Suicide risk factors among trans feminine individuals in Lebanon.

Transgender women are disproportionately affected by high rates of depression and suicide attempts. It is therefore important to identify factors that influence suicidal risk, particularly in the Middle East where little research has examined the mental health of transgender women. We examined risk factors associated with suicide attempts among 54 trans feminine individuals in Beirut, Lebanon. Data were collected using interviewer-administered questionnaires and analyzed using bivariate statistics. Twenty-five (46%) participants reported having ever attempted suicide. Among them, only one participant received some kind of counseling in response to the attempted suicide. Low general social support, low social integration, and low support from peers were significantly associated with a history of attempted suicide, as were being more open about transgender identity in public and any hormone use (past or current). These findings suggest that progression in gender transition can have unintended consequences related to mental health and suicide risk, while social support systems can mitigate the impact of mental health problems. Some of these findings mirror other contexts around the globe and can inform mental health services for trans feminine individuals in Lebanon, the greater Middle East region, and other international settings.

The Affordable Care Act: an opportunity for improving care for substance use disorders?

The Patient Protection and Affordable Care Act (ACA) will greatly increase coverage for treatment of substance use disorders. To realize the benefits of this opportunity, it is critical to develop reliable, valid, and feasible measures of quality to ensure that treatment is accessible and of high quality. The authors review the availability of current quality measures for substance use disorder treatment and conclude there is a pressing need for development, validation, and use of quality measures. They provide recommendations for research and policy changes to increase the likelihood that patients, families, and society benefit from the increased coverage provided by the ACA.

Bundled payment fails to gain a foothold In California: the experience of the IHA bundled payment demonstration.

To determine whether bundled payment could be an effective payment model for California, the Integrated Healthcare Association convened a group of stakeholders (health plans, hospitals, ambulatory surgery centers, physician organizations, and vendors) to develop, through a consensus process, the methods and means of implementing bundled payment. In spite of a high level of enthusiasm and effort, the pilot did not succeed in its goal to implement bundled payment for orthopedic procedures across multiple payers and hospital-physician partners. An evaluation of the pilot documented a number of barriers, such as administrative burden, state regulatory uncertainty, and disagreements about bundle definition and assumption of risk. Ultimately, few contracts were signed, which resulted in insufficient volume to test hypotheses about the impact of bundled payment on quality and costs. Although bundled payment failed to gain a foothold in California, the evaluation provides lessons for future bundled payment initiatives.

A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells.

Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells among which a tumor-initiating and treatment-resistant subpopulation, here termed GBM stem cells, have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GBM stem cells. The paradigm uses a tissue culture model to enrich for GBM stem cells derived from human GBM resections and combines a phenotype-based screen with gene target-specific screens for compound identification. We used 31,624 small molecules from 7 chemical libraries that we characterized and ranked based on their effect on a panel of GBM stem cell-enriched cultures and their effect on the expression of a module of genes whose expression negatively correlates with clinical outcome: MELK, ASPM, TOP2A, and FOXM1b. Of the 11 compounds meeting criteria for exerting differential effects across cell types used, 4 compounds showed selectivity by inhibiting multiple GBM stem cells-enriched cultures compared with nonenriched cultures: emetine, n-arachidonoyl dopamine, n-oleoyldopamine (OLDA), and n-palmitoyl dopamine. ChemBridge compounds #5560509 and #5256360 inhibited the expression of the 4 mitotic module genes. OLDA, emetine, and compounds #5560509 and #5256360 were chosen for more detailed study and inhibited GBM stem cells in self-renewal assays in vitro and in a xenograft model in vivo. These studies show that our screening strategy provides potential candidates and a blueprint for lead compound identification in larger scale screens or screens involving other cancer types.

Mapping of the full length and the truncated interleukin-18 receptor alpha in the mouse brain.

The cytokine IL-18 acts on the CNS both in physiological and pathological conditions. Its action occurs through the heterodimeric receptor IL-18Ralpha\beta. To better understand IL-18 central effects, we investigated in the mouse brain the distribution of two IL-18Ralpha transcripts, a full length and an isoform lacking the intracellular domain hypothesized to be a decoy receptor. Both isoforms were expressed in neurons throughout the brain primarily with overlapping distribution but also with some unique pattern. These data suggest that IL-18 may modulate neuronal functions and that its action may be regulated through expression of a decoy receptor.