Crystallographic investigation, Hirshfeld surface analysis, NLO characterization and experimental spectral (UV and NMR) studies with DFT probe on(R)-9-(2-hydroxy propyl)adenine.

In this study, (R)-9-(2-hydroxy propyl)adenine (HPA) is the molecule of interest for investigation. The XRD from single crystal of HPA has been used to extract its structural features. Since HPA crystallised in a non-centro symmetric space group P212121, its NLO property was studied and it was found to exhibit very good SHG activity. To explore the intermolecular interactions the generated Hirshfeld surface has been investigated along with 2D-fingerprint plots. The experimental electronic and NMR spectra taken in the UV-visible and radio frequency regions respectively for HPA have been corroborated in correlation with theoretical predictions at Density Function Theory using 6-311++g (d, p) basis set. The experimental XRD geometrical parameters, chemical shifts of 13C and 1H and λmax values of HPA fit satisfactorily with the corresponding theoretically obtained numerical values as well as the stimulated spectrograms with the experimental ones. Further to explore the electronic structure, the MESP surface has been generated and investigated. The thermodynamic, kinetic and chemical reactivity features have been explored by means of frontier molecular orbitals of HPA.

Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity.

Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD's localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below membrane headgroups. To determine the functional implications of these findings, we used a gramicidin-based fluorescence assay to show that CBD alters membrane elasticity or thickness, which could alter Nav function through bilayer-mediated regulation. Site-directed mutagenesis in the vicinity of the Nav1.4 pore revealed that removing the local anesthetic binding site with F1586A reduces the block of INa by CBD. Altering the fenestrations in the bilayer-spanning domain with Nav1.4-WWWW blocked CBD access from the membrane into the Nav1.4 pore (as judged by MD). The stabilization of inactivation, however, persisted in WWWW, which we ascribe to CBD-induced changes in membrane elasticity. To investigate the potential therapeutic value of CBD against Nav1.4 channelopathies, we used a pathogenic Nav1.4 variant, P1158S, which causes myotonia and periodic paralysis. CBD reduces excitability in both wild-type and the P1158S variant. Our in vitro and in silico results suggest that CBD may have therapeutic value against Nav1.4 hyperexcitability.

Poor sleep is associated with higher blood pressure and uterine artery pulsatility index in pregnancy: a prospective cohort study.

OBJECTIVE: To elucidate the association between sleep disturbances and blood pressure as well as uterine artery Doppler during pregnancy in women with no pre-existing hypertension. DESIGN: Prospective cohort study. SETTING: Outpatient specialist clinics at KK Women's and Children's Hospital, Singapore. POPULATION: Women with viable singleton pregnancies confirmed by ultrasonography at less than 14 weeks of amenorrhoea at first visit. METHODS: In all, 926 subjects were recruited for this study in the outpatient specialist clinics at KK Women's and Children's Hospital, Singapore, between 1 September 2010 and 31 August 2014. They were followed up throughout pregnancy with sleep quality, blood pressure and uterine artery Doppler assessed at each visit. MAIN OUTCOME MEASURES: Sleep quality, blood pressure and uterine artery Doppler. RESULTS: Sleep progressively worsened as pregnancy advanced. Shorter sleep duration and poorer sleep efficiency were associated with higher blood pressure, especially in the first trimester. Mixed model analysis demonstrated an overall positive association between sleep quality represented by Pittsburgh Sleep Quality Index (PSQI) score and diastolic blood pressure (DBP) (P < 0.001) and mean arterial pressure (MAP) (P = 0.005) during pregnancy after considering all trimesters. Sleep duration was found to be negatively associated with both systolic blood pressure (SBP) (P = 0.029) and DBP (P = 0.002), whereas sleep efficiency was negatively correlated with DBP (P = 0.002) only. Overall poor sleep during pregnancy was also found to be associated with a higher uterine artery pulsatility index. CONCLUSION: Our prospective study demonstrated that poor sleep quality is significantly associated with higher blood pressure and uterine artery pulsatility index during pregnancy. TWEETABLE ABSTRACT: Poor sleep quality is significantly associated with higher blood pressure and higher uterine artery pulsatility index during pregnancy.

Uterine conservation in placenta accrete spectrum (PAS) disorders: A retrospective case series: Is expectant management beneficial in reducing maternal morbidity?

OBJECTIVE: To examine whether expectant management confers any benefit on operative morbidity for the management of placenta accrete spectrum (PAS) disorders. STUDY DESIGN: This was a single center retrospective cohort study at a tertiary referral center In Singapore. Women with PAS disorder between January 2006 and December 2017 were identified from the hospital register. Antenatal features, surgical factors and post-operative morbidity were compared between women having caesarean hysterectomy, those having caesarean section with placental removal and women having expectant management, defined as caesarean section with retention of placenta using the student's t and Chi square tests. The natural course, complications and preservation of fertility were examined for women having expectant management. RESULTS: Ninety women with PAS were included. The incidence of PAS was 0.064 %. Mean gestational age (GA) at diagnosis was 26.4 weeks. Elective and emergency deliveries were performed at 36.7 and 32.4 weeks respectively (p = <0.0001). Caesarean hysterectomy, Caesarean section with placenta removal and expectant management (EM) were performed in 51(56.7 %),16(17.8 %) and 23(25.6 %) women respectively. The mean blood loss (MBL) and surgical time for EM were significantly lower than those for caesarean hysterectomy 0.52 L vs 3.17 L (p < 0.0001) and 70.8 min vs 171.6 min (p < 0.0001). The advantage of lower blood loss with expectant management persisted even after blood loss at delayed hysterectomy was considered (1284.09 mL vs 3168.72 mL (p-value <0.0001)). Uterine preservation with EM was successful in 61 % (14/23) women. Although nine women (39 %) in this group needed hysterectomy most complications were minor and presented within three months. The mean follow up overall was 13 months. CONCLUSION: Traditionally caesarean hysterectomy has been the main surgical approach for PAS. Our study consolidates existing evidence for expectant management being an option for a select group of patients to avoid complications associated with hysterectomy and allow uterine preservation.

Crystallographic, spectral and computational studies on (S)-4-(4-aminobenzyl) oxazolidin-2-one.

The experimental geometry (XRD), vibrational (IR and Raman), electronic (UV-visible) and NMR spectra of (S)-4-(4-Amino-benzyl)-oxazolidin-2-one (ABO) have been corroborated with the corresponding first principle calculated values at DFT using hybrid B3LYP exchange correlation functional invoking 6-311++g(d, p) basis set. The optimized geometrical parameters were found to be in satisfactory agreement with the experimental values obtained from the X-ray diffraction structural features of ABO. The scaled down computed vibrational frequencies with appropriate scaling factors were in good correspondence with the experimental observations. Room-temperature 1H and 13C nuclear magnetic resonance (NMR) studies were supported by advanced density functional theory calculations. The theoretical spectrograms of FT-IR, FT-Raman, 1H NMR, 13C NMR and UV of the title compound have been constructed and compared with experimental spectra and Hirshfeld surface analysis has also been made to study the intermolecular interactions. The electronic structure of the title compound has also been studied in terms of HOMO, LUMO and MESP diagrams.

Complications and pregnancy outcome following uterine compression suture for postpartum haemorrhage: a single centre experience.

In the treatment of postpartum haemorrhage from uterine atony, uterine compression sutures, such as the B-Lynch suture and its modifications have a role with the advantage of preservation of the uterus for fertility. There is however, a risk that apposition of the anterior and posterior walls of the uterus will impede drainage of lochia, resulting in undesirable complications. We undertook a five-year retrospective study of all women who underwent uterine compression sutures at the KK Women's and Children's Hospital, between 2008 and 2012. In total, 23 women had uterine compression sutures during the study period, of which, nineteen women managed to conserve their uterus. Our complication rate was 25%, which included persistent vaginal discharge, pyometra and endometritis. There were three conceptions, with two successful pregnancies. Our study shows uterine compression suture to be a safe and effective alternative to avoid hysterectomy with preservation of fertility at the time of major postpartum haemorrhage. The outcome of subsequent pregnancies is reassuring.

Foetal sacrococcygeal teratoma: extremes in clinical presentation.

Sacrococcygeal teratoma (SCT) is a congenital tumour that can be diagnosed by ultrasonography (USG). We present our experience with the management of two cases of SCT in our institution between 2008 and 2009. In the first case, SCT was diagnosed at 17 weeks' gestation. The patient was followed up with fortnightly USG to monitor the tumour size, foetal growth and signs of foetal hydrops. The patient delivered a baby girl by Caesarean section at 37 weeks, with good Apgar scores. The neonate underwent an uneventful resection of SCT on Day 1 of life. In the second case, SCT was diagnosed at 20 weeks during screening. In view of foetal hydrops and anaemia, the patient underwent three in utero foetal blood transfusions. A baby boy was delivered by Caesarean section at 28 weeks. There was a large friable SCT with massive haemorrhage. Despite maximal resuscitative efforts, the neonate died 30 minutes after birth.

Dengue haemorrhagic fever complicated by eclampsia in pregnancy.

A 28-year-old primigravida presented at 36 weeks of gestation with a one-week history of fever with myalgia. Diagnosis of dengue fever was made based on viral polymerase chain reaction. She progressed to dengue shock syndrome by day nine and subsequently recovered. She delivered a healthy male baby by the vaginal route, but within 24 hours of delivery, had an eclamptic seizure, which was controlled with intravenous magnesium sulphate. Mother and the baby were well at discharge and on the follow-up visit at three months.