GPs understanding of how depression affects gay and HIV positive men

In contrast to the broad literature on depression in the general population, little is known about the management of depression affecting gay men and HIV-positive men attending general practice clinics. GPs identified a range of features in their experience of managing depression in gay men and in HIV-positive men. Some were common to the care of other groups with depression, but this paper reports on features unique to this patient group. These include capitalizing on the high frequency of contact with this patient group, taking advantage of the specialist multidisciplinary teams who provide support, building upon the unusual willingness of this patient group to take medication, appreciating the central importance to many gay men of sexual functioning, and recreational drug use, responding to social isolation in this patient group and coping with increasing challenges for the HIV general practice workforce

Diet-induced leukocyte telomere shortening in a baboon model for early stage atherosclerosis

Reported associations between leukocyte telomere length (LTL) attrition, diet and cardiovascular disease (CVD) are inconsistent. This study explores effects of prolonged exposure to a high cholesterol high fat (HCHF) diet on LTL in a baboon model of atherosclerosis. We measured LTL by qPCR in pedigreed baboons fed a chow (n = 105) or HCHF (n = 106) diet for 2 years, tested for effects of diet on LTL, and association between CVD risk factors and atherosclerotic lesions with LTL. Though not different at baseline, after 2 years median LTL is shorter in HCHF fed baboons (P \u3c 0.0001). Diet predicts sex- and age-adjusted LTL and LTL attrition (P = 0.0009 and 0.0156, respectively). Serum concentrations of CVD biomarkers are associated with LTL at the 2-year endpoint and LTL accounts approximately 6% of the variance in aortic lesions (P = 0.04). Although heritable at baseline (h2 = 0.27, P = 0.027) and after 2 years (h2 = 0.46, P = 0.0038), baseline LTL does not predict lesion extent after 2 years. Atherogenic diet influences LTL, and LTL is a potential biomarker for early atherosclerosis. Prolonged exposure to an atherogenic diet decreases LTL and increases LTL attrition, and shortened LTL is associated with early-stage atherosclerosis in pedigreed baboons

Hepatic transcript signatures predict atherosclerotic lesion burden prior to a 2-year high cholesterol, high fat diet challenge

The purpose of this study was to identify molecular mechanisms by which the liver influences total lesion burden in a nonhuman primate model (NHP) of cardiovascular disease with acute and chronic feeding of a high cholesterol, high fat (HCHF) diet. Baboons (47 females, 64 males) were fed a HCHF diet for 2 years (y); liver biopsies were collected at baseline, 7 weeks (w) and 2y, and lesions were quantified in aortic arch, descending aorta, and common iliac at 2y. Unbiased weighted gene co-expression network analysis (WGCNA) revealed several modules of hepatic genes correlated with lesions at different time points of dietary challenge. Pathway and network analyses were performed to study the roles of hepatic module genes. More significant pathways were observed in males than females. In males, we found modules enriched for genes in oxidative phosphorylation at baseline, opioid signaling at 7w, and EIF2 signaling and HNF1A and HNF4A networks at baseline and 2y. One module enriched for fatty acid β oxidation pathway genes was found in males and females at 2y. To our knowledge, this is the first study of a large NHP cohort to identify hepatic genes that correlate with lesion burden. Correlations of baseline and 7w module genes with lesions at 2y were observed in males but not in females. Pathway analyses of baseline and 7w module genes indicate EIF2 signaling, oxidative phosphorylation, and μ-opioid signaling are possible mechanisms that predict lesion formation induced by HCHF diet consumption in males. Our findings of coordinated hepatic transcriptional response in male baboons but not female baboons indicate underlying molecular mechanisms differ between female and male primate atherosclerosis

Experiences in managing problematic crystal methamphetamine use and associated depression in gay men and HIV positive men: in-depth interviews with general practitioners in Sydney, Australia

© 2008 Saltman et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background This paper describes the experiences of Australian general practitioners (GPs) in managing problematic crystal methamphetamine (crystal meth) use among two groups of male patients: gay men and HIV positive men. Methods Semi-structured qualitative interviews with GPs with HIV medication prescribing rights were conducted in Sydney, Adelaide and a rural-coastal town in New South Wales between August and October 2006. Participants were recruited from practices with high caseloads of gay and HIV positive men. Results Sixteen GPs were recruited from seven practices to take part in interviews. Participants included 14 male GPs and two female GPs, and the number of years each had been working in HIV medicine ranged from two to 24. Eleven of the GPs who were based in Sydney raised the issue of problematic crystal meth use in these two patient populations. Five key themes were identified: an increasing problem; associations with depression; treatment challenges; health services and health care; workforce issues. Conclusion Despite study limitations, key implications can be identified. Health practitioners may benefit from broadening their understandings of how to anticipate and respond to problematic levels of crystal meth use in their patients. Early intervention can mitigate the impact of crystal meth use on co-morbid mental illness and other health issues. Management of the complex relationships between drug use, depression, sexuality and HIV can be addressed following a 'stepped care' approach. General practice guidelines for the management of crystal meth use problems should address specific issues associated with gay men and HIV positive men. GPs and other health practitioners must appreciate drug use as a social practice in order to build trust with gay men to encourage full disclosure of drug use. Education programs should train health practitioners in these issues, and increased resourcing provided to support the often difficult task of caring for people who use crystal meth. Greater resourcing of acute care and referral services can shift the burden away from primary care and community services. Further investigation should consider whether these findings are reproducible in other general practice settings, the relationship between depression, drug use and HIV medication, and challenges facing the HIV general practice workforce in Australia

An evaluation of the integration of non-traditional learning tools into a community based breast and cervical cancer education program: The witness project of Buffalo

BACKGROUND: Breast and cervical cancer continue to represent major health challenges for African American women. among Caucasian women. The underlying reasons for this disparity are multifactorial and include lack of education and awareness of screening and early detection. Traditional educational methods have enjoyed varied success in the African American community and spawned development of novel educational approaches. Community based education programs employing a variety of educational models have been introduced. Successful programs must train and provide lay community members with the tools necessary to deliver strong educational programs. METHODS: The Witness Project is a theory-based, breast and cervical cancer educational program, delivered by African American women, that stresses the importance of early detection and screening to improve survival and teaches women how to perform breast self examination. Implementing this program in the Buffalo Witness Project of Buffalo required several modifications in the curriculum, integration of non-traditional learning tools and focused training in clinical study participation. The educational approaches utilized included repetition, modeling, building comprehension, reinforcement, hands on learning, a social story on breast health for African American women, and role play conversations about breast and cervical health and support. RESULTS: Incorporating non-traditional educational approaches into the Witness Project training resulted in a 79% improvement in the number of women who mastered the didactic information. A seventy-two percent study participation rate was achieved by educating the community organizations that hosted Witness Project programs about the informed consent process and study participation. CONCLUSION: Incorporating non-traditional educational approaches into community outreach programs increases training success as well as community participation

Assessment of F/HN-Pseudotyped Lentivirus as a Clinically Relevant Vector for Lung Gene Therapy

RATIONALE: Ongoing efforts to improve pulmonary gene transfer thereby enabling gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF), has led to the assessment of a lentiviral vector (simian immunodeficiency virus [SIV]) pseudotyped with the Sendai virus envelope proteins F and HN. OBJECTIVES: To place this vector onto a translational pathway to the clinic by addressing some key milestones that have to be achieved. METHODS: F/HN-SIV transduction efficiency, duration of expression, and toxicity were assessed in mice. In addition, F/HN-SIV was assessed in differentiated human air-liquid interface cultures, primary human nasal epithelial cells, and human and sheep lung slices. MEASUREMENTS AND MAIN RESULTS: A single dose produces lung expression for the lifetime of the mouse (~2 yr). Only brief contact time is needed to achieve transduction. Repeated daily administration leads to a dose-related increase in gene expression. Repeated monthly administration to mouse lower airways is feasible without loss of gene expression. There is no evidence of chronic toxicity during a 2-year study period. F/HN-SIV leads to persistent gene expression in human differentiated airway cultures and human lung slices and transduces freshly obtained primary human airway epithelial cells. CONCLUSIONS: The data support F/HN-pseudotyped SIV as a promising vector for pulmonary gene therapy for several diseases including CF. We are now undertaking the necessary refinements to progress this vector into clinical trials

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

The Efficacy of Auditory Perceptual Training for Tinnitus: A Systematic Review

Auditory perceptual training affects neural plasticity and so represents a potential strategy for tinnitus management. We assessed the effects of auditory perceptual training on tinnitus perception and/or its intrusiveness via a systematic review of published literature. An electronic database search using the keywords ‘tinnitus and learning’ or ‘tinnitus and training’ was conducted, updated by a hand search. The ten studies identified were reviewed independently by two reviewers, data were extracted, study quality was assessed according to a number of specific criteria and the information was synthesised using a narrative approach. Nine out of the ten studies reported some significant change in either self-reported or psychoacoustic outcome measures after auditory training. However, all studies were quality rated as providing low or moderate levels of evidence for an effect. We identify a need for appropriately randomised and controlled studies that will generate high-quality unbiased and generalisable evidence to ascertain whether or not auditory perceptual training has a clinically relevant effect on tinnitus

Genetic variant rs1205 is associated with COVID-19 outcomes: The Strong Heart Study and Strong Heart Family Study

Background Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. Methodology/Principal findings The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 3’ untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001–3.453, p = 0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. Conclusion A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted