Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene.

Etiology of preterm birth (PTB) is multifactorial; therefore, decreasing the incidence of PTB is a major challenge in the field of obstetrics. Epidemiological studies have reported an association between toxicants and PTB. However, there are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, in the incidence of PTB. We first assessed the effects of BaP (150 and 300 µg kg(-1) body weight) dosed via gavage from day 14 to 17 of pregnancy on gestation length in Long Evans rats. We further assessed the histopathology of the uterus, expression of inflammatory cytokines, contractile-associated factors, histone deacetylases (HDACs) and NFқB-p65 in myometrium collected on day 22 postpartum versus vehicle-treated controls. In our study, rats exposed to BaP delivered prematurely (P < 0.05) compared to control. Hematoxylin and eosin staining of uterus showed squamous metaplasia, glandular and stromal hyperplasia in BaP-exposed rats versus control. The concentrations of BaP metabolites measured by high-pressure liquid chromatography were higher in uterine myometrium of BaP-exposed rats while they were undetectable in controls. Quantitative real-time polymerase chain reaction showed significant increases in mRNA expression of interleukin-1ß and -8, tumor necrosis factor-α, connexin 43, cyclo-oxygenase-2 and prostaglandin F2α receptor as compared to controls (P < 0.05). Western blot analysis revealed that BaP exposure caused decreases in class I HDACs 1 and 3 and increases in class II HDAC 5, cyclo-oxygenase-2 and nuclear translocation of NFκB-p65 relative to controls. Our results suggest that gestational exposure to BaP increases incidence of PTB through epigenetic changes that causes increases in the expression of contractile-associated factors through the NFκB pathway. Copyright © 2015 John Wiley & Sons, Ltd.

Higher Prevalence of Human Papillomavirus-Related Cervical Precancerous Abnormalities in HIV-Infected Compared to HIV-Uninfected Women.

INTRODUCTION: Persistent high risk human papillomavirus (hrHPV) has been associated with cervical abnormalities and cancer. There are few studies comparing HIV-infected with uninfected African American women from the Southern U.S. We evaluated medical records of a women's cohort in an urban clinic in Tennessee to assess the prevalence of hrHPV and cytology correlates, as well as HPV vaccination rates. METHODS: We reviewed medical records of 50 HIV infected and 304 HIV uninfected women, including Pap smears and hrHPV. RESULTS: HIV-infected women were older than HIV-uninfected women (p<0.0001) and were more likely to have hrHPV (p=<0.0001) and LGSIL/HGSIL (p=0.006). Within the HIV uninfected group, Hispanic women were younger than non-Hispanic African American women (p=0.04) and non-Hispanic white women (p=0.0002). Non-Hispanic African-American women were younger (p=0.004) than non-Hispanic white women. Both HIV-uninfected and HIV-infected women had an 11-fold and 5-fold odds, respectively, of having precancerous lesions when harboring hrHPV, compared to hrHPV-uninfected women. Of the 125 HIV-uninfected women, only 17% had received at least one dose of the HPV vaccine. None of the 21 vaccine recipients had evidence of SILs compared to 9% of vaccine non-recipients (p=0.35, Fisher's exact test). CONCLUSION: HIV-infected women remained at significantly higher risk for developing cervical precancerous lesions when exposed to hrHPV than their uninfected counterparts. Hispanic women were least likely to have been vaccinated. Missed HPV vaccination trended towards being associated with a higher odds of precancerous lesions. Routine HPV vaccination should be reinforced for adolescents and young women using public hospital facilities of all races and ethnic backgrounds.

Vitamin D regulates contractile profile in human uterine myometrial cells via NF-κB pathway.

OBJECTIVE: Infection triggers inflammation that, in turn, enhances the expression of contractile-associated factors in myometrium and increases the risk of preterm delivery. In this study, we assessed vitamin D regulation of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NFκB pathway proteins in human uterine myometrial smooth muscle (UtSM) cells that were cultured in an inflammatory environment. STUDY DESIGN: Inflammatory environment was simulated for UtSM cells by coculturing them with monocyte lineage (THP1) cells. We measured the expression of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NFκB pathway proteins in UtSM cells that were cultured with THP1 cells in the presence and absence of vitamin D by real time polymerase chain reaction and Western blot analysis. RESULTS: Monocytes secreted monocyte inflammatory protein-1α and -1ß, interleukin (IL)-1ß and 6, and tumor necrosis factor-α into the conditioned medium. In the UtSM cells that had been cocultured with THP1 cells, there was a significant (P < .05) increase in the expression of inflammatory markers IL-1ß, -6, and -13 and tumor necrosis factor-α; the contractile-associated factors connexin-43, Cox-2, and prostaglandin F2α receptor; the estrogen receptor α, and progesterone receptors A and B. Vitamin D treatment of cocultures decreased (P < .05) the expression of inflammatory markers and contractile-associated factors in UtSM cells. Similarly, vitamin D decreased estrogen receptor α and progesterone receptors A-to-B ratio in UtSM cells that were cocultured with THP1 cells. In addition, vitamin D treatment significantly (P < .05) decreased monocyte-induced p-IκBα in cytosol and NFκB-p65 in the nucleus and increased IκBα in cytosol in UtSM cells. CONCLUSION: Our results suggest that vitamin D treatment decreases inflammation-induced cytokines and contractile-associated factors in the uterine myometrial smooth muscle cells through the NFκB pathway.

Evaluation of serotype-specific immunity to Streptococcus pneumoniae in pregnant women and cord blood of infants: impact of race and ethnicity.

BACKGROUND: Although invasive pneumococcal disease (IPD) has significantly decreased in children since the introduction of the pneumococcal conjugate vaccine, instances of IPD from non-PCV7 serotypes have increased. Concerns remain regarding the risk for IPD during the neonatal period. Our objective was to measure quantitative antibody levels to 16 serotypes of Streptococcus pneumoniae in pregnant non-Hispanic black, non-Hispanic white, and Hispanic mothers, and in cord blood samples. METHODS: Antibody levels were evaluated by Luminex assay. RESULTS: Forty-two percent of all mothers had protective (-0.35 microg/mL) antibody levels to 16 serotypes. Hispanic mothers were most likely to possess protective antibody levels for 12 serotypes but were less likely to possess protective antibody levels for serotypes 9V, 12F, and 18C, compared to non-Hispanic white or black mothers. Thirty-three percent of cord blood samples demonstrated protective antibody levels. Hispanic infants had a higher prevalence of protective antibodies to all serotypes except 11A, 14, 18C, and 23F. Non-Hispanic black infants had a higher prevalence of protective immunity to serotypes 11A, 14, and 18C, and non-Hispanic white infants to only serotype 23F. CONCLUSIONS: Hispanic mothers and their infants have a higher prevalence of protective immunity to most serotypes of S pneumoniae, compared to white or black mothers/infants. We found no evidence of a lower prevalence of protective immunity to specific serotypes in non-Hispanic black vs. non-Hispanic white infants that might account for the reported higher incidence of IPDs in blacks. Environmental factors in Hispanic mothers may be responsible for their enhanced level of immunity. A significant number of cord blood samples had inadequate levels of protective immunity to a variety of S pneumoniae serotypes.

Does polycystic ovary syndrome increase the disparity in metabolic syndrome and cardiovascular-related health for African-American women?

There have been few formal studies of differences in the phenotype of PCOS among women of African-American ancestry. Generally, African-American women tend to have an adverse cardiovascular risk profile when compared with women of other racial groups. The metabolic syndrome is a clinical disorder that identifies individuals at risk for diabetes and cardiovascular disease. Preliminary studies support that both African-American and White women with PCOS have similar prevalences of the metabolic syndrome, suggesting that the diagnosis may not be associated with racial differences in cardiovascular risk factors.

Immunity to measles in pregnant mothers and in cord blood of their infants: impact of HIV status and mother's place of birth.

Antibody levels to measles were evaluated in 16 HIV-seropositive and 34 seronegative pregnant women and in cord blood samples of their infants. Infants were followed prospectively, and a second blood sample was taken at 3-7 months of age. Antibody levels were significantly lower in HIV-seropositive pregnant women and HIV-exposed cord bloods at birth (p=0.01 and 0.04, respectively) compared to controls. The prevalence of protective immunity (> or =1.09 optical density ratio) was also significantly lower (p=0.02) in HIV-seropositive pregnant women. T-cell counts were lower in HIV-seropositive women who were nonimmune (268/mm3) to measles compared to those who were immune (618/mm3), but the difference did not reach significance (p=0.07). Immunity to measles declined significantly to nonprotective levels in all infant samples obtained at 3-7 months of age. A secondary analysis determined the impact of mother's place of birth. Antibody levels were significantly higher (p=0.03) in foreign-born HIV-seronegative pregnant women and cord blood samples (p=0.01) compared to U.S.-born HIV-seronegative pregnant women seen in our inner-city clinic. Thus, HIV-seropositive and even some seronegative U.S.-born women may need a booster vaccine to ensure passage of adequate levels of passive immunity.

Poor Sleep Quality Is Associated with Higher Hemoglobin A1c in Pregnant Women: A Pilot Observational Study.

We hypothesized that poor sleep quality exacerbates glucose intolerance manifested as elevated glycosylated hemoglobin (HbA1c), which increases the risk for gestational diabetes. To test this, 38 pregnant and 22 non-pregnant (age, 18⁻35 years; body-mass index, 20⁻35 kg/m²) otherwise healthy women were enrolled in the study. Sleep quality was assessed during gestational week 24 (pregnant), or outside of the menstrual period (non-pregnant), using qualitative (Pittsburgh Sleep Quality Index) and objective (actigraphic wrist-watch) measures. Blood glucose, total cortisol, and depression status were evaluated. Eight pregnant and one non-pregnant women were lost to follow-up, or withdrew from the study. There was a higher incidence of poor sleep quality in pregnant (73%) relative to non-pregnant women (43%). Although actigraphic data revealed no differences in actual sleep hours between pregnant and non-pregnant women, the number of wake episodes and sleep fragmentation were higher in pregnant women. Poor sleep quality was positively correlated with higher HbA1c in both pregnant (r = 0.46, n = 26, p = 0.0151) and non-pregnant women (r = 0.50, n = 19, p = 0.0217), reflecting higher average blood glucose concentrations. In contrast, poor sleep was negatively correlated with cortisol responses in pregnant women (r = -0.46, n = 25, p = 0.0167). Three pregnant women had elevated one-hour oral glucose tolerance test results (>153 mg/dL glucose). These same pregnant women exhibited poor sleep quality. These results support the suggestion that poor sleep quality is an important risk factor that is associated with glucose intolerance and attendant health complications in pregnancy.

An assessment of cultural competence of first- and second-year medical students at a historically diverse medical school.

OBJECTIVE: The purpose of this study was to measure knowledge of cultural variations of health beliefs and practices, especially among Hispanic patients, in a population of medical students at a historically black medical college. STUDY DESIGN: The modified clinical culture competency questionnaire tapped demographic, self-perceived knowledge, skills, encounter-situations, attitudes, education, and training of medical students. The survey was administered on a course management system. The Hispanic health knowledge questionnaire measured student knowledge of Hispanic culture. RESULTS: The response rate was 51%. No significant gender or racial differences were noted. First-year medical students were more skilled in managing sociocultural issues (40.07 vs 33.70; P = .0089) and less skilled in education and training (1.35 vs 0.57; P = .0222) than second-year students. All students scored below the 60th percentile on the Hispanic health knowledge questionnaire. CONCLUSION: These data point to the importance of cultural competency training in Hispanic health and may be used to develop an educational intervention to better address the health care needs of the local Hispanic population.

Determination of vitamin D in relation to body mass index and race in a defined population of black and white women.

OBJECTIVE: To examine the contributions of obesity and race to levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) in a defined cohort of black and white women. METHODS: An interventional study was conducted from October 2004 to March 2008, among 219 healthy female volunteers. Serum 25(OH)D and PTH levels were determined in 117 African American women and 102 white women and the results were compared with body mass index (BMI), percentage body fat, serum lipids, and PTH levels. RESULTS: Black women had lower median levels of 25(OH)D compared with white women (27.3 nmol/L vs 52.4 nmol/L; P<0.001). Serum levels of 25(OH)D below 50 nmol/L were found in 98% of black women and 45% of white women (P<0.001). The differences between the racial groups in the levels of 25(OH)D persisted despite adjustments for body weight, percentage body fat, and BMI. Black women had higher median serum levels of PTH than white women (31.9 pg/mL vs 22.3 pg/mL; P<0.01). CONCLUSION: African American women are at significant risk for low vitamin D levels. Studies are needed to determine if low vitamin D status in young African American women is associated with a greater risk for vitamin D-related chronic diseases that can be reduced with vitamin D supplementation.

Waning immunity to varicella in infants of human immunodeficiency virus-seropositive and -seronegative mothers.

Immunity to varicella in HIV-exposed and -unexposed infants born to unvaccinated mothers, acquiring protective antibodies at birth declined to nonprotective (<1:8) levels by 5 months of age. Therefore, infants become susceptible to varicella before 12 months, which is the recommended time for varicella immunizations in the United States. Vaccination of susceptible HIV-seronegative women in the postpartum period may be important to consider.

The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study.

OBJECTIVE: To determine if the combination of lifestyle (caloric restriction and exercise) and metformin (MET) would be superior to lifestyle and placebo (PBO) in improving the polycystic ovary syndrome (PCOS) phenotype. DESIGN: Double-blind randomized 6-month trial of MET versus PBO. SETTING: Two academic medical centers. PATIENT(S): One hundred fourteen subjects with PCOS were randomized to MET (N = 55) or PBO (N = 59). INTERVENTION(S): Subjects collected urine daily for ovulation monitoring, had monthly monitoring of hormones and weight and determination of body composition by dual-energy x-ray absorptiometry, glucose tolerance, and were evaluated for quality of life at baseline and completion. MAIN OUTCOME MEASURE(S): Ovulation rates and testosterone levels. RESULT(S): Dropout rates were high. There was no significant difference in ovulation rates. Testosterone levels were significantly lower compared with baseline in the MET group at 3 mos but not at 6 mos. There were no differences in weight loss between groups, but MET showed a significant decline at 6 months compared with baseline (-3.4 kg, 95% confidence interval -5.3 to -1.5 kg). We noted divergent effects of MET versus PBO on oral glucose tolerance test indices of insulin sensitivity (increased) and secretion (worsened). Total bone mineral density increased significantly in MET. There were no differences in quality of life measures between the groups. The MET group had increased diarrhea and headache, but fewer bladder infections and musculoskeletal complaints. CONCLUSION(S): The addition of metformin to lifestyle therapy produced little reproductive or glycemic benefit in women with PCOS, although our study had limited power owing to a high dropout rate. It is not possible at baseline to identify women likely to drop out.

Racial influence on the polycystic ovary syndrome phenotype: a black and white case-control study.

OBJECTIVE: To estimate racial disparities in the polycystic ovary syndrome (PCOS) phenotype between white and black women with PCOS. DESIGN: Case-control study. SETTING: Two academic medical centers. PATIENT(S): A total of 242 women not taking confounding medications in otherwise good health. INTERVENTION(S): Phenotyping during the follicular phase or anovulation after an overnight fast in women. MAIN OUTCOME MEASURE(S): Biometric, serum hormones, glycemic and metabolic parameters, and body composition by dual-energy x-ray absorptiometry. RESULT(S): We studied 77 white and 43 black women with PCOS and 35 white and 87 black controls. Black women with PCOS were similar reproductively to white women with PCOS. Black women with PCOS had lower levels of serum transaminases, higher high-density lipoprotein cholesterol levels (mean difference [MD], 18.2 mg/dL; 95% confidence intervals [CI], 14.3, 22.1 mg/dL), lower triglyceride levels (MD, -43.2 mg/dL; 95% CI, -64.5, -21.9), and enhanced insulinogenic index on the oral glucose tolerance test compared with white women with PCOS. Black women with PCOS had higher bone mineral density (MD, 0.1 g/cm(2); 95% CI, 0.1, 0.2 g/cm(2)), lower percent body fat on dual-energy x-ray absorptiometry (MD, -2.8%; 95% CI, -5.1%, -0.5%), and overall a higher quality of life. Although most of these findings disappeared when the differences with racially matched controls were compared, black women with PCOS compared with black controls had lower estradiol levels than white women with PCOS compared with white controls (MD, -12.9 pg/mL; 95% CI, -24.9, -0.8 pg/mL), higher systolic blood pressure (MD, 9.1 mm Hg; 95% CI, 0.8, 17.4 mm Hg), and lower fasting glucose levels (MD, -12.0 mg/dL; 95% CI, -22.3, -1.7 mg/dL). CONCLUSION(S): Racial disparities in PCOS phenotype are minor and mixed. Future studies should explore if race impacts treatment effects.

Effects of metformin in adolescents with polycystic ovary syndrome undertaking lifestyle therapy: a pilot randomized double-blind study.

Our small study does not support the addition of metformin to the lifestyle of adolescents. Although there are favorable trends toward hyperandrogenism with metformin, these must be balanced against the increased rate of gastrointestinal side effects. However, other treatments were associated with an improved quality of life.