Health literacy and the framing of health messages in the gay community

An aim of current UK health policy is to ‘fully engage’ not only sick but also well people in pursuit of health (Wanless 2004). In this policy discourse, it is assumed that ‘health literacy’ is one of the vehicles for achieving that full engagement: namely, individuals must understand the best information about how to pursue health, not only have access to it. The present project focuses on three related issues: (1) how health information is ‘framed’, and (2) how that information is understood, evaluated and acted on by those who receive it and (3) in light of the results, what dimensions ‘health literacy’ must have if changes in health-related behaviour are to ensue. Our focus is men’s health. It is widely recognised that men are less likely to engage with their own health than women with theirs. We choose gay men as a critical case. We single out varieties of gay men in Manchester and specifically the health issues they share with other men

Getting students out there; using community partnerships to engage students

Purpose The purpose of the paper is to discuss the “Q-Step in the Community” programme, part of the Q-Step Centre based in the Sociology Department at Manchester Metropolitan University, designed to help address the skills gap in quantitative methods (QM) that is evident across parts of the UK higher-education sector. “Q-Step in the Community” is a data-driven work-based learning programme that works in partnership with local organisations to provide placement opportunities for final year undergraduates and postgraduates. Students conduct a quantitative research project, which is typically identified by the placement provider. Design/methodology/approach The authors use quantitative and qualitative feedback from students and placement providers, along with our own reflections on the process to evaluate the placement programme. Data were collected through a focus group and email interviews with placement providers, along with a questionnaire, which was distributed to “Q-Step in the Community” alumni. Findings Data-driven work-based learning opportunities allow students to develop and demonstrate their quantitative skills and support networking opportunities whilst also developing valuable soft-skills experience of the workplace that develops their career-readiness. In addition, those opportunities provide valuable research for placement providers, which support their sustainability and enhance their service delivery. Research limitations/implications The research focusses solely on one programme at one university offering quantitative data driven work-based learning opportunities at undergraduate and post-graduate level. It is not possible to make valid comparisons between those who do a placement with those who do not. Originality/value Views of key stakeholders in the process have been sought for this research, which can be useful to consider for others considering developing similar programmes for their students

Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy

<p>Abstract</p> <p>Background</p> <p>Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer.</p> <p>Results</p> <p>Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of <it>NRF2 </it>exon 2 and <it>KEAP1 </it>exons 2-6 in these cell lines identified no mutations in <it>NRF2 </it>and only synonomous mutations in <it>KEAP1</it>. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P < 0.001).</p> <p>Conclusions</p> <p>Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas. This may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions. Nrf2 also appears to support proliferation in certain pancreatic adenocarinomas. Therefore, strategies to pharmacologically manipulate the levels and/or activity of Nrf2 may have the potential to reduce pancreatic tumor growth, and increase sensitivity to therapeutics.</p

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms

The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicological properties need to be assessed. Accepted methods for gathering the information required by law for approval of substances are often animal methods. To reduce, refine, and replace animal testing, innovative organotypic in vitro models have emerged. Such models appear at different levels of complexity ranging from simpler, self-organized three-dimensional (3D) cell cultures up to more advanced scaffold-based co-cultures consisting of multiple cell types. This review provides an overview of recent developments in the field of toxicity testing with in vitro models for three major organ types: heart, skin, and liver. This review also examines regulatory aspects of such models in Europe and the UK, and summarizes best practices to facilitate the acceptance and appropriate use of advanced in vitro models

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

Funded by Asthma UK grant number 09/ 36

Detection of Hepatic Drug Metabolite-Specific T-Cell Responses Using a Human Hepatocyte, Immune Cell Coculture System

Drug-responsive T-cells are activated with the parent compound or metabolites, often via different pathways (pharmacological interaction and hapten). An obstacle to the investigation of drug hypersensitivity is the scarcity of reactive metabolites for functional studies and the absence of coculture systems to generate metabolites in situ. Thus, the aim of this study was to utilize dapsone metabolite-responsive T-cells from hypersensitive patients, alongside primary human hepatocytes to drive metabolite formation, and subsequent drug-specific T-cell responses. Nitroso dapsone-responsive T-cell clones were generated from hypersensitive patients and characterized in terms of cross-reactivity and pathways of T-cell activation. Primary human hepatocytes, antigen-presenting cells, and T-cell cocultures were established in various formats with the liver and immune cells separated to avoid cell contact. Cultures were exposed to dapsone, and metabolite formation and T-cell activation were measured by LC-MS and proliferation assessment, respectively. Nitroso dapsone-responsive CD4+ T-cell clones from hypersensitive patients were found to proliferate and secrete cytokines in a dose-dependent manner when exposed to the drug metabolite. Clones were activated with nitroso dapsone-pulsed antigen-presenting cells, while fixation of antigen-presenting cells or omission of antigen-presenting cells from the assay abrogated the nitroso dapsone-specific T-cell response. Importantly, clones displayed no cross-reactivity with the parent drug. Nitroso dapsone glutathione conjugates were detected in the supernatant of hepatocyte immune cell cocultures, indicating that hepatocyte-derived metabolites are formed and transferred to the immune cell compartment. Similarly, nitroso dapsone-responsive clones were stimulated to proliferate with dapsone, when hepatocytes were added to the coculture system. Collectively, our study demonstrates the use of hepatocyte immune cell coculture systems to detect in situ metabolite formation and metabolite-specific T-cell responses. Similar systems should be used in future diagnostic and predictive assays to detect metabolite-specific T-cell responses when synthetic metabolites are not available

The INT6 Cancer Gene and MEK Signaling Pathways Converge during Zebrafish Development

BACKGROUND: Int-6 (integration site 6) was identified as an oncogene in a screen of tumorigenic mouse mammary tumor virus (MMTV) insertions. INT6 expression is altered in human cancers, but the precise role of disrupted INT6 in tumorigenesis remains unclear, and an animal model to study Int-6 physiological function has been lacking. PRINCIPAL FINDINGS: Here, we create an in vivo model of Int6 function in zebrafish, and through genetic and chemical-genetic approaches implicate Int6 as a tissue-specific modulator of MEK-ERK signaling. We find that Int6 is required for normal expression of MEK1 protein in human cells, and for Erk signaling in zebrafish embryos. Loss of either Int6 or Mek signaling causes defects in craniofacial development, and Int6 and Erk-signaling have overlapping domains of tissue expression. SIGNIFICANCE: Our results provide new insight into the physiological role of vertebrate Int6, and have implications for the treatment of human tumors displaying altered INT6 expression

High blood pressure in school children: prevalence and risk factors

BACKGROUND: The purpose of this study was to determine the prevalence of high blood pressure (HBP) and associated risk factors in school children 8 to 13 years of age. METHODS: Elementary school children (n = 1,066) were examined. Associations between HBP, body mass index (BMI), gender, ethnicity, and acanthosis nigricans (AN) were investigated using a school based cross-sectional study. Blood pressure was measured and the 95(th )percentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association. RESULTS: Females, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI ≥ 85(th )percentile) and those with AN were at least twice as likely to present with HBP after controlling for confounding factors. CONCLUSION: Twenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children