Methylation profiling of benign and malignant breast lesions and its application to cytopathology.

Methylation of tumor suppressor genes has been implicated in breast cancer development. However, methylation profiles of different breast lesions, subtypes of carcinoma in particular, have not been examined in detail. In this study, we use methylation-specific PCR (MSP) to generate gene methylation profiles of different breast lesions and to test the clinical utility of such profiles. We examined the methylation status of three genes, RARbeta2, RASSF1A, and cyclin D2, on 102 samples of breast tissue, from benign (n = 36), to in situ carcinoma (n = 21), to invasive carcinoma (n = 45). We found that almost all cases of invasive carcinoma (96%) contained at least one methylated gene from our panel, whereas gene methylation was less common among benign lesions (42%) and in situ carcinoma (76%). Of the three genes, cyclin D2 methylation was most specific for malignancy because only 1 of 35 benign cases was methylated at this gene (1 case was not informative). The major histologic subtypes of invasive carcinoma show similar methylation profiles in the genes examined. We next performed MSP analysis on archival breast fine-needle aspiration (FNA) biopsy samples and corresponding surgical biopsy specimens and found a high concordance between the two types of specimens. We then analyzed 17 breast FNA biopsy samples with an indeterminate diagnosis. In this setting, MSP had a high specificity (100%) and modest sensitivity (67%) for identifying malignancy.     

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.