Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence.

Considerable evidence suggests that transmission at hypocretin-1 (orexin-1) receptors (Hcrt-R1) plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV) cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg) dose-dependently decreased cocaine (0.5 mg/kg/infusion) self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg) also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg) on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts

Twice-daily versus once-daily antiretroviral therapy and coformulation strategies in HIV-infected adults: benefits, risks, or burden?

The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices

Acceptability and feasibility of point-of-care CD4 testing on HIV continuum of care in low and middle income countries: a systematic review

Background: CD4 testing is, and will remain an important part of HIV treatment and care in low and middle income countries (LMICs). We report the findings of a systematic review assessing acceptability and feasibility of POC CD4 testing in field settings. Methods: Electronic databases were searched for studies published in English between 2005 and 2015 that describe POC CD4 platforms. Studies conducted in LMICs and under field conditions outside a laboratory environment were eligible. Qualitative and descriptive data analysis was used to present the findings. Results: Twelve studies were included, 11 of which were conducted in sub-Saharan countries and used one POC CD4 test (The Alere Pima CD4). Patients reported positively regarding the implementation of POC CD4 testing at primary health care and community level with ≥90 % of patients accepting the test across various study settings. Health service providers expressed preference toward POC CD4 testing as it is easy-to-use, efficient and satisfied patients\u27 needs to a greater extent as compared to conventional methods. However, operational challenges including preference toward venous blood rather than finger-prick sampling, frequent device failures and operator errors, quality of training for test operators and supervisors, and increased staff workload were also identified. Conclusions: POC CD4 testing seems acceptable and feasible in LIMCs under field conditions. Further studies using different POC CD4 tests available on the market are required to provide critical data to support countries in selection and implementation of appropriate POC CD4 technologies

Erratum : GEOTRACES radium isotopes interlaboratory comparison experiment

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2012. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography: Methods 10 (2012): 617, doi:10.4319/lom.2012.10.617.In our original paper, Charette, M. A., H. Dulaiova, M. E. Gonneea, P. B. Henderson, W. S. Moore, J. C. Scholten, and M. K. Pham. 2012. GEOTRACES radium isotopes interlaboratory comparison experiment. Limonol. Oceanogr.: Methods 10:451, the incorrect headers were used for Table 9

GEOTRACES radium isotopes interlaboratory comparison experiment

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2012. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography: Methods 10 (2012): 451-463, doi:10.4319/lom.2012.10.451.In anticipation of the international GEOTRACES program, which will study the global marine biogeochemistry of trace elements and isotopes, we conducted a multi-lab intercomparison for radium isotopes. The intercomparison was in two parts involving the distribution of: (1) samples collected from four marine environments (open ocean, continental slope, shelf, and estuary) and (2) a suite of four reference materials prepared with isotopic standards (circulated to participants as 'unknowns'). Most labs performed well with 228Ra and 224Ra determination, however, there were a number of participants that reported 226Ra, 223Ra, and 228Th (supported 224Ra) well outside the 95% confidence interval. Many outliers were suspected to be a result of poorly calibrated detectors, though other method specific factors likely played a role (e.g., detector leakage, insufficient equilibration). Most methods for radium analysis in seawater involve a MnO2 fiber column preconcentration step; as such, we evaluated the extraction efficiency of this procedure and found that it ranged from an average of 87% to 94% for the four stations. Hence, nonquantitative radium recovery from seawater samples may also have played a role in lab-to-lab variability.This work was funded by grants from the National Science Foundation (OCE- 0751461to M.A.C and H.D. and OCE- 0751867 to W.S.M.)

Factors associated with HIV testing among young men who have sex with men in Myanmar: a cross-sectional study

Introduction: In Myanmar, men who have sex with men (MSM) experience high risk of HIV infection. However, access to HIV testing and prevention services remains a challenge among this marginalized population. The objective of this study was to estimate population prevalence and correlates of prior HIV testing among young MSM (YMSM) and informs the development of HIV testing and intervention programmes that respond to the specific needs of this population. Methods: Five hundred and eighty-five YMSM aged 18 to 24 years were recruited using respondent-driven sampling (RDS) in a cross-sectional survey conducted in six townships of Myanmar. RDS-adjusted population estimates were calculated to estimate prevalence of HIV testing; RDS-weighted logistic regression was used to examine correlates of HIV testing in the past 6 months and in a lifetime. Results: There were 12 participants who reported receiving a HIV-positive test; of those, five were tested in the past 6 months. The RDS-weighted prevalence estimates of lifetime (any prior) HIV testing was 60.6% (95% CI: 53.3% to 66.4%) and of recent (≤ 6 months) HIV testing was 50.1% (95% CI: 44.1% to 55.5%). In multivariable analysis, sexual identity was associated with lifetime but not recent HIV testing. Lifetime and recent HIV testing were associated with having three or more male sexual partners in the past 12 months (adjusted ORs (aORs) = 2.28, 95% CIs: 1.21 to 4.32 and 2.69, 95% CI: 1.59 to 4.56), having good HIV-related knowledge (aORs = 1.96, 95% CIs: 1.11 to 3.44 and 1.77, 95% CI: 1.08 to 2.89), reporting high HIV testing self-efficacy (aORs = 13.5, 95% CIs: 6.0 to 30.1 and 9.81, 95% CI: 4.27 to 22.6) and having access to and use of non-HIV health-related services in the past 12 months (aORs = 13.2, 95% CIs: 6.85 to 25.6 and 7.15, 95% CI: 4.08 to 12.5) respectively. Conclusions: HIV testing coverage among YMSM aged 18 to 24 years old in Myanmar is still suboptimal. Integrated HIV testing and prevention services in existing health service provision systems with tailored HIV information and education programmes targeting YMSM to improve HIV-related knowledge and self-efficacy may help to promote regular HIV testing behaviour and contribute to sustainable control of the HIV epidemic among this marginalized population in Myanmar

Relationship between self-efficacy and HIV testing uptake among young men who have sex with men in Myanmar: a cross-sectional analysis

Men who have sex with men (MSM) are disproportionally affected by the HIV epidemic. Self-efficacy is an important individual psychosocial factor associated with access to and use of health and HIV-related services. We estimated HIV testing prevalence and examined the relationship between HIV testing self-efficacy and self-reported HIV testing behavior among young MSM (YMSM) in Myanmar. We enrolled 585 MSM aged 18–24 years from six urban areas using respondent-driven sampling (RDS) technique. RDS analyses were performed to provide estimates for the key outcome of interest. More than a third (34.5%) had never been tested for HIV, whereas 27.5% and 38.0% had their most recent HIV test more than three months and within the past three months from the time of interview, respectively. Young MSM who reported high self-efficacy (adjusted relative risk ratio [ARR]=7.35, 95%CI = 2.29–23.5) and moderate self-efficacy (ARR = 8.61, 95%CI = 3.09–24.0) were more likely to report having tested for HIV in the past three months compared to their counterparts who reported low self-efficacy. Findings highlight a positive association between self-efficacy and HIV testing uptake, indicating a potential causal relationship. Further research is needed to examine the direction of this association and inform future public health interventions targeting YMSM in Myanmar

Microstructural Alterations and Oligodendrocyte Dysmaturation in White Matter After Cardiopulmonary Bypass in a Juvenile Porcine Model.

BACKGROUND: Newly developed white matter (WM) injury is common after cardiopulmonary bypass (CPB) in severe/complex congenital heart disease. Fractional anisotropy (FA) allows measurement of macroscopic organization of WM pathology but has rarely been applied after CPB. The aims of our animal study were to define CPB-induced FA alterations and to determine correlations between these changes and cellular events after congenital heart disease surgery. METHODS AND RESULTS: Normal porcine WM development was first assessed between 3 and 7 weeks of age: 3-week-old piglets were randomly assigned to 1 of 3 CPB-induced insults. FA was analyzed in 31 WM structures. WM oligodendrocytes, astrocytes, and microglia were assessed immunohistologically. Normal porcine WM development resembles human WM development in early infancy. We found region-specific WM vulnerability to insults associated with CPB. FA changes after CPB were also insult dependent. Within various WM areas, WM within the frontal cortex was susceptible, suggesting that FA in the frontal cortex should be a biomarker for WM injury after CPB. FA increases occur parallel to cellular processes of WM maturation during normal development; however, they are altered following surgery. CPB-induced oligodendrocyte dysmaturation, astrogliosis, and microglial expansion affect these changes. FA enabled capturing CPB-induced cellular events 4 weeks postoperatively. Regions most resilient to CPB-induced FA reduction were those that maintained mature oligodendrocytes. CONCLUSIONS: Reducing alterations of oligodendrocyte development in the frontal cortex can be both a metric and a goal to improve neurodevelopmental impairment in the congenital heart disease population. Studies using this model can provide important data needed to better interpret human imaging studies