Transient association between semen exposure and biomarkers of genital inflammation in South African women at risk of HIV infection

IntroductionSemen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen‐induced alterations are likely short‐lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations.MethodsWe assessed stored genital specimens from 152 HIV‐negative KwaZulu‐Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014. During the two‐year study period, 651 vaginal specimens were collected biannually (mean five samples per woman). Cervicovaginal lavage (CVL) was screened for prostate‐specific antigen (PSA) by ELISA, whereas Y‐chromosome DNA (YcDNA) detection and quantification were conducted by RT‐PCR, representing semen exposure within 48 hours (PSA+YcDNA+) and semen exposure within three to fifteen days (PSA−YcDNA+). Soluble protein concentrations were measured in CVLs by multiplexed ELISA. T‐cell frequencies were assessed in cytobrushes by flow‐cytometry, and vulvovaginal swabs were used to detect common vaginal microbes by PCR. Linear mixed models adjusting for factors associated with genital inflammation and HIV risk were used to assess the impact of semen exposure on biomarkers of inflammation over multiple visits.ResultsHere, 19% (125/651) of CVLs were PSA+YcDNA+, 14% (93/651) were PSA−YcDNA+ and 67% (433/651) were PSA−YcDNA−. Semen exposure was associated with how often women saw their partners, the frequency of vaginal sex in the past month, HSV‐2 antibody detection, current gonorrhoea infection and Nugent Score. Both PSA detection (PSA+YcDNA+) and higher cervicovaginal YcDNA concentrations predicted increases in several cytokines, barrier‐related proteins (MMP‐2, TIMP‐1 and TIMP‐4) and activated CD4+CCR5+HLA‐DR+ T cells (β = 0.050; CI 0.001 to 0.098; p = 0.046) and CD4+HLA‐DR+ T cells (β = 0.177; CI 0.016 to 0.339; p = 0.032) respectively. PSA detection was specifically associated with raised pro‐inflammatory cytokines (including IL‐6, TNF‐α, IP‐10 and RANTES), and with the detection of BVAB2 (OR = 1.755; CI 1.116 to 2.760; p = 0.015), P. bivia (OR = 1.886; CI 1.102 to 3.228; p = 0.021) and Gardnerella vaginalis (OR = 1.815; CI 1.093 to 3.015; p = 0.021).ConclusionsMore recent semen exposure was associated with raised levels of inflammatory biomarkers and the detection of BV‐associated microbes, which declined by three to fifteen days of post‐exposure. Although transient, semen‐induced alterations may have implications for HIV susceptibility in women.     

The Relationship Between Social Support,HIV Serostatus,and Perceived Likelihood of Being HIV Positive Among Self-Settled Female,Foreign Migrants in Cape Town,South Africa

Female cross-border migrants experience elevated risks for HIV, and migrants in South Africa may face additional risks due to the country’s underlying HIV prevalence. These risks may be mitigated by the receipt of social support. A behavioral risk-factor survey was administered using respondent-driven sampling. Multivariable regression models assessed the relationships between social support and two HIV outcomes: HIV serostatus and perceived HIV status. Low social support was not significantly associated with HIV status (aOR?=?1.03, 95?% CI 0.43–2.46), but was significantly related to a perception of being HIV positive (aPR?=?1.36, 95?% CI 1.04–1.78). Age, marital status, and education level were significantly associated with HIV serostatus. Illegal border-crossing, length of time in South Africa, anal sex, and transactional sex were significantly associated with aperception of being HIV positive. Future research should investigate how HIV risks and the receipt of social support change throughout the migration process.     

Chlorhexidine vaginal wipes prior to elective cesarean section: does it reduce infectious morbidity? A randomized trial

Objective: To evaluate the efficacy of preoperative vaginal cleansing using chlorhexidine 0.25% antiseptic wipes on rates of postcesarean section (CS) infectious morbidities (endometritis, febrile morbidity and wound infection).

Methods: This prospective randomized trial was conducted among 218 pregnant women scheduled for term elective CS. Patients were equally divided into two groups by simple randomization. After spinal anesthesia and catheterization under aseptic technique, the study group had preoperative vaginal cleansing using chlorhexidine 0.25% antiseptic wipes for about 1?min, while the control group did not. All cases received the prophylactic antibiotics and the usual abdominal scrub. All participants received the routine postoperative care without other interventions. Adverse postcesarean infectious morbidities such as endometritis, febrile morbidity and wound infection were observed at the time of hospital discharge and weekly for 6 weeks postpartum.

Results: Both groups were matched regarding the baseline patients’ characteristics (age, gestational age, BMI, operative time and postoperative hospital stay). Overall, post-CS infectious morbidity were significantly reduced from 24.4% in the control group to 8.8% in the intervention group; p value?<0.05. Marked reduction was seen in the incidence of endometritis (13.2% in the control group versus 2.9% in the intervention group; p value?<0.05). However, fever and wound infection showed no significant difference between both groups.

Conclusion: Cleansing the birth canal with chlorhexidine 0.25% wipes prior to elective CS appears to be effective in reducing rates of post-CS infectious morbidity mainly endometritis.     

Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

Background: Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity.Objective: Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation.Methods: We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation.Results: In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10^–7. Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10^–11) and blood arsenic concentrations (p = 1.48 × 10^–11). Three additional novel methylation loci—SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)—were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci.Conclusions: We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions.Citation: Argos M, Chen L, Jasmine F, Tong L, Pierce BL, Roy S, Paul-Brutus R, Gamble MV, Harper KN, Parvez F, Rahman M, Rakibuz-Zaman M, Slavkovich V, Baron JA, Graziano JH, Kibriya MG, Ahsan H. 2015. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect 123:64–71; http://dx.doi.org/10.1289/ehp.1307884     

Fractography and oxidative analysis of gamma inert sterilized posterior-stabilized tibial insert post fractures: Report of two cases

BackgroundHighly crosslinked ultra-high molecular weight polyethylene (UHMWPE) has shown success in reducing wear in hip arthroplasty but there remains skepticism about its use in Total Knee Replacement (TKR) inserts that are known to experience fatigue loading and higher local cyclic contact stresses.MethodsTwo Legacy Posterior-Stabilized (LPS) Zimmer NexGen tibial implants sterilized by gamma irradiation in an inert environment with posts that fractured in vivo were analyzed. Failure mechanisms were determined using optical and scanning electron microscopy along with oxidative analysis via Fourier Transform Infra-Red (FTIR) spectroscopy.ResultsMicrographs of one retrieval revealed fatigue crack initiation on opposite sides of the post and quasi-brittle micromechanisms of crack propagation. FTIR of this retrieval revealed no oxidation. The fracture surface image of the second retrieval indicated a brittle fracture process and FTIR revealed oxidation in the explant.ConclusionsThese two cases suggest that crosslinking of UHMWPE as a manufacturing process or sterilization method in conjunction with designs that incorporate high stress concentrations, such as the tibial post, may reduce material strength. Moreover, free radicals generated from ionizing radiation can render the polymer susceptible to oxidative embrittlement.Clinical relevanceOur findings suggest that tibial post fractures may be the results of in vivo oxidation and low level crosslinking. These and previous reports of fractured crosslinked UHMWPE devices implores caution when used with high stress concentrations, particularly when considering the potential for in vivo oxidation in TKR.     

Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis

Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology.     

Perceived peer safer sex norms and sexual risk behaviors among substance-using Latino adolescents

We investigated the association between perceived peer norms and safer sexual behaviors among substance using Latino youth. Between 2005 and 2006, cross-sectional data were collected from 92 Latino adolescents recruited from clinic- and community-based settings in two U.S. cities. Separate multivariate logistic regression models were used to assess the relationship between perceived peer norms around safer sex and two different outcomes: consistent condom use and multiple sexual partnerships. Among these participants, perceived peer norms encouraging safer sex were associated with consistent condom use even after controlling for individual- and partner-related factors. Perceived peer norms supporting safer sex were inversely associated with recently having two or more sexual partners after controlling for demographic characteristics. Perceived peer norms around safer sexual behavior contribute to a lower likelihood of engaging in two HIV/STI risk behaviors: inconsistent condom use and multiple partnering. These findings suggest that further development of peer-based interventions for Latino youth is warranted.