Local sequence features that influence AP-1 cis-regulatory activity

In the genome, most occurrences of transcription factor binding sites (TFBS) have no cis-regulatory activity, which suggests that flanking sequences contain information that distinguishes functional from nonfunctional TFBS. We interrogated the role of flanking sequences near Activator Protein 1 (AP-1) binding sites that reside in DNase I Hypersensitive Sites (DHS) and regions annotated as Enhancers. In these regions, we found that sequence features directly adjacent to the core motif distinguish high from low activity AP-1 sites. Some nearby features are motifs for other TFs that genetically interact with the AP-1 site. Other features are extensions of the AP-1 core motif, which cause the extended sites to match motifs of multiple AP-1 binding proteins. Computational models trained on these data distinguish between sequences with high and low activity AP-1 sites and also predict changes in cis-regulatory activity due to mutations in AP-1 core sites and their flanking sequences. Our results suggest that extended AP-1 binding sites, together with adjacent binding sites for additional TFs, encode part of the information that governs TFBS activity in the genome.</jats:p

Ultrasonographic measurement of uterine lower segment scar thickness in cases of previous one caesarean section and obstetric outcome

Background: Vaginal birth after caesarean section (VBAC) has become an integral part of modern obstetrics with more than 1lakh VBACs achieved each year nationwide. Several studies have reported perinatal risks associated with failed trial of labour and uterine rupture in women attempting VBAC, due to concerns about these complications, the rate of VBAC deliveries has continued to fall in developed countries, with an inverse increase in Caesarean Sections (CS). To better assess the risk of uterine rupture, many authors have proposed sonographic measurement of scar or lower uterine segment (LUS) thickness near term, assuming that there is an inverse correlation between LUS thickness and the risk of uterine scar defect. Therefore, this assessment for the management of women with prior CS has increased safety by selecting women with the lowest risk of uterine rupture.Methods: Present study was a prospective observational study which assessed the obstetric outcome in women with previous lower segment caesarean section willing for trial of labour. Secondly, authors aimed to ascertain the best cut off values for predicting uterine rupture.Results: Present study found that as duration between previous LSCS and next pregnancy increased there was better chance of VBAC. As the baby weight increased VBAC rate reduced. Study also showed that scar thickness of 2.55mm and above measured by transabdominal method in the third trimester can be safely given trial of VBAC.Conclusions: Authors thus conclude that measurement of lower uterine segment/ scar thickness can help obstetrician decide whether VBAC is safe or not in patients with previous one LSCS willing for VBAC. Scar thickness of more than 2.55mm can be given safe trial of labour in women with previous one lower segment caesarean section

Connective tissue disorders in pregnancy: maternal and fetal perspective

Background: The objective of this study was to study maternal and fetal outcome in connective tissue disorders in pregnancy.Methods: This was a retrospective type of observational study done in department of obstetrics and gynecology and department of rheumatology at a King Edward Memorial hospital over a period of 1.5 years. 48 women were included in this study after informed consent. All these women presented with collagen disorders to ANC outpatient department or to rheumatology outpatient department or in emergency. All postpartum patients having connective tissue disorders not recruited during ANC were also included in this study after taking their written, informed and valid consent.Results: Connective tissue disorders are associated with multiple voluntary and involuntary abortions as well as intrauterine fetal deaths. Even in those women having live births, many undergo cesarean sections due to various indications like fetal distress, poor biophysical profile, non-reassuring non stress test etc. Neonates born to mothers with connective tissue disorders are growth restricted and many of them need intensive care admission. Also, these women were found to have multiple associated medical comorbidities in pregnancy.Conclusions: The data collected and the results arrived upon should help contribute significant literature regarding collagen disorders in pregnancy and help in better fetal and maternal management during pregnancy

Audit on maternal mortality in a tertiary care centre in India of 6 years, a retrospective analysis

Background: This study is carried out on 382 cases of maternal deaths from July 2010 to June 2016 at the department of obstetrics and gynaecology of tertiary centre to evaluate causes and risk factor associated with maternal deaths.Methods: Retrospective analysis of all maternal deaths occurred in department of obstetrics and gynaecology of tertiary care hospital from July 2010 to June 2016.Results: The MMR in the study period was 915/100000 live births. Maximum no. of maternal death 42.7% were in age group of 21-25 years, majority of them residing in urban area. 117 patients referred from sub-district/district hospital. 76.4% patients were registered. 60% maternal deaths were seen in postnatal period. In present study majority of maternal deaths 60% were due to indirect cause while 40% patients died due to direct cause. Major causes of maternal deaths were hypertensive disorder 12%, obstetric haemorrhage 11% tuberculosis 11%, hepatitis E 8% and pregnancy related infections 5.6%.Conclusions: High maternal mortality can be due to the fact that the study was conducted in tertiary care referral centre. Referral of moribund cases from rural, sub-district, district and peripheral hospital to our institute have inflated this mortality ratio. All of these being preventable causes of death can be avoided by improving standard of obstetric care, increasing number of health professionals, upgradation of healthcare facilities at first referral units and by making better health policies

PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs

A large number of RNA binding proteins (RBPs) and miRNAs bind to the 3′ untranslated regions of mRNA, but methods to dissect their function and interactions are lacking. Here the authors introduce post-transcriptional regulatory element sequencing (PTRE-seq) to dissect sequence preferences, interactions and consequences of RBP and miRNA binding

To study and compare the obstetric and neonatal outcome of pregnancies complicated with hypothyroidism amongst antenatally detected and treated hypothyroid patients and patients found to be hypothyroid at the time of labor

Background: To evaluate pregnancy outcome in women with elevated serum thyroid stimulating hormone (TSH) values as compared to those in whom hypothyroidism was treated.Methods: A prospective interventional comparative study was conducted in the department of obstetrics and gynaecology in King Edward Memorial Hospital, Mumbai, India from 2014 to 2015. A cohort of 60 hypothyroid patients was divided into two groups of 30 each. Group 1, euthyroid (treated hypothyroid) and group 2, hypothyroid at the time of labor and pregnancy outcomes were compared.Results: All patients in group 1 delivered at term; whereas in group 2, 9 (30%) patients had preterm deliveries and 21 (70%) delivered at term, amongst which 5 patients delivered babies with severe intrauterine growth restriction (IUGR). Neonatal intensive-care unit (NICU) admission were required for 3 neonates in group 1 and 11 (36.67%) neonates in group 2. Group 1 delivered 5 (16.67%) low birth weight babies (weight <2.5 kg) whereas 16 (53.34%) babies had low birth weight in group 2.Conclusions: Treatment of patients diagnosed with hypothyroidism during pregnancy significantly (p value <0.05) reduced the risk of preterm labor, low birth weight, need for NICU admission

An unusual presentation of degenerating fibroid

Degeneration in a fibroid is seen when the blood supply falls inadequate to support the center of fibroid. Usually degeneration in a fibroid requires a symptomatic medical management. This is a case report of a degenerating fibroid that uncommonly presented in postpartum period as a retroperitoneal abscess requiring exploratory laparotomy

Vaginal birth in singleton breech:revisited

Background: The purpose of the study was to analyze maternal and perinatal outcome according to mode of delivery in singleton breech presentation retrospectively in a tertiary care center.Methods: This was a retrospective observational study done in KEM Hospital, during 2012 to 2013. Maternal and perinatal outcome was studied retrospectively. The data was collected from the mother's medical records. The neonatology records were also examined. Primary outcomes included neonatal mortality, morbidity and maternal morbidity.Results: Out of 100 selected patients; 27 delivered vaginally and 73 underwent lower segment caesarean section (LSCS). Perinatal mortality was 3%. Two out of 3 were delivered vaginally and 1 underwent LSCS. Perinatal morbidity was 1% in vaginal delivery. Maternal morbidity was 2%, both patients underwent emergency LSCS. There was no maternal mortality in the study.Conclusions: Delivery of breech fetus when labor and delivery is supervised and or conducted by experienced obstetrician lowers maternal morbidity, neonatal morbidity and mortality

An unusual case of labial fusion

Labial fusion is sealing of labia minora in midline. It is also known as Labial adhesion or Labial agglutination or synechia vulvae. This condition is common in pre-pubertal females when estrogen levels are low and commonly resolves spontaneously post-puberty. Usually asymptomatic and typically treated conservatively. Medical treatment includes use of estrogen cream or betamethasone cream. Surgical treatment rarely required, if not responding to medical treatment or dense adhesions. This case report is unusual as it presented in a post-pubertal female and which needed surgical management

High-throughput functional testing of ENCODE segmentation predictions

The histone modification state of genomic regions is hypothesized to reflect the regulatory activity of the underlying genomic DNA. Based on this hypothesis, the ENCODE Project Consortium measured the status of multiple histone modifications across the genome in several cell types and used these data to segment the genome into regions with different predicted regulatory activities. We measured the cis-regulatory activity of more than 2000 of these predictions in the K562 leukemia cell line. We tested genomic segments predicted to be Enhancers, Weak Enhancers, or Repressed elements in K562 cells, along with other sequences predicted to be Enhancers specific to the H1 human embryonic stem cell line (H1-hESC). Both Enhancer and Weak Enhancer sequences in K562 cells were more active than negative controls, although surprisingly, Weak Enhancer segmentations drove expression higher than did Enhancer segmentations. Lower levels of the covalent histone modifications H3K36me3 and H3K27ac, thought to mark active enhancers and transcribed gene bodies, associate with higher expression and partly explain the higher activity of Weak Enhancers over Enhancer predictions. While DNase I hypersensitivity (HS) is a good predictor of active sequences in our assay, transcription factor (TF) binding models need to be included in order to accurately identify highly expressed sequences. Overall, our results show that a significant fraction (∼26%) of the ENCODE enhancer predictions have regulatory activity, suggesting that histone modification states can reflect the cis-regulatory activity of sequences in the genome, but that specific sequence preferences, such as TF-binding sites, are the causal determinants of cis-regulatory activity