Pan-tissue transcriptome analysis of long noncoding RNAs in the American beaver Castor canadensis.

BACKGROUND: Long noncoding RNAs (lncRNAs) have roles in gene regulation, epigenetics, and molecular scaffolding and it is hypothesized that they underlie some mammalian evolutionary adaptations. However, for many mammalian species, the absence of a genome assembly precludes the comprehensive identification of lncRNAs. The genome of the American beaver (Castor canadensis) has recently been sequenced, setting the stage for the systematic identification of beaver lncRNAs and the characterization of their expression in various tissues. The objective of this study was to discover and profile polyadenylated lncRNAs in the beaver using high-throughput short-read sequencing of RNA from sixteen beaver tissues and to annotate the resulting lncRNAs based on their potential for orthology with known lncRNAs in other species. RESULTS: Using de novo transcriptome assembly, we found 9528 potential lncRNA contigs and 187 high-confidence lncRNA contigs. Of the high-confidence lncRNA contigs, 147 have no known orthologs (and thus are putative novel lncRNAs) and 40 have mammalian orthologs. The novel lncRNAs mapped to the Oregon State University (OSU) reference beaver genome with greater than 90% sequence identity. While the novel lncRNAs were on average shorter than their annotated counterparts, they were similar to the annotated lncRNAs in terms of the relationships between contig length and minimum free energy (MFE) and between coverage and contig length. We identified beaver orthologs of known lncRNAs such as XIST, MEG3, TINCR, and NIPBL-DT. We profiled the expression of the 187 high-confidence lncRNAs across 16 beaver tissues (whole blood, brain, lung, liver, heart, stomach, intestine, skeletal muscle, kidney, spleen, ovary, placenta, castor gland, tail, toe-webbing, and tongue) and identified both tissue-specific and ubiquitous lncRNAs. CONCLUSIONS: To our knowledge this is the first report of systematic identification of lncRNAs and their expression atlas in beaver. LncRNAs-both novel and those with known orthologs-are expressed in each of the beaver tissues that we analyzed. For some beaver lncRNAs with known orthologs, the tissue-specific expression patterns were phylogenetically conserved. The lncRNA sequence data files and raw sequence files are available via the web supplement and the NCBI Sequence Read Archive, respectively.

Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach.

BACKGROUND: Feline injection-site sarcoma (FISS), an aggressive iatrogenic subcutaneous malignancy, is challenging to manage clinically and little is known about the molecular basis of its pathogenesis. Tumor transcriptome profiling has proved valuable for gaining insights into the molecular basis of cancers and for identifying new therapeutic targets. Here, we report the first study of the FISS transcriptome and the first cross-species comparison of the FISS transcriptome with those of anatomically similar soft-tissue sarcomas in dogs and humans. METHODS: Using high-throughput short-read paired-end sequencing, we comparatively profiled FISS tumors vs. normal tissue samples as well as cultured FISS-derived cell lines vs. skin-derived fibroblasts. We analyzed the mRNA-seq data to compare cancer/normal gene expression level, identify biological processes and molecular pathways that are associated with the pathogenesis of FISS, and identify multimegabase genomic regions of potential somatic copy number alteration (SCNA) in FISS. We additionally conducted cross-species analyses to compare the transcriptome of FISS to those of soft-tissue sarcomas in dogs and humans, at the level of cancer/normal gene expression ratios. RESULTS: We found: (1) substantial differential expression biases in feline orthologs of human oncogenes and tumor suppressor genes suggesting conserved functions in FISS; (2) a genomic region with recurrent SCNA in human sarcomas that is syntenic to a feline genomic region of probable SCNA in FISS; and (3) significant overlap of the pattern of transcriptional alterations in FISS with the patterns of transcriptional alterations in soft-tissue sarcomas in humans and in dogs. We demonstrated that a protein, BarH-like homeobox 1 (BARX1), has increased expression in FISS cells at the protein level. We identified 11 drugs and four target proteins as potential new therapies for FISS, and validated that one of them (GSK-1059615) inhibits growth of FISS-derived cells in vitro. CONCLUSIONS: (1) Window-based analysis of mRNA-seq data can uncover SCNAs. (2) The transcriptome of FISS-derived cells is highly consistent with that of FISS tumors. (3) FISS is highly similar to soft-tissue sarcomas in dogs and humans, at the level of gene expression. This work underscores the potential utility of comparative oncology in improving understanding and treatment of FISS.

Cross-species analysis of the canine and human bladder cancer transcriptome and exome.

We investigated the correspondence between transcriptome and exome alterations in canine bladder cancer and the correspondence between these alterations and cancer-driving genes and transcriptional alterations in human bladder cancer. We profiled canine bladder tumors using mRNA-seq and exome-seq in order to investigate the similarity of transcriptional alterations in bladder cancer, in humans and canines, at the levels of gene functions, pathways, and cytogenetic regions. We found that the transcriptomes of canine and human bladder cancer are remarkably similar at the functional and pathway levels. We demonstrated that canine bladder cancer involves coordinated differential expression of genes within cytogenetic bands, and that these patterns are consistent with those seen in human bladder cancer. We found that genes that are mutated in canine bladder cancer are more likely to be transcriptionally downregulated than non-mutated genes, in the tumor. Finally we report three novel mutations (FAM133B, RAB3GAP2, and ANKRD52) for canine bladder cancer.

A preliminary clinico-epidemiological portrayal of COVID-19 pandemic at a premier medical institution of North India.

CONTEXT: The outbreak and spread of severe acute respiratory syndrome coronavirus 2 has led to a global exigency of colossal and monstrous proportions in terms of public health and economic crisis. Till date, no pharmaceutical agent is known to manage in terms of prevention and treatment of coronavirus disease 2019 (COVID-19), the disease caused by a novel virus. AIMS: The aim of the present work was to understand the underlying disease profile and dynamics that could provide relevant inputs and insight into pathophysiology and prevent further spread and evolve management strategies of COVID-19 patients from data-driven techniques. SETTINGS AND DESIGN: A retrospective observational descriptive study was conducted on 29 COVID-19 patients admitted at a premier medical institution of North India in the months of February and March 2020. METHODS: The patients were diagnosed with reverse transcription-polymerase chain reaction test. Demographic, clinical, and laboratory data were collected. RESULTS: The mean age of population was 38.8 years with male preponderance, of which two patients were residents of Italy, and others hailed from semi-arid and Western sandy arid regions of Rajasthan (urban population). The major presenting symptom complex of said COVID-19 sample population included fever (48%), cough (31%), and shortness of breath (17%). Most of the patients (83%) had no comorbidity. No clinical correlation (r) could be appreciated between the duration of test positivity and age of afflicted COVID-19 patients (r = -0.0976). CONCLUSIONS: The present evaluation of various facets of the ongoing global pandemic of COVID-19 is an attempt to portray early clinical and epidemiological parameters of the menace of COVID-19 patients admitted at SMS Medical College and Attached Hospitals, Jaipur.

Assessment of road traffic behavior using Youth Risk Behavior Survey questionnaire among school-going adolescents of Jaipur city, Rajasthan: An observational analysis.

BACKGROUND: Adolescents are a relatively healthy group, but their developmental stage makes them vulnerable to many risk-taking behaviors. One such major issue is road safety practices and their risk on roads. OBJECTIVE: To determine road safety risk behavior among school-going adolescents of Jaipur city and factors associated with it. MATERIALS AND METHODS: An observational, cross-sectional study was conducted from July 2015 to February 2016. A total of 900 school-going adolescents were enrolled from eight schools of Jaipur city and the Youth Risk Behavior Survey (YRBS) questionnaire was administered. RESULTS: Most of the participants (67.56%) were in the age group of 13-16 years. A total of 682 (75%) adolescents were driving one or other type of vehicle to commute. Out of the 682 vehicle-using adolescents, 603 (88%) had risky behavior on roads. Driving under the influence was found more among those using four-wheelers (10%) than two-wheelers (5%). Almost half of drivers used mobile phones while driving a car or two-wheeler. There was statistically significant association between risk on roads with respect to rising education and occupation of parents. A majority (88.41%) of the school-going students were found to be at risk on roads while driving. Safety-belt was not used by 28% of the students while half did not use a helmet. More than 70% of the car drivers and two-wheeler drivers drove without license. CONCLUSION: Majority of the adolescent drivers are at risk on roads. Driving without license and/or helmet and using mobile phone are the main risk factors.

National Mental Health Survey of India, 2016 - Rationale, design and methods.

Understanding the burden and pattern of mental disorders as well as mapping the existing resources for delivery of mental health services in India, has been a felt need over decades. Recognizing this necessity, the Ministry of Health and Family Welfare, Government of India, commissioned the National Mental Health Survey (NMHS) in the year 2014-15. The NMHS aimed to estimate the prevalence and burden of mental health disorders in India and identify current treatment gaps, existing patterns of health-care seeking, service utilization patterns, along with an understanding of the impact and disability due to these disorders. This paper describes the design, steps and the methodology adopted for phase 1 of the NMHS conducted in India. The NMHS phase 1 covered a representative population of 39,532 from 12 states across 6 regions of India, namely, the states of Punjab and Uttar Pradesh (North); Tamil Nadu and Kerala (South); Jharkhand and West Bengal (East); Rajasthan and Gujarat (West); Madhya Pradesh and Chhattisgarh (Central) and Assam and Manipur (North East). The NMHS of India (2015-16) is a unique representative survey which adopted a uniform and standardized methodology which sought to overcome limitations of previous surveys. It employed a multi-stage, stratified, random cluster sampling technique, with random selection of clusters based on Probability Proportionate to Size. It was expected that the findings from the NMHS 2015-16 would reveal the burden of mental disorders, the magnitude of the treatment gap, existing challenges and prevailing barriers in the mental-health delivery systems in the country at a single point in time. It is hoped that the results of NMHS will provide the evidence to strengthen and implement mental health policies and programs in the near future and provide the rationale to enhance investment in mental health care in India. It is also hoped that the NMHS will provide a framework for conducting similar population based surveys on mental health and other public health problems in low and middle-income countries.

Prevalence and pattern of risk factors for non-communicable diseases in urban population of Jaipur, Rajasthan

Background: Majority of the risk factors for NCDs are measurable and modifiable thus continuous surveillance of the levels and pattern of these risk factors is of fundamental importance. Taking cognizance of Jaipur city rapidly adopting to metropolitan culture; this study may mark an important milestone in surveillance activities and setting preventive priorities for NCDs in the state of Rajasthan. Aim of the study is to measure prevalence and associated variables of major risk factors for NCDs in the age group of 25-64 years.Methods: It is a cross sectional, descriptive study, conducted on 1454 person aged 25 to 64 years, residing in Jaipur city, from 1st June 2012 to 31st December 2013, using two steps of ‘standard WHO STEPS structured instrument’. Categorical data were expressed in form of percentage. Chi-square test was used to analyse difference in proportions. Continuous data were summarized in form of mean and SD. The differences in means were analysed by student’s t test.Results: At least one risk factor was present in all persons moreover 35% had multiple risk factors. Multiple risk factors were present even in 20% of relatively young adults (25-34 years). Tobacco and alcohol consumption was seen in 28% and 29% respectively. Standard of living index was associated with obesity, hypertension and low physical activity but not with alcohol use, smoking and daily consumption of fruit & vegetable. Male consumed more alcohol, indulged in less physical activity and smoked more than twelve times than females.Conclusions: Educating younger population for healthy lifestyle adoption and focused educational intervention with strict enforcement of existing laws will be helpful in controlling this epidemic of NCD.

Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders.

Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose regulation, Lipid metabolism and nerve signaling. Emphasis is laid on BCHE's diverse functions whose impediment affects the above mentioned metabolic pathways. Insilco techniques were employed to analyze the sequence, structural and functional similarities of the two proteins. A point mutation is focused which is common to both BCHE and Neuroligin. The mutation occurs at the homologous position in both the proteins making them deficient. This affects the three metabolic pathways leading to the respective disorders. The work describes the pathway that describes the role of BCHE in the onset of obesity mediated diabetes. The pathway further explains the association between Diabetes, Obesity and neurological disturbances.

Non-compliance to Antiretroviral Therapy:Road Blocks and Possible Solutions.

A hospital based interventional study was done at Anti Retroviral Therapy centre (ART) of SMS Medical College during August 2010 to January 2011 with the objectives of finding out the proportion of patients who did not adhere to ART, its associated factors, reasons for non-compliance and determine the effect of reinforced counselling through interpersonal communication addressing patient specific reasons and solution for increasing compliance. There were 2841 HIV patients on ART during study period and on an average 381 (13%) of them did not adhere to ART. Age, literacy, unemployment, presence of co-infections were significantly associated with non-compliance while marital status, sex of patient, area of living, family size, distance from ART centre and type of ART regime were not associated with non-compliance. Reasons stated for not coming to collect drugs or not consuming them were mainly patients were travelling, forget to take the pills, no one was there to accompany them, no money for fare, busy in agriculture or other day to day activities. 100 randomly selected non-compliant patients were offered reinforced counselling with focus on patient specific reasons for non compliance and with an intention to encourage the patients to come up with solutions in prevailing circumstances. 74 patients started taking drugs regularly at the end of study. One patient out of these hundred died during study period.

H1N1 Deaths Reported at SMS Hospital.

Background: The influenza virus has unique ability to cause recurrent epidemics and global pandemics. Very few information is available regarding death pattern and associated factors till now so this study was conducted with the objective to evaluate the profile of H1N1 deaths reported at SMS hospital, Jaipur and it’s associated factors. Methods: The present study was conducted at SMS hospital, Jaipur during 22nd August 2009 to 13th January 2010. The secondary data related to case reports of death due to H1N1 2009 was collected. Data on following variables were collected age, sex, urban / rural, presenting clinical symptoms, associated illness if any, investigation done, time lag between admission and death, time lag of sample taken and reporting. The data so collected were analyzed with appropriate statistical procedures. Observation: There were total 34 deaths reported due to H1N1 related cause. Almost one fourth (8 /34) of deaths occurred in the age group of 21 to 25 years. Majority of the patients reported with high grade fever (88.2%), cough and breathlessness (79.4%) each, sore throat was present in 23.5%, 11.7% had some associating complications when admitted to the hospital. In 71.8% deaths were due to problems related to respiratory system. There were five H1N1 positive pregnant women who were admitted at SMS hospital and all five died.