Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler.

Virtually all aspects of cell biology are regulated by a ubiquitin code where distinct ubiquitin chain architectures guide the binding events and itineraries of modified substrates. Various combinations of E2 and E3 enzymes accomplish chain formation by forging isopeptide bonds between the C terminus of their transiently linked donor ubiquitin and a specific nucleophilic amino acid on the acceptor ubiquitin, yet it is unknown whether the fundamental feature of most acceptors-the lysine side chain-affects catalysis. Here, use of synthetic ubiquitins with non-natural acceptor site replacements reveals that the aliphatic side chain specifying reactive amine geometry is a determinant of the ubiquitin code, through unanticipated and complex reliance of many distinct ubiquitin-carrying enzymes on a canonical acceptor lysine.

Inconsistent condom use with known HIV-positive partners among newly diagnosed HIV-positive men who have sex with men interviewed for partner services in New York City, 2014.

OBJECTIVES: Condomless anal intercourse contributes significantly to the spread of HIV among men who have sex with men (MSM). Factors related to condomless anal intercourse with known HIV-positive partners among MSM are not well understood. The authors describe factors associated with inconsistent condom use with known HIV-positive partners prior to participants' diagnosis with HIV. METHODS: New York City health department disease intervention specialists interviewed newly HIV-diagnosed MSM ages ≥13 years reporting knowingly having anal sex with HIV-positive partners between June 2013 and October 2014. Univariate and bivariate statistics were calculated, in addition to logistic regression analysis. RESULTS: Among 95 MSM interviewed, 56% were >30 years and 74% had higher than a high school education. Respondents reported a median of 2 known HIV-positive sex partners. Drug or alcohol use during last sex with their last known HIV-positive partner was reported by 53% of participants. Sixty-five per cent of participants reported inconsistent condom use with last known HIV-positive partner. Inconsistent condom use with all HIV-positive partners was higher among individuals reporting two or more known HIV-positive partners since sexual debut than among those with one (90% vs 59%, p<0.01) and among those reporting feelings of love/emotional attachment as a reason for having sex (85% vs 63%, p=0.02). In the bivariate logistic regression models for inconsistent condom use, feelings of love or emotional attachment were the only significant predictor of inconsistent condom use (OR 3.43, 95% CI 1.23 to 9.58). After adjusting for confounding, the relationship feelings of love or emotional attachment continued to be the only significant predictor of inconsistent condom use (OR 3.69, 95% CI 1.06 to 12.82). CONCLUSIONS: Surveyed MSM engaged in high-risk behaviours, including condomless anal sex and drug or alcohol use during sex with persons known to be HIV-positive. These findings can inform interventions with MSM in serodiscordant partnerships.

Risk Factors for HIV Acquisition in Urban Latinos and Implications for Prevention.

The risk of HIV in the Latino population in the United States is increasing. This population has a disproportionate number of new HIV cases, with the largest burden in the seventeen southern states. The purpose of this study is to assess risk factors for HIV among HIV-positive Latinos in care in New Orleans, Louisiana, through a retrospective chart review. The Chi square test of proportions, Student's t-test, and Wilcox rank sum test were used to test differences by sex and immigration status. Men were more likely to be incarcerated, use drugs, and drink alcohol. Undocumented Latinos were younger and had increased language barriers. Legally documented participants were more likely to use drugs, have a psychiatric diagnosis, and syphilis. Understanding the complex risk factors that surround HIV in the Latino population is useful for the development of effective and comprehensive prevention programs.

A stakeholder-driven method for selecting implementation strategies: a case example of pediatric hypertension clinical practice guideline implementation.

BACKGROUND: This article provides a generalizable method, rooted in co-design and stakeholder engagement, to identify, specify, and prioritize implementation strategies. To illustrate this method, we present a case example focused on identifying strategies to promote pediatric hypertension (pHTN) Clinical Practice Guideline (CPG) implementation in community health center-based primary care practices that involved meaningful engagement of pediatric clinicians, clinic staff, and patients/caregivers. This example was chosen based on the difficulty clinicians and organizations experience in implementing the pHTN CPG, as evidenced by low rates of guideline-adherent pHTN diagnosis and treatment. METHODS: We convened a Stakeholder Advisory Panel (SAP), comprising 6 pediatricians and 5 academic partners, for 8 meetings (~12 h total) to rigorously identify determinants of pHTN CPG adherence and to ultimately develop a testable multilevel, multicomponent implementation strategy. Our approach expanded upon the Expert Recommendations for Implementation Change (ERIC) protocol by incorporating a modified Delphi approach, user-centered design methods, and the Implementation Research Logic Model (IRLM). At the recommendation of our SAP, we gathered further input from youth with or at-risk for pHTN and their caregivers, as well as clinic staff who would be responsible for carrying out facets of the implementation strategy. RESULTS: First, the SAP identified 17 determinants, and 18 discrete strategies were prioritized for inclusion. The strategies primarily targeted determinants in the domains of intervention characteristics, inner setting, and characteristics of the implementers. Based on SAP ratings of strategy effectiveness, feasibility, and priority, three tiers of strategies emerged, with 7 strategies comprising the top tier implementation strategy package. Next, input from caregivers and clinic staff confirmed the feasibility and acceptability of the implementation strategies and provided further detail in the definition and specification of those strategies. CONCLUSIONS: This method-an adaptation of the ERIC protocol-provided a pragmatic structure to work with stakeholders to efficiently identify implementation strategies, particularly when supplemented with user-centered design activities and the intuitive organizing framework of the IRLM. This generalizable method can help researchers identify and prioritize strategies that align with the implementation context with an increased likelihood of adoption and sustained use.

Prevalence, patterns and predictors of substance use among Latino migrant men in a new receiving community.

BACKGROUND: The purpose of this study was to evaluate the prevalence, patterns and predictors (individual, social, cultural, and environmental) of illicit drug use and binge drinking in a cohort of Latino migrant men (LMM) in a new receiving community. METHODS: A cohort of LMM in New Orleans (n=125) was assembled in 2007 using respondent driven sampling and interviewed quarterly for 18 months regarding past month substance use and other potential covariates. Baseline frequencies were weighted using RDSAT and longitudinal analyses included generalized estimating equations (GEE) and the Cochran-Armitage test for trends. RESULTS: At baseline, substance use behaviors were: drug use 15.0% (range 7.3-25.0%) and binge drinking 58.3% (range 43.6-74.6%). All three of these behaviors decreased over follow-up (P<0.01). Baseline alcohol dependence and drug problem were 11.8% (range 5.6-24.3%) and 0.08% (range 0.00-2.7%) and both remained the same over time. Baseline rate of chlamydia was 9% (range 0.00-22.4%); all men tested negative for gonorrhea, HIV, and syphilis. For both binge drinking and drug use, having sex with a female sex worker was associated with increased risk, whereas belonging to a club or organization was associated with less risk. Additional factors associated with increased drug use were: having a friend in New Orleans upon arrival, symptoms of depression, and working in construction. An additional factor associated with less binge drinking was having family in New Orleans upon arrival. CONCLUSION: Among LMM, substance use is influenced by social and environmental factors. Interventions increase community connectedness may help decrease usage.

Sex and drug risk behavior pre- and post-emigration among Latino migrant men in post-Hurricane Katrina New Orleans.

High rates of sex and drug risk behaviors have been documented among Latino migrant men in the US. Whether these behaviors were established in the migrants' home countries or were adopted in the US has not been described and has implications for prevention strategies. Quarterly surveys were conducted to gather information on selected sex and drug risk practices of Latino migrant men who arrived in New Orleans after Hurricane Katrina seeking work. Both kappa scores and McNemar's tests were performed to determine if practice of these behaviors in home country was similar to practice post-emigration to the US. Female sex worker (FSW) patronage, same sex encounters (MSM), and crack cocaine use was more likely to occur post- rather than pre-emigration. Of those who ever engaged in these selected behaviors, most adopted the behavior in the US (i.e., 75.8% of FSW patrons, 72.7% of MSM participants, and 85.7% of crack cocaine users), with the exception of binge drinking (26.8%). Men who were living with a family member were less likely to adopt FSW patronage OR = 0.27, CI = 0.10-0.76, whereas men who earned >$465 per week were more likely to adopt crack cocaine use OR = 6.29 CI = 1.29, 30.57. Interventions that facilitate the maintenance of family cohesion and provide strategies for financial management may be useful for reducing sex and drug risk among newly arrived migrants.

Factors associated with mortality and default among patients with tuberculosis attending a teaching hospital clinic in Accra, Ghana.

Tuberculosis (TB) remains a major cause of mortality despite availability of effective chemotherapy. This study was performed to identify contributing factors for poor outcome during anti-tuberculosis treatment at a teaching hospital chest clinic. Medical records of registered patients treated for TB between 1 January and 31 December, 2009 were reviewed and abstracted for demographic, clinical and outcome data. Risk factors for mortality during therapy were assessed using bivariate and multivariate logistics approaches. Of 599 patients, 355 (58.9%) completed therapy and/or were cured, 192 (32.1%) died, and 39 (6.5%) defaulted. In multivariate analysis, independent risk factors for mortality included pulmonary cases for which sputum smear status was unknown (odds ratio [OR] 13.7; 95% confidence interval [CI] 6.0, 31.4), HIV coinfection (OR, 3.6; 95% CI 2.4, 5.4), disseminated TB (OR, 2.2; 95% CI 1.0, 4.9), TB meningitis (OR, 2.8; 95% CI 1.5, 5.3), not having a treatment supporter (OR, 2.0; 95% CI 1.3, 3.1), and low body weight (OR, 11.0; 95% CI 3.1, 38.6). Not having a treatment supporter (OR, 3.2; 95% CI 1.6, 6.6) and HIV coinfection (OR, 2.4; 95% CI 1.2, 5.2) were also independently associated with treatment default. Our findings suggest that enhanced measures to reduce mortality and default in TB patients with HIV coinfection, disseminated or meningeal disease and those who have no treatment supporters may help improve treatment outcomes in Ghana.