Browsing by Author "Sharma, S."

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    Lessons Learned from Cohort Studies, and Hospital-Based Studies and Their Implications in Precision Medicine
    (Elsevier Inc., 2017) Munshi, Anjana; Sharma, V.; Sharma, S.
    Advances in human genomics and cutting-edge technologies have created space for integrating personalized or precise medicine into the practice of medicine and thereby improving the public health. Achieving the goal of quantitatively improving the quality and effectiveness of health care for all requires both knowledge of classical, genomics, and pharmacogenomic studies carried out worldwide on different subsets of population. Since the disease outcome and therapeutic effectiveness may vary according to geographical areas, ethnicity, race, and genetic makeup, the complex pathways, including gene-environment, gene-drug, and gene-gene interactions, play a significant role in the development of disease as well as in determining an individual's response toward prescribed medicine. The decision-making process in selecting or identifying precise medicine via clinicians depends on the large effort carried out by researchers and pharmaceutical companies conducting clinical trials, cohort studies, and hospital-based retrospective and prospective studies (e.g., The Strengthening the Reporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) study. However, the evidence based on gene-disease associations is fraught with certain methodological problems such as inadequate sample size, reporting of results, even from well-conducted studies, hampers the assessment of a study's strengths and weaknesses and hence the integration of evidence into clinical practice (Little et al., 2009).Precision Medicine Initiative, a research cohort, launched by NIH, including more than a million Americans, is one of the brilliant steps toward precision medicine which will contain genomic, clinical, and other health-related information. This U.S. Research Cohort may provide a platform for scientists to conduct rapid and efficient randomized trials that use cohorts and registries for further research (Baker et al., 2015). Appropriate decision making on the basis of previously established studies or trials and with available evidence in hand, based on genomic profiling have revolutionized the current paradigm of clinical practice. Now, the trend of giving importance to therapies rather than to diagnostics may need to be revisited to ensure and to speed up innovation in the area of personalized or precision medicine. ? 2017 Elsevier Inc.
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    Phytotoxic selectivity analysis of Eucalyptus tereticornisessential oil against rice, Oryza sativa and its weeds,Echinochloa crus-galli and Cyperus rotundus
    (Sadhna, 2015) Vishwakarma, G. S.; Sharma, S.; Mittal, Sunil
    The present study was undertaken to explore the phytotoxic potential of essential oil (EO) fromEucalyptus tereticornis against two major weeds of rice viz Echinochloa crus-galli and Cyperusrotundus. The effect of essential oil was studied on growth (percentage germination, root length andshoot length development) physiological parameters (chlorophyll content and per cent respiration)under controlled conditions in the laboratory. Studies revealed that E tereticornis essential oil (indifferent concentrations ranging from 25 to 250 g/ml) affected the growth and physiology of all thetest plants. However the effect was more predominant on weeds compared to the rice seedlings.When the seeds of test plants were exposed to 100 and 250 g/ml oil concentration seed germinationand seedling development of test weeds were highly affected as compared to rice. C rotundus wasfound to be the most sensitive weed among test plants. In chlorophyll content the reduction at 250 g/ml of essential oil was 60, 80 and 99 per cent in O sativa, E crus-galli and C rotundus respectively.Similarly reduction in respiratory activity on exposure to 250 g/ml of essential oil was 20, 40 and99 per cent in O sativa, E crus-galli and C rotundus respectively. The present study concludes thatessential oil of E tereticornis shows the toxicity selectively towards the E crus-galli and C rotunduscompared to O sativa
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    Shared and unique common genetic determinants between pediatric and adult celiac disease
    (BioMed Central Ltd., 2016) Senapati, S.; Sood, A.; Midha, V.; Sood, N.; Sharma, S.; Kumar, L.; Thelma, B.K.
    Background: Based on age of presentation, celiac disease (CD) is categorised as pediatric CD and adult CD. It however remains unclear if these are genetically and/or phenotypically distinct disorders or just different spectrum of the same disease. We therefore explored the common genetic components underlying pediatric and adult CD in a well characterized north Indian cohort. Methods: A retrospective analysis of children (n = 531) and adult (n = 871) patients with CD between January 2001 and December 2010 was done. The database included basic demographic characteristics, clinical presentations, associated diseases and complications, if any. The genotype dataset was acquired for children (n = 217) and adult CD patients (n = 340) and controls (n = 736) using Immunochip. Association analysis was performed using logistic regression model to identify susceptibility genetic variants. Results: The predominant form of CD was classical CD in both pediatric and adult CD groups. There was remarkable similarity between pediatric and adult CD except for quantitative differences between the two groups such as female preponderance, non-classical presentation, co-occurrence of other autoimmune diseases being more common amongst adult CD. Notably, same HLA-DQ2 and -DQ8 haplotypes were established as the major risk factors in both types of CD. In addition, a few suggestively associated (p < 5 ? 10-4) non-HLA markers were identified of which only ANK3 (rs4948256-A; rs10994257-T) was found to be shared and explain risk for ?45 % of CD patients with HLA allele. Discussion: Overall phenotypic similarity between pediatric and adult CD groups can be explained by contribution of same HLA risk alleles. Different non-HLA genes/loci with minor risk seem to play crucial role in disease onset and extra intestinal manifestation of CD. None of the non-HLA risk variants reached genome-wide significance, however most of them were shown to have functional implication to disease pathogenesis. Functional relevance of our findings needs to be investigated to address clinical heterogeneity of CD. Conclusions: This present study is the first comparative study based on common genetic markers to suggest that CD in pediatric age group and in adults are the spectrum of the same disease with novel and shared genetic risk determinants. Follow-up fine mapping studies with larger study cohorts are warranted for further genetic investigation. ? 2016 The Author(s).
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    Time to Educate Physicians and Hospital Staff in Electronic Medical Records for Precision Medicine
    (Elsevier Inc., 2017) Sharma, S.; Munshi, Anjana; Sharma, V.
    Over the past decade, inexpensive and dense sequencing technologies have led to many genetic discoveries. Single nucleotide polymorphisms associated with over 250 different phenotypes have been identified by genome-wide association studies. Lack of large cohorts with adequately defined phenotypes has hindered further progress. This hindrance in genetic research can be overcome by electronic health records. These electronic health records have been recognized as a viable and efficient model for genetic research. The drawback of currently existing digitalized data and information in multiple unstructured formats continue to generate huge amount of information leading to difficulty in accessing invaluable and newly discovered knowledge. Connecting molecular data, individual genome sequence, patient phenotype, experimental data, and follow-up details is a big task. Road block to this monumental task of integration and interoperability are ethical, legal, and logistics. Data security and protection of patient rights are a must to maintain public support. In this chapter we have highlighted the advantages and challenges of using electronic health record data for genetic research as well as novel approaches and significant initiatives contributing toward precision medicine. ? 2017 Elsevier Inc.