Factors in Accessing Routine Health Care: Mental Health and Postpartum Mothers.

OBJECTIVES: One strategy proposed to decrease the maternal mortality and morbidity in the United States is to increase the rate which new mothers access routine postpartum care. Using Missouri's Pregnancy Risk Assessment Monitoring System (MO PRAMS) data, this retrospective study analyzed whether a self-reported history of depressive symptoms during the postpartum period was associated with a decreased rate of accessing the postpartum care visit (PPCV). METHODS: Data were collected on 7,357 new mothers who completed the Missouri PRAMS survey between 2009-2014. New mothers, in the Missouri's registry of birth certificates who have given birth in the last 2-4 months, were randomly selected for inclusion in the survey. A mixed-mode survey method with a prescribed protocol for data collection was utilized. RESULTS: Fourteen percent of the respondents (1,093 new mothers) reported symptoms associated with postpartum depression. A logistic regression analysis showed that among these women a weak association was found between not accessing routine PPCV and the report of depressive symptoms (p=.0254; OR=1.344 with 95%CI=1.037-1.741). This association is a new finding. CONCLUSIONS: The study finds a weakly negative association between self-reported symptoms of postpartum depression and accessing routine postpartum care. As this is a new finding, further research is needed for verification of this association.

Association between contraceptive use and gestational diabetes: Missouri Pregnancy Risk Assessment Monitoring System, 2007-2008.

INTRODUCTION: The efficacy and safety of contraceptives have been questioned for decades; however, whether a relationship exists between hormonal contraceptives and gestational diabetes (GDM) is undetermined. The aim of this study was to investigate whether maternal risk for GDM was influenced by type of contraceptive method used before pregnancy. METHODS: Data collected in 2007 and 2008 by the Missouri Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed to determine if type of contraception before pregnancy influenced maternal risk for GDM. We used a logistic regression model to determine the adjusted odds for GDM given exposure to hormonal forms of contraception. RESULTS: Of the 2,741 women who completed the 2007-2008 PRAMS survey, 8.3% were diagnosed with gestational diabetes, and 17.9% of the respondents had used hormonal contraceptive methods. Women who used hormonal methods of birth control had higher odds for gestational diabetes (adjusted odds ratio [AOR] = 1.43; 95% confidence interval [CI], 1.32-1.55) than did women who used no contraception. A protective effect was also observed for women who had used barrier methods of contraception (AOR = 0.79; 95% CI, 0.72-0.86). CONCLUSION: Findings suggest there may be a relationship between type of contraceptive method and GDM. More research is needed to verify contraception as a potential risk factor for GDM.

Therapeutic starvation and autophagy in prostate cancer: a new paradigm for targeting metabolism in cancer therapy.

BACKGROUND: Autophagy is a starvation induced cellular process of self-digestion that allows cells to degrade cytoplasmic contents. The understanding of autophagy, as either a mechanism of resistance to therapies that induce metabolic stress, or as a means to cell death, is rapidly expanding and supportive of a new paradigm of therapeutic starvation. METHODS: To determine the effect of therapeutic starvation in prostate cancer, we studied the effect of the prototypical inhibitor of metabolism, 2-deoxy-D-glucose (2DG), in multiple cellular models including a transfected pEGFP-LC3 autophagy reporter construct in PC-3 and LNCaP cells. RESULTS: We found that 2DG induced cytotoxicity in PC-3 and LNCaP cells in a dose dependent fashion. We also found that 2DG modulated checkpoint proteins cdk4, and cdk6. Using the transfected pEGFP-LC3 autophagy reporter construct, we found that 2DG induced LC3 membrane translocation, characteristic of autophagy. Furthermore, knockdown of beclin1, an essential regulator of autophagy, abrogated 2DG induced autophagy. Using Western analysis for LC3 protein, we also found increased LC3-II expression in 2DG treated cells, again consistent with autophagy. In an effort to develop markers that may be predictive of autophagy, for assessment in clinical trials, we stained human prostate tumors for Beclin1 by immunohistochemistry (IHC). Additionally, we used a digitized imaging algorithm to quantify Beclin1 staining assessment. These data demonstrate the induction of autophagy in prostate cancer by therapeutic starvation with 2DG, and support the feasibility of assessment of markers predictive of autophagy such as Beclin1 that can be utilized in clinical trials. Prostate 68: 1743-1752 (c) 2008 Wiley-Liss, Inc. These data demonstrate the induction of autophagy in prostate cancer by therapeutic starvation with 2DG, and support the feasibility of assessment of markers predictive of autophagy such as Beclin1 that can be utilized in clinical trials.

Folic acid consumption among Missouri women in the periconceptional period.

Periconceptional folic acid consumption significantly reduces the risk for neural tube defects. The purpose of this study was to identify the risk factors for poor periconceptional folic acid supplementation among Missouri women. Sixty-five percent of Missouri women reported not taking periconceptional multivitamins regularly. Unintended pregnancy (aOR = 0.49), maternal adolescent age (aOR = 0.44) and smoking before pregnancy (aOR = 0.53) were significantly associated with poor periconceptional multivitamin use. Folic acid interventions targeting specific sub-groups of women are needed in Missouri.

Association of maternal smoking status with breastfeeding practices: Missouri, 2005.

OBJECTIVE: We sought to determine the association of smoking status as a risk factor for reduced initiation and duration of breastfeeding. METHODS: The Missouri Pregnancy Related Assessment and Monitoring System collected a stratified sample of new mothers in 2005. Surveys were mailed, with telephone follow-up, and completed within 2 to 12 months after delivery. Respondents were classified as nonsmokers, smokers who quit during pregnancy, light smokers (10 cigarettes per day). Multivariable binomial regression and Cox proportional hazards models were used to assess breastfeeding initiation and duration according to smoking status. RESULTS: Overall, 1789 women participated (weighted response rate: 61%). Approximately 74% of the women ever breastfed; 31% of the women ever smoked while pregnant. Compared with nonsmokers, the moderate/heavy smokers and light smokers were less likely to initiate breastfeeding, after controlling for sociodemographic characteristics, the presence of other smokers in the household, alcohol use, mode of delivery, and infant hospitalization. Compared with nonsmokers, the moderate/heavy smokers, light smokers, and smokers who quit during pregnancy were more likely to wean over time, controlling for the same covariates. There were no significant differences between nonsmokers and smokers regarding reasons for not initiating or ceasing breastfeeding. CONCLUSIONS: Mothers who smoked initiated breastfeeding less often and weaned earlier than nonsmoking mothers. Incorporating knowledge of the association between smoking and breastfeeding into existing smoking-cessation and breastfeeding programs could provide opportunities to reduce perinatal exposure to tobacco smoke, improve interest in breastfeeding, and address other barriers to breastfeeding that smoking mothers may face.

Preclinical toxicological examination of a putative prostate cancer-specific 4-methyl-1-nitroacridine derivative in rodents.

Nitroacridines are potent DNA-binding and cytotoxic agents in cancer cells, but could not be developed clinically due to high systemic toxicities. We are developing a 1-nitroacridine derivative, 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), as an effective chemotherapeutic agent for prostate cancer. C-1748 demonstrates high antitumor efficacy against human prostate cancer xenografts with markedly low mutagenicity and toxicity in dogs compared with its parent 9-(2'-hydroxyethylamino)-1-nitroacridine (C-857). A surprising feature of C-1748 is the 40-fold difference in 50% inhibitory concentration between DU145 prostate cancer and HL-60 leukemia cells. In this study, we report the preclinical toxicity study of a single acute dose of C-1748 in Copenhagen rats and BALB/c mice, intraperitoneally and intravenously for 24 h and 7 days. The effect of C-1748 on hematology, cardiac and liver enzymes, and renal electrolytes was assessed by blood and serum analysis. The LD50 (lethal dose, 50%) for C-1748 was 9 and 13.42 mg/kg compared with 2.2 and 3 mg/kg for C-857 intraperitoneally and intravenously, respectively, in mice. In Copenhagen rats, LD50 was 15 and 14.4 mg/kg intraperitoneally and intravenously, respectively, compared to 4 and 1.3 mg/kg for C-857. No changes in blood cell counts were observed, which were in the normal range for rodents. No changes were observed in clinical chemistries of enzymes such as aspartate aminotransferase, alkaline phosphatase and creatine phosphokinase, which were within the normal range of values. No genome alterations were seen in prostate cancer cell lines by comparative genomic hybridization together with a lack of systemic toxicity, making it a unique cancer cell-type-specific drug that needs further clinical evaluation for toxicity and synergy in combination chemotherapy regimens.

Synthetic dimer of indole-3-carbinol: second generation diet derived anti-cancer agent in hormone sensitive prostate cancer.

BACKGROUND: Cruciferous vegetables have been found to have anti-prostate cancer effects. The active compounds mediating these effects include indoles such as indole-3-carbinol (I3C) and isothiocyanates. I3C is unstable having tissue tropic effects and clinical utility has been partly addressed by the synthesis of a more stable dimer diindolylmethane (DIM). METHODS: Anti-proliferative activity was measured by XTT assay and cytosolic proteins quantitated by Western blot analysis. RESULTS: DIM (IC(50) 50 microM) is a better anti-proliferative agent than I3C (IC(50) 150 microM) in androgen dependent LNCaP cells, inhibits DNA synthesis, and growth of R1881 stimulated LNCaP cells. Androgen receptor (AR), cyclin D1, and cdk4, induced by R1881, are downregulated by DIM. DIM downregulates phosphorylated Akt and phosphatidyl inositol 3-kinase and downstream inhibition of cyclin D1 and cdk4. CONCLUSION: These studies provide evidence that DIM is a second-generation chemopreventive agent with a viable cellular target and has clinical potential as an anti-prostate cancer chemopreventive.

3,3'-Diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer.

Epidemiological evidences suggest that the progression and promotion of prostate cancer (CaP) can be modulated by diet. Since all men die with prostate cancer rather than of the disease, it is of particular interest to prevent or delay the progression of the disease by chemopreventive strategies. We have been studying the anticancer properties of compounds present in cruciferous vegetables such as indole-3-carbinol (I3C). Diindolylmethane (DIM) is a dimer of I3C that is formed under acidic conditions and unlike I3C is more stable with higher anti-cancer effects. In the present report, we demonstrate that DIM is a potent anti-proliferative agent compared to I3C in the hormone independent DU 145 CaP cells. The anti-prostate cancer effect is mediated by the inhibition of the Akt signal transduction pathway as DIM, in sharp contrast to I3C, induces the downregulation of Akt, p-Akt, and PI3 kinase. DIM also induced a G1 arrest in DU 145 cells by flow cytometry and downstream concurrent inhibition of cell cycle parameters such as cyclin D1, cdk4, and cdk6. Our data suggest a need for further development of DIM, as a chemopreventive agent for CaP, which justifies epidemiological evidences and molecular targets that are determinants for CaP dissemination/progression. The ingestion of DIM may benefit CaP patients and reduce disease recurrence by eliminating micro-metastases that may be present in patients who undergo radical prostatectomy.