Publications by authors named "Neha Sharma"

269 Publications

Novel Antiplasmodial Compounds Leveraged with Multistage Potency against the Parasite : and Evaluations and Pharmacokinetic Studies.

J Med Chem 2021 Jun 14. Epub 2021 Jun 14.

Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi 110007, India.

Hydroxyethylamine (HEA)-based novel compounds were synthesized and their activity against 3D7 was assessed, identifying a few hits without any apparent toxicity. Hits and also exhibited activity against resistant field strains, RKL-9 and C580Y. A single dose, 50 mg/Kg, of hits administered to the rodent parasite ANKA exhibited up to 70% reduction in the parasite load. Compound tested in combination with artesunate produced an additional antiparasitic effect with a prolonged survival period. Additionally, compound showed 50% inhibition against hepatic infection at 1.56 ± 0.56 μM concentration. This compound also considerably delayed the progression of transmission stages, ookinete and oocyst. Furthermore, the toxicity of assessed in mice supported the normal liver and kidney functions. Altogether, HEA analogues (), particularly , are nontoxic multistage antiplasmodial agents with therapeutic and transmission-blocking efficacy, along with favorable preliminary pharmacokinetic properties.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00659DOI Listing
June 2021

Combating COVID-19 pandemic in India: Demystifying the concept of herd immunity.

J Family Med Prim Care 2021 Apr 29;10(4):1515-1519. Epub 2021 Apr 29.

Chairperson, Primary Care and Public Health Policy Forum, Academy of Family Physicians of India, New Delhi, India.

The concept of Herd immunity is a key factor for epidemic control. According to it only a proportion of entire population needs to be immune either via natural infection or vaccination. The idea of herd immunity via natural infection rather than vaccination is a bit controversial, as it is not clear how long will the antibodies last, and whether re-infection or re-activation of the virus can occur after the antibodies starts weaning from the body. It has been suggested that coronavirus will likely become similar to a seasonal flu once the herd immunity is attained. Till then, it will continue causing outbreaks year-round and there could be multiple waves of virus transmission before achieving herd immunity. Therefore, the public needs to learn to live with it, and continue practising the best prevention measures, including wearing of masks, physical distancing, hand hygiene, and avoidance of gathering.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1971_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144793PMC
April 2021

An unrecognised risk in endotracheal intubation by a Truview laryngoscope.

Indian J Anaesth 2021 Apr 15;65(4):337-338. Epub 2021 Apr 15.

Department of Anaesthesia, Lady Hardinge Medical College and Smt Sucheta Kriplani and Kalawati Saran Children's Hospital, New Delhi, India.

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http://dx.doi.org/10.4103/ija.IJA_1137_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174588PMC
April 2021

Electrochemical detection of hydrocortisone using green-synthesized cobalt oxide nanoparticles with nafion-modified glassy carbon electrode.

Chemosphere 2021 May 28;282:131029. Epub 2021 May 28.

Department of Bionanotechnology, Gachon University, Gyeonggi-Do, 13120, Republic of Korea. Electronic address:

Developing highly sensitive and selective sensors is important for the detection of steroid hormones. Electrochemical sensors are of great interest in this regard. Also utilization of bio-derived substances as an electrode material is environment friendly. In this study, we used green-synthesized cobalt oxide nanoparticles (CoO NPs) along with nafion (Naf) on a glassy carbon electrode to detect hydrocortisone (HC) by voltammetry. Electron microscopy, X-ray diffraction, Raman spectroscopy, ultraviolet-visible spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy were used to characterize the CoO NPs prepared using Nigella sativa seeds extract. Cyclic voltammetry and differential pulse voltammetry was utilized for the detection of HC. Only one reduction peak at -0.5 V was observed in the presence of HC in 0.1 M sodium hydroxide, indicating an irreversible electrode process. The Naf-CoO NPs enhanced the active surface area of the glassy carbon electrode (GCE) that resulted in a good response for detecting HC with two linear ranges: 0.001-1 μM and 1-9 μM. In comparison to other published electrochemical sensors, the current sensor displayed a low limit of detection of 0.49 nM, as well as remarkable stability and reproducibility. The sensor exhibited credibility for the sensing of HC in pharmaceutical injections and blood serum samples with recovery percentages ranging from 97.7% to 102.5%. The electrochemical sensor has proved to be valuable for HC detection.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131029DOI Listing
May 2021

Mechanistic Studies of Dnase I Activity: Impact of Heparin Variants and PAD4.

Shock 2021 May 24. Epub 2021 May 24.

Department of Medical Sciences, McMaster University, Hamilton ON, Canada Thrombosis and Atherosclerosis Research Institute (TaARI), Hamilton ON, Canada . Department of Medicine, McMaster University, Hamilton ON, Canada.

Background: Excessive production of neutrophil extracellular traps (NETs) in sepsis contributes to vascular occlusion by acting as a scaffold and stimulus for thrombus formation. Removal of extracellular DNA, the major structural component of NETs, by DNase I may reduce host injury.

Objectives: (1) To determine how heparin variants (unfractionated heparin, enoxaparin, Vasoflux, and fondaparinux) affect DNase I activity, (2) to measure temporal changes in circulating DNA and DNase I in septic patients.

Methods: DNA-histone complexes were treated with DNase I ± heparin variants and visualized via agarose gels. We compared the ability of DNase I ± heparin variants to digest NETs released by PMA-stimulated neutrophils versus DNA-histone complexes released by necrotic HEK293 cells. Plasma DNA and DNase I levels were measured longitudinally in 76 septic patients.

Results: Heparin enhances DNase I-mediated digestion of DNA-histone complexes in a size-dependent manner that does not require the antithrombin-binding region. In contrast, DNase I alone was able to degrade the DNA-histone component of NETs presumably due to PAD4-mediated histone citrullination that weakens DNA-histone interactions. In purified systems, PAD4 treatment of DNA-histone complexes enhanced the ability of DNase I to degrade histone-bound DNA. In septic patients, endogenous DNase I levels remained persistently low over 28 days, and there were no significant correlations between DNA and DNase I levels.

Conclusion: Heparin enhances DNA-mediated digestion of DNA-histone complexes in a size-dependent manner that is independent of its anticoagulant properties. Citrullination of histones by PAD4 renders DNA-histone complexes susceptible to DNase I digestion. Endogenous DNase I levels are persistently decreased in septic patients, which supports the potential utility of DNase I as a therapy for sepsis.
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http://dx.doi.org/10.1097/SHK.0000000000001804DOI Listing
May 2021

A Tailored Heptazine-Based Porous Polymeric Network as a Versatile Heterogeneous (Photo)catalyst.

Chemistry 2021 May 24. Epub 2021 May 24.

Advanced Functional Nanomaterials, Nanotechnology for Energy and Environment, Institute of Nano Science and Technology (INST), Knowledge city, Sector-81, 140306, Manauli, SAS Nagar, Mohali, Punjab, India) .

A heptazine-based microporous polymeric network, HMP-TAPA was synthesised by direct coupling of trichloroheptazine and tris(4-aminophenyl)amine (TAPA). A high surface area of 424 m /g was achieved, which is the highest surface area among heptazine-based polymeric networks (HMPs). The tailored electron-donor and -acceptor units in HMP-TAPA give broad visible-light absorption. HMP-TAPA was employed as metal-free photocatalyst for oxidative coupling of amines to imines under visible light irradiation with 98 % selectivity. Furthermore, the surface basicity of HMP-TAPA was used to achieve metal-free heterogeneous base catalysis for Knoevenagel condensation under base-free conditions with >99 % conversion. In addition, HMP-TAPA showed extreme robustness over a wide pH range (1-14). The versatility and flexibility of the current material design is beneficial for understanding its photoactivity and surface basicity so as to design dual active (photo)catalyst materials for specific applications.
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http://dx.doi.org/10.1002/chem.202100595DOI Listing
May 2021

A computational model for predicting changes in infection dynamics due to leakage through N95 respirators.

Sci Rep 2021 May 21;11(1):10690. Epub 2021 May 21.

Division of Applied Mechanics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, USA.

In the absence of fit-testing, leakage of aerosolized pathogens through the gaps between the face and N95 respirators could compromise the effectiveness of the device and increase the risk of infection for the exposed population. To address this issue, we have developed a model to estimate the increase in risk of infection resulting from aerosols leaking through gaps between the face and N95 respirators. The gaps between anthropometric face-geometry and N95 respirators were scanned using computed tomography. The gap profiles were subsequently input into CFD models. The amount of aerosol leakage was predicted by the CFD simulations. Leakage levels were validated using experimental data obtained using manikins. The computed amounts of aerosol transmitted to the respiratory system, with and without leaks, were then linked to a risk-assessment model to predict the infection risk for a sample population. An influenza outbreak in which 50% of the population deployed respirators was considered for risk assessment. Our results showed that the leakage predicted by the CFD model matched the experimental data within about 13%. Depending upon the fit between the headform and the respirator, the inward leakage for the aerosols ranged between 30 and 95%. In addition, the non-fit-tested respirator lowered the infection rate from 97% (for no protection) to between 42 and 80%, but not to the same level as the fit-tested respirators (12%). The CFD-based leakage model, combined with the risk-assessment model, can be useful in optimizing protection strategies for a given population exposed to a pathogenic aerosol.
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http://dx.doi.org/10.1038/s41598-021-89604-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140115PMC
May 2021

Convexal Subarachnoid Hemorrhage Caused by Infective Endocarditis in a Patient with Advanced Human Immunodeficiency Virus (HIV): The Culprits and Bystanders.

Am J Case Rep 2021 May 14;22:e931376. Epub 2021 May 14.

Department of Infectious Disease, Rockledge Regional Medical Center, Rockledge, FL, USA.

BACKGROUND Convexal subarachnoid hemorrhage (cSAH), a rare form of non-aneurysmal subarachnoid hemorrhage, is confined to cerebral convexities without extension into basal cisterns or ventricles. Typical presentation includes thunderclap/progressive headache or transient focal neurological symptoms; rare manifestations include seizures, intractable vomiting, or altered mental status. Here, we report the first case of convexal subarachnoid hemorrhage and multifocal ischemic lesions caused by infective endocarditis (IE) in a treatment-naïve advanced HIV patient. CASE REPORT A 52-year-old HAART-naïve, HIV-positive, African American man presented with altered mental status, shortness of breath, nonproductive cough, and generalized weakness. His past medical history was significant for congestive heart failure, chronic obstructive pulmonary disease, and end-stage renal disease (noncompliant with hemodialysis). Head computed tomography (CT) showed an isolated sulcal hemorrhage in the mid-left frontal lobe. Fluid-attenuated inversion recovery/gradient recalled echo sequences confirmed a hemorrhage in the left-mid-frontal sulcus, and diffusion-weighted imaging revealed multifocal bilateral ischemic lesions. Transesophageal echocardiography exhibited mitral valve vegetations. Multifocal ischemic lesions and cSAH caused by infectious endocarditis were confirmed. Initiation of intravenous vancomycin and piperacillin-tazobactam allowed the patient to have resolution of his altered mental status. A head CT 5 days later revealed the resolution of cSAH. CONCLUSIONS Infective endocarditis should be considered as an underlying etiology of cSAH, especially when present with multifocal ischemic lesions. Risk factors contributing to the development of cSAH in the IE patient population should be explored in future studies. HIV has not been previously reported in this subgroup and its prevalence should be considered. The prognosis for cSAH in relation to IE is generally favorable.
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http://dx.doi.org/10.12659/AJCR.931376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130978PMC
May 2021

Use of ivabradine for treatment of junctional ectopic tachycardia in post congenital heart surgery.

Indian J Thorac Cardiovasc Surg 2021 May 7;37(3):323-325. Epub 2020 Oct 7.

Department of Pharmacology, SMS Medical College & Attached Hospitals, J L N Marg, Jaipur, Rajasthan 302001 India.

Cardiac surgeries especially involving crux of the heart as performed in tetralogy of Fallot (TOF) and pulmonary stenosis are mainly responsible for junctional ectopic tachycardia (JET). Diversified antiarrhythmic agents have been used in an impressive way to treat JET but showed suboptimal efficacy and varied associated adverse effects. But, ivabradine has proved as final crusader for its treatment. We report our initial experience of 4 cases in last 6 months with ivabradine in the management of postoperative JET. Encouraged by various reports and our increasing experience with ivabradine in heart failure population, we have moved to ivabradine as the first drug of choice for postoperative JET. Bradycardia was the only significant adverse effect in our series. The availability of atrial and ventricular pacing wires or at least transvenous temporary pacing should be ensured before starting ivabradine.
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http://dx.doi.org/10.1007/s12055-020-01056-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079487PMC
May 2021

Cell-free DNA in the surveillance of heart transplant rejection.

Indian J Thorac Cardiovasc Surg 2021 May 2;37(3):257-264. Epub 2021 Feb 2.

Department of Anatomy, SMS Medical College & Attached Hospitals, J L N Marg, Jaipur, Rajasthan 302001 India.

Background: Circulating cell-free deoxyribonucleic acid (cfDNA) is promptly materializing as a highly useful tool for the surveillance of solid-organ transplant rejection. Donor-specific fraction (DF) cfDNA is a potential marker of selective donor organ injury. It is emerging as a promising analytical target in the near future. The aim of this systematic review is to throw light on the importance of cfDNA and future perspective in detecting acute rejection in heart transplantation.

Methods: An exhaustive search was carried out for this review article on the basis of literature available including scientific databases of PubMed, Embase, and ClinicalTrials.gov. The search engines were systematically explored using the search terms "cell free DNA," "Heart transplant," and "Rejection" from inception until August 2020, and narrative analysis was accomplished. Majority of the studies described endomyocardial biopsy-proven acute rejection as reference standard.

Results: After initial screening of 331 articles, 11 studies were included and discussed in detail in the present review article. Majority of the studies showed prospective designs. A firm correlation was noted between acute rejection (identified on endomyocardial biopsy) and cfDNA levels by most of the studies.

Conclusions: cfDNA is a promising tool to replace repeated biopsies to detect rejection. The development in the area of digital droplet polymerase chain reaction and massive parallel sequencing, along with the overall reduction in cost of sequencing with its automation, has helped establish its role in the transplant population.
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http://dx.doi.org/10.1007/s12055-020-01130-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079572PMC
May 2021

N-Acetylcysteine Ameliorates Neurotoxic Effects of Manganese Intoxication in Rats: A Biochemical and Behavioral Study.

Neurochem Res 2021 May 5. Epub 2021 May 5.

Department of Biophysics, Basic Medical Sciences Block II, Panjab University, Chandigarh, 160014, India.

Clinical and experimental evidences reveal that excess exposure to manganese is neurotoxic and leads to cellular damage. However, the mechanism underlying manganese neurotoxicity remains poorly understood but oxidative stress has been implicated to be one of the key pathophysiological features related to it. The present study investigates the effects associated with manganese induced toxicity in rats and further to combat these alterations with a well-known antioxidant N-acetylcysteine which is being used in mitigating the damage by its radical scavenging activity. The study was designed to note the sequential changes along with the motor and memory dysfunction associated with biochemical and histo-pathological alterations following exposure and treatment for 2 weeks. The results so obtained showed decrease in the body weights, behavioral deficits with increased stress markers and also neuronal degeneration in histo-pathological examination after manganese intoxication in rats. To overcome the neurotoxic effects of manganese, N-acetylcysteine was used in the current study due to its pleiotropic potential in several pathological ailments. Taken together, N-acetylcysteine helped in ameliorating manganese induced neurotoxic effects by diminishing the behavioral deficits, normalizing acetylcholinesterase activity, and augmentation of redox status.
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http://dx.doi.org/10.1007/s11064-021-03312-2DOI Listing
May 2021

Seasonal variation in fluorescence characteristics of dissolved organic matter in wastewater and identification of proteins through HRLC-MS/MS.

J Hazard Mater 2021 07 18;413:125453. Epub 2021 Feb 18.

Environmental Science and Engineering Department (ESED), IIT Bombay, Mumbai, India. Electronic address:

In the present study, wastewater samples acquired from five wastewater treatment plants (WWTPs), located in western India were characterized using fluorescence spectroscopy, and resin-based fractionation was conducted to fractionate DOM into hydrophobic and hydrophilic base, acid, and neutral fractions. Among several fractions, the hydrophilic acid (HIA) and hydrophilic neutral (HIN) fractions were present in higher abundance (more than 50% of DOC) compared to the hydrophilic base (HIB) fraction in both influent and effluent wastewater stream obtained from WWTPs. Tryptophan-like and tyrosine-like substances were also abundant in the influent and effluent stream of WWTPs. Further, LC-MS/MS analysis could identify 235 and 288 DOM proteins in the influent and effluent stream of WWTP-1, respectively. These proteins revealed varying percentage of tryptophan and tyrosine residues. The tryptophan residues primarily contributed to protein-like fluorescence in wastewater. The proteins were further classified based on their role in biological processes, location in the cell, and molecular function. Among several proteins, Alzheimer's and Huntington disease biomarkers were identified at WWTP-1. Their presence in the surface water can serve as an early warning system for wastewater-based epidemiology.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125453DOI Listing
July 2021

Pharmacological evaluation of vanillic acid in rotenone-induced Parkinson's disease rat model.

Eur J Pharmacol 2021 Jul 24;903:174112. Epub 2021 Apr 24.

Faculty of Pharmaceutical Sciences, PCTE Group of Institutes, Ludhiana, Punjab, 142 021, India. Electronic address:

In the present study, we investigated the anti-Parkinson's effect of vanillic acid (VA) (12 mg/kg, 25 mg/kg, 50 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson's disease (PD) in rats. The continuous administration of rotenone for 35 days resulted in rigidity in muscles, catalepsy, and decrease in locomotor activity, body weight, and rearing behaviour along with the generation of oxidative stress in the brain (rise in the TBARS, and SAG level and reduced CAT, and GSH levels). Co-treatment of VA and levodopa-carbidopa (100 mg/kg + 25 mg/kg p.o.) lead to a significant (P < 0.001) reduction in the muscle rigidity and catalepsy along with a significant (P < 0.001) increase in body weight, rearing behaviour, locomotion and muscle activity as compared to the rotenone-treated group in the dose dependent manner, showing maximum effect at the 50 mg/kg. It also showed reversal of levels of oxidative stress parameters thus, reducing the neuronal oxidative stress. The level of DA was also estimated which showed an increase in the level of DA in the VA plus standard drug treated animals as compared to rotenone treated group. Histopathological evaluation showed a high number of eosinophilic lesions in the rotenone group which were found to be very less in the VA co-treated group. The study thus proved that co-treatment of VA and levodopa-carbidopa, significantly protected the brain from neuronal damage due to oxidative stress and attenuated the motor defects indicating the possible therapeutic potential of VA as a neuroprotective in PD.
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http://dx.doi.org/10.1016/j.ejphar.2021.174112DOI Listing
July 2021

Design and Additive Manufacturing of a Biomimetic Customized Cranial Implant Based on Voronoi Diagram.

Front Physiol 2021 9;12:647923. Epub 2021 Apr 9.

Clinic of Oral and Cranio-Maxillofacial Surgery, University Hospital Basel, Basel, Switzerland.

Reconstruction of cranial defects is an arduous task for craniomaxillofacial surgeons. Additive manufacturing (AM) or three-dimensional (3D) printing of titanium patient-specific implants (PSIs) made its way into cranioplasty, improving the clinical outcomes in complex surgical procedures. There has been a significant interest within the medical community in redesigning implants based on natural analogies. This paper proposes a workflow to create a biomimetic patient-specific cranial prosthesis with an interconnected strut macrostructure mimicking bone trabeculae. The method implements an interactive generative design approach based on the Voronoi diagram or tessellations. Furthermore, the quasi-self-supporting fabrication feasibility of the biomimetic, lightweight titanium cranial prosthesis design is assessed using Selective Laser Melting (SLM) technology.
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http://dx.doi.org/10.3389/fphys.2021.647923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063040PMC
April 2021

Structure, properties, and bioactivity of 3D printed PAEKs for implant applications: A systematic review.

J Biomed Mater Res B Appl Biomater 2021 Apr 15. Epub 2021 Apr 15.

Implant Research Core, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.

Additive manufacturing (AM) of high temperature polymers, specifically polyaryletherketones (PAEK), is gaining significant attention for medical implant applications. As 3D printing systems evolve toward point of care manufacturing, research on this topic continues to expand. Specific regulatory guidance is being developed for the safe management of 3D printing systems in a hospital environment. PAEK implants can benefit from many advantages of AM such as design freedom, material and antibacterial drug incorporation, and enhanced bioactivity provided by cancellous bone-like porous designs. In addition to AM PAEK bioactivity, the biomechanical strength of 3D printed implants is crucial to their performance and thus widely studied. In this review, we discuss the printing conditions that have been investigated so far for additively manufactured PAEK implant applications. The effect of processing parameters on the biomechanical strength of implants is summarized, and the bioactivity of PAEKs, along with material and drug incorporation, is also covered in detail. Finally, the therapeutic areas in which 3D printed PAEK implants are investigated and utilized are reviewed.
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http://dx.doi.org/10.1002/jbm.b.34845DOI Listing
April 2021

The emerging paradigm of calcium homeostasis as a new therapeutic target for protozoan parasites.

Med Res Rev 2021 Apr 13. Epub 2021 Apr 13.

Infectious Diseases, Mayo Clinic, Jacksonville, Florida, 32224, USA.

Calcium channels (CCs), a group of ubiquitously expressed membrane proteins, are involved in many pathophysiological processes of protozoan parasites. Our understanding of CCs in cell signaling, organelle function, cellular homeostasis, and cell cycle control has led to improved insights into their structure and functions. In this article, we discuss CCs characteristics of five major protozoan parasites Plasmodium, Leishmania, Toxoplasma, Trypanosoma, and Cryptosporidium. We provide a comprehensive review of current antiparasitic drugs and the potential of using CCs as new therapeutic targets. Interestingly, previous studies have demonstrated that human CC modulators can kill or sensitize parasites to antiparasitic drugs. Still, none of the parasite CCs, pumps, or transporters has been validated as drug targets. Information for this review draws from extensive data mining of genome sequences, chemical library screenings, and drug design studies. Parasitic resistance to currently approved therapeutics is a serious and emerging threat to both disease control and management efforts. In this article, we suggest that the disruption of calcium homeostasis may be an effective approach to develop new anti-parasite drug candidates and reduce parasite resistance.
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http://dx.doi.org/10.1002/med.21804DOI Listing
April 2021

Demographic and clinico-radiological profile on High-Resolution Computerized Tomography (HRCT) thorax in mild or asymptomatic clinically suspected COVID-19 patients in high-endemicity area of India-Can HRCT be the first screening tool? -The DECRYPTION study.

Indian J Radiol Imaging 2021 Jan 23;31(Suppl 1):S122-S127. Epub 2021 Jan 23.

Gujarat Adani Institute of Medical Sciences, Affiliated to K S K V University, Bhuj, Gujarat, India.

Background: With COVID-19 cases rising, despite CT chest being of value in diagnosis and prognostication in COVID-19, its role in mild or asymptomatic suspected COVID-19, before RT-PCR test is lacking.

Method: This is a retrospective observational study involving asymptomatic or mildly symptomatic clinically suspected COVID-19 infection in a high endemicity area. Of 2532 HRCT chest database, 376 eligible cases were analyzed for clinico-radiological correlation for CT findings based CORADS and CT severity score between positive vs negative group.

Results: Of 376, 186 (48.46%) had COVID-19 features on HRCT in mild and asymptomatic suspected patients. 98 (26.06%) had CO-RARDS - 5, 88 (23.40%) had CO-RADS - 4. 48 (12.76%), 128 (34.04%), 14 (3.72%) had CO-RADS score of 3,2,1, respectively. Positive CT findings were more likely beyond 3 days of symptoms compared to those presenting earlier {days: (Mean) 4.2 vs 2.76} Positive CT was significantly associated with patients with anosmia and dyspnea. The common presenting symptoms were Fever 196 (52.12%) and followed by sore throat in 173 (46.01%). The common HRCT findings were Ground glass opacity (GGO) (74.60%), followed by Lymphadenopathy (LN) (27.92%). LN which was more prevalent in symptomatic patients {99/343 (28.86%) vs {6/33 (18.18%)} asymptomatics (: 0.04)}. Consolidation was significantly more in asymptomatics with COPD (: 0.004). 6 (3.22%) patients had CT score >17/25.

Conclusion: Chest HRCT picked 48.46% positive cases in mildly symptomatic and asymptomatic patients of which 3.22% had severe involvement (>17). Being a noninvasive, rapid, sensitive, low risk of cross infection with high reproducibility, chest CT is worth evaluating as screening modality even in asymptomatic and mildly symptomatic clinically suspected COVID-19.
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http://dx.doi.org/10.4103/ijri.IJRI_796_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996708PMC
January 2021

RipA Dampens TLR4-Mediated Host Protective Response Using a Multi-Pronged Approach Involving Autophagy, Apoptosis, Metabolic Repurposing, and Immune Modulation.

Front Immunol 2021 4;12:636644. Epub 2021 Mar 4.

Indian Council of Medical Research-National Institute of Pathology, New Delhi, India.

Reductive evolution has endowed () with moonlighting in protein functions. We demonstrate that RipA (Rv1477), a peptidoglycan hydrolase, activates the NFκB signaling pathway and elicits the production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-12, through the activation of an innate immune-receptor, toll-like receptor (TLR)4. RipA also induces an enhanced expression of macrophage activation markers MHC-II, CD80, and CD86, suggestive of M1 polarization. RipA harbors LC3 (Microtubule-associated protein 1A/1B-light chain 3) motifs known to be involved in autophagy regulation and indeed alters the levels of autophagy markers LC3BII and P62/SQSTM1 (Sequestosome-1), along with an increase in the ratio of P62/Beclin1, a hallmark of autophagy inhibition. The use of pharmacological agents, rapamycin and bafilomycin A1, reveals that RipA activates PI3K-AKT-mTORC1 signaling cascade that ultimately culminates in the inhibition of autophagy initiating kinase ULK1 (Unc-51 like autophagy activating kinase). This inhibition of autophagy translates into efficient intracellular survival, within macrophages, of recombinant expressing RipA. RipA, which also localizes into mitochondria, inhibits the production of oxidative phosphorylation enzymes to promote a Warburg-like phenotype in macrophages that favors bacterial replication. Furthermore, RipA also inhibited caspase-dependent programed cell death in macrophages, thus hindering an efficient innate antibacterial response. Collectively, our results highlight the role of an endopeptidase to create a permissive replication niche in host cells by inducing the repression of autophagy and apoptosis, along with metabolic reprogramming, and pointing to the role of RipA in disease pathogenesis.
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http://dx.doi.org/10.3389/fimmu.2021.636644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969667PMC
March 2021

National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research.

Intensive Care Med Exp 2021 Mar 19;9(1):14. Epub 2021 Mar 19.

Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.

Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations of single-laboratory methodology. To overcome some of these shortcomings, multicentre preclinical studies-defined as a research experiment conducted in two or more research laboratories with a common protocol and analysis-are expected to maximize transparency, improve reproducibility, and enhance generalizability. The ultimate objective is to increase the efficiency and efficacy of bench-to-bedside translation for preclinical sepsis research and improve outcomes for patients with life-threatening infection. To this end, we organized the first meeting of the National Preclinical Sepsis Platform (NPSP). This multicentre preclinical  research collaboration of Canadian sepsis researchers and stakeholders was established to study the pathophysiology of sepsis and accelerate movement of promising therapeutics into early phase clinical trials. Integrated knowledge translation and shared decision-making were emphasized to ensure the goals of the platform align with clinical researchers and patient partners. 29 participants from 10 independent labs attended and discussed four main topics: (1) objectives of the platform; (2) animal models of sepsis; (3) multicentre methodology and (4) outcomes for evaluation. A PIRO model (predisposition, insult, response, organ dysfunction) for experimental design was proposed to strengthen linkages with interdisciplinary researchers and key stakeholders. This platform represents an important resource for maximizing translational impact of preclinical sepsis research.
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http://dx.doi.org/10.1186/s40635-020-00366-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973346PMC
March 2021

Complete androgen insensitivity syndrome with intra-abdominal seminoma in a phenotypic female: A rare presentation.

J Cancer Res Ther 2021 Jan-Mar;17(1):272-275

Department of Radiotherapy, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India.

Androgen insensitivity syndrome (AIS) is a rare, X-linked recessive disorder which causes alterations in androgen receptor gene leading to hormone resistance, which may present clinically under three phenotypes: complete AIS (CAIS), partial AIS, or mild AIS. The symptoms range from phenotypically normal males with impaired spermatogenesis to phenotypically normal women with primary amenorrhea. We report a case of a 35-year-old woman who was diagnosed with CAIS and presented with malignant transformation of the undescended testis. The histopathology confirmed the presence of seminoma. In this case report, we reviewed the literature which describes the biochemical and endocrinological abnormalities leading to the syndrome. It also highlights the potential for malignant changes of the undescended testes, diagnosis, and therapeutic management.
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http://dx.doi.org/10.4103/jcrt.JCRT_302_18DOI Listing
March 2021

Effect of pulp density on the bioleaching of metals from petroleum refinery spent catalyst.

3 Biotech 2021 Mar 25;11(3):143. Epub 2021 Feb 25.

Department of Microbiology, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, 305817 Rajasthan India.

Bioleaching is one of the well-known methods of metal recovery with Environmental benefits. This process has been extensively used for combating improper waste management issues along with metal reclamation. The aim of this study is to bioleach spent petroleum refinery catalyst at variant pulp densities (PD) (5, 10 and 15%) using microorganisms in acidic pH (1.5-1.6) and mesophilic temperature (30-35 °C). The study includes leaching yields of metals like nickel, molybdenum, copper and aluminum. The three bioleaching experiments with different pulp densities yielded a maximum of more than 90% nickel, 73% copper, 87% molybdenum and 24% aluminum. The results are validated 5, 10, and 15% pulp density and the result is validated with pH, Redox potential, microbial population, sulphate concentration and ferrous iron, concentration. The time saving due to faster nickel dissolution using iron and sulphur oxidizing microorganisms would be economical for the bioleaching process.
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http://dx.doi.org/10.1007/s13205-021-02686-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907300PMC
March 2021

Review of investigational drugs for coronavirus disease 2019.

J Educ Health Promot 2021 28;10:31. Epub 2021 Jan 28.

Institute of Heart and Lung Transplant and Mechanical Circulatory Support, MGM Healthcare, Chennai, Tamil Nadu, India.

In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became evident in Wuhan, China, and then spread rapidly worldwide. Numerous drugs and vaccines are under clinical trial pipeline for investigation against coronavirus disease 2019 (COVID-19) infection. The aim of this systematic review was to discuss about investigational new as well as repurposed drugs currently under trial for COVID-19 infection. An exhaustive search was carried out for this review article including scientific databases of PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Web of Science, ScienceDirect, ProQuest, Google Scholar, and Scopus search engines using keywords of "Coronavirus," "COVID-19," "MERS-CoV," "MERS," "SARS-CoV-2," and "SARS-CoV-1" and "Solidarity trial" and their Persian-equivalent keywords from inception until May 2020. After screening the 296 articles searched from different databases (PubMed = 97 and other search engines = 199), 52 articles were included in the final systematic review. It was found that the World Health Organization introduced a Solidarity international clinical trial to discover an effectual treatment of COVID-19. Based on established and activity against different strains of coronaviruses, four repurposed drugs - remdesivir, lopinavir/ ritonavir combination, lopinavir/ritonavir with beta-1a, chloroquine, and hydroxychloroquine - were considered for clinical trial against COVID-19. A number of other drugs and vaccines are under clinical trial pipeline for investigation against COVID-19 infection. Despite multitude of treatment options available, treatment of choice is still not well established. Moreover, optimum supportive care and monitoring of seriously ill patients is the need of the hour.
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http://dx.doi.org/10.4103/jehp.jehp_457_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933614PMC
January 2021

Validation of molecular response of tuberization in response to elevated temperature by using a transient Virus Induced Gene Silencing (VIGS) in potato.

Funct Integr Genomics 2021 Mar 21;21(2):215-229. Epub 2021 Feb 21.

Lovely Professional University, Jalandhar, Punjab, 144411, India.

Temperature plays an important role in potato tuberization. The ideal night temperature for tuber formation is ~17 °C while temperature beyond 22 °C drastically reduces the tuber yield. Moreover, high temperature has several undesirable effects on the plant and tubers. Investigation of the genes involved in tuberization under heat stress can be helpful in the generation of heat-tolerant potato varieties. Five genes, including StSSH2 (succinic semialdehyde reductase isoform 2), StWTF (WRKY transcription factor), StUGT (UDP-glucosyltransferase), StBHP (Bel1 homeotic protein), and StFLTP (FLOWERING LOCUS T protein), involved in tuberization and heat stress in potato were investigated. The results of our microarray analysis suggested that these genes regulate and function as transcriptional factors, hormonal signaling, cellular homeostasis, and mobile tuberization signals under elevated temperature in contrasting KS (Kufri Surya) and KCM (Kufri Chandramukhi) potato cultivars. However, no detailed report is available which establishes functions of these genes in tuberization under heat stress. Thus, the present study was designed to validate the functions of these genes in tuber signaling and heat tolerance using virus-induced gene silencing (VIGS). Results indicated that VIGS transformed plants had a consequential reduction in StSSH2, StWTF, StUGT, StBHP, and StFLTP transcripts compared to the control plants. Phenotypic observations suggest an increase in plant senescence, reductions to both number and size of tubers, and a decrease in plant dry matter compared to the control plants. We also establish the potency of VIGS as a high-throughput technique for functional validation of genes.
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http://dx.doi.org/10.1007/s10142-021-00771-2DOI Listing
March 2021

Antioxidant properties, phenolics and flavonoids content of some economically important plants from North-west Indian Himalaya.

Nat Prod Res 2021 Feb 11:1-5. Epub 2021 Feb 11.

G. B. Pant National Institute of Himalayan Environment, Himachal Regional Centre, Mohal-Kullu, India.

The present study investigated antioxidant properties, total phenolic and flavonoid contents in methanol extract of the leaf, stem bark, and fruit of Royle, L., and L. grow naturally in the north-west Indian Himalaya. Phenolics and flavonoids content was found to be maximum in methanol extracts of stem bark and leaf (9.28 mg GAE/g fw and 14.73 mg QE/g fw, respectively) of plants. Ferric reducing antioxidant power and DPPH radical scavenging activity were found to be maximum in leaf and stem bark (38.88 mM AAE/g fw and 20.31 mM AAE/g fw, respectively) of plants, whereas maximum ABTS radical scavenging activity (4.52 mM AAE/g fw) was recorded with stem bark of plants. These tree species were found rich in natural compounds and also possess antioxidant activities. Therefore, their pharmaceutical and local uses for the health benefits are suggested.
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http://dx.doi.org/10.1080/14786419.2021.1881959DOI Listing
February 2021

In-Hospital 3D Printed Scaphoid Prosthesis Using Medical-Grade Polyetheretherketone (PEEK) Biomaterial.

Biomed Res Int 2021 11;2021:1301028. Epub 2021 Jan 11.

Medical Additive Manufacturing Research Group, Department of Biomedical Engineering, University of Basel, Gewerbestrasse 16, 4123 Allschwil, Switzerland.

Recently, three-dimensional (3D) printing has become increasingly popular in the medical sector for the production of anatomical biomodels, surgical guides, and prosthetics. With the availability of low-cost desktop 3D printers and affordable materials, the in-house or point-of-care manufacturing of biomodels and Class II medical devices has gained considerable attention in personalized medicine. Another projected development in medical 3D printing for personalized treatment is the in-house production of patient-specific implants (PSIs) for partial and total bone replacements made of medical-grade material such as polyetheretherketone (PEEK). We present the first in-hospital 3D printed scaphoid prosthesis using medical-grade PEEK with fused filament fabrication (FFF) 3D printing technology.
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http://dx.doi.org/10.1155/2021/1301028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815413PMC
May 2021

Hypoxia-inducible factor (HIF): fuel for cancer progression.

Curr Mol Pharmacol 2021 Jan 20. Epub 2021 Jan 20.

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

Hypoxia is an integral part of tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mchanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.
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http://dx.doi.org/10.2174/1874467214666210120154929DOI Listing
January 2021

Students' perception regarding pedagogy, andragogy, and heutagogy as teaching-learning methods in undergraduate medical education.

J Educ Health Promot 2020 26;9:301. Epub 2020 Nov 26.

Department of Pharmacology, SMS Medical College, Jaipur, Rajasthan, India.

Introduction: Medical education is tricky to imbibe and difficult to apply. Various teaching-learning (TL) methods have been tried from time to time to enhance the proficiency of students. The aim was to assess the students' perception toward three different TL methods (pedagogy, andragogy, and heutagogy) in medical education.

Materials And Methods: A comparative experimentalquestionnaire-based study was done on population of second-year MBBS students of SMS Medical College, Jaipur, in October 2019. They were taught topic of anticancer drugs using pedagogy, andragogy, and heutagogy methods. Then, their opinion regarding these methods was collected and evaluated. The reliability of the questionnaire was ascertained by Cronbach's alpha value which turned out to be 0.89. The data collected were analyzed statistically using one-way Analysis of Variance (ANOVA) and Principal Component Analysis (PCA).

Results: The results showed that all these methods differ significantly from each other as the < 0.05 considering 5% as level of significance. PCA revealed that andragogy and heutagogy were found to be most effective in this study.

Conclusion: Competency-based andragogy and capability-based heutagogy are more effective TL methods than didactic lecture-based pedagogy for MBBS undergraduate students.
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http://dx.doi.org/10.4103/jehp.jehp_221_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774633PMC
November 2020

3D-Printer-Assisted Patient-Specific Polymethyl Methacrylate Cranioplasty: A Case Series of 16 Consecutive Patients.

World Neurosurg 2021 Apr 5;148:e356-e362. Epub 2021 Jan 5.

Department of Cranio-Maxillo-Facial Surgery and 3D Print Lab, University Hospital Basel, University of Basel, Basel, Switzerland; Medical Additive Manufacturing Research Group, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.

Background: To develop a novel 3D-printer-assisted method to fabricate patient-specific implants for cranioplasty and to demonstrate its feasibility and its use in 16 consecutive cases.

Methods: We report on 16 consecutive patients who have undergone cranioplasty surgery for an extensive skull defect after decompressive surgery and in which the bone flap was not available. We present the workflow for the implant production using a 3D-printer-assisted molding technique. Preoperative, intraoperative, and postoperative data were analyzed/evaluated.

Results: Eleven out of our 16 patients (68.7%) presented with extensive hemispheric bone defects. Indication for initial craniotomy were traumatic brain injury (4; 25%), acute subdural hematoma (4; 25%), ischemic stroke (3; 18.8%), tumor (3; 18.8%), and ruptured aneurysm (2; 12.5%). Median (range) operation time was 121 (89-206) minutes. Median (range) intraoperative blood loss was 300 (100-3300) mL. The mean (range) follow-up period is 6 (0-21) months. Complications occurred in 7 out of our 16 patients (43.8%), in 6 (37.5%) of which a reoperation was required to evacuate an extra-axial hematoma (3; 50%), for shunting of an epidural fluid collection (1; 16.7%), or for skin flap necrosis (1; 16.7%). One patient (16.7%) developed a chronic asymptomatic subdural fluid collection that was stable over the follow-up period.

Conclusions: Our workflow to intraoperatively produce patient-specific implants in a timely manner to cover cranial defects proved to be feasible. The results are cosmetically appealing, and postoperative CT scans show well-fitting implants. As implantable printable substrates are already available, we aim to advance and certify 3D-printed patient-specific implants in the near future.
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http://dx.doi.org/10.1016/j.wneu.2020.12.138DOI Listing
April 2021

Understanding the role of soft linkers in designing hepatzine-based polymeric frameworks as heterogeneous (photo)catalyst.

J Colloid Interface Sci 2021 Apr 21;588:138-146. Epub 2020 Dec 21.

Advanced Functional Nanomaterials, Institute of Nano Science and Technology, Knowledge City, Sector 81, Manauli, SAS Nagar 140306, Punjab, India. Electronic address:

The emerging class of heptazine-based polymeric materials has shown potential candidature as photocatalyst materials for hydrogen evolution. At the same time, they have shown promising application as solid base materials to catalyse various organic transformations. Thus, the material design rationale needs to be developed around the heptazine-based polymeric frameworks in order to specifically design task specific materials. Herein, we utilised controlled reaction conditions to synthesize the desired polymeric networks with trichloroheptazine as precursor. Material design strategy employed nitrogen rich [tris(2-aminoethylamine) and hydrazine] as soft linkers to understand the effect on band structure of developed heptazine-based polymeric networks. The developed polymeric networks were explored as platform to study systematically the effect on their respective photophysical properties and understand their surface basicity. The framework having aminoalkyl linker showed superior activity in photocatalysis as well as heterogeneous base catalysis. Further, model catalysts revealed the importance of N-atoms as active basic sites in these systems.
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http://dx.doi.org/10.1016/j.jcis.2020.12.040DOI Listing
April 2021

Isolated Pulvinar/Hockey Stick Sign in Nonalcoholic Wernicke's Encephalopathy.

Am J Case Rep 2020 Dec 31;21:e928272. Epub 2020 Dec 31.

Department of Neuroradiology, Radiology Partners Gulf Coast, Houston, TX, USA.

BACKGROUND Wernicke's encephalopathy (WE), a commonly misdiagnosed and underdiagnosed pathology, presents with altered mental status, ataxia, and ophthalmoplegia. WE is most commonly caused by excessive alcohol use, but also has diverse nonalcoholic etiologies. Here we describe 2 cases of nonalcoholic WE with different etiologies that were initially misdiagnosed due to lack of correlation of magnetic resonance imaging (MRI) findings with clinical information. CASE REPORT Patient A, a 50-year-old woman with recent gastric sleeve surgery, presented with horizontal gaze-evoked nystagmus, ataxia, and altered mental status. MRI fluid-attenuated inversion recovery (FLAIR) revealed isolated bilateral, symmetrical, thalamic hyperintensities, initially diagnosed as variant Creutzfeldt-Jakob disease. A review of imaging and clinical presentation provided an alternate diagnosis of nonalcoholic WE secondary to nutritional deficiency. Intravenous (IV) thiamine improved symptoms with resolution of MRI findings 6 months later. Patient B, a 64-year-old woman, presented with nausea, vomiting, dizziness, altered mental status, and weight loss. MRI FLAIR revealed isolated bilateral, symmetrical, thalamic hyperintensities, initially determined to be ischemia, prompting stroke management. A diagnosis of nonalcoholic WE was suggested, given the patient's low thiamine levels and history of malnutrition, and was confirmed by her excellent therapeutic response to IV thiamine. CONCLUSIONS Nonalcoholic WE remains a challenging diagnosis because of the variable clinical presentation, myriad of underlying etiologies, and lack of standardized diagnostic laboratory tests. A multidisciplinary approach with close collaboration between the radiologist and clinical care team is critical to narrow down the differential and initiate correct management. WE is a reversible disease with catastrophic consequences if it is not recognized and treated promptly.
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http://dx.doi.org/10.12659/AJCR.928272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784713PMC
December 2020