A Multistep Tumor Growth Model of High Grade Serous Ovarian Carcinoma Identifies Hypoxia Associated Signatures.

High-grade serous ovarian carcinoma (HGSC) is associated with late-stage disease presentation and poor prognosis, with limited understanding of early transformation events. Our study presents a comprehensive analysis of tumor progression and organ-specific metastatic dissemination to identify hypoxia-associated molecular, cellular, and histological alterations during HGSC tumor growth. H&E staining and subsequent histological assessment of tumor volume-based categories revealed recapitulation of numerous clinical features, including the prevalence of >0.0625≤0.5cm3 volume tumors and metastatic spread by orthotopic xenografts. The constant evolution of the tissue architecture concerning increased hyaluronic acid deposition, tumor vasculature, necrosis, altered proliferative potential, and gland forming ability of the tumor cells was identified. Flow cytometry and label chase-based molecular profiling across the tumor regenerative hierarchy identified the hypoxia-vasculogenic niche and the hybrid epithelial-mesenchymal tumor-cell state as determinants of self-renewal capabilities of progenitors and cancer stem cells (CSCs). A regulatory network and mathematical model based on tumor histology and molecular signatures predicted hypoxia-inducible factor 1-alpha (HIF1A) as a central node connecting epithelial-mesenchymal transition, metabolic and necrotic pathways in HGSC tumors. Thus, our findings provide a temporal resolution of hypoxia-associated events that sculpt HGSC tumor growth, and an in-depth understanding of it may aid in the early detection and treatment of HGSC.

Functional balance between Tcf21-Slug defines cellular plasticity and migratory modalities in high grade serous ovarian cancer cell lines.

Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis that can be initiated by single cell epithelial to mesenchymal transition (EMT) or cooperative cell migration (CCM). Our study identifies novel regulatory cross-talks between Tcf21 and Slug in mediating phenotypic and migration plasticity in high-grade serous ovarian adenocarcinoma (HGSC). Differential expression and subcellular localization associate Tcf21, Slug with epithelial, mesenchymal phenotypes, respectively; however, gene manipulation approaches identify their association with additional intermediate phenotypic states, implying the existence of a multistep epithelial-mesenchymal transition program. Live imaging further associated distinct migratory modalities with the Tcf21/Slug status of cell systems and discerned proliferative/passive CCM, active CCM and EMT modes of migration. Tcf21-Slug balance identified across a phenotypic spectrum in HGSC cell lines, associated with microenvironment-induced transitions and the emergence of an epithelial phenotype following drug exposure. Phenotypic transitions and associated functionalities following drug exposure were affirmed to ensue from occupancy of Slug promoter E-box sequences by Tcf21. Our study effectively provides a framework for understanding the relevance of ovarian cancer plasticity as a function of two transcription factors.

A Prospective Study on Post Covid Sudden Onset Sensory Neural Hearing Loss and Its Recovery.

Sudden sensorineural hearing loss (SSNHL) is a known complication of a number of viral infections, but there is little literature to date on its association to Corona virus disease 2019(COVID-19).This study aimed to investigate the incidence and recovery from SSNHL in post COVID-19 patients. A study was conducted in 6 months of duration at our tertiary care COVID dedicated hospital. Total 280 patients with age group of 12-70 years, laboratory confirmed COVID 19 positive patients having mild to moderate COVID symptoms were included. Patients were examined clinically along with all safety measures to analyze incidence and their recoveries from SSNHL by clinical examination and using Pure Tone Audiometry (PTA). Out of 280 patients the incidence of only SSNHL is 1.07% (3 patients) and SSNHL with tinnitus is 2.14%(6 patients).Total recovery(TR) regained in 2 patients of SSNHL, Partial recovery(PR) in 4 patients, Slight improvement(SI) in 1 patient and no recovery(NR) in 2 patients. The incidence of SSNHL in time of COVID 19 pandemic appears to be higher (3.2%) than before the pandemic (0.005%-0.16%). Incidence among younger age group and patients with no comorbidities has been also increased. In diagnosed case of SSNHL, early treatment with short term course of oral steroids and neuromodulator drugs are the mainstay treatment. Awareness of such non-specific presentation of COVID 19 patients is crucial and shared decision making with the patient and providing health care personnel is necessary for decreasing the hearing loss associated morbidity.

Prevalence and Recovery from Newly Onset Anosmia and Ageusia in Covid 19 Patients at our Teritary Care Centre.

Anosmia (loss of smell) and Ageusia (loss of taste) are newly presenting independent symptoms in association with multiple symptoms such as Fever, Dry cough and Breathlessness in COVID 19 Patients.The Study of aims is to estimate Prevalence of Anosmia & Ageusia in Confirmed Covid 19 cases and to assess their Recovery rates. A Study conducted between June 2020 and September 2020 at a tertiary care COVID Dedicated hospital. Total 200 patients with age group 12-70 years Confirmed COVID 19 Positive Patients using RTPCR having mild to moderate symptoms were included. Patients were examined Clinically alongwith all safety measures to analyse prevalence & estimate their recoveries from sensory impairement using 10 item based DyNaCHRON questionnaire(concerned with taste and smell) at 10th, 14th & 21st Day. Out of 200 patients, Prevalence of Isolated Ageusia is 7%, Isolated Anosmia 4.5% and with Anosmia and Ageusia 4%. Complete Recovery regained in Ageusia within 14 days, while Rest all patients of Anosmia and both (Anosmia and Ageusia) within 21 days, Except 2 patients where long term Anosmia persists. Newly onset Anosmia and Ageusia are common in early stages of Covid 19 disease. They are Prevalent in mild to moderate symptomatic form of Diseases. Recovery in most cases is rapid and complete.Early Screening tests performed in suspected COVID 19 patients with loss of taste and smell sensation allows early diagnosis and treatment.