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Background and study aims Patients with primary sclerosing cholangitis and inflammatory bowel disease (IBD) have a high risk of colorectal cancer. There is no agreement on the best technique for surveillance for colorectal neoplasia. We aimed to assess whether chromoendoscopy and/or high-definition endoscopy is associated with increased detection of neoplasia in patients with primary sclerosing cholangitis undergoing surveillance compared with when they were not used.

Introduction Air pollution presents a major public health threat to India, affecting more than three quarters of the country’s population. In the current project, GEOHealth Health Effects of Selected Environmental Exposomes Across the Life CourSe–India, we aim to study the effect of environmental exposomes—fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and extremes of temperature—on multiple health outcomes using a modified life course approach. The associated training grant aims to build capacity in India to address the unique environmental health problems.Methods and analysis The project aims to (A) Develop exposure assessments in seven cities, namely Delhi, Chennai, Sonipat, Vizag, Pune, Hyderabad and Bikaner, for: (1) A fine-scale spatiotemporal model for multiple pollutants (PM2.5, NO2, O3, temperature); (2) Combined ground monitoring and modelling for major chemical species of ambient PM2.5 at seven cities; and (3) Personal exposure assessment in a subsample from the six cities, except Pune, and (B) Conduct health association studies covering a range of chronic non-communicable diseases and their risk factors leveraging a unique approach using interdigitating cohorts. We have assembled existing pregnancy, child, adolescent, adult and older adult cohorts across India to explore health effects of exposomes using causal analyses. We propose to use Bayesian kernel machine regression to assess the effects of mixtures of all pollutants including species of PM2.5 on health while accounting for potential non-linearities and interactions between exposures. This builds on earlier work that constructed a fine spatiotemporal model for PM2.5 exposure to study health outcomes in two Indian cities.Ethics and dissemination Ethical clearance for conduct of the study was obtained from the Institutional Ethics Committee (IEC) of the Centre for Chronic Disease Control, and all the participating institutes and organisations. National-level permission was provided by the Indian Council of Medical Research. The research findings will be disseminated through peer-reviewed publications, policy briefs, print and social media, and communicating with the participating communities and stakeholders. Training of Indian scientists will build the capacity to undertake research on selected adverse environmental exposures on population health in India.

This article presents a mathematical framework that characterizes a transversely isotropic piezo-visco-thermo-elastic medium within the context of the dual-phase lags heat transfer law (PVID) applied to an elastic medium (ES). Specifically, the study investigates the propagation of plane waves within the elastic medium and their interaction with the imperfect interface of the ES/PVID media. This interaction results in two waves reflecting back into the elastic medium and four waves propagating through the piezo-visco-thermo-elastic medium. The research explores the distribution of energy between the reflected and transmitted waves by analyzing amplitude ratios at the boundary interfaces, considering factors such as phase delays, viscosity effects, and wave frequency. The study illustrates the influence of boundary stiffness and viscosity parameters on these energy ratios through graphical representations. The study's findings are consistent with the principles of the energy balance law, and the research also delves into specific cases of interest. Overall, this investigation provides insights into wave behavior within complex media and offers potential applications across various fields.

This study introduces a two-dimensional thermoelastic model for a homogeneous isotropic half-space with double porosity underlying an inviscid liquid half-space featuring temperature variations. The model incorporates the three-phase lag (TPL) heat equation and reveals that in the solid half-space, four coupled longitudinal waves intertwine with one uncoupled transverse wave, while one mechanical wave ripples through the liquid half-space. The investigation highlights dispersion, attenuation, and other effects affected by the thermal properties and the presence of voids. Using plane wave solutions and boundary conditions at the interface, a concise expression for the frequency equation of the model has been derived. Furthermore, the magnitudes of the displacements in the solid half-space and liquid half-spaces, the temperature change, and the volume fractional fields at the interface have been precisely determined. In the graphical section, computer-simulated results of various wave profiles for magnesium crystal material have been generated for different heat conduction thermoelastic models. The study's implications span various fields, such as hydrology, engineering, ultrasonics, navigation, and electronics.

Abstract This paper investigates the intricate energy distribution patterns emerging at an orthotropic piezothermoelastic half-space interface by considering the influence of a higher-order three-phase lags heat conduction law, accompanied by memory-dependent derivatives (referred to as HPS) within the underlying thermoelastic half-space (referred to as TS). This study explores the amplitude and energy ratios of reflected and transmitted waves. These waves span various incident types, including longitudinal, thermal, and transversal, as they propagate through the TS and interact at the interface. Upon encountering the interface, an intriguing dynamic unfolds: three waves experience reflection within the TS medium, while four waves undergo transmission into the HPS medium. A graphical representation effectively illustrates the impact of higher-order time differential parameters and memory to offer comprehensive insights. This visual representation reveals the nuanced fluctuations of energy ratios with the incidence angle. The model astutely captures diverse scenarios, showcasing its ability to interpret complex interface dynamics.

Background: Determining the DNA fragmentation index (DFI) by the sperm chromatin dispersion (SCD) test involves manual counting of stained sperms with halo and no halo. Aims: The aim of this study is to build a robust artificial intelligence-based solution to predict the DFI. Settings and Design: This is a retrospective experimental study conducted in a secondary in vitro fertilisation setup. Materials and Methods: We obtained 24,415 images from 30 patients after the SCD test using a phase-contrast microscope. We classified the dataset into two, binary (halo/no halo) and multiclass (big/medium/small halo/degraded (DEG)/dust). Our approach consists of a training and prediction phase. The 30 patients' images were divided into training (24) and prediction (6) sets. A pre-processing method M was developed to automatically segment the images to detect sperm-like regions and was annotated by three embryologists. Statistical Analysis Used: To interpret the findings, the precision-recall curve and F1 score were utilised. Results: Binary and multiclass datasets containing 8887 and 15,528 cropped sperm image regions showed an accuracy of 80.15% versus 75.25%. A precision-recall curve was determined and the binary and multiclass datasets obtained an F1 score of 0.81 versus 0.72. A confusion matrix was applied for predicted and actuals for the multiclass approach where small halo and medium halo confusion were found to be highest. Conclusion: Our proposed machine learning model can standardise and aid in arriving at accurate results without using expensive software. It provides accurate information about healthy and DEG sperms in a given sample, thereby attaining better clinical outcomes. The binary approach performed better with our model than the multiclass approach. However, the multiclass approach can highlight the distribution of fragmented and non-fragmented sperms.

Low birth weight is one of the leading factors for infant morbidity and mortality. To a large extent affect, various maternal risk factors are associated with pregnancy outcomes by increasing odds of delivering an infant with low birth weight. Despite this association, understanding the maternal risk factors affecting term low birth weight has been a challenging task. To date, limited studies have been conducted in India that exert independent magnitude of these effects on term low birth weight. The aim of this review is to examine the current knowledge of maternal risk factors that contribute to term low birth weight in the Indian population. In order to identify the potentially relevant articles, an extensive literature search was conducted using PubMed, Goggle Scholar and IndMed databases (1993 – Dec 2020). Our results indi­cate that maternal age, educational status, socio-economic status, ethnicity, parity, pre-pregnancy weight, maternal stature, maternal body mass index, obstetric history, maternal anaemia, gestational weight gain, short pregnancy outcome, hypertension during pregnancy, infection, antepartum haemorrhage, tobacco consumption, maternal occupation, maternal psychological stress, alcohol consumption, antenatal care and mid-upper arm circumference have all independent effects on term low birth weight in the Indian pop­ulation. Further, we argue that exploration for various other dimensions of maternal factors and underlying pathways can be useful for a better understanding of how it exerts independent association on term low birth weight in the Indian sub-continent.

The propagation of plane waves in a rotating homogeneous, isotropic, thermoelastic solid with double porosity following Lord-Shulman’s theory of thermoelasticity has been investigated. It is assumed that the medium rotates about an axis normal to the surface with a uniform angular velocity. There may exist five coupled waves that evolved due to the longitudinal, transverse disturbance, voids of type-I and type-II, and temperature change in the medium. The secular equation for the model under consideration has been derived with the help of formal solutions and boundary conditions. The amplitude of displacements, temperature change and volume fraction fields for voids of type-I and type-II have also been computed analytically. Finally, numerical computations have been carried out for magnesium crystal material to understand the behavior of amplitude of phase velocity, penetration depth, specific loss, displacement components, temperature change, and volume fraction field due to type-I and type-II voids corresponding to the different rotation rates. Various graphs have been plotted to support the analytical findings. The study may be used in the development of rotation sensors, material design and thermal efficiency.

Short structures when they are designed using base isolation, dynamic wind effects may be more, and it may govern the design. This issue is taken care to some extent using Lead plug bearings. This puts the limits on effective seismic performance only for design basis or beyond. At lower seismic excitation levels, it may not be that effective. In view of this a suitable passive control system using the knowledge of isolators and absorbers is developed and analysed. Five storey shear building models with fixed base, base isolated separately supported on laminated rubber bearing (LRB), lead plug bearing (LPB) and isolated with LRB and install with tuned mass damper (TMD) are developed. These structures are numerically analysed considering six Indian earthquakes and dynamic wind load. TMD used in LRB supported building is provided in LPB supported building and responses of building models also observed under wind load which is more than design basis. Results of all cases are compared. Combined passive isolation along with absorber found suitable for multi-hazards like earthquakes where peak displacement increases by 0.76 times to 38 times, peak acceleration decreases by 73% to 99%, maximum inter-storey drift decreases by 71% to 99% when comparing with fixed base structure and for wind, values of peak displacement, peak acceleration, maximum inter-storey drift decreases by 45%, 46%, 44% when comparing with LRB provided structure.

Summary What microbiology beholds after a decade and a half in the future requires a vision based on the facts and ongoing trends in research and technological advancements. While the latter, assisted by microbial dark matter, presents a greater potential of creating an upsurge in in‐situ and ex‐situ rapid microbial detection techniques, this anticipated change will also set forth a revolution in microbial cultivation and diversity analyses. The availability of a microbial genetic toolbox at the expanse will help complement the current understanding of the microbiome and assist in real‐time monitoring of the dynamics for detecting the health status of the host with utmost precision. Alongside, in light of the emerging infectious diseases, antimicrobial resistance (AMR) and social demands for safer and better health care alternatives, microbiology laboratories are prospected to drift in terms of the volume and nature of research and outcomes. With today’s microbiological lens, one can predict with certainty that in the years to come, microbes will play a significant role in therapeutic treatment and the designing of novel diagnostic techniques. Another area where the scope of microbial application seems to be promising is the use of novel probiotics as a method to offer health benefits whilst promoting metabolic outputs specific for microbiome replenishment. Nonetheless, the evolution of extraterrestrial microbes or the adaptation of earth microbes as extraterrestrial residents are also yet another prominent microbial event one may witness in the upcoming years. But like the two sides of the coin, there is also an urgent need to dampen the bloom of urbanization, overpopulation and global trade and adopting sustainable approaches to control the recurrence of epidemics and pandemics.

Background: Metastasis of the lymph node is one of the most significant prognostic factors for breast cancer (BC). Aim: To predict positivity of the lymph node in BC patients with help of USG and USG-guided FNAC and thus to prevent unnecessary morbidity. Methods: 50 patients of incisional/true cut biopsy-proven BC patients were included. All were subjected to mammography, USG and FNAC of the lump breast. USG-guided FNAC of the axillary lymph node was done in 25 of these patients. These findings were assessed by histological examination following dissection of the axillary lymph node. Results: Axillary lymph node (ALN) metastasis was present in 42 patients on histopathology; 21 patients suspicious of malignancy on preoperative USG were confirmed by HPE. Out of 88 confirmed lymph nodes evaluated on ultrasonography, 4 were benign, 18 were indeterminate and 66 were suspicious. The most promising features were tumour length/depth ratio of

BackgroundMore than 250 loci have been identified by genome-wide scans for type 2 diabetes in different populations. South Asians have a very different manifestation of the diseases and hence role of these loci need to be investigated among Indians with huge burden of cardio-metabolic disorders. Thus the present study aims to validate the recently identified GWAS loci in an endogamous caste population in North India.Methods219 T2D cases and 184 controls were recruited from hospitals and genotyped for 15 GWAS loci of T2D. Regression models adjusted for covariates were run to examine the association for T2D and fasting glucose levels.ResultsWe validated three variants for T2D namely, rs11634397 at ZFAND6 (OR = 3.05, 95%CI = 1.02-9.19, p = 0.047) and rs8042680 at PRC1 (OR = 3.67, 95%CI = 1.13-11.93, p = 0.031) showing higher risk and rs6813195 at TMEM154 (OR = 0.28, 95%CI = 0.09-0.90, p = 0.033) showing protective effect. The combined risk of 9 directionally consistent variants was also found to be significantly associated with T2D (OR = 1.91, 95%CI = 1.18-3.08, p = 0.008). One variant rs10842994 at KLHDC5 was validated for 9.15mg/dl decreased fasting glucose levels (SE = -17.25-1.05, p = 0.027).ConclusionWe confirm the role of ZFAND6, PRC1 and TMEM154 in the pathophysiology of type 2 diabetes among Indians. More efforts are needed with larger sample sizes to validate the diabetes GWAS loci in South Asian populations for wider applicability.

Aim: The study aimed to investigate the prevalence of undernutrition in terms of low birth weight, stunting, wasting, and underweight among children up to 3 years of age. Materials and Methods: We recruited 150 children of the Bhoksa Tribe aged between 2 to 36 months. Information related to nutritional indicators (length-for-age, weight-for-age, and weight-for-length) of the child and socio-demographic variables of the household were collected. Results: The prevalence of undernutrition in terms of low birth weight, stunting, wasting, and underweight was 15.4%, 32%, 29.98%, and 36.66%, respectively. The prevalence percentage of undernutrition was high among girls but the difference based on sex was not significant. A significant difference in mean birth weight was observed between low and high SES (2.45 kg v/s 2.93 kg). Conclusion: High prevalence of undernutrition concerning birth weight among the children of the Bhoksa Tribe was observed which may be due to socioeconomic inequality in the population.

Background/Aims Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC. Methods Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS’ index (ulcerative colitis index of severity >6 at day 1+fecal calprotectin >1,000 μg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome. Results Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0–2,700,000] vs. 116 copies/mg [0–27,220]; P2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6–39.7; P2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.

Background/Aims Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P=0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P=0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P=0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P=0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P=0.046) predicted response to EEN. Conclusions EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.

Abstract Context Multiple observational studies have reported an inverse relationship between 25-hydroxyvitamin D concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results of short- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been inconsistent. Objectives and methods To evaluate the causal role of reduced blood 25(OH)D in T2D, here we have performed a bidirectional Mendelian randomization study using 59,890 individuals (5,862 T2D cases and 54,028 controls) from European and Asian Indian ancestries. We used six known SNPs, including three T2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluate the causality and direction of the association between T2D and circulating 25(OH)D concentration. Results Results of the combined meta-analysis of eight participating studies showed that a composite score of three T2D SNPs would significantly increase T2D risk by an odds ratio (OR) of 1.24, p = 1.82 × 10–32; Z score 11.86, which, however, had no significant association with 25(OH)D status (Beta -0.02nmol/L ± SE 0.01nmol/L; p = 0.83; Z score -0.21). Likewise, the genetically instrumented composite score of 25(OH)D lowering alleles significantly decreased 25(OH)D concentrations (-2.1nmol/L ± SE 0.1nmol/L, p = 7.92 × 10–78; Z score -18.68) but was not associated with increased risk for T2D (OR 1.00, p = 0.12; Z score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as an individual genetic instrument, a per allele reduction of 25(OH)D concentration (-4.2nmol/L ± SE 0.3nmol/L) was predicted to increase T2D risk by 5%, p = 0.004; Z score 2.84. This effect, however, was not seen in other 25(OH)D SNPs (GC rs2282679, CYP2R1 rs12794714) when used as an individual instrument. Conclusion Our new data on this bidirectional Mendelian randomization study suggests that genetically instrumented T2D risk does not cause changes in 25(OH)D levels. However, genetically regulated 25(OH)D deficiency due to vitamin D synthesis gene (DHCR7) may influence the risk of T2D.

We describe a case of late-onset periodic catatonia with atypical course in an elderly male with onset at the age of 70 years with brief episodes of sudden agitation lasting for a few hours of the day, followed by immobility, mutism, ambitendency, withdrawal, and urinary incontinence for the next few days. Four such episodes with complete recovery over the next few days and no residual behavioral symptoms lasting for several years (up to 7 years) without any long-term prophylactic psychotropic use. During the fourth such episode, the patient presented to our facility with a similar abrupt onset of symptoms. All biochemical investigations and neuroimaging findings were found to be noncontributory. On clinical examination, a diagnosis of periodic catatonia was suspected, which was later confirmed by immediate response to the intravenous diazepam challenge given under vitals monitoring in a high-dependency unit setting.

Background/Aims Gluten-free diet has an excess of fats and simple sugars and puts patients with celiac disease at risk of metabolic complications including metabolic syndrome and fatty liver. We assessed prevalence of metabolic syndrome and fatty liver in two cohorts of celiac disease. Methods Study was done in 2 groups. In group 1, 54 treatment naïve patients with celiac disease were recruited. Of them, 44 returned after 1-year of gluten-free diet and were reassessed. In group 2, 130 celiac disease patients on gluten-free diet for ≥1 year were recruited. All patients were assessed for anthropometric and metabolic parameters and fatty liver. Metabolic syndrome was defined as per consensus definition for Asian Indians. Fatty liver was defined as controlled attenuation parameter value >263 decibels by FibroScan. Results In group 1, of 44 treatment naïve patients with celiac disease, metabolic syndrome was present in 5 patients (11.4%) at baseline and 9 (18.2%) after 1 year of gluten-free diet. Patients having fatty liver increased from 6 patients (14.3%) at baseline to 13 (29.5%) after 1year of gluten-free diet (P=0.002). In group 2, of 130 patients with celiac disease on gluten-free diet for a median duration of 4 years, 30 out of 114 (26.3%) and 30 out of 130 patients (23%) had metabolic syndrome and fatty liver, respectively. Conclusions Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver, which increases further with gluten-free diet. These patients should be assessed for nutritional and metabolic features and counseled about balanced diet and physical activity regularly.

Serrated polyps are considered precursor lesions that account for 15% to 30% of colorectal cancers, and they are overrepresented as a cause of interval cancers. They are difficult to detect and resect comprehensively; however, recent data suggest that high definition endoscopy, chromoendoscopy (via spray catheter, pump or orally), narrow band imaging, split-dose bowel preparation and a slower withdrawal (>6 minutes) can all improve detection. Cold snare resection is effective and safe for these lesions, including cold snare piecemeal endoscopic mucosal resection, which is likely to become the standard of care for lesions >10 mm in size. Sessile serrated lesions ≥10 mm in size, those exhbiting dysplasia, or traditional serrated adenomas increase the chance of future advanced neoplasia. Thus, a consensus is emerging: a surveillance examination at 3 years should be recommended if these lesions are detected. Serrated lesions likely carry equivalent risk to adenomas, so future guidelines may consider serrated class lesions and adenomas together for risk stratification. Patients with serrated polyposis syndrome should undergo surveillance every 1 to 2 years once the colon is cleared of larger lesions, and their first degree relatives should undergo screening every 5 years starting at age 40.

Purpose – Even though there is a growing recognition of the externality costs of low environmental performance by firms, there continue to be significant inter-firm differentials in environmental performance management. We build on the theories of strategic management to inquire into the factors contributing to these differentials. Design/methodology/approach – Using a 2015 survey sample of Chinese small and medium enterprises, we empirically investigate the alternative thesis that the profit maximization motive constitutes the appropriate heuristic for the performance management of corporate social responsibility factors. Findings –The green capability of a firm is an aggregate of green trading and the investments that the firm has made in green initiatives that are complementary to its strategic business model. The profit aspiration level of firms has a negative influence on their green programing, while transformational leadership has a positive influence. Originality/value – We develop seven propositions represented as algebraic relationships to interpret these factors.

ABSTRACT Secondary metabolites produced by Actinobacteria are an important source of antibiotics, drugs, and antimicrobial peptides. However, the large genome size of actinobacteria with high gene coding density makes it difficult to understand the complex regulation of biosynthesis of such critically and economically important products. In the last few decades, apart from genomics sequences, high-throughput proteomics has proven beneficial to understand the key players regulating the expression pattern of secondary metabolite and antibiotic production in different experimental set-ups. In the past, we have been analyzing the genomics data and mass spectrometry-based proteomics to predict the regulation dynamics and crucial regulatory hubs in Actinobacteria. The multidirectional regulation and expression of the biosynthetic gene cluster responsible for the production of important metabolite take their cue from the other primary metabolism pathways with which they show intricate interactions in the interactome. The regulation occurs by not only the action and expression of the biosynthetic gene cluster but also the role of transcription factors and primary metabolic pathways. Using the key players of these interactomes, we can regulate the synthesis/production of these valuable peptides/metabolites. Simultaneously, the multi-omics approach has now opened new gateways in investigation, screening, and identification of naturally occurring antimicrobial peptides from actinobacteria which are beneficial for humans and also provide economic and industrial benefits to humankind.

ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in 92 million cases in a span of 1 year. The study focuses on understanding population-specific variations attributing its high rate of infections in specific geographical regions particularly in the United States. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d, and e (subtypes e1 and e2). Clade d and subclade e2 were found exclusively comprised of U.S. strains. Clades were distinguished by 10 co-mutational combinations in Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2, and Nsp6. Our analysis revealed that only 67.46% of single nucleotide polymorphism (SNP) mutations were at the amino acid level. T1103P mutation in Nsp3 was predicted to increase protein stability in 238 strains except for 6 strains which were marked as ancestral type, whereas co-mutation (P409L and Y446C) in Nsp13 were found in 64 genomes from the United States highlighting its 100% co-occurrence. Docking highlighted mutation (D614G) caused reduction in binding of spike proteins with angiotensin-converting enzyme 2 (ACE2), but it also showed better interaction with the TMPRSS2 receptor contributing to high transmissibility among U.S. strains. We also found host proteins, MYO5A, MYO5B, and MYO5C, that had maximum interaction with viral proteins (nucleocapsid [N], spike [S], and membrane [M] proteins). Thus, blocking the internalization pathway by inhibiting MYO5 proteins which could be an effective target for coronavirus disease 2019 (COVID-19) treatment. The functional annotations of the host-pathogen interaction (HPI) network were found to be closely associated with hypoxia and thrombotic conditions, confirming the vulnerability and severity of infection. We also screened CpG islands in Nsp1 and N conferring the ability of SARS-CoV-2 to enter and trigger zinc antiviral protein (ZAP) activity inside the host cell. IMPORTANCE In the current study, we presented a global view of mutational pattern observed in SARS-CoV-2 virus transmission. This provided a who-infect-whom geographical model since the early pandemic. This is hitherto the most comprehensive comparative genomics analysis of full-length genomes for co-mutations at different geographical regions especially in U.S. strains. Compositional structural biology results suggested that mutations have a balance of opposing forces affecting pathogenicity suggesting that only a few mutations are effective at the translation level. Novel HPI analysis and CpG predictions elucidate the proof of concept of hypoxia and thrombotic conditions in several patients. Thus, the current study focuses the understanding of population-specific variations attributing a high rate of SARS-CoV-2 infections in specific geographical regions which may eventually be vital for the most severely affected countries and regions for sharp development of custom-made vindication strategies.

ABSTRACT The outbreak of coronavirus disease 2019 (COVID-19) that started in Wuhan, China, in December 2019 has spread worldwide, emerging as a global pandemic. The severe respiratory pneumonia caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far claimed more than 0.38 million lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 virus displays high transmission rates, the underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries, suggesting that its spread is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nonstructural protein 13 (nsp13), nsp14, nsp15, and nsp16 (ORF1b polyproteins) and in the S-protein within 10 viral isolates from the United States. These viral proteins are involved in RNA replication and binding with the human receptors, indicating that the viral variants that are circulating in the population of the United States are different from those circulating in the populations of other countries. In addition, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of a U.S. isolate (GenBank accession no. MT188341.1) leading to a shift in the amino acid frame from position 2540 onward. Through comparative structural analysis of the wild-type and mutant proteins, we showed that this addition of a phenylalanine residue renders the protein in the mutant less stable, which might affect mRNA cap-1 methyltransferase function. We further analyzed the SARS-CoV-2–human interactome, which revealed that the interferon signaling pathway is targeted by orf1ab during infection and that it also interacts with NF-κB-repressing factor (NKRF), which is a potential regulator of interleukin-8 (IL-8). We propose that targeting this interaction may subsequently improve the health condition of COVID-19 patients. Our analysis also emphasized that SARS-CoV-2 manipulates spliceosome machinery during infection; hence, targeting splicing might affect viral replication. In conclusion, the replicative machinery of SARS-CoV-2 is targeting interferon and the notch signaling pathway along with spliceosome machinery to evade host challenges. IMPORTANCE The COVID-19 pandemic continues to storm the world, with over 6.5 million cases worldwide. The severity of the disease varies with the territories and is mainly influenced by population density and age factor. In this study, we analyzed the transmission pattern of 95 SARS-CoV-2 genomes isolated from 11 different countries. Our study also revealed several nonsynonymous mutations in ORF1b and S-proteins and the impact on their structural stability. Our analysis showed the manipulation of host system by viral proteins through SARS-CoV-2–human protein interactome, which can be useful to understand the impact of virus on human health.

BackgroundUndernutrition during intrauterine life and early childhood is hypothesised to increase the risk of cardiovascular disease (Developmental Origins of Health and Disease Hypothesis), but experimental evidence from humans is limited. This hypothesis has major implications for control of the cardiovascular disease epidemic in South Asia (home to a quarter of world's population), where a quarter of newborns have low birth weight. We investigated whether, in an area with prevalent undernutrition, supplemental nutrition offered to pregnant women and their offspring below the age of 6 years was associated with a lower risk of cardiovascular disease in the offspring when they were young adults.Methods and findingsThe Hyderabad Nutrition Trial was a community-based nonrandomised controlled intervention trial conducted in 29 villages near Hyderabad, India (1987-1990). Protein-calorie food supplement was offered daily to pregnant and lactating women (2.09 MJ energy and 20-25 g protein) and their offspring (1.25 MJ energy and 8-10 g protein) until the age of six years in the 15 intervention villages, but not in the 14 control villages. A total of 1,826 participants (949 from the intervention villages and 877 from the control villages, representing 70% of the cohort) at a mean age of 21.6 years (62% males) were examined between 2009 and 2012. The mean body mass index (BMI) of the participants was 20 kg/m2 and the mean systolic blood pressure was 115 mm Hg. The age, sex, socioeconomic position, and urbanisation-adjusted effects of intervention (beta coefficients and 95% confidence intervals) on outcomes were as follows: carotid intima-media thickness, 0.01 mm (-0.01 to 0.03), p = 0.36; arterial stiffness (augmentation index), -1.1% (-2.5 to 0.3), p = 0.097; systolic blood pressure, 0.5 mm Hg (-0.6 to 1.6), p = 0.36; BMI, -0.13 kg/m2 (-0.75 to 0.09), p = 0.093; low-density lipoprotein (LDL) cholesterol, 0.06 mmol/L (-0.07 to 0.2), p = 0.37; and fasting insulin (log), -0.06 mU/L (-0.19 to 0.07), p = 0.43. The limitations of this study include nonrandomised allocation of intervention and lack of data on compliance, and potential for selection bias due to incomplete follow-up.ConclusionsOur results showed that in an area with prevalent undernutrition, protein-calorie food supplements offered to pregnant women and their offspring below the age of 6 years were not associated with lower levels of cardiovascular risk factors among offspring when they were young adults. Our findings, coupled with evidence from other intervention studies to date, suggest that policy makers should attach limited value to cardiovascular health benefits of maternal and child protein-calorie food supplementation programmes.

BackgroundDyslipidemia and abnormal glycemic traits are leading causes of morbidity and mortality. Although the association between the two traits is well established, there still exists a gap in the evidence for the direction of causality.ObjectiveThis study aimed to examine the direction of the causal relationship between lipids and glycemic traits in an Indian population using bidirectional Mendelian randomization (BMR).MethodsThe BMR analysis was conducted on 4900 individuals (2450 sib-pairs) from the Indian Migration Study. Instrument variables were generated for each lipid and glycemic trait (fasting insulin, fasting glucose, HOMA-IR, HOMA-β, LDL-cholesterol, HDL-cholesterol, total cholesterol and triglycerides) to examine the causal relationship by applying two-stage least squares (2SLS) regression in both directions.ResultsLipid and glycemic traits were found to be associated observationally, however, results from 2SLS showed that only triglycerides, defined by weighted genetic risk score (wGRS) of 3 SNPs (rs662799 at APOAV, rs780094 at GCKR and rs4420638 at APOE/C1/C4), were observed to be causally effecting 1.15% variation in HOMA-IR (SE = 0.22, P = 0.010), 1.53% in HOMA- β (SE = 0.21, P = 0.001) and 1.18% in fasting insulin (SE = 0.23, P = 0.009). No evidence for a causal effect was observed in the reverse direction or between any other lipid and glycemic traits.ConclusionThe study findings suggest that triglycerides may causally impact various glycemic traits. However, the findings need to be replicated in larger studies.

Background/Aims The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed. Methods This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated). Results Of 69 patients (22 ulcerative colitis/47 Crohn’s disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5–48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0–84.5 weeks) of IFX. Of these 8 patients’ none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn’s disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation. Conclusions There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX.

Background/Aims: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV) and hepatitis C (HCV) and human immunodeficiency virus (HIV). In the present study, we assessed the prevalence of these infections in patients with IBD.Methods: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327) who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB) were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method). HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%).Results: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541) had HBV, 1.7% (9/517) had HCV, and 0.2% (1/499) had HIV. Among the 327 patients with CD, 2.8% (8/288) had HBV, 0.7% (2/273) had HCV, and 0% (0/277) had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67), 1.8% (1/57), and 1.2% (1/84), respectively.Conclusions: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.

The increased prevalence of non-communicable chronic diseases (NCDs) is reflected in the rising economic burden of health conditions. Observational studies conducted in health economics research are detecting associations of NCDs or related risk factors with economic measures like health insurance, economic inequalities, accessibility of jobs, education, annual income, health expenditure, etc. The inferences of such relationships do not prove causation and are limited to associations which are many times influenced by confounding factors and reverse causation. Mendelian randomization (MR) approach is a useful method for exploring causal relations between modifiable risk factors and measures of health economics. The application of MR in economic assessment of health conditions has been started and is producing fruitful results.

BACKGROUNDFat mass is variably associated with bone mass, possibly due to differential mechanical and biological effects of fat mass. We examined the association of fat mass with bone mass in a lean population.OBJECTIVETo investigate association between hip bone mineral density and fat and lean mass in a cross-sectional study from southern India.DESIGNThe Andhra Pradesh Children and Parents Study is a prospective cohort study in Hyderabad, India. In 2009-2012, the study collected data on anthropometric measures, bone mineral density (BMD), fat mass, and lean mass measured by dual-energy x-ray absorptiometry, and socioeconomic data of the adult participants (n = 1760; mean age = 34.9 years old for women; 2130 and 32.3 for men).RESULTSThe median BMI (kg/m2) was 20.1 kg/m2. Women had relatively higher fat mass as compared to men. In models adjusted for lean mass, there was an association between hip bone mineral density and fat mass in women (β (95% confidence interval): premenopausal 0.025 (0.006 to 0.045); postmenopausal 0.045 (0.014 to 0.076)) but not in men (0.001 (-0.012 to 0.0014)). The association between hip BMD and fat mass was stronger in postmenopausal than premenopausal women. Hip BMD was consistently associated with lean mass, in both men and women.CONCLUSIONSIn this relatively lean population, lean mass was more consistently associated with hip BMD than fat mass. Weight gain through lean mass improvement may be a more reliable public health strategy for strengthening bone health in transitional settings.

Recently, there has been an increased interest in the family business organization. Traditionally, the ideal typical organizational model was one where the management, governance, and ownership entities are kept separate. This principal agent model has been a subject of public debate in the wake of several corporate scandals. In the family business organization, significant management, governance and ownership is often with the members of a family & its trusted partners. It is common in the US to regulate the management, governance, and ownership roles of the family members by using competitive criteria for the involvement of different members. In Southern Asia cluster (Gupta & Hanges, 2004), on the other hand, it is quite common for the family involvement to be holistic and undivided, where the family collectively owns the shares in the family business. In this work, this organizational model of the Southern Asian family businesses is investigated. Keywords: Southern Asia, family business, organizational model

Introduction: Necrotizing enterocolitis (NEC) is a common in neonatal intensive care unit (NICU) patients; especially in premature and low birth weight ones. Surgery is indicated when there is pneumoperitoneum. Other therapies include conservative observation or primary peritoneal drain (PPD). This study was conceived to evaluate peritoneal tapping, rather than primary peritoneal drain (PPD) as a treatment of NEC. Material and Methods- This prospective observational study conducted from December 2012 to December 2014 and including all patients of NEC having pneumoperitoneum on X-ray. Results- There were 12 patients of NEC. Seven patients responded to single peritoneal tapping. Three patients needed one more tapping. Laparotomy was required in remaining two patients. One patient, who underwent laparotomy, expired due to severe sepsis. The mean duration of follow up was 4.83 months (range 2 to 8). Conclusion- Peritoneal tapping in NEC who develops pneumoperitoneum appears to be a viable option. Further studies in this regard may substantiate this mode of therapy.

Recently, there has been an increased interest in the family business organization. Traditionally, the ideal typical organizational model was one where the management, governance, and ownership entities are kept separate. This principal agent model has been a subject of public debate in the wake of several corporate scandals. In the family business organization, significant management, governance and ownership is often with the members of a family & its trusted partners. It is common in the US to regulate the management, governance, and ownership roles of the family members by using competitive criteria for the involvement of different members. In Southern Asia cluster (Gupta & Hanges, 2004), on the other hand, it is quite common for the family involvement to be holistic and undivided, where the family collectively owns the shares in the family business. In this work, this organizational model of the Southern Asian family businesses is investigated.

Duplication of the alimentary tract is an important surgical condition. It may occur anywhere in the gastrointestinal tract. An important complication of this entity is perforation of the normal or abnormal gut. Malrotation with midgut volvulus can be a surgical emergency. We present a patient, who presented as malrotation with midgut volvulus associated with perforated ileal duplication. The patient was successfully managed.

Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations.

Obesity is an established risk factor for type 2 diabetes (T2D) and they are metabolically related through the mechanism of insulin resistance. In order to explore how common genetic variants associated with T2D correlate with body mass index (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associations of variants in CXCR4 (rs932206) and HHEX (rs5015480) with higher body mass index (BMI) (β=0.13, p=0.001) and (β=0.09, p=0.002), respectively and weight (β=0.13, p=0.001) and (β=0.09, p=0.001), respectively. CXCR4 variant was also strongly associated with body fat (β=0.10, p=0.0004). In addition, we demonstrated associations of CXCR4 and HHEX with overweight/obesity (OR=1.6, p=0.003) and (OR=1.4, p=0.002), respectively, in 1333 sib-pairs (2666 individuals). We observed marginal evidence of associations between variants at six loci (TCF7L2, NGN3, FOXA2, LOC646279, FLJ39370 and THADA) and waist hip ratio (WHR), BMI and/or overweight which needs to be validated in larger set of samples. All the above findings were independent of daily energy consumption and physical activity level. The risk score estimates based on eight significant loci (including nominal associations) showed associations with WHR and body fat which were independent of BMI. In summary, we establish the role of T2D associated loci in influencing the measures of obesity in Indian population, suggesting common underlying pathophysiology across populations.