Publications by authors named "Kumar Ankur"

49 Publications

Conformational dynamics of 13 amino acids long NSP11 of SARS-CoV-2 under membrane mimetics and different solvent conditions.

Microb Pathog 2021 Jun 10;158:105041. Epub 2021 Jun 10.

School of Basic Sciences, Indian Institute of Technology Mandi, Kamand, Himachal Pradesh, 175005, India. Electronic address:

The intrinsically disordered proteins/regions (IDPs/IDPRs) are known to be responsible for multiple cellular processes and are associated with many chronic diseases. In viruses, the existence of a disordered proteome is also proven and is related to its conformational dynamics inside the host. The SARS-CoV-2 has a large proteome, in which, structure and functions of all proteins are not known yet, along with non-structural protein 11 (nsp11). In this study, we have performed extensive experimentation on nsp11. Our results based on the CD spectroscopy gives characteristic disordered spectrum for IDPs. Further, we investigated the conformational behavior of nsp11 in the presence of membrane mimetic environment, α-helix inducer, and natural osmolyte. In the presence of negatively charged and neutral liposomes, nsp11 remains disordered. However, with SDS micelle, it adopted an α-helical conformation, suggesting the helical propensity of nsp11. Finally, we again confirmed the IDP behavior of nsp11 using MD simulations. In future, this conformational dynamic study could help to clarify its functional importance in SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micpath.2021.105041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191288PMC
June 2021

Salvianolic acid B noncovalently interacts with disordered c-Myc: a computational and spectroscopic-based study.

Future Med Chem 2021 Jun 11. Epub 2021 Jun 11.

Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.

c-Myc, along with its partner MAX, regulates the expression of several genes, leading to an oncogenic phenotype. The MAX interacting interface of c-Myc is disordered and uncharacterized for small molecule binding. Salvianolic acid B possesses numerous therapeutic properties, including anticancer activity. The current study was designed to elucidate the interaction of the Sal_Ac_B with the disordered bHLH domain of c-Myc using computational and biophysical techniques. The binding of Sal_Ac_B with Myc was studied using computational and biophysical techniques, including molecular docking and simulation, fluorescence lifetime, circular dichroism and anisotropy. The study demonstrated a high binding potential of Sal_Ac_B against the disordered Myc peptide. The binding of the compounds leads to an overall conformational change in Myc. Moreover, an extensive simulation study showed a stable Sal_Ac_B/Myc binding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2021-0087DOI Listing
June 2021

Complexities of pyridoxine response in PNPO deficiency.

Epilepsy Behav Rep 2021 3;16:100443. Epub 2021 Apr 3.

Pediatric Neurology, Department of Pediatrics, Kalawati Saran Children's Hospital, Delhi, India.

Pyridox(am)ine- 5- phosphate Oxidase deficiency (PNPO) is a rare cause of neonatal metabolic encephalopathy associated with refractory status epilepticus. We report a case of a premature neonate presenting with drug-resistant seizures beginning at 2 hours of life. The baby showed initial transient response to pyridoxine followed by recurrence. Genetic report confirmed the diagnosis of PNPO deficiency. A literature review on phenotypic variants in terms of response to pyridoxine is also presented along with a proposed algorithm to manage a case of suspected vitamin responsive epilepsy. This case highlights our limited understanding of why variation in response to treatment exists in children with PNPO deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebr.2021.100443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082192PMC
April 2021

Tumor Occupancy Ratio-An Imaging Characteristic Prognosticating the Surgical Outcome of Benign Intradural Extramedullary Spinal Cord Tumors.

Int J Spine Surg 2021 Jun 7;15(3):570-576. Epub 2021 May 7.

Department of Neurosurgery, Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow, India.

Background: Intradural extramedullary (IDEM) spinal cord tumors are two thirds of all spinal tumors. We have prospectively analyzed the importance of the tumor occupancy ratio as a factor for predicting the course of the disease and in prognosticating the surgical outcome in patients with IDEM tumors.

Methods: We prospectively analyzed 44 consecutive cases of IDEM tumors, diagnosed as cervical, thoracic, and lumbar IDEM tumors (excluding conus/cauda equina lesion) by magnetic resonance imaging (MRI), that were operated on at our institution between 2014 and 2016. We measured the tumor occupancy ratio and noted the sagittal and axial location of the tumor in the preoperative MRI and performed the laminectomy and unilateral medial facetectomy. A primary outcome has been noted according to the gait disability score in the preoperative period and in the follow-up period of 1 year. In the statistical analysis, categorical variables were compared using a chi-square test, and an analysis of variance and student tests were used for the continuous variables. < .05 was considered statistically significant.

Results: The tumor occupancy ratio showed a significant association to the preoperative gait disability score ( < .001) and also predicted that the surgical outcome is much better in patients with tumors with a low tumor occupancy ratio than in patients with tumors with a high occupancy ratio ( < .001). No difference in the tumor occupancy ratio was noted in 2 different pathological tumors, and there was also no difference in the tumor occupancy ratio at different sagittal and axial locations of the tumor.

Conclusion: Tumor occupancy ratio has shown a significant impact on the preoperative course and also predicts the surgical outcome in patients with IDEM tumors. Hence, it is an important imaging characteristic to prognosticate the outcome in IDEM tumors and should be noted in each case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14444/8077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176837PMC
June 2021

Pleura-based mass clinicoradiologically construed as lung carcinoma, revealing an occult primary papillary thyroid carcinoma (BRAF positive).

Indian J Pathol Microbiol 2021 Apr-Jun;64(2):432-434

Department of Radiodiagnosis, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/IJPM.IJPM_93_20DOI Listing
April 2021

Development and Evaluation of Active Case Detection Methods to Support Visceral Leishmaniasis Elimination in India.

Front Cell Infect Microbiol 2021 24;11:648903. Epub 2021 Mar 24.

Independent Consultant, Bangkok, Thailand.

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 ACD (15 (0.8%) house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with <30 days as the referent). ACD and younger age were associated with shorter time to diagnosis, while male sex and HIV infection were associated with longer illness durations. The advantage of ACD over PCD was more marked for longer illness durations: the adjusted odds ratios for having illness durations of 30-59, 60-89 and >=90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.648903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024686PMC
March 2021

Mixed Cutaneous Infection Caused by Leishmania and Dermatophytes: A Rare Coincidence or Immunological Fact.

Case Rep Dermatol Med 2021 8;2021:5526435. Epub 2021 Mar 8.

Department of Biochemistry, Baba Raghav Das Medical College, Gorakhpur, Uttar Pradesh 273013, India.

Leishmaniasis was first described in 1824, in the Jessore district of Bengal (now Bangladesh) and more prevalent in Bihar, Uttar Pradesh, Jharkhand, and West Bengal. The disease is associated with depressed cellular immunity. Tinea is a fungal infection of the skin, which can become more extensively pathogenic particularly in patients with depressed cell-mediated immunity. Regulatory T cells and Th17 cells have been shown to be responsible for post-kala-azar dermal leishmaniasis (PKDL). We present a rare case of a 52-year-old house wife with a history of recurrent itching, depigmentation of the skin of extremities, and loss of appetite for 2-3 months followed by progressive spread of such lesion all over the body in an apparently healthy female. On examination, there were many hypopigmented scaly lesions mainly over the extensor aspect of the body. Skin lesions were characteristics of tinea infection with or without PKDL. A diagnosis of PKDL with tinea was made based on the history of kala-azar and on the skin slit smear for amastigote forms, test, and KOH mount. Routine blood investigations showed negative serology for HIV and lower normal CD4+T counts. The patient was advised for treatment on systemic antifungal therapy with antihistaminics and later with miltefosine. We have highlighted that PKDL, although uncommon, is a distinct manifestation of VL. In our case study, we also tried to find the reason of coinfection; this was probably due to the depressed cellular immunity, skin abruptions, and acquired dermatophytic infection which is prevalent and associated with lower CD4+ T cell count.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5526435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963913PMC
March 2021

Treatment Outcomes in Aspirin-Exacerbated Respiratory Disease Based on the 12-Item Short Form Survey.

Am J Rhinol Allergy 2021 Mar 10:19458924211001640. Epub 2021 Mar 10.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Aspirin-exacerbated respiratory disease (AERD) is optimally managed by endoscopic sinus surgery (ESS) followed by aspirin therapy after desensitization (ATAD). Most AERD quality of life (QOL) studies use the 22-item Sinonasal Outcomes Test (SNOT-22), which focuses predominantly on sinonasal outcomes.

Objective: This study seeks to assess QOL outcomes in AERD patients after ESS and ATAD via the 12-item Short Form Survey (SF-12), a well-validated QOL measure for general health status of chronic conditions.

Methods: Retrospective review of 112 AERD patients who underwent ESS followed by ATAD at our institution between 2016 and 2019. SF-12 was collected preoperatively, postoperatively/pre-AD, and serially post-AD (1-3, 4-6, 7-12, and >12 months). Optum® PRO CoRE software was used to compare data to national norms. ANOVA was performed comparing physical component summary (PCS), mental component summary (MCS) and eight health domains (physical functioning, role physical, general health, bodily pain, vitality, social functioning, role emotional, and mental health).

Results: AERD patients showed improvement in PCS scores across all timepoints after ESS and ATAD (p = 0.004). When stratified by gender, women demonstrated an improvement in PCS scores (p = 0.004). Within the domains, there were significant improvements in social functioning (SF), role physical (RP), and bodily pain (BP) at all timepoints (SF: p = 0.006; RP: p = 0.005; BP: p < 0.001).

Conclusions: AERD patients undergoing ESS and ATAD show improvement in physical QOL and 3 of the 8 health domains as measured by the SF-12. Future studies can use the SF-12 to study the impact of AERD treatment versus other chronic diseases and health demographics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/19458924211001640DOI Listing
March 2021

Effectiveness of endoscopic sinus surgery and aspirin therapy in the management of aspirin-exacerbated respiratory disease.

Allergy Asthma Proc 2021 03;42(2):136-141

Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania; and.

Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2500/aap.2021.42.210002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133012PMC
March 2021

Experiments and simulation on ZIKV NS2B-NS3 protease reveal its complex folding.

Virology 2021 Apr 30;556:110-123. Epub 2021 Jan 30.

School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, 175005, Himachal Pradesh, India. Electronic address:

Zika virus has been identified in various body fluids such as semen, urine, saliva, cerebrospinal fluid, and vaginal secretion of an infected individual. The pH of these fluids varies from mildly acidic to mildly alkaline. So it is imperative to understand the impact of these conditions on viral protein functioning. We investigated the NS2B-NS3 protease stability and its activity in different denaturing environments. Finding indicates that NS2B-NS3 protease maintains stability at pH 4.8-8.7. Thus it suggests that the complex remains functionally active to hydrolyze the polyprotein within a diverse environmental condition such as variable pH. Despite a stable structure at a broad pH range, a change in environmental conditions dramatically influence its protease activity. Moreover, it is susceptible to structural transformation leading to increased β-strand or helix content in the presence of alcohol. This study may help further to understand the folding-function relationship of the general flaviviral protease complex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2021.01.014DOI Listing
April 2021

Quality attributes of convective hot air dried spine gourd (Momordica dioica Roxb. Ex Willd) slices.

Food Chem 2021 Jun 12;347:129041. Epub 2021 Jan 12.

Central Instrumentation Lab, Department of Basic and Applied Sciences, NIFTEM, HR, India.

In the present study, spine gourd slices were dried in a convective dryer at 40, 50, 60 and 70 °C temperature. The change in quality of spine guard was determined by analyzing the change in proximate, minerals, functional group, chlorophyll, ascorbic acid, and antioxidant characteristics. Increase in drying temperature changed the protein (4.62-12.88 g/100 g), fiber (3.14-3.53 g/100 g), total phenolic (14.85-14.99 mg gallic acid equivalent/g) and total flavonoid (30.1-64.8 mg quercetin equivalent/100 g) content while reduction occurred in fat (4.02-3.07 g/100 g), carbohydrate (76.13-55.22 g/100 g), chlorophyll (0.34-0.100 mg/g), ascorbic acid (29.94-4.50 mg/100 g) and antioxidant activity (96.58-85.06%). Mineral content of fresh SG differed significantly with dried samples (p < 0.05), while variable effects were associated with the change in drying temperatures. Changes in functional groups were analyzed by Fourier transform infrared spectrophotometer. The observed parameters were optimized using principal component analysis. The sample dried at 40 °C was superior in quality whereas higher protein and antioxidants were found at 70 °C.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2021.129041DOI Listing
June 2021

Reprofiling of approved drugs against SARS-CoV-2 main protease: an in-silico study.

J Biomol Struct Dyn 2020 Nov 12:1-15. Epub 2020 Nov 12.

School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India.

Given the COVID-19 pandemic, currently, there are many drugs in clinical trials against this virus. Among the excellent drug targets of SARS-CoV-2 are its proteases (Nsp3 and Nsp5) that plays vital role in polyprotein processing giving rise to functional nonstructural proteins, essential for viral replication and survival. Nsp5 (also known as M) hydrolyzes replicase polyprotein (1ab) at eleven different sites. For targeting M, we have employed drug repurposing approach to identify potential inhibitors of SARS-CoV-2 in a shorter time span. Screening of approved drugs through docking reveals Hyaluronic acid and Acarbose among the top hits which are showing strong interactions with catalytic site residues of M. We have also performed docking of drugs Lopinavir, Ribavirin, and Azithromycin on SARS-CoV-2 M. Further, binding of these compounds (Hyaluronic acid, Acarbose, and Lopinavir) is validated by extensive molecular dynamics simulation of 500 ns where these drugs show stable binding with M. We believe that the high-affinity binding of these compounds will help in designing novel strategies for structure-based drug discovery against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1845976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678354PMC
November 2020

Zika virus NS4A N-Terminal region (1-48) acts as a cofactor for inducing NTPase activity of NS3 helicase but not NS3 protease.

Arch Biochem Biophys 2020 11 17;695:108631. Epub 2020 Oct 17.

School of Basic Sciences, Indian Institute of Technology Mandi, VPO Kamand, Himachal Pradesh, 175005, India; BioX Centre, Indian Institute of Technology Mandi, Himachal Pradesh, India. Electronic address:

Among Flaviviridae, in West Nile virus (WNV) and Hepatitis C virus (HCV), the non-structural protein NS4A modulates the NTPase activity of viral helicases during nucleic acid unwinding through its N-terminal disordered residues (1-50). In HCV, the acidic NS4A also serves as a cofactor for regulating the NS3 protease activity. However, in case of Zika virus (ZIKV), the role of NS4A and its impact on activities of NS3 helicase and protease is not known. In order to elucidate the role of NS4A, we checked the NTPase activity of NS3 helicase and protease activity of NS3 protease in presence of NS4A N-terminal region (residues 1-48) peptide. Our enzyme kinetics results together with binding experiment clearly demonstrate that NS3 helicase in presence of NS4A peptide increased the rate of ATP hydrolysis whereas the protease activity of NS3 protease was not affected. Therefore, like WNV and HCV, our results establish a role of ZIKV NS4A being a cofactor for modulating the NTPase activity of ZIKV NS3 helicase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2020.108631DOI Listing
November 2020

Zika virus NS4A cytosolic region (residues 1-48) is an intrinsically disordered domain and folds upon binding to lipids.

Virology 2020 11 20;550:27-36. Epub 2020 Aug 20.

School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh, India; BioX Center, Indian Institute of Technology Mandi, Himachal Pradesh, India. Electronic address:

In flaviviruses, the NS4A is an integral transmembrane protein that contributes to form virus-induced membrane curvature. However, structural features of NS4A are not documented in Zika virus, and it is one of the least characterized proteins. Thus, this work focused on investigating the secondary structural elements of the Zika virus NS4A, where we characterized the cytosolic region of protein NS4A (residues 1-48) under variable environmental conditions. We found NS4A (residues 1-48) as an intrinsically disordered domain that has an intrinsic ability to form helical fold in the presence of membranous environment, osmolyte, and fluoro alcohol. The conformational change in NS4A (residues 1-48) secondary structure upon interaction with lipid vesicles can be correlated with the disorder-function paradigm concept. This change in NS4A (residues 1-48) secondary structure may suggest its implication in membrane rearrangement and replication complex formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2020.07.017DOI Listing
November 2020

Relevance of Nanomaterials in Food Packaging and its Advanced Future Prospects.

J Inorg Organomet Polym Mater 2020 Jul 19:1-13. Epub 2020 Jul 19.

Department of Horticulture, Sardar Vallabh Bhai Patel University of Agriculture and Technology, Meerut, Uttar Pradesh India.

Biopolymers have been used in packaged foods to tackle environmental hazards due to their biodegradability and non-toxic nature. In addition to these merits, they have also several demerits such as poor mechanical properties and low resistance towards water. Nanomaterials have attracted great interest in recent years due to their phenomenal properties that makes them precedent in applications for food packaging as they enhance the mechanical, thermal and gas barriers properties, without compromising with the ability to become non-toxic and biodegradable. The most important nanomaterials used in food packaging are montmorillonite (MMT), zinc oxide (ZnO-NPs) coated silicate, kaolinite, silver NPs (Ag-NPs) and titanium dioxide (TiONPs) as these, nanomaterials coated films makes a barrier against oxygen, carbon dioxide and favour compounds. They also possess oxygen scavenging capability, antimicrobial activity and tolerance towards temperature. The most difficult task related to the preparation of these nanocomposites is their complete distribution within the polymer matrix and their compatibility. Therefore, there is an increasing demand for improvement in the performance of nano-packaging materials including mechanical stability, degradability and effectiveness of antibacterial property.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10904-020-01674-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368925PMC
July 2020

Major complications of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease.

Int Forum Allergy Rhinol 2021 Feb 16;11(2):115-119. Epub 2020 Jul 16.

Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA.

Background: Treatment of aspirin-exacerbated respiratory disease (AERD) includes endoscopic sinus surgery (ESS) and aspirin desensitization (AD) with aspirin therapy after desensitization (ATAD). The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy.

Methods: This study was a retrospective chart review of patients with AERD who underwent ESS, AD, and ATAD at a single AERD tertiary center between July 2016 and February 2019. Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression.

Results: In total, 109 AERD patients underwent ESS with subsequent AD. Ten patients (9.2%) discontinued therapy after AD, before starting ATAD. Eight patients (7.3%) discontinued therapy after starting ATAD. There were 91 patients (83.5%) with no complications throughout ATAD. Reasons for discontinuation included gastritis, upper gastrointestinal (GI) bleed, anaphylaxis, persistent sinonasal symptoms, recurrent epistaxis, asthma exacerbation, and a nummular rash. There was no significant correlation between complication rate and (1) aspirin doses (analysis of variance [ANOVA] F: 0.69; p = 0.51), (2) gender (odds ratio [OR] 0.56; 95% confidence interval [CI], 0.19 to 1.65; p = 0.30), (3) age (OR 1.04; 95% CI, 0.96 to 1.09; p = 0.06), or (4) race/ethnicity (OR 1.12; 95% CI, 0.88 to 1.44; p = 0.36).

Conclusion: AD with ATAD was associated with only a 0.92% incidence of a clinically significant GI bleed, and only a 0.92% incidence of anaphylaxis. A remaining 16 patients (14.7%) discontinued aspirin therapy due to minor clinical sequelae. These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22643DOI Listing
February 2021

Statistical inferences from measured data on concentrations of naturally occurring radon, thoron, and decay products in Kumaun Himalayan belt.

Environ Sci Pollut Res Int 2020 Nov 13;27(32):40229-40243. Epub 2020 Jul 13.

Department of Physics, HNBGU Badshahithaul New Tehri, New Tehri, Uttarakhand, India.

Regional averages of radon, thoron, and associated decay product concentration are reported to be higher than their respective global averages in recent studies conducted in Indian Himalayan belt. The present study explores another region in Indian Himalayan belt by conducting measurements of radon, thoron, and decay product's activity concentration in 92 dwellings of Bageshwar district. The year-long measurements were performed in all 3 seasons distinguishing dwellings as per their construction material. The average radon and thoron concentration for the study region was measured as 57 Bq/m and 66 Bq/m, respectively. Analysis of the measured data in terms of seasonal effects and construction material led to well established inferences, i.e., higher concentration for mud houses and for winter season. In addition, the present study focuses on lesser probed statistical inferences. One of them is related to the appropriateness of frequency distribution function for the measured data and other dwells upon the correlation analysis of inter-related factors for high concentration cases. Three distribution functions (Lognormal, Weibull, and Gamma) were found to be following the trend of frequency distribution curve of the measured data. For mud houses in winter season, variations of radon/thoron concentration were attempted to correlate with mass/surface exhalation rate, emanation rate, and source term content. More than 80% of the dwellings of the study region were found to have gas and decay product's concentration levels, higher than the respective global average values. However, these values were mostly within the reference levels for residential environments. Nevertheless, this region requires further studies to pinpoint the causes for elevated levels and suggest simple remedial modifications if required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-09920-9DOI Listing
November 2020

H-Bond Surrogate-Stabilized Shortest Single-Turn α-Helices: sp Constraints and Residue Preferences for the Highest α-Helicities.

ACS Omega 2020 Jun 2;5(23):13902-13912. Epub 2020 Jun 2.

Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India.

Short α-helical sequences of proteins fail to maintain their native conformation when taken out of their protein context. Several covalent constraints have been designed, including the covalent H-bond surrogate (HBS)-where a peptide backbone + 4 → H-bond is replaced by a covalent surrogate-to nucleate α-helix in short sequences (>7 < 15 amino acids). But constraining the shortest sequences (four amino acids) into a single α-helical turn is still a significant challenge. Here, we introduce an HBS model that can be placed in unstructured tetrapeptides without excising any of its residues, and that biases them predominantly into remarkably stable single α-helical turns in varying solvents, pH values, and temperatures. Circular dichroism (CD), Fourier transform infrared (FT-IR) absorption, one-dimensional (1D)-NMR, two-dimensional (2D)-NMR spectral and computational analyses of the HBS-constrained tetrapeptide analogues reveal that (a) the number of sp atoms in the HBS-constrained backbone influences their predominance and rigidity in the α-helical conformation; and (b) residue preferences at the unnatural HBS-constrained positions influence their α-helicities, with Moc[GFA]G-OMe () showing the highest known α-helicity (θ ∼-25.3 × 10 deg cm dmol at 228 nm) for a single α-helical turn. Current findings benefit chemical biological applications desiring predictable access to single α-helical turns in tetrapeptides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.0c01277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301546PMC
June 2020

Evaluation of Taenia solium cyst fluid-based enzyme linked immunoelectro transfer blot for Neurocysticercosis diagnosis in urban and highly endemic rural population of North India.

Clin Chim Acta 2020 Sep 7;508:16-21. Epub 2020 May 7.

School of Basic Sciences, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh 175005, India. Electronic address:

Background: Neurocysticercosis (NCC) is infection by cestode Taenia solium/pork tapeworm. Sero-diagnosis of NCC is still a challenge. Radiological imaging (CT/MRI) are cost intensive, requires technical expertise and resource intensive. Hence, its availability is restricted in endemic zone. Existing Enzyme electro immune transfer blot (EITB) antigens are difficult to make and is not standardized for endemic population. Therefore, there is a definite need for easy and reliable EITB tool.

Methods: T. solium metacestode were harvested from naturally infected swine post slaughter. The cyst fluid/vesicular fluid was aspirated and processed with ultracentrifugation and immune blot was performed with this antigen.

Results: A total of 406 cases [rural 256 (NCC 78, seizures other than NCC 108 and healthy controls 70); urban 150 (NCC 41, seizures other than NCC 59 and healthy controls 50)] were enrolled. Positive EITB (detection of band <50 kDa) was significantly associated with NCC patients of urban population only (p < 0.001) but not in rural populations (p = 0.292). However, identification of 15 kDa band had significant association with NCC both in urban and rural populations with overall sensitivity of 91.5% and specificity of 91.6%. Presence of 35 kDa band was associated with multiple NCC (p < 0.001). The study shows that 15 kDa reactive band on EITB is highly sensitive and specific for diagnosis of NCC in endemic population.

Conclusions: Presence of 35 kDa band on EITB was associated with infection by multiple cysticerci. The observations demand purification of cyst fluid antigens to develop simple and easy to execute test in field studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2020.05.006DOI Listing
September 2020

Investigating into the molecular interactions of flavonoids targeting NS2B-NS3 protease from ZIKA virus through approaches.

J Biomol Struct Dyn 2021 Jan 10;39(1):272-284. Epub 2020 Jan 10.

School of Basic Science, Indian Institute of Technology Mandi, Mandi, India.

Zika virus (ZIKV), belongs to the flavivirus genus and Flaviviridae family that associated with serious diseased conditions like microcephaly and other neurological disorders (Guillan-Barré syndrome). As there is no vaccine or therapies available against ZIKV to date. Hence, it is an unmet need to find potential drug candidates and target sites against Zika virus infection. NS2B-NS3 protease making an attractive target for therapeutic intervention in ZIKV infections because of its critical role in hydrolysis of a single polyprotein encoded by Zika virus. Recently, there are some experimental evidence about the flavonoids as Zika virus NS2B-NS3 protease inhibitors. However, molecular interaction between protease complex and inhibitors at atomic levels has not been explored. Here, we have taken the experimentally validated thirty-eight flavonoids inhibitors against NS2B-NS3 protease to examine the molecular interaction using molecular docking and molecular dynamics simulations. We found out few flavonoids such as EGCG and its two derivatives, isoquercetin, rutin and sanggenon O showing interaction with catalytic triad (His51, Asp75, and Ser135) of the active site of NS2B-NS3 protease and found to be stable throughout the simulation. Therefore it is evident that interaction with the catalytic triad playing a vital role in the inhibition of the enzyme activity as a result inhibition of the virus propagation. However these compounds can be explored further for understanding the mechanism of action of these compounds targeting NS2B-NS3 protease for inhibition of Zika virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2019.1709546DOI Listing
January 2021

Mental Wellbeing, Quality of Life, and Perception of Chronic Illness in Yoga-Experienced Compared with Yoga-Naïve Patients.

Med Sci Monit Basic Res 2019 May 20;25:153-163. Epub 2019 May 20.

Department of Yoga Research, Patanjali Research Foundation, Haridwar, Uttarakhand, India.

BACKGROUND Perception of chronic illness and a positive outlook improve recovery, and yoga can improve wellbeing. This study aimed to compare perception, mental wellbeing, and quality of life in yoga-experienced compared with yoga-naïve patients with chronic illness and to determine whether the duration of yoga practice in the yoga-experienced group had any correlation with the perception of illness, mental wellbeing, and quality of life. MATERIAL AND METHODS A cross-sectional comparative study recruited 419 patients with chronic non-communicable disease. Yoga-experienced patients (n=150) (mean age, 41.9±13.6 years) and yoga-naïve patients (n=269) (mean age, 41.2±12.6 years) were assessed for the perception of their illness, mental wellbeing, and quality of life using the Warwick-Edinburgh mental wellbeing scale (WEMWBS) and the World Health Organization quality of life (WHOQOL-BREF) self-reporting questionnaire. RESULTS The yoga-experienced group had significantly increased mental wellbeing, personal control as a dimension of their perception of illness, and psychological and environmental quality of life compared with the yoga-naïve group (all, p<0.05), when comparisons were made using the Mann-Whitney U test. The duration of yoga practised in months was positively-correlated with mental wellbeing and different aspects of quality of life. There was a negative correlation with the perception of illness suggesting that the illness was perceived to be less severe (all, p<0.05) when correlations were made using Spearman's rank correlation coefficient. CONCLUSIONS In patients with chronic illness, yoga improved mental wellbeing, aspects of quality of life, and resulted in a positive perception of illness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSMBR.914663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542302PMC
May 2019

Epidemiological characterization of dermatophytes at a tertiary care hospital in Eastern Uttar Pradesh, India.

Curr Med Mycol 2019 Mar;5(1):1-6

Department of Microbiology, Baba Raghav Das Medical College, Gorakhpur, Uttar Pradesh, India.

Background And Purpose: Superficial mycosis is more prevalent in tropical and subtropical countries, such as India. Regarding this, the present study was conducted to determine the epidemiology of superficial mycosis and identify the most common dermatophytic species in this region.

Materials And Methods: For the purpose of the study, a total of 220 skin scraping, nail, and hair root specimens were collected. Direct microscopic examination was performed using potassium hydroxide mount. Additionally, the samples were inoculated onto Sabouraud dextrose agar (SDA) and dermatophyte test medium (DTM). The fungal colony of each isolates was stained with lactophenol cotton blue mount, and observed under microscope for species identification.

Results: Out of 220 isolates, 172 samples, obtained from 108 males 64 females, were positive for skin fungal infections by either KOH mount or culture. Furthermore, 113 isolates were identified as dermatophytes, while 59 samples were found to be non-dermatophytes. Among the dermatophytes isolated from different clinical samples, (42/113, 38%) was the most common species, and was the most common infection (36.2%).

Conclusion: As the findings indicated, dermatophytes had an isolation rate of 78%, which is higher than normal. This can be due to the fact that the majority of the patients were from a rural background (71.7%) with a low socioeconomic status and poor personal hygiene who were exposed to climatic changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18502/cmm.5.1.530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488285PMC
March 2019

Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease.

ACS Omega 2018 Dec 24;3(12):18132-18141. Epub 2018 Dec 24.

Indian Institute of Technology Mandi, Mandi 175005, Himachal Pradesh, India.

Zika virus is a mosquito-transmitted flavivirus that causes devastating fetal outcomes in the context of maternal infection during pregnancy. An important target for drugs combatting Zika virus pathogenicity is NS2B-NS3 protease, which plays an essential role in hydrolysis and maturation of the flavivirus polyprotein. We identify hydroxychloroquine, a drug that already has approved uses in pregnancy, as a possible inhibitor of NS2B-NS3 protease by using a Food and Drug Administration-approved drug library, molecular docking, and molecular dynamics simulations. Further, to gain insight into its inhibitory potential toward NS2B-NS3 protease, we performed enzyme kinetic studies, which revealed that hydroxychloroquine inhibits protease activity with an inhibition constant () of 92.34 ± 11.91 μM. Additionally, hydroxychloroquine significantly decreases Zika virus infection in placental cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.8b01002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312647PMC
December 2018

Utilization of Open Source Technology to Create Cost-Effective Microscope Camera Systems for Teaching.

J Pathol Inform 2018 25;9:19. Epub 2018 May 25.

Department of Pathology, Shri B. M. Patil Medical College Hospital and Research Center, BLDE (Deemed to be University), Vijayapura, Karnataka, India.

Background: Open source technologies and mobile innovations have radically changed the way people interact with technology. These innovations and advancements have been used across various disciplines and already have a significant impact. Microscopy, with focus on visually appealing contrasting colors for better appreciation of morphology, forms the core of the disciplines such as Pathology, microbiology, and anatomy. Here, learning happens with the aid of multi-head microscopes and digital camera systems for teaching larger groups and in organizing interactive sessions for students or faculty of other departments.

Methods: The cost of the original equipment manufacturer (OEM) camera systems in bringing this useful technology at all the locations is a limiting factor. To avoid this, we have used the low-cost technologies like Raspberry Pi, Mobile high definition link and 3D printing for adapters to create portable camera systems.

Results: Adopting these open source technologies enabled us to convert any binocular or trinocular microscope be connected to a projector or HD television at a fraction of the cost of the OEM camera systems with comparable quality.

Conclusion: These systems, in addition to being cost-effective, have also provided the added advantage of portability, thus providing the much-needed flexibility at various teaching locations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jpi.jpi_15_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989535PMC
May 2018

Deciphering the dark proteome of Chikungunya virus.

Sci Rep 2018 04 11;8(1):5822. Epub 2018 Apr 11.

School of Basic Sciences, Indian Institute of Technology Mandi, Himachal Pradesh, 175005, India.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. The outbreak of CHIKV infection has been seen in many tropical and subtropical regions of the biosphere. Current reports evidenced that after outbreaks in 2005-06, the fitness of this virus propagating in Aedes albopictus enhanced due to the epistatic mutational changes in its envelope protein. In our study, we evaluated the prevalence of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) in CHIKV proteome. IDPs/IDPRs are known as members of a 'Dark Proteome' that defined as a set of polypeptide segments or whole protein without unique three-dimensional structure within the cellular milieu but with significant biological functions, such as cell cycle regulation, control of signaling pathways, and maintenance of viral proteomes. However, the intrinsically disordered aspects of CHIKV proteome and roles of IDPs/IDPRs in the pathogenic mechanism of this important virus have not been evaluated as of yet. There are no existing reports on the analysis of intrinsic disorder status of CHIKV. To fulfil this goal, we have analyzed the abundance and functionality of IDPs/IDPRs in CHIKV proteins, involved in the replication and maturation. It is likely that these IDPs/IDPRs can serve as novel targets for disorder based drug design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-23969-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895634PMC
April 2018

Recent advances in pediatric rheumatology: October to December 2016.

Int J Rheum Dis 2018 Feb 17;21(2):544-545. Epub 2017 Oct 17.

Pediatric Allergy Immunology Unit, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.13200DOI Listing
February 2018

Comparative evaluation of apical microleakage in immediate and delayed postspace preparation using four different root canal sealers: An study.

J Conserv Dent 2017 Mar-Apr;20(2):86-90

Department of Conservative Dentistry and Endodontics, M R Ambedkar Dental College and Hospital, Bengaluru, Karnataka, India.

Background: Endodontically treated teeth often lack sufficient support for a permanent restoration. During post space preparation, it is important not to disturb the integrity of the apical seal.

Aim: This study compared the effect of immediate versus delayed post space preparation on the apical seal using four different sealers.

Materials And Methods: One hundred and thirty single rooted teeth were biomechanically prepared and obturated with single cone gutta-percha and 4 sealers: Endoflas FS, AH Plus, Gutta flow and MTA. Teeth were divided randomly into eight groups, post spaces were prepared using Gates Glidden drills immediately for group I, III, IV and VII. For groups II, IV, VI and VIII prepared after storage of the specimens in 100% humidity for one week. The samples were kept in methylene blue dye, centrifuged at 3000 rpm for 3 min sectioned and then measured under stereomicroscope for apical leakage.

Statistical Analysis: The data was analysed using one way ANOVA and Tukey test.

Results: All the specimens showed dye leakage, and a statistically significant difference was seen among all the groups ( > 0.05) except Gutta flow.

Conclusion: Less leakage is seen when post space is prepared immediately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0972-0707.212230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564250PMC
September 2017

Viscoelastic-augmented trabeculectomy: A newer concept.

Indian J Ophthalmol 2017 Aug;65(8):705-711

Department of Ophthalmology, SMS Medical College, Anand Eye Hospital, Jaipur, Rajasthan, India.

Purpose: Comparison of conventional trabeculectomy (CT) and viscoelastic-augmented trabeculectomy (VAT) in primary open-angle glaucoma.

Methods: A total of 65 primary open-angle glaucoma cases were taken for each of the two groups, i.e., CT and VAT. Viscoelastic-augmented trabeculectomy constituted lamellar scleral flap, deep scleral flap, penetrating trabeculectomy, peripheral iridectomy, filling of the anterior chamber with viscoelastic (sodium hyaluronate) and balanced salt solution, movement of visco in bleb, and tight flap closure. Success criteria included intraocular pressure (IOP) <14 mmHg with no devastating complications. P < 0.05 was considered statistically significant.

Results: Mean IOP was significantly lower after VAT compared to CT at 6 weeks, 12 weeks, and 6 months postoperatively. Target IOP was achieved in 60% cases in VAT group compared to 36.92% in CT group.

Conclusion: VAT is effective in reducing IOP to the target level for advanced glaucoma with lower postoperative complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijo.IJO_162_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598181PMC
August 2017