Cancers of esophagus, stomach and lungs have a high incidence both in men and women in Kashmir. Future studies on sources and types of environmental pollution and exposures in relation to these cancers may improve our understanding of risk factors held responsible for causation of these malignancies in this region. This will help in the allocation of available resources for prevention and treatment strategies.

Background: Gestational hypertension is a significant threat both to maternal and fetal health. However, it is still a distant dream to predict accurately its occurrence in early pregnancy. Objective was to find out if β HCG levels determined between 13 to 20 weeks of gestation can be used as a predictor for gestational hypertension.Methods: This prospective observational cohort study was conducted from August 2014 to January 2016. Serum β HCG levels were determined at 13 to 20 weeks of gestation of 190 normotensive pregnant women attending the antenatal clinics. They were followed for the development of gestational hypertension till 40 weeks of gestation or delivery.Results: Out of the total 190 women, 25 (13.1%) developed gestation hypertension. Of those who developed gestational hypertension, 22 (88%) were having β HCG levels >2 MOM (p<0.001). Absolute β HCG levels (Mean±SD) were also significantly higher (54907±29509 V/S 41095±19103; p<0.001) in subjects who later developed gestational hypertension. Sensitivity, specificity, positive predictive value and the negative predictive value for β HCG at >2 MOM were 83.3, 96.9, 80.0 and 97.5 respectively (95% CI).Conclusions: Pregnant women with high Beta HCG levels in early pregnancy have significantly higher risk for development of gestational hypertension.

Background: Intrahepatic cholestasis of pregnancy (ICP) typically occurs in late pregnancy affecting 1.5-2% pregnancies. Limited data is available regarding its fetal and maternal implications. This study aims to assess the impact of ICP on maternal and fetal outcome.Methods: A total 200 patients with pruritus in later half of pregnancy were studied over a period of 18 months out of which 135 were diagnosed as ICP. Clinical and biochemical parameters like serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, and gamma glutamyl transferase was recorded. Maternal and fetal outcome was noted in the form of LSCS rate, preterm births, fetal distress and neonatal ICU admissions.Results: In this study, most common symptom was pruritus. Most of cases had onset of symptoms between 32-36 weeks. High LSCS rates were seen among cases. Intrapartum complications viz. meconium staining of amniotic fluid (57.8%), preterm delivery (11.9%), fetal distress (42.2%) were significantly higher in study population and there was high incidence of NICU admissions (49. 6% neonates) among cases mostly due to meconium aspiration and prematurity.Conclusions: ICP increases maternal morbidity and is associated with adverse perinatal outcome viz. increased risk of fetal distress, preterm births and sudden IUD at term as evidenced in this study. A timely intervention at 37-38 weeks will reduce the adverse outcomes.

PNCK, or CAMK1b, is an understudied kinase of the calcium-calmodulin dependent kinase family which recently has been identified as a marker of cancer progression and survival in several large-scale multi-omics studies. The biology of PNCK and its relation to oncogenesis has also begun to be elucidated, with data suggesting various roles in DNA damage response, cell cycle control, apoptosis and HIF-1-alpha related pathways. To further explore PNCK as a clinical target, potent small-molecule molecular probes must be developed. Currently, there are no targeted small molecule inhibitors in pre-clinical or clinical studies for the CAMK family. Additionally, there exists no experimentally derived crystal structure for PNCK. We herein report a three-pronged chemical probe discovery campaign which utilized homology modeling, machine learning, virtual screening and molecular dynamics to identify small molecules with low-micromolar potency against PNCK activity from commercially available compound libraries. We report the first described inhibitor hit series for PNCK that will serve as the starting point for future medicinal chemistry efforts for hit-to-lead optimization of potent chemical probes.

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