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Assisted Reproductive Technologies Helping Infertile Couples or Using Minor Girls in Poverty; Boon or Bane?

Abstract: According to WHO data, one in every four couples in developing countries is affected by infertility, and the prevalence remains high year by year. Infertility is considered to be a globally concerned health issue, which affects millions of people of reproductive age worldwide. Nowadays in our modern and developing field of medicine, we have different solutions and treatments for almost each and every disease. Treatment for infertility varies based on the cause, from simple psychological therapy to some complicated procedures. All these procedures are regulated by World Health Organization and their own country’s legislation. Each country has uniqueness in their legislation, but almost all countries mainly focus on ethics, medical outcomes and health of both donor and recipients. However, in some parts of the world, laws are sometimes over-ruled and not abided properly. One of such recent incident took part in southern part of India (4 private hospitals in Tamilnadu, and 2 more hospitals in Andhra Pradesh and Kerala), which made a shocking news for people all over the country. The minor girl aged 16 years was exploited as egg (oocyte) donor. In the modern world, we are focusing and researching more and more on female related health problems, but such incidents worry us. We have a responsibility to prevent from such dreadful incidents in future, since respective governments and courts proceed the case for veracity and justice. As doctors or medical professionals, we have to follow our own medical and professional ethics. And as a citizen, all people including doctors and patients must obey our countries own rules and regulations accordingly. Further we request government authorities to make procedures and laws to be more strict and highly punishable when violated.

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Abstract A018: Characterization of macrophage population in head and neck squamous cell carcinoma and renal cell carcinoma and their role in modulating immune checkpoint blockade response

Abstract Tumor-associated macrophages (TAMs) and monocytes are an integral part of tumor microenvironment (TME) which modulates disease progression. M1 and M2 are the two well-defined subtypes of TAMs whose polarization influence response to immune checkpoint inhibitors (ICIs). Unavailability of data from complex models poses limitations to extensive characterization of these immune subpopulations. In this study, we have evaluated the role of monocytes and TAMs in modulating response to ICI, using the FarcastTM TruTumor histoculture platform. Two different cancer indications, Head and Neck Squamous Cell Carcinoma (HNSCC) and Renal Cell Carcinoma (RCC) were used in the study. HNSCC (n = 25) and RCC (n = 24) tissue samples were collected along with matched blood from the consented patients, post-surgery. Tissue explants were generated and allotted to arms and cultured for 72 hours. Fifteen samples from both indication were treated with anti-PD1 ICI, Nivolumab at a concentration of 132 µg/ml. Macrophage and monocyte sub-populations were characterized by performing flow cytometry, and cytokine (tumor necrosis factor-α (TNF-α), and interferon gamma (IFN-γ)) analysis. In HNSCC, a higher proportion of monocytes compared to RCC (p = 0.02) was observed. Though total TAM proportions in the two indications exhibited no significant difference, a significantly higher proportion of M1/M2 was observed in RCC (p = 0.006) as compared to HNSCC. In addition, RCC also exhibited higher secretion of TNF-α (p = 0.08) as compared to HNSCC. Eleven out of fifteen HNSCC samples (73%) exhibited more than 1.2-fold increase in IFN-γ secretion as opposed to only 6/13 RCC samples (46%), on treatment with Nivolumab. However, the correlation between fold change, with respect to control, in IFN- γ secretion and tumor content was much stronger in RCC (ρ=-0.82; p=0.0009) as compared to HNSCC (ρ=-0.07; p=0.81). This observation could be explained by a comparatively higher immunosuppressive microenvironment in HNSCC, potentially mediated by a higher monocyte subpopulation. On the other hand, the relatively higher M1/M2 ratio in RCC seemed to potentially enhance Nivolumab treatment efficacy as compared to HNSCC. Spatial orientation of macrophage sub-population could give further insights into the role they play in TME. Thus, FarcastTM TruTumor is a relevant platform to characterize the monocyte and TAM population in TME across different cancer indications and to investigate their role in modulating ICI response. Citation Format: Moumita Nath, Nandini Pal Basak, Kowshik Jaganathan, Oliyarasi M, Rajashekar M, Saurabh Bhargava, Amritha Suresh, Lalitha Laxhmi, Jayaprakash Chandra Reddy, Ganesh Mandakulutur Subramanya, Amritha Prabha, Prakash BV, Biswajit Das, Syamkumar V, Chandan Bhowal, Mouniss M, Dharanidharan M, Ritu Malhotra, Govindraj K, Mohit Malhotra, Satish Sankaran. Characterization of macrophage population in head and neck squamous cell carcinoma and renal cell carcinoma and their role in modulating immune checkpoint blockade response [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A018.

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Impact of Artificial Intelligence on Colorectal Polyp Detection and Characterization

AbstractColorectal cancer (CRC) is the third most common cancer in the world. Colonoscopy has contributed significantly to reduction of incidence and mortality of CRC. Integration of artificial intelligence (AI) into colonoscopy practice has addressed the various shortcomings of screening colonoscopies. AI-assisted colonoscopy will help in real-time recognition of type of polyp with probable histology. This will not only save time but will also help to mitigate human errors. Computer-aided detection and computer-aided characterization are two applications of AI, which are being studied extensively with a goal of improvement of polyp and adenoma detection rates. Several studies are being conducted across the globe, which either involve simple decision-making algorithms or complex patterns through neural networks, which imitate the human brain. Most data are collected retrospectively and the research is limited to single-center studies, which might have bias. Therefore, the future research on AI in colonoscopy should aim to develop more sophisticated convolutional neural network and deep learning models that will help to standardize the practice and ensure the same degree of accuracy with all the colonoscopies, irrespective of experience of performing endoscopists. In this review, we will take a closer look at the current state of AI and its integration into the field of colonoscopy.

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Alterations in Immune Responses Are Associated with Dysfunctional Intracellular Signaling in Peripheral Blood Mononuclear Cells of Men and Women with Mild Cognitive Impairment and Alzheimer's disease.

Deficits in the neuroendocrine-immune network in the periphery associated with the onset and progression of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have not been extensively studied. The present study correlatively examines the association between cell-mediated immune responses, stress hormones, amyloid precursor protein (APP) expression, peripheral blood mononuclear cells (PBMC), and intracellular signaling molecules in the pathophysiology of MCI and AD compared to adults. Serum APP, lymphocyte proliferation, total cholinesterase (TChE), butyrylcholinesterase (BChE) activities, cytokines (IL-2, IFN-γ, IL-6, and TNF-α), and intracellular signaling molecules (p-ERK, p-CREB, and p-Akt) were measured in the PBMCs of adult, old, MCI, and AD men and women initially and after 3years in the same population. An age- and disease-associated decline in mini-mental state examination (MMSE) scores and lymphocyte proliferation of MCI and AD men and women were observed. An age- and disease-related increase in serum APP, cortisol levels, and TChE activity were observed in men and women. Enhanced production of Th1 cytokine, IL-2, pro-inflammatory cytokines, and suppressed intracellular transcription factors may promote the inflammatory environment in MCI and AD patients. The expression of CREB and Akt was lower in MCI and AD men, while the expression of p-ERK was higher, and p-CREB was lower in MCI and AD women after 3years. These results suggest that changes in specific intracellular signaling pathways may influence alterations in cell-mediated immunity to promote disease progression in MCI and AD patients.

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Ruptured sinus of valsalva aneurysm - a rare cause of heart failure, challenges in transcatheter closure and mid-term outcomes

Abstract Introduction The ruptured sinus of valsalva aneurysm (RSOV) portends an important cause for acute heart failure. Closure of the defect either percutaneously or surgically is of paramount importance. We report 38 cases of RSOV who presented with cardiac failure, among which 22 cases were selected and amenable for transcatheter closure.Transcatheter closure of RSOV has favorable outcomes in the short-term and mid-term follow-up. Purpose of the study To assess the short-term and midterm outcomes of transcatheter closure of RSOV. Methods All patients who presented with cardiac failure and diagnosed as RSOV by transthoracic echo, from June 2012 to Dec 2022 were included in the study.Age group was between 12 to 73 years.All the 38subjects (Males -24, Females -14) of RSOV, underwent trans esophageal echo (TEE). 22 casesere selected for device closure..The subjects were classified according to New York Heart Association (NYHA) class III - 82%, class IV- 18 %. Size of the defect was measured at the aortic end by TEE and aortogram, and upsized by 2-4 mm from the aortic end. In 21 subjects, the RSOV was entered from the aorta, and an arterio-venous loop was created, and various devices, duct occluders and atrial septal occluder and muscular ventricular septal occluder were used to close the defects. In one patient the RSOV was acquired following surgical closure of perimembranous ventricular septal defect, which was small measuring 3mm at aortic end and hence closed using 4/6 ADO II without forming the arterio-venous loop. Patients were followed up post discharge 1 week, 1 month, 3 months, 6 months, 1 year and every year till 10 years by clinical examination, ECG, and transthoracic echo. Results All 22 patients who underwent successful RSOV device closure improved to NYHA functional class II within 48 hours post procedure and to functional class I at 3 months of follow-up. 3 female patients underwent successful pregnancy and labor after RSOV device closure without any intrapartum or postpartum complications. Two patients had trivial aortic regurgitation pre-procedure remained the same status on follow up post-procedure. One patient developed) severe right coronary artery spasm, due to inadvertent RCA cannulation while crossing the defect, which cleared with nasal oxygen and intracoronary nitroglycerine. A minimal residual shunt was found in 2 patients which gradually disappeared at 6 months. One patient with a large defect (15mm), an atrial septal occluder - 20mm was deployed, developed hemolysis, and hence referred for surgery. Transient global LV systolic dysfunction was present in two patients due to afterload mismatch, whose LV function recovered after 72 hours. Conclusion Percutaneous device closure of RSOV is a feasible and an enticing alternative to surgery in selected patients, as inferred by the short and mid-term outcomes. The age group 12 to 73 years encompasses the youngest and oldest age group yet reported.PROFILE OF RSOV DEVICE CLOSURE CASESRSOV CASE SELECTION AND OUTCOMES

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Etiology and predictors of heart failure in pregnancy. Newer Insights from the M-PAC registry

Abstract Background Women with heart disease undergoing pregnancy is on the increase, along with an increasing cardiac contribution to maternal mortality. Aim To identify the proposition of pregnant women with heart disease, who develop heart failure as a complication and to identify the predictors of heart failure in pregnancy Methods The Madras medical college Pregnancy And Cardiac (M-PAC) registry (1) is a single-centre prospective observational registry conducted at a tertiary care public hospital in Tamil Nadu, India from July 2016 to December 2019. Patient with new or worsening heart failure during pregnancy and up to 1 week post-delivery were included in the present analysis. When heart failure was the presenting symptom, it was considered as the primary event and when patient presented with failure symptoms secondary to another inciting event, heart failure was considered as secondary event. This cohort of patient were evaluated for the aetiology, predictors and outcome of heart failure and were placed on extended follow up. The accuracy of mWHO and CARPREG I score to predict heart failure were assessed. Results 1005 women with 1029 pregnancies were enrolled. Heart failure was observed in 127 (%) pregnancies, in 103 as primary event and in 24 as a secondary event. The common aetiologies of heart failure include rheumatic valvar heart diseases (n=45), peripartum cardiomyopathy (n=45) and congenital heart diseases (n=18). The univariable predictors of heart failure include, NYHA class at first visit, mWHO class of disease, first diagnosis of heart disease, during current pregnancy, pulmonary hypertension, left ventricular ejection fraction ≤ 45%, significant mitral stenosis, mechanical prosthetic heart valve and history of prior cardiac events. However, when peripartum cardiomyopathy was excluded from the analysis, current pregnancy diagnosis was no longer a predictor. Multivariable predictors of heart failure are shown in Figure-1. CARPREG-1 score was marginally more effective than modified World Health Organisation (mWHO) score (C-statistic of 0.820 vs 0.802) in predicting heart failure (Figure-2). Maternal death was 15.7% (20/127). Caesarean delivery was more common in patients with heart failure (53/119; 44.5%; vs 318/838; 38%) Patients with heart failure had significantly higher proportion of composite adverse fetal outcome (46.5% vs 31.9%, P<0.001), preterm birth (9.2% vs 4.5%, P=0.029) and low birth weight (41.2% vs 26%, P <0.001) Conclusion Heart failure is the commonest complication of pregnant women with heart disease. Mortality is very high in patients presenting with heart failure. Modified WHO classification and CARPREG 1 score have moderate accuracy to predict heart failure in pregnancy.Fig-1: Predictors of Heart FailueFig-2: Prediction by CARPREG-1 and mWHO

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Gender differences in lifestyle and psycho-social aspects of medical students. A cross sectional study

Abstract Background Incidence of premature cardiovascular deaths in medical practitioners is on the increase. Lifestyle habits, psychosocial and emotional status of medical students has the potential to initiate the premature onset of cardiovascular disease. Gender differences in diagnosis and management of cardiovascular diseases is well known. However, data on gender differences in heart healthy status of medical students are sparce. Purpose To investigate the gender differences heart healthy lifestyle habits among undergraduate medical students of a medical college from low-and-middle income country in south Asia. Methods All students pursing MBBS between 2017 and 2018 were included in the cross-sectional study. The study had Institutional ethics committee approval and the participation was voluntary. Anthropometric measurements (weight using digital weighting scale, height, waist and hip circumference using measuring tape), vital signs (pulse and blood pressure using digital manometer) and self-reported lifestyle/psychosocial cum behavioural pattern (using a specially designed proforma) were collected for all the participants. (525) Results 824 medical students were enrolled in the study of whom 377 (45.8%) were women. Overall 37.1% had abnormal body mass index (BMI) and 27.8% had abnormal waist hip ratio (WHR). Overall 14% and 10.3% students had abnormal systolic (≤ 85 mm of Hg) or diastolic blood pressure(BP) (≤ 135 mm of Hg) readings respectively. 19.4% of students had either systolic or diastolic abnormal BP values. Gender differences: Abnormal BMI and abnormal WHR (Figure 1A) were found in similar proportion among women and men. However less women has abnormal BP readings compared to men. More men has abnormal diastolic BP and abnormal systolic BP compared to women. Either systolic or diastolic BP values were abnormal in lower proportion of women (7.8% vs 29.4%; P<0.001). Women had less physically active minutes per day compared to men (71.15 ± 68.2 vs 109. 38± 81.7; P < 0.001). A feeling of lack of self-worth (73.5%) was common among medical students, however no significant gender differences were observed (Figure 1B). Significantly more women students have harbored suicidal thoughts than men. Women students were more likely to feel life style counseling is necessary for medical students and were more likely to implement lifestyle changes if advised. Conclusion High blood pressure and feeling of lack of self-worth is commonly observed in medical students. Women were more likely to harbor suicidal thoughts, bitterness and anger more likely to implement lifestyle modifications if advised. Interventions warranted at improving heart healthy lifestyle patterns is warranted, and must be optimized by observed gender differences.Figure 1Gender and life style habits

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