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Atrial fibrillation is a well recognized side effects of several drugs. However it is ignored since most studies have failed to show that it impacts survival adversely. This is not the case with ibrutinib, especially amongst patients with pre-existing cardiac morbidities. In this article, we provide practical consensus guidelines for cancer patients being commenced on therapy with ibrutinib.

Objectives: This study is about the challenges faced by the women doctors in India during the first wave of the COVID-19 pandemic. Material and Methods: We conducted an online survey in 2020 for women doctors who were professionally engaged in active patient management in India before the onset of the current pandemic. Results: A total of 260 valid responses were received. Only 28% (73/260) were able to provide at least 50% of professional services as compared to the pre COVID-19 lockdown period. Statistically significant differences related to emotional health (feelings), physical activity, changes in how family sees the lady professional, personal free time availability, and family bonding. Conclusion: COVID-19 has led to the following important concerns for professional women - academic productivity; work-life balance; missed opportunities for collaborating; mental health, the need for equity-minded academic leadership, and decision-making. Our study showed that majority were stressed during the COVID-19 lockdown – with the impact being highest among those giving more than 50% of their time to professional medical services outside their homes.

Objectives: We present the survey data on molecular testing and its implications among lung cancer specialists in the South Asian Association for Regional Cooperation (SAARC) region. Material and Methods: An online survey Google form was developed that could be completed in Results: We had 354 responders from 8 SAARC countries, 58.9% (209/354) being medical oncologists, and 30.1% (107/354) radiation oncologists. Nearly 50% of responders were seeing patients in the second wave of coronavirus disease 2019 and 89% had seen reduction in their lung cancer patients during first wave. Biomarker testing in advanced lung cancer using next-generation sequencing as the preferred method was more among medical oncologists (76%) as compared to all the other specialists (24%); (Pearson Chi-square = 0.006). The practice of waiting for the molecular testing report before starting first line treatment was 55.4% in corporate/private hospitals as compared to 27% in the government/charity hospital sectors (Pearson Chi-square = 0.015). A total of 89.6% responders believed that targeted therapy has resulted in improved overall survival in advanced lung cancer. Conclusion: Educational activities need to be strengthened so that lung cancer specialists follow comprehensive NGS testing in appropriate settings, as shown by medical oncologists

Our objectives were to stabilize a non-clinical suspension for use in toxicological studies and to develop methods to investigate the stability of the formulation in terms of salt disproportionation. The compound under research was a hydrochloride salt of a practically insoluble discovery compound ODM-203. The first of the three formulation approaches was a suspension prepared and stored at room temperature. The second formulation was stabilized by pH adjustment. In the third approach cooling was used to prevent salt disproportionation. 5 mg/mL aqueous suspension consisting of 20 mg/mL PVP/VA and 5 mg/mL Tween 80 was prepared for each of the approaches. The polymer was used as precipitation inhibitor to provide prolonged supersaturation while Tween 80 was used to enhance dissolution and homogeneity of the suspension. The consequences of salt disproportionation were studied by a small-scale in vitro dissolution method and by an in vivo pharmacokinetic study in rats. Our results show that disproportionation was successfully suppressed by applying cooling of the suspension in an ice bath at 2-8 degrees C. This procedure enabled us to proceed to the toxicological studies in rats. The in vivo study results obtained for the practically insoluble compound showed adequate exposures with acceptable variation at each dose level.

A HPLC method has been validated for identifying five markers (gallic acid, rosmarinic acid, catechin, andrographolide and curcumin) and quantifying curcumin in SynacinnTM formulation. The validation (bracketed strengths of 10 mg/mL and 100 mg/mL) involved assessment of selectivity, precision, Limit of Detection (LOD), Limit of Quantification (LOQ), linearity, accuracy, stability in diluent and formulation stability. Meanwhile, in vivo bone marrow micronucleus test data was presented to evaluate the toxicity potential of Synacinn™ to cause clastogenicity and/or disruption of the mitotic apparatus, as measured by its ability to induce micronucleated polychromatic erythrocytes (MN PCE) in Sprague Dawley rat bone marrow. The test was conducted in two phases viz., Phase I (Dose Range Finding experiment) and Phase II (Definitive experiment). Phase I was conducted to assess general toxicity and bone marrow cytotoxicity of Synacinn™, and to select the doses for the definitive experiment. In-life observations included mortality, clinical signs of toxicity and body weight. Bone marrow samples were collected and extracted from the femur bone using fetal bovine serum. The pellet obtained after the centrifugation was used for preparing bone marrow smears to evaluate the number of immature and mature erythrocytes.

Introduction: Medical education requires a long duration of education and training. Medical stream is a diverse field; an assortment of clinical specialties of number of areas; clinical, psychological, surgical, field work, public health to name a few, with varied clinical environment, duties, and contact with patients. Methodology: Study was conducted in ten Medical colleges from three northern states of India (Uttar Pradesh, Punjab and Chandigarh). 677 final year medical students were included in the study. The study was designed as a cross-sectional self- administered questionnaire-based survey. Data were analyzed based on Frequencies, percentage, weighted scores and Chi square test. The findings were tabulated and represented with the help of suitable diagrammatic and graphical presentation. Results: revealed that around two-third were males (67.50%), majority were under 25 years, Hindus, from urban areas, joint families and 6.79% were married. Majority belonged to HIG. Statistically significant association of some demographic Characteristics (area of residence, gender, marital status and type of family) in selection of Internal medicine as specialty choice, whereas the association was not significant for age, religion and income group.

With evolution of different newer radiotherapy techniques, still the role of brachytherapy in different gynecological malignancies has not sublimed. Most commonly used form of brachytherapy in carcinoma cervix patients is intracavitary brachytherapy. However, all the patients do not qualify for the treatment with intracavitary brachytherapy due to certain clinicopathological conditions. This warrants use of interstitial brachytherapy technique for treatment. For getting good results from interstitial brachytherapy, a good expertise and a proper infrastructure are needed. For perineal interstitial brachytherapy, different templates have been designed, used, and published by authors in different literature over the period. Among all these different templates, Martinez Universal Perineal Interstitial Template (MUPIT) has been used in gynecological, urological, and anorectal malignancies. In this literature review, we have discussed mainly MUPIT.

Background: Inhibition of Bromodomain and extra-terminal (BET) family proteins by small molecules is actively being pursued as a therapeutic strategy in the clinics. Targeted protein degradation is an emerging therapeutic modality that has shown initial promise in the clinic. BET protein degradation has inherent advantages over inhibition viz. expansion of indication scope and amenability to intermittent dosing schedules. While many BET degraders have been disclosed earlier, inferior pharmacokinetic properties limit their further development. Methods and Results: We have designed and synthesized various hetero bi-functional molecules by conjugating novel and selective BET BRD ligands with VHL or CRBN ligands. This exercise led to the identification of several potent and selective BRD4 protein degraders with activity in a wide range of hematological and solid tumor cell lines. We have profiled one of the lead compounds extensively in vitro to gain insights on the mechanism of action. The lead compound showed lasting effect on BET protein abundance post compound washout while leading to apoptosis. This compound has favorable IV PK profile in rodents had has clean CYP and hERG profiles. Additionally, the lead compound exhibited significant tumor growth inhibition in MV4-11 xenograft model when dosed via i.v. route. Both QD and Q48h dosing regimens were well tolerated and produced efficacy in mouse models. Further SAR in the linker portion resulted in compounds with lower iv clearance and oral bioavailability either as prodrugs or as such. The proteomics study revealed a high selectivity towards BET proteins for the lead compound. Conclusions: Potent and selective BET protein degraders were identified by conjugating novel BET BRD ligands with both VHL and CRBN ligands. Optimization of these first generation BET degraders led to improved metabolic stability, translating into low iv clearance in rodents. Further evaluation of these compounds as prodrugs resulted in good oral exposures. Lead compounds from both the series have low iv clearance and are orally bioavailable in a simple formulation. We believe these compounds serve as valuable tools to fully understand the clinical scope of BET degraders. Citation Format: Chandrasekhar Abbineni, Mahaboobi Jaleel, Subhendu Mukherjee, Sivapriya Marappan, Nirbhay Kumar Tiwari, DS Samiulla, AB Aravind, Naveen R Kumar, Indu Bansal, Raghurami B Reddy, NVM Rao Bandaru, Akhila Srinivas, Janith Mary Maben, Suraj Tgore, Avainash Kumar, Rakesh P. Nankar, Chandranath D. Naik, Thomas Antony, Kavitha Nellore, Sanjeev Giri, Girish Daginakatte, Shekar Chelur, Olli Törmäkangas, Gerd Wohlfahrt, Mari Björkman, Elina Mattila, Laura Ravanti, Anu Moilanen, Murali Ramachandra, Susanta Samajdar. First in class orally bioavailable BETBRD degraders [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1754.

For the study Faizabad regions of state Uttar Pradesh were selected as locales. Faizabad region included districts namely-Faizabad, Barabanki, Sultanpur, Ambedkar Nagar and Gonda. Four Schools and hundred children from each district were selected. Hence a total of 500 primary school children were assessed for peer acceptance and rejection and interpersonal social problem-solving skills. Result of this study showed the relationship between peer acceptance and rejection and interpersonal social problem-solving skills. Positively rated children suggested more number of relevant strategies and flexibility than their less accepted counter parts. Also positively rated children were more likely to suggest prosocial strategies for obtaining access to an object in another child's possession, while reverse was seen among negatively rated children.

Purpose: The aim of this study is to report a preliminary analysis of our clinical experience with extended field pelvic (conformal) radiation, with or without concurrent chemotherapy, in gynaecological malignancies. Materials and Methods: 27 women with gynaecological malignancies (17 with Carcinoma Cervix and 10 with Carcinoma Endometrium) were treated between November 2009 and October 2015 with Extended Field abdomino-pelvic radiation. All patients were treated with conformal radiation (Intensity Modulated Radiotherpy or Volumetric Modulated Arc Therapy). All patients underwent CT Simulation followed by target and OAR delineation as per RTOG guidelines. Dose prescriped was 45-50 Gy in 1.8 Gy per fraction and boost to gross node upto 54-56 Gy. Planning was done on Eclipse Planning system, and treatment was delivered on 6 MV linac. Concurrent chemotherapy was given when indicated. All toxicities were scored according to Common Terminology Criteria for Adverse Events (CTCAE v 4.03). Dosimetric parameters were correlated with toxicities. Results: Median follow up was 9.5 months (Range 0-52 months). 14 (51.8%) patients developed Grade 1 and 2 acute hematological toxicity and 1 (0.04%) developed Grade 3 toxicity. 10 (37%) patients developed Grade 1 and 2 acute gastrointestinal toxicity and 1 (0.04%) developed grade 4 toxicity. 3 (11.12%) patients had late toxicity in the form of prolonged leucopenia, SAIO, and Irritable Bowel Syndrome. 1 patient did not complete her treatment due to persistent leucopenia (Grade 3). Conclusion: Extended field Radiation in Gynaecological malignancies is a reasonably well tolerated procedure when treated with IMRT or VMAT, with acceptable toxicity profile.

This study aimed to investigate perception of parent-adolescent interaction, outcomes and also to find out gender differences (girl Vs mother, girls Vs father and boy Vs mother, boy Vs father). Data were collected from 1719 adolescents (692 girls, 1027 boys) studying in 7th (329 boys, 263 girls), 9th (320 boys, 244 girls) and 11th (378 boys, 185 girls) classes of some selected schools of Delhi. Age ranged from 11-17 years. Self constructed questionnaire was used to find out parent-adolescent interaction and outcomes, categorized into 5 dimensions namely; Quality of interaction, Parental support, Kind of Treatment, Punishment and Reward and Criticism/Complaints between adolescents and their parents. Students were asked to mark their responses separately for father and mother, as per instructions provided for each section. Means and standard deviations were calculated. ‘t’ test was used to find out significance of difference between means. The result revealed that there are significant differences in parental interaction and outcomes with adolescent of different age groups and sex.

This study has been designed to find out stress in early and late entrants in medical education and also age and gender interaction effect on stressor. The study was conducted on 1200 first year medical students ten randomly selected medical colleges of North Indian states of India. Stress of medical students was measured in terms of various stressors. Medical Student Stressor Questionnaire (MSSQ) developed by Muhamad S. B. Yusoff, Ahmad F. A. Rahim and Mohd J. Yaacob was used to identify six domains of stressor including – Academic related stressors (ARS), Intrapersonal and interpersonal related stressors (IRS), Teaching and learning-related stressors (TLRS), Social related stressors (SRS), Drive and desire related stressors (DRS) and Group activities related stressors (GARS). Data were collected in person with each respondent. Means, Standard deviations for each domain were calculated separately for boys and girls and age groups and F test was used to find out the main effects and the interaction effects for each domain of stress. Significant interaction effects were found in all the domains of stressor except two ARS and IRS among groups. Our brief survey suggests that there are substantial differences expressed by these older students in regard to stressor prevalence. Current study demonstrated that early entrant boys and late entrant girls feel more academic related stress. For all other domains early entrants were having more stress than were their younger counterparts. The findings can help understand harms and stresses in early and late entrants in medical education and prepare intervention and guidance programmes for new medical entrants to beat stress and healthier amendment.

This report presents features of mesoblastic nephroma, a rare benign tumor of kidney observed in perinatal period of life and highlights the role of imaging investigations in the proper management of this tumor. Awareness of this tumor may facilitate prevention and management of severe obstetric and neonatal complications and inadvertent and vigorous therapy compatible with that of Wilms' tumor can be avoided.