Publications by authors named "Amit Sharma"

726 Publications

No evidence to support the impact of migration background on treatment response rates and cancer survival: a retrospective matched-pair analysis in Germany.

BMC Cancer 2021 May 10;21(1):526. Epub 2021 May 10.

Department of Integrated Oncology, CIO Bonn, Center for Integrated Oncology ABCD, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Background: Immigration has taken the central stage in world politics, especially in the developed countries like Germany, where the continuous flow of immigrants has been well documented since 1960s. Strikingly, emerging data suggest that migrant patients have a poorer response to the treatment and lower survival rates in their new host country, raising concerns about health disparities. Herein, we present our investigation on the treatment response rate and cancer survival in German patients with and without an immigrant background that were treated at our comprehensive cancer center in Germany.

Methods: Initially, we considered 8162 cancer patients treated at the Center for Integrated Oncology (CIO), University Hospital Bonn, Germany (April 2002-December 2015) for matched-pair analysis. Subsequently, the German patients with a migration background and those from the native German population were manually identified and catalogued using a highly specific name-based algorithm. The clinical parameters such as demographic characteristics, tumor characteristics, defined staging criteria, and primary therapy were further adjusted. Using these stringent criteria, a total of 422 patients (n = 211, Germans with migration background; n = 211, native German population) were screened to compare for the treatment response and survival rates (i.e., 5-year overall survival, progression-free survival, and time to progression).

Results: Compared to the cohort with migration background, the cohort without migration background was slightly older (54.9 vs. 57.9 years) while having the same sex distribution (54.5% vs. 55.0% female) and longer follow-up time (36.9 vs. 42.6 months). We did not find significant differences in cancer survival (5-year overall survival, P = 0.771) and the response rates (Overall Remission Rate; McNemar's test, P = 0.346) between both collectives.

Conclusion: Contrary to prior reports, we found no significant differences in cancer survival between German patients with immigrant background and native German patients. Nevertheless, the advanced treatment protocols implemented at our comprehensive cancer center may possibly account for the low variance in outcome. To conduct similar studies with a broader perspective, we propose that certain risk factors (country-of-origin-specific infections, dietary habits, epigenetics for chronic diseases etc.) should be considered, specially in the future studies that will recruit new arrivals from the 2015 German refugee crisis.
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http://dx.doi.org/10.1186/s12885-021-08141-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108356PMC
May 2021

Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via a piperidine-ring scaffold inspired Cladosporin analogues.

Chembiochem 2021 May 9. Epub 2021 May 9.

National Institute of Malaria Research, Director, Sector 8 Dwarka, Dwarka, New Delhi, Delhi 110077, 110077, delhi, INDIA.

Plasmodium falciparum lysyl tRNA synthetase ( Pf KRS) represent a promising therapeutic anti-malarial target. Cladosporin, a tool compound was identified as a selective and potent PfKRS inhibitor but lacks metabolic stability. Here, we report chemical synthesis, biological evaluation and structural characterization of analogues where the tetrahydropyran (THP) frame of cladosporin is replaced with the piperidine ring bearing functional group variations. Thermal binding, enzymatic, kinetic and parasitic assays complemented with x-ray crystallography reveals compounds to be of moderate potency. Co-crystals of Cla-B and Cla-C with PfKRS reveals key atomic configurations that allow drug binding to, and inhibition of the enzyme. Collectively, these piperidine ring scaffold inhibitors lays a framework for further structural editing and functional modifications of cladosporin scaffold to obtain a potent lead.
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http://dx.doi.org/10.1002/cbic.202100212DOI Listing
May 2021

Inhibition of the ERK1/2 Phosphorylation by Dextromethorphan Protects against Core Autistic Symptoms in VPA Induced Autistic Rats: and Drug Repurposition Study.

ACS Chem Neurosci 2021 Apr 29. Epub 2021 Apr 29.

Department of Pharmacology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India.

The imbalance between excitatory and inhibitory neurotransmitters is explicitly related to the pathophysiology of autism spectrum disorder (ASD). The role of an NMDA receptor antagonist, dextromethorphan, was studied in ameliorating the ASD-like symptoms by regulating the excitatory and inhibitory imbalance using the valproic acid (VPA) model of ASD. Female Wistar rats were administered VPA [600 mg/kg on embryonic day ED-12.5] through intraperitoneal (ip) injection to induce ASD in pups. Autistic pups were then given dextromethorphan (10, 15, and 30 mg/kg; ip) and risperidone (2.5 mg/kg; ip) from PND 23 to 43 in different groups. Behavioral tests (three chamber sociability, self-grooming, Morris water maze, elevated plus maze, open field, rotarod, grip strength), oxidative stress and inflammatory markers, histological evaluation (H&E, Nissil staining), and NMDA and ERK1/2 expression by immunohistochemistry and RT-PCR were done. The modeling of dextromethorphan against PPDA, TCN-201, MK-22, EVT-101 on NMDA receptors was also performed. Dextromethorphan (30 mg/kg) rescued the impaired behavioral patterns including social excitability, hyperactivity, repetitive and restricted behaviors as well as mitigation of the memory and motor coordination. The levels of various oxidative stress markers (GSH, SOD, catalase, MDA) and inflammatory markers (IL-1β, IL-6, IL-10, TNF-α) were ameliorated by different doses of dextromethorphan. It also reduced the neuronal injury score and rescued the overly expressed pERK1/2 and NMDA signaling in both the prefrontal cortex and hippocampus of the autistic pups. results showed favorable binding of dextromethorphan against TCN-201 and MK-22 binding sites. The present study provided experimental evidence for the potential therapeutic role of dextromethorphan in attenuating autism symptomatology in the ASD model of rats. Thus, modulation of the glutamatergic signaling can be a potential target for ASD treatment.
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http://dx.doi.org/10.1021/acschemneuro.0c00672DOI Listing
April 2021

Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.

N Engl J Med 2021 04;384(17):1589-1600

From Stanford University School of Medicine, Palo Alto, CA (G.M.C., E.F.L.); Renal Associates, San Antonio (P.E.P.), U.S. Renal Care, Plano (G.A.B.), Baylor University Medical Center, Baylor Heart and Vascular Hospital, Baylor Heart and Vascular Institute, Dallas (P.A.M.), and the Section of Nephrology, Baylor College of Medicine, Houston (W.C.W.) - all in Texas; Akebia Therapeutics, Cambridge (Y.M.K.F., S.B., Z.K., W.L., B.J.M., A.S., D.L.V.), and the Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston (M.J.S.) - both in Massachusetts; the Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis (R.A.); Excellentis Clinical Trial Consultants, George, South Africa (S.A.); Bihor County Hospital Oradea, Oradea, Romania (G.B.); Qway Research, Hialeah, FL (F.P.C.); the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (A.G.J.); the Department of Medicine, Vanderbilt University Medical Center, Nashville (M.J.K.); Firma Clinical Research, Hunt Valley (T.L.), and the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore (K.M.) - both in Maryland; the Department of Medicine, Memorial University of Newfoundland, St. John's, Canada (P.S.P.); the Division of Nephrology and Hypertension, University of North Carolina Kidney Center, Chapel Hill, and the W.G. (Bill) Hefner Veterans Affairs Medical Center, Salisbury - both in North Carolina (P.R.-C.); the Division of Nephrology, New York-Presbyterian Queens, Flushing (B.S.); Firma Clinical Research, Chicago (C.T.); Emory University School of Medicine, Atlanta (J.T.); Statistics Collaborative, Washington, DC (K.A.W., J.W.); and the Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Berlin (K.-U.E.).

Background: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production.

Methods: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52.

Results: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter.

Conclusions: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PROTECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).
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http://dx.doi.org/10.1056/NEJMoa2035938DOI Listing
April 2021

Giant Pituitary Adenoma Causing a Split in Optic Chiasm.

Neurol India 2021 Mar-Apr;69(2):532-533

Department of Neurosurgery and Gamma-Knife, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/0028-3886.314530DOI Listing
April 2021

Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse Model.

J Am Soc Nephrol 2021 Apr 23. Epub 2021 Apr 23.

CardioMetabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut.

Background: Fractalkine receptor 1 (CX3CR1) mediates macrophage infiltration and accumulation, causing venous neointimal hyperplasia (VNH)/venous stenosis (VS) in arteriovenous fistula (AVF). The effect of blocking CX3CR1 using an anti-human variable VHH molecule (hCX3CR1 VHH, BI 655088) on VNH/VS was determined using a humanized mouse in which the human () gene was knocked in (KI).

Methods: Whole-transcriptomic RNA sequencing with bioinformatics analysis was used on human stenotic AVF samples, C57BL/6J, KI mice with AVF and CKD, and in experiments to identify the pathways involved in preventing VNH/VS formation after hCX3CR1 VHH administration.

Results: Accumulation of CX3CR1 and CD68 was significantly increased in stenotic human AVFs. In C57BL/6J mice with AVF, there was increased , and gene expression, and increased immunostaining of CX3CR1 and CD68. In hCX3CR1-KI mice treated with hCX3CR1 VHH molecule (KI-A), compared with vehicle controls (KI-V), there was increased lumen vessel area and patency, and decreased neointima in the AVF outflow veins. RNA-seq analysis identified TNF- and NF-B as potential targets of CX3CR1 inhibition. In KI-A-treated vessels compared with KI-V, there was decreased gene expression of , , and ; with reduction of , NF-B, and ; decreased M1, Ly6C, smooth muscle cells, fibroblast-activated protein, fibronectin, and proliferation; and increased TUNEL and M2 staining. In cell culture, monocytes stimulated with PMA and treated with hCX3CR1 VHH had decreased , , proliferation, and migration.

Conclusions: CX3CR1 blockade reduces VNH/VS formation by decreasing proinflammatory cues.
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http://dx.doi.org/10.1681/ASN.2020101458DOI Listing
April 2021

"Pearls & Oy-sters:" Paradoxical Head Tilt in a Congenital Fourth Nerve Palsy.

Neurology 2021 Apr 23. Epub 2021 Apr 23.

Amit Kumar Sharma, Department of Clinical Neurological Sciences, London Health Sciences Centre, London, Ontario; David Dongkyung Kim, Department of Clinical Neurological Sciences, London Health Sciences Centre, London, Ontario; John A. Fraser, Department of Clinical Neurological Sciences, London Health Sciences Centre, London, Ontario.

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http://dx.doi.org/10.1212/WNL.0000000000012082DOI Listing
April 2021

Is Compliance with Guideline Recommended Follow-Up after Aortic Dissection associated with Survival?

Ann Thorac Surg 2021 Apr 17. Epub 2021 Apr 17.

Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN. Electronic address:

Background: Patients with acute aortic dissection remain at risk for long-term complications and thus are recommended to closely adhere to ACC/AHA aorta guideline-based follow-up imaging and clinic visits. The long term outcomes of compliance with such a model is not well understood.

Methods: Retrospective cohort study of patients at a regional aortic dissection center surviving hospital discharge for AD were analyzed by compliance with initial follow-up at 3 months and long term after aortic dissection. The primary endpoint was death.

Results: 172 (66% type A, 33% type B) patients survived hospitalization and were followed over 48 IQR (21, 88) months. 122 (71%) attended the first follow-up appointment and 90 (52%) of patients attended over 2/3 of recommended appointments. Patients who attended the first follow-up visit, had improved long-term follow up compliance (75% IQR (50, 91) compared to those not attending the first visit (18% IQR (0, 57)). Noncompliance with the scheduled long term follow-up was associated with 50% increase in the risk of death: HR=1.6 with 95% Confidence Interval of (1.2, 2.1), p<0.001. Furthermore, in low-compliance (consistently attending <1/3 of follow-ups) the life-time risk of death following AD was more than double that of high compliance (consistently attending >2/3 of appointments): HR=2.2 95% Confidence interval (1.5, 3.1), p<0.001.

Conclusions: Nearly 1/3 of aortic dissection patients do not attend the first recommended follow up visit and such failure was associated with later noncompliance with subsequent follow-up. Low-compliant patients have double the lifetime risk of death after aortic dissection than high-compliant patients.
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.010DOI Listing
April 2021

Isolated Leptomeningeal Recurrence of Multiple Myeloma.

Neurohospitalist 2021 Jan 1;11(1):87-88. Epub 2020 Jul 1.

Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

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http://dx.doi.org/10.1177/1941874420937562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022179PMC
January 2021

Synthesis of dextrin-polyacrylamide and boric acid based tough and transparent, self-healing, superabsorbent film.

Int J Biol Macromol 2021 Apr 16;182:712-721. Epub 2021 Apr 16.

Department of Chemistry, Dr B R Ambedkar National Institute of Technology, Jalandhar 144 011, Punjab, India. Electronic address:

Stretchabiliy, transparency and self-healing ability of bio-based materials are some of the important features for their utilization in the biomedical field. Recently, robust self-healing super porous materials possessing multifunctional nature have raised enormous interest among the researchers in order to design different materials which can be used in industrial, biomedical and pharmaceutical fields. Herein, a novel self-healing, stretchable and transparent superabsorbent film based on Dextrin-polyacrylamide and Boric Acid (D-cl-polyAAm) was synthesized using a free radical reaction mechanism. In distilled water, the maximum water absorptivity of the synthesized film was reported to be 3156% after the optimization of various reaction parameters. The film was also found to show structural integrity in urea solution, phosphate buffer and solutions of different pH. Lastly, the viscoelastic and self-healing analysis of the film suggested its utility towards biomedical field.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.028DOI Listing
April 2021

Safety and Efficacy of Trans-Perineal Urethroplasty for Management of Post-Traumatic Urethral Strictures in Pediatric Age-Group.

Urol Int 2021 Apr 13:1-5. Epub 2021 Apr 13.

Department of Urology, TNMC & BYL Nair Hospital, Mumbai, India.

Introduction: Trans-perineal urethroplasty is the preferred treatment for distraction urethral injuries in adults. However, management of such injuries in children is challenging because of functional implications in a growing child. In the present study, we aim to evaluate the safety and efficacy of perineal urethroplasty for distraction urethral injuries in children.

Methods: The medical records of prepubertal pediatric patients (age <14 years) with traumatic urethral distraction injuries managed by perineal urethroplasty were retrospectively reviewed and analyzed with respect to demographics, stricture characteristics, management, complications, follow-up, and outcome.

Results: A total of 14 patients were included in the study. Ten had membranous, and 4 had bulbar urethral strictures. All membranous strictures were secondary to pelvic trauma; bulbar strictures were secondary to blunt perineal trauma; 7 patients had associated pelvic fractures. Anastomotic urethroplasty was used in 10 patients (71.4%) and buccal mucosal graft urethroplasty was done in 4 patients (38.6%). The mean follow-up duration was 56 months (range 24-76). Surgery was primarily successful in 85.7%. Failed repair in 2 patients was successfully managed with augmented anastomotic urethroplasty. Post-operatively, the mean maximal urinary flow rate was 26.4 mL/s. No significant complications occurred. All boys are continent. There was no chordee or urethral diverticula, during follow-up.

Conclusion: In pediatric patients, bulbar and membranous strictures can be treated successfully with urethroplasty using the perineal approach. Longer follow-up is needed to confirm that these good results are maintained as these patients cross into adulthood, especially as these repairs were done before puberty.
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http://dx.doi.org/10.1159/000515612DOI Listing
April 2021

Recent advancement in topical drug delivery for psoriasis: Clinical Pertinence and Potential Market.

Curr Drug Targets 2021 Apr 12. Epub 2021 Apr 12.

Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001. India.

Psoriasis is an immune-mediated chronic skin inflammation. This disease can be associated with several manifestation like red flaks, silver scale, patches, plaques and silvery-white squams. Approximately 70% of the patients treated with topical dosage forms have a mild-to-moderate form of psoriasis, whereas a moderate-to-severe form of psoriasis is treated with systemic, photo, and biological therapies. Considering the big fraction that topicals cover, we present the current market potential, clinical relevance, and recent advances in the topical delivery of the drug for psoriasis. Though we witnessed several advancements in the recent few decades, delivering new immunomodulatory and biological molecules for topical psoriatic treatment have been proved efficient and safe option for the large percentage of patients for whom systemic therapy is not indicated. This article enumerates the promising topical dosage forms at present under assessment for their clinical pertinence. The competency of conventional topicals to reach and transform the world market is enumerated in terms of their success rate after proving the clinical pertinence against psoriasis. However, the entrance of novel drug delivery systems based advanced topical products in the global market is highly anticipated as they have immense potential to precedent tremendous impact on psoriasis treatment in near future.
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http://dx.doi.org/10.2174/1389450122666210412124256DOI Listing
April 2021

Gossypiboma: An uncommon but avoidable dreadful complication.

Urologia 2021 Apr 12:3915603211010636. Epub 2021 Apr 12.

All India Institute of Medical Sciences - Raipur, Raipur, CT, India.

Gossypiboma or retained surgical sponge in abdominal cavity is an avoidable complication which has wide variety of clinical presentations and associated medico-legal issues as well. The incidence is under-reported. Pre-operative diagnosis is difficult and management is surgical. We present a case of gossypiboma in a male with multiple vesico-cutaneous and colo-vesical fistulae.
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http://dx.doi.org/10.1177/03915603211010636DOI Listing
April 2021

Design, Synthesis, and Structural Analysis of Cladosporin-Based Inhibitors of Malaria Parasites.

ACS Infect Dis 2021 Apr 12. Epub 2021 Apr 12.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite () lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with pharmacokinetics. Co-crystallization of the most potent compound in our series () with KRS revealed its structural basis of enzymatic binding and potency. Further, we report that has performed better than cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold.
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http://dx.doi.org/10.1021/acsinfecdis.1c00092DOI Listing
April 2021

Epidemiology and clinical outcomes of severe Plasmodium vivax malaria in India.

J Infect 2021 Apr 5. Epub 2021 Apr 5.

ICMR-National Institute of Malaria Research, Sector 8, Dwarka, New Delhi 110077, India. Electronic address:

Objectives: A systematic review and meta-analysis (SR-MA) of the available Indian literature on severe vivax malaria (SVM) was undertaken.

Methods: Relevant studies in eight electronic databases were retrieved and reviewed. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed. The methodological quality of the studies included in the MA was assessed.

Results: Overall, 162 studies were included in the work. The pooled proportion of SVM was 29.3%. The main severity signs/symptoms seen in SVM were jaundice, severe thrombocytopenia (ST), multi-organ dysfunction, and severe anaemia with pooled proportion of 37.4%, 37.2%, 24.2% and 20.4%, respectively. P. falciparum was inducing 6% less ST (RR = 0.94, 95% CI 0.5-1.5, I = 77.87%), 10% less thrombocytopenia (RR = 0.9, 95% CI 0.7-1.1, I = 91.68%) and 20% less DIC (RR = 0.8, 95% CI 0.3-1.9, I = 0%) than P. vivax. An atypical condition like myocarditis, was most commonly observed among the studied SVM cases. The mortality rate in SVM cases ranged from 0 to 12.9% among hospital patients with P. vivax mono-infections.

Conclusions: The present SR-MA provides evidence for P. vivax as the etiologic agent of severe malaria leading to deaths in few cases as seen recently in India. However, research gaps outlined here emphasise the need for further studies on SVM in pregnancy, SVM in drug resistance and correlations with cytoadherence in disease severity due to P. vivax.
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http://dx.doi.org/10.1016/j.jinf.2021.03.028DOI Listing
April 2021

Introducing Tb in (Ce/Eu)TbMoO Metal Oxide at Room Temperature and Its Use in Amyloid Defibrillation.

ACS Appl Mater Interfaces 2021 Apr 7;13(15):18184-18193. Epub 2021 Apr 7.

Department of Chemistry, National Sun Yat-Sen University, No. 70, Lien-Hai Road, Kaohsiung 804, Taiwan.

Tunable optical properties in nanomaterials enable a variety of applications in multidisciplinary areas. These properties are directly related to several different factors such as solvent conditions, synthesis methods, and most significantly, the oxidation states of metals participating in the absorption or emission properties. Lanthanide metals containing ABO perovskites are among such nanomaterials that can be tuned to a great extent by only modifying the charged states on the metals in the composition. We report a green synthesis method through sonication to synthesize ABO perovskites to incorporate Tb into the perovskite composition at room temperature. The optical properties of the nanomaterial show emission in the entire ultraviolet-visible-near-infrared spectral regions through charge transfer between europium and terbium. The combination of cerium (C), molybdenum (M), europium (E), and terbium (T) results in a sheet-like CMET perovskite obeying hexagonal geometry. The nanomaterial is highly stable in an aqueous medium, showing finely suspended Tyndall effect due to particle size <300 nm. Owing to their wide range of emission behavior, surface charge, and aqueous stability, CMET perovskites were used to study the defibrillation of hen egg-white lysozyme (HEWL) as an amyloid model protein. The intrinsic property of the nanomaterial assists in the interaction of the fibrils with the perovskite and the emission range becomes the reporter of the defibrillation. Infrared spectroscopy shows the change in the material properties during the defibrillation. A preliminary test on the varying concentration of HEWL incubated with CMET perovskites shows linear behavior with = 0.9841. The tunable emission characteristic and aqueous stability of the perovskite material make it suitable for future biological applications.
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http://dx.doi.org/10.1021/acsami.0c17806DOI Listing
April 2021

Malaria elimination in India requires additional surveillance mechanisms.

J Public Health (Oxf) 2021 Apr 5. Epub 2021 Apr 5.

National Institute of Malaria Research, New Delhi 110 077, India.

Malaria surveillance is weak in high malaria burden countries. Surveillance is considered as one of the core interventions for malaria elimination. Impressive reductions in malaria-associated morbidity and mortality have been achieved across the globe, but sustained efforts need to be bolstered up to achieve malaria elimination in endemic countries like India. Poor surveillance data become a hindrance in assessing the progress achieved towards malaria elimination and in channelizing focused interventions to the hotspots. A major obstacle in strengthening India's reporting systems is that the surveillance data are captured in a fragmented manner by multiple players, in silos, and is distributed across geographic regions. In addition, the data are not reported in near real-time. Furthermore, multiplicity of malaria data resources limits interoperability between them. Here, we deliberate on the acute need of updating India's surveillance systems from the use of aggregated data to near real-time case-based surveillance. This will help in identifying the drivers of malaria transmission in any locale and therefore will facilitate formulation of appropriate interventional responses rapidly.
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http://dx.doi.org/10.1093/pubmed/fdab106DOI Listing
April 2021

Respiratory setback associated with extubation failure in extremely preterm infants.

Pediatr Pulmonol 2021 Apr 5. Epub 2021 Apr 5.

Department of Pediatrics, Central Michigan University, Detroit, Michigan, USA.

Background And Objectives: Extubation failure in preterm infants is associated with an increased risk of mortality and morbidity. There is limited evidence to suggest if the increased morbidities are due to inherent differences among infants who fail or succeed; or whether these are due to a true respiratory setback among those who fail extubation. The aim of this study was to evaluate the respiratory status of infants who fail extubation and to assess the time taken for these infants to achieve pre-extubation respiratory status.

Methods: This was a retrospective study of infants with birth weight ≤ 1250 g who were born between January 2009 and December 2016. Infants were eligible if they failed first elective extubation. Extubation failure was defined as need for re-intubation within 5 days of extubation. Ventilator settings, blood gas parameters, respiratory severity score (RSS), and ventilation index (VI) were used to assess the respiratory status of infants.

Results: Out of 384 infants, 76% were successful and 24% failed extubation. Among those who failed extubation 91%, 77%, and 56% infants remained intubated at 24 h, 72 h, and 7 days, respectively. Respiratory status was worse at 24 and 72 h after re-intubation when compared to pre-extubation levels. The median times for RSS and VI to reach pre-extubation levels were 4 and 7 days, respectively.

Conclusion: Among preterm infants, failed elective extubation is associated with a significant setback in the respiratory status. Infants who fail an extubation attempt may not achieve pre-extubation respiratory status for many days after reintubation.
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http://dx.doi.org/10.1002/ppul.25387DOI Listing
April 2021

Tetanus Complicated by Dysautonomia: A Case Report and Review of Management.

Case Rep Crit Care 2021 16;2021:8842522. Epub 2021 Mar 16.

Geisinger Community Medical Center, 1800 Mulberry Street, Scranton, PA 18510, USA.

Tetanus is a life-threatening infectious neurological disorder that is now a rare disease due to the institution of wide-spread vaccination strategies. We present an uncommon case of generalized severe tetanus with consequent respiratory failure requiring mechanical ventilation, which was associated with dysautonomia. A 20-year-old unvaccinated female presented with neck stiffness and diffuse muscle spasms following a laceration sustained 3 weeks prior. She was admitted to the intensive care unit for mechanical ventilation and was treated with immunoglobulin, tetanus toxoid, metronidazole, and high doses of sedatives. She also developed dysautonomia, with alternating bradycardia and tachycardia, as well as fluctuating blood pressure. She was successfully extubated and discharged. We also review the epidemiology, pathophysiology, and management of tetanus and discuss dysautonomia in the setting of tetanus.
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http://dx.doi.org/10.1155/2021/8842522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987407PMC
March 2021

Medial Medullary Infarction With Acute Bilateral Vertebral Artery Occlusions.

Neurohospitalist 2021 Apr 11;11(2):181-182. Epub 2020 Sep 11.

Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

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http://dx.doi.org/10.1177/1941874420957167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958683PMC
April 2021

Geographical spread and structural basis of sulfadoxine-pyrimethamine drug-resistant malaria parasites.

Int J Parasitol 2021 Mar 26. Epub 2021 Mar 26.

Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India; National Institute of Malaria Research, Dwarka, New Delhi, India. Electronic address:

The global spread of sulfadoxine (Sdx, S) and pyrimethamine (Pyr, P) resistance is attributed to increasing number of mutations in DHPS and DHFR enzymes encoded by malaria parasites. The association between drug resistance mutations and SP efficacy is complex. Here we provide an overview of the geographical spread of SP resistance mutations in Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) encoded dhps and dhfr genes. In addition, we have collated the mutation data and mapped it on to the three-dimensional structures of DHPS and DHFR which have become available. Data from genomic databases and 286 studies were collated to provide a comprehensive landscape of mutational data from 2005 to 2019. Our analyses show that the Pyr-resistant double mutations are widespread in Pf/PvDHFR (P. falciparum ∼61% in Asia and the Middle East, and in the Indian sub-continent; in P. vivax ∼33% globally) with triple mutations prevailing in Africa (∼66%) and South America (∼33%). For PfDHPS, triple mutations dominate South America (∼44%), Asia and the Middle East (∼34%) and the Indian sub-continent (∼27%), while single mutations are widespread in Africa (∼45%). Contrary to the status for P. falciparum, Sdx-resistant single point mutations in PvDHPS dominate globally. Alarmingly, highly resistant quintuple and sextuple mutations are rising in Africa (PfDHFR-DHPS) and Asia (Pf/PvDHFR-DHPS). Structural analyses of DHFR and DHPS proteins in complexes with substrates/drugs have revealed that resistance mutations map proximal to Sdx and Pyr binding sites. Thus new studies can focus on discovery of novel inhibitors that target the non-substrate binding grooves in these two validated malaria parasite drug targets.
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http://dx.doi.org/10.1016/j.ijpara.2020.12.011DOI Listing
March 2021

Simultaneous knockout of multiple LHCF genes using single sgRNAs and engineering of a high-fidelity Cas9 for precise genome editing in marine algae.

Plant Biotechnol J 2021 Mar 24. Epub 2021 Mar 24.

Cell, Molecular Biology and Genomics Group, Department of Biology, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

The CRISPR/Cas9 system is an RNA-guided sequence-specific genome editing tool, which has been adopted for single or multiple gene editing in a wide range of organisms. When working with gene families with functional redundancy, knocking out multiple genes within the same family may be required to generate a phenotype. In this study, we tested the possibility of exploiting the known tolerance of Cas9 for mismatches between the single-guide RNA (sgRNA) and target site to simultaneously introduce indels in multiple homologous genes in the marine diatom Phaeodactylum tricornutum. As a proof of concept, we designed two sgRNAs that could potentially target the same six light-harvesting complex (LHC) genes belonging to the LHCF subgroup. Mutations in up to five genes were achieved simultaneously using a previously established CRISPR/Cas9 system for P. tricornutum. A visible colour change was observed in knockout mutants with multiple LHCF lesions. A combination of pigment, LHCF protein and growth analyses was used to further investigate the phenotypic differences between the multiple LHCF mutants and WT. Furthermore, we used the two same sgRNAs in combination with a variant of the existing Cas9 where four amino acids substitutions had been introduced that previously have been shown to increase Cas9 specificity. A significant reduction of off-target editing events was observed, indicating that the altered Cas9 functioned as a high-fidelity (HiFi) Cas9 nuclease.
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http://dx.doi.org/10.1111/pbi.13582DOI Listing
March 2021

Enhancement of dynamical robustness in a mean-field coupled network through self-feedback delay.

Chaos 2021 Jan;31(1):013114

Department of Mathematics, Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Coimbatore 641 112, India.

The network of self-sustained oscillators plays an important role in exploring complex phenomena in many areas of science and technology. The aging of an oscillator is referred to as turning non-oscillatory due to some local perturbations that might have adverse effects in macroscopic dynamical activities of a network. In this article, we propose an efficient technique to enhance the dynamical activities for a network of coupled oscillators experiencing aging transition. In particular, we present a control mechanism based on delayed negative self-feedback, which can effectively enhance dynamical robustness in a mean-field coupled network of active and inactive oscillators. Even for a small value of delay, robustness gets enhanced to a significant level. In our proposed scheme, the enhancing effect is more pronounced for strong coupling. To our surprise even if all the oscillators perturbed to equilibrium mode were delayed negative self-feedback is able to restore oscillatory activities in the network for strong coupling strength. We demonstrate that our proposed mechanism is independent of coupling topology. For a globally coupled network, we provide numerical and analytical treatment to verify our claim. To show that our scheme is independent of network topology, we also provide numerical results for the local mean-field coupled complex network. Also, for global coupling to establish the generality of our scheme, we validate our results for both Stuart-Landau limit cycle oscillators and chaotic Rössler oscillators.
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http://dx.doi.org/10.1063/5.0015821DOI Listing
January 2021

Impact of physical activity and cooking oil amongst diabetes with coexisting hypertension patients on economic cost and length of stay: A 1914 patient's observational study.

Int J Clin Pract 2021 Mar 20:e14163. Epub 2021 Mar 20.

Department of Pharmaceutics, Himalayan Institute of Pharmacy and Research, Abdullapur, Uttarakhand, India.

Aim Of The Study: The study aimed to investigate the impact of the patients' physical activity status and the type of cooking oil consumed by patients in their daily routine on glycaemic profile, lipid profile, the hypertensive profile of the patients, the length of stay and overall cost of the treatment.

Methods: This is a prospective observational study. All the patients referred to the medicine department of the three different hospitals located in Moga, City Punjab, and those hospitalised due to diabetes mellitus (types I and II) with coexisting hypertension were asked to participate in the study.

Results: The patients' mean age was found to be M = 53.85, SD = 11.54 years. Out of 1914 patients, 914 were male (47.8%); it was observed that the majority of the patients 525 (27.43%) in North India using butter or ghee-clarified butter as edible oil, followed by mustard oil 517 (27.01%) patients. About 345 (18.03%) of the patients consume soybean oil, whereas 226 (11.81%) of the patients like sunflower oil.

Conclusion: This study explored that cooking oil and physical activity are associated with length of stay in days and overall cost of the treatment, respectively. Our study results revealed that the type of oil compared with the treatment's overall cost was significant for olive oil, soybean oil and groundnut oil. The study revealed that moderate and low physical activity increases the length of stay compared to high physical activity. The consumption of olive oil as a regular food habit in daily routine decreases patients' length of stay with diabetes with coexisting hypertension when doing high physical activity but increases the overall cost of treatment.
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http://dx.doi.org/10.1111/ijcp.14163DOI Listing
March 2021

Clinical features, severity and outcome of acute pancreatitis in systemic lupus erythematosus.

Rheumatol Int 2021 Mar 16. Epub 2021 Mar 16.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.

Acute pancreatitis (AP) is a rare but life threatening manifestation of Systemic Lupus Erythematosus (SLE). The current study aims to study the clinical characteristics, severity, mortality, and outcome of SLE-related AP in Indian population. We retrospectively reviewed medical records of patients with SLE who had AP in the past. Data from 13 rheumatology centers across India were compiled. All patients satisfied SLICC criteria for SLE and ATLANTA criteria for AP. AP was classified in to mild, moderate and severe using revised Atlanta classification. Patients with known risk factors like gall stone and alcohol were excluded.Sixty-six patients (six, children) were studied. Majority of patients were females (82%). The median age of presentation was 24 (11-63) years and most patients (57.5%) presented within first year of diagnosis of lupus. AP occurred mostly in the setting of active lupus (89%). Active nephritis was seen in 39% while a fourth had CNS disease. Patients with severe AP had lower C3. Ascites and sepsis were most common local and systemic complications, respectively. Mortality was 17%. Hypocalcemia, presence of sepsis and shock predicted mortality. In the multivariate analysis, only presence of shock remained as independent predictor of death (OR 63.0, 95% CI: 5.2-760.3). Pancreatitis is an early manifestation of SLE and is associated with active disease. Significant mortality is seen particularly with severe pancreatitis.
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http://dx.doi.org/10.1007/s00296-021-04834-2DOI Listing
March 2021

Identification of novel therapeutic targets for contrast induced acute kidney injury (CI-AKI): alpha blockers as a therapeutic strategy for CI-AKI.

Transl Res 2021 Mar 9. Epub 2021 Mar 9.

Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Department of Pulmonary and Critical Care Medicine Mayo Clinic, Rochester, Minnesota. Electronic address:

Iodinated contrast is used for imaging and invasive procedures and it can cause contrast induced acute kidney injury (CI-AKI), which is the third leading hospital-acquired health problem. The purpose of the present study was to determine the effect of α-adrenergic receptor-1b (Adra1b) inhibition by using terazosin on change in kidney function, gene, and protein expression in C57BL/6J male mice, 6-8 weeks with chronic kidney disease (CKD). CKD was induced by surgical nephrectomy. Twenty eight days later, 100-µL of iodinated contrast (CI group) or saline (S group) was given via the carotid artery. Whole-transcriptome RNA-sequencing (RNA-Seq) analysis of the kidneys was performed at day 2. Mice received either 50-µL of saline ip or terazosin (2 mg/kg) in 50-µL of saline ip 1 hour before contrast administration which was continued every 12 hours until the animals were euthanized 2 and 7 days later. The kidneys were removed for gene expression, immunohistochemical analysis, and blood serum analyzed for kidney function. Differential gene expression analysis identified 21 upregulated and 436 downregulated genes (fold change >2; P < 0.05) that were common to all sample (n = 3 for both contrast and saline). We identified Adra1b using bioinformatic analysis. Mice treated with terazosin had a significant decrease in serum creatinine, urinary Kim-1 levels, HIF-1α, apoptosis, and downstream Adrab1 genes including Ece1, Edn1, pMAPK14 with increased cell proliferation. Contrast exposure upregulated Adra1b gene expression in HK-2 cells. Inhibition of Adra1b with terazosin abrogated Ece1, Edn1, and contrast-induced Fsp-1, Mmp-2, Mmp-9 expression, and caspase-3/7 activity in HK-2 cells.
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http://dx.doi.org/10.1016/j.trsl.2021.03.005DOI Listing
March 2021

An Unusual Case of Primary Intracranial Germinoma with Diffuse Subarachnoid Spread Masquerading as Tuberculous Meningitis.

Asian J Neurosurg 2020 Oct-Dec;15(4):1027-1030. Epub 2020 Oct 19.

Department of Pathology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.

Central nervous system (CNS) germinomas often extend or disseminate into the ventricular and subarachnoid space. We present a case of primary CNS germinoma consisting mainly of meningeal dissemination, which is extremely unusual and must be kept in the differential diagnosis.
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http://dx.doi.org/10.4103/ajns.AJNS_174_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869262PMC
October 2020

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India.

Virology 2021 06 5;558:13-21. Epub 2021 Mar 5.

ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India. Electronic address:

India is one of the most affected countries by COVID-19 pandemic; but little is understood regarding immune responses to SARS-CoV-2 in this region. Herein we examined SARS-CoV-2 neutralizing antibodies, IgG, IgM, IgA and memory B cells in COVID-19 recovered individual from India. While a vast majority of COVID-19 recovered individuals showed SARS-CoV-2 RBD-specific IgG, IgA and IgM antibodies (38/42, 90.47%; 21/42, 50%; 33/42, 78.57% respectively), only half of them had appreciable neutralizing antibody titers. RBD-specific IgG, but not IgA or IgM titers, correlated with neutralizing antibody titers and RBD-specific memory B cell frequencies. These findings have timely significance for identifying potential donors for plasma therapy using RBD-specific IgG assays as surrogate measurement for neutralizing antibodies in India. Further, this study provides useful information needed for designing large-scale studies towards understanding of inter-individual variation in immune memory to SARS CoV-2 natural infection for future vaccine evaluation and implementation efforts.
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http://dx.doi.org/10.1016/j.virol.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934698PMC
June 2021

Epidemiological profiles of SARS-CoV and SARS-Cov-2 in Singapore and its promising containment strategies.

J Glob Health 2021 Jan 30;11:03027. Epub 2021 Jan 30.

Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

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http://dx.doi.org/10.7189/jogh.11.03027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914380PMC
January 2021

Colistin Resistance Among Multiple Sequence Types of Is Associated With Diverse Resistance Mechanisms: A Report From India.

Front Microbiol 2021 22;12:609840. Epub 2021 Feb 22.

ICMR-National Institute of Pathology, New Delhi, India.

The resistance to colistin and carbapenems in infections have been associated with increased morbidity and mortality worldwide. A retrospective observational study was conducted to determine the prevalence and molecular events contributing to colistin resistance. Clinical samples were screened for colistin resistance and underlying mechanisms were studied by PCR-based amplification and sequence analysis of genes of two-component regulatory system ( and ), regulatory transmembrane protein-coding , and mobilized colistin resistance genes (). Gene expression of and was analyzed by qRT-PCR, and the genetic relationship was assessed by MLST. The putative effect of amino-acid substitutions was predicted by a combination of bioinformatics tools. Of 335 spp. screened, 11 (3.2%) were identified as colistin-resistant (MIC range, 8 to >128 μg/ml). isolates belonged to clonal complex-11 (CC11) with sequence types (STs): 14, 16, 43, 54, 147 and 395, whereby four isolates conferred three novel STs (3986, 3987 and 3988) profiles. Sequence analysis revealed non-synonymous potentially deleterious mutations in (T151A), (del87-90, del263-264, L30Q, and A351D), (G53S), (D150V, T157P, L237R, G250C, A252G, R315P, and Q331H), and (C28G) genes. The gene in three strains was disrupted by insertion sequences encoding IS-like and IS/IS family-like transposase genes. All 11 isolates showed an elevation in the transcription level of gene. Mobilized colistin-resistance () genes were not detected. All but one of the colistin-resistant isolates was also resistant to carbapenems; β-lactamase genes , , and were detected in eight, five, and nine isolates, respectively. All the studied colistin- and carbapenem-resistant isolates were genetically distinct, and various mechanisms of colistin resistance were detected, indicating its spontaneous emergence in this bacterial species.
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http://dx.doi.org/10.3389/fmicb.2021.609840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937630PMC
February 2021