Sortilin Participates in Light-dependent Photoreceptor Degeneration in Vivo

Both proNGF and the neurotrophin receptor p75 (p75NTR) are known to regulate photoreceptor cell death caused by exposure of albino mice to intense illumination. ProNGF-induced apoptosis requires the participation of sortilin as a necessary p75NTR co-receptor, suggesting that sortilin may participate in the photoreceptor degeneration triggered by intense lighting. We report here that light-exposed albino mice showed sortilin, p75NTR, and proNGF expression in the outer nuclear layer, the retinal layer where photoreceptor cell bodies are located. In addition, cone progenitor-derived 661W cells subjected to intense illumination expressed sortilin and p75NTR and released proNGF into the culture medium. Pharmacological blockade of sortilin with either neurotensin or the “pro” domain of proNGF (pro-peptide) favored the survival of 661W cells subjected to intense light. In vivo, the pro-peptide attenuated retinal cell death in light-exposed albino mice. We propose that an auto/paracrine proapoptotic mechanism based on the interaction of proNGF with the receptor complex p75NTR/sortilin participates in intense light-dependent photoreceptor cell death. We therefore propose sortilin as a putative target for intervention in hereditary retinal dystrophies

A systematic review of mental disorder, suicide, and deliberate self harm in lesbian, gay and bisexual people

Background: Lesbian, gay and bisexual (LGB) people may be at higher risk of mental disorders than heterosexual people.Method: We conducted a systematic review and meta-analysis of the prevalence of mental disorder, substance misuse, suicide, suicidal ideation and deliberate self harm in LGB people. We searched Medline, Embase, PsycInfo, Cinahl, the Cochrane Library Database, the Web of Knowledge, the Applied Social Sciences Index and Abstracts, the International Bibliography of the Social Sciences, Sociological Abstracts, the Campbell Collaboration and grey literature databases for articles published January 1966 to April 2005. We also used Google and Google Scholar and contacted authors where necessary. We searched all terms related to homosexual, lesbian and bisexual people and all terms related to mental disorders, suicide, and deliberate self harm. We included papers on population based studies which contained concurrent heterosexual comparison groups and valid definition of sexual orientation and mental health outcomes.Results: Of 13706 papers identified, 476 were initially selected and 28 (25 studies) met inclusion criteria. Only one study met all our four quality criteria and seven met three of these criteria. Data was extracted on 214,344 heterosexual and 11,971 non heterosexual people. Meta-analyses revealed a two fold excess in suicide attempts in lesbian, gay and bisexual people [ pooled risk ratio for lifetime risk 2.47 (CI 1.87, 3.28)]. The risk for depression and anxiety disorders (over a period of 12 months or a lifetime) on meta-analyses were at least 1.5 times higher in lesbian, gay and bisexual people (RR range 1.54-2.58) and alcohol and other substance dependence over 12 months was also 1.5 times higher (RR range 1.51-4.00). Results were similar in both sexes but meta analyses revealed that lesbian and bisexual women were particularly at risk of substance dependence (alcohol 12 months: RR 4.00, CI 2.85, 5.61; drug dependence: RR 3.50, CI 1.87, 6.53; any substance use disorder RR 3.42, CI 1.97-5.92), while lifetime prevalence of suicide attempt was especially high in gay and bisexual men (RR 4.28, CI 2.32, 7.88).Conclusion: LGB people are at higher risk of mental disorder, suicidal ideation, substance misuse, and deliberate self harm than heterosexual people

Perceptions of clinicians and staff about the use of digital technology in primary care: qualitative interviews prior to implementation of a computer-facilitated 5As intervention

BACKGROUND: Digital health interventions using hybrid delivery models may offer efficient alternatives to traditional behavioral counseling by addressing obstacles of time, resources, and knowledge. Using a computer-facilitated 5As (ask, advise, assess, assist, arrange) model as an example (CF5As), we aimed to identify factors from the perspectives of primary care providers and clinical staff that were likely to influence introduction of digital technology and a CF5As smoking cessation counseling intervention. In the CF5As model, patients self-administer a tablet intervention that provides 5As smoking cessation counseling, produces patient and provider handouts recommending next steps, and is followed by a patient-provider encounter to reinforce key cessation messages, provide assistance, and arrange follow-up. METHODS: Semi-structured in-person interviews of administrative and clinical staff and primary care providers from three primary care clinics. RESULTS: Thirty-five interviews were completed (12 administrative staff, ten clinical staff, and 13 primary care providers). Twelve were from an academic internal medicine practice, 12 from a public hospital academic general medicine clinic, and 11 from a public hospital HIV clinic. Most were women (91 %); mean age (SD) was 42 years (11.1). Perceived usefulness of the CF5As focused on its relevance for various health behavior counseling purposes, potential gains in counseling efficiency, confidentiality of data collection, occupying patients while waiting, and serving as a cue to action. Perceived ease of use was viewed to depend on the ability to accommodate: clinic workflow; heavy patient volumes; and patient characterisitics, e.g., low literacy. Social norms potentially affecting implementation included beliefs in the promise/burden of technology, priority of smoking cessation counseling relative to other patient needs, and perception of CF5As as just “one more thing to do” in an overburdened system. The most frequently cited facilitating conditions were staffing levels and smoking cessation resources and training; the most cited hindering factors were visit time constraints and patients’ complex health care needs. CONCLUSIONS: Integrating CF5As and other technology-enhanced behavioral counseling interventions in primary care requires flexibility to accommodate work flow and perceptions of overload in dynamic environments. Identifying factors that promote and hinder CF5As adoption could inform implementation of other CF behavioral health interventions in primary care