Publications by authors named "Geir Bjorklund"

209 Publications

Iron Deficiency in Obesity and after Bariatric Surgery.

Biomolecules 2021 Apr 21;11(5). Epub 2021 Apr 21.

Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania.

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, parallel to the increased concentrations of hepcidin. Obese subjects often get decreased inflammatory response after bariatric surgery, accompanied by decreased serum hepcidin and therefore improved iron absorption. Bariatric surgery can induce the mitigation or resolution of obesity-associated complications, such as hypertension, insulin resistance, diabetes mellitus, and hyperlipidemia, adjusting many parameters in the metabolism. However, gastric bypass surgery and sleeve gastrectomy can induce malabsorption and may accentuate ID. The present review explores the burden and characteristics of ID and anemia in obese patients after bariatric surgery, accounting for gastric bypass technique (Roux-en-Y gastric bypass-RYGB) and sleeve gastrectomy (SG). After bariatric surgery, obese subjects' iron status should be monitored, and they should be motivated to use adequate and recommended iron supplementation.
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http://dx.doi.org/10.3390/biom11050613DOI Listing
April 2021

Environmental barium: potential exposure and health-hazards.

Arch Toxicol 2021 Apr 19. Epub 2021 Apr 19.

Council for Nutritional and Environmental Medicine, Toften 24, 8610, Mo i Rana, Norway.

The relatively widespread presence of environmental barium is raising a growing public awareness as it can lead to different health conditions. Its presence in humans may produce several effects, especially among those chronically exposed from low to moderate doses. Barium accumulation can mainly occur by exposure in the workplace or from drinking contaminated water. However, this element is also assumed with the diet, mainly from plant foods. The average amount of barium intake worldwide and its geographical variation is little known due to the lack of research attention. Barium was never considered as an essential nutrient for humans, although it is undoubtedly naturally abundant enough and distinctive in its chemical properties that it might well have some biochemical function, e.g., for regulatory purposes, both in animals and plants. The information on the potential health effects of barium exposure is primarily based on animal studies and reported as comprising kidney diseases, neurological, cardiovascular, mental, and metabolic disorders. The present paper considers exposure and potential health concerns on environmental barium, giving evidence to information that can be used in future epidemiological and experimental studies.
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http://dx.doi.org/10.1007/s00204-021-03049-5DOI Listing
April 2021

Individual risk management strategy for SARS-CoV-2 infection: A step toward personalized healthcare.

Int Immunopharmacol 2021 Apr 1;96:107629. Epub 2021 Apr 1.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway. Electronic address:

Lethal or critical COVID-19 occurs most in infected hosts with certain risk factors such as advanced age or pre-existing disease. Host metabolic status significantly affects the clinical presentations of SARS-CoV-2 infection. Individual risk management is thus crucial for preventing severe COVID-19. Such susceptibility is individual, depending on a multitude of factors. Personalized risk assessment requires the inclusive analysis of big health data to stratify individual risk and derive a customized action plan. Personalized medicine requires shifting from the virology aspect per se to the whole individual's consideration, including dietary pattern, nutritional status, supporting lifestyle, co-existing diseases, and environmental factors. In this short communication, we discuss the individual management strategy for SARS-CoV2 infection as a step towards future personalized healthcare.
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http://dx.doi.org/10.1016/j.intimp.2021.107629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015431PMC
April 2021

Relationship between gestational diabetes and serum trace element levels in pregnant women from Eastern Iran: a multivariate approach.

Environ Sci Pollut Res Int 2021 Apr 16. Epub 2021 Apr 16.

Council for Nutritional and Environmental Medicine, Mo i Rana, Norway.

The prevalence of gestational diabetes mellitus (GDM) has increased over the recent decades. Exposure to environmental contaminants may be a risk factor for the development of GDM, but this is heavily dependent on particular circumstances. Studies on various areas linking various factors are therefore needed. We examined the associations between serum trace element levels and incidents of GDM among 102 pregnant women (diabetic n = 60 and healthy n = 42) living in Birjand (Iran). Blood serum samples were analyzed for concentrations of elements linked to particulate matter air pollution such as As, Cd, Cu, Hg, Mn, Ni, V, and Zn. Concentrations of As (8.58 vs. 3.15 μg/L), Cd (6.74 vs. 0.52 μg/L), and Hg (2.60 vs. 0.90 μg/L) were significantly higher in women with GDM. Risk difference (RD) estimation showed that As, 0.516 (0.355, 0.677); Cd, 0.719 (0.534, 0.904); and Hg, 0.505 (0.276, 0.735) increase GDM probability, while V lower that risk, -0.139 (-0.237, -0.042). With the principal component analysis, we were able to separate subjects according to their GDM status based on element levels. Such classification revealed very high efficiency with a true positive rate of 93%, according to linear discriminant analysis. GDM subjects presented higher levels of As, Cd, and Hg, indicating that these elements may disturb insulin metabolism and promote the development of GDM. Therefore, we conclude that systematic monitoring of trace elements followed by multivariate modeling in women planning pregnancy should be carried out to prevent the development of GDM.
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http://dx.doi.org/10.1007/s11356-021-13927-1DOI Listing
April 2021

The microbiota-mediated dietary and nutritional interventions for COVID-19.

Clin Immunol 2021 05 9;226:108725. Epub 2021 Apr 9.

Council for Nutritional and Environmental Medicine, Mo i Rana, Norway. Electronic address:

Worldwide, scientists are looking for specific treatment for COVID-19. Apart from the antiviral approach, the interventions to support healthy immune responses to the virus are feasible through diet, nutrition, and lifestyle approaches. This narrative review explores the recent studies on dietary, nutritional, and lifestyle interventions that influence the microbiota-mediated immunomodulatory effects against viral infections. Cumulative studies reported that the airway microbiota and SARS-CoV-2 leverage each other and determine the pathogen-microbiota-host responses. Cigarette smoking can disrupt microbiota abundance. The composition and diversification of intestinal microbiota influence the airway microbiota and the innate and adaptive immunity, which require supports from the balance of macro- and micronutrients from the diet. Colorful vegetables supplied fermentable prebiotics and anti-inflammatory, antioxidant phytonutrients. Fermented foods and beverages support intestinal microbiota. In sensitive individuals, the avoidance of the high immunoreactive food antigens contributes to antiviral immunity. This review suggests associations between airway and intestinal microbiota, antiviral host immunity, and the influences of dietary, nutritional, and lifestyle interventions to prevent the clinical course toward severe COVID-19.
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http://dx.doi.org/10.1016/j.clim.2021.108725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032598PMC
May 2021

A SARS-CoV-2 -human metalloproteome interaction map.

J Inorg Biochem 2021 Mar 13;219:111423. Epub 2021 Mar 13.

Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.

The recent pandemic caused by the novel coronavirus resulted in the greatest global health crisis since the Spanish flu pandemic of 1918. There is limited knowledge of whether SARS-CoV-2 is physically associated with human metalloproteins. Recently, high-confidence, experimentally supported protein-protein interactions between SARS-CoV-2 and human proteins were reported. In this work, 58 metalloproteins among these human targets have been identified by a structure-based approach. This study reveals that most human metalloproteins interact with the recently discovered SARS-CoV-2 orf8 protein, whose antibodies are one of the principal markers of SARS-CoV-2 infections. Furthermore, this work provides sufficient evidence to conclude that Zn plays an important role in the interplay between the novel coronavirus and humans. First, the content of Zn-binding proteins in the involved human metalloproteome is significantly higher than that of the other metal ions. Second, a molecular linkage between the identified human Zn-binding proteome with underlying medical conditions, that might increase the risk of severe illness from the SARS-CoV-2 virus, has been found. Likely perturbations of host cellular metal homeostasis by SARS-CoV-2 infection are highlighted.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955571PMC
March 2021

The continuum of disrupted metabolic tempo, mitochondrial substrate congestion, and metabolic gridlock toward the development of non-communicable diseases.

Crit Rev Food Sci Nutr 2021 Apr 2:1-17. Epub 2021 Apr 2.

Nutritional and Environmental Section, Thailand Initiatives for Functional Medicine, Bangkok Thailand.

Non-communicable diseases (NCD) are the slow-motion disasters with imminent global health care burden. The current dietary management for NCD is dominated by the calorie balance model. Apart from the quantitative balance of calorie, healthy bioenergetics requires temporal eating and fasting rhythms, and the subsequent switching for different metabolic fuels. We herein term these three bioenergetic attributes, i.e., caloric balance, diurnal eating-fasting rhythm, and metabolic flexibility, as the metabolic tempo. These three attributes are intertwined with each other; alteration of one attribute affects one or more other attributes. Lifestyle-induced disrupted metabolic tempo presents a high flux of mixed carbon substrates to mitochondria, with the resulting congestion and indecisiveness of metabolic switches. Such indecisiveness impairs metabolic flexibility, promotes anabolism, and accumulates the energy storage pools. The triggers from hypoxic inducible factor expression could further promote the metabolic gridlock and adipocyte maladaptation. The maladaptive adipocytes lead to ectopic fat deposition, increased circulating lipid levels, insulin resistance, and chronic systemic inflammation. These continuum set stages for clinical NCDs. We propose that the restoration of all tempo attributes through the combined diet-, time-, and calorie-restricted interventions could be the preferred strategy for NCD management.
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http://dx.doi.org/10.1080/10408398.2021.1907299DOI Listing
April 2021

The role of B vitamins in stroke prevention.

Crit Rev Food Sci Nutr 2021 Mar 16:1-14. Epub 2021 Mar 16.

Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania.

Elevated plasma levels of homocysteine (Hcy) are a recognized risk factor for stroke. This relationship represents one aspect of the debated `Hcy hypothesis'. Elevated Hcy may be an independent and treatable cause of atherosclerosis and thrombotic vascular diseases. Further observations indicate that proper dietary supplementation with B-vitamins decreases total plasma Hcy concentrations and may be an effective intervention for stroke prevention. Metabolic vitamin B deficiency is a nutritional determinant of total Hcy and stroke risk. Genetic factors may link B vitamins with stroke severity due to the impact on Hcy metabolism of polymorphism in the genes coding for methylenetetrahydrofolate reductase, methionine-synthase, methionine synthase reductase, and cystathionine β-synthase. Several meta-analyses of large randomized controlled trials exist. However, they are not completely in agreement about B vitamins' role, particularly folic acid levels, vitamin B, and B, in lowering the homocysteine concentrations in people at high stroke risk. A very complex relationship exists between Hcy and B vitamins, and several factors appear to modify the preventive effects of B vitamins in stroke. This review highlights the regulating factors of the active role of B vitamins active in stroke prevention. Also, inputs for further large, well-designed studies, for specific, particularly sensitive subgroups are given.
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http://dx.doi.org/10.1080/10408398.2021.1885341DOI Listing
March 2021

Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis.

Arch Toxicol 2021 04 2;95(4):1161-1178. Epub 2021 Mar 2.

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway.

A fundamental metabolic feature of cancerous tissues is high glucose consumption. The rate of glucose consumption in a cancer cell can be 10-15 times higher than in normal cells. Isolation and cultivation of tumor cells in vitro highlight properties that are associated with intensive glucose utilization, the presence of minimal oxidative metabolism, an increase in lactate concentrations in the culture medium and a reduced rate of oxygen consumption. Although glycolysis is suggested as a general feature of malignant cells and recently identified as a possible contributing factor to tumor progression, several studies highlight distinct metabolic characteristics in some tumors, including a relative decrease in avidity compared to glucose and/or a glutamine dependency of lactate and even proliferative tumor cells. The aim of this review is to determine the particularities in the energy metabolism of cancer cells, focusing on the main nutritional substrates, such as glucose and glutamine, evaluating lactate dehydrogenase as a potential marker of malignancy and estimating activators and inhibitors in cancer treatment.
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http://dx.doi.org/10.1007/s00204-021-02974-9DOI Listing
April 2021

The Role of Diet and Supplementation of Natural Products in COVID-19 Prevention.

Biol Trace Elem Res 2021 Feb 25. Epub 2021 Feb 25.

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway.

Recently, a discussion has begun on the global management strategy against COVID-19 based on the hypothesis that individuals' macro- and micronutrient status combined with antiviral drugs and herbs can be an ally against the infection. The hypothesis is that people's nutritional and oxidative scavenging capacity may provide fundamental data to predict severe and acute pulmonary distress following SARS-Cov2 infection. Consequently, the scientific community has addressed the role of balanced diets, nutritional supplements, and micronutrients, including folk herbal formulations, in reducing hospitalization and the severity of pulmonary impact in COVID-19 by preventing the most serious forms of the infection. This led to an animated debate on the potential effectiveness of some vitamins, micronutrients, and traditional Chinese medicine in preventing COVID-19, with some authors convinced that plant extracts could act oppositely, exacerbating the effect of the infection. While current research is still far to assess the suggestions and issues raised in this short communication, it is undoubtedly true that determining an individual's current metabolic status, including macro- and micronutrients, is an essential factor in defining any individuals' deficiencies, which will need to be addressed urgently through a proper diet, specific personalized nutritional supplementation, and lifestyle changes.
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http://dx.doi.org/10.1007/s12011-021-02623-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905195PMC
February 2021

Prevalence and Risk Factors of Dysphagia in Patients with Multiple Sclerosis.

Dysphagia 2021 Feb 12. Epub 2021 Feb 12.

Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Dysphagia is one of the most common symptoms in multiple sclerosis (MS) patients. It can reduce the quality of life and increase the risk of mortality by developing complications such as aspiration pneumonia. The present study was conducted to estimate the prevalence of dysphagia in MS patients and investigate the associations between dysphagia and disease characteristics. The Persian version of the DYMUS questionnaire was used to assess dysphagia in 865 patients with MS, including 738 (85.3%) relapsing-remitting MS (RRMS), 106 (12.3%) secondary progressive MS (SPMS), and 21 (2.4%) primary progressive MS (PPMS). Also, demographic and clinical data, including age, sex, smoking status, Expanded Disability Status Scale (EDSS) score, disease duration, disease-modifying therapies exposure, initial symptoms of MS, were recorded. The mean (SD) age was 37.95(9.25) years, and 83.1% of the participants were female. The prevalence of dysphagia was estimated to be 25.4% among all patients. According to the DYMUS questionnaire results, the prevalence of dysphagia in RRMS, SPMS, and PPMS patients was 22.2%, 44.3%, and 42.9%, respectively. After multivariate analysis the current EDSS score (OR = 1.197, CI: 1.062, 1.350, p = 0.003), cerebellar impairment (OR = 1.335, CI: 1.450, 4.716, p = 0.004) and motor dysfunction (OR = 1.651, CI: 1.004, 2.715, p = 0.048) emerged as the risk factors for dysphagia. Since dysphagia, as previously mentioned, is a common symptom in multiple sclerosis, particularly in SPMS and PPMS courses, active screening for this condition is recommended in all patients, particularly those with identified risk factors.
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http://dx.doi.org/10.1007/s00455-021-10245-zDOI Listing
February 2021

Chloroquine and hydroxychloroquine in the treatment of COVID-19: the never-ending story.

Appl Microbiol Biotechnol 2021 Feb 30;105(4):1333-1343. Epub 2021 Jan 30.

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway.

The anti-malarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have been suggested as promising agents against the new coronavirus SARS-CoV-2 that induces COVID-19 and as a possible therapy for shortening the duration of the viral disease. The antiviral effects of CQ and HCQ have been demonstrated in vitro due to their ability to block viruses like coronavirus SARS in cell culture. CQ and HCQ have been proposed to reduce immune reactions to infectious agents, inhibit pneumonia exacerbation, and improve lung imaging investigations. CQ analogs have also revealed the anti-inflammatory and immunomodulatory effects in treating viral infections and related ailments. There was, moreover, convincing evidence from early trials in China about the efficacy of CQ and HCQ in the anti-COVID-19 procedure. Since then, research and studies have been massive to ascertain these drugs' efficacy and safety in treating the viral disease. In the present review, we construct a synopsis of the main properties and current data concerning the metabolism of CQ/HCQ, which were the basis of assessing their potential therapeutic roles against the new coronavirus infection. The effective role of QC and HCQ in the prophylaxis and therapy of COVID-19 infection is discussed in light of the latest international medical-scientific research results. KEY POINTS: • Data concerning metabolism and properties of CQ/HCQ are discussed. • The efficacy of CQ/HCQ against COVID-19 has been the subject of contradictory results. • CQ/HCQ has little or no effect in reducing mortality in SARS-CoV-2-affected patients.
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http://dx.doi.org/10.1007/s00253-021-11094-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847229PMC
February 2021

The Role of Sugar-Rich Diet and Salivary Proteins in Dental Plaque Formation and Oral Health.

J Oral Biosci 2021 Jan 23. Epub 2021 Jan 23.

Council for Nutritional and Environmental Medicine, Mo I Rana, Norway. Electronic address:

Background: Dental plaque is a complex colorless film of bacteria that develops on the surfaces of teeth. Different mechanisms of microbial adhesion to tooth surfaces exist. Both non-specific and specific types of adherence have been anticipated.

Highlight: The present review evaluated the effect of sugar-rich diet and salivary proteins on oral hygiene and dental plaque development.

Conclusion: The oral microbiota is essential for maintaining and reestablishing a healthy oral cavity. Different types of sugars have different effects on the inhibition and formation of dental plaque. The peptides, proteins, and amino acids secreted by parotid glands in the oral cavity facilitate in neutralizing the acidity in dental plaque and preventing dental caries. A properly balanced diet is crucial for both a healthy oral cavity and the oral microbiome.
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http://dx.doi.org/10.1016/j.job.2021.01.007DOI Listing
January 2021

The impact of glutathione metabolism in autism spectrum disorder.

Pharmacol Res 2021 Apr 22;166:105437. Epub 2021 Jan 22.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; CONEM Scientific Secretary, Verona, Italy.

This paper reviews the potential role of glutathione (GSH) in autism spectrum disorder (ASD). GSH plays a key role in the detoxification of xenobiotics and maintenance of balance in intracellular redox pathways. Recent data showed that imbalances in the GSH redox system are an important factor in the pathophysiology of ASD. Furthermore, ASD is accompanied by decreased concentrations of reduced GSH in part caused by oxidation of GSH into glutathione disulfide (GSSG). GSSG can react with protein sulfhydryl (SH) groups, thereby causing proteotoxic stress and other abnormalities in SH-containing enzymes in the brain and blood. Moreover, alterations in the GSH metabolism via its effects on redox-independent mechanisms are other processes associated with the pathophysiology of ASD. GSH-related regulation of glutamate receptors such as the N-methyl-D-aspartate receptor can contribute to glutamate excitotoxicity. Synergistic and antagonistic interactions between glutamate and GSH can result in neuronal dysfunction. These interactions can involve transcription factors of the immune pathway, such as activator protein 1 and nuclear factor (NF)-κB, thereby interacting with neuroinflammatory mechanisms, ultimately leading to neuronal damage. Neuronal apoptosis and mitochondrial dysfunction are recently outlined as significant factors linking GSH impairments with the pathophysiology of ASD. Moreover, GSH regulates the methylation of DNA and modulates epigenetics. Existing data support a protective role of the GSH system in ASD development. Future research should focus on the effects of GSH redox signaling in ASD and should explore new therapeutic approaches by targeting the GSH system.
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http://dx.doi.org/10.1016/j.phrs.2021.105437DOI Listing
April 2021

Interrelations between COVID-19 and other disorders.

Clin Immunol 2021 03 14;224:108651. Epub 2020 Dec 14.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway. Electronic address:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory tract virus that causes Coronavirus disease (COVID-19). The virus originated in Wuhan, China, in December 2019 and has spread across the globe to-date. The disease ranges from asymptomatic carriers to symptoms such as fever, sore throat, cough, lung infections, and in severe cases, acute respiratory distress syndrome, sepsis, and death. As many as 50% of patients reported having at least one comorbidities with COVID-19 upon hospital admission. Hypertension, diabetes, chronic obstructive pulmonary disease, obesity, and cardiovascular diseases are among the most commonly reported. Comorbidities are contributing to acute disease prognosis and increased risk of severe symptoms. Around 70% of patients who require ICU care have been observed to have comorbidities. This review intends to understand how some of these comorbidities affect the disease's prognosis and how severe the outcome can be expected.
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http://dx.doi.org/10.1016/j.clim.2020.108651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833539PMC
March 2021

High-fat diet-induced obesity and impairment of brain neurotransmitter pool.

Transl Neurosci 2020 1;11(1):147-160. Epub 2020 Jun 1.

Central Laboratory, Female Centre for Scientific and Medical Studies, King Saud University, Riyadh, Saudi Arabia.

Obesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione--transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group ( > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.
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http://dx.doi.org/10.1515/tnsci-2020-0099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705990PMC
June 2020

The glutathione system in Parkinson's disease and its progression.

Neurosci Biobehav Rev 2021 01 14;120:470-478. Epub 2020 Oct 14.

Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania.

Redox dysfunctions and neuro-oxidative stress play a major role in the pathophysiology and progression of Parkinson's disease (PD). Glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio are lowered in oxidative stress conditions and may lead to increased oxidative toxicity. GSH is involved not only in neuro-immune and neuro-oxidative processes, including thiol redox signaling, but also in cell proliferation and differentiation and in the regulation of cell death, including apoptotic pathways. Lowered GSH metabolism and a low GSH/GSSG ratio following oxidative stress are associated with mitochondrial dysfunctions and constitute a critical factor in the neuroinflammatory and neurodegenerative processes accompanying PD. This review provides indirect evidence that GSH redox signaling is associated with the pathophysiology of PD. Nevertheless, it has not been delineated whether GSH redox imbalances are a causative factor in PD or whether PD-associated pathways cause the GSH redox imbalances in PD. The results show that antioxidant approaches, including neuroprotective and anti-neuroinflammatory agents, which neutralize reactive oxygen species, may have therapeutic efficacy in the treatment of PD and its progression.
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http://dx.doi.org/10.1016/j.neubiorev.2020.10.004DOI Listing
January 2021

Neurological Involvements of SARS-CoV2 Infection.

Mol Neurobiol 2021 Mar 16;58(3):944-949. Epub 2020 Oct 16.

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway.

COVID-19 is a pandemic viral infection caused by a novel coronavirus, SARS-CoV2, which is a global concern of the twenty-first century for its rapid spreading in a short period. Apart from its known acute respiratory involvements, the CNS manifestations of COVID-19 are common. These neurological symptoms are diverse and could range from mild nonspecific or specific symptoms such as the loss of various sensory perceptions, the worrying autoimmune Guillain-Barré syndrome, to the life-threatening acute disseminated encephalomyelitis, and the CNS-mediated respiratory distress. An autopsy report documented the presence of SARS-CoV2 in brain tissues of a COVID-19 patient. However, there is no definite conclusion on the mechanisms of SARS-CoV2 neuroinvasion. These proposed mechanisms include the direct viral invasion, the systemic blood circulation, or the distribution of infected immune cells. Concerning these different neuropathophysiologies, COVID-19 patients who are presenting with either the early-onset, multiple, and severe CNS symptoms or rapid respiratory deterioration should be suspected for the direct viral neuroinvasion, and appropriate management options should be considered. This article reviews the neurological manifestations, the proposed neuroinvasive mechanisms, and the potential neurological sequelae of SARS-CoV2.
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http://dx.doi.org/10.1007/s12035-020-02070-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562688PMC
March 2021

Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures.

Curr Med Chem 2021 ;28(8):1471-1488

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway.

Human life expectancy is increasing significantly over time thanks to the improved possibility for people to take care of themselves and the higher availability of food, drugs, hygiene, services, and assistance. The increase in the average age of the population worldwide is, however, becoming a real concern, since aging is associated with the rapid increase in chronic inflammatory pathologies and degenerative diseases, very frequently dependent on senescent phenomena that occur alongside with senescence. Therefore, the search for reliable biomarkers that can diagnose the possible onset or predict the risk of developing a disease associated with aging is a crucial target of current medicine. In this review, we construct a synopsis of the main addressable biomarkers to study the development of aging and the associated ailments.
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http://dx.doi.org/10.2174/0929867327999200917150652DOI Listing
May 2021

Sulfhydryl groups as targets of mercury toxicity.

Coord Chem Rev 2020 Aug 7;417. Epub 2020 May 7.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway.

The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. , Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg, CHHg, CHHg, CHHg) protein. At the Cys residue, Hg binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys), thioredoxin reductase (TrxR) (Cys) activity, as well as limiting GSH (GS-HgCH) and Trx (Cys) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload.
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http://dx.doi.org/10.1016/j.ccr.2020.213343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470069PMC
August 2020

The Proteomics Study of Compounded HFE/TF/TfR2/HJV Genetic Variations in a Thai Family with Iron Overload, Chronic Anemia, and Motor Neuron Disorder.

J Mol Neurosci 2021 Mar 7;71(3):545-555. Epub 2020 Sep 7.

Proteomics Research Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani, Thailand.

The mutation of the homeostatic iron regulatory genes (HFE) impaired the hepatic hepcidin transcription leading to the chronic excess of the iron pool, with the adverse consequences of free radical oxidative damages. We herein reported the findings of Thai family members who had the compound of uncommon HFE rs2794719, together with transferrin (TF) rs1867504, transferrin receptor 2 (TfR2) rs7385804, and hemojuvelin (HJV) rs16827043 genetic variants involved in the hepcidin transcriptional pathway. These compounded genetic variants could produce the spectrum of clinical phenotypes that spanned from mild to moderate symptoms of chronic anemia to an established motor neuron disorder. The feasible pathophysiologies were the impairment of the transferrin receptor functions, which affected the endocytic uptake of halo-transferrin into the erythroblast precursors. Such a defect left the erythropoiesis depleted of their iron supply. These alterations also promoted the TfR-independent uptake of iron into other target tissues and left the TrF2/BMP-dependent-hepcidin activation pathway unattended. We used the predicted molecular interactive proteomes to support our speculated dysregulated iron metabolism. During the early stage of an elevated ferritin level, there was no inhibition of ferroportin activities from hepcidin. These pathophysiological processes went on to the point of an iron overload threshold. After that, the hepcidin transcription started to kick in with the resulting decreased serum iron levels and deterioration of clinical symptoms.
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http://dx.doi.org/10.1007/s12031-020-01676-8DOI Listing
March 2021

The association between the incidence of COVID-19 and the distance from the virus epicenter in Iran.

Arch Virol 2020 Nov 2;165(11):2555-2560. Epub 2020 Sep 2.

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

Since the first official report of the spread of SARS-CoV-2 infections in the city of Qom in mid-February, Iran has become the country most affected by the COVID-19 epidemic in the Middle East. All Iranian provinces are now affected, although to a different extent. The aim of the present study was to evaluate whether the distance from the epicenter of the infection (Qom) or demographic factors such as population density and the ratio of the elderly population are associated with the incidence of COVID-19 in different Iranian provinces. For the purpose of determining whether the distance from the virus epicenter could be associated with the spread of infection, linear regression analysis was performed using STATA 12.0 software. The association of the incidence of COVID-19 with the population density and the ratio of the population over 65 years old in 31 Iranian provinces was also evaluated. According to our results, a strong association was found between the incidence of COVID-19 in Iranian provinces and their respective distance from Qom (p < 0.001; C = -0.68). The incidence of COVID-19 in Iranian provinces was also positively associated with the ratio of the population over 65 years old (p = 0.002; C = 0.53), while no significant association with population density was found (p = 0.39; C = 0.16). These results suggest that the implementation of travel restrictions from highly affected areas to other provinces could considerably reduce the rate of transmission of the disease throughout the country. Also, provinces with a higher proportion of elderly people (over 65) were identified as particularly at risk for the spread of SARS-CoV-2 infections. These results will contribute to better management of the COVID-19 outbreak in Iran, taking into account demographic and geographic characteristics of different provinces.
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http://dx.doi.org/10.1007/s00705-020-04774-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466924PMC
November 2020

Obesity and Insulin Resistance: Associations with Chronic Inflammation, Genetic and Epigenetic Factors.

Curr Med Chem 2021 ;28(4):800-826

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610 Mo i Rana, Norway.

Background: Obesity is known to be a multifactorial disease. In its pathogenesis, different factors such as chronic inflammation, oxidative stress, insulin resistance, genetic factors, environmental effects, vegetative disturbance, and unbalanced nutrition play a significant role.

Methodology: This study describes the association of obesity and insulin resistance with chronic inflammation, genetic, and epigenetic factors. Previous literature has been reviewed to explain the relation of obesity with those factors involved in chronic low-grade inflammation and insulin.

Results: Obesity is associated with a decrease in ghrelin secretion, elevated plasma leptin levels, oxidative stress, increased macrophage phagocytic activity, and the induction of proinflammatory synthesis of cytokines and interferon-gamma. Obesity is linked to decreased levels of cytochrome P450 (CYP) enzymes and impaired detoxification processes. Deficiency of vitamins and minerals can also play a significant role in the development of oxidative stress and chronic inflammation in obesity. There is evidence of associations between a genetic predisposition to obesity in children with elevated levels of certain miRNAs.

Conclusion: The purpose of the present review is an analysis of the multiple factors associated with obesity.
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http://dx.doi.org/10.2174/0929867327666200824112056DOI Listing
March 2021

Association between the gut and oral microbiome with obesity.

Anaerobe 2020 Aug 14:102248. Epub 2020 Aug 14.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway. Electronic address:

In recent decades, obesity has become one of the most common lifestyle-associated disorders. Obesity is a major contributing factor for several other lifestyles associated disorders such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. Although genetics and lifestyle have been directly implicated in the onset and progression of obesity, recent studies have established that gut microbiome plays a crucial role in obesity progression. A higher proportion of Firmicutes and a skewed Firmicutes/Bacteroidetes ratio may contribute to gut dysbiosis and subsequent disturbances in the overall body metabolisms. Like gut microbiome, the oral cavity of humans also harbors a characteristic microbial population called "oral microbiome". The oral microbiome has also been implicated in the development of obesity due to its modulating effects on the gut microbiome. Due to its critical role in obesity, alteration in the gut microbiome has been suggested as one of the therapeutic strategies to manage obesity itself. For example, fecal microbiome transfer, or the use of probiotics and prebiotics have been suggested. These therapies not only restore the gut microbiome to the "pre-obese stage" but also ameliorate many functional aspects of the metabolic syndrome such as systemic inflammation, insulin resistance, and fat accumulation. However, the efficacy and safety of some of the methods have not been tested for their long-term implications, and further research in this area is warranted to understand the molecular mechanisms involved in this process completely.
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http://dx.doi.org/10.1016/j.anaerobe.2020.102248DOI Listing
August 2020

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome.

Mol Neurobiol 2020 Nov 6;57(11):4598-4607. Epub 2020 Aug 6.

Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions. The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS. Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS. The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS. This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.
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http://dx.doi.org/10.1007/s12035-020-01939-wDOI Listing
November 2020

The role of glutathione redox imbalance in autism spectrum disorder: A review.

Free Radic Biol Med 2020 11 31;160:149-162. Epub 2020 Jul 31.

IM Sechenov First Moscow State Medical University, Moscow, Russia; Federal Research Centre of Biological Systems, Agro-technologies of the Russian Academy of Sciences, Orenburg, Russia.

The role of glutathione in autism spectrum disorder (ASD) is emerging as a major topic, due to its role in the maintenance of the intracellular redox balance. Several studies have implicated glutathione redox imbalance as a leading factor in ASD, and both ASD and many other neurodevelopmental disorders involve low levels of reduced glutathione (GSH), high levels of oxidized glutathione (GSSG), and abnormalities in the expressions of glutathione-related enzymes in the blood or brain. Glutathione metabolism, through its impact on redox environment or redox-independent mechanisms, interferes with multiple mechanisms involved in ASD pathogenesis. Glutathione-mediated regulation of glutamate receptors [e.g., N-methyl-d-aspartate (NMDA) receptor], as well as the role of glutamate as a substrate for glutathione synthesis, may be involved in the regulation of glutamate excitotoxicity. However, the interaction between glutathione and glutamate in the pathogenesis of brain diseases may vary from synergism to antagonism. Modulation of glutathione is also associated with regulation of redox-sensitive transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) and downstream signaling (proinflammatory cytokines and inducible enzymes), thus providing a significant impact on neuroinflammation. Mitochondrial dysfunction, as well as neuronal apoptosis, may also provide a significant link between glutathione metabolism and ASD. Furthermore, it has been recently highlighted that glutathione can affect and modulate DNA methylation and epigenetics. Review analysis including research studies meeting the required criteria for analysis showed statistically significant differences between the plasma GSH and GSSG levels as well as GSH:GSSG ratio in autistic patients compared with healthy individuals (P = 0.0145, P = 0.0150 and P = 0.0202, respectively). Therefore, the existing data provide a strong background on the role of the glutathione system in ASD pathogenesis. Future research is necessary to investigate the role of glutathione redox signaling in ASD, which could potentially also lead to promising therapeutics.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.07.017DOI Listing
November 2020

Is Fertility Affected in Women of Childbearing Age with Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder?

J Mol Neurosci 2020 Nov 1;70(11):1829-1835. Epub 2020 Aug 1.

Isfahan Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system (CNS), which is more prevalent among women of childbearing age. Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease of the CNS with similar prevalence features to MS and has recently been considered a different entity from MS. Measuring ovarian reserve is one way of evaluating fertility. Anti-Müllerian hormone (AMH) is a peptide hormone produced by ovarian granulosa cells of early follicles and is considered to be a marker for ovarian reserve. With MS and NMOSD predominance in young women, the present study aimed to address the possibility of these diseases affecting fertility by measuring AMH levels in MS and NMOSD patients and comparing it with healthy controls. The present study included 23 relapsing-remitting MS (RRMS) patients, 23 seronegative NMOSD patients, and 23 healthy age-matched controls between 18 and 45 years of age. Serum samples of the three groups were collected, and the AMH levels were measured with AMH Gen II Enzyme-Linked Immunosorbent Assay, Beckman Coulter kit. In the present study, the AMH levels did not differ significantly between the groups (p = 0.996). The mean AMH in the RRMS group was 3.59 ± 0.55 ng/ml compared with the mean of 3.60 ± 0.50 ng/ml in healthy controls. The mean AMH levels in the NMOSD group were 3.66 ± 0.61 ng/ml. Lower levels of AMH were found to be negatively associated with annualized relapse rate (in both groups of patients) and MS severity score. However, the difference was not significant. In NMOSD patients, the serum levels of AMH were negatively associated with disease duration (r = - 0.42, p = 0.023). There had been a significant negative correlation between mean AMH serum levels with Expanded Disability Status Scale (EDSS) at the time of diagnosis and at the time of study in the NMOSD group (r = - 0.402, p = 0.03 and r = - 0.457, p = 0.014, respectively). There was not a significant difference in mean serum AMH levels between RRMS and NMOSD patients compared with that of healthy controls. Further studies with larger sample sizes should be conducted, which take more variables affecting fertility in women with either RRMS or NMOSD into account to put an end to the controversial issue of fertility in this area.
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http://dx.doi.org/10.1007/s12031-020-01576-xDOI Listing
November 2020

Micronutrients as immunomodulatory tools for COVID-19 management.

Clin Immunol 2020 11 22;220:108545. Epub 2020 Jul 22.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway. Electronic address:

COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.
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http://dx.doi.org/10.1016/j.clim.2020.108545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833875PMC
November 2020

Relationship between Gut Microbiota, Gut Hyperpermeability and Obesity.

Curr Med Chem 2021 ;28(4):827-839

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610 Mo i Rana, Norway.

Intestinal hyperpermeability is a complex metabolic process mediated by different pathways in close relation to the gut microbiota. Previous studies suggested that the gut microbiota is involved in different metabolic regulations, and its imbalance is associated with several metabolic diseases, including obesity. It is well known that intestinal hyperpermeability is associated with dysbiosis, and the combination of these two conditions can lead to an increase in the level of low-grade inflammation in obese patients due to an increase in pro-inflammatory cytokine levels. Inflammatory bowel syndrome often accompanies this condition causing an alteration of the intestinal mucosa and thus reinforcing the dysbiosis and gut hyperpermeability. The onset of metabolic disorders depends on violations of the integrity of the intestinal barrier as a result of increased intestinal permeability. Chronic inflammation due to endotoxemia is responsible for the development of obesity. Metabolic disorders are associated with dysregulation of the microbiota-gut-brain axis and with an altered composition of gut flora. In this review, we will discuss the mechanisms that illustrate the relationship between hyperpermeability, the composition of the gut microbiota, and obesity.
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http://dx.doi.org/10.2174/0929867327666200721160313DOI Listing
March 2021

Wheat and chaffs in the interpretation of the current COVID19 outbreak in Italy.

Virusdisease 2020 Jun 5;31(2):85-93. Epub 2020 Jun 5.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway.

The COVID19 outbreak in Italy is still a big concern. The Italian Government has recommended citizens to respect faithfully any compulsory legal disposition in order to stay home and so contributing in escaping viral contacts and slowing down epidemic. Emergency has raised a widely animated debate about how to read and comprehend the daily case numbers, the medical and caregivers availability, the needs to swab asymptomatic subjects. In this review the authors discuss about the many wheat and chaffs of how this virus disease is addressed .
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http://dx.doi.org/10.1007/s13337-020-00602-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274266PMC
June 2020