Melissa Wilson | University of Southern California (original) (raw)
Papers by Melissa Wilson
Journal of Womens Health, Sep 1, 2011
Objective: Depression is common among HIV-infected women, predicts treatment nonadherence, and co... more Objective: Depression is common among HIV-infected women, predicts treatment nonadherence, and consequently may impact vertical transmission of HIV. We report findings from a study evaluating preconception, pregnancy, and postpartum depressive symptoms in HIV-infected vs. at-risk, HIV-uninfected women. Methods: We examined the prevalence and predictors of elevated perinatal (i.e., pregnancy and/or postpartum) depressive symptoms using a Center for Epidemiological Studies-Depression (CES-D) scale score of ‡ 16 in 139 HIV-infected and 105 HIV-uninfected women (62% African American) from the Women's Interagency HIV Study (WIHS). Results: The prevalence of elevated perinatal depressive symptoms did not differ by HIV serostatus (HIV-infected 44%, HIV-uninfected 50%, p = 0.44). Among HIV-infected women, the strongest predictor of elevated symptoms was preconception depression (odds ratio [OR] 5.71, 95% confidence interval [CI] 2.67-12.19, p < 0.001); crack, cocaine, and/or heroin use during preconception was marginally significant (OR 3.10, 95% CI 0.96-10.01, p = 0.06). In the overall sample, additional significant predictors of perinatal depression included having multiple sex partners preconception (OR 2.20, 95% CI 1.12-4.32, p = 0.02), use of preconception mental health services (OR 2.51, 95% CI 1.03-6.13, p = 0.04), and not graduating from high school (OR 1.92, 95% CI 1.06-3.46, p = 0.03). Conclusions: Elevated perinatal depressive symptoms are common among HIV-infected and at-risk HIVuninfected women. Depressive symptoms before pregnancy were the strongest predictor of perinatal symptoms. Findings underscore the importance of early and ongoing assessment and treatment to ensure low vertical transmission rates and improving postpregnancy outcomes for mothers and children.
Hypertension, Aug 1, 2018
The genetic susceptibility to preeclampsia, a pregnancy-specific complication with significant ma... more The genetic susceptibility to preeclampsia, a pregnancy-specific complication with significant maternal and fetal morbidity, has been poorly characterized. To identify maternal genes associated with preeclampsia risk, we assembled 498 cases and 1864 controls of European ancestry from preeclampsia case-control collections in 5 different US sites (with additional matched population controls), genotyped samples on a cardiovascular gene-centric array composed of variants from ≈2000 genes selected based on prior genetic studies of cardiovascular and metabolic diseases and performed case-control genetic association analysis on 27 429 variants passing quality control. In silico replication testing of 9 lead signals with P<10 −4 was performed in independent European samples from the SOPHIA (Study of Pregnancy Hypertension in Iowa) and Inova cohorts (212 cases, 456 controls). Multiethnic assessment of lead signals was then performed in samples of black (26 cases, 136 controls), Hispanic (132 cases, 468 controls), and East Asian (9 cases, 80 controls) ancestry. Multiethnic meta-analysis (877 cases, 3004 controls) revealed a study-wide statistically significant association of the rs9478812 variant in the pleiotropic PLEKHG1 gene (odds ratio, 1.40 [1.23-1.60]; P meta =5.90×10 −7). The rs9478812 effect was even stronger in the subset of European cases with known early-onset preeclampsia (236 cases diagnosed <37 weeks, 1864 controls; odds ratio, 1.59 [1.27-1.98]; P=4.01×10 −5). PLEKHG1 variants have previously been implicated in genome-wide association studies of blood pressure, body weight, and neurological disorders. Although larger studies are required to further define maternal preeclampsia heritability, this study identifies a novel maternal risk locus for further investigation.
Environmental Research, May 1, 2013
Background-Exposure to ambient air pollution is linked to adverse pregnancy outcomes. Previous re... more Background-Exposure to ambient air pollution is linked to adverse pregnancy outcomes. Previous reports examining the relationship between ambient air pollution and Hypertensive Disorders of Pregnancy have been inconsistent. Objectives-We evaluated the effects of ambient air pollution on the odds of Hypertensive Disorder of Pregnancy and whether these associations varied by body mass index (BMI). Methods-We conducted a retrospective, case-control study among 298 predominantly Hispanic women (136 clinically-confirmed cases) who attended the Los Angeles County + University of Southern California Women's and Children's Hospital during 1996-2008. Trimester-specific carbon monoxide (CO), nitrogen dioxide (NO 2), ozone (O 3), and particulate matter with aerodynamic diameter <10µm and <2.5µm (PM 10 , PM 2.5) exposure were estimated based on 24-hr exposure level at residential address. Logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 2 standard deviation increase in exposure levels. Results-Exposures to CO and PM 2.5 in the first trimester were significantly associated with Hypertensive Disorders of Pregnancy, and these associations were modified by BMI. In non-obese women (BMI <30), first trimester exposures to PM 2.5 and CO were significantly associated with increased odds of Hypertensive Disorder of Pregnancy (ORs per 2-standard deviation increase in PM 2.5 (7µg/m 3) and CO (1ppm) exposures were 9.10 [95% CI: 3.33-24.6] and 4.96 [95% CI: 1.85-13.31], respectively). Additionally, there was a significantly positive association between exposure to O 3 in the second trimester and Hypertensive Disorder of Pregnancy (OR per 15ppb=2.05; 95% CI: 1.22-3.46).
Healthcare, Sep 30, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Human Molecular Genetics, Jan 13, 2012
SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a s... more SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a serine protease inhibitor involved in a wide range of biological processes. Recently, it has been shown to be upregulated in human placental diseases in association with a hypomethylation of the 5 ′ region of the gene. In the present study, we show that the promoter of SERPINA3 is transcriptionally activated by three transcription factors (TFs) (SP1, MZF1 and ZBTB7B), the level of induction being dependent on the rs1884082 single nucleotide polymorphism (SNP) located inside the promoter, the T allele being consistently induced to a higher level than the G, with or without added TFs. When the promoter was methylated, the response to ZBTB7B was allele specific (the G allele was strongly induced, while the T allele was strongly downregulated). We propose an adaptive model to explain the interest of such a regulation for placental function and homeostasis. Overexpression of SERPINA3 in JEG-3 cells, a trophoblast cell model, decreased cell adhesion to the extracellular matrix and to neighboring cells, but protects them from apoptosis, suggesting a way by which this factor could be deleterious at high doses. In addition, we show in different human populations that the T allele appears to predispose to Intra Uterine Growth Restriction (IUGR), while a G allele at a second SNP located in the second exon (rs4634) increases the risk of preeclampsia. Our results provide mechanistic views inside the involvement of SERPINA3 in placental diseases, through its regulation by a combination of epigenetic, genetic and TF-mediated regulations.
American Journal of Obstetrics and Gynecology, Sep 1, 2009
Objective-To determine if polymorphisms in the Transforming Growth Factor Beta-3 (TGF-β3) gene ar... more Objective-To determine if polymorphisms in the Transforming Growth Factor Beta-3 (TGF-β3) gene are associated with risk of pregnancy-induced hypertension (PIH) in case-control mother-baby dyads. Study Design-Cases (N=136) and controls (N=169) were recruited from the Los Angeles County + University of Southern California Women's and Children's Hospital. We genotyped four TGF-β3 polymorphisms and examined association with PIH using logistic regression, adjusting for parity, maternal age, gestational age at delivery, fetal (or maternal) genotypes for the polymorphism in question, and for the three other polymorphisms within the TGF-β3 gene. Results-Only one of the TGF-β3 polymorphisms (rs11466414) was associated with PIH. Mothers who carried a baby with a minor allele were at decreased risk (OR multi-locus adj = 0.32, 95% CI: 0.14, 0.77). Maternal TGF-β3 variants had no effect on risk of PIH. Conclusion-A fetal TGF-beta3 polymorphism (rs11466414) is associated with pregnancyinduced hypertension in a predominantly Hispanic population.
Nutrients, Apr 30, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Preeclampsia remains a major problem worldwide for mothers and babies. It is estimated that yearl... more Preeclampsia remains a major problem worldwide for mothers and babies. It is estimated that yearly 50 000 women die in developing countries from preeclampsia. Careful maternal observation for the signs of preeclampsia and delivery of women with increasingly severe preeclampsia is the cornerstone of management (as it has been for the past 100 years). Maternal mortality is, therefore, much less in developed countries with the capacity for careful perinatal observation, but morbidity is considerable and remains the leading cause of admissions to intensive care for pregnant women. Also, the appropriate delivery of women who develop increasingly severe preeclampsia early in gestation accounts for 8% of all preterm births.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2012
share the presence of increased left ventricular mass and increased left atrial diameter. Whether... more share the presence of increased left ventricular mass and increased left atrial diameter. Whether these increases are also present in the preclinical phase of chronic hypertension in women with a history of preeclampsia is still unknown. Objectives: To evaluate whether increased left ventricular mass index and/or left atrial widening in normotensive formerly preeclamptic women are associated with the development of chronic hypertension. Methods: 324 Women with a history of preeclampsia, who were normotensive at the time of a diagnostic work-up 4 months postpartum, were included in this study. The tests employed included cardiac ultrasound and blood pressure measurements. Left ventricular mass was indexed (LVMi) for length in meters 2.7. To follow up on the health state, we send a health checklist to each screened former patient once every two years. The information of the diagnostic work-up and the one of the returned checklists were used for the statistical analysis by Uni-and Multivariate Cox regression analysis. Results: Women who had developed chronic hypertension during a medium follow-up period of 6 years showed a significant Hazard Ratio (HR) of 1.11 (95% CI 1.03-1.18) for Left ventricular mass index, 1.13 (95% CI 1.06-1.20) for diastolic BP, 1.07 (95% CI 1.02-1.11) for systolic BP, 1.05 (95% CI 1.01-1.10) for Heart Rate and 0.215 (95% CI 0.055-0.848) for EA ratio. The multivariate top-down analysis showed a significant HR only for LVMi and diastolic BP, 1.08 (95% CI 1.00-1.18) and 1.10 (95% CI 1.02-1.19), respectively. Conclusion: Increased diastolic blood pressure and increased LVMi in normotensive formerly preeclamptic women are both associated with the development of chronic hypertension.
Healthcare, 2021
Despite the demonstrated need for sustainable and effective carceral health care, justice-involve... more Despite the demonstrated need for sustainable and effective carceral health care, justice-involved medical education curricula are limited, and it’s unclear if informal clinical education is sufficient. Investigators aimed to quantify medical student involvement with carceral populations and explore how students’ knowledge of and attitudes towards justice-involved patients changed over the course of their training. A survey was designed by the investigators and sent to all current medical students at a single United States medical school. Stata 14.0 was used to compare results between the years of medical school. Differences between groups were tested using linear regression. Most 4th year students reported working in a carceral health setting. An increase in overall knowledge of justice-involved patients was observed as carceral medicine education (ptrend = 0.02), hours worked in a jail (ptrend < 0.01), and substance abuse training (ptrend < 0.01) increased. Overall attitude ...
Pregnancy hypertension, Jan 15, 2017
The purpose of this study was to validate our previous genetic association findings related to th... more The purpose of this study was to validate our previous genetic association findings related to the endoglin (ENG) pathway from an American Caucasian preeclampsia cohort in independent preeclampsia cohorts. We also sought to explore the ENG pathway for new genetic associations in these independent cohorts. We used a tagging single nucleotide (tSNP) approach to assess genetic variability across five ENG pathway genes (ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2) in a Caucasian cohort from Norway (n = 77 preeclampsia cases & n = 63 normotensive controls) and a White Hispanic cohort from Southern California (n = 69 preeclampsia cases & n = 106 normotensive controls). Univariate analyses (Chi Square, Fisher's Exact) and multivariate logistic regression were conducted to evaluate the association between tSNP genotype distributions and pregnancy outcome in each cohort. Logistic regression models were adjusted for maternal age at delivery, infant sex, parity, smoking during pregnancy, and pre-...
BMC Pregnancy and Childbirth, 2019
Background: The burden of childhood and adult obesity disproportionally affects Hispanic and Afri... more Background: The burden of childhood and adult obesity disproportionally affects Hispanic and African-American populations in the US, and these groups as well as populations with lower income and education levels are disproportionately affected by environmental pollution. Pregnancy is a critical developmental period where maternal exposures may have significant impacts on infant and childhood growth as well as the future health of the mother. We initiated the "Maternal And Developmental Risks from Environmental and Social Stressors (MADRES)" cohort study to address critical gaps in understanding the increased risk for childhood obesity and maternal obesity outcomes among minority and low-income women in urban Los Angeles. Methods: The MADRES cohort is specifically examining whether pre-and postpartum environmental exposures, in addition to exposures to psychosocial and built environment stressors, lead to excessive gestational weight gain and postpartum weight retention in women and to perturbed infant growth trajectories and increased childhood obesity risk through altered psychological, behavioral and/or metabolic responses. The ongoing MADRES study is a prospective pregnancy cohort of 1000 predominantly lower-income, Hispanic women in Los Angeles, CA. Enrollment in the MADRES cohort is initiated prior to 30 weeks gestation from partner community health clinics in Los Angeles. Cohort participants are followed through their pregnancies, at birth, and during the infant's first year of life through a series of in-person visits with interviewer-administered questionnaires, anthropometric measurements and biospecimen collection as well as telephone interviews conducted with the mother.
Biomedicines
Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks a... more Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks and consequent transcriptomic changes. Here, we analyzed genome-wide DNA methylation and transcriptome data to reveal the epigenetic basis of disease pathways that may lead to benign or malignant GTDs. RNA-Seq, mRNA microarray, and Human Methylation 450 BeadChip data from complete moles and choriocarcinoma cells were bioinformatically analyzed. Paraffin-embedded tissues from complete moles and control placentas were used for tissue microarray construction, DNMT3B immunostaining and immunoscoring. We found that DNA methylation increases with disease severity in GTDs. Differentially expressed genes are mainly upregulated in moles while predominantly downregulated in choriocarcinoma. DNA methylation principally influences the gene expression of villous trophoblast differentiation-related or predominantly placenta-expressed genes in moles and choriocarcinoma cells. Affected genes in these sub...
full-text repositories, the corrected article has also been resubmitted to those repositories.
Nutrients, 2021
There has been increasing interest in time-restricted eating to attain intermittent fasting’s met... more There has been increasing interest in time-restricted eating to attain intermittent fasting’s metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve (AUC0–4) that were non-inferior to those who continued with the water fast (p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC0–4 in the FMD group was non-inferior to that in the water fast group (p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expe...
JMIR Public Health and Surveillance, 2021
Background Public health organizations have begun to use social media to increase awareness of he... more Background Public health organizations have begun to use social media to increase awareness of health harm and positively improve health behavior. Little is known about effective strategies to disseminate health education messages digitally and ultimately achieve optimal audience engagement. Objective This study aims to assess the difference in audience engagement with identical antismoking health messages on three social media sites (Twitter, Facebook, and Instagram) and with a referring link to a tobacco prevention website cited in these messages. We hypothesized that health messages might not receive the same user engagement on these media, although these messages were identical and distributed at the same time. Methods We measured the effect of health promotion messages on the risk of smoking among users of three social media sites (Twitter, Facebook, and Instagram) and disseminated 1275 health messages between April 19 and July 12, 2017 (85 days). The identical messages were di...
Pregnancy hypertension, 2013
Previously preeclamptic women may express cognitive difficulties, which have largely been unappre... more Previously preeclamptic women may express cognitive difficulties, which have largely been unappreciated or attributed to stresses of a complicated pregnancy. This study aimed to explore the scope of perceived neurocognitive and psychosocial problems as well as quality of life following preeclampsia. Observational study. Through website promotion and e-mail, registrants of the USA-based Preeclampsia Foundation who experienced preeclampsia in the past 20years were invited to complete a web-based survey. Participants were requested to ask an acquaintance that had a normotensive pregnancy to also complete the survey (controls). The Cognitive Failures Questionnaire (CFQ), abbreviated WHO Quality Of Life questionnaire (WHOQOL-BREF), Social Functioning Questionnaire (SFQ) and Breslau Short Screening Scale for DSM-IV Posttraumatic Stress Disorder were used in the survey. Analysis was performed using Mann-Whitney U tests and linear regression. 966 cases and 342 controls completed the survey ...
ABSTRACTObjectiveTo assess whether women with a genetic predisposition to medical conditions know... more ABSTRACTObjectiveTo assess whether women with a genetic predisposition to medical conditions known to increase preeclampsia risk have an increased risk of preeclampsia in pregnancy.DesignCase-control study.Setting and populationPreeclampsia cases (n=498) and controls (n=1864) of European ancestry from 5 US sites genotyped on a cardiovascular gene-centric array.MethodsSignificant single nucleotide polymorphisms (SNPs) from 21 traits in 7 disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal, thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous, scaled genetic instrument with preeclampsia. Odds of preeclampsia were compared across quartiles of the genetic instrument and evaluated for significance using a test for trend.Main Outcome Measurespreeclampsia.ResultsAn increasing burden ...
International Journal of Molecular Sciences
Gene expression studies of molar pregnancy have been limited to a small number of candidate loci.... more Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10...
JMIR Public Health and Surveillance, 2021
[This corrects the article DOI: 10.2196/24429.].
Journal of Womens Health, Sep 1, 2011
Objective: Depression is common among HIV-infected women, predicts treatment nonadherence, and co... more Objective: Depression is common among HIV-infected women, predicts treatment nonadherence, and consequently may impact vertical transmission of HIV. We report findings from a study evaluating preconception, pregnancy, and postpartum depressive symptoms in HIV-infected vs. at-risk, HIV-uninfected women. Methods: We examined the prevalence and predictors of elevated perinatal (i.e., pregnancy and/or postpartum) depressive symptoms using a Center for Epidemiological Studies-Depression (CES-D) scale score of ‡ 16 in 139 HIV-infected and 105 HIV-uninfected women (62% African American) from the Women's Interagency HIV Study (WIHS). Results: The prevalence of elevated perinatal depressive symptoms did not differ by HIV serostatus (HIV-infected 44%, HIV-uninfected 50%, p = 0.44). Among HIV-infected women, the strongest predictor of elevated symptoms was preconception depression (odds ratio [OR] 5.71, 95% confidence interval [CI] 2.67-12.19, p < 0.001); crack, cocaine, and/or heroin use during preconception was marginally significant (OR 3.10, 95% CI 0.96-10.01, p = 0.06). In the overall sample, additional significant predictors of perinatal depression included having multiple sex partners preconception (OR 2.20, 95% CI 1.12-4.32, p = 0.02), use of preconception mental health services (OR 2.51, 95% CI 1.03-6.13, p = 0.04), and not graduating from high school (OR 1.92, 95% CI 1.06-3.46, p = 0.03). Conclusions: Elevated perinatal depressive symptoms are common among HIV-infected and at-risk HIVuninfected women. Depressive symptoms before pregnancy were the strongest predictor of perinatal symptoms. Findings underscore the importance of early and ongoing assessment and treatment to ensure low vertical transmission rates and improving postpregnancy outcomes for mothers and children.
Hypertension, Aug 1, 2018
The genetic susceptibility to preeclampsia, a pregnancy-specific complication with significant ma... more The genetic susceptibility to preeclampsia, a pregnancy-specific complication with significant maternal and fetal morbidity, has been poorly characterized. To identify maternal genes associated with preeclampsia risk, we assembled 498 cases and 1864 controls of European ancestry from preeclampsia case-control collections in 5 different US sites (with additional matched population controls), genotyped samples on a cardiovascular gene-centric array composed of variants from ≈2000 genes selected based on prior genetic studies of cardiovascular and metabolic diseases and performed case-control genetic association analysis on 27 429 variants passing quality control. In silico replication testing of 9 lead signals with P<10 −4 was performed in independent European samples from the SOPHIA (Study of Pregnancy Hypertension in Iowa) and Inova cohorts (212 cases, 456 controls). Multiethnic assessment of lead signals was then performed in samples of black (26 cases, 136 controls), Hispanic (132 cases, 468 controls), and East Asian (9 cases, 80 controls) ancestry. Multiethnic meta-analysis (877 cases, 3004 controls) revealed a study-wide statistically significant association of the rs9478812 variant in the pleiotropic PLEKHG1 gene (odds ratio, 1.40 [1.23-1.60]; P meta =5.90×10 −7). The rs9478812 effect was even stronger in the subset of European cases with known early-onset preeclampsia (236 cases diagnosed <37 weeks, 1864 controls; odds ratio, 1.59 [1.27-1.98]; P=4.01×10 −5). PLEKHG1 variants have previously been implicated in genome-wide association studies of blood pressure, body weight, and neurological disorders. Although larger studies are required to further define maternal preeclampsia heritability, this study identifies a novel maternal risk locus for further investigation.
Environmental Research, May 1, 2013
Background-Exposure to ambient air pollution is linked to adverse pregnancy outcomes. Previous re... more Background-Exposure to ambient air pollution is linked to adverse pregnancy outcomes. Previous reports examining the relationship between ambient air pollution and Hypertensive Disorders of Pregnancy have been inconsistent. Objectives-We evaluated the effects of ambient air pollution on the odds of Hypertensive Disorder of Pregnancy and whether these associations varied by body mass index (BMI). Methods-We conducted a retrospective, case-control study among 298 predominantly Hispanic women (136 clinically-confirmed cases) who attended the Los Angeles County + University of Southern California Women's and Children's Hospital during 1996-2008. Trimester-specific carbon monoxide (CO), nitrogen dioxide (NO 2), ozone (O 3), and particulate matter with aerodynamic diameter <10µm and <2.5µm (PM 10 , PM 2.5) exposure were estimated based on 24-hr exposure level at residential address. Logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 2 standard deviation increase in exposure levels. Results-Exposures to CO and PM 2.5 in the first trimester were significantly associated with Hypertensive Disorders of Pregnancy, and these associations were modified by BMI. In non-obese women (BMI <30), first trimester exposures to PM 2.5 and CO were significantly associated with increased odds of Hypertensive Disorder of Pregnancy (ORs per 2-standard deviation increase in PM 2.5 (7µg/m 3) and CO (1ppm) exposures were 9.10 [95% CI: 3.33-24.6] and 4.96 [95% CI: 1.85-13.31], respectively). Additionally, there was a significantly positive association between exposure to O 3 in the second trimester and Hypertensive Disorder of Pregnancy (OR per 15ppb=2.05; 95% CI: 1.22-3.46).
Healthcare, Sep 30, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Human Molecular Genetics, Jan 13, 2012
SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a s... more SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a serine protease inhibitor involved in a wide range of biological processes. Recently, it has been shown to be upregulated in human placental diseases in association with a hypomethylation of the 5 ′ region of the gene. In the present study, we show that the promoter of SERPINA3 is transcriptionally activated by three transcription factors (TFs) (SP1, MZF1 and ZBTB7B), the level of induction being dependent on the rs1884082 single nucleotide polymorphism (SNP) located inside the promoter, the T allele being consistently induced to a higher level than the G, with or without added TFs. When the promoter was methylated, the response to ZBTB7B was allele specific (the G allele was strongly induced, while the T allele was strongly downregulated). We propose an adaptive model to explain the interest of such a regulation for placental function and homeostasis. Overexpression of SERPINA3 in JEG-3 cells, a trophoblast cell model, decreased cell adhesion to the extracellular matrix and to neighboring cells, but protects them from apoptosis, suggesting a way by which this factor could be deleterious at high doses. In addition, we show in different human populations that the T allele appears to predispose to Intra Uterine Growth Restriction (IUGR), while a G allele at a second SNP located in the second exon (rs4634) increases the risk of preeclampsia. Our results provide mechanistic views inside the involvement of SERPINA3 in placental diseases, through its regulation by a combination of epigenetic, genetic and TF-mediated regulations.
American Journal of Obstetrics and Gynecology, Sep 1, 2009
Objective-To determine if polymorphisms in the Transforming Growth Factor Beta-3 (TGF-β3) gene ar... more Objective-To determine if polymorphisms in the Transforming Growth Factor Beta-3 (TGF-β3) gene are associated with risk of pregnancy-induced hypertension (PIH) in case-control mother-baby dyads. Study Design-Cases (N=136) and controls (N=169) were recruited from the Los Angeles County + University of Southern California Women's and Children's Hospital. We genotyped four TGF-β3 polymorphisms and examined association with PIH using logistic regression, adjusting for parity, maternal age, gestational age at delivery, fetal (or maternal) genotypes for the polymorphism in question, and for the three other polymorphisms within the TGF-β3 gene. Results-Only one of the TGF-β3 polymorphisms (rs11466414) was associated with PIH. Mothers who carried a baby with a minor allele were at decreased risk (OR multi-locus adj = 0.32, 95% CI: 0.14, 0.77). Maternal TGF-β3 variants had no effect on risk of PIH. Conclusion-A fetal TGF-beta3 polymorphism (rs11466414) is associated with pregnancyinduced hypertension in a predominantly Hispanic population.
Nutrients, Apr 30, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Preeclampsia remains a major problem worldwide for mothers and babies. It is estimated that yearl... more Preeclampsia remains a major problem worldwide for mothers and babies. It is estimated that yearly 50 000 women die in developing countries from preeclampsia. Careful maternal observation for the signs of preeclampsia and delivery of women with increasingly severe preeclampsia is the cornerstone of management (as it has been for the past 100 years). Maternal mortality is, therefore, much less in developed countries with the capacity for careful perinatal observation, but morbidity is considerable and remains the leading cause of admissions to intensive care for pregnant women. Also, the appropriate delivery of women who develop increasingly severe preeclampsia early in gestation accounts for 8% of all preterm births.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2012
share the presence of increased left ventricular mass and increased left atrial diameter. Whether... more share the presence of increased left ventricular mass and increased left atrial diameter. Whether these increases are also present in the preclinical phase of chronic hypertension in women with a history of preeclampsia is still unknown. Objectives: To evaluate whether increased left ventricular mass index and/or left atrial widening in normotensive formerly preeclamptic women are associated with the development of chronic hypertension. Methods: 324 Women with a history of preeclampsia, who were normotensive at the time of a diagnostic work-up 4 months postpartum, were included in this study. The tests employed included cardiac ultrasound and blood pressure measurements. Left ventricular mass was indexed (LVMi) for length in meters 2.7. To follow up on the health state, we send a health checklist to each screened former patient once every two years. The information of the diagnostic work-up and the one of the returned checklists were used for the statistical analysis by Uni-and Multivariate Cox regression analysis. Results: Women who had developed chronic hypertension during a medium follow-up period of 6 years showed a significant Hazard Ratio (HR) of 1.11 (95% CI 1.03-1.18) for Left ventricular mass index, 1.13 (95% CI 1.06-1.20) for diastolic BP, 1.07 (95% CI 1.02-1.11) for systolic BP, 1.05 (95% CI 1.01-1.10) for Heart Rate and 0.215 (95% CI 0.055-0.848) for EA ratio. The multivariate top-down analysis showed a significant HR only for LVMi and diastolic BP, 1.08 (95% CI 1.00-1.18) and 1.10 (95% CI 1.02-1.19), respectively. Conclusion: Increased diastolic blood pressure and increased LVMi in normotensive formerly preeclamptic women are both associated with the development of chronic hypertension.
Healthcare, 2021
Despite the demonstrated need for sustainable and effective carceral health care, justice-involve... more Despite the demonstrated need for sustainable and effective carceral health care, justice-involved medical education curricula are limited, and it’s unclear if informal clinical education is sufficient. Investigators aimed to quantify medical student involvement with carceral populations and explore how students’ knowledge of and attitudes towards justice-involved patients changed over the course of their training. A survey was designed by the investigators and sent to all current medical students at a single United States medical school. Stata 14.0 was used to compare results between the years of medical school. Differences between groups were tested using linear regression. Most 4th year students reported working in a carceral health setting. An increase in overall knowledge of justice-involved patients was observed as carceral medicine education (ptrend = 0.02), hours worked in a jail (ptrend < 0.01), and substance abuse training (ptrend < 0.01) increased. Overall attitude ...
Pregnancy hypertension, Jan 15, 2017
The purpose of this study was to validate our previous genetic association findings related to th... more The purpose of this study was to validate our previous genetic association findings related to the endoglin (ENG) pathway from an American Caucasian preeclampsia cohort in independent preeclampsia cohorts. We also sought to explore the ENG pathway for new genetic associations in these independent cohorts. We used a tagging single nucleotide (tSNP) approach to assess genetic variability across five ENG pathway genes (ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2) in a Caucasian cohort from Norway (n = 77 preeclampsia cases & n = 63 normotensive controls) and a White Hispanic cohort from Southern California (n = 69 preeclampsia cases & n = 106 normotensive controls). Univariate analyses (Chi Square, Fisher's Exact) and multivariate logistic regression were conducted to evaluate the association between tSNP genotype distributions and pregnancy outcome in each cohort. Logistic regression models were adjusted for maternal age at delivery, infant sex, parity, smoking during pregnancy, and pre-...
BMC Pregnancy and Childbirth, 2019
Background: The burden of childhood and adult obesity disproportionally affects Hispanic and Afri... more Background: The burden of childhood and adult obesity disproportionally affects Hispanic and African-American populations in the US, and these groups as well as populations with lower income and education levels are disproportionately affected by environmental pollution. Pregnancy is a critical developmental period where maternal exposures may have significant impacts on infant and childhood growth as well as the future health of the mother. We initiated the "Maternal And Developmental Risks from Environmental and Social Stressors (MADRES)" cohort study to address critical gaps in understanding the increased risk for childhood obesity and maternal obesity outcomes among minority and low-income women in urban Los Angeles. Methods: The MADRES cohort is specifically examining whether pre-and postpartum environmental exposures, in addition to exposures to psychosocial and built environment stressors, lead to excessive gestational weight gain and postpartum weight retention in women and to perturbed infant growth trajectories and increased childhood obesity risk through altered psychological, behavioral and/or metabolic responses. The ongoing MADRES study is a prospective pregnancy cohort of 1000 predominantly lower-income, Hispanic women in Los Angeles, CA. Enrollment in the MADRES cohort is initiated prior to 30 weeks gestation from partner community health clinics in Los Angeles. Cohort participants are followed through their pregnancies, at birth, and during the infant's first year of life through a series of in-person visits with interviewer-administered questionnaires, anthropometric measurements and biospecimen collection as well as telephone interviews conducted with the mother.
Biomedicines
Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks a... more Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks and consequent transcriptomic changes. Here, we analyzed genome-wide DNA methylation and transcriptome data to reveal the epigenetic basis of disease pathways that may lead to benign or malignant GTDs. RNA-Seq, mRNA microarray, and Human Methylation 450 BeadChip data from complete moles and choriocarcinoma cells were bioinformatically analyzed. Paraffin-embedded tissues from complete moles and control placentas were used for tissue microarray construction, DNMT3B immunostaining and immunoscoring. We found that DNA methylation increases with disease severity in GTDs. Differentially expressed genes are mainly upregulated in moles while predominantly downregulated in choriocarcinoma. DNA methylation principally influences the gene expression of villous trophoblast differentiation-related or predominantly placenta-expressed genes in moles and choriocarcinoma cells. Affected genes in these sub...
full-text repositories, the corrected article has also been resubmitted to those repositories.
Nutrients, 2021
There has been increasing interest in time-restricted eating to attain intermittent fasting’s met... more There has been increasing interest in time-restricted eating to attain intermittent fasting’s metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve (AUC0–4) that were non-inferior to those who continued with the water fast (p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC0–4 in the FMD group was non-inferior to that in the water fast group (p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expe...
JMIR Public Health and Surveillance, 2021
Background Public health organizations have begun to use social media to increase awareness of he... more Background Public health organizations have begun to use social media to increase awareness of health harm and positively improve health behavior. Little is known about effective strategies to disseminate health education messages digitally and ultimately achieve optimal audience engagement. Objective This study aims to assess the difference in audience engagement with identical antismoking health messages on three social media sites (Twitter, Facebook, and Instagram) and with a referring link to a tobacco prevention website cited in these messages. We hypothesized that health messages might not receive the same user engagement on these media, although these messages were identical and distributed at the same time. Methods We measured the effect of health promotion messages on the risk of smoking among users of three social media sites (Twitter, Facebook, and Instagram) and disseminated 1275 health messages between April 19 and July 12, 2017 (85 days). The identical messages were di...
Pregnancy hypertension, 2013
Previously preeclamptic women may express cognitive difficulties, which have largely been unappre... more Previously preeclamptic women may express cognitive difficulties, which have largely been unappreciated or attributed to stresses of a complicated pregnancy. This study aimed to explore the scope of perceived neurocognitive and psychosocial problems as well as quality of life following preeclampsia. Observational study. Through website promotion and e-mail, registrants of the USA-based Preeclampsia Foundation who experienced preeclampsia in the past 20years were invited to complete a web-based survey. Participants were requested to ask an acquaintance that had a normotensive pregnancy to also complete the survey (controls). The Cognitive Failures Questionnaire (CFQ), abbreviated WHO Quality Of Life questionnaire (WHOQOL-BREF), Social Functioning Questionnaire (SFQ) and Breslau Short Screening Scale for DSM-IV Posttraumatic Stress Disorder were used in the survey. Analysis was performed using Mann-Whitney U tests and linear regression. 966 cases and 342 controls completed the survey ...
ABSTRACTObjectiveTo assess whether women with a genetic predisposition to medical conditions know... more ABSTRACTObjectiveTo assess whether women with a genetic predisposition to medical conditions known to increase preeclampsia risk have an increased risk of preeclampsia in pregnancy.DesignCase-control study.Setting and populationPreeclampsia cases (n=498) and controls (n=1864) of European ancestry from 5 US sites genotyped on a cardiovascular gene-centric array.MethodsSignificant single nucleotide polymorphisms (SNPs) from 21 traits in 7 disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal, thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous, scaled genetic instrument with preeclampsia. Odds of preeclampsia were compared across quartiles of the genetic instrument and evaluated for significance using a test for trend.Main Outcome Measurespreeclampsia.ResultsAn increasing burden ...
International Journal of Molecular Sciences
Gene expression studies of molar pregnancy have been limited to a small number of candidate loci.... more Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10...
JMIR Public Health and Surveillance, 2021
[This corrects the article DOI: 10.2196/24429.].