Role of vaginal progesterone in reducing the rate of preterm labour in women with a sonographic short cervix

Background: Preterm labour is responsible for not only neonatal morbidity and mortality but also has long term consequences .Till now there is no effective method of prevention. Progesterone has shown promising result. But ideal candidate, ideal route and when to start the treatment are still in dilemma. The present study was undertaken to know the role of progesterone on pregnant women with sonographically short cervix.Methods: This prospective case control study was started on 100 pregnant women with sonographic short cervix (≤2.5 cm) and between 19 – 29 weeks of gestation. 60 women, some with history of midtrimester abortion or preterm labour and some without this history were treated as cases and were given vaginal progesterone pessary 200 mg once daily till rupture of membrane or onset of labour or up to 36 weeks of gestation whichever is earlier. 40 women without any history of midtrimester abortion or preterm labour were treated as control and followed up.Results: Among the cases 18.3%, delivered preterm and 81.7% were term deliveries. Respective proportions among control were 40% and 60% respectively. 26 among the cases and all women of control group did not have history of preterm labour and mid trimester abortion. In the case group 26.9% and in the control group 40% had preterm deliveries. Though the proportion of labour was lower among the cases it is not statistically significant (p = 0.276). There is mean prolongation of gestational age by 8.4± 1.29 weeks in case group in present pregnancy compared the previous one in cases with history of preterm labour and midtrimester abortion which was statistically significant .When neonatal complication are compared there is no significant difference between the two groups.Conclusions: Vaginal progesterone started from midtrimester in pregnant ladies with short cervix with previous history of midtrimester abortion or preterm labour is effective in reducing the rate of preterm birth

Study of Doppler indices of umbilical artery and middle cerebral artery in pregnancies at and beyond forty weeks of gestation

Background: The optimal management of pregnancies beyond date is still debated. Prolonged pregnancies carry risk to the fetus and routine induction increases the rate of primary cesarean section. Hence as there is evidence that placental reserve diminishes beyond term this study was conducted to know the effect of advanced gestation on Doppler indices and its correlation with perinatal outcome.Methods: This prospective study was conducted on 80 pregnant women who are at or beyond 40 weeks of gestation. Doppler indices of umbilical artery and middle cerebral artery were taken. Data were analyzed with obstetrics and perinatal outcome.Results: Umbilical artery mean RI increased with gestational age (p=0.003). There was no significant difference in PI and S/D ratio in different gestational age groups. Middle cerebral artery Doppler indices did not show any significant difference in different gestational age groups. In abnormal Doppler group, perinatal outcome was also not significantly different, but neonatal intensive care unit admission was increased, which was statistically significant (p=0.007).Conclusions: Vascular resistance in the umbilical artery and middle cerebral artery does not change abruptly when gestation exceeds 280 days. It also cannot be taken as the sole method of fetal surveillance when date is crossed

Plasmid-encoded NP73-102 modulates atrial natriuretic peptide receptor signaling and plays a critical role in inducing tolerogenic dendritic cells

Abstract Background Atrial natriuretic peptide (ANP) is an important endogenous hormone that controls inflammation and immunity by acting on dendritic cells (DCs); however, the mechanism remains unclear. Objective We analyzed the downstream signaling events resulting from the binding of ANP to its receptor, NPRA, and sought to determine what aspects of this signaling modulate DC function. Methods We utilized the inhibitory peptide, NP73-102, to block NPRA signaling in human monocyte-derived DCs (hmDCs) and examined the effect on DC maturation and induced immune responses. The potential downstream molecules and interactions among these molecules involved in NPRA signaling were identified by immunoprecipitation and immunoblotting. Changes in T cell phenotype and function were determined by flow cytometry and BrdU proliferation ELISA. To determine if adoptively transferred DCs could alter the in vivo immune response, bone marrow-derived DCs from wild-type C57BL/6 mice were incubated with ovalbumin (OVA) and injected i.v. into C57BL/6 NPRA-/- knockout mice sensitized and challenged with OVA. Lung sections were stained and examined for inflammation and cytokines were measured in bronchoalveolar lavage fluid collected from parallel groups of mice. Results Inhibition of NPRA signaling in DCs primes them to induce regulatory T cells. Adoptive transfer of wild type DCs into NPRA-/- mice reverses the attenuation of lung inflammation seen in the NPRA-knockout model. NPRA is associated with TLR-2, SOCS3 and STAT3, and inhibiting NPRA alters expression of IL-6, IL-10 and TGF-β, but not IL-12. Conclusions Modulation of NPRA signaling in DCs leads to immune tolerance and TLR2 and SOCS3 are involved in this induction. </jats:sec

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA\u27s research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC

Respiratory Syncytial Virus NS1 Protein Colocalizes with Mitochondrial Antiviral Signaling Protein MAVS following Infection

Respiratory syncytial virus (RSV) nonstructural protein 1(NS1) attenuates type-I interferon (IFN) production during RSV infection; however the precise role of RSV NS1 protein in orchestrating the early host-virus interaction during infection is poorly understood. Since NS1 constitutes the first RSV gene transcribed and the production of IFN depends upon RLR (RIG-I-like receptor) signaling, we reasoned that NS1 may interfere with this signaling. Herein, we report that NS1 is localized to mitochondria and binds to mitochondrial antiviral signaling protein (MAVS). Live-cell imaging of rgRSV-infected A549 human epithelial cells showed that RSV replication and transcription occurs in proximity to mitochondria. NS1 localization to mitochondria was directly visualized by confocal microscopy using a cell-permeable chemical probe for His6-NS1. Further, NS1 colocalization with MAVS in A549 cells infected with RSV was shown by confocal laser microscopy and immuno-electron microscopy. NS1 protein is present in the mitochondrial fraction and co-immunoprecipitates with MAVS in total cell lysatesof A549 cells transfected with the plasmid pNS1-Flag. By immunoprecipitation with anti-RIG-I antibody, RSV NS1 was shown to associate with MAVS at an early stage of RSV infection, and to disrupt MAVS interaction with RIG-I (retinoic acid inducible gene) and the downstream IFN antiviral and inflammatory response. Together, these results demonstrate that NS1 binds to MAVS and that this binding inhibits the MAVS-RIG-I interaction required for IFN production