Septate uterus: incidental finding in multiparous woman with breech with bad obstetric history who had an emergency caesarean

The most common anomalies of reproductive tract are Mullerian duct anomalies, among which septate uterus is the commonest with highest reproductive failure rate. As there are some pitfalls in diagnosis therefore the incidence is difficult to be mentioned as many remain asymptomatic. A 20 year old G5P1L0A3 with 36+4 weeks of gestation with breech presentation in active labour came to our hospital. Patient had previous history of intrauterine death at 8 months of amenorrhea and previous abortions at 5, 5 and 4 months of amenorrhoea in the year 2011, 2013, and 2014 respectively. She underwent emergency caesarean section due to breech at 36+4 weeks in active labour with the delivery of a live late preterm female baby extracted by complete breech of weight 2.28kgs with bilateral CTEV of the baby. Intraoperative findings- of septate uterus–septum extending from fundus to external os, fundal dimpling present. Though rare but uterine anomalies should be suspected in patients with recurrent pregnancy loss, preterm birth and malpresentation

Obstetric outcome in pregnancy complicated by ovarian cysts

Background: Ovarian masses are diagnosed in 0.5-1% pregnancies. During pregnancy ovarian cysts can undergo: resolution of the cyst, change of ultrasound pattern, occurrence of ovarian torsion and intra-cystic haemorrhage or rupture. Ovarian masses (esp torsion) is a cause of pain abdomen during pregnancy. The choice of treatment is mainly conservative, provided the patient is asymptomatic. Dilemma in management arises when the patient is symptomatic. Optimal timing for a planned surgery is the second trimester as it is shown to have least neonatal outcome. The objective of this study was to evaluate management options for ovarian cyst in pregnancy and its effect on outcome of pregnancy.Methods: This study was conducted for 2 years from June 2014 to June 2016, at RL Jalappa Hospital, Kolar. A total of 46 pregnant women were included. The pregnancy outcome and the management used were studied. Also studied were the complications most likely to occur in pregnancies complicated by ovarian masses ovarian masses.Results: Out of 46 patients, 2 (4.3%) patients with ovarian cyst torsion underwent emergency laparotomy. 8 patients underwent surgery (6 in 2nd trimester and 2 at term) for various complications. Only one patient had miscarriage and remaining patients continued till term. Histopathological report of all the masses excised were obtained and 6 were reported to be benign serous cystadenomas,1 benign mucinous cystadenoma and 3 simple cysts.Conclusions: Optimal management for ovarian cyst is conservative in pregnancy provided patient remain asymptomatic and characteristic of cyst are consistent with benign pathology. Surgical management is to be reserved for symptomatic patient

NMR quality control of fragment libraries for screening

Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of "poised fragments" with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients

Investigations into a putative role for the novel BRASSIKIN pseudokinases in compatible pollen-stigma interactions in Arabidopsis thaliana.

BACKGROUND: In the Brassicaceae, the early stages of compatible pollen-stigma interactions are tightly controlled with early checkpoints regulating pollen adhesion, hydration and germination, and pollen tube entry into the stigmatic surface. However, the early signalling events in the stigma which trigger these compatible interactions remain unknown. RESULTS: A set of stigma-expressed pseudokinase genes, termed BRASSIKINs (BKNs), were identified and found to be present in only core Brassicaceae genomes. In Arabidopsis thaliana Col-0, BKN1 displayed stigma-specific expression while the BKN2 gene was expressed in other tissues as well. CRISPR deletion mutations were generated for the two tandemly linked BKNs, and very mild hydration defects were observed for wild-type Col-0 pollen when placed on the bkn1/2 mutant stigmas. In further analyses, the predominant transcript for the stigma-specific BKN1 was found to have a premature stop codon in the Col-0 ecotype, but a survey of the 1001 Arabidopsis genomes uncovered three ecotypes that encoded a full-length BKN1 protein. Furthermore, phylogenetic analyses identified intact BKN1 orthologues in the closely related outcrossing Arabidopsis species, A. lyrata and A. halleri. Finally, the BKN pseudokinases were found to be plasma-membrane localized through the dual lipid modification of myristoylation and palmitoylation, and this localization would be consistent with a role in signaling complexes. CONCLUSION: In this study, we have characterized the novel Brassicaceae-specific family of BKN pseudokinase genes, and examined the function of BKN1 and BKN2 in the context of pollen-stigma interactions in A. thaliana Col-0. Additionally, premature stop codons were identified in the predicted stigma specific BKN1 gene in a number of the 1001 A. thaliana ecotype genomes, and this was in contrast to the out-crossing Arabidopsis species which carried intact copies of BKN1. Thus, understanding the function of BKN1 in other Brassicaceae species will be a key direction for future studies

Laparoscopic cholecystectomy: Our experience in a rural setup

Background: Laparoscopic cholecystectomy has become the gold standard in symptomatic gallstone disease. Today more than 80% of cholecystectomies worldwide are carried out laparoscopically. The present study describes our experience with laparoscopic cholecystectomy in a rural setup. Aim: To study the results of laparoscopic cholecystectomy in a rural setup. Settings and Design: Prospective study done at R. L. Jallapa Hospital Tamaka Kolar from January 2003 to November 2012. Materials and Methods: A total of 120 patients undergoing laparoscopic cholecystectomy by the same surgeon were included. Results: Out of the 120 patients, 108 (90%) were females and 12 (10%) were males. Their age ranged from 16 to 75 years. Majority were in fourth decade of life. Majority of the patients [70 (58.3%)] had gallstones. The procedure was converted to open cholecystectomy in six patients. Twenty-four patients had minor complications. Majority of the patients stayed in the hospital postoperatively for less than 5 days. Conclusion: Laparoscopic cholecystectomy in our setup proved to be a safe procedure and an effective treatment for gallstone disease

Correlation of prognostic factors of carcinoma breast with Ki 67 proliferation assay

Prognostic factors are important for the diagnosis of breast cancer as it helps in identification of high risk patients.  The objective of the study is to assess the proliferation index, Ki-67 and correlate it with other markers. The present study was a cohort study conducted in the Department of General Surgery at Tertiary Care Teaching Hospital over a period of 1 year with a sample size of 98. All the patients meeting the inclusion and exclusion criteria are recruited sequentially by convenient sampling until the sample size is attained, with the agreement of the institutional ethics committee. A total of 98 patients with a mean age of 53.61 ± 12.48 years were studied in the final analysis. The mean duration of lump was 4.62 ± 2.18 months and only 6.12% had the complaint of pain.  Majority of them had stage IIIB carcinoma at 43.88%, followed by stage IIA at 27.55%, 15.31% stage IIB, 13.27% stage IIIA.  At cut off 20, 69(70.40%) had ki67 proliferation index ≥20 and 29(29.59%) had<20. Correlation of Ki-67 Index with expression of estrogen receptor status had a p value of 0.019 and with progesterone receptor status, p 0.003 which was significant.&nbsp

Meckel's Diverticulum as a Conduit in Abdominal Mesothelial Nodular Hyperplasia Due To Cancer Stomach: a Case Report

A 23-year-old male patient presented to surgical department for acute intestinal obstruction of 3 days duration, emergency laparotomy revealed 500-600 ml of ascetic fluid, most of the small and whole of the large bowel omentum and anterior wall of the stomach was studded with numerous tubercles, the mesentery was tethered to the posterior abdominal wall due to extensive fibroses and the ileo-caecal junction was also fibrosed. During surgery we encountered technical difficulty of mobilizing any part of bowel for diversion, it so happened that a patient was blessed to have Meckel's diverticulum and diversion was performed similar to loop illeostomy. Histopathology of the omentum revealed nodular mesothelial hyperplasia, Oesopho-gastroduodenoscopy revealed antral growth of the stomach. Whole of case scenario been depicted