Category: Nevin Manimala

J Matern Fetal Neonatal Med. 2022 Oct 23:1-7. doi: 10.1080/14767058.2022.2139175. Online ahead of print.

ABSTRACT

BACKGROUND: Gestational diabetes mellitus (GDM) prevalence has risen in the U.S. and worldwide over the past decade. Minority groups, especially Asian and Hispanic women, are often disproportionately affected by GDM. Identifying modifiable risk factors such as sleep-disordered breathing and smoking and their interaction with race/ethnicity could play a pivotal role in preventing GDM.

METHODS: Data from the 2017-2018 National Health and Nutrition Examination Surveys (NHANES) were used to run a survey-weighted multivariable logistic regression assessing the association between sleep-disordered breathing and smoking with GDM among women aged 15-60 (n = 1326). The interaction term of the two predictors and race/ethnicity was introduced to the model to assess the interaction effect. The analyses were adjusted for age, marital status, education level, and BMI.

RESULTS: Approximately 13% of the participants reported having GDM. The lowest prevalence was observed among Non-Hispanic Blacks (7.8%) and the highest was among Other (15.5%). Sleep-disordered breathing was significantly associated with GDM (OR = 1.69, 95% CI 1.05, 2.73). No statistically significant association was observed between smoking and GDM (OR = 1.03, 95% CI 0.47, 2.27), and neither was the association between race/ethnicity and GDM. Furthermore, none of the interaction effects were statistically significant.

CONCLUSION: Preventive strategies targeting GDM should focus on improving modifiable risk factors, such as sleep-disordered breathing. It is important to screen women with sleep-disordered breathing and monitor their blood sugar before becoming pregnant to prevent the development of GDM. Future studies are recommended to understand the lower prevalence of GDM among Black women and the higher prevalence among “Other” race group which mostly includes Asian women.

PMID:36273849 | DOI:10.1080/14767058.2022.2139175

Am J Obstet Gynecol MFM. 2022 Oct 20:100776. doi: 10.1016/j.ajogmf.2022.100776. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with a hypertensive disorder of pregnancy are more likely to have underlying cardiovascular risk factors and are at increased risk of future cardiovascular disease. These patients are more likely to be diagnosed with new onset chronic hypertension and meet the criteria for Metabolic Syndrome postpartum. High-sensitivity C-reactive protein is a marker of general inflammation and may be used to identify increased risk for cardiovascular disease.

OBJECTIVE: This collaborative data sharing study between Yale University, United States (Yale Heart Moms study) and Queen’s University, Canada (Maternal Health Clinic) is to better study the utility of high-sensitivity C-reactive protein in postpartum cardiovascular risk screening, as determined by 30-year risk (Framingham) and Metabolic Syndrome 6-12 months postpartum.

STUDY DESIGN: Patients with a hypertensive disorder of pregnancy (n=478) or an uncomplicated, term pregnancy (n=90) had cardiovascular risk screening and risk scoring performed at 6-12 months postpartum. Patients were excluded if they had a multiple gestation or chronic hypertension, diabetes or cardiovascular disease diagnosed before pregnancy. Patients were categorized according to high-sensitivity C-reactive protein (mg/L) into Normal (<3.0), High (3.1 to <10.0), and Acute (≥10.0) groups. The primary outcome of the study is risk for future cardiovascular events, calculated through surrogate measures such as hypertension and cholesterol. Kruskal Wallis and Chi Square tests were used to compare groups, with post-hoc tests corrected using the Bonferroni method. Multivariable logistic regression was used to assess the association between high-sensitivity C-reactive protein and cardiovascular risk, adjusting for relevant medical and sociodemographic variables. Analysis was completed with IBM SPSS Statistics v27.

RESULTS: Patients in the High and Acute hsCRP groups were more likely to have a BMI≥30, have experienced a hypertensive disorder of pregnancy, have a lower household income, and to have not breastfed or breastfed <6 month, when compared to the Normal hsCRP group (all p<0.05). Patients in the High and Acute hsCRP groups had higher 30-year cardiovascular risk scores and were more likely to have Metabolic Syndrome, when compared to the Normal hsCRP group (all p<0.05). Patients with High hsCRP had a 2-fold odds of Metabolic Syndrome 6-12 months after delivery, compared to those in the Normal hsCRP group (aOR 2.85 (95% CI 1.66, 4.91)), adjusting for hypertensive disorder of pregnancy, body mass index, clinic site, breastfeeding, income, and family history of cardiovascular disease. Those with Acute hsCRP also appeared to have elevated odds of Metabolic Syndrome compared to the Normal hsCRP group (aOR 2.52 (95% CI 1.24, 5.12)). The odds of chronic hypertension were significantly higher (p<0.05) in the High hsCRP group [aOR 1.72 [95% CI 1.12, 2.65]] compared to the Normal group.

CONCLUSIONS: Individuals with elevated postpartum high-sensitivity C-reactive protein are at an increased risk of cardiovascular disease 6-12 months postpartum after a pregnancy complicated by a hypertensive disorder of pregnancy. Future research is critical to determine the most comprehensive and accurate method and timing of postpartum cardiovascular risk screening in order to decrease the incidence of preventable cardiovascular mortality among women.

PMID:36273813 | DOI:10.1016/j.ajogmf.2022.100776

Genet Epidemiol. 2022 Oct 23. doi: 10.1002/gepi.22506. Online ahead of print.

ABSTRACT

Mendelian randomization (MR) is the use of genetic variants to assess the existence of a causal relationship between a risk factor and an outcome of interest. Here, we focus on two-sample summary-data MR analyses with many correlated variants from a single gene region, particularly on cis-MR studies which use protein expression as a risk factor. Such studies must rely on a small, curated set of variants from the studied region; using all variants in the region requires inverting an ill-conditioned genetic correlation matrix and results in numerically unstable causal effect estimates. We review methods for variable selection and estimation in cis-MR with summary-level data, ranging from stepwise pruning and conditional analysis to principal components analysis, factor analysis, and Bayesian variable selection. In a simulation study, we show that the various methods have comparable performance in analyses with large sample sizes and strong genetic instruments. However, when weak instrument bias is suspected, factor analysis and Bayesian variable selection produce more reliable inferences than simple pruning approaches, which are often used in practice. We conclude by examining two case studies, assessing the effects of low-density lipoprotein-cholesterol and serum testosterone on coronary heart disease risk using variants in the HMGCR and SHBG gene regions, respectively.

PMID:36273411 | DOI:10.1002/gepi.22506

Bull Math Biol. 2022 Oct 23;84(12):137. doi: 10.1007/s11538-022-01088-2.

ABSTRACT

The MEK/ERK signalling pathway is involved in cell division, cell specialisation, survival and cell death (Shaul and Seger in Biochim Biophys Acta (BBA)-Mol Cell Res 1773(8):1213-1226, 2007). Here we study a polynomial dynamical system describing the dynamics of MEK/ERK proposed by Yeung et al. (Curr Biol 2019, https://doi.org/10.1016/j.cub.2019.12.052 ) with their experimental setup, data and known biological information. The experimental dataset is a time-course of ERK measurements in different phosphorylation states following activation of either wild-type MEK or MEK mutations associated with cancer or developmental defects. We demonstrate how methods from computational algebraic geometry, differential algebra, Bayesian statistics and computational algebraic topology can inform the model reduction, identification and parameter inference of MEK variants, respectively. Throughout, we show how this algebraic viewpoint offers a rigorous and systematic analysis of such models.

PMID:36273372 | DOI:10.1007/s11538-022-01088-2

Breast Cancer Res Treat. 2022 Oct 23. doi: 10.1007/s10549-022-06749-3. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer.

METHODS: A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC.

RESULTS: Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC.

CONCLUSION: In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.

PMID:36273358 | DOI:10.1007/s10549-022-06749-3

Abdom Radiol (NY). 2022 Oct 23. doi: 10.1007/s00261-022-03708-w. Online ahead of print.

ABSTRACT

PURPOSE: To characterize intraplacental blood flow patterns in placenta accreta spectrum (PAS) with color and spectral Doppler imaging.

METHODS: Thirty-two patients at risk for PAS underwent ultrasound imaging with both color and spectral Doppler. The placenta was inspected for areas of vascularity by color Doppler, particularly within the lower uterine segment. Spectral Doppler waveforms were obtained from these vessels and categorized as either intraplacental or subplacental (myometrial), venous or arterial, fetal or maternal (based on heart rate). Arterial waveforms were measured for heart rate, peak systolic velocity, end diastolic velocity, and resistive index. Statistical comparisons were made between cases with and without PAS using Fisher exact tests (categorical variables) and Mann-Whitney U tests (numerical indices). Interobserver agreement was characterized with kappa coefficients.

RESULTS: At delivery, there were 19 cases with PAS and 13 without PAS. On ultrasound studies, clustered intraplacental vascularity was found in the lower uterine segment in 66% of cases (95% of PAS cases and 23% cases without PAS; p < 0.0001). Maternal arterial waveforms were found within the vascular cluster in 84% of PAS cases and 15% of cases without PAS (p < 0.0001). A traversing fetal artery was found within the vascular cluster in 56% of cases (84% PAS cases and 15% cases without PAS; p = 0.001). Venous waveforms were found in 84% of PAS cases and 15% of cases without PAS. Interobserver agreement was good to excellent.

CONCLUSION: Intraplacental blood flow pattern in PAS is characterized by an intraplacental vascular cluster containing low-resistance maternal arterial flow and transplacental fetal arteries.

PMID:36273328 | DOI:10.1007/s00261-022-03708-w

Int J Fertil Steril. 2022 Oct 1;16(4):286-291. doi: 10.22074/ijfs.2021.534736.1163.

ABSTRACT

BACKGROUND: Impaired expression of genes which act on hormone signaling pathways is one of the factors affecting miscarriage. In this study, the expression levels of insulin receptor (INSR) and insulin receptor substrates-1 (IRS-1) genes in endometrial tissue of infertile women and fertile women with miscarriage in less than twenty weeks gestation for unknown reasons were evaluated.

MATERIALS AND METHODS: In this case-control study, forty-two fertile women with children and 42 infertile women, who underwent in vitro fertilization (IVF), were selected. Both groups had abortions under twenty weeks gestation for unknown reasons. The endometrial tissue of all patients was prepared to evaluate the expression of INSR and IRS-1 genes by quantitative real-time polymerase chain reaction (PCR) method after RNA extraction.

RESULTS: There was a statistically significant relationship between the expressions of INSR and IRS-1 genes in the endometrial tissue of the infertile women compared with the fertile women (P=0.002 and P=0.008, respectively). The expression level of genes was decreased in both groups by age and increasing body mass index (BMI). Comparison of genes expression levels in healthy and diabetic participants in each group showed a significant difference (P<0.0001), but no meaningful difference was indicated between diabetic infertile and fertile groups in terms of gene expression. INSR gene expression levels showed an increase in the fertile group in the second 10 weeks and a decrease in IRS-1 gene expression. But in the infertile group, both genes showed a slight increase in expression.

CONCLUSION: It seems a decreased expression of insulin signaling pathway genes in the endometrial tissue of infertile women can be one of reasons for unspecified abortion. These genes may be strong molecular markers for infertility.

PMID:36273315 | DOI:10.22074/ijfs.2021.534736.1163

Int J Fertil Steril. 2022 Oct 1;16(4):281-285. doi: 10.22074/ijfs.2021.537125.1171.

ABSTRACT

BACKGROUND: Granulocyte colony stimulating factor (GCSF) has been introduced as an immunomodulatory agent by increasing implantation rate in vitro fertilization (IVF) patients but it has not been studied in intrauterine insemination (IUI) patients. The aim of this study is to answer the role of GCSF in implantation rate of IUI.

MATERIALS AND METHODS: In this prospective double-blind randomized control trial, 320 eligible patients were enrolled, who were referred to the referral infertility clinic of Shiraz University of Medical Sciences from February 2018 till the end of 2019. They were divided into two groups randomly. After collecting the demographic data, all patients received clomiphene citrate from the 5th day of the menstruation cycle for 5 days. 50-150 units of recombinant purified follicle-stimulating factor (FSH) were started from the 8th day of the cycle. Follicle monitoring was done by transvaginal sonography till a mature follicle of 18 mm or more was developed. Human chorionic gonadotropin (HCG) injection was done in both groups with intrauterine administration of 300 μg GCSF in the case group and normal saline in the control group simultaneously. After 36 hours, IUI was performed. The clinical pregnancy, miscarriage, and ongoing pregnancy rates of both groups were calculated by SPSS software.

RESULTS: The results showed improvement of clinical pregnancy rate [15.38% vs. 13.81% OR=1.17 (0.62-2.21)], miscarriage rate [3.84% vs. 5.26% OR=0.74 (0.25-2.20)] and ongoing pregnancy rate [11.53% vs. 8.55% OR=1.37 (0.65-2.92)] in the GCSF group compared to the control. However, the results revealed no statistically significance (P>0.05).

CONCLUSION: Although it was not statistically significant, 300 μg Intrauterine GCSF administration simultaneously with hCG injection in standard IUI procedure might increase the pregnancy outcomes. Further studies are warranted (registration number: IRCT201212079281N2).

PMID:36273314 | DOI:10.22074/ijfs.2021.537125.1171

Int J Fertil Steril. 2022 Oct 1;16(4):275-280. doi: 10.22074/ijfs.2022.540919.1203.

ABSTRACT

BACKGROUND: The aim of this study was to determine the effect of couples coping enhancement counseling (CCEC) on stress and dyadic coping of infertile couples.

MATERIALS AND METHODS: In this parallel randomized controlled trial study in 2020, seventy infertile couples were randomly divided into case and control groups. The intervention was performed in 7 sessions of couple counseling based on CCEC for the intervention group, no intervention was performed in the control group. Fertility Problem Inventory, Dyadic Coping Inventory and demographics questionnaires were completed by both couples separately before the intervention and 4 weeks after the last consultation session. Data were analyzed using IBM SPSS statistics 24 and statistical tests such as mean ± SD, frequency, percentage, Independent t test, Mann-Whitney test, Chi-square test or Fisher’s exact test and Analysis of covariance. Significant level was considered less than 0.05.

RESULTS: The mean stress scores of women in the intervention group before and after intervention decreased from (156.83 ± 23.57) to (139.43 ± 22.39) and the mean scores of dyadic coping increased from (126.83 ± 19.89) to (138.26 ± 16.92), these differences were statistically significant (P<0.001), also the mean stress scores of men in the intervention group before and after the intervention decreased from (143.80 ± 23.40) to (128.03 ± 22.24), the mean scores of dyadic coping increased (131.34 ± 20.67) to (136.40 ± 19.38), these differences were statistically significant (P<0.001).

CONCLUSION: Positive effects of CCEC were observed in reducing infertility stress and increasing dyadic coping in both women and men after the intervention, the effect of the intervention on women was greater than that of men. As a result, this intervention can play an important role in reducing stress and increasing the solidarity and support of infertile couples for infertility treatments (registration number: IRCT20120215009014N367).

PMID:36273313 | DOI:10.22074/ijfs.2022.540919.1203

Int J Fertil Steril. 2022 Oct 1;16(4):263-267. doi: 10.22074/ijfs.2021.535199.1167.

ABSTRACT

BACKGROUND: Deep infiltrating endometriosis (DIE) is described as an endometriotic tissue that penetrates more than 5 mm under the peritoneal surface. It’s suggested that trans vaginal sonography (TVS) is 79% sensitive and 94% specific in the assessment of intestinal DIE. Considering the possibility that DIE ultrasonography (rectal andor vaginal ultrasonography) might be more accurate, we designed this study to assess this study to evaluate the accuracy of DIE ultrasonography.

MATERIALS AND METHODS: In this retrospective cross-sectional study, we designed and conducted this study from 2019 to 2020 on patients suspected of severe endometriosis. Our patients underwent ultrasonographic imaging and based on the results became candidates for surgery. We compared histopathological results with sonographic findings using crosstabulation and chi-square tests were used to measure accuracy. P<0.05 were considered statistically significant.

RESULTS: Following pathological assessments of 109 cases, 97 cases had ovarian endometrioma, 42 cases had intestinal involvement and 56 cases had uterosacral DIE. The results for accuracy were as the following; uterosacral ligament (USL) involvement SE: 96.4% and SP: 59.1%; intestinal involvement SE: 97.6% and SP: 73.8%; and Cul de sac involvement with SE: 100% and SP: 50.8%. With regards to ovarian endometrioma, ultrasonographic imaging was 99.0% sensitive and 84.6% specific. With regards to intestinal involvement, ultrasonography performed a reliable overall diagnosis (97.6% sensitive and 73.8% specific). However, the results showed lower accuracy regarding the level of intestinal involvement. The accuracy for other sites and cavities was low except for ovarian endometrioma.

CONCLUSION: The results of the present study demonstrated that pre-operative TVS and Transrectal ultrasound (TRUS) can be a helpful paraclinical tool in the assessment and diagnosis of DIE and endometriosis in general and particularly with adnexal and bowel lesions, it can have some shortcomings with respect to cul de sac and USLs.

PMID:36273311 | DOI:10.22074/ijfs.2021.535199.1167