Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG; (ii) the US National Strategy for combating antimicrobial-resistant bacteria; (iii) surveillance needs, challenges, and novel technologies; (iv) plasmid-mediated and chromosomally mediated mechanisms of AMR in NG; (v) novel therapeutic (eg, sialic acid analogs, factor H [FH]/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (eg, peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives, and collaborations across academic and commercial research and public health programs

Cardiac Conduction System: Delineation of Anatomic Landmarks With Multidetector CT

Major components of the cardiac conduction system including the sinoatrial node (SAN), atrioventricular node (AVN), the His Bundle, and the right and left bundle branches are too small to be directly visualized by multidetector CT (MDCT) given the limited spatial resolution of current scanners. However, the related anatomic landmarks and variants of this system a well as the areas with special interest to electrophysiologists can be reliably demonstrated by MDCT. Some of these structures and landmarks include the right SAN artery, right atrial cavotricuspid isthmus, Koch triangle, AVN artery, interatrial muscle bundles, and pulmonary veins. In addition, MDCT has an imperative role in demarcating potential arrhythmogenic structures. The aim of this review will be to assess the extent at which MDCT can outline the described anatomic landmarks and therefore provide crucial information used in clinical practice

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Risk behavior dislcosure during HIV test counseling

Personalized risk assessments during Human Immunodeficiency Virus (HIV) testing are an integral component of HIV prevention counseling, an individual-level behavior change intervention to reduce the spread of HIV. Aggregated data from risk assessments are used to track behaviors in the testing population, evaluate federally-funded Counseling, Testing and Referral (CTR) programs, and inform prevention programs and allocation of resources. Unfortunately, risks disclosed during HIV test counseling may not be accurate, with stigmatizing behaviors underreported during face-to-face assessments. To understand the limitations of the CTR risk data and guide interventions to improve the validity of the risk assessment, we conducted a mixed methods study in young men in North Carolina (NC). We linked two statewide HIV databases that contain individual-level data on young men newly diagnosed with HIV in NC, comparing client-reported gender of sex partners at the time of testing to those reported during post-diagnosis partner notification (n=641). Of the 212 men who told their HIV test counselor that they had only had female sexual partner(s) in their lifetime, 62 (29.2%) provided contact information for male sex partner(s) during partner notification. Of the 25 men who reported no lifetime sex partners during test counseling, 22 (88.0%) provided partner notification information for sex partners in the last year. We then interviewed young men accessing HIV testing services in a southeastern United States city. Based on data collected via an Audio and Computer Self-Administered Interview (n=203), over 30% of young men reported that they were not accurate during the risk assessment. Participants reported numerous interpersonal barriers to accuracy during the risk assessment. During qualitative interviews (n=25), many participants revealed that they did not understand the purpose of the risk assessment nor perceive an individual benefit to complete risk behavior disclosure. Findings from this study suggest that the risk assessment completed during HIV test counseling may be incomplete which has implications for both the efficacy of individual prevention counseling and aggregate behavioral statistics. Modifications to the risk assessment process, including better explaining the role of the risk assessment in prevention counseling and using alternate assessment methods, may increase the validity of the data

Chlamydia Prevalence Trends among Women and Men Entering the National Job Training Program from 1990 Through 2012

Background Evaluating chlamydia prevalence trends from sentinel surveillance is important for understanding population disease burden over time. However, prevalence trend estimates from surveillance data may be misleading if they do not account for changes in risk profiles of individuals who are screened (case mix) and changing performance of the screening tests used. Methods We analyzed chlamydia screening data from a sentinel surveillance population of 389,555 young women (1990-2012) and 303,699 young men (2003-2012) entering the US National Job Training Program. This period follows the introduction of national chlamydia screening programs designed to prevent transmission and reduce population disease burden. After ruling out bias due to case mix, we used an expectation-maximization-based maximum likelihood approach to account for measurement error from changing screening tests, and generated minimally biased long-term chlamydia prevalence trend estimates among youth and young adults in this sentinel surveillance population. Results Adjusted chlamydia prevalence among women was high throughout the study period, but fell from 20% in 1990 to 12% in 2003, and remained between 12% and 14% through 2012. Adjusted prevalence among men was steady throughout the study period at approximately 7%. For both women and men, adjusted prevalence was highest among Black and American Indian youth and young adults, and in the Southern and Midwestern regions of the United States throughout the study period. Conclusions Our minimally biased trend estimates provide support for an initial decrease in chlamydia prevalence among women soon after the introduction of national chlamydia screening programs. Constant chlamydia prevalence in more recent years suggests that screening may not be sufficient to further reduce chlamydia prevalence among high-risk youth and young adults

Urban Adolescents Readily Comply with a Complicated Asthma Research Protocol

Purpose: Adolescents are often cited as having poor rates of compliance with medical regimens and research protocols. We quantified compliance in a cohort of urban adolescents participating in a complex research protocol in which measures were obtained without direct supervision by research personnel. Methods: A total of 54 early adolescents ages 10–13 were asked to wear a vest containing a personal air pollutant exposure monitor for two 24-hour periods and to perform daily peak expiratory flow (PEF) for six consecutive days. Compliance with wearing the vest was measured by comparing accelerometer data from a device within the vest to one worn continuously on the child's wrist. Daily PEF data were recorded using an electronic meter. Results: A priori definition of compliance was met by 85% of the adolescents by wearing the exposure monitoring vest and 72% by performing PEF. Conclusions: These findings suggest that early adolescents can be compliant with complex research protocols that are needed to help bridge gaps in pediatric asthma research

A flexible Bayesian hierarchical model of preterm birth risk among US Hispanic subgroups in relation to maternal nativity and education

Abstract: Background: Previous research has documented heterogeneity in the effects of maternal education on adverse birth outcomes by nativity and Hispanic subgroup in the United States. In this article, we considered the risk of preterm birth (PTB) using 9 years of vital statistics birth data from New York City. We employed finer categorizations of exposure than used previously and estimated the risk dose-response across the range of education by nativity and ethnicity. Methods: Using Bayesian random effects logistic regression models with restricted quadratic spline terms for years of completed maternal education, we calculated and plotted the estimated posterior probabilities of PTB (gestational age < 37 weeks) for each year of education by ethnic and nativity subgroups adjusted for only maternal age, as well as with more extensive covariate adjustments. We then estimated the posterior risk difference between native and foreign born mothers by ethnicity over the continuous range of education exposures. Results: The risk of PTB varied substantially by education, nativity and ethnicity. Native born groups showed higher absolute risk of PTB and declining risk associated with higher levels of education beyond about 10 years, as did foreign-born Puerto Ricans. For most other foreign born groups, however, risk of PTB was flatter across the education range. For Mexicans, Central Americans, Dominicans, South Americans and “Others”, the protective effect of foreign birth diminished progressively across the educational range. Only for Puerto Ricans was there no nativity advantage for the foreign born, although small numbers of foreign born Cubans limited precision of estimates for that group. Conclusions: Using flexible Bayesian regression models with random effects allowed us to estimate absolute risks without strong modeling assumptions. Risk comparisons for any sub-groups at any exposure level were simple to calculate. Shrinkage of posterior estimates through the use of random effects allowed for finer categorization of exposures without restricting joint effects to follow a fixed parametric scale. Although foreign born Hispanic women with the least education appeared to generally have low risk, this seems likely to be a marker for unmeasured environmental and behavioral factors, rather than a causally protective effect of low education itself

DNA methylation of the allergy regulatory gene interferon gamma varies by age, sex, and tissue type in asthmatics

Background Asthma is associated with allergic sensitization in about half of all cases, and asthma phenotypes can vary by age and sex. DNA methylation in the promoter of the allergy regulatory gene interferon gamma (IFNγ) has been linked to the maintenance of allergic immune function in human cell and mouse models. We hypothesized that IFNγ promoter methylation at two well-studied, key cytosine phosphate guanine (CpG) sites (-186 and -54), may differ by age, sex, and airway versus systemic tissue in a cohort of 74 allergic asthmatics. Results After sampling buccal cells, a surrogate for airway epithelial cells, and CD4+ lymphocytes, we found that CD4+ lymphocyte methylation was significantly higher in children compared to adults at both CpG sites (P <0.01). Buccal cell methylation was significantly higher in children at CpG -186 (P = 0.03) but not CpG -54 (P = 0.66). Methylation was higher in males compared to females at both CpG sites in CD4+ lymphocytes (-186: P <0.01, -54: P = 0.02) but not buccal cells (-186: P = 0.14, -54: P = 0.60). In addition, methylation was lower in CD4+ lymphocytes compared to buccal cells (P <0.01) and neighboring CpG sites were strongly correlated in CD4+ lymphocytes (r = 0.84, P <0.01) and weakly correlated in buccal cells (r = 0.24, P = 0.04). At CpG -186, there was significant correlation between CD4+ lymphocytes and buccal cells (r = 0.24, P = 0.04) but not at CpG -54 (r = -0.03, P = 0.78). Conclusions These findings highlight significant age, sex, and tissue-related differences in IFNγ promoter methylation that further our understanding of methylation in the allergic asthma pathway and in the application of biomarkers in clinical research

Pregnancy and HIV Infection in Young Women in North Carolina

We described young women in North Carolina (NC) who were pregnant at the time of diagnosis with human immunodeficiency virus (HIV) infection to identify an at-risk population that could be targeted for increased HIV screening. We investigated the combined effect of partner counseling and referral services (PCRS) and comprehensive prenatal HIV screening

Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children

BACKGROUND: Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 μm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children. METHODS: Six day integrated levels of air pollutants were measured from children's homes (age 9-14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A), arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. RESULTS: Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4 and IFNγ. In exploratory analyses, V levels were associated with lower methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V, appeared associated with lower lung function (i.e., reduced z-scores for forced expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and forced expiratory flow at 25-75% of FVC [FEF25-75]). CONCLUSIONS: Exposure to V was associated with altered DNA methylation of allergic and proinflammatory asthma genes implicated in air pollution related asthma. However, short-term exposure to PM2.5, but not V, appeared associated with decrements in lung function among urban children