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Abstract Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC.

Formulating a research question and selecting an appropriate study design for answering that question are crucial initial steps in the research process. The population, intervention, control group, and outcomes measures (PICO time and setting [TS]) framework provides a practical guide in this regard, which stands for population, intervention, control, outcome, type of research question, and study design. The various study designs have their own merits and demerits, and implementing the methodology meticulously requires knowledge of all of these. Similarly, different methods of sample size calculation are warranted based on the most appropriate study design and outcome variables of interest. Sometimes, a post hoc power analysis can be performed after the sample size calculation, to check whether the study was adequately powered or not. There are multiple validated free software tools for sample size calculation, including Open-Epi, R, StatCalc, etc. The practice by most researchers of reporting significant P values is to be replaced by reporting effect sizes, as the latter is a much better estimate of the strength of association. This review provides a comprehensive, ready reckoner for busy family physicians to quickly identify the appropriate study design for answering any applied research questions in their minds and estimating the sample size required for the same.

Introduction: Inflammatory Myofibroblastic Tumour (IMT) is an unusual neoplasm with intermediate malignant potential, which rarely metastasises. IMT occurs in various anatomical sites, and the initial descriptions were primarily centered on its manifestation in the lungs. Although the age range is broad, IMT is most common in the first three decades of life, with a slight female predominance. Recent data and Anaplastic Lymphoma Kinase (ALK) gene aberrations confirm a neoplastic process for these lesions. Aim: To study the clinicopathological features of IMTs in a regional cancer centre in South India. Materials and Methods: A cross-sectional study included 17 cases of IMT over six years, from May 2014 to May 2020, at Memorial Kidwai Memorial Institute of Oncology (KMIO), Bengaluru, Karnataka, India. The clinicopathologic and immunophenotypic features were analysed on needle biopsies and resected specimens. Correlation between the expression of ALK-1 and histological patterns, mimickers, metastasis, and prognosis were described. Results were analysed using Microsoft Excel 2019 and Medcalc calculator. Results: Seventeen cases of IMTs were included in this study, out of which two were in the lung, and the rest were extrapulmonary. Sixteen cases were unifocal on presentation; however, one IMT of extremity showed evidence of secondaries on bone scan. The mean age at presentation was 33.47 years, and the male-to-female ratio was 1:1.12. Among the seventeen cases, sites are as follows: one each in the retroperitoneum, liver, soft-tissue (extremity), two each in the breast, lung, female genital tract, urinary bladder, and three each in the head and neck region (maxilla, trachea, and alveolus) and mesentery. Microscopically, IMTs showed various histological patterns. Immunostaining for ALK-1 was positive in seven out of seventeen cases, and the rest were diagnosed by excluding closer mimickers. Conclusion: The present study provides crucial insights into the clinicopathological features of IMTs. Immunohistochemistry (IHC) is an essential diagnostic tool that helps accurately differentiate IMT from its mimickers by identifying ALK protein expression. This distinction is essential for guiding targeted therapy in recurrent or metastatic cases.

Introduction: Extragonadal germ cell tumors (EGGCTs) are tumors arising at extragonadal ana-tomical locations. The biological behavior and prognosis of these tumors differ from their gonadal counterparts. Our study aims to analyze their histological subtypes, the outcome, and the prognosis of these lesions at various age groups. Material and Methods: We carried out a retrospective analysis of all patients with EGGCTs diag-nosed from January 2017 to December 2019. Results: Our study included 61 cases of EGGCTs. These cases were divided into neonatal (birth to six months), prepubertal (more than six months to 12 years), and post-pubertal group (>12 years). The most frequently affected group was prepubertal (44.2%). The age ranged from birth to 45 years with a male-to-female ratio of 1:1.03. The frequently involved site was sacrococcyx (36%) followed by mediastinum (31.1%). The common histologic subtype was mature teratoma (39.3%), followed by yolk sac tumor (YST) (18%), mixed germ cell tumor (18%), immature teratoma (14.7%), and germinoma (9.8%). Four cases of teratoma had somatic malignancies. There were 48 stage I, 8 stage II, and 2 stage III tumors. Statistical analysis revealed a significant association of age group concerning primary site (p=0.004), histological type (p=0.002), and clinical stage (p=0.034). In a median follow-up of 30 months, an Overall Survival (OS) of 93.2% and Event Free Survival (EFS) of 90.4% were noted across all age groups. OS of 100% (neon tal), 96% (prepubertal) and 88.0% (post-pubertal) revealing a declining trend (p=0.324) with increasing age was noted. The important prognostic factors include histological subtype (mixed germ cell tumors and teratomas with somatic malignancies had reduced overall survival) and stage (I vs II and III) for OS and stage alone for EFS (P

Objective: The main objective of this study was to analyze the serum levels of Nuclear factor-kappa B (NFкB) in breast cancer as compared to age-matched healthy individuals. It also aimed to investigate variations in NFкB levels across stages, types of breast cancer and also its correlation with Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR). Methodology: Blood samples of 40 female breast cancer patients and 33 healthy controls were collected in anticoagulant and plain tubes. Hematological parameters were evaluated with an automatic analyzer, and NFкB levels were measured using ELISA. Statistical analysis was performed with GraphPad Prism 8 software. Results: Significant elevation of serum NFкB levels (p

Abstract Background Breast cancer (BC) is the most common malignancy with very high incidence and relatively high mortality in women. The PIK3CA gene plays a pivotal role in the pathogenicity of breast cancer. Despite this, the mutational status of all exons except exons 9 and 20 still remains unknown. Methods This study uses the whole exome sequencing (WES) based approach to identify somatic PIK3CA mutations in Indian BC cohorts. The resultant hotspot mutations were validated by droplet digital PCR (ddPCR). Further, molecular dynamics (MD) simulation was applied to elucidate the conformational and functional effects of hotspot position on PIK3CA protein. Results In our cohort, PIK3CA showed a 44.4% somatic mutation rate and was among the top mutated genes. The mutations of PIK3CA were confined in Exons 5, 9, 11, 18, and 20, whereas the maximum number of mutations lies within exons 9 and 20. A total of 9 variants were found in our study, of which 2 were novel mutations observed on exons 9 (p.H554L) and 11 (p.S629P). However, H1047R was the hotspot mutation at exon 20 (20%). In tumor tissues, there was a considerable difference between copy number of wild-type and H1047R mutant was detected by ddPCR. Significant structural and conformational changes were observed during MD simulation, induced due to point mutation at H1047R/L position. Conclusions The current study provides a comprehensive view of novel as well as reported single nucleotide variants (SNVs) in PIK3CA gene associated with Indian breast cancer cases. The mutation status of H1047R/L could serve as a prognostic value in terms of selecting targeted therapy in BC.

Introduction The sirtuin (Silent mating type information regulation 2 homolog)1(SIRT1) protein plays a vital role in many disorders such as diabetes, cancer, obesity, inflammation, and neurodegenerative and cardiovascular diseases. The objective of this in silico analysis of SIRT1's functional single nucleotide polymorphisms (SNPs) was to gain valuable insight into the harmful effects of non-synonymous SNPs (nsSNPs) on the protein. The objective of the study was to use bioinformatics methods to investigate the genetic variations and modifications that may have an impact on the SIRT1 gene's expression and function. Methods nsSNPs of SIRT1 protein were collected from the dbSNP site, from its three (3) different protein accession IDs. These were then fed to various bioinformatic tools such as SIFT, Provean, and I- Mutant to find the most deleterious ones. Functional and structural effects were examined using the HOPE server and I-Tasser. Gene interactions were predicted by STRING software. The SIFT, Provean, and I-Mutant tools detected the most deleterious three nsSNPs (rs769519031, rs778184510, and rs199983221). Results Out of 252 nsSNPs, SIFT analysis showed that 94 were deleterious, Provean listed 67 dangerous, and I-Mutant found 58 nsSNPs resulting in lowered stability of proteins. HOPE modelling of rs199983221 and rs769519031 suggested reduced hydrophobicity due to Ile 4Thr and Ile223Ser resulting in decreased hydrophobic interactions. In contrast, on modelling rs778184510, the mutant protein had a higher hydrophobicity than the wild type. Conclusions Our study reports that three nsSNPs (D357A, I223S, I4T) are the most damaging mutations of the SIRT1 gene. Mutations may result in altered protein structure and functions. Such altered protein may be the basis for various disorders. Our findings may be a crucial guide in establishing the pathogenesis of various disorders.

This research emphasizes a meta-heuristic modified ant lion optimizer (MALO) optimization approach for the simultaneous utilization of DSTATCOM devices and distributed photovoltaic (PV) sources with network reconfiguration in a radial power distribution scheme. In a radial power distribution network with network reconfiguration, the majority of the research is based on constant power model analysis. However, it is noticed that load models have a substantial impact on the distributed PV sources and the DSTATCOM device’s optimal size and position. The effect of the constant power (CP) and polynomial (ZIP) with load growth load models for the simultaneous insertion of distributed PV sources and DSTATCOM devices with network reconfiguration is examined in this research work for power system planning. The penetration levels of distributed PV sources considered for the investigation are 25%, 50%, 75%, and 100%. The principal objective of this research is to reduce network total power losses, enhance the voltage magnitude profile at all buses, and reduce the overall operating cost while adhering to equality and inequality constraints. The proposed algorithm is verified on 118-node test systems. The investigation is carried out for planning network upgrading to a high-voltage distribution system (HVDS) on 317 nodes in the rural Bangalore Electricity Supply Company Limited (BESCOM) radial distribution scheme. The simulated results obtained with this method are validated with the BAT algorithm and techniques available in the literature. It is observed that in the IEEE 118-bus system, via the simultaneous placement and sizing of PV sources considering a 25% penetration level and DSTATCOM devices during network reconfiguration, the total power loss reduction is 41.47% and 42.98% for the constant power model and ZIP with the load growth model. For the 317-bus system, the total power loss reduction observed for 11 kV is 49.77% and 59.34% for the constant power model and ZIP model with load growth. Similarly, for the 22 kV system, the power loss reduction observed is 51.69% and 55.75% for the constant power model and ZIP with the load growth model.

Abstract Background Melghat in India is a hilly, forested, difficult to access, impoverished rural area in northeast part of Maharashtra (Central India) with difficult healthcare access. Melghat has very high Mortality rates, because of grossly inadequate medical facilities. (1) Home deaths contribute to 67% of deaths,(2) which are difficult to track and where cause of death is mostly unknown. Methods A feasibility study was carried out in 93 rural villages and 5 hospitals to assess feasibility of tracking real-time community mortality and to ascertain cause of death in 0–60 months and 16–60 years age group using Minimal Invasive Tissue Sampling (MITS) in purpose-modified ambulance. We used the network of village health workers (VHW)s, to establish real-time community mortality tracking. Upon receipt of reports of home death, we performed MITS within 4 h of death in the vicinity of the village. Results We conducted 16 MITS. Nine, in MITS ambulance in community and seven at MAHAN hospital. The acceptance rate of MITS was 59.26%. Standard operating procedure (SOP) of conducting community MITS in an ambulance, is established. Major challenges were, Covid19 lockdown, reluctance of tribal parents for consent for MITS due to illiteracy, superstitions and fear of organ removal. Ambulance was an easy to reach transport means in remote area, provided a well-designed and discrete facility to perform MITS in community, winning the confidence of bereaved family. This has reduced time interval between time of death and performing MITS. Conclusions MITS in purpose-modified Ambulance can be used worldwide for community MITS especially in areas which are remote and lack healthcare access. This solution needs to be assessed in different cultural settings to document culture specific issues.

Objective: To compare sensitivity, specificity, positive predictive value and negative predictive values of three different techniques such as, urine culture, urinary heparin binding protein assay by ELISA and identification of pathogens by multiplex PCR in gestational diabetes mellitus (GDM). Study design: An observational study was conducted in 50 GDM patients. Urine samples were collected and cultured. Antibiotic sensitivity testing was performed by the modified disc diffusion method. Urine heparin binding protein (UHBP) was estimated in the sample by ELISA. DNA was extracted from urine samples and pathogens were identified by multiplex PCR. Results: Prevalence of asymptomatic bacteriuria (ASB) among GDM patients on basis of urine culture was found to be 6%. A significant association was noted between detection of organisms and multiplex PCR findings compared to urine culture (p

Background: One of the metabolic processes of sodium valproate (SV) metabolism is cytochrome P450 (CYP)-mediated oxidation. Polymorphism of the genes coding CYP enzymes can cause the changes in steady state SV concentration and clinical outcome. The study's objective was to explore the CYP gene polymorphism patterns in pediatric epileptic patients and its influence on SV concentration and clinical outcome. Methods: Ninety-nine pediatric epileptics aged 2–18 years who were receiving SV monotherapy were included in this cohort study. Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) method was adopted to examine the genetic polymorphism patterns of CYP2C9*2 and CYP3A4*1B. HPLC was used to estimate the serum valproate concentration at the trough level. SPSS 23 was used to examine the relationship between SV concentration and CYP genotypes. Analysis of variance test was utilized, and a P < 0.05 was regarded statistically significant. Results: PCR-RFLP showed homozygous pattern (GG wild type) was observed in 37.3%, whereas heterozygous in 46.6% (mutant GA) and homozygous recessive (AA) in 16.1% patients in CYP3A4*1B (G331A). Homozygous (CC-Wild) and heterozygous (CT) pattern of polymorphism was observed in 90% and 10% patients in CYP2C9*2 (C430T). The mean serum valproate concentration assayed was 105.40 ± 49.9 μg/ml. The associations between the gene polymorphism of CYP3A4*1B (G331A) and CYP2C9*2 (C375T) with SV concentration were insignificant, The SNPs were not in equilibrium. The study findings indicated that patients of homozygous (wild type) CYP2C9*2 had bad clinical outcome compared to other patterns, although statistically insignificant. Conclusions: The association of serum concentration of SV with the different alleles of CYP3A4*1B and CYP2C9*2 was insignificant. SV should be cautiously used in patients with homozygous pattern of CYP2C9*2 due to concern of recurrent seizure episodes. The study may be of great use in personalized therapy in pediatric epilepsy.

Objective: The successful management of cancer depends on proper screening and treatment methods. Bioimpedance spectroscopy (BIS) is an established technique in detecting breast cancer, cervical cancer, and prostate cancer. This systematic review sought to investigate the current evidence regarding the clinical application of bioimpedance in the detection of oral squamous cell carcinoma and oral potentially malignant disorders. Study Design: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to perform this review. Electronic databases such as PubMed, MEDLINE, Embase, EBSCOhost, and Google Scholar were searched till March 2022. Articles published in the English medical literature on human participants report on the application of BIS in the screening of precancerous and cancerous lesions. The primary endpoint was defined as the ability to differentiate between normal and cancerous tissue. Results: A total of 6754 articles were identified; of which 481 were eligible for inclusion. Only five articles met the eligibility criteria and were included in the study. Qualitative analysis for each study was done to assess the data provided. All the studies demonstrated a significant divergence in BIS metrics between cancerous and normal tissue at 20 Hz and 50 KHz. Conclusion: Bioimpedance appears to be a promising novel tool for the detection of various malignancies which can be used in community screening due to its noninvasiveness and portability.

A 50-year-old male presented with abdominal pain, pain during defaecation, constipation, bleeding per rectum for 2 months. Colonoscopy showed an ulcero-proliferative growth, that is 2.5 cm from anal verge. Further PET-CT confirmed the growth in the lower rectum with mesorectal fat stranding and an irregular, lobulated, encapsulated solid-cystic mass in right perinephric fat, separated from the kidney (suggestive of metastasis), with intact bilateral kidneys. Biopsy of the rectum revealed an adenocarcinoma and biopsy of right perinephric mass revealed a papillary neoplasm. Following which abdominoperineal resection with perinephric mass excision was performed, due to encapsulation of mass. Histopathological evaluation and further immunohistochemistry performed was positive for vimentin, AMACR, CD10 and negative for other markers to rule out metastasis of either. This led to the diagnosis of synchronous primaries i.e., Extra-renal papillary renal cell carcinoma and adenocarcinoma of rectum.

Background: The World Health Organization declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Identifying the infected people and isolating them was the only measure that was available to control the viral spread, as there were no standardized treatment interventions available. Various public health measures, including vaccination, have been implemented to control the spread of the virus worldwide. India, being a densely populated country, required laboratories in different zones of the country with the capacity to test a large number of samples and report test results at the earliest. The Indian Council of Medical Research (ICMR) took the lead role in developing policies, generating advisories, formulating guidelines, and establishing and approving testing centers for COVID-19 testing. With advisories of ICMR, the National Institute of Cancer Prevention and Research (NICPR) established a high-throughput viral diagnostic laboratory (HTVDL) for RT-PCR-based diagnosis of SARS-CoV-2 in April 2020. HTVDL was established during the first lockdown to serve the nation in developing and adopting rapid testing procedures and to expand the testing capacity using “Real-Time PCR.” The HTVDL provided its testing support to the national capital territory of Delhi and western Uttar Pradesh, with a testing capacity of 6000 tests per day. The experience of establishing a high-throughput laboratory with all standard operating procedures against varied challenges in a developing country such as India is explained in the current manuscript which will be useful globally to enhance the knowledge on establishing an HTVDL in pandemic or non-pandemic times.

Objectives of this review is to evaluate the role of cytochrome P450 gene polymorphisms in COVID-19 infected patients with pre-existing OA on corticosteroids. The purpose of this review is to analyze whether polymorphisms of Cytochrome p450 isoforms (CYP2C9 and CYP3A4) affect the dosage of steroids in OA patients in COVID-19 infected patients. This review may provide more therapeutic options; suggest a few guidelines which may be useful in managing COVID-19 patients with pre-existing osteoarthritis. The important role of corticosteroids in treating patients infected with COVID-19 with preexisting osteoarthritis, its influence on incidence of mortality or morbidity may be highlighted. The influence of CYP enzymes and their polymorphisms suggest safety of treatments as well as the possible need for the dosage adjustment or their discontinuation.

Cell division, wherein 1 cell divides into 2 daughter cells, is fundamental to all living organisms. Cytokinesis, the final step in cell division, begins with the formation of an actomyosin contractile ring, positioned midway between the segregated chromosomes. Constriction of the ring with concomitant membrane deposition in a specified spatiotemporal manner generates a cleavage furrow that physically separates the cytoplasm. Unique lipids with specific biophysical properties have been shown to localize to intercellular bridges (also called midbody) connecting the 2 dividing cells; however, their biological roles and delivery mechanisms remain largely unknown. In this study, we show that ceramide phosphoethanolamine (CPE), the structural analog of sphingomyelin, has unique acyl chain anchors in Drosophila spermatocytes and is essential for meiotic cytokinesis. The head group of CPE is also important for spermatogenesis. We find that aberrant central spindle and contractile ring behavior but not mislocalization of phosphatidylinositol phosphates (PIPs) at the plasma membrane is responsible for the male meiotic cytokinesis defect in CPE-deficient animals. Further, we demonstrate the enrichment of CPE in multivesicular bodies marked by Rab7, which in turn localize to cleavage furrow. Volume electron microscopy analysis using correlative light and focused ion beam scanning electron microscopy shows that CPE-enriched Rab7 positive endosomes are juxtaposed on contractile ring material. Correlative light and transmission electron microscopy reveal Rab7 positive endosomes as a multivesicular body-like organelle that releases its intraluminal vesicles in the vicinity of ingressing furrows. Genetic ablation of Rab7 or Rab35 or expression of dominant negative Rab11 results in significant meiotic cytokinesis defects. Further, we show that Rab11 function is required for localization of CPE positive endosomes to the cleavage furrow. Our results imply that endosomal delivery of CPE to ingressing membranes is crucial for meiotic cytokinesis.

Introduction: Leptin is an adipokine hormone that regulates insulin sensitivity and lipid profile, which may contribute to complications like gestational diabetes.The goal of the study was to examine if there was a link between the leptin (LEP)/leptin receptor (LEPR) gene polymorphism and insulin resistance in pregnant women, and to determine the extent to which the leptin gene polymorphism could cause insulin resistance.. Methods: 208 pregnant women participated in this cross-sectional study of which 74 were insulin resistant cases and 134 were insulin sensitive controls. The study was carried out from December 2018 to December 2020 at a charitable hospital in Mangalore, Karnataka, India. Genotyping of leptin and its receptor gene were carried out using the Polymerase Chain Reaction- Restriction fragment Length Polymorphism (PCR-RFLP) method. Serum levels of leptin, insulin, and C peptide were assayed using Enzyme Linked Immuno Sorbent Assay (ELISA) and lipid profile by automated chemistry analyzer. Statistical analysis was carried out using SPSS 23. Results: Insignificant association was observed between leptin receptor gene polymorphisms and insulin resistance, and leptin gene and insulin resistant women. There was no significant difference in the serum leptin levels among the cases and control (61.62±29.23 and 59.88±22.25). However, fasting blood sugar, insulin, C peptide, Triglycerides (TG), and very low-density Lipoprotein (VLDL) levels were significantly higher in cases as compared to controls (p=0.0068, p

Background: Uridine 5′-diphospho glucuronosyl transferase (UGT) is the main enzyme responsible for the glucuronide conjugation, the principal metabolic pathway of sodium valproate. The objective of the study was to explore if there was an association between the UGT2B7 genetic polymorphism and clinical efficacy and safety in paediatric epileptic patients on sodium valproate monotherapy.Methods and materials: The cohort study included 100 pediatric epileptic patients aged 2–18 years who had been on sodium valproate monotherapy for at least 1 month. PCR-RFLP was carried out to assess the genetic polymorphism patterns of UGT2B7 (C161T, A268G, G211T). Based on the extent of seizure control throughout the 1-year follow-up, clinical outcome was assessed in terms of responders and non-responders. Hepatic, renal, and other lab parameters were assayed to determine safety. The SNPstat web software was used to calculate linkage disequilibrium.Results: Out of 100 patients, CC (38%), CT (43%), TT (19%) pattern was observed in UGT2B7 (C161T) gene, AA (15%), AG (39%), GG (46%) in (A268G) gene and GG (80%), GT (18%), TT (02%) in (G211T) gene. There was no statistical difference in clinical outcome with distinct UGT2B7 genetic polymorphism patterns, according to the findings. With low D′ and R2 values, linkage disequilibrium between alleles was statistically insignificant. However, the associations of C161T and G211T with treatment response were significant (p = 0.014) in determining treatment response.Conclusion: Our findings show that the genetic variation of UGT2B7 had no bearing on the clinical outcome of epilepsy. Gene interactions, on the other hand, had an impact on treatment response.

It is known that the rhythms of speech are visible on the face, accurately mirroring changes in the vocal tract. These low-frequency visual temporal movements are tightly correlated with speech output, and both visual speech (e.g., mouth motion) and the acoustic speech amplitude envelope entrain neural oscillations. Low-frequency visual temporal information ('visual prosody') is known from behavioural studies to be perceived by infants, but oscillatory studies are currently lacking. Here we measure cortical tracking of low-frequency visual temporal information by 5- and 8-month-old infants using a rhythmic speech paradigm (repetition of the syllable 'ta' at 2 Hz). Eye-tracking data were collected simultaneously with EEG, enabling computation of cortical tracking and phase angle during visual-only speech presentation. Significantly higher power at the stimulus frequency indicated that cortical tracking occurred across both ages. Further, individual differences in preferred phase to visual speech related to subsequent measures of language acquisition. The difference in phase between visual-only speech and the same speech presented as auditory-visual at 6- and 9-months was also examined. These neural data suggest that individual differences in early language acquisition may be related to the phase of entrainment to visual rhythmic input in infancy.

Background: The role of genetics in pathophysiology of gestational diabetes mellitus (GDM) is least explored. Objective of the study is to find the association of leptin receptor (LEPR) gene polymorphism with GDM and its role in altered leptin levels, insulin resistance, and dyslipidemia in GDM. Methods: Hundred GDM patients and an equal number of BMI and gestational age matched normal glucose tolerant pregnant women were recruited as cases and controls. Five milliliters of venous blood was drawn for biochemical and genetic analysis. Genotyping of LEPR (Gln223Arg) was performed by PCR-RFLP. Fasting blood sugar, leptin, insulin, C-peptide, and lipid profile estimations were done. Various insulin resistance models were constructed using suitable formulae. The statistical analysis was performed using SPSS 23.0 software. Results: There was no significant association found between LEPR gene polymorphism with leptin levels and insulin resistance in GDM. However, Odd’s ratio showed that individuals with the “A” allele were at 1.25 times higher risk of developing GDM. HOMA B-cell significantly varied among LEPR genotypes (p

PURPOSE: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Introduction: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histologic variant of adenocarcinomas comprising about 2%–10% of lung adenocarcinomas. A large proportion of IMAs carry KRAS mutations and only rarely epidermal growth factor receptor (EGFR) mutations or ALK/ROS translocations; thus, most cases are not amenable for targeted therapy at present. This study was conducted to elicit the unique clinicopathological characteristics of IMA. Materials and Methods: Medical records of patients diagnosed with IMA by needle biopsy at Kidwai Cancer Institute, Bangalore, from 2013 to 2018, were retrieved and reviewed. Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). Results: Four hundred and ninety cases of needle biopsy of the lung were diagonosed at our institute between January 2013 and December 2018. Nine cases (1.8%) were diagnosed as IMA. The median age of presentation was 59 years. Six (66.7%) were current smokers with pack-year > 20. Three (33.3%) of the cases were initially misdiagnosed as pneumonia in view of computed tomography findings. The lung was the most common site of metastasis (77.8%). Serum Carcinoembryonic Antigen (CEA) was elevated in six cases (66.7%). None of the cases had any driver mutations in EGFR gene or ALK and ROS1 translocations. All cases were treated with pemetrexed–carboplatin doublet followed by pemetrexed maintenance till progression. The median progression-free survival (PFS) was 15 months (range: 5–18 months). Docetaxel was given as the second-line chemotherapy in all progressed patients. Best response noted was stable disease, seen in 4 (57.1%) cases. The median PFS for docetaxel was 6 months (range: 3–8 months). The median overall survival was 22 months (range: 9–27 months). Patients with initially raised CEA at progression had a serial rise in serum CEA. Conclusions: IMA is rarely diagnosed on needle biopsies due to insufficient tissue. They mimic pneumonia on imaging, thus delaying diagnosis. EGFR mutations, ALK, and ROS1 translocations are usually negative making them ineligible for tyrosine kinase inhibitors. Response to chemotherapy is modest.

Abstract: Serine palmitoyltransferase (SPT) long-chain base subunit 1 (SPTLC1) is 1 of the 2 main catalytic subunits of the SPT complex, which catalyzes the first and rate-limiting step of sphingolipid biosynthesis. Here, we show that Sptlc1 deletion in adult bone marrow (BM) cells results in defective myeloid differentiation. In chimeric mice from noncompetitive BM transplant assays, there was an expansion of the Lin− c-Kit+ Sca-1+ compartment due to increased multipotent progenitor production, but myeloid differentiation was severely compromised. We also show that defective biogenesis of sphingolipids in the endoplasmic reticulum (ER) leads to ER stress that affects myeloid differentiation. Furthermore, we demonstrate that transient accumulation of fatty acid, a substrate for sphingolipid biosynthesis, could be partially responsible for the ER stress. Independently, we find that ER stress in general, such as that induced by the chemical thapsigargin or the fatty acid palmitic acid, compromises myeloid differentiation in culture. These results identify perturbed sphingolipid metabolism as a source of ER stress, which may produce diverse pathological effects related to differential cell-type sensitivity.

Abstract Rice is a major cereal food crop and staple food in most of the developing countries. India stands second in the production of rice next to China. Though almost 40,000 varieties of rice are said to exist, at present, only a few varieties are cultivated extensively, milled and polished. Even if white rice is consumed by most people around the world, some specialty rice cultivars are also grown. These include the coloured and aromatic rice varieties. The nutritional profile of the specialty rice is high when compared to the white rice varieties. The coloured rice, which usually gets its colour due to the deposition of anthocyanin pigments in the bran layer of the grain, is rich in phytochemicals and antioxidants. Rice bran, a by-product of the rice milling industry is under-utilised, is rich in dietary fibre which finds application in the development of functional foods and various other value-added products. Thus, more focus on specialty rice and its by-products will not only save it from becoming extinct but also lead a step forward towards nutrition security of the country as they are abundant in vitamins, minerals and polyphenols.

Abstract The Green Revolution in India was initiated in the 1960s by introducing high-yielding varieties of rice and wheat to increase food production in order to alleviate hunger and poverty. Post-Green Revolution, the production of wheat and rice doubled due to initiatives of the government, but the production of other food crops such as indigenous rice varieties and millets declined. This led to the loss of distinct indigenous crops from cultivation and also caused extinction. This review deals with the impacts the Green Revolution had on the production of indigenous crops, its effects on society, environment, nutrition intake, and per capita availability of foods, and also the methods that can be implemented to revive the indigenous crops back into cultivation and carry the knowledge to the future generation forward.

The plasma membrane of eukaryotic cells is composed of a large number of lipid species that are laterally segregated into functional domains as well as asymmetrically distributed between the outer and inner leaflets. Additionally, the spatial distribution and organization of these lipids dramatically change in response to various cellular states, such as cell division, differentiation, and apoptosis. Division of one cell into two daughter cells is one of the most fundamental requirements for the sustenance of growth in all living organisms. The successful completion of cytokinesis, the final stage of cell division, is critically dependent on the spatial distribution and organization of specific lipids. In this review, we discuss the properties of various lipid species associated with cytokinesis and the mechanisms involved in their polarization, including forward trafficking, endocytic recycling, local synthesis, and cortical flow models. The differences in lipid species requirements and distribution in mitotic vs. male meiotic cells will be discussed. We will concentrate on sphingolipids and phosphatidylinositols because their transbilayer organization and movement may be linked via the cytoskeleton and thus critically regulate various steps of cytokinesis.

The term collision tumor is used to describe two neoplasms occurring in the same anatomic location with juxtaposition of different tumor elements. Such a coexistence of tumors anywhere in the body is relatively rare. We report a case of 32-year-old female with collision tumor of rectum. The tumor showed two distinct histological patterns with predominant component consisting of malignant melanoma and a minor component of squamous cell carcinoma. The morphological picture of collision was further confirmed by specific immunohistochemical profile of the two tumors. Collision tumors of rectum are uncommon with most of the reported cases comprising adenocarcinoma and neuroendocrine tumors. To the best of our knowledge this is the first case of collision tumor of malignant melanoma and squamous cell carcinoma in the rectum.

Aims of the study were to compare liver markers in T2DM patients with that in non-diabetic healthy volunteers and also to find the correlation between insulin resistance(IR) and liver markers. The objective of the study was also to find out whether PON1 can be an alternative liver marker. The cross-sectional study was conducted in the Clinical Biochemistry laboratory. 114 type 2 DM patients in the age group 18-65 years, diagnosed as per ADA guidelines were recruited in the study.100 age and gender-matched non-diabetics, healthy volunteers or those having health packages were taken as controls. The blood sample was collected and fasting blood glucose, transaminases and Alkaline phosphatase, bilirubin (total and direct), total protein, albumin, and insulin were assayed. HOMA-IR was calculated. Statistical analysis was done by using SPSS 16. A significant elevation was seen in AST, ALT, ALP, GGT, TB, DB, TP, A: G ratio in diabetics. A lowered albumin and A: G ratio were observed in diabetics as compared to controls. Fasting insulin levels were 1.7 times higher in diabetics compared controls, suggesting hyperinsulinemia in cases. Homeostatic model for assessment of insulin resistance (insulin based) was 2.7 times greater in T2DM compared to controls. A significant positive correlation was found between insulin levels and total and direct bilirubin, (r=0.279, P=0.003, and r=0.233, P=0.014 respectively). ALP, total and direct bilirubin had a significant positive correlation with HOMA-IR (r=0.228,P=0.033,; r=0.231,P=0.030 ; r=0.242. P=0.023 respectively).A very significant negative correlation was found between albumin and HOMA- IR (r= -0.306, P=0.004). A significant positive correlation was observed between PON1 and HOMA-IR (P=0.000), PON and insulin (P=0.015). It can be concluded from that diabetics had high liver enzymes as compared to non-diabetics. An association was found between T2DM, liver markers, and IR. It was observed that PON1 was not a good liver marker in T2DM.

Breast cancer is the most common cancer among Indian women with a significant increase in incidence in young women. To identify risk factors for breast cancer in young women, study of BRCA1 and BRCA2 germ line mutations was done in a cohort of 204 Indian breast cancer patients. The study showed a total of 18 mutations in 2.94% of the tested patients, 44% BRCA1 and 78% BRCA2 mutations were found unique to the Indian population. Association of low penetrance genes mainly CYP17, VDR gene and AR-CAG repeat polymorphisms with breast cancer risk showed CYP17 A2 and VDR Poly-A L as high risk alleles, the risk of developing breast cancer among women carrying three high-risk alleles is 4.68 (95% confidence interval [CI]: 0.77–28.0; p for trend = 0.10) compared with women carrying none. CYP17 A2 allele was also found associated with development of breast cancer at young age and can also serve as a target for therapy. Betel quid chewing has been found as a significant and independent risk factor for developing breast cancer in North East Indian women which induces genetic alterations leading to breast carcinogenesis. Studies to assess the predictive role of various tumor markers showed that expression of p-glycoprotein in pretreatment biopsy predicts a poor clinical response to neoadjuvant chemotherapy (NACT) in patients having locally advanced breast cancer. The chemotherapy-induced toxicity (vomiting and alopecia) correlated significantly with clinical and immunohistochemical response (reduction in bcl2/bax ratio) and were found to be a cost-effective and reliable predictor of response to NACT. Androgen receptor (AR) has been identified as independent predictive marker for response to NACT in locally advanced breast cancer cases and can serve as novel therapeutic target for triple negative breast cancers.

Background: Medical comorbidities have varied effects on the management of a patient for dentoalveolar surgeries. Prior diagnosis and prudence in such conditions is of utmost importance for avoidance of complications and overall welfare of the patient. There is a dilemma on the extent of investigations required to evidently ascertain the medical status and fitness of a patient for a dental procedure. The objective of this study was to evaluate the prevalence of medical comorbidities in patients reporting for dentoalveolar surgeries, which would help provide data to establish an evidence-based protocol for perioperative workup of all dental surgeries. Methodology: A total of 2872 patients were included in this study age ranging from 13 years to 84 years. Detailed case history of the patient and baseline blood investigations were recorded. Physician's consultation was acquired to identify any medical comorbidity the patient may be suffering from. Results: It was observed that 17.8% of the patients were detected with medical co-morbidities. Hypertension and Diabetes being the most prevalent (Hypertension: 9.1% and Diabetes: 6.2%). This study has shown that 8.8% of all patients in our study were either newly diagnosed with comorbidities or were inappropriately treated for a prediagnosed comorbidity. Conclusion: We conclude that only relying on the medical history provided by the patient is not sufficient to rule out any medical comorbidities and there is a chance of missing out on any undiagnosed medical condition that the patient may be suffering from.