It's Not About "Freudian Couches and Personality Changing Drugs": An Investigation Into Men's Mental Health Help-Seeking Enablers.

Enabling factors that influenced men to seek assistance for mental health concerns--a previous underresearched area--was the primary focus of this research. Past research spanning four decades has focused on men's barriers to mental health help-seeking with limited research positing social norms within men's peer groups and reciprocity as potential mental health help-seeking enablers. Using a qualitative design, nine men were interviewed to identify the positive factors they believed assisted their help-seeking decisions. Social norms, reciprocity, a significant other, and helpfulness of their general practitioner were domains identified in the analysis of participant narratives. The study revealed the participants' mental health and treatment illiteracy. Ignorance and misplaced stereotypes, initially acted as barriers to help-seeking, leading to denial of illness, impeding treatment, and perpetuating stigma. Sportsmen disclosing their mental health issues were identified as a positive influence for other men's help-seeking and assisted in the development of help-seeking as a social norm. The results of this study contribute to understanding the factors that enable men to seek mental health help.

Nurr1 dependent regulation of pro-inflammatory mediators in immortalised synovial fibroblasts.

BACKGROUND: Nurr1 is an orphan member of the nuclear receptor superfamily; these orphan receptors are a group for which a ligand has yet to be identified. Nurr1 has been shown to regulate the expression of a small number of genes as a monomeric, constitutively active receptor. These Nurr1 regulated genes are primarily associated with dopamine cell maturation and survival. However, previous reports have shown an increased expression of Nurr1 in the synovium of patients with rheumatoid arthritis (RA) suggesting a pro-inflammatory role for Nurr1 in RA. In this study we investigate the potential pro-inflammatory role of Nurr1 by monitoring Nurr1 dependent gene expression in an immortalised synoviocyte cell line, K4IM. METHODS: We overexpressed the wild type and a dominant negative form of the orphan nuclear receptor Nurr1, in a model synoviocyte cell line. Using the Affymetrix HG-U133 Genechips we demonstrate the effects on the transcriptome by the receptor. Further evidence of gene expression change was demonstrated using quantitative RT-PCR and ELISA analysis. RESULTS: We show that Nurr1 regulates transcription of a small number of genes for pro-inflammatory modulators of which the most significant is interleukin-8 (IL-8). We also demonstrate increased synthesis and secretion of IL-8 further supporting a role for Nurr1 in inflammatory signalling pathways. CONCLUSION: Using microarray analysis we show that elevated levels of Nurr1 leads to increased gene expression of pro-inflammatory genes: IL-8, Amphiregulin and Kit ligand in a model cell line. This data provides further evidence for an additional role for Nurr1 in inflammation and may play a role in the pathogenesis of rheumatoid arthritis.

It's a rave new world: estimating the prevalence and perceived harm of ecstasy and other drug use among club rave attendees.

The use of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") appears to be increasing worldwide, with "rave" attendees being one high-risk population. To date, however, only one study has collected ecstasy use information from rave attendees in the United States. To address this limitation, we collected self-report drug use information from 70 adult "club rave" attendees within the Baltimore-Washington corridor in April and May 2002. Data collection was scheduled between 12 A.M. and 5 A.M. Participation rates were high, with 85 percent of the club rave attendees completing the interview. Eighty-six percent of the respondents reported lifetime ecstasy use, 51 percent reported 30-day use, and 30 percent reported using ecstasy within the two days preceding the interview. While past-year ecstasy users were comparable to non-users with respect to a host of demographic and drug use variables, non-ecstasy users were significantly more likely than past-year users to perceive risks associated with the regular use of alcohol and ecstasy. Not surprisingly, non-ecstasy users were significantly more likely than past-year users to perceive harmful long-term physical and psychological effects associated with ecstasy ingestion. These findings suggest that rave attendees may be an important population for ecstasy-related prevention efforts.

Hit-to-lead studies: the discovery of potent, orally active, thiophenecarboxamide IKK-2 inhibitors.

A hit-to-lead optimisation programme was carried out on the thiophenecarboxamide high throughput screening hits 1 and 2 resulting in the discovery of the potent and orally bioavailable IKK-2 inhibitor 22.