Intrauterine infection/inflammation during pregnancy and offspring brain damages: Possible mechanisms involved

Intrauterine infection is considered as one of the major maternal insults during pregnancy. Intrauterine infection during pregnancy could lead to brain damage of the developmental fetus and offspring. Effects on the fetal, newborn, and adult central nervous system (CNS) may include signs of neurological problems, developmental abnormalities and delays, and intellectual deficits. However, the mechanisms or pathophysiology that leads to permanent brain damage during development are complex and not fully understood. This damage may affect morphogenic and behavioral phenotypes of the developed offspring, and that mice brain damage could be mediated through a final common pathway, which includes over-stimulation of excitatory amino acid receptor, over-production of vascularization/angiogenesis, pro-inflammatory cytokines, neurotrophic factors and apoptotic-inducing factors

ZYG11A Is Expressed in Epithelial Ovarian Cancer and Correlates With Low Grade Disease

The insulin-like growth factors (IGF) are important players in the development of gynecological malignancies, including epithelial ovarian cancer (EOC). The identification of biomarkers that can help in the diagnosis and scoring of EOC patients is of fundamental importance in clinical oncology. We have recently identified the ZYG11A gene as a new candidate target of IGF1 action. The aim of the present study was to evaluate the expression of ZYG11A in EOC patients and to correlate its pattern of expression with histological grade and pathological stage. Furthermore, and in view of previous analyses showing an interplay between ZYG11A, p53 and the IGF1 receptor (IGF1R), we assessed a potential coordinated expression of these proteins in EOC. In addition, zyg11a expression was assessed in ovaries and uteri of growth hormone receptor (GHR) knock-out mice. Tissue microarray analysis was conducted on 36 patients with EOC and expression of ZYG11A, IGF1R and p53 was assessed by immunohistochemistry. Expression levels were correlated with clinical parameters. qPCR was employed to assess zyg11a mRNA levels in mice tissues. Our analyses provide evidence of reduced ZYG11A expression in high grade tumors, consistent with a putative tumor suppressor role. In addition, an inverse correlation between ZYG11A and p53 levels in individual tumors was noticed. Taken together, our data justify further exploration of the role of ZYG11A as a novel biomarker in EOC

Parity and Interval from Previous Delivery—Influence on Perinatal Outcome in Advanced Maternal Age Parturients

Objective: To investigate the effect of parity and interpregnancy interval (IPI) on perinatal outcomes in advanced maternal age (AMA) parturients. Methods: A population-based retrospective cohort study of all women older than 40 years, who had a singleton live birth after 24 weeks in the United States in 2017 Women were categorized to three groups by parity and interval from last delivery: primiparas, multiparas with IPI ≤ 5 years, and multiparas with IPI > 5 years. Primary outcome was composite adverse neonatal outcome (preterm delivery <34 weeks, birthweight <2000 g, neonatal seizure, neonatal intensive care unit admission, Apgar score <7 at 5 min, or assisted ventilation >6 h). Secondary outcome was composite adverse maternal outcome and other adverse perinatal outcomes. Univariate and multivariate analysis were used to compare between groups. Results: During 2017, 3,864,754 deliveries were recorded into the database. Following exclusion, 109,564 AMA gravidas entered analysis. Of them, 24,769 (22.6%) were nulliparas, 39,933 (36.4%) were multiparas with IPI ≤ 5 years, and 44,862 (40.9%) were multiparas with IPI > 5 years. Composite neonatal outcome was higher in nulliparas and in multiparas with IPI > 5 years, in comparison to multiparas with IPI ≤ 5 years (16% vs. 13% vs. 10%, respectively, p < 0.05). Maternal composite outcome was similar between groups. In the multivariable analysis, relative to nulliparas, only multiparity with IPI ≤ 5 years had a protective effect against the composite neonatal outcome (aOR 0.97, 95% CI 0.95–0.99, p < 0.001). Conclusion: Among AMA gravidas, multiparity with IPI ≤ 5 years has a significant protective effect against adverse neonatal outcomes when compared to nulliparas. Multiparity with IPI > 5 years is no longer protective

The Role of the Insulin-Like Growth Factor 1 Pathway in Immune Tumor Microenvironment and Its Clinical Ramifications in Gynecologic Malignancies

Treatment of patients with gynecologic malignancies diagnosed at advanced stages remains a therapeutic challenge. Survival rates of these patients remain significantly low, despite surgery and chemotherapy. Advances in understanding the role of the immune system in the pathogenesis of cancer have led to the rapid evolution of immunotherapeutic approaches. Immunotherapeutic strategies, including targeting specific immune checkpoints, as well as dendritic cell (DC) immunotherapy are being investigated in several malignancies, including gynecological cancers. Another important approach in cancer therapy is to inhibit molecular pathways that are crucial for tumor growth and maintenance, such as the insulin-like growth factor-1 (IGF1) pathway. The IGF axis has been shown to play a significant role in carcinogenesis of several types of tissue, including ovarian cancer. Preclinical studies reported significant anti-proliferative activity of IGF1 receptor (IGF1R) inhibitors in gynecologic malignancies. However, recent clinical studies have shown variable response rates with advanced solid tumors. This study provides an overview on current immunotherapy strategies and on IGF-targeted therapy for gynecologic malignancies. We focus on the involvement of IGF1R signaling in DCs and present our preliminary results which imply that the IGF axis contributes to an immunosuppressive tumor microenvironment (TME). For the long term, we believe that restoring the TME function by IGF1R targeting in combination with immunotherapy can serve as a new clinical approach for gynecological cancers

Oral Glucose Tolerance Test Performed after 28 Gestational Weeks and Risk for Future Diabetes—A 5-Year Cohort Study

Gestational diabetes mellitus (GDM) is diagnosed by an oral glucose tolerance test (oGTT), preferably performed at 24 + 0–28 + 6 gestational weeks, and is considered a risk factor for type 2 diabetes (T2DM). In this study, we aimed to evaluate the risk of T2DM associated with abnormal oGTT performed after 28 weeks. We conducted a retrospective cohort study that included parturients with available glucose levels during pregnancy and up to 5 years of follow-up after pregnancy. Data were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes (INRD). The women were stratified into two groups: late oGTT (performed after 28 + 6 weeks) and on-time oGTT (performed at 24 + 0–28 + 6 weeks). The incidence of T2DM was evaluated and compared using univariate analysis followed by survival analysis adjusted to confounders. Overall, 78,326 parturients entered the analysis. Of them, 6195 (7.9%) performed on-time oGTT and 5288 (6.8%) performed late oGTT. The rest—66,846 (85.3%)—had normal glucose tolerance. Women who performed late oGTT had lower rates of GDM and T2DM. However, once GDM was diagnosed, regardless of oGTT timing, the risk of T2DM was increased (2.93 (1.69–5.1) vs. 3.64 (2.44–5.44), aHR (95% CI), late vs. on-time oGTT, p < 0.001 for both). Unlike in oGTT performed on time, one single abnormal value in late oGTT was not associated with an increased risk for T2DM

Continuous Maternal Hemodynamics Monitoring at Delivery Using a Novel, Noninvasive, Wireless, PPG-Based Sensor

Objective: To evaluate continuous monitoring of maternal hemodynamics during labor and delivery utilizing an innovative, noninvasive, reflective photoplethysmography-based device. Study design: The Biobeat Monitoring Platform includes a wearable wristwatch monitor that automatically samples cardiac output (CO), blood pressure (BP), stroke volume (SV), systemic vascular resistance (SVR), heart rate (HR) every 5 s and uploads all data to a smartphone-based app and to a data cloud, enabling remote patient monitoring and analysis of data. Low-risk parturients at term, carrying singletons pregnancies, were recruited at early delivery prior to the active phase. Big data analysis of the collected data was performed using the Power BI analysis tool (Microsoft). Next, data were normalized to visual presentation using Excel Data Analysis and the regression tool. Average measurements were compared before and after rupture of membranes, epidural anesthesia, fetal delivery, and placental expulsion. Results: Eighty-one parturients entered analysis. Epidural anesthesia was associated with a slight elevation in CO (5.5 vs. 5.6, L/min, 10 min before and after EA, p &lt; 0.05) attributed to a non-significant increase in both HR and SV. BP remained stable as of counter decrease in SVR (1361 vs. 1319 mmHg&sdot;min&sdot;mL&minus;1, 10 min before and after EA, p &lt; 0.05). Fetal delivery was associated with a peak in CO after which it rapidly declined (6.0 vs. 7.2 vs. 6.1 L/min, 30 min before vs. point of delivery vs. after delivery, p &lt; 0.05). The mean BP remained stable throughout delivery with a slight increase at fetal delivery (92 vs. 95 vs. 92.1 mmHg, p &lt; 0.05), reflecting the increase in CO and decrease in SVR (1284 vs. 1112 vs. 1280 mmHg&sdot;min&sdot;mL&minus;1, p &lt; 0.05)with delivery. Placental expulsion was associated with a second peak in CO and decrease in SVR. Conclusions: We presented a novel application of noninvasive hemodynamic maternal monitoring throughout labor and delivery for both research and clinical use