2,013 results match your criteria Toxicity Monoamine Oxidase Inhibitor

DNA damage and biochemical responses in estuarine bivalve Donax incarnatus (Gmelin, 1791) exposed to sub-lethal concentrations of an organophosphate pesticide monocrotophos.

Environ Monit Assess 2021 May 3;193(6):317. Epub 2021 May 3.

Department of Zoology, Goa University, University Road, Taleigao, Goa, 403206, India.

Monocrotophos (MCP) is a highly toxic and broad-spectrum pesticide extensively used for agricultural and household purposes. The present study was aimed to evaluate the genotoxicity and alterations in the biochemical and physiological conditions induced by monocrotophos in a non-target organism, an estuarine bivalve, Donax incarnatus. The bivalves were exposed to three sub-lethal concentrations (6. Read More

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Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B.

Pharmaceuticals (Basel) 2021 Apr 22;14(5). Epub 2021 Apr 22.

Division of Drug Discovery, Department of Infectious Diseases, Southern Research, Birmingham, AL 35205, USA.

8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. Read More

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Georgian Med News 2021 Feb(311):143-146

North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, Russia.

The number of demyelinating diseases of central nervous system are prone to grow nowadays. The most socially significant and well studied one is multiple sclerosis. The search of susbstances that would stop demyelinisation or reinforce the process of remyelination is in great request. Read More

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February 2021

Toxicity and detoxification of monocrotophos from ecosystem using different approaches: A review.

Chemosphere 2021 Jul 23;275:130051. Epub 2021 Feb 23.

Interdisciplinary Centre for Water Research (ICWaR), Indian Institute of Sciences, Bangalore, 560012, India. Electronic address:

Monocrotophos (MCP) is an organophosphate insecticide with broad application in agricultural crops like rice, maize, sugarcane, cotton, soybeans, groundnut and vegetables. MCP solubilize in water readily and thus reduced sorption occurs in soil. This leads to MCP leaching into the groundwater and pose a significant threat of contamination. Read More

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Design, synthesis and evaluation of novel dimethylamino chalcone-O-alkylamines derivatives as potential multifunctional agents against Alzheimer's disease.

Eur J Med Chem 2021 Apr 23;216:113310. Epub 2021 Feb 23.

Department of Elderly Digestive, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, 610072, China. Electronic address:

A novel series of dimethylamino chalcone-O-alkylamines derivatives was designed and synthesized as multifunctional agents for the treatment of AD. All the target compounds exhibited significant abilities to inhibit and disaggregate Aβ aggregation, and acted as potential selective AChE inhibitors, biometal chelators and selective MAO-B inhibitors. Among these compounds, compound TM-6 showed the greatest inhibitory activity against self-induced Aβ aggregation (IC50 = 0. Read More

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Design and synthesis of novel 3,4-dihydrocoumarins as potent and selective monoamine oxidase-B inhibitors with the neuroprotection against Parkinson's disease.

Bioorg Chem 2021 Apr 2;109:104685. Epub 2021 Feb 2.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Experiment Center of Teaching & Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

The monoamine oxidase-B (MAO-B) inhibitors with neuroprotective effects are better for Parkinson's disease (PD) treatment, due to the complicated pathogenesis of PD. To develop new hMAO-B inhibitors with neuroprotection, a novel series of 3,4-dihydrocoumarins was designed as selective and reversible hMAO-B inhibitors to treat PD. Most compounds showed potent and selective inhibition for hMAO-B over hMAO-A with IC values ranging from nanomolar to sub-nanomolar. Read More

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Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease.

RSC Med Chem 2020 Feb 7;11(2):225-233. Epub 2020 Jan 7.

Jiangsu Key Laboratory of Bioactive Natural Product Research and , State Key Laboratory of Natural Medicines , Department of Natural Medicinal Chemistry , School of Traditional Chinese Pharmacy , China Pharmaceutical University , 24 Tong Jia Xiang , Nanjing 210009 , People's Republic of China . Email: ; ; Tel: +86 25 83271405.

A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for MAO-B. In particular, compound presented the most balanced potential for ChE inhibition (BuChE: IC = 5. Read More

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February 2020

Multitarget Biological Profiling of New Naphthoquinone and Anthraquinone-Based Derivatives for the Treatment of Alzheimer's Disease.

ACS Chem Neurosci 2021 02 11;12(3):447-461. Epub 2021 Jan 11.

Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132 Genoa, Italy.

Two series of naphthoquinone and anthraquinone derivatives decorated with an aromatic/heteroaromatic chain have been synthesized and evaluated as potential promiscuous agents capable of targeting different factors playing a key role in Alzheimer's disease (AD) pathogenesis. On the basis of the biological profiling, most of them exhibited a significant ability to inhibit amyloid aggregation, PHF6 tau sequence aggregation, acetylcholinesterase (AChE), and monoamine oxidase (MAO) B. In particular, naphthoquinone resulted as one of the best performing multitarget-directed ligand (MTDL) experiencing a high potency profile in inhibiting β-amyloid (Aβ) aggregation (IC = 3. Read More

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February 2021

Vanadium-dependent activation of glucose transport in adipocytes by catecholamines is not mediated adrenoceptor stimulation or monoamine oxidase activity.

World J Diabetes 2020 Dec;11(12):622-643

Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale, INSERM UMR1048, Université Paul Sabatier Toulouse III, Toulouse 31432, France.

Background: Benzylamine and methylamine activate glucose uptake in adipocytes. For tyramine, this effect has even been extended to cardiomyocytes.

Aim: To investigate the effects of catecholamines and other amines on glucose uptake. Read More

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December 2020

Synthetic approaches to unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles and their MAO-B inhibitory activity. A review.

Bioorg Med Chem 2021 01 27;29:115888. Epub 2020 Nov 27.

Laboratory "Drug metabolism and drug toxicity", Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University-Sofia, Bulgaria; Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, Bulgaria. Electronic address:

Selective monoamine oxidase type B (MAO-B) inhibitors are currently used as coadjuvants for treating early motor symptoms of Parkinson's disease. Aiming at the elucidation of MAO-B inhibitors with 1,3,4-oxadiazole scaffolds, we make a comprehensive update on the new and old chemical methods employed for the synthesis of the unsymmetrical oxadiazole derivatives that lead to high yield compounds. We summarize a state of the selective MAO-B inhibitors with oxadiazole scaffold, describing the results, structures, structure-activity relationships (SARs) and medicinal chemistry strategies over the years. Read More

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January 2021

Effects of novel 17β-hydroxysteroid dehydrogenase type 10 inhibitors on mitochondrial respiration.

Toxicol Lett 2021 Mar 24;339:12-19. Epub 2020 Dec 24.

Charles University and General University Hospital in Prague, First Faculty of Medicine, Department of Psychiatry, Ke Karlovu 11, 120 00, Prague 2, Czech Republic.

Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17β-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of AD and is one of the targets of new potential AD drugs. The in vitro effects of frentizole, riluzole, AG18051, and 42 novel modulators of HSD10 (potential AD drugs) on citrate synthase (CS) activity, monoamine oxidase (MAO) activity, complex I- or complex II-linked mitochondrial respiratory rate, and complex I activity were measured in isolated pig brain mitochondria. Read More

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Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study.

Int J Mol Sci 2020 Dec 12;21(24). Epub 2020 Dec 12.

Department of Radiation Convergence Engineering, College of Health Sciences, Yonsei University, Wonju, Gangwondo 26493, Korea.

Background: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST.

Method: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. Read More

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December 2020

The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis.

Chemosphere 2021 Jan 4;263:128238. Epub 2020 Sep 4.

Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, 430073, China; Key Laboratory of Virtual Geographic Environment (Ministry of Education), Nanjing Normal University, Nanjing, 210023, China. Electronic address:

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g. Read More

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January 2021

Effect of Etazolate upon Cuprizone-induced Demyelination In Vivo: Behavioral and Myelin Gene Analysis.

Neuroscience 2021 02 24;455:240-250. Epub 2020 Nov 24.

INSERM UMR-S 1124, Université de Paris, UFR des Sciences Fondamentales et Biomédicales, Campus Saint Germain des Prés, 45 rue des Saints Pères, 75006 Paris, France.

Demyelination is a well-known pathological process in CNS disorders such as multiple sclerosis (MS). It provokes progressive axonal degeneration and functional impairments and no efficient therapy is presently available to combat such insults. Recently, we have shown that etazolate, a pyrazolopyridine compound and an α-secretase activator, was able to promote myelin protection and remyelination after cuprizone (CPZ)-induced acute demyelination in C57Bl/6 mice. Read More

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February 2021

Harmine Combined with Knockdown Inhibits the Viability of by Enhancing DNA Damage.

DNA Cell Biol 2021 Jan 10;40(1):1-9. Epub 2020 Nov 10.

First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.

This study aimed at exploring the role of and the effect of harmine (HM) or HM derivatives (HMDs) on DNA damage in DNA damage in protoscoleces (PSCs) was assessed by using a comet assay, after treatment with HM or HMDs. Efficiency of electroporation-based transfection of PSCs and subsequent knockdown was evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR) and fluorescence intensity. Viability of PSCs was determined via eosin exclusion test, and expression of related genes was analyzed via RT-qPCR. Read More

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January 2021

Ferroptosis Mediates Cuprizone-Induced Loss of Oligodendrocytes and Demyelination.

J Neurosci 2020 11 26;40(48):9327-9341. Epub 2020 Oct 26.

Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada

Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS. Cuprizone (CZ), a copper chelator, is widely used to study demyelination and remyelination in the CNS, in the context of MS. However, the mechanisms underlying oligodendrocyte (OL) cell loss and demyelination are not known. Read More

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November 2020

Machine learning based white matter models with permeability: An experimental study in cuprizone treated in-vivo mouse model of axonal demyelination.

Neuroimage 2021 01 6;224:117425. Epub 2020 Oct 6.

Centre for Medical Image Computing and Dept of Computer Science, University College London, London, UK.

The intra-axonal water exchange time (τ), a parameter associated with axonal permeability, could be an important biomarker for understanding and treating demyelinating pathologies such as Multiple Sclerosis. Diffusion-Weighted MRI (DW-MRI) is sensitive to changes in permeability; however, the parameter has so far remained elusive due to the lack of general biophysical models that incorporate it. Machine learning based computational models can potentially be used to estimate such parameters. Read More

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January 2021

Design, Synthesis, In Vitro and In Silico Studies of New Thiazolylhydrazine-Piperazine Derivatives as Selective MAO-A Inhibitors.

Molecules 2020 Sep 22;25(18). Epub 2020 Sep 22.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.

Monoamine oxidase (MAO) isoenzymes are very important drug targets among neurological disorders. Herein, novel series of thiazolylhydrazine-piperazine derivatives were designed, synthesized and evaluated for their MAO-A and -B inhibitory activity. The structures of the synthesized compounds were assigned using different spectroscopic techniques such as H-NMR, C-NMR and HRMS. Read More

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September 2020

Novel coumarin-pyridazine hybrids as selective MAO-B inhibitors for the Parkinson's disease therapy.

Bioorg Chem 2020 11 2;104:104203. Epub 2020 Sep 2.

Departamento de Química Orgánica e Instituto de Investigación Sanitaria Galicia Sur (IISGS), Universidade de Vigo, 36310 Vigo, Spain. Electronic address:

The 3-pyridazinylcoumarin scaffold was previously reported as an efficient core for the discovery of reversible and selective inhibitors of MAO-B, a validated drug target for PD therapy which also plays an important role in the AD progress. Looking for its structural optimization, novel compounds of hybrid structure coumarin-pyridazine, differing in polarizability and lipophilicity properties, were synthesized and tested against the two MAO isoforms, MAO-A and MAO-B (compounds 17a-f and 18a-f). All the designed compounds selectively inhibited the MAO-B isoenzyme, exhibiting many of them IC values ranging from sub-micromolar to nanomolar grade and lacking neuronal toxicity. Read More

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November 2020

The impact of quetiapine on the brain lipidome in a cuprizone-induced mouse model of schizophrenia.

Biomed Pharmacother 2020 Nov 6;131:110707. Epub 2020 Sep 6.

Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, 710032, China. Electronic address:

The antipsychotic effect of Quetiapine (Que) has been extensively studied and growing evidence suggests that Que has a beneficial effect, improving cognitive functions and promoting myelin repair. However, the effects of Que on the brain lipidome and the association between Que-associated cognitive improvement and changes in lipids remain elusive. In the present study, we assessed the cognitive protective effects of Que treatment and used a mass spectrometry-based lipidomic approach to evaluated changes in lipid composition in the hippocampus, prefrontal cortex (PFC), and striatum in a mouse model of cuprizone (CPZ)-induced demyelination. Read More

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November 2020

Neuropsychiatric Effects of Antiviral Drugs.

Cureus 2020 Aug 3;12(8):e9536. Epub 2020 Aug 3.

Department of Internal Medicine, University of Patras, School of Health Sciences, Patras, GRC.

The adverse events of antiviral drugs are dose-dependent and often reversible. The nervous system is often affected and to date, many studies have been published regarding the central nervous system toxicity of antiviral agents. They may cause significant neuropsychiatric complications, which range from mild symptoms such as irritability and difficulty sleeping to severe complications such as depression, psychosis, and painful peripheral neuropathy, side effects which may necessitate discontinuation of treatment. Read More

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ReN VM spheroids in matrix: A neural progenitor three-dimensional in vitro model reveals DYRK1A inhibitors as potential regulators of radio-sensitivity.

Biochem Biophys Res Commun 2020 10 14;531(4):535-542. Epub 2020 Aug 14.

Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7FZ, Oxford, England, UK. Electronic address:

Introduction: Pre-clinical testing of small molecules for therapeutic development across many pathologies relies on the use of in-vitro and in-vivo models. When designed and implemented well, these models serve to predict the clinical outcome as well as the toxicity of the evaluated therapies. The two-dimensional (2D) reductionist approach where cells are incubated in a mono-layer on hard plastic microtiter plates is relatively inexpensive but not physiologically relevant. Read More

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October 2020

PAMs inhibits monoamine oxidase a activity and reduces glioma tumor growth, a potential adjuvant treatment for glioma.

BMC Complement Med Ther 2020 Aug 15;20(1):252. Epub 2020 Aug 15.

Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Rm. 518, 1985 Zonal Ave, Los Angeles, CA, 90089, USA.

Background: Monoamine oxidase (MAO) A catalyzes oxidative deamination of monoamine neurotransmitters and dietary amines and regulates brain development and functions. Recently, we showed that MAO A mediates the progression and migration of glioma and MAO A inhibitors reduce glioma cell growth. Glioblastoma (GBM) is a common and most malignant brain tumor which is difficult to treat. Read More

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Four-week repeated dose oral toxicity study of KDS2010, a novel selective monoamine oxidase B inhibitor, in Sprague Dawley rats.

Regul Toxicol Pharmacol 2020 Nov 3;117:104733. Epub 2020 Aug 3.

Jeonbuk Branch Institute, Korea Institute of Toxicology, Jeonbuk, 56212, Republic of Korea. Electronic address:

Repeated dose oral toxicity and toxicokinetic of KDS2010, a new drug for Parkinson's disease, was investigated after 4-week repeated oral administration at 30, 50, 75, or 100 mg/kg/day in rats. Body weight and body weight gain decreased in rats of both sexes in the 75 and 100 mg/kg groups, and food consumption was reduced in male rats of the 75 and 100 mg/kg male groups. Histological alterations were observed in the kidney (urothelial hyperplasia, inflammatory cell infiltration in the renal pelvis, tubular vacuolation/degeneration, basophilic tubules, and hyaline droplets in the proximal tubules) of the 75 and 100 mg/kg male groups and the 50 and 100 mg/kg female groups. Read More

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November 2020

Melatonin improves memory defects in a mouse model of multiple sclerosis by up-regulating cAMP-response element-binding protein and synapse-associated proteins in the prefrontal cortex.

J Integr Neurosci 2020 Jun;19(2):229-237

Department of Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.

Multiple sclerosis is a progressive autoimmune disorder of the myelin sheath and is the most common inflammatory disease of young adults. Up to 65% of multiple sclerosis patients have cognitive impairments such as memory loss and difficulty in understanding and maintaining attention and concentration. Many pharmacological interventions have been used to reverse motor impairments in multiple sclerosis patients; however, none of these drugs improve cognitive function. Read More

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[Dihydrotanshinone I (DHTS1) attenuates cuprizone-induced demyelination via regulating microglia polarization].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 May;36(5):404-412

Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong 037009, China. *Corresponding authors, E-mail:

Objective To evaluate whether dihydrotanshinone I (DHTS1) attenuates cuprizone-induced demyelination. Methods DHTS1 was dissolved in 5 g/L sodium carboxymethyl cellulose (CMC-Na). The cuprizone model was induced via feeding with the diet containing 2 g/L cuprizone. Read More

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Neuroprotective and neuro-survival properties of safinamide against methamphetamine-induced neurodegeneration: Hypothetic possible role of BDNF/TrkB/PGC-1α signaling pathway and mitochondrial uncoupling protein -2(UCP-2).

Med Hypotheses 2020 Oct 11;143:110094. Epub 2020 Jul 11.

Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.

Methamphetamine is a behavioral psychostimulant that has a high potential for misuse and induction of neurotoxicity. Safinamide is a novel inhibitor of monoamine oxidase B (MAOB) with neuroprotective properties. Methamphetamine abuse causes dysfunction in the respiratory chain of the mitochondria, but the specific signaling mechanism and role of the uncoupling protein-2(UCP-2) remain unclear. Read More

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October 2020

Integrated Binary QSAR-Driven Virtual Screening and In Vitro Studies for Finding Novel hMAO-B-Selective Inhibitors.

J Chem Inf Model 2020 08 3;60(8):4047-4055. Epub 2020 Aug 3.

Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, 34734 Istanbul, Turkey.

The increased activity of monoamine oxidase (MAO) enzymes may lead to serious consequences since they reduce the level of neurotransmitters and are associated with severe neurodegenerative diseases. The inhibition of this enzyme, especially the B isoform, plays a vital role in the treatment of Parkinson's disease (PD). This study is aimed to find novel human MAO-B (hMAO-B) selective inhibitors. Read More

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Design, synthesis and biological evaluation of rasagiline-clorgyline hybrids as novel dual inhibitors of monoamine oxidase-B and amyloid-β aggregation against Alzheimer's disease.

Eur J Med Chem 2020 Sep 30;202:112475. Epub 2020 Jun 30.

Department of Pharmacy, Affiated Tumor Hospital of Guangxi Medical University, Nanning, PR China. Electronic address:

A series of rasagiline-clorgyline hybrids was designed, synthesized and investigated in vitro for their inhibition of monoamine oxidase and amyloid-β aggregation. Most of compounds were found to be selective and highly potent hMAO-B inhibitors showing IC values in the nanomolar, and exhibited a moderate inhibition of amyloid-β aggregation. 7-((5-(methyl(prop-2-yn-1-yl)amino) pentyl)oxy)chroman-4-one (6j) was the most interesting compound identified in this research, endowed with higher hMAO-B potency (IC = 4 nM) and selectivity (SI > 25000) compared to the reference selective inhibitor rasagiline (IC = 141 nM, SI > 355), and exhibited good inhibitory activity against Aβ aggregation (40. Read More

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September 2020

F-SMBT-1: A Selective and Reversible PET Tracer for Monoamine Oxidase-B Imaging.

J Nucl Med 2021 02 9;62(2):253-258. Epub 2020 Jul 9.

Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.

Reactive astrocytes play a key role in the pathogenesis of various neurodegenerative diseases. Monoamine oxidase-B (MAO-B) is one of the promising targets for the imaging of astrogliosis in the human brain. A novel selective and reversible MAO-B tracer, ()-(2-methylpyrid-5-yl)-6-[(3-F-fluoro-2-hydroxy)propoxy]quinoline (F-SMBT-1), was successfully developed via lead optimization from the first-generation tau PET tracer F-THK-5351. Read More

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February 2021