Faculty Bibliography

The feasibility of long-term extended-release naltrexone (XR-NTX) alcohol treatment is unknown. Following an initial 12-week, single-arm, observational trial of XR-NTX plus medical management (MM) in primary care, we offered 48 additional weeks of XR-NTX treatment (12 additional monthly injections) in two public primary care clinics as a naturalistic extension study. Of 65 alcohol dependent adults initiating XR-NTX treatment, 40 (62%) completed the initial 12-week XR-NTX observational trial, and 19 (29%) continued treatment for a median of 38weeks total (range, 16-72weeks; median 8 total XR-NTX injections). Among active extension phase participants, self-reported rates of drinking days (vs. last 30 days pre-treatment baseline) were low: median 0.2 vs. 6.0drinks per day; 82 vs. 38% days abstinent; 11 vs. 61% heavy drinking days. Long-term XR-NTX treatment in a primary care MM model was feasible and may promote lasting drinking reductions or alcohol abstinence (clinical trial: NCT00620750).

The Affordable Care Act (ACA) includes provisions to shift the U.S. health care system to address achieving wellness rather than just treating illness. In this Open Forum, the Prevention Committee of the Group for the Advancement of Psychiatry describes opportunities created by the ACA for improving prevention of mental illnesses and promotion of mental health. These include improved coverage of preventive services, models to integrate primary and behavioral health care, and establishment of the National Prevention, Health Promotion, and Public Health Council, which has developed a National Prevention Strategy. The authors describe the important role that psychiatrists can play in advancing prevention of mental illnesses, in particular by working to incorporate prevention strategies in integrated care initiatives and by collaborating with primary care providers to screen for risk factors and promote mental and emotional well-being.

Though altruism and patient advocacy are promoted in medical education curricula, students are given few opportunities to develop these skills. Student-run clinics focusing on the health needs of the underserved can provide important health services to needy patients while providing students with career-influencing primary care experiences. The Columbia-Harlem Homeless Medical Partnership (CHHMP)-a project initiated by medical students to provide primary care to Northern Manhattan's homeless population-serves as a new model of service learning in medical education. Unlike many other student-run clinics, CHHMP has developed direct patient outreach, continuous care (stable "student-patient teams" and a weekly commitment for all volunteers), and regular internal data review. Chart review data presented demonstrate the project's success in providing care to the clinic's target population of homeless and unstably housed patients. Targeted outreach efforts among clients have increased rates of patient follow-up at each subsequent review period. Additionally, CHHMP has used review data to develop services concordant with identified patient needs (psychiatric care and social services). CHHMP has recruited a committed group of volunteers and continues to engender an interest in the health needs of the underserved among students. Not only does CHHMP provide a "medical home" for homeless patients, it also provides a space in which students can develop skills unaddressed in large teaching hospitals. This project, a "win-win" for patients and students, serves as a unique model for community health-based service learning in medical education.

The EXPLORE study evaluated a behavioral intervention to prevent HIV infection among MSM. We examined depressive symptoms, utilization of mental health care, substance use and HIV risk taking behaviors in YMSM aged 16-25 years compared with their older counterparts. YMSM were more likely to report depressive symptoms (OR = 1.55) and less likely to report use of counseling (OR = 0.39) or medication (OR = 0.20) for psychiatric conditions. YMSM were more likely to report heavy alcohol and drug use. YMSM more often reported engaging in unprotected insertive (OR = 1.60) and receptive (OR = 2.07) anal intercourse with presumed HIV-uninfected partners, and unprotected receptive (OR = 1.72) anal intercourse with partners of unknown-HIV status. These findings suggest the need for more appropriate and accessible mental health care and substance use services for YMSM. Additionally, HIV prevention work with this population should provide comprehensive education about HIV testing and risk reduction counseling that focuses on communication about serostatus and safety in sexual situations.

The EXPLORE study evaluated a behavioral intervention to prevent HIV seroconversion among men who have sex with men (MSM). The present ancillary study enrolled 345 EXPLORE participants at one study site (Boston) and assessed high-risk sexual behavior with other EXPLORE participants. It also assessed sexual intentions across other EXPLORE participants, HIV-negative individuals, and unknown HIV serostatus partners. Thirty-one percent reported having sex with another EXPLORE participant: 27% unprotected receptive oral sex with ejaculation (UO), 30% unprotected insertive anal sex (UIA), and 34% reported unprotected receptive anal sex (URA). Significant relationships between intentions to engage in UO, UIA, and URA, and type of partner emerged with intentions to engage in UO, UIA, and URA higher in HIV-negative partners, other EXPLORE participants, and unknown-HIV serostatus partners. Future HIV-prevention studies recruiting MSM at increased sexual risk of HIV infection should address participants potentially becoming sexual partners with each other.

Despite irrefutable evidence that asbestos causes asbestosis, lung cancer, and mesothelioma, asbestos mining, milling, and manufacturing continue. The authors discuss three scientific debates over the roles of fiber types, viruses, and genetics in the development of mesothelioma. While these controversies might appear internal to science and unconnected to policies of the global asbestos industry, they argue that scientific debates, whether or not fostered by industry, play a central role in shaping conceptualization of the problem of asbestos-related disease. In South Africa, India, and elsewhere, these controversies help to make the disease experience of asbestos-exposed workers and people in asbestos-contaminated communities invisible, allowing the asbestos industry to escape accountability for its practices.

In past reports we illustrated the importance of Y131, Y322, and T137 within the intracellular (IC) face of the rat bradykinin B2 receptor (rBKB2R) for signal transduction and receptor maintenance (Prado et al. [1997] J. Biol. Chem. 272:14638-14642; Prado et al. [1998] J. Biol. Chem. 273:33548-33555). In this report, we mutate the remaining hydroxyl possessing residues located within the rBKB2R IC region. Exchange of S139A (IC2) or T239V (IC3) did not affect BK activated phosphatidylinositol (PI) turnover or receptor internalization. Chimeric exchange of the last 34 amino acids of BKB2R C-terminus with the corresponding 34 amino acids of the rat angiotensin II AT1a receptor (rAT1aR), both containing an S/T cluster, resulted in a mutant with normal endocytosis and BK activated PI turnover. A more selective chimera of these S/T clusters, with an exchange of BKB2R (333-351) with a rAT1aR fragment (326-342), resulted in a receptor with a retarded internalization but a normal BK activated PI turnover. Subsequent mutation of rBKB2R T344V showed little change in receptor uptake but a pronounced loss of BK activated PI turnover. The mutation of S335A, S341A, S348A, and S350A resulted in very poor receptor internalization and loss of activated PI turnover. Closer examination of this serine cluster illustrated that the replacement of S348A led to poor internalization; whereas the retention of S348 and mutation of S341A resulted in a receptor with a much greater internalization than WT. These and other results suggest that the presence of S348 promotes internalization while the presence of S341 dampens it. Conversely, S341 and S350 proved important for receptor signaling. In sum, our results illustrate that the distal C-terminus including its S/T cluster is important for both rBKB2R internalization and signal transduction. Individual S/T residues within this cluster appear involved in either signal transmission or receptor uptake capacity. However, replacement of the entire distal tail region with the corresponding rAT1aR sequence, also containing an S/T cluster, enables the BKB2R/AT1aR chimera to act in a very similar manner to wild type rBKB2R.