Methylome-wide and meQTL analysis helps to distinguish treatment response from non-response and pathogenesis markers in schizophrenia.

Schizophrenia is a complex condition with entwined genetic and epigenetic risk factors, posing a challenge to disentangle the intermixed pathological and therapeutic epigenetic signatures. To resolve this, we performed 850K methylome-wide and 700K genome-wide studies on the same set of schizophrenia patients by stratifying them into responders, non-responders, and drug-naïve patients. The key genes that signified the response were followed up using real-time gene expression studies to understand the effect of antipsychotics at the gene transcription level. The study primarily implicates hypermethylation in therapeutic response and hypomethylation in the drug-non-responsive state. Several differentially methylated sites and regions colocalized with the schizophrenia genome-wide association study (GWAS) risk genes and variants, supporting the convoluted gene-environment association. Gene ontology and protein-protein interaction (PPI) network analyses revealed distinct patterns that differentiated the treatment response from drug resistance. The study highlights the strong involvement of several processes related to nervous system development, cell adhesion, and signaling in the antipsychotic response. The ability of antipsychotic medications to alter the pathology by modulating gene expression or methylation patterns is evident from the general increase in the gene expression of response markers and histone modifiers and the decrease in class II human leukocyte antigen (HLA) genes following treatment with varying concentrations of medications like clozapine, olanzapine, risperidone, and haloperidol. The study indicates a directional overlap of methylation markers between pathogenesis and therapeutic response, thereby suggesting a careful distinction of methylation markers of pathogenesis from treatment response. In addition, there is a need to understand the trade-off between genetic and epigenetic observations. It is suggested that methylomic changes brought about by drugs need careful evaluation for their positive effects on pathogenesis, course of disease progression, symptom severity, side effects, and refractoriness.

Association of molecular subgroups with pathological parameters in endometrial carcinomas.

BACKGROUND: The integration of molecular features into the already existing pathological classification of endometrial carcinomas will offer significant prognostic information. As the literature search reveals, there are no studies from India that have classified these carcinomas based on molecular subtypes. The aim of the study was to classify endometrial carcinomas into four subtypes based on their molecular and immunohistochemical features and to find out the association of each of these molecular subtypes with the other pathological parameters. METHODS: A prospective study was done on 37 consecutive cases of fresh hysterectomy specimens, biopsy-proven as endometrial carcinomas between November 2019 and August 2020. Three immunohistochemical markers (p53, mismatch repair proteins,MutS homolog6 and Postmeiotic seggregation 2 respectively[MSH6, and PMS2]), along with DNA (deoxyribonucleic acid) sequencing of selected regions of the POLE gene was performed in each of the 37 cases. Endometrial carcinomas were subclassified into four subtypes, and the association of each of these four subtypes with the other pathological parameters was also explored. Statistical analysis was done using the IBM Statistical Package for the Social Science (SPSS) Version 20.0 software (IBM SPSS, USA). RESULTS: Among the 37 cases studied, eight (21.6%) cases were p53 abnormal, eight (21.6%) cases showed MMR-D (mismatch repair deficient), one case (2.7%) showed mutation of POLE, and 21 cases (56.8%) were assembled under p53 wild-type. Higher grade endometrial carcinomas showed more (80.0%) p53 abnormal (P < 0.001). All the p53 wild-type (100%) were of Type 1 endometrial carcinoma subtype (P = 0.001) and low-grade type (90.5%; P = 0.005). CONCLUSION: Our study confirms that the type of carcinoma and grade correlates with p53 expression, p53 abnormal being associated with higher grade and type 2 endometrial carcinomas, whereas p53 wild-type is associated with low-grade and type 1 endometrial carcinoma. There was only one case of the POLE subtype identifiable in our study.

An Unusual Antenatal Presentation of a Mature Pericardial Teratoma Masquerading as Congenital Pulmonary Airway Malformation.

We report an antenatal presentation of a huge pericardial mature teratoma that was referred as congenital pulmonary airway malformation (CPAM) in the late third trimester of pregnancy. Initial ultrasound evaluation revealed a huge predominantly cystic lesion with mixed echogenicity in the left hemithorax. A provisional diagnosis of pleural tumor was considered in view of previous scans at 20‒28 weeks being normal and associated pleural effusion. Magnetic resonance imaging of the fetus reported the lesion to be CPAM which was supported by postnatal computed tomographic imaging done on day 2 of life. However, intraoperatively, the lesion was found to be of pericardial origin which on subsequent histopathological examination was confirmed to be mature teratoma. We recommend considering potential differential diagnosis other than CPAM, especially when the lesion is found for the first time in the late third trimester.

Comparative study of surgical outcomes of twin-site phacotrabeculectomy with mitomycin C in primary open-angle glaucoma versus primary angle-closure glaucoma.

Purpose: To compare the surgical outcomes of twin-site phacotrabeculectomy with Mitomycin C (MMC) in primary open-angle glaucoma (POAG) versus primary angle-closure glaucoma (PACG). Methods: Prospective, comparative, observational study. Patients with visually significant cataract and primary glaucoma were divided into two groups: POAG and PACG. They underwent twin-site phacotrabeculectomy with MMC and followed up on days 1, 15, 1 month, 6 months, and 12 months. Baseline and follow-up visits were compared to find the differences in intraocular pressure (IOP), antiglaucoma medications (AGM), success rates, anterior chamber depth (ACD), and axial length (AXL). Results: There were 50 eyes each in POAG and PACG groups. Mean IOP reduction from baseline to 12 months (21.22 ± 6.0 to 11.40 ± 2.8-POAG group vs 24.16 ± 7.6 to 12.42 ± 3.2-PACG group) was statistically significant in both groups (P < 0.001), but no significant difference between groups (P = 0.095). There was a statistically significant decline in the number of AGM in POAG [1.66 (0.7) to 0.38 (0.7), P < 0.001] and PACG [2.10 (0.7) to 0.70 (0.8), P < 0.001]; the decline was more in POAG (P = 0.012) at last visit. Probability of overall (complete and qualified) success at 12 months postop was 72.0% [95% confidence interval (CI): 57.4-82.4] in PACG and 84.0% (95% CI: 70.5-91.7) in POAG group. There was a significant increase in ACD and a decrease in AXL in both groups (P < 0.001). More interventions were required in the PACG group (38, P = 0.012). Conclusion: Phacotrabeculectomy with MMC causes a significant reduction in IOP and improvement in biometric parameters in both POAG and PACG. Patients with PACG required more postoperative interventions, while a lesser number of antiglaucoma medications were needed in POAG patients.

Endometriosis in clear cell and endometrioid carcinoma ovary: its impact on clinicopathological characteristics and survival outcomes.

Background: Malignant transformation in endometriosis was first described by Sampson in 1925. There is now sufficient evidence of its association specifically with endometrioid (EOC) and clear cell ovarian cancer (CCOC). Whether endometriosis-associated ovarian cancer (EAOC) is a distinct clinicopathological entity from non-endometriosis-associated ovarian cancer (NEAOC) remains uncertain. Objectives: This study aimed to assess the impact of endometriosis on clinical characteristics and survival outcomes in EOC and CCOC. Methods: This is a retrospective single-institution analysis of patients diagnosed with CCOC AND EOC between 2010 and 2021. Demographic and clinical presentation data were obtained from medical records. Patients were followed up till March 2023. Statistical analysis was done using the IBM SPSS Statistics 20 Windows. Results: Of the 77 cases of CCOC and EOC ovary, 38 had histopathologically proven endometriosis. There was no difference in age (51.62 and 50.05 years, respectively), body mass index, parity, menopausal status and CA 125 levels at presentation. Ascites was more frequent in the absence of endometriosis (30% versus 8.1%, p = 0.015). However, this did not translate to a statistical difference in the stage, with the majority presenting in the early stage. (94% versus 83%). All 78 patients underwent primary cytoreduction with equal rates of optimal resection.There was no difference in the mean disease-free interval between EAOC and NEAOC (107.6 and 109.4 months, p 0.484). Recurrences were predominantly pelvic in both groups. The disease-specific survival was 111.7 and 120.1 months, respectively, with and without endometriosis. This was however not statistically significant (p 0.751). Conclusion: In the Indian population, endometriosis did not have any impact on the age at presentation, CA 125 levels, stage of the disease and survival outcomes in EOC and CCOC ovary.

Validating saliva as a biological sample for cost-effective, rapid and routine screening for SARS-CoV-2.

PURPOSE: Compared to nasopharyngeal/oropharyngeal swabs (N/OPS-VTM), non-invasive saliva samples have enormous potential for scalability and routine population screening of SARS-CoV-2. In this study, we investigate the efficacy of saliva samples relative to N/OPS-VTM for use as a direct source for RT-PCR based SARS-CoV-2 detection. METHODS: We collected paired nasopharyngeal/oropharyngeal swabs and saliva samples from suspected positive SARS-CoV-2 patients and tested using RT-PCR. We used generalized linear models to investigate factors that explain result agreement. Further, we used simulations to evaluate the effectiveness of saliva-based screening in restricting the spread of infection in a large campus such as an educational institution. RESULTS: We observed a 75.4% agreement between saliva and N/OPS-VTM, that increased drastically to 83% in samples stored for less than three days. Such samples processed within two days of collection showed 74.5% test sensitivity. Our simulations suggest that a test with 75% sensitivity, but high daily capacity can be very effective in limiting the size of infection clusters in a workspace. Guided by these results, we successfully implemented a saliva-based screening in the Bangalore Life Sciences Cluster (BLiSC) campus. CONCLUSION: These results suggest that saliva may be a viable alternate source for SARS-CoV-2 surveillance if samples are processed immediately. Although saliva shows slightly lower sensitivity levels when compared to N/OPS-VTM, saliva collection is logistically advantageous. We strongly recommend the implementation of saliva-based screening strategies for large workplaces and in schools, as well as for population-level screening and routine surveillance as we learn to live with the SARS-CoV-2 virus.

Establishing an effective antimicrobial stewardship program at four secondary-care hospitals in India using a hub-and-spoke model.

Background: The high burden of antimicrobial resistance in India necessitates the urgent implementation of antimicrobial stewardship programs (ASPs) in all healthcare settings in India. Most ASPs are based at tertiary-care centers, with sparse data available regarding the effectiveness of an ASP in a low-resource primary/secondary-care setting. Methods: We adopted a hub-and-spoke model to implement ASPs in 4 low-resource, secondary-care healthcare settings. The study included 3 phases measuring antimicrobial consumption data. In the baseline phase, we measured days on antimicrobial therapy (DOTs) with no feedback provided. This was followed by the implementation of a customized intervention package. In the postintervention phase, prospective review and feedback were offered by a trained physician or ASP pharmacist, and days of therapy (DOT) were measured. Results: In the baseline phase, 1,459 patients from all 4 sites were enrolled; 1,233 patients were enrolled in the postintervention phase. Both groups had comparable baseline characteristics. The key outcome, DOT per 1,000 patient days, was 1,952.63 in the baseline phase and significantly lower in the post-intervention period, at 1,483.06 (P = .001). Usage of quinolone, macrolide, cephalosporin, clindamycin, and nitroimidazole significantly decreased in the postintervention phase. Also, the rate of antibiotic de-escalation was significantly higher in the postintervention phase than the baseline phase (44% vs 12.5%; P < .0001), which suggests a definite trend toward judicious use of antibiotics. In the postintervention phase, 79.9% of antibiotic use was justified. Overall, the recommendations given by the ASP team were fully followed in 946 cases (77.7%), partially followed in 59 cases (4.8%), and not followed in 137 cases (35.7%). No adverse events were noted. Conclusion: Our hub-and-spoke model of ASP was successful in implementing ASPs in secondary-care hospitals in India, which are urgently needed.

Squalene hopene cyclases and oxido squalene cyclases: potential targets for regulating cyclisation reactions.

Squalene hopene cyclases (SHC) convert squalene, the linear triterpene to fused ring product hopanoid by the cationic cyclization mechanism. The main function of hopanoids, a class of pentacyclic triterpenoids in bacteria involves the maintenance of membrane fluidity and stability. 2, 3-oxido squalene cyclases are functional analogues of SHC in eukaryotes and both these enzymes have fascinated researchers for the high stereo selectivity, complexity, and efficiency they possess. The peculiar property of the enzyme squalene hopene cyclase to accommodate substrates other than its natural substrate can be exploited for the use of these enzymes in an industrial perspective. Here, we present an extensive overview of the enzyme squalene hopene cyclase with emphasis on the cloning and overexpression strategies. An attempt has been made to explore recent research trends around squalene cyclase mediated cyclization reactions of flavour and pharmaceutical significance by using non-natural molecules as substrates.

How hairfall saved the patient from cancer twice - A postmenopausal patient with synchronous endometrial and endocervical carcinomas presenting with endocrine symptoms.

Ovarian stromal hyperthecosis is an uncommon nonneoplastic cause of ovarian hyperandrogenism mainly in postmenopausal women. Here, we present a case of a postmenopausal woman who presented with features of virilization like alopecia and hirsutism. During its workup, two malignancies were diagnosed at a very early stage. Microscopic focus of endometrial adenocarcinoma in a polyp and similar focus of endocervical adenocarcinoma in the subsequent hysterectomy specimen were noted. Presence of synchronous malignancies in the uterus is very rare and it being detected in a patient who presented with a non-related symptom of hairfall makes it an interesting case scenario.

Diabetes IN hospital - Glucose and Outcomes in the COVID-19 pandemic (DINGO COVID-19): the 2020 Melbourne hospital experience prior to novel variants and vaccinations.

BACKGROUND AND AIMS: A relationship between diabetes, glucose and COVID-19 outcomes has been reported in international cohorts. This study aimed to assess the relationship between diabetes, hyperglycaemia and patient outcomes in those hospitalised with COVID-19 during the first year of the Victorian pandemic prior to novel variants and vaccinations. DESIGN, SETTING: Retrospective cohort study from March to November 2020 across five public health services in Melbourne, Australia. PARTICIPANTS: All consecutive adult patients admitted to acute wards of participating institutions during the study period with a diagnosis of COVID-19, comprising a large proportion of patients from residential care facilities and following dexamethasone becoming standard-of-care. Admissions in patients without known diabetes and without inpatient glucose testing were excluded. RESULTS: The DINGO COVID-19 cohort comprised 840 admissions. In 438 admissions (52%), there was no known diabetes or in-hospital hyperglycaemia, in 298 (35%) patients had known diabetes, and in 104 (12%) patients had hyperglycaemia without known diabetes. ICU admission was more common in those with diabetes (20%) and hyperglycaemia without diabetes (49%) than those with neither (11%, P < 0.001 for all comparisons). Mortality was higher in those with diabetes (24%) than those without diabetes or hyperglycaemia (16%, P = 0.02) but no difference between those with in-hospital hyperglycaemia and either of the other groups. On multivariable analysis, hyperglycaemia was associated with increased ICU admission (adjusted odds ratio (aOR) 6.7, 95% confidence interval (95% CI) 4.0-12, P < 0.001) and longer length of stay (aOR 173, 95% CI 11-2793, P < 0.001), while diabetes was associated with reduced ICU admission (aOR 0.55, 95% CI 0.33-0.94, P = 0.03). Neither diabetes nor hyperglycaemia was independently associated with in-hospital mortality. CONCLUSIONS: During the first year of the COVID-19 pandemic, in-hospital hyperglycaemia and known diabetes were not associated with in-hospital mortality, contrasting with published international experiences. This likely mainly relates to hyperglycaemia indicating receipt of mortality-reducing dexamethasone therapy. These differences in published experiences underscore the importance of understanding population and clinical treatment factors affecting glycaemia and COVID-19 morbidity within both local and global contexts.

Myo-D-inositol Trisphosphate Signalling in Oomycetes.

Oomycetes are pathogens of plants and animals, which cause billions of dollars of global losses to the agriculture, aquaculture and forestry sectors each year. These organisms superficially resemble fungi, with an archetype being Phytophthora infestans, the cause of late blight of tomatoes and potatoes. Comparison of the physiology of oomycetes with that of other organisms, such as plants and animals, may provide new routes to selectively combat these pathogens. In most eukaryotes, myo-inositol 1,4,5 trisphosphate is a key second messenger that links extracellular stimuli to increases in cytoplasmic Ca2+, to regulate cellular activities. In the work presented in this study, investigation of the molecular components of myo-inositol 1,4,5 trisphosphate signaling in oomycetes has unveiled similarities and differences with that in other eukaryotes. Most striking is that several oomycete species lack detectable phosphoinositide-selective phospholipase C homologues, the enzyme family that generates this second messenger, but still possess relatives of myo-inositol 1,4,5 trisphosphate-gated Ca2+-channels.

Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background.

The immune system seems to play a significant role in the development of schizophrenia. This becomes more evident with the emerging role of MHC complex and cytokines in schizophrenia. In the recent past, several GWAS have implied that the 6p21 region was associated with schizophrenia. However, the majority of these studies were performed in European populations. Considering tremendous variations in this region and the probability of South Indian populations being quite different from the European gene-pool from an immunogenetic point, the present study was initiated to screen SNPs in the 2.28 MB region, spanning the extended MHC locus, in 492 cases and controls from a South Indian population. We found a very strong association of rs3815087 with schizophrenia at both allelic and genotypic levels with a 7.3-fold increased risk in the recessive model. Interestingly, the association of none of the earlier reported GWAS hits, such as rs3130375, rs3131296, rs9272219, or rs3130297 were found to be replicable in our study population. rs3815087 lies in the 5'UTR region of the psoriasis susceptibility 1 candidate 1 (PSORS1C1) gene, which further suggests that inflammatory processes might be an important common pathogenic pathway leading to both schizophrenia and psoriasis. The study hints at ethnic specific gene-environment interaction in determining the critical threshold for disease initiation and progression.

Role of fibroblast growth factor-23 (FGF-23) in the prediction of postoperative atrial fibrillation after coronary artery bypass surgery.

Introduction: Fibroblast growth factor-23 (FGF-23) is a bone-derived hormone which had shown a significant association with the occurrence of atrial fibrillation (AF) in patients with chronic kidney disease. We hypothesized that FGF-23 could be a very useful predictive biomarker for atrial remodeling and in turn for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). We also looked at the correlation of cardiac remodeling in right atrial biopsy and its correlation with POAF and with the FGF-23 level. Methods: This study was a single-center cross-sectional observational study. All the patients who were planned for CABG with no prior history of AF were included in the study. All the patients were tested for preoperative serum FGF-23 level. During CABG, biopsy specimen of the right atrial appendage was sent for histopathology evaluation. All patients were monitored for POAF until discharge from the hospital. Results: This study involved 60 patients who underwent elective CABG. Multivariate analysis revealed a significant association between preoperative FGF-23 levels with the occurrence of POAF (p < 0.001). The area under the curve of FGF-23 was 0.894 with a sensitivity of 92.3% and specificity of 87.23%. The cut-off value for serum FGF-23 levels was found to be 6.50 ng/ml. Analysis of biopsy specimens revealed that the presence of hypertrophic myocytes had a significant association with the occurrence of POAF/POAE and with FGF-23. Conclusion: Preoperative FGF-23 levels can predict the incidence of POAF in post-CABG patients. Histopathologically, the presence of hypertrophic myocytes correlated well with the occurrence of POAF.

Innovator Versus Biosimilar Ranibizumab in Polypoidal Choroidal Vasculopathy: Real-World Evidence.

INTRODUCTION: To analyze the efficacy and safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India; BRm; Razumab®) and the innovator ranibizumab drug (IRm; LUCENTIS®) in Indian patients with polypoidal choroidal vasculopathy (PCV) under real-world conditions. METHODS: This was a retrospective study of treatment-naïve and previously treated PCV eyes undergoing intravitreal therapy with either BRm or IRm from January 2019 to September 2020 as three loading doses followed by a pro-re-nata (PRN) regimen. Changes in the best-corrected visual acuity (BCVA), subretinal fluid (SRF), intraretinal fluid (IRF), SRF height, and subfoveal choroidal thickness (SFCT) and the safety profiles were assessed at weeks 12, 24, and 52, respectively. RESULTS: A total of 22 eyes received IRm and 19 eyes underwent BRm therapy, respectively. Both the groups were comparable in age (P = 0.41) and gender distribution, although the BRm arm had significantly more eyes that were previously treated (P < 0.00001) with a greater median number of injections (P < 0.0001). At week 52, both groups had similar gains in visual acuity (P = 0.19), SRF resolution (P = 0.8), IRF resolution (P = 0.47), and SRF height (P = 0.71). The IRm eyes exhibited a significant improvement in BCVA (P = 0.001) at all visits with a greater mean number of injections (IRm: 5.41 ± 0.94; BRm: 4 ± 1.45; P = 0.0004), while the BRm eyes showed a similar increase in BCVA but did not reach statistical significance until week 52. The SFCT decreased significantly in the BRm arm at week 52 (P = 0.045). One eye (5.26%) in the BRm arm experienced mild anterior uveitis, which was treated with topical corticosteroids. In either arm, no other ocular or systemic adverse effects were observed. CONCLUSIONS: Our real-world data demonstrated the ranibizumab biosimilar Razumab to have comparable visual acuity outcomes to the innovator ranibizumab molecule with an adequate safety profile in the management of PCV. Although these encouraging results support its use as a viable alternative to the innovator molecule, further prospective studies in a diverse patient population are needed to validate our findings.

COVID-19 symptoms are reduced by targeted hydration of the nose, larynx and trachea.

Dehydration of the upper airways increases risks of respiratory diseases from COVID-19 to asthma and COPD. We find in human volunteer studies involving 464 human subjects in Germany, the US, and India that respiratory droplet generation increases by up to 4 orders of magnitude in dehydration-associated states of advanced age (n = 357), elevated BMI-age (n = 148), strenuous exercise (n = 20) and SARS-CoV-2 infection (n = 87), and falls with hydration of the nose, larynx and trachea by calcium-rich hypertonic salts. We also find in a protocol of exercise-induced airway dehydration that hydration of the airways by calcium-rich salts increases oxygenation relative to a non-treatment control (P < 0.05). In a random control study of COVID-19 positive subjects (n = 40), thrice-a-day delivery of the calcium-rich hypertonic salts (active) suppressed respiratory droplet generation by 51% ± 11% and increased oxygen saturation over three days of treatment by 48.08% ± 9.61% (P < 0.001), while no changes were observed in the nasal-saline control group. Self-reported symptoms significantly declined in the active group and did not decline in the control group. Hydration of the upper airways appears promising as a non-drug approach for reducing risks of respiratory diseases such as COVID-19.

Recurrent extramedullary plasmacytomas without multiple myeloma: A case report with review of the literature.

BACKGROUND: Extramedullary plasmacytoma (EMP) is an uncommon presentation and usually occurs in conjunction with multiple myeloma (MM). An EMP without developing MM at any point is an extremely rare presentation, and only seven such cases have been reported in the literature to date. PRESENTATION OF CASE: We present a case of EMP, who presented with multiple recurrent lesions in rare sites like nasal cavity, testis and skin without the involvement of bone marrow at any point of disease course. He was treated with multiagent chemotherapy (DT-PACE) and continues to be in remission at 29 months post-chemotherapy, which is the longest amongst all the cases reported so far. DISCUSSION AND CONCLUSIONS: There are no clearly defined guidelines to treat EMP. Our case had a clinical presentation at very unusual sites and was treated with DT-PACE regimen as against the previous seven reported cases and had the most prolonged period of remission.

Idiopathic lenticular surface neovascularization: An unusual presentation.

PURPOSE: To present a case of posterior lenticular surface neovascularization in the absence of any ocular or systemic pathology. OBSERVATIONS: A 29-year-old asymptomatic male was detected with the right eye (OD) posterior lenticular surface neovascularization extending for six-clock hours in the temporal portion along with the presence of mild posterior capsular haze. His best-corrected visual acuity was 20/25 in OD and 20/20 in the left eye (OS). No additional abnormality was identified in the remainder of the OD anterior segment and the fundus respectively. OS evaluation was unremarkable. OD imaging including B-scan ultrasonography and ultrasound biomicroscopy (UBM) were essentially normal. The anterior segment optical coherence tomography (AS-OCT) thickened lens capsule with a dense hyperreflective layer adhered to its posterior surface and separating from the capsule in the periphery. Few hyperreflective dots were visible posterior to the ciliary body although no CB thickening was noted. No systemic abnormality was detected. The patient is being managed conservatively and has shown no signs of progression of the neovascularization over six months. CONCLUSIONS AND IMPORTANCE: This is the first reported case of an isolated idiopathic posterior lenticular surface neovascularization occurring in an otherwise healthy patient. Although an unspecified breach in the posterior capsule or undetermined cyclitis can trigger such neovascularization, further histopathological studies of the capsular biopsy and ciliary body can provide better insight into its etiopathogenesis. Additionally, considering the asymptomatic nature of the condition, these patients can be observed and closely monitored.

Impact of Intraoperative Tumor Spillage in Uterine Leiomyosarcoma: a Retrospective Single-Institution Analysis.

Uterine leiomyosarcoma is a rare female reproductive system tumor which is difficult to distinguish from uterine leiomyoma preoperatively. Manual and power morcellation are used to remove the large uterus through the vagina or small abdominal incision. Worse outcome with use of power morcellation is now clear but impact of manual morcellation on survival outcome not established till date. The objective of the present study was to find impact of tumor spillage and to evaluate influencing factors for oncological outcome and prognosis in uterine leiomyosarcoma patients. This is a single-institutional retrospective cohort study including all uterine leiomyosarcoma patients from January 2005 to December 2017. Role of intraoperative tumor spillage and other influencing factors on oncological outcome were assessed. Thirty-three patients with median follow-up period of 49.7 months were evaluated. Stage 1 and absence of tumor spill had significant association with prolonged progression-free survival. Stage 1 uterine leiomyosarcoma (56.8 vs 6.8 months, p = < 0.001), intraoperative tumor spillage (p = 0.03) and progression-free survival > 15 months (68.5 vs 12.2 months, p = < 0.001) were favourable prognostic factors to predict better survival outcome but unable to establish significance on multivariate analysis. Survival plot did not reach median limit for stage I uterine leiomyosarcoma patients with preoperative suspicion. Age, site of recurrence and mitotic index had no significant association with better survival in the present study. Stage I disease and absence of tumor spillage during surgery improved progression-free survival but did not affect overall survival. Progression-free survival more than 15 months can predict better overall survival.

Finite element modelling to assess the submarine groundwater discharge in an over exploited multilayered coastal aquifer.

A three-dimensional variable-density finite element model was developed to quantify the impact of groundwater over use on submarine groundwater discharge (SGD). The model was applied to the Arani-Korttalaiyar river basin, north of Chennai, India. This region has an upper unconfined and lower semi-confined aquifer extending up to 30 km inland from the coast and beyond this distance; the two aquifers merge and become a single unconfined aquifer. The model simulated that during the period from 2000 to 2012, the flux of seawater to the aquifer has increased from 17,000 to 24,500 m3/day due to over-exploitation of groundwater from the semi-confined aquifer. Where as in the unconfined aquifer, SGD has been taking place. Scenarios showing the impact of newly constructed  managed aquifer recharge structures, 10% additional increase in rainfall recharge, and termination of pumping from five well-fields on the groundwater conditions in the area were studied. The model predicted a SGD of 85,243 m3/day from the unconfined aquifer and 22,414 m3/day from the semi-confined aquifer by the end of 2030. By adopting managed aquifer recharge methods, seawater intrusion (rate of 4,408 m3/day) can be reduced and SGD (rate of 22,414 m3/day) increased. The rate of SGD increase and the movement of seawater to aquifer can be completely prevented in the semi-confined aquifer by adopting these management options by 2030. Findings from this study have enhanced the understanding of SGD and water budget, which can be used by decision-makers for the sustainable management of groundwater resources in coastal aquifers.