Publications by authors named "Arun Kumar"

1,060 Publications

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Phytochemicals from Plant Foods as Potential Source of Antiviral Agents: An Overview.

Pharmaceuticals (Basel) 2021 Apr 19;14(4). Epub 2021 Apr 19.

Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being.
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http://dx.doi.org/10.3390/ph14040381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073840PMC
April 2021

A comparative study on the safety and efficacy of naltrexone versus baclofen versus acamprosate in the management of alcohol dependence.

Indian J Psychiatry 2020 Nov-Dec;62(6):650-658. Epub 2020 Dec 12.

Department of Psychiatry, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India.

Background: The efficacy of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence has been successfully established over the past several years. The knowledge about their relative efficacies can facilitate in developing relapse prevention strategies that would give rise to a greater personal and socioeconomic benefits.

Aims And Objective: To assess and compare the safety and efficacy profile of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence. In addition to this, the pattern of relapse and attitude of patients toward the treatment were also assessed.

Materials And Methods: This was a prospective study carried out at a tertiary care center. It comprised of thirty alcohol-dependent patients each assigned to naltrexone, baclofen, and acamprosate group after detoxification. The patients were assessed for craving, relapse risk, and medication adherence using the respective scales and questionnaires.

Results: In terms of Obsessive Compulsive Drinking Scale score decline, the decline seen in the naltrexone group (26.72 ± 13.05) was maximum, followed by baclofen and acamprosate. In terms of decreasing Advance Warning of Relapse (AWARE) questionnaire score, again naltrexone was most effective, with the maximum decline in AWARE score (64.72 ± 45.65), followed by baclofen and acamprosate. The attitude toward treatment with all the three medications was positive, as per the Hogan Drug Attitude Inventory score.

Conclusion: Naltrexone was most effective in decreasing craving and drinking behavior. Baclofen showed best tolerability in terms of liver function tests and least number of side effects reported. Naltrexone group reported the least number of relapses but maximum number of side effects. Acamprosate group had the maximum dropout rate.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_201_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052868PMC
December 2020

Pharmacogenetic evaluation of 6-mercaptopurine-mediated toxicity in pediatric acute lymphoblastic leukemia patients from a South Indian population.

Pharmacogenomics 2021 Apr 20. Epub 2021 Apr 20.

Department of Human Genetics, Sri Ramachandra Institute of Higher Education & Research, Chennai, India.

To evaluate the variants in the genes coding for the proteins involved in thiopurine and folate metabolism with treatment related adverse effects (TRAEs). Eleven variants in seven candidate genes were genotyped in 127 pediatric acute lymphoblastic leukemia patients under 6-mercaptopurine (6-MP) treatment to infer the association of selected genotypes with TRAEs. Among the genotypes inspected, (c.415C>T) and (c.80G>A) showed a significant association with the TRAEs (odds ratio = 4.01, p = 0.002 and odds ratio = 7.78, p = 0.002). and play an important role in the metabolism of 6-MP and it is necessary to spot other variants in associated pathways and investigate the factors that can impact 6-MP metabolism.
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http://dx.doi.org/10.2217/pgs-2020-0193DOI Listing
April 2021

Status Report on COVID-19 Vaccines Development.

Curr Infect Dis Rep 2021 14;23(6). Epub 2021 Apr 14.

Vaccine Research and Development, Coalition for Epidemic Preparedness Innovation (CEPI), Marcus Thranes Gate, 0473 Oslo, Norway.

Purpose Of Review: The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected lives of billions of individuals, globally. There is an urgent need to develop interventions including vaccines to control the ongoing pandemic.

Recent Findings: Development of tools for fast-tracked testing including small and large animal models for vaccine efficacy analysis, assays for immunogenicity assessment, critical reagents, international biological standards, and data sharing allowed accelerated development of vaccines. More than 300 vaccines are under development and 9 of them are approved for emergency use in various countries, with impressive efficacy ranging from 50 to 95%. Recently, several new SARS-CoV-2 variants have emerged and are circulating globally, and preliminary findings imply that some of them may escape immune responses against previous variants and diminish efficacy of current vaccines. Most of these variants acquired new mutations in their surface protein (Spike) which is the antigen in most of the approved/under development vaccines.

Summary: In this review, we summarize novel and traditional approaches for COVID-19 vaccine development including inactivated, attenuated, nucleic acid, vector and protein based. Critical assessment of humoral and cell-mediated immune responses induced by vaccines has shown comparative immunogenicity profiles of various vaccines in clinical phases. Recent reports confirmed that some currently available vaccines provide partial to complete protection against emerging SARS-CoV-2 variants. If more mutated variants emerge, current vaccines might need to be updated accordingly either by developing vaccines matching the circulating strain or designing multivalent vaccines to extend the breadth.
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http://dx.doi.org/10.1007/s11908-021-00752-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043838PMC
April 2021

The presence of Wormian bones increases the fracture resistance of equine cranial bone.

PLoS One 2021 16;16(4):e0249451. Epub 2021 Apr 16.

School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland.

Wormian (intrasutural) bones are small, irregular bones, that are found in the cranial sutures of the skull. The occurrence of Wormian bones in human skulls has been well documented but few studies have detected the presence of such bones in domestic animals. Although some research has linked the presence of Wormian bones to bone pathology, its anatomical significance in healthy individuals is not known. To the best of our knowledge, no previous study has examined the biomechanical features of Wormian bone. This study uses microCT imaging of the parietal bone region to determine the frequency of occurrence of Wormian bones in horse skulls and, through 3-point bending tests, to calculate the mechanical differences that result from the presence of such bones. In addition, bone properties such as bone mineral density (BMD) and stiffness were measured and analysed to determine the influence of Wormian bone. Our findings on 54 specimens taken from 10 horses (ages ranging from 4 to 29 years) showed that Wormian bone was present in 70% of subjects and that its occurrence was unrelated to age or sex. 3-point bend tests revealed that the stiffness normalised by cross section area (P = 0.038) was lower in samples where Wormian bone was present. An idealised Finite Element simulation confirmed that the presence of Wormian bone reduced the maximum stress and strain, as well as their distribution throughout the sample. We consequently conclude that the presence of Wormian bones, which are confined to the calvaria, increase the compliance of the bone and reduce the likelihood of skull fracture. As all skull samples were collected from a local abattoir, ethical approval was not required for this work.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249451PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051753PMC
April 2021

Materials for Improving Immune Cell Transfection.

Adv Mater 2021 Apr 15:e2007421. Epub 2021 Apr 15.

Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.

Chimeric antigen receptor T cell (CAR-T) therapy holds great promise for preventing and treating deadly diseases such as cancer. However, it remains challenging to transfect and engineer primary immune cells for clinical cell manufacturing. Conventional tools using viral vectors and bulk electroporation suffer from low efficiency while posing risks like viral transgene integration and excessive biological perturbations. Emerging techniques using microfluidics, nanoparticles, and high-aspect-ratio nanostructures can overcome these challenges, and on top of that, provide universal and high-throughput cargo delivery. Herein, the strengths and limitations of traditional and emerging materials for immune cell transfection, and commercial development of these tools, are discussed. To enhance the characterization of transfection techniques and uptake by the clinical community, a list of in vitro and in vivo assays to perform, along with relevant protocols, is recommended. The overall aim, herein, is to motivate the development of novel materials to meet rising demand in transfection for clinical CAR-T cell manufacturing.
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http://dx.doi.org/10.1002/adma.202007421DOI Listing
April 2021

Recent Advancements in Pharmaceutical Cocrystals, Preparation Methods and Their Applications.

Curr Pharm Des 2021 Apr 14. Epub 2021 Apr 14.

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak (Haryana). India.

The issue of poor aqueous solubility is a major hurdle in pharmaceutical dosage forms design. A large number of active molecules in the research and development pipeline are known to possess poor aqueous solubility and hence are not suitable for further development. Therefore, the pharmaceutical industry is continuously in search of techniques to tackle the issue of poor solubility. Cocrystallization has gained popularity as one such technique for the modulation of physicochemical properties of an active pharmaceutical ingredient (API). Pharmaceutical cocrystals consists of an API non-covalently linked to a crystal former or coformer that plays an important role in the imparting the desired properties to the cocrystal. Cocrystallization of an API with a suitable coformer not only enhances solubility but also helps in tweaking other physiochemical properties such as stability, bioavailability, mechanical properties, etc. without any change in the pharmacological activity of the API. The past decade saw an enormous growth in cocrystal research which paved the way for drug-drug, higher order and nano-sized cocrystals and further exploration of the applications of cocrystals is still going on. Recently FDA and EMA released regulatory guidelines for pharmaceutical cocrystals which grant them a status similar to that of polymorphs and salts which in turn opened a wider prospect for pharmaceutical cocrystals in terms of intellectual property.
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http://dx.doi.org/10.2174/1381612827666210415104411DOI Listing
April 2021

Mixed-Ligand Cobalt(III) Complexes of a Naturally Occurring Coumarin and Phenanthroline Bases as Mitochondria-Targeted Dual-Purpose Photochemotherapeutics.

Inorg Chem 2021 May 15;60(9):6649-6662. Epub 2021 Apr 15.

Department of Chemistry, Handique Girls' College, Guwahati 781001, Assam, India.

The bioessential nature of cobalt and the rich photochemistry of its coordination complexes can be exploited to develop potential next-generation photochemotherapeutics. A series of six novel mixed-ligand cobalt(III) complexes of the formulation [Co(B)(L)]ClO (-), where B is an N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in and ), dipyrido[3,2-:2',3'-]quinoxaline (dpq in and ), and dipyrido[3,2-:2',3'-]phenazine (dppz in and ), and L is an O,O-donor dianionic ligand derived from catechol (1,2-dihydroxybenzene, cat, in -) or esculetin (6,7-dihydoxycoumarin, esc, in -), have been prepared and characterized, and their light-triggered cytotoxicity has been studied in cancer cells. The single-crystal X-ray diffraction structures of complexes (as PF salt, ) and show distorted octahedral geometries around the cobalt(III) center formed by the set of NO donor atoms. The low-spin and 1:1 electrolytic complexes - display a d-d transition around 700 nm. Complexes - with a coordinated esc ligand additionally display a π → π* intraligand transition centered at 403 nm. Complexes - possessing a naturally occurring and photoactive esc ligand show high visible-light-triggered cytotoxicity against HeLa and MCF-7 cancer cells, yielding remarkably low micromolar IC values while being much less toxic under dark conditions. Control complexes - possessing the photoinactive cat ligand show significantly less cytotoxicity either in the presence of light or in the dark. The complex-induced cell death is apoptotic in nature caused by the formation of reactive oxygen species via a type 1 photoredox pathway. Fluorescence microscopy of HeLa cells treated with complex reveals mitochondrial localization of the complex. A significant decrease in the dark toxicity of free esculetin and dppz base is observed upon coordination to cobalt(III). Complexes bind to calf-thymus DNA with significant affinity, but binds with the greatest affinity. Complex efficiently photocleaves supercoiled DNA to its nicked circular form when irradiated with visible light via a photoredox type 1 pathway involving hydroxyl radicals (HO). Thus, complex showing remarkable visible-light-triggered cytotoxicity but negligible toxicity in the dark is a good candidate for cancer photochemotherapy applications.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00444DOI Listing
May 2021

Considerations for bioanalytical characterization and batch release of COVID-19 vaccines.

NPJ Vaccines 2021 Apr 13;6(1):53. Epub 2021 Apr 13.

Vaccine Research and Development, Coalition for Epidemics Preparedness Innovations, CEPI, Torshov, Oslo, Norway.

The COVID-19 pandemic has prompted hundreds of laboratories around the world to employ traditional as well as novel technologies to develop vaccines against SARS-CoV-2. The hallmarks of a successful vaccine are safety and efficacy. Analytical evaluation methods, that can ensure the high quality of the products and that can be executed speedily, must be in place as an integral component of Chemistry, Manufacturing, and Control (CMC). These methods or assays are developed to quantitatively test for critical quality attributes (CQAs) of a vaccine product. While clinical (human) efficacy of a vaccine can never be predicted from pre-clinical evaluation of CQA, precise and accurate measurements of antigen content and a relevant biological activity (termed "potency") elicited by the antigen allow selection of potentially safe and immunogenic doses for entry into clinical trials. All available vaccine technology platforms, novel and traditional, are being utilized by different developers to produce vaccines against SARS-CoV-2. It took less than a year from the publication of SARS-CoV-2 gene sequence to Emergency Use Authorization (EUA) of the first vaccine, setting a record for speed in the history of vaccine development. The largest ever global demand for vaccines has prompted some vaccine developers to enter multiple manufacturing partnerships in different countries in addition to implementing unprecedented scale-up plans. Quantitative, robust, and rapid analytical testing for CQA of a product is essential in ensuring smooth technology transfer between partners and allowing analytical bridging between vaccine batches used in different clinical phases leading up to regulatory approvals and commercialization. We discuss here opportunities to improve the speed and quality of the critical batch release and characterization assays.
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http://dx.doi.org/10.1038/s41541-021-00317-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044082PMC
April 2021

Assessment of arsenic exposure in the population of Sabalpur village of Saran District of Bihar with mitigation approach.

Environ Sci Pollut Res Int 2021 Apr 11. Epub 2021 Apr 11.

Mahavir Cancer Sansthan and Research Centre, Phulwarisharif, Patna, Bihar, 801505, India.

Arsenic poisoning through groundwater is the world's greatest normal groundwater catastrophe which got an immense effect on worldwide general wellbeing. India is confronting the outcomes of arsenic poisoning in the zone of Ganga Brahmaputra alluvial plains. In Bihar, out of 38 districts, 18 districts are exceptionally influenced with groundwater arsenic defilement. In the present study, we have assessed the current situation of arsenic exposure in Sabalpur village of Saran district of Bihar after reporting of breast, renal, skin and thyroid cancer cases from this village along with typical symptoms of arsenicosis. Such cancer patients were identified at our institute and were taken for the study. The present investigation deals with the quantification of arsenic in groundwater, hair and nail samples of subjects as well as the survey of entire village to know the overall health status of the village people. A total of n=128 household handpump water samples as well as n=128 human hair and nail samples were collected from over n=520 households. Using the graphite furnace atomic absorption spectrophotometer (GF-AAS), all the samples were analysed. The investigation resulted that the 61% of the analysed samples particularly the groundwater had the arsenic levels more than the permissible limit of WHO (> 10 μg/L) with 244.20 μg/L as the highest arsenic contamination in one of the handpump water sample. The exposure effect of hair sample was worst as 88% of all the collected samples were having high arsenic levels more than the permissible limit (> 0.2 mg/Kg). In case of nail samples, 92% of the samples were having high arsenic concentration more than the permissible limit (> 0.5 mg/Kg). The health survey study revealed high magnitude of disease burden in the exposed population with symptoms such as asthma, anaemia, hepatomegaly, diabetes, cardiac problem, skin fungal infections, breathlessness and mental disability. Few cancer cases of renal, skin, breast and cervix were also found among the exposed population of this village. The percentage of cancer cases in this village was 0.94% that was low, but it would be an aggravated situation in the near future if people will continue drinking arsenic-contaminated water. Therefore, a mitigation intervention was carried out in March 2020 by installing an arsenic filter plant. The health situation in the village in the present scenario is hope to improve in the coming years. However, motivation and awareness among the village population are still required.
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http://dx.doi.org/10.1007/s11356-021-13521-5DOI Listing
April 2021

A Descriptive Study Exploring Semen Quality Among Indian Cancer Patients.

J Adolesc Young Adult Oncol 2021 Apr 9. Epub 2021 Apr 9.

Department of Reproductive Medicine, Gunasheela Surgical and Maternity Hospital, Bangalore, India.

To descriptively explore semen quality among Indian men with various types of malignancies. We evaluated semen parameters of male patients referred to our hospital before commencing their cancer treatment. Four hundred sixty-one male patients who were within the age range of 15-50 years were recruited with diagnosed malignancies. Pre-treatment semen analyses were performed on these patients to collect data on the volume, sperm concentration, motility, and normal forms (morphology). These semen parameters were compared between cancer groups (testicular cancer, hematological cancer, and other cancers). Further comparisons were also drawn to World Health Organization (WHO) semen parameter levels (2010, fifth edition) for normal outcomes. There were no notable variations observed in semen volume (mL) and progressive motility (%) between cancer groups. These parameters were within the WHO normal semen criteria. Differences in normal forms (%) between cancer groups were not observed either; however, they were marginally lower compared with the WHO criteria. Sperm concentration was evidently lower in testicular cancer 34 × 10/mL (IQR: 10.1-60 × 10/mL) compared with hematological cancers 66 × 10/mL (IQR: 23-84.21 × 10/mL) and other cancers (IQR: 27-86.3 × 10/mL). Testicular cancer patients also presented with the largest semen disorder diagnosis ) compared with two other groups. Males with testicular cancer have shown to have lower semen quality between cancer groups and compared with WHO criteria, increasing their likelihood of them being infertile. This study further allows us to understand these outcomes, particularly in the Indian subpopulation, propagating changes in guidelines in oncofertility and medical counseling. Clinical Trials Registry-India number: CTRI/2020/09/027720.
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http://dx.doi.org/10.1089/jayao.2021.0005DOI Listing
April 2021

Oncogenic role of MiR-130a in oral squamous cell carcinoma.

Sci Rep 2021 Apr 8;11(1):7787. Epub 2021 Apr 8.

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.

Aberrant activation of the PI3K/AKT/mTOR pathway is attributed to the pathogenesis of oral squamous cell carcinoma (OSCC). In recent years, increasing evidence suggests the involvement of microRNAs (miRNAs) in oral carcinogenesis by acting as tumor suppressors or oncogenes. TSC1, as a component of the above pathway, regulates several cellular functions such as cell proliferation, apoptosis, migration and invasion. Downregulation of TSC1 is reported in oral as well as several other cancers and is associated with an unfavourable clinical outcome in patients. Here we show that oncogenic miR-130a binds to the 3'UTR of TSC1 and represses its expression. MiR-130a-mediated repression of TSC1 increases cell proliferation, anchorage independent growth and invasion of OSCC cells, which is dependent on the presence of the 3'UTR in TSC1. We observe an inverse correlation between the expression levels of miR-130a and TSC1 in OSCC samples, suggesting that their interaction is physiologically relevant. Delivery of antagomiR-130a to OSCC cells results in a significant decrease in xenograft size. Taken together, the findings of the study indicate that miR-130a-mediated TSC1 downregulation is not only a novel mechanism in OSCC, but also the restoration of TSC1 levels by antagomiR-130a may be a potential therapeutic strategy for the treatment of OSCC.
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http://dx.doi.org/10.1038/s41598-021-87388-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032739PMC
April 2021

T1 mapping and conditional survival in paediatric dilated cardiomyopathy with advanced heart failure.

Cardiol Young 2021 Apr 8:1-5. Epub 2021 Apr 8.

Department of Cardiac Imaging, Narayana Institute of Cardiac Sciences, NH Health City, Bengaluru, India.

Myocardial fibrosis is associated with adverse events in idiopathic dilated cardiomyopathy. Cardiac MRI with late gadolinium enhancement can detect myocardial fibrosis. We evaluated the conditional survival of children and adolescents based on native T1 mapping (combined proton signal from myocytes and interstitium prior to contrast administration by the measurement of myocardial and blood relaxation time) as a means to assess myocardial fibrosis. This retrospective case-cohort over a 3-year period included all consecutive patients (aged ≤ 21 years) with advanced heart failure from dilated cardiomyopathy (echocardiographic left ventricular ejection fraction ≤ 45% and NYHA class ≥ 2) who underwent cardiac MRI.Conditional survival (follow-up ≥ 6 months after cardiac MRI) was assessed to include NYHA functional class and time to event (death or heart transplantation). A total of 57 patients (mean age 11.7 ± 6.1 years; 58% male) had a median NYHA Class III (31/57) and median left ventricular ejection fraction 25% (20-38%). Survival data were available in 82% patients (46/57) and the crude mortality rate was 24% (11/46) and one patient (2%) underwent heart transplantation. The median native T1 was elevated at 1351 ms (95% CI 1332, 1394) and it showed no difference between the groups who survived to those who died. Performing a multilevel regression analysis on prognosis failed to predict 6-month conditional survival.
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http://dx.doi.org/10.1017/S1047951121001268DOI Listing
April 2021

Association of MC4R (rs17782313) gene polymorphism with obesity measures in Western India.

Diabetes Metab Syndr 2021 Mar 19;15(3):661-665. Epub 2021 Mar 19.

Department of Anthropology, University of Delhi, India. Electronic address:

Background And Aims: The association of melanocortin receptor 4 (MC4R) gene with adiposity measures is widely studied in European populations. Only six studies have investigated the role of MC4R gene with adiposity measures among Indian populations. We have evaluated the role of MC4R (rs17782313) gene polymorphism in influencing adiposity measures in India among children and adults.

Materials And Methods: The present population based cross sectional study was conducted among 303 individuals (208 children and 95 adults) of age group 10-30 years, belonging to Rajasthan. Somatometric measurements (standing height, weight, and waist and hip girths) and blood samples were taken after obtaining written informed consent. Genotyping of MC4R rs17782313 single nucleotide polymorphism was done using restriction fragment length polymorphism method for polymerase chain reaction amplified fragments. We examined association between rs17782313 and different adiposity measures (height, weight, BMI, WHR, and waist and hip girths) using linear regression models.

Results: The MC4R variant (rs17782313) predicted increased body weight (0.15 kg, S.E ± 0.076, P = 0.043) among children. In combined population, the rs17782313 variant was moderately associated with body weight (0.13 kg, S.E ± 0.070, P = 0.057). This variant was not found to be associated with any other adiposity measure.

Conclusion: Further studies are needed to evaluate the association of MC4R variants through sequencing and functional genomics with different adiposity measures in Indian populations for understanding the genetic underpinnings of adiposity in India.
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http://dx.doi.org/10.1016/j.dsx.2021.03.013DOI Listing
March 2021

Effect of Cryogenic Grinding on Fatigue Life of Additively Manufactured Maraging Steel.

Materials (Basel) 2021 Mar 5;14(5). Epub 2021 Mar 5.

Department of Production Engineering, Faculty of Mechanical Engineering, Koszalin University of Technology, Raclawicka 15-17, 75-620 Koszalin, Poland.

Additive manufacturing (AM) is replacing conventional manufacturing techniques due to its ability to manufacture complex structures with near-net shape and reduced material wastage. However, the poor surface integrity of the AM parts deteriorates the service life of the components. The AM parts should be subjected to post-processing treatment for improving surface integrity and fatigue life. In this research, maraging steel is printed using direct metal laser sintering (DMLS) process and the influence of grinding on the fatigue life of this additively manufactured material was investigated. For this purpose, the grinding experiments were performed under two different grinding environments such as dry and cryogenic conditions using a cubic boron nitride (CBN) grinding wheel. The results revealed that surface roughness could be reduced by about 87% under cryogenic condition over dry grinding. The fatigue tests carried out on the additive manufactured materials exposed a substantial increase of about 170% in their fatigue life when subjected to cryogenic grinding.
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http://dx.doi.org/10.3390/ma14051245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961498PMC
March 2021

Enhanced recovery after pancreatoduodenectomy-does age have a bearing?

Langenbecks Arch Surg 2021 Mar 27. Epub 2021 Mar 27.

Division of GI Surgery, GI Oncology, Minimal Access and Bariatric Surgery, Institute of Digestive and Hepatobiliary Sciences, Medanta - the Medicity, Sector 38, Gurugram, Haryana, 122001, India.

Introduction: With the proven benefits of enhanced recovery protocols (ERP) after pancreatoduodenectomy (PD), their implementation has become a well-accepted clinical practice across the major pancreatic surgery centres of the world. The impact of age on the execution of ERP has remained an area of ambiguity. The aim of this study was to assess the impact of age on the feasibility of various postoperative elements of ERP after PD.

Methods: A retrospective study was conducted which included 548 patients undergoing PD, managed using ERP, from March 2013 to September 2020. Patients were divided into two groups: < 70 years and ≥ 70 years. Compliance to recovery parameters and postoperative outcomes, including, the incidence of major complications, length of stay (LOS), mortality rates and re-admissions, were compared between the two groups. The impact of age, as a continuous variable, was also studied on the feasibility of each postoperative element.

Results: One-fifth (113/548) of the cohort comprised of patients aged 70 years and above. The 'elderly' patients had a significantly higher prevalence of diabetes, hypertension, and cardiac disease. They were also more likely to get admitted to the intensive care unit for postoperative monitoring (p < 0.001). The median LOS was 8.0 days in the young and 9.0 days in the elderly (p = 0.253). Rate of major complications (age < 70, n = 37 (8.5%) vs age ≥ 70, n = 7 (6.2%), p = 0.421) and 30-day mortality (age < 70, n = 15 (3.4%) vs age ≥ 70, n = 7 (6.2%), p = 0.185) was not statistically different between the two groups. Compliance of various postoperative elements was similar between the two groups. When studied as a continuous variable, age did not seem to be associated with higher non-compliance of any of the postoperative recovery elements.

Conclusion: Age is not a barrier in the safe implementation of postoperative element of ERPs after PD. Enhanced recovery protocols do not need to be modified for the aged.
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http://dx.doi.org/10.1007/s00423-021-02108-wDOI Listing
March 2021

Vermiwash: An agent of disease and pest control in soil, a review.

Heliyon 2021 Mar 8;7(3):e06434. Epub 2021 Mar 8.

Shoolini University Biotechnology and Management Sciences, School of Biological and Environmental Sciences, Solan 173212, Himachal Pradesh, India.

Vermiwash is a liquid extract produced from vermicompost in a medium where earthworms are richly populated. It comprises a massive decomposer bacteria count, mucus, vitamins, different bioavailable minerals, hormones, enzymes, different antimicrobial peptides, etc. This paper aimed to assess how these natural products in vermiwash suppressed the pathogen and pests. Thus, we have reviewed the importance of vermiwash/vermicompost in disease control, the mechanism of disease suppression, the components of vermiwash applied in disease suppression, and pest control to use the scientific facts in agriculture to enhance the productivity of the crops. The bioactive macromolecules from the skin secretion of earthworm, coelomic fluid, and mucus directly able to defend pathogenic soil microbes against the worm and thereby freed the environment from the disease. Earthworms establish symbiotic relations with microbes, produce an essential product that supports the growth of plants, and suppress plant's root disease. It is recomended that earthworm should be inoculated in an agricultural field, or prepare and apply its vermiwash/vermicompost as a spray or as additive bio-fertilizer in the soil to enhance the productivities of the crops.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944038PMC
March 2021

Ligand decorated biodegradable nanomedicine in the treatment of cancer.

Pharmacol Res 2021 May 13;167:105544. Epub 2021 Mar 13.

Central Molecular Laboratory, Govind Ballabh Pant, Postgraduate Institute of Medica, Education and Research (GIPMER), New Delhi 110002, India; Department of GI Surgery, Govind Ballabh Pant, Postgraduate Institute of Medica, Education and Research (GIPMER), New Delhi 110002, India. Electronic address:

Cancer is one of the major global health problems, responsible for the second-highest number of deaths. The genetic and epigenetic changes in the oncogenes or tumor suppressor genes alter the regulatory pathways leading to its onset and progression. Conventional methods are used in appropriate combinations for the treatment. Surgery effectively treats localized tumors; however, it fails to treat metastatic tumors, leading to a spread in other organs, causing a high recurrence rate and death. Among the different strategies, the nanocarriers-based approach is highly sought for, but its nonspecific delivery can cause a profound side effect on healthy cells. Targeted nanomedicine has the advantage of targeting cancer cells specifically by interacting with the receptors overexpressed on their surface, overcoming its non-specificity to target healthy cells. Nanocarriers prepared from biodegradable and biocompatible materials are decorated with different ligands by encapsulating therapeutic or diagnostic agents or both to target cancer cells overexpressing the receptors. Scientists are now utilizing a theranostic approach to simultaneously evaluate nanocarrier bio-distribution and its effect on the treatment regime. Herein, we have summarized the recent 5-year efforts in the development of the ligands decorated biodegradable nanocarriers, as a targeted nanomedicine approach, which has been highly promising in the treatment of cancer.
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http://dx.doi.org/10.1016/j.phrs.2021.105544DOI Listing
May 2021

Genome-wide identification and expression profiling of basic leucine zipper transcription factors following abiotic stresses in potato (Solanum tuberosum L.).

PLoS One 2021 12;16(3):e0247864. Epub 2021 Mar 12.

Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India.

Potato (Solanum tuberosum L.) is an important food crop that is grown and consumed worldwide. The growth and productivity of this crop are severely affected by various abiotic stresses. Basic leucine zipper (bZIP) transcription factors (TFs) in plants are well known for their function during growth and development. However, systematic and in-depth identification and functional characterization of the bZIP gene family of potato is lacking. In the current study, we identified a total of 90 bZIPs (StbZIP) distributed on 12 linkage groups of potato. Based on the previous functional annotation and classification of bZIPs in Arabidopsis, wheat, and rice, a phylogenetic tree of potato bZIPs was constructed and genes were categorized into various functional groups (A to I, S, and U) as previously annotated in Arabidopsis thaliana. Analyses of the transcript sequence (RNA-seq) data led to identifying a total of 18 candidate StbZIPs [four in roots, eight in the tuber, six in mesocarp and endocarp] that were expressed in a tissue-specific manner. Differential expression analysis under the various abiotic conditions (salt, mannitol, water, and heat stress) and treatment with phytohormones (ABA, GA, IAA, and BAP) led to the identification of forty-two [thirteen under salt stress, two under mannitol stress, ten under water stress, and eighteen under heat stress], and eleven [eight and three StbZIPs upon treatment with ABA, and IAA, respectively] candidate StbZIPs, respectively. Using sequence information of candidate StbZIPs, a total of 22 SSR markers were also identified in this study. In conclusion, the genome-wide identification analysis coupled with RNA-Seq expression data led to identifying candidate StbZIPs, which are dysregulated, and may play a pivotal role under various abiotic stress conditions. This study will pave the way for future functional studies using forward and reverse genetics to improve abiotic stress tolerance in potato.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247864PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954325PMC
March 2021

Exome sequencing and functional studies in zebrafish identify WDR8 as the causative gene for isolated Microspherophakia in Indian families.

Hum Mol Genet 2021 Mar 9. Epub 2021 Mar 9.

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, 560012, India.

Isolated Microspherophakia (MSP) is an autosomal recessive disorder characterised by a smaller than normal spherical lens. Till date, LTBP2 is the only gene shown to cause MSP. We used homozygosity mapping and whole-exome sequencing and identified a homozygous mutation, c.1148C > T (p.Pro383Leu), in the WDR8 (or WRAP73) gene in two Indian MSP families. In vitro experiments showed that the missense mutation renders the protein unstable. WDR8 is a centriolar protein that has important roles in centrosomal assembly, spindle pole formation, and ciliogenesis. Co-immunoprecipitation experiments from HeLa cells indicated that the mutation interferes with the interaction of WDR8 with its binding partners. In zebrafish, both morpholino-mediated knockdown and CRISPR/Cas knockout of wdr8 resulted in decreased eye and lens size. The lack of wdr8 affected cell cycle progression in the retinal cells, causing a reduction in cell numbers in the retina and lens. The reduction in eye size and the cell cycle defects were rescued by exogenous expression of the human wild type WDR8. However, the human mutant WDR8 (p.Pro383Leu) was unable to rescue the eye defects, indicating that the missense mutation abrogates WDR8 protein function. Thus, our zebrafish results suggested that WDR8 is the causative gene for MSP in these Indian families.
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http://dx.doi.org/10.1093/hmg/ddab061DOI Listing
March 2021

Role of TLR2 and TLR4 Signaling in Parkinson's Disease: An Insight into Associated Therapeutic Potential.

J Mol Neurosci 2021 Mar 9. Epub 2021 Mar 9.

Department of Pharmacy, Faculty of Pharmacy, University of Oradea, Oradea, Romania.

Toll-like receptors (TLRs) belong to a pattern recognition receptor class which is an integral part of innate immunity. During Parkinson's disease (PD), activation of the immune response is a well-established feature in both, the periphery and the brain. The role of TLR is considered to be a salient part of the established framework during inflammation and neurodegenerative disease such as PD. The link between inflammation-mediated TLR expression and the molecular hallmark of PD pathogenesis is well established. Various evidence in support of the review has proved the presence of α-synuclein-positive inclusions, inciting the activated microglia to promote the expression of microglial and neuronal TLRs. Thus, the long-established inflammatory environment is considered as the pivotal element in the progression of the PD pathology. This review aims to delineate the importance of TLRs (TLR2/4) and their altered signaling in the pathogenesis of PD via cascade of proinflammatory pathways and the new therapeutic propositions to modulate the TLR expression. The microglia-mediated inflammatory pathway and aggregated α-synuclein potentiates multiple mechanisms through which inflammation contributes to progression of neurodegeneration in PD via upregulation of TLR2 and TLR4. TLR targeting is a site of interest to facilitate effective treatment for PD.
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http://dx.doi.org/10.1007/s12031-021-01811-zDOI Listing
March 2021

Digitized smart surveillance and micromanagement using information technology for malaria elimination in Mangaluru, India: an analysis of five-year post-digitization data.

Malar J 2021 Mar 8;20(1):139. Epub 2021 Mar 8.

ICMR-National Institute of Malaria Research (Field Unit), Nirmal Bhawan, ICMR Campus, Poojanahalli, Kannamangla Post, Devanahalli Taluk, Bangalore, Karnataka, 562110, India.

Background: Malaria control system (MCS), an Information technology (IT)-driven surveillance and monitoring intervention is being adopted for elimination of malaria in Mangaluru city, Karnataka, India since October 2015. This has facilitated 'smart surveillance' followed by required field response within a timeline. The system facilitated data collection of individual case, data driven mapping and strategies for malaria elimination programme. This paper aims to present the analysis of post-digitization data of 5 years, discuss the current operational functionalities of MCS and its impact on the malaria incidence.

Methods: IT system developed for robust malaria surveillance and field response is being continued in the sixth year. Protocol for surveillance control was followed as per the national programme guidelines mentioned in an earlier publication. Secondary data from the malaria control system was collated and analysed. Incidence of malaria, active surveillance, malariogenic conditions and its management, malariometric indices, shrinking malaria maps were also analysed.

Results: Smart surveillance and subsequent response for control was sustained and performance improved in five years with participation of all stakeholders. Overall malaria incidence significantly reduced by 83% at the end of 5 years when compared with year of digitization (DY) (p < 0.001). Early reporting of new cases (within 48 h) was near total followed by complete treatment and vector control. Slide positivity rate (SPR) decreased from 10.36 (DY) to 6.5 (PDY 5). Annual parasite incidence (API) decreased from 16.17 (DY) to 2.64 (PDY 5). There was a negative correlation between contact smears and incidence of malaria. Five-year data analyses indicated declining trends in overall malaria incidence and correlation between closures by 14 days. The best impact on reduction in incidence of malaria was recorded in the pre-monsoon months (~ 85%) compared to lower impact in July-August months (~ 40%).

Conclusion: MCS helped to micromanage control activities, such as robust reporting, incidence-centric active surveillance, early and complete treatment, documentation of full treatment of each malaria patient, targeted mosquito control measures in houses surrounding reported cases. The learnings and analytical output from the data helped to modify strategies for control of both disease and the vector, heralding the city into the elimination stage.
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http://dx.doi.org/10.1186/s12936-021-03656-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938374PMC
March 2021

Dissolved carbon and silica fluxes from Kali, Sharavati and Sita-Swarna rivers, Southwestern India.

J Environ Manage 2021 May 4;286:112273. Epub 2021 Mar 4.

Department of Civil Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576 107, India. Electronic address:

Spatio-temporal behaviour of dissolved organic carbon (DOC), inorganic carbon (DIC) and silica (DSi) along the salinity gradient of three south-west Indian monsoonal estuaries are presented. This study showed both conservative and non-conservative behaviour of DOC along the salinity gradient under varying physico-chemical conditions. The gross flux of DOC arriving at the estuary from the rivers was estimated as 0.9 × 10 g/yr for Sita-Swarna river, 4.2 × 10 g/yr for Sharavati river and 5.6 × 10 g/yr for Kali river. Similarly, the net fluxes of DOC estimated beyond the estuarine zone was 5.5 × 10 g/yr (Sita-Swarna), 8.0 × 10 g/yr (Sharavati) and 7.7 × 10 g/yr (Kali). This indicates that these estuaries are the sources of organic carbon to the ocean. The DIC linearly increased towards the higher salinity with net fluxes of 38 × 10 g/yr (Sita-Swarna), 75 × 10 g/yr (Sharavati) and 97 × 10 g/yr (Kali). The combined DIC flux of Sita-Swarna, Sharavati and Kali rivers is ~8% of the total DIC fluxes received from the west flowing rivers of India, to the Arabian Sea. The DSi showed a biogenic removal of 80-85% in all the studied estuaries. From this study it is concluded that the west flowing river estuaries are net sources of DOC and DIC and net sink for DSi. Consideration of the role of west flowing rivers of peninsular India is important for the better understanding of the carbon dynamics in the river-estuary-ocean boundary.
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http://dx.doi.org/10.1016/j.jenvman.2021.112273DOI Listing
May 2021

Assessment of root phenotypes in mungbean mini-core collection (MMC) from the World Vegetable Center (AVRDC) Taiwan.

PLoS One 2021 4;16(3):e0247810. Epub 2021 Mar 4.

World Vegetable Center Taiwan, Molecular Genetics, Flagship Leader, Vegetable Diversity & Improvement Shanhua, Tainan, Taiwan.

Mungbean (Vigna radiata L.) is an important food grain legume, but its production capacity is threatened by global warming, which can intensify plant stress and limit future production. Identifying new variation of key root traits in mungbean will provide the basis for breeding lines with effective root characteristics for improved water uptake to mitigate heat and drought stress. The AVRDC mungbean mini core collection consisting of 296 genotypes was screened under modified semi-hydroponic screening conditions to determine the variation for fourteen root-related traits. The AVRDC mungbean mini core collection displayed wide variations for the primary root length, total surface area, and total root length, and based on agglomerative hierarchical clustering eight homogeneous groups displaying different root traits could be identified. Germplasm with potentially favorable root traits has been identified for further studies to identify the donor genotypes for breeding cultivars with enhanced adaptation to water-deficit stress and other stress conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932546PMC
March 2021

Setting guidelines for co-occurring nanoparticles in water medium.

Sci Total Environ 2021 Jul 10;776:145175. Epub 2021 Feb 10.

Department of Civil Engineering, Indian Institute of Technology, New Delhi, India. Electronic address:

This study developed a framework termed as "mixNanohealthrisk" hereafter, for the first time as per literature review, to provide exposure limit or reference dose for co-occurring nanoparticles (NPs) in water for different regions of the world. The effect of interaction of NPs on (i) NP occurrence in environment and (ii) toxic effects were incorporated for estimating NP exposure dose and associated risks (in terms of risk quotient (RQ) and hazard index (HI). Reference dose (RfD) values for SiO, CeO, TiO, AlO, FeO, CNT, C, ZnO and CuO NPs were calculated for the first time in this study based on toxicity studies. RfD values for top three risk-posing nanoparticles when co-occurring together were found to be 0.1 mg/kg/d (CuO), 0.12 mg/kg/d (ZnO) and 0.19 mg/kg/d (TiO). Calculated maximum allowable concentration values for these nanoparticles were found to be 70.8, 84.4 and 136 mg/L for CuO, ZnO and TiO NPs. Exposures to nanoparticles aggregate (ZnO NP + CuO NP) in mixture suspension was found to have allowable ZnO and CuO concentration values of 24.7 mg/L and 175.2 mg/L respectively when present as aggregate. Top three regions identified with highest risk quotient were found to be USA followed by Switzerland and whole of Europe. During use of NP-interaction data for estimating risks, Ag, TiO and CuO NPs were found to have lowest maximum allowable concentration values. The identified top three risk-posing NPs can be used for conducting toxicity studies for mixture of NPs and long-term monitoring so that it can be used for setting up guideline concentration values for NPs in mixture for water environment.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145175DOI Listing
July 2021

Outcomes of concomitant percutaneous coronary interventions and transcatheter aortic valve replacement.

Arch Med Sci Atheroscler Dis 2020 27;5:e284-e289. Epub 2020 Dec 27.

Harbor-University of California, Log Angeles Medical Center, Los Angeles, CA, USA.

Introduction: Coronary artery disease is a common diagnosis among patients undergoing transcatheter aortic valve replacement (TAVR). The treatment and timing of percutaneous coronary intervention (PCI) remain controversial. We sought to compare in-hospital periprocedural outcomes of combined TAVR and PCI during the same index hospitalization versus the isolated TAVR procedure.

Material And Methods: The study population was extracted from the 2016 Nationwide Readmissions Data (NRD) using International Classification of Diseases, tenth edition, clinical modifications/procedure coding system codes for TAVR, coronary PCI, and post-procedural complications. Study endpoints included in-hospital all-cause mortality, length of index hospital stay, cardiogenic shock, need for mechanical circulatory support (MCS) devices, mechanical complications of prosthetic valve, paravalvular leak (PVL), acute kidney injury (AKI), bleeding and total hospital charges. Propensity matching was used to adjust for baseline characteristics.

Results: There were 23,604 TAVRs in the 2016 NRD, of which 852 were combined with PCI during the same index hospitalization. Mean age was 80.5 years and 45.9% were female. In comparison to isolated TAVR, TAVR-PCI was associated with higher in-hospital all-cause mortality (4.5% vs. 1.7%, < 0.01), longer length of stay (10.5 vs. 5.4 days, < 0.01), and higher incidence of cardiogenic shock (9.4% vs. 2.1%, < 0.01), use of MCS devices (6.8% vs. 0.7%, < 0.01), mechanical complications of prosthetic valve (6.8% vs. 0.7%, < 0.01), PVL (0.9% vs. 0.4%, = 0.01), AKI (25.5% vs. 11.5%, < 0.01), bleeding (25.2% vs. 18.1%, < 0.01), and total hospital charges ($354,725 vs. $220474, < 0.01).

Conclusions: In comparison to isolated TAVR, combined TAVR-PCI was associated with a higher incidence of in-hospital morbidity and mortality. The association and mechanism of increased mortality warrant further study.
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http://dx.doi.org/10.5114/amsad.2020.103092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885813PMC
December 2020

High susceptibility to varicella among urban and rural pregnant women in South India: a brief report.

Epidemiol Infect 2021 02 26;149:e63. Epub 2021 Feb 26.

Department of Infectious Diseases, Christian Medical College, Vellore, India.

Varicella infection during pregnancy has serious and/or difficult implications and in some cases lethal outcome. Though epidemiological studies in developing countries reveal that a significant proportion of patients may remain susceptible during pregnancy, such an estimate of susceptible women is not known in India. We designed this study to study the prevalence and factors associated with susceptibility to varicella among rural and urban pregnant women in South India. We prospectively recruited 430 pregnant women and analysed their serum varicella IgG antibodies as surrogates for protection. We estimated seroprevalence, the validity of self-reported history of chickenpox and factors associated with varicella susceptibility. We found 23 (95% CI 19.1-27.3) of women were susceptible. Nearly a quarter (22.2%) of the susceptible women had a history of exposure to chickenpox anytime in the past or during the current pregnancy. Self-reported history of varicella had a positive predictive value of 82.4%. Negative history of chickenpox (adjusted prevalence ratio (PR) 1.85, 95% CI 1.15-3.0) and receiving antenatal care from a rural secondary hospital (adjusted PR 4.08, 95% CI 2.1-7.65) were significantly associated with susceptibility. We conclude that high varicella susceptibility rates during pregnancy were noted and self-reported history of varicella may not be a reliable surrogate for protection.
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http://dx.doi.org/10.1017/S0950268821000492DOI Listing
February 2021

Morpho-physiological characterization coupled with expressional accord of exclusion mechanism in wild and cultivated lentil under aluminum stress.

Protoplasma 2021 Feb 17. Epub 2021 Feb 17.

Division of Plant Physiology, Indian Agricultural Research Institute, New Delhi, 110012, India.

Aluminum stress deteriorates lentil production under acidic soils. Enhanced insight into Al tolerance traits is needed to improve its productivity. Therefore, Al-resistant (L-4602, PAL-8) and Al-sensitive (BM-4, EC-223229) cultivars along with a resistant wild (ILWL-15) were characterized for morpho-physiological traits viz. seedling root architecture (SRA), Al accumulation, and localization via fluorescent and non-fluorescent staining under control and Al-treated conditions. Also, antioxidant activities and organic acid secretion were quantified, and expressions of 10 associated genes were analyzed. Roots of Al-resistant cultivars and wild genotype showed higher root growth, antioxidant enzyme activities, and organic acid secretion than Al-sensitive ones. Among these traits, higher organic acid secretion was influenced by enhanced expression of genes, especially-aluminum sensitive-3 (ALS 3), aluminum-activated malate transporter (ALMT), multidrug and toxic compound extrusion (MATE), citrate synthase (CS), and phospho enol pyruvate carboxylase (PEPC)-which helped in reducing Al and callose accumulation. These genes were located on lentil chromosomes via sequence alignment with lentil draft genome. A strong link between morpho-physiological variation and organic acid secretion was noted which reinforced the prominence of exclusion mechanism. It was complemented by enhanced antioxidant activities at seedling stage which mitigated Al stress effects on SRA. Wild outperformed over cultivars indicating its impregnable evolution which can be exploited to better understand tolerance mechanisms. Al-resistant cultivars had significantly higher seed yield than Al-sensitive and national checks on Al-toxic fields, confirming-tolerance is sustained till reproductive stage in lentil. This study elucidated role of gene families in eliminating Al toxicity that will assist breeders to formulate strategies for developing Al-resistant cultivars.
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http://dx.doi.org/10.1007/s00709-021-01619-zDOI Listing
February 2021

Elucidation of Epigenetic Landscape in Coronary Artery Disease: A Review on Basic Concept to Personalized Medicine.

Epigenet Insights 2021 28;14:2516865720988567. Epub 2021 Jan 28.

Central Molecular Laboratory, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research (GIPMER), University of Delhi, New Delhi, India.

Despite extensive clinical research and management protocols applied in the field of coronary artery diseases (CAD), it still holds the number 1 position in mortality worldwide. This indicates that we need to work on precision medicine to discover the diagnostic, therapeutic, and prognostic targets to improve the outcome of CAD. In precision medicine, epigenetic changes play a vital role in disease onset and progression. Epigenetics is the study of heritable changes that do not affect the alterations of DNA sequence in the genome. It comprises various covalent modifications that occur in DNA or histone proteins affecting the spatial arrangement of the DNA and histones. These multiple modifications include DNA/histone methylation, acetylation, phosphorylation, and SUMOylation. Besides these covalent modifications, non-coding RNAs-viz. miRNA, lncRNA, and circRNA are also involved in epigenetics. Smoking, alcohol, diet, environmental pollutants, obesity, and lifestyle are some of the prime factors affecting epigenetic alterations. Novel molecular techniques such as next-generation sequencing, chromatin immunoprecipitation, and mass spectrometry have been developed to identify important cross points in the epigenetic web in relation to various diseases. The studies regarding exploration of epigenetics, have led researchers to identify multiple diagnostic markers and therapeutic targets that are being used in different disease diagnosis and management. Here in this review, we will discuss various ground-breaking contributions of past and recent studies in the epigenetic field in concert with coronary artery diseases. Future prospects of epigenetics and its implication in CAD personalized medicine will also be discussed in brief.
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http://dx.doi.org/10.1177/2516865720988567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863167PMC
January 2021

Understanding metal dissolution from solar photovoltaics in MSW leachate under standard waste characterization conditions for informing end-of-life photovoltaic waste management.

Waste Manag 2021 Mar 10;123:97-110. Epub 2021 Feb 10.

Department of Civil Engineering, Indian Institute of Technology, New Delhi, India. Electronic address:

The upcoming end-of-life solar photovoltaics (PV) waste stream is a huge concern before solid waste professionals due to presence of hazardous metals like lead or cadmium. The objective of present study was to understand the metal dissolution from PVs under four standard waste characterization regulatory tests of U.S., Germany, and Japan and their representativeness with actual landfill leachate. Modules were exposed to real municipal solid waste (MSW) landfill leachate for extended extraction duration, agitation and diluted leachate to investigate the effect of various parameters on metal dissolution. The results indicated that extractions using landfill leachates resulted in lower metal release than standard methods. The leached metal concentrations were found to be within the threshold limits except for cadmium, copper, lead and selenium, with maximum lead release from amorphous-PV of 8.68 mg/L and 6.91 mg/L with respect to TCLP and WET tests, respectively. Arsenic showed negligible release with maximum concentration of 0.046 mg/L from copper indium gallium de-selenide(CIGS) PV. Regardless of small size (1-2 cm pieces) and agitation, Germany and Japan's standard tests resulted in minimal release except of copper from copper indium gallium de-selenide PV. Leaching without agitation, showed negligible release from all photovoltaics whereas when agitation is applied to diluted leachate, significant release was observed with aluminum and copper leached up to 145.32 mg/L (multi-crystalline silicon) and 139.01 mg/L (amorphous-PV), respectively. CIGS was found to be most hazardous with a Metal Hazard Score (calculated on the basis of magnitude of leached metals with respect to their threshold limit and subsequent health effects) of 23.19, when exposed to standard tests. For all scenarios, increased metal release was observed with decrease in sample size and increase in leachate dilution and thus, leaching in highly acidic conditions are by no means representative for modules dumping in realistic conditions.
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http://dx.doi.org/10.1016/j.wasman.2021.01.013DOI Listing
March 2021