in school. Several different terms are used for this new kind of reading assessment: portfolio assessment, performance-based assessment, and authentic assessment (see, for example, Brandt 1993; Gough

This study found that the key components of the Los Angeles Universal Preschool’s quality support coaching model include: (1) research and evidence-based practices by experienced and committed coaches; (2) support, such as positive and collaborative relationships and observation of instruction with feedback loops; and (3) outcomes associated in the literature with improved quality, such as motivation for improving quality and reflective practice. The model followed some of the best practices of effective coaching models, namely a strong emphasis on the coach-provider relationship and active engagement of providers in developing their own knowledge and practices.

This issue brief describes children's development in the Los Angeles Universal Preschool program during 2010–2011. English-proficient students showed significant growth in early literacy skills from fall to spring, with their mean scores exceeding the national average. However, their vocabulary concepts and math skills were below the national average in spring. Language and math skills for English language learners continued to be below the national average, but literacy skills approached the national mean by spring 2011. At that time, the percentage of children scoring in the expected range exceeded the national average for attention, activity level, and sociability.

This research brief describes instructional practices that support English language learners and presents findings on how those practices are applied in Los Angeles Universal preschool center-based classrooms and family child care programs.

This paper relates our experience at the Engineering & Science Library at Queen’s University, melding Library resources into the design engineering curriculum in the Faculty of Applied Science. Effective library support of design engineering comprises people, curriculum, collections and assessment. Moreover, effective support is seamless and fully embedded in the design students’ learning over time. We discuss our experience to date and identify areas for future growth.

This study provides a preliminary contribution to the development of an industrial process for the UV/TiO2 water treatment by introducing a novel support for TiO2 immobilization. For the following study, Methylene Blue (MB) was chosen as the model dye to evaluate this novel immobilization system. The results showed that TiO2 immobilized in a Ca–alginate bead retained its photoactivity during all of the experiments and the TiO2-gel beads presented good stability in water for maintaining its shape after several uses. When a proportion of 10% (v/v) of these beads was used, the configuration system demonstrated an improved mass transfer and consequently enhanced degradation efficiency. Experiments were also performed using ‘recycled’ beads. The results showed an increase in the degradation efficiency when the beads were reused, with an eventual ‘self-destructive’ effect. These studies showed great promise regarding the recyclable reagents with a reduction in waste at no greater cost or reduction in efficiency. Therefore, the potential of TiO2-gel beads as a simple and environmentally friendly catalyst for continuous use was developed.

This paper demonstrates how information literacy is a hidden attribute woven throughout CEAB’s recent accreditation criteria. The paper focuses in particular on life-long learning and describes how such a model can be developed and transferred in different engineering programs.

The author reflects on issues on electronic science (e-science) and science librarianship discussed at the Re-inventing Science Librarianship forum held in Arlington, Virginia in 2008. One of the topics tackled was the need for science and engineering librarians to include researchers in the existing relationships. Another issue addressed at the forum was the local landscape in the respective universities of librarians. She stresses the role of librarians in light of the emergence of networked, accessible and re-usable data.

Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-κB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-κB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-κB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis–fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-κB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-κB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS., Author Summary The normal response to infection is rapid and effective clearance of pathogenic microbes. However, this immune response may occasionally cause collateral inflammatory damage to host tissue and in severe cases, such as systemic sepsis, results in organ failure. Various cellular mechanisms, including regulatory T cells, protect against aggressive immune responses. However, environmental agents which promote regulatory T cells are not well understood. We and others have previously shown that non-pathogenic or commensal micro-organisms can protect the host from aberrant pro-inflammatory activity within the gut, but the influence of these microbes on regulatory T cells in the context of systemic infection has not been examined. In this study, we demonstrate that consumption of a single commensal bacterium induces regulatory T cells in vivo which protect the host from pathogen-induced inflammatory responses by limiting activation of the pro-inflammatory transcription factor NF-κB via the toll-like receptor 4 (TLR-4) pathway. This report conclusively demonstrates a cellular and molecular basis for the commensal-host-pathogen trilogue resulting in enhanced protection from systemic infection whilst limiting pro-inflammatory damage mediated by activation of the innate immune system.

Urinary tract stones are an important clinical problem in human and veterinary medicine. Hyperoxaluria is the single strongest promoter of kidney stone formation. The aims of the present study were to (a) evaluate oxalate degradation by a range of Bifidobacteria species and Lactobacillus species isolated from the canine and feline gastrointestinal tract in vitro and (b) to determine the impact of oxalate degradation by selected strains in vivo. The bacteria were grown in oxalate-containing media and their ability to degrade oxalate in vitro was determined using reverse-phased HPLC. Bifidobacteria species and Lactobacillus species that degraded oxalate in vitro and survived gastric transit were selected for further examination. The selected probiotics were fed to rats for 4 weeks. Urine was collected at week's 0, 2 and 4 and oxalate levels determined by HPLC. In vitro degradation was detected for 11/18 of the Lactobacillus species. In contrast, the capacity to degrade oxalate was not detected for any of the 13 Bifidobacterium species tested. Lactobacillus animalis 223C, Lactobacillus murinus 1222, L. animalis 5323 and L. murinus 3133 were selected for further investigation in a rat model. Urinary oxalate levels were significantly reduced (p

Peripheral T-cell lymphomas (PTCL) other than anaplastic large cell lymphoma (ALCL) are rare in young patients. While a high proportion of adults with PTCL have poor risk disease, pediatric PTCL is not well characterized. This study examines the outcome of localized and advanced PTCL in pediatric patients treated in standardized fashion.We identified 20 pediatric patients diagnosed with PTCL whose tumor cells did not express CD30 and/or ALK, as determined by immunohistochemistry, between 1992 and 2000 on one of two treatment protocols for localized NHL (POG 9219) or advanced stage large cell lymphoma (POG 9315). All cases were centrally reviewed.The median age was 12.6 (range 0.7-16.9)-9 male and 11 female. Histological subtypes in the WHO Classification included PTCL, unspecified (12), extra-nodal NK/T-cell lymphoma of nasal type (4), subcutaneous panniculitis-like T cell lymphoma (1) and enteropathy-type T-cell lymphoma (1). Two cases exhibited both T-cell and histiocyte markers and were reclassified as histiocytic sarcoma per the WHO, although T-lineage remains possible. Of 10 patients with localized disease, only two relapsed and 9 survive. Of 10 patients with advanced disease, six relapsed and five (50%) survive.These results suggest that localized PTCL in children and adolescents is frequently cured with modern therapy, but that advanced stage cases may require novel therapy.

This paper provides an exploratory overview of the current state of teaching of and access to standards, focusing on the experiences at Queen’s University and at the University of Toronto. We argue that standards education is a core experience for engineering students and that it is incumbent on academic libraries to provide access to them.

Background: Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect. Results: Following 4 hours of infection with Salmonella typhimurium, NF-B activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-B response. In vitro anti-CD3/CD28 stimulated Peyer’s patch cells secreted significantly less TNF-a and IFN-g following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers. Conclusion: Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of proinflammatory transcription factor activation in response to an infectious insult associated with modulation of proinflammatory cytokine production within the mucosa. The cellular mechanism underpinning Bifidobacterium animalis AHC7 mediated attenuation of NF-B activation may include recognition of the bacterium by dendritic cells and induction of CD25+Foxp3+ T cells.

Background Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect. Results Following 4 hours of infection with Salmonella typhimurium, NF-κB activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-κB response. In vitro anti-CD3/CD28 stimulated Peyer's patch cells secreted significantly less TNF-α and IFN-γ following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers. Conclusion Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of pro-inflammatory transcription factor activation in response to an infectious insult associated with modulation of pro-inflammatory cytokine production within the mucosa. The cellular mechanism underpinning Bifidobacterium animalis AHC7 mediated attenuation of NF-κB activation may include recognition of the bacterium by dendritic cells and induction of CD25+Foxp3+ T cells.

COMMERCIALS are communication, forms of composition, just as truly as is the more traditional essay or term paper. They can be used in studying written and oral persuasion, nonverbal communication, as well as film grammar and technique, television and advertising. In fact, a fine package is prepared yearly by the American Television Commercials Festival in New York, including a reel of the Best Commercials of the year and a visually attractive hard cover book, containing the commentaries by the commercials' creators on how they made their prize winners. The only drawback to use of this professionally produced package is its expense, its scheduling, and the fact that rental films can be kept only a relatively short time. Creative use of commercially produced media offers many possibilities for designing and preparing instructional packages without great expense and with the potential of tailoring the package to the needs of individual learner groups. A request to the local TV studio (via its public service department) to save discarded commercials and public service announcements; an evening or two with a movie editor and splicer; careful selection of the PSA's which offer the greatest potential learning for the teacher's purposes-and the average teacher can have an extremely inexpensive and very adaptable set of teaching tools. To enhance the total learning process, the instructor selecting PSA's for study might involve students in the selecting-editingsplicing process. When the package has been completed, the unused PSA's and commercials often contain mines of valuable vis