Publications by authors named "Rajesh Kumar"

1,669 Publications

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Expanding Arsenal against Neurodegenerative Diseases using Quercetin based Nanoformulations: Breakthroughs and Bottlenecks.

Curr Neuropharmacol 2022 Aug 10. Epub 2022 Aug 10.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411 Punjab, India.

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level.
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http://dx.doi.org/10.2174/1570159X20666220810105421DOI Listing
August 2022

Vascular Manifestations of Tuberculous Meningitis: MR Angiography and Venography Study.

J Neurosci Rural Pract 2022 Jul 8;13(3):529-536. Epub 2022 Jun 8.

Department of Neurology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India.

 The purpose of this study is to evaluate magnetic resonance (MR) angiography (MRA) and venography (MRV) findings in tuberculous meningitis (TBM).  Thirty consecutive patients of clinically diagnosed TBM were enrolled. Apart from T2-weighted imaging, T1-weighted imaging (T1WI), diffusion-weighted imaging, susceptibility-weighted imaging, fluid-attenuated inversion recovery, and postcontrast T1WI, time-of-flight (TOF) MRA and postcontrast MRV were done in all the patients. MRV was done after intravenous administration of gadolinium-based contrast agent followed by postcontrast T1WI. MRA and MRV findings were analyzed.  Mean age of the patients was 33.13 ± 14.93 years. Duration of symptom was 34.90 ± 33.82 (range: 10-150) days. Out of 30 patients, 11 were categorized as definite TBM and 19 probable TBM. Eighteen (60%) were grade I, 7 (23%) grade II, and 5 (16%) grade III TBM based on severity. MR abnormalities were in varying combinations of leptomeningeal enhancement in 24 (80%), pachymeningeal in 2, both in 3, tuberculomas in 13 (43.3%), ventriculitis in 1, hydrocephalus in 16 (53.3%), and infarcts in 10 (33.3%) patients out of which the tubercular zone infarct in 9 patients. TOF MRA showed arterial abnormality in 13 patients. Anterior cerebral artery and middle cerebral artery have commonly involved vessels. Dural sinus thrombosis was noted in two patients. Both were female. One patient had subacute thrombus in the posterior part of superior sagittal sinus, left transverse sinus, and proximal right transverse sinus. The second patient had a filling defect in the transverse sinus.  In TBM, there is predominant arterial involvement causing infarcts which are usually seen in the tubercular zone. However, occasionally, there may be venous involvement causing cerebral venous sinus thrombosis.
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http://dx.doi.org/10.1055/s-0042-1748175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357502PMC
July 2022

Assessing the Antioxidant and Anti-inflammatory Activity of Crude Extract.

J Contemp Dent Pract 2022 Apr 1;23(4):437-442. Epub 2022 Apr 1.

Tagore Dental College and Hospital, Chennai, Tamil Nadu, India.

Background: Chronic inflammation and oxidative stress play a vital role in the pathogenesis of various diseases of the oral cavity including periodontal disease. Phytochemicals present in plants with antioxidant (AO) and anti-inflammatory properties could aid as a therapeutic adjunct in the management of these diseases.

Aim: To assess the antioxidant and anti-inflammatory effects of aqueous and ethanolic extracts of Lam. (MOL) in an environment.

Materials And Methods: Aqueous and ethanolic extracts of Lam. were prepared by maceration. Antioxidant activity was assessed by FRAP, hydroxyl radical scavenging activity, and DPPH radical scavenging assay. Anti-inflammatory activity was assessed by Albumin Denaturation Assay. Experiments were repeated thrice, and mean and standard deviation were calculated.

Results: Both the test substances exhibited significant antioxidant and anti-inflammatory activity, and aqueous extracts exhibited higher activity than ethanolic extract.

Summary And Conclusion: The anti-inflammatory and antioxidant activity of Lam. could be further explored for the management of periodontal disease as a local drug delivery system with the extract could be developed.
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April 2022

CHA DS -VASc score, a simple clinical tool for early prediction of no-reflow phenomenon in patients undergoing emergency percutaneous coronary revascularization.

J Cardiovasc Thorac Res 2022 25;14(2):122-127. Epub 2022 Jun 25.

National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan.

Slow flow/no reflow (SF/NR) phenomenon during emergency percutaneous revascularization is a feared complication associated with increased risk of adverse outcomes. CHA DS -VASc score has been proposed for the risk stratification but a very limited evidences are available regarding the accuracy of this system. Therefore, we conducted this study to assess the predictive value of CHA DS -VASc score for predicting SF/NR phenomenon during primary percutaneous coronary intervention (PCI). This analytical cross-sectional study included 596 consecutive patients undergoing PCI for STEMI at a tertiary care cardiac center of Karachi, Pakistan. Baseline -VASc sore was calculated and development of SF/NR phenomenon during primary PCI was recorded. Predictive value of the score was assessed through area under the curve (AUC) of receiver operating characteristic curve analysis and sensitivity and specificity were computed. Logistic regression analysis was performed to assess the predictive strength of the score. A total of 596 patients were included, mean age was 56.28±11.44 years, and 75.7%(451) were male. The slow/no reflow phenomenon during the procedure was observed in 36.6%(218) of the patients. CHA DS -VASc≥2 was observed in 50.2%(299) of the patients. The CHA DS -VASc score was significantly higher in SF/NR patients, 2.06±1.25 vs. 1.37±1.33; <0.001. The AUC of CHA DS -VASc score was 0.652 [0.607-0.696], CHA DS -VASc≥2 had sensitivity and specificity of 65.6% [58.9% to 71.9%] and 58.3% [53.6% to 63.7%] respectively for predicting SF/NR. CHA DS -VASc≥2 was insignificant on multivariate with odds ratio of 1.48 [0.72 -3.04]; =0.283. CHA DS -VASc risk stratification system has moderate discriminating power for the stratification of SF/NR phenomenon during primary PCI.
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http://dx.doi.org/10.34172/jcvtr.2022.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339737PMC
June 2022

Mechanical Non-ST-Segment Elevation Myocardial Infarction Secondary to Left Ventricular Outflow Tract Pseudoaneurysm: A Unique Entity.

JACC Case Rep 2022 Aug 3;4(15):972-976. Epub 2022 Aug 3.

Department of Cardiology, St. James's Hospital, Dublin, Ireland.

We present a unique case of acute coronary syndrome (ACS) secondary to external coronary artery compression from a left ventricular outflow tract pseudoaneurysm in a postsurgical aortic valve replacement (AVR) patient, subsequently sealed with a pericardial patch. We highlight this rare presentation of ACS in postsurgical AVR patients and the importance of multimodality imaging and treatment of this unique, potentially serious sequela. ().
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http://dx.doi.org/10.1016/j.jaccas.2022.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350894PMC
August 2022

Augmentation of photophysical features and Judd-Ofelt analysis of extensively green glowing terbium (III) complexes with nitrogen donor ancillary ligands.

Photochem Photobiol Sci 2022 Aug 6. Epub 2022 Aug 6.

University Institute of Engineering and Technology, Maharshi Dayanand University, Rohtak, 124001, India.

Six green glowing terbium (III) complexes were fabricated via grinding method utilizing a prime organic ligand (L) and nitrogen donor ancillary ligands. Characterization of synthesized complexes was accomplished through various spectroscopic techniques. The significant thermal stability was determined by thermogravimetric analysis while the energy bandgap and Urbach energy were investigated through diffused reflectance spectra of these complexes. The peak observed at 548 nm in emission spectra is responsible for the virescent color of these complexes. Color purity, decay time, quantum yield, and emission intensities of ternary complexes were significantly improved as compared to binary ones due to the synergistic effect of ancillary ligands. Judd-Ofelt parameters were determined by the NIR absorption spectrum, which claims the asymmetric environment around the terbium (III) ion. CCT values advocate the applicability of these complexes in green light-emitting materials as a cool light source. The biological assignments reveal the significance of these complexes as potent antioxidants and antimicrobial agents. The energy transfer process highlights the enhancement of luminescence in these complexes via the synergic effect of ligands. Our investigation portrays that these complexes can be employed in laser technology, display devices, semiconductors, biological fields, and optoelectronic devices.
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http://dx.doi.org/10.1007/s43630-022-00275-3DOI Listing
August 2022

Relationships between brain tissue damage, oxygen desaturation, and disease severity in obstructive sleep apnea evaluated by diffusion tensor imaging.

J Clin Sleep Med 2022 Aug 5. Epub 2022 Aug 5.

Department of Anesthesiology, University of California Los Angeles, Los Angeles, CA.

Study Objectives: Obstructive sleep apnea (OSA) subjects show brain injury in sites responsible for autonomic, cognitive, and respiratory functions. Brain changes in OSA may vary with disease severity, as assessed by the apnea-hypopnea-index (AHI) that does not provide information about the apnea depth and length in contrast to oxygen desaturation. Although significant associations with brain injury and AHI are known in OSA, it is unclear whether AHI or extent of oxygen desaturations better correlate with brain damage. We evaluated associations between brain changes, AHI, and oxygen desaturation using diffusion tensor imaging (DTI)-based measures.

Methods: We acquired DTI data from 19 OSA patients using a 3.0-Tesla MRI scanner, and calculated, normalized, and smoothed mean, axial, and radial (MD, AD and RD) diffusivity maps that were used for correlations between brain changes, oxygen desaturation, and AHI values.

Results: Positive correlations with extent of injury (MD, AD and RD) and AHI appeared in the frontal areas, cingulate and insula, amygdala, hippocampus, and basal-pons, and negative associations emerged in the putamen, internal-capsule, globus-pallidus, and cerebellar cortices. Regional diffusivity values and oxygen desaturation showed positive correlations in the cingulate, frontal, putamen, and cerebellar sites, and negative relationships in several areas, including the occipital cortex.

Conclusions: OSA subjects show negative and positive correlations, indicating increase and decrease diffusivity values, resulting from chronic and acute changes in those areas. The extent of injury in OSA partially depends on the extent of AHI and O desaturation, with the effects representing continued development from acute to chronic processes.
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http://dx.doi.org/10.5664/jcsm.10192DOI Listing
August 2022

Characterization of a broadly cross reactive tetravalent human monoclonal antibody, recognizing conformational epitopes in receptor binding domain of SARS-CoV-2.

3 Biotech 2022 Sep 2;12(9):202. Epub 2022 Aug 2.

Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad - Gurgaon Expressway, PO Box # 04, Faridabad, Haryana 121001 India.

We used human semi-synthetic phage antibody gene libraries to select anti-SARS-CoV-2 RBD scFv antibody fragment and subsequent characterization of this novel tetravalent monoclonal antibody targeting conformational epitopes in the receptor binding domain of SARS-CoV-2. Binding studies suggest that II62 tetravalent antibody cross-reacts with RBD protein of SARS-CoV2 and its different variants of concerns. The epitope mapping data reveals that II62 tetravalent antibody targets an epitope that does not directly interferes with RBD: ACE2 interaction. Neutralization studies with live authentic SARS-CoV2 virus suggests that increase in valency of II62 mAb from monovalent to tetravalent doesn't perturbate virus interactions with the ACE2 expressing host cells in cytopathic effect-based (CPE) assay.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03272-6.
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http://dx.doi.org/10.1007/s13205-022-03272-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345016PMC
September 2022

Synergistic property of piperonyl butoxide, diethyl maleate, triphenyl phosphate and verapamil hydrochloride with deltamethrin and ivermectin against Rhipicephalus microplus ticks.

Ticks Tick Borne Dis 2022 Jul 17;13(6):102006. Epub 2022 Jul 17.

Entomology Laboratory, Division of Parasitology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh 243112, India. Electronic address:

The present study was taken up to evaluate the synergistic properties of piperonyl butoxide (PBO), diethyl maleate (DEM), triphenyl phosphate (TPP) and verapamil (VER) with deltamethrin (DLM) and ivermectin (IVM) against DLM and IVM resistant tick populations collected from Madhya Pradesh and Punjab states of India. The collected field tick populations were resistant to DLM (Resistance Factor [RF] in the range of 21.71-32.98) and IVM (RF in the range of 1.89-4.98). A strong synergism between DLM and, IVM with PBO and IVM with VER was noticed. The synergistic efficacy of PBO and VER with IVM in reducing the lethal concentration 50 (LC50) value (1.69-5.72 times for PBO and 3.00-10.62 times for VER) of IVM in resistant ticks suggest that a combination of these synergists with IVM can significantly enhance the effectiveness of IVM against IVM-resistant Rhipicephlaus microplus populations gradually establishing in the different parts of the country. The synergistic efficiency of PBO with DLM in reducing the LC50 value was 2.65 and 18.01 times, respectively, against DLM- resistant two R. microplus populations (KTN and LDH). The study revealed the gradual establishment of DLM and IVM resistant populations in the surveyed states suggesting the need to adopt required resistance management strategies. The use of synergists with DLM and IVM has emerged as an effective approach for controlling the acaricide-resistant ticks.
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http://dx.doi.org/10.1016/j.ttbdis.2022.102006DOI Listing
July 2022

Use and Product Characteristics of "Tobacco Free Nicotine" E-Cigarettes Among Young Adults.

Nicotine Tob Res 2022 Aug 1. Epub 2022 Aug 1.

Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States of America.

Introduction: E-cigarettes are increasingly being marketed as containing tobacco-free nicotine (TFN). There is no data examining use of TFN e-cigarettes by young adults and how use may differ from non-TFN e-cigarettes. The current study aims to characterize young adult TFN e-cigarette use and examine differences between those who report using TFN and non-TFN e-cigarettes.

Method: U.S. young adults (18-25) with lifetime e-cigarette use (n=927) were recruited via online panels in Fall 2021 and answered questions about TFN and non-TFN e-cigarettes. Participants were categorized by lifetime TFN e-cigarette use status (yes vs. no; 34% yes). Bivariate comparisons examined differences in e-cigarette characteristics (device type, flavors, nicotine concentration) between the TFN and non-TFN groups. Binary logistic regression models examined associations between lifetime frequency of vaping (<100 vs. ≥100 times), and other tobacco product, cannabis, and/or alcohol use and lifetime TFN e-cigarette use (yes vs. no). Adjusted models include age, race/ethnicity, vaping onset age, and sex.

Results: In multivariable adjusted models, lifetime TFN e-cigarette use was associated with younger age, greater lifetime vaping, and nicotine pouch use. Young adults who used TFN e-cigarettes were more likely to report fruit, mint, menthol, and beverage flavors and know their e-liquid nicotine concentration compared with those who used non-TFN e-cigarettes.

Conclusion: Among young adults who have used e-cigarettes, more frequent e-cigarette use and use of nicotine pouches, which can also contain TFN, were associated with TFN e-cigarette use. Understanding behaviors and characteristics of those using TFN e-cigarettes is critical to regulation of TFN containing products.

Implications: This study characterizes young adults who report experience with tobacco free nicotine (TFN) e-cigarettes and compares them to those who have not used TFN e-cigarettes. Young adults with more frequent e-cigarette use and use of nicotine pouches are more likely to report TFN e-cigarette use.
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http://dx.doi.org/10.1093/ntr/ntac188DOI Listing
August 2022

Chemometric approach to evaluate the chemical behavior of rainwater at high altitude in Shaune Garang catchment, Western Himalaya.

Sci Rep 2022 Jul 27;12(1):12774. Epub 2022 Jul 27.

Environmental Biology Laboratory, Department of Zoology, Patna University, Patna, Bihar, India.

The present research has been performed to analyze the chemical behavior of rainwater of the Shaune Garang catchment (32.19° N, 78.20° E) in the Baspa basin, located at a high elevation (4221 m above mean sea level) in the Himachal Himalaya, India. During the study period, sixteen rainwater samples were collected from the Shaune Garang catchment at five different sites. The volume-weighted mean (VWM) pH value of rainwater ranged between 4.59 and 6.73, with an average value of 5.47 ± 0.69, indicating the alkaline nature of rainfall. The total ionic strength in the rainwater ranged from 113.4 to 263.3 µeq/l with an average value of 169.1 ± 40.4 µeq/l. The major dominant cations were Ca (43.10%) and Na (31.97%) and anions were Cl (37.68%), SO (28.71%) and NO (23.85%) in rainwater. The ionic ratios were calculated among all the ions. The fraction of (NO  +Cl) with SO was measured as 2.3, which specifies sour faces of rainwater due to HNO, HSO, and HCl. A multivariate statistical assessment of rainwater chemistry through Principal Component Analysis (PCA) shows the significance of four factors controlling 78.37% of the total variance, including four-component (PC1 explained 27.89%, PC2 explained 24.98%, PC3 explained 14.64%, PC4 explained 10.85%). However, the individual contribution of Factor 1(PC1) explains 27.89% of the total variance (78.37%) and displays a strong optimistic loading for Ca and Cl. Further, high loading of Ca and NO and moderate loading of SO signify the contribution of burning fossil fuel and soil dust. Anthropogenic and natural pollutants influence the composition of rainwater in the pristine Himalayas due to local and long-distance transportation. The study area receives precipitation from the West and North-West, transporting dust and fossil fuel emissions from the Thar Desert and Northwestern countries.
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http://dx.doi.org/10.1038/s41598-022-15422-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329433PMC
July 2022

Current Scenario of Pathogen Detection Techniques in Agro-Food Sector.

Biosensors (Basel) 2022 Jul 4;12(7). Epub 2022 Jul 4.

Department of Bio and Nano Technology, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana, India.

Over the past-decade, agricultural products (such as vegetables and fruits) have been reported as the major vehicles for foodborne diseases, which are limiting food resources. The spread of infectious diseases due to foodborne pathogens poses a global threat to human health and the economy. The accurate and timely detection of infectious disease and of causative pathogens is crucial in the prevention and treatment of disease. Negligence in the detection of pathogenic substances can be catastrophic and lead to a pandemic. Despite the revolution in health diagnostics, much attention has been paid to the agro-food sector regarding the detection of food contaminants (such as pathogens). The conventional analytical techniques for pathogen detection are reliable and still in operation. However, laborious procedures and time-consuming detection via these approaches emphasize the need for simple, easy-to-use, and affordable detection techniques. The rapid detection of pathogens from food is essential to avoid the morbidity and mortality originating from the suboptimal nature of empiric pathogen treatment. This review critically discusses both the conventional and emerging bio-molecular approaches for pathogen detection in agro-food.
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http://dx.doi.org/10.3390/bios12070489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313409PMC
July 2022

Isolation of functional ligninolytic from paper mill sludge and its lignin degradation potential.

Biotechnol Rep (Amst) 2022 Sep 18;35:e00755. Epub 2022 Jul 18.

Environmental Microbiology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, Uttar Pradesh, India.

Kraft lignin (KL), is the major pollutant in pulp and paper effluent and due to its heterogeneous structure, it is resistant to the depolymerization process. It has drawn much attention from the researcher due to its challenging degradation process. In this study, a KL-degrading bacterium was isolated and screened from paper mill sludge. This bacterium was identified as ligninolytic using biochemical and 16SrRNA gene analysis. showed maximum activities of lignin peroxidase-LiP (0.74 IU mL) and manganese peroxidase-MnP (9.2 IU mL) on the 4th day, and 5th day, respectively. A total 84% of KL (500 mg  ) reduction was observed after 14 days. The KL bio-degradation was confirmed based on changes in chemical stracture of KL and new metabolites identification using FTIR and GC-MS, respectively. The study concluded that maybe becomes a potential biological agent in KL biodegradation and treatment of other lignin-containing industrial effluents.
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http://dx.doi.org/10.1016/j.btre.2022.e00755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307452PMC
September 2022

FGFR4-targeted chimeric antigen receptors (CARs) combined with anti-myeloid poly-pharmacy effectively treats orthotopic rhabdomyosarcoma.

Mol Cancer Ther 2022 Jul 25. Epub 2022 Jul 25.

Caring Cross, Inc., Gaithersburg, MD, United States.

Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Treatment outcomes, particularly for relapsed/refractory or metastatic disease, have not improved in decades. The current lack of novel therapies and low tumor mutational burden suggest that CAR T therapy could be a promising approach to treating RMS. Previous work identified Fibroblast Growth Factor Receptor 4 (FGFR4, CD334) as being specifically upregulated in RMS, making it a candidate target for CAR-T cells. We tested the feasibility of an FGFR4 targeted CAR for treating RMS using an NSG mouse with RH30 orthotopic (intramuscular) tumors. The first barrier we noted was that RMS tumors produce a collagen-rich stroma, replete with immunosuppressive myeloid cells, when T cell therapy is initiated. This stromal response is not seen in tumor-only xenografts. When scFV-based binders were selected from phage display, CARs targeting FGFR4 were not effective until our screening approach was refined to identify binders to the membrane-proximal domain of FGFR4. Having improved the CAR, we devised a pharmacologic strategy to augment CAR-T activity by inhibiting the myeloid component of the T cell-induced tumor stroma. The combined treatment of mice with anti-myeloid polypharmacy (targeting CSF1R, IDO1, iNOS, TGFbeta, PDL1, MIF and myeloid mis-differentiation) allowed FGFR4 CAR-T to successfully clear orthotopic RMS tumors, demonstrating that RMS tumors, even with very low copy number targets, can be targeted by CAR-T upon reversal of an immunosuppressive microenvironment.
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http://dx.doi.org/10.1158/1535-7163.MCT-22-0059DOI Listing
July 2022

Protocol for High Throughput Screening of Antibody Phage Libraries.

Bio Protoc 2022 Jun 20;12(12):e4450. Epub 2022 Jun 20.

Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana-121001, India.

Phage display is a proven and widely used technology for selecting specific antibodies against desired targets. However, an immense amount of effort is required to identify and screen the desired positive clones from large and diverse combinatorial libraries. On the other hand, the selection of positive binding clones from synthetic and semi-synthetic libraries has an inherent bias toward clones with randomly produced amber stop codons, making it more difficult to identify desirable binding antibodies. To overcome the screening of desired clones with amber codons, we present a step-by-step approach for effective phage library screening to isolate useful antibodies. The procedure calls for creating a simple new vector system for soluble production of phage ELISA positive binding clones with one or more amber stop codons in their single-chain antibody fragment (scFv) gene sequences, which is otherwise difficult in standard screening. Graphical abstract.
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http://dx.doi.org/10.21769/BioProtoc.4450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257838PMC
June 2022

Clinical profile of COVID-19 infection in postvaccination individuals.

Am J Manag Care 2022 07 1;28(7):e244-e247. Epub 2022 Jul 1.

Department of Internal Medicine, 7 Air Force Hospital, Nathu Singh Rd, Kanpur, India 208001. Email:

Objectives: Covishield and Covaxin vaccines have been introduced after rapid approval in India, the nation that has the second most COVID-19 cases globally. These vaccines have been administered in a 2-dose schedule since January 16, 2021. This study deals with the clinical profile of individuals who developed COVID-19 infection post COVID-19 vaccination. This is the first study of its kind in India.

Study Design: Descriptive cross-sectional study.

Methods: The study population was composed of individuals who were COVID-19 positive more than 4 weeks post vaccination and were compared with individuals who were COVID-19 positive within the first 4 weeks of vaccination. Data were collected in a digital questionnaire format and analyzed with SPSS version 23 software. Clinical features were profiled in detail. Chi-square analysis was done to find out the association of various demographic features with the severity of the disease.

Results: In the study population, fever was the most common symptom (75.1%), followed by anosmia (72.1%) and shortness of breath (16.3%). There was a lower incidence of fever, cough, dyspnea, and requirement of hospitalization in the study population compared with the control group and previous epidemiological data. The time required for complete recovery and disease severity was favorable in our study population. There was a significant correlation in the rate of hospitalization among the study group and the comparative group (P = .0001) and between the number of doses of COVID-19 vaccine and the lowest oxygen saturation recorded (P = .001).

Conclusions: The findings of this study should boost the ongoing initiative of maximizing the vaccinated population countrywide and emphasize the need for 2 doses of vaccination.
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http://dx.doi.org/10.37765/ajmc.2022.89182DOI Listing
July 2022

Percutaneous coronary intervention with peripheral artery disease in the contemporary era: Still life or limb?

Atherosclerosis 2022 Jul 3. Epub 2022 Jul 3.

Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2022.06.1022DOI Listing
July 2022

Generation of soluble, cleaved, well-ordered, native-like dimers of dengue virus 4 envelope protein ectodomain (sE) suitable for vaccine immunogen design.

Int J Biol Macromol 2022 Jul 9;217:19-26. Epub 2022 Jul 9.

Infection and Immunology, Translational Health Science and Technology Institute, Faridabad, Haryana, India. Electronic address:

Dengue virus is transmitted by Aedes mosquitoes and dengue is endemic in many regions of the world. Severe dengue results in complications that may lead to death. Although some vaccine candidates are in clinical trials and one vaccine Dengvaxia, with restricted efficacy, is available, there are currently no specific therapies to completely prevent or treat dengue. The dengue virus structural protein E (envelope) exists as a head-to-tail dimer on mature virus, is targeted by broadly neutralizing antibodies and is suitable for developing vaccine immunogens. Here, we have used a redesigned dengue prME expression construct and immunoaffinity chromatography with conformational/quaternary antibody A11 to purify soluble DENV4 sE(A259C) (E ectodomain) dimers from mammalian expression system to ~99 % purity. These dimers retain glycosylation reported for native DENV E, display the three major broadly neutralizing antibody epitopes, and form well-ordered structure. This strategy can be used for developing subunit vaccine candidates against dengue and other flaviviruses.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.028DOI Listing
July 2022

Does Treatment of Erectile Dysfunction With PDE 5 Inhibitor Tadalafil Improve Quality of Life in Male Patients With Compensated Chronic Liver Disease? A Prospective Pilot Study.

J Clin Exp Hepatol 2022 Jul-Aug;12(4):1083-1090. Epub 2022 Jan 23.

Department of Community Medicine, Rajendra Institute of Medical Sciences, Ranchi, JH, India.

Background And Aims: Erectile dysfunction (ED) is common in patients with compensated cirrhosis but its impact on the quality of life (QOL) is usually overlooked. This study aimed at determining the frequency of ED in male patients with compensated chronic liver disease (CLD), assessing their QOL and the response to treatment with tadalafil. A secondary aim was to assess the effect of the tadalafil therapy on liver fibrosis, if any.

Methods: Consecutive patients with compensated CLD and advanced liver fibrosis were screened at the baseline with the International Index of Erectile Function-5 (IIEF-5), QOL questionnaire (WHOQOL-BREF), liver stiffness measurements (LSM) made with Fibroscan™ (Echosens, France), and fibrosis index based on 4 factors (FIB-4) scores. Patients with ED meeting eligibility criteria were prescribed PDE5 inhibitor tadalafil 20 mg on alternate days. During the follow-up, IIEF-5, LSM, and FIB-4 were monitored after 3 and 6 months while the WHOQOL-BREF questionnaire was administered at the baseline and at 6 months.

Results: Among 89 patients with CLD and advanced liver fibrosis, ED was present in 43 (48%) and tadalafil was prescribed to 34 patients (38%) meeting exclusion and inclusion criteria. At 3 months follow-up, the mean IIEF 5 score increased from 15.57 ± 4 to 20.78 ± 3.6, ( = 0.0001) and the improvement persisted at 6 months (IIEF-5 score 21.87 ± 2.2;  = 0.12). The physical, social relationships, and environment domains in the WHOQOL-BREF questionnaire showed significant improvement at six months ( < 0.05) but not the psychological domain ( = ns). From a baseline value of 12.69 ± 3.1 kPa, the mean LSM decreased to 11.37 ± 3.9 kPa, ( = 0.02) after 3 months on tadalafil. After 6 months, the LSM further decreased from 11 ± 0.9 to 8.2 ± 3.2 kPa ( = 0.034). FIB-4 values showed a decline from the baseline at 3 months, from 1.52 ± 0.58 to 1.32 ± 0.55, < 0.05 and at 6 months, from 1.25 ± 0.53 to 0.97 ± 0.36, > 0.05. The CAP values did not show any significant change. There was an insignificant decline in the SGOT and SGPT levels ( > 0.05) with no significant change in CTP or MELD scores.

Conclusions: In the short term, tadalafil improves ED and QOL in patients with CLD and advanced liver fibrosis. It may also reduce liver fibrosis in them. Further studies that include liver histology are needed to confirm this preliminary observation of a possible antifibrotic effect.
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http://dx.doi.org/10.1016/j.jceh.2022.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257884PMC
January 2022

A Unified Citywide Dashboard for Allocation and Scheduling Dialysis for COVID-19 Patients on Maintenance Hemodialysis.

Indian J Nephrol 2022 May-Jun;32(3):197-205. Epub 2022 Jan 5.

Municipal Corporation of Greater Mumbai, India.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused significant global disruption, especially for chronic care like hemodialysis treatments. Approximately 10,000 end-stage kidney disease (ESKD) patients are receiving maintenance hemodialysis (MHD) at 174 dialysis centers in Greater Mumbai. Because of the fear of transmission of infection and inability to isolate patients in dialysis centers, chronic hemodialysis care was disrupted for COVID-19-infected patients. Hence, we embarked on a citywide initiative to ensure uninterrupted dialysis for these patients.

Materials And Methods: The Municipal Corporation of Greater Mumbai (MCGM) designated 23 hemodialysis facilities as COVID-positive centers, two as COVID-suspect centers, and the rest continued as COVID-negative centers to avoid transmission of infection and continuation of chronic hemodialysis treatment. Nephrologists and engineers of the city developed a web-based-portal so that information about the availability of dialysis slots for COVID-infected patients was easily available in real time to all those providing care to chronic hemodialysis patients.

Results: The portal became operational on May 20, 2020, and as of December 31, 2020, has enrolled 1,418 COVID-positive ESKD patients. This initiative has helped 97% of enrolled COVID-infected ESKD patients to secure a dialysis slot within 48 hours. The portal also tracked outcomes and as of December 31, 2020, 370 (27%) patients died, 960 patients recovered, and 88 patients still had an active infection.

Conclusions: The portal aided the timely and smooth transfer of COVID-19-positive ESKD patients to designated facilities, thus averting mortality arising from delayed or denied dialysis. Additionally, the portal also documented the natural history of the COVID-19 pandemic in the city and provided information on the overall incidence and outcomes. This aided the city administration in the projected resource needs to handle the pandemic.
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http://dx.doi.org/10.4103/ijn.IJN_48_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267080PMC
January 2022

What changed in the cyber-security after COVID-19?

Comput Secur 2022 Sep 5;120:102821. Epub 2022 Jul 5.

Department of Computer Science and Information systems, Birla Institute of Technology and Science, Pilani, India.

This paper examines the transition in the cyber-security discipline induced by the ongoing COVID-19 pandemic. Using the classical information retrieval techniques, a more than twenty thousand documents are analyzed for the cyber content. In particular, we build the topic models using the Latent Dirichlet Allocation (LDA) unsupervised machine learning algorithm. The literature corpus is build through a uniform keyword search process made on the scholarly and the non-scholarly platforms filtered through the years 2010-2021. To qualitatively know the impact of COVID-19 pandemic on cyber-security, and perform a trend analysis of key themes, we organize the entire corpus into various (combination of) categories based on time period and whether the literature has undergone peer review process. Based on the weighted distribution of keywords in the aggregated corpus, we identify the key themes. While in the pre-COVID-19 period, the topics of cyber-threats to technology, privacy policy, blockchain remain popular, in the post-COVID-19 period, focus has shifted to challenges directly or indirectly brought by the pandemic. In particular, we observe post-COVID-19 cyber-security themes of privacy in healthcare, cyber insurance, cyber risks in supply chain gaining recognition. Few cyber-topics such as of malware, control system security remain important in perpetuity. We believe our work represents the evolving nature of the cyber-security discipline and reaffirms the need to tailor appropriate interventions by noting the key trends.
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http://dx.doi.org/10.1016/j.cose.2022.102821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254575PMC
September 2022

Superdry poly(vinylidene fluoride-co-hexafluoropropylene) coating on a lithium anode as a protective layer and separator for a high-performance lithium-oxygen battery.

J Colloid Interface Sci 2022 Jul 3;626:524-534. Epub 2022 Jul 3.

Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan City 333, Taiwan; Department of Safety, Health and Environment Engineering, Ming Chi University of Technology, New Taipei City 243, Taiwan; Division of Joint Reconstruction, Department of Orthopedics, Chang Gung Medical Center at Linkou, Taoyuan City 333, Taiwan. Electronic address:

In this study, a dense polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) coating is fabricated on a lithium (Li) anode sheet, which acts as a synergistic protective layer and electrolyte separator for Li-oxygen (Li-O) batteries. This thin coating is dried through slow solvent evaporation and vacuum drying methods. The solvent-free, dense PVDF-HFP coating has a thickness of 45 µm and can absorb 62% of electrolyte. The battery containing the PVDF-HFP coating demonstrates a maximum peak power density of 3 mW cm, significantly higher than that of the battery with the PVDF coating (0.8 mW cm) but lower than that without coating (equipped with a commercial glass fiber separator, 7.3 mW cm). However, the PVDF-HFP coating enables the Li-O battery to reach a capacity of 4400 mA h g, much higher than that without the coating (glass fiber separator, 850 mA h g). The symmetric Li-Li cells further confirm steady and low overpotentials using the anode coating at a high current density of 1.0 mA cm, indicating stable Li plating/stripping process. The PVDF-HFP-coated battery has a longer cycling lifetime (1700 h) than those with the PVDF coating (120 h) and a glass fiber separator (670 h). The Raman spectra show that there are lithium compounds (mainly lithium hydroxide) and residual PVDF-HFP on the aged anode surface. The dense PVDF-HFP coating on the Li anode plays dual roles: it creates a strong protective layer for stabilizing the solid-electrolyte interface (in the solid phase), and acts as a separator for modulating the Li metal deposition and stripping behaviors in liquid electrolyte.
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http://dx.doi.org/10.1016/j.jcis.2022.06.172DOI Listing
July 2022

Association of youth impulsivity and use of e-cigarette devices, flavors, and frequency of use.

Addict Behav 2022 Jun 9;134:107386. Epub 2022 Jun 9.

Department of Psychiatry, Yale School of Medicine, 34 Park Street, New Haven, CT, United States of America.

Introduction: Given high youth e-cigarette use, it is important to investigate how traits, like impulsivity, may be associated with youth e-cigarette use behaviors. The study aim is to determine if impulsivity is associated with trying more e-cigarette flavors and device types, and greater frequency of e-cigarette use.

Method: Cross sectional survey data from CT high schoolers (n = 4875, 6 schools) were collected in 2019. Lifetime (ever) e-cigarette users (n = 2313) completed the Brief Barrett Impulsivity Scale, which contains two subscales; behavioral impulsivity and impaired self-control. Among lifetime users, associations between impulsivity subscales and number of e-cigarette flavors tried, e-cigarette devices tried, and past 30-day frequency of e-cigarette use were examined using regression models. Additionally, associations of impulsivity and use frequency were examined among only current e-cigarette users (≥1 day of use in past 30; n = 1327). School, age, race/ethnicity, vaping initiation age, other tobacco product use, and sex were included as covariates in models.

Results: Higher behavioral impulsivity was associated with greater number of e-cigarette flavors tried (AOR: 1.06, 95% CI: 1.02, 1.11, p <.008) and higher frequency of past 30-day use both among ever and current e-cigarette users (AOR: 1.26, 95%CI:1.10,1.44, p <.001; AOR: 1.12, 95%CI:1.02,1.22, p <.02), but not number of e-cigarette devices tried. Impaired self-control was not associated with any outcomes.

Conclusion: Youth with higher behavioral impulsivity may be more at risk for using more e-cigarette flavors and using e-cigarettes more frequently. Regulations aimed at reducing flavor availability among youth and interventions targeting impulsive behavior may be important for this population.
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http://dx.doi.org/10.1016/j.addbeh.2022.107386DOI Listing
June 2022

Healthcare professionals are "corona saviors" not "warriors".

J Family Med Prim Care 2022 May 14;11(5):1602-1603. Epub 2022 May 14.

Department of Nephrology and Renal Transplant Medicine, V.M.M.C. & Safdarjung Hospital, New Delhi, India.

During the coronavirus disease 2019 (COVID-19) pandemic, the role of doctors and healthcare professionals came into highlight as they are at the forefront since the onset of the pandemic, keeping themselves and their families at risk just to treat this disease and save lives. However, healthcare workers are not warriors. Let our healthcare professionals be called as "Corona Saviors" instead of "Corona Warriors" without any prejudice; they are the "Angels of Saviors of Health."
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1737_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254818PMC
May 2022

Early biomolecular changes in brain microvascular endothelial cells under Epstein-Barr virus influence: a Raman microspectroscopic investigation.

Integr Biol (Camb) 2022 07;14(4):89-97

Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, India.

The brain microvascular endothelial cells (ECs) play an important role in protecting the brain from hazardous pathogens. However, some viral pathogens can smartly modulate the endothelial pathways to gain entry inside the brain. Further, these viruses can cause endothelial dysfunction which could develop serious neurological ailments. Epstein-Barr virus (EBV), an oncogenic virus, has also been linked to various neurological disorders. The virus primarily infects epithelial and B cells, however, it also has a tendency to infect ECs and cause endothelial activation. However, the impact of EBV influence on ECs is still underexplored. Studying the early events of virus-mediated cellular modulation could help in understanding the virus' infection strategy or aftermath. Raman microspectroscopy has been widely utilized in biomedical sciences to decipher cellular changes. To understand the EBV-influenced EC modulation by studying intracellular biomolecular changes at early time points, we utilized the Raman microspectroscopy tool. We treated the ECs with EBV and acquired the Raman spectra at different time points (2, 4, 6, 12, 24 and 36 h) and different sites (nucleus and periphery) to check changes in Raman intensities associated with specific biomolecules. In the EBV-treated cells, the status of various biomolecules in terms of Raman intensities was observed to be altered compared with uninfected cells. Specifically, the cholesterol, polysaccharide, nucleotides, nucleic acid and proline moieties were altered at different time points. We also investigated the possible correlation between these molecules using molecular network analysis and observed various associated factors. These factors could be influenced by EBV to alter the associated biomolecular levels. Our study paves the pathway to study EBV infection in human brain microvascular ECs and highlights specific biomolecular alterations, which can be focused for further mechanistic investigations.
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http://dx.doi.org/10.1093/intbio/zyac009DOI Listing
July 2022

Identification of QTNs Associated With Flowering Time, Maturity, and Plant Height Traits in L. Using Genome-Wide Association Study.

Front Genet 2022 14;13:811924. Epub 2022 Jun 14.

Division of Genomic Resources, Indian Council of Agricultural Research (ICAR)-National Bureau of Plant Genetic Resources, New Delhi, India.

Early flowering, maturity, and plant height are important traits for linseed to fit in rice fallows, for rainfed agriculture, and for economically viable cultivation. Here, Multi-Locus Genome-Wide Association Study (ML-GWAS) was undertaken in an association mapping panel of 131 accessions, genotyped using 68,925 SNPs identified by genotyping by sequencing approach. Phenotypic evaluation data of five environments comprising 3 years and two locations were used. GWAS was performed for three flowering time traits including days to 5%, 50%, and 95% flowering, days to maturity, and plant height by employing five ML-GWAS methods: FASTmrEMMA, FASTmrMLM, ISIS EM-BLASSO, mrMLM, and pLARmEB. A total of 335 unique QTNs have been identified for five traits across five environments. 109 QTNs were stable as observed in ≥2 methods and/or environments, explaining up to 36.6% phenotypic variance. For three flowering time traits, days to maturity, and plant height, 53, 30, and 27 stable QTNs, respectively, were identified. Candidate genes having roles in flower, pollen, embryo, seed and fruit development, and xylem/phloem histogenesis have been identified. Gene expression of candidate genes for flowering and plant height were studied using transcriptome of an early maturing variety (IC0523807). The present study unravels QTNs/candidate genes underlying complex flowering, days to maturity, and plant height traits in linseed.
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http://dx.doi.org/10.3389/fgene.2022.811924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237403PMC
June 2022

Genomic analysis of the first cases of extensively drug-resistant, travel-related serovar Typhi in Oman.

IJID Reg 2021 Dec 1;1:135-141. Epub 2021 Nov 1.

Central Public Health Laboratories, DGDSC, Ministry of Health, Muscat, Oman.

Objectives: To highlight the importance of molecular testing in characterizing extensively drug-resistant (XDR) Typhi ( Typhi), and linking it to the current outbreak in Sindh, Pakistan.

Methods: Our study reports three travel-related typhoid fever cases caused by XDR Typhi that presented between January 2019 and August 2019. Antimicrobial susceptibility and genotyping with pulse-field gel electrophoresis (PFGE) were carried out. Whole-genome sequencing (WGS) was performed to characterize the genomic clonality in relation to the emerging outbreak of Typhi in Sindh, Pakistan, and to study the molecular resistance profiles.

Results: Laboratory testing revealed resistance to all first-line antibiotics (i.e ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole), as well as to quinolones and third-generation cephalosporins, leading to a change in the patients' therapy to the use of carbapenems. Classical MLST (cMLST) revealed that the strains were of sequence type 1 (ST1) and the core genome sequence (cgWGS) analysis closely clustered our strains with internationally reported strains from Pakistan, India, and the UK. The strains were found to carry a gene-harbouring IncY plasmid, which encodes resistance to ceftriaxone.

Conclusions: Our report alerts clinicians to the use of appropriate empirical treatments in such scenarios, and highlights the significance of the global spread of XDR Typhi.
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http://dx.doi.org/10.1016/j.ijregi.2021.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216381PMC
December 2021

Recycling of silicon-rich agro-wastes by their combined application with phosphate solubilizing microbe to solubilize the native soil phosphorus in a sub-tropical Alfisol.

J Environ Manage 2022 Sep 23;318:115559. Epub 2022 Jun 23.

Division of Nematology, ICAR-Indian Agricultural Research Institute, New Delhi, 110012, India.

It is imperative to find suitable strategies to utilize the native soil phosphorus (P), as natural rock phosphate deposits are at a verge of depletion. We explored two such cost-effective and eco-friendly strategies for native soil P solubilization: silicon (Si)-rich agro-wastes (as Si source) and phosphate solubilizing microorganism (PSM). An incubation study was conducted in a sub-tropical Alfisol for 90 days at 25 °C under field capacity moisture. A factorial completely randomized design with 3 factors, namely: Si sources (three levels: sugarcane bagasse ash, rice husk ash, and corn cob ash), PSM (two levels: without PSM, and with PSM); and Si doses [three levels: no Si (Si), 125 (Si) and 250 (Si) mg Si kg soil] was followed. The PSM increased solution P and soluble Si level by ∼22.2 and 1.88%, respectively, over no PSM; whereas, Si and Si increased solution P by ∼60.4 and 77.1%, as well as soluble Si by ∼41.5 and 55.5%, respectively, over Si. Also, interaction of PSM × Si doses was found significant (P<0.05). Activities of soil enzymes (dehydrogenase, acid phosphatase) and microbial biomass P also increased significantly both with PSM and Si application. Overall, PSM solubilized ∼4.18 mg kg of inorganic P and mineralized ∼5.92 mg kg of organic P; whereas, Si and Si solubilized ∼3.85 and 5.72 mg kg of inorganic P, and mineralized ∼4.15 and 5.37 mg kg of organic P, respectively. Path analysis revealed that inorganic P majorly contributed to total P solubilization; whereas, soluble and loosely bound, iron bound and aluminium bound P significantly influenced the inorganic P solubilization. Thus, utilization of such wastes as Si sources will not only complement the costly P fertilizers, but also address the waste disposal issue in a sustainable manner.
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http://dx.doi.org/10.1016/j.jenvman.2022.115559DOI Listing
September 2022

Expression optimization, purification, and biophysical characterization of a GluN2D-containing NMDA receptor.

Protein Expr Purif 2022 10 23;198:106129. Epub 2022 Jun 23.

Physical Biochemistry and Molecular Design, Biotherapeutics and Medicinal Sciences, Biogen, Cambridge, MA, 02142, USA. Electronic address:

N-methyl-d-aspartate (NMDA) receptors are hetero-tetrameric ion channels typically consisting of two GluN1 and two GluN2 subunits. A GluN2D subunit containing NMDA receptor dysfunction has been implicated in several neurological diseases, including schizophrenia; however, the lack of a purified GluN2D containing NMDA receptor has been a hurdle for structural and biophysical studies. Here, we present expression and purification strategies to generate human GluN2D containing NMDA receptor, confirm its hetero-tetrameric form using fluorescence size exclusion chromatography (FSEC) and evaluated its suitability for structural studies. The purification methodology outlined here will help in the development of GluN2D specific channel modulators and enable structure activity relationship (SAR) studies.
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http://dx.doi.org/10.1016/j.pep.2022.106129DOI Listing
October 2022
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