Publications by authors named "Dimitrios P Bogdanos"

204 Publications

Lack of association between TREM2 rs75932628 variant and amyotrophic lateral sclerosis.

Mol Biol Rep 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Larissa, Greece.

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease. Inflammatory processes are among the mechanisms that are implicated in ALS pathogenesis. The TREM2 rs75932628 T variant may influence the regulatory effect of TREM2 on inflammation. Studies regarding the role of the rs75932628 variant in ALS have yielded inconsistent results, so far. To assess the role of TREM2 rs75932628 on ALS risk. We genotyped 155 patients with sporadic ALS and 155 healthy controls for TREM2 rs75932628. We also merged and meta-analyzed our data with data from previous studies (with a total of 7524 ALS cases and 14,675 controls), regarding TREM2 rs75932628 and ALS. No ALS or healthy subjects carried the TREM2 rs75932628-T variant. Results from meta-analyses (overall approach and sensitivity analyses) yielded no significant results for possible connection between TREM2 rs75932628-T variant and ALS. Based on our results, TREM2 rs75932628 does not seem to play a determining role to the pathophysiology of ALS.
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http://dx.doi.org/10.1007/s11033-021-06312-1DOI Listing
April 2021

CD33 rs3865444 as a risk factor for Parkinson's disease.

Neurosci Lett 2021 03 11;748:135709. Epub 2021 Feb 11.

Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Greece, Faculty of Medicine, School of Health Sciences, University of Thessaly, Mezourlo Hill, 41100 Larissa, Greece. Electronic address:

Background: Alzheimer's (AD) and Parkinson's diseases (PD) share a few elements of their clinical, pathological and genetic backgrounds. The CD33 rs3865444 has emerged as a strong genetic locus associated with AD through genome-wide association study (GWAS). However, little is known for its role in PD.

Objective: To assess the role of CD33 rs3865444 on PD risk.

Methods: We genotyped 358 patients with PD and 358 healthy controls for theCD33 rs3865444. Odds ratios (ORs) with the respective 95% confidence intervals (CIs)], were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant and log-additive), with the G allele as the reference allele.

Results: The CD33 rs3865444 was associated with decreased PD risk in the dominant [GG vs GT + TT; OR (95% CI) = 0.61 (0.45-0.82), p = 0.001], the over-dominant [GG + TT vs GT; OR (95% CI) = 0.65 (0.48-0.89), p = 0.0061], log-additive [OR (95% CI) = 0.67 (0.52-0.86), p = 0.0014], and co-dominant [with overall p = 0.0043, and OR (95% CI) = 0.62 (0.45-0.84) for the TG genotype compared to the GG], modes of inheritance.

Conclusions: The CD33 rs3865444 is associated with decreased PD risk, and larger studies investigating the role of CD33 rs3865444 on PD are needed.
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http://dx.doi.org/10.1016/j.neulet.2021.135709DOI Listing
March 2021

Thinking outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke.

J Clin Med 2021 Feb 7;10(4). Epub 2021 Feb 7.

Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.

Ischemic stroke (IS) is a major cause of death and disability, despite early intervention. Thrombo-inflammation, the inflammatory process triggered by ischemia, is a concept that ties IS with multiple sclerosis (MS), under the wider 'umbrella' of neuroinflammation, i.e., the inflammation of the nervous tissue. Drawing from this, numerous studies have explored the potential of MS disease-modifying drugs in the setting of IS. In this review, we present the available studies and discuss their potential in ameliorating IS outcomes. Based on our search, the vast majority of the studies have been conducted on animals, yielding mostly positive results. Two clinical trials involving natalizumab showed that it does not confer any benefits, but four human studies regarding fingolimod have showcased its potential in improving recovery prospects. However, concerns on safety and other issues are raised, and basic questions still need to be answered.
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http://dx.doi.org/10.3390/jcm10040630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914575PMC
February 2021

Disease Activity, Functional Ability and Nutritional Status in Patients with Rheumatoid Arthritis: An Observational Study in Greece.

Mediterr J Rheumatol 2020 Dec 28;31(4):406-411. Epub 2020 Dec 28.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Aim: The aim of the present pilot study was to assess differences in the nutritional status, Mediterranean diet (MD) adherence, and functional ability among patients with rheumatoid arthritis (RA), according to disease activity.

Methods: A total of 48 patients with RA, outpatients of a hospital in Athens, Greece were recruited. Disease activity was evaluated with DAS28, functional status with the Health Assessment Questionnaire (HAQ), MD adherence with the MedDietScore and malnutrition with the patient-generated subjective global assessment (PG-SGA).

Results: A relationship was noted between DAS28 and HAQ, indicating a reduced functional status with increased RA activity. Although MD adherence differed between DAS28 categories, no specific differences were noted in the PG-SGA or the MedDietScore in the post-hoc analyses. According to the PG-SGA, no need for nutritional intervention was noted among participants.

Conclusions: The origin of the participants might have reduced the differences between MD adherence and DAS28. In parallel, the PG-SGA does not appear sensitive in detecting muscle-related malnutrition among patients with RA.
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http://dx.doi.org/10.31138/mjr.31.4.406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841099PMC
December 2020

Social Media as Tools to Study Dietary Habits of Patients with Rheumatic Diseases: Learning from Relevant Work on Inflammatory Bowel Diseases.

Mediterr J Rheumatol 2020 Dec 22;31(4):382-383. Epub 2020 Dec 22.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

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http://dx.doi.org/10.31138/mjr.31.4.382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841103PMC
December 2020

Searching for Possible Links between Alzheimer's Disease and Systemic Sclerosis.

Mediterr J Rheumatol 2020 Dec 28;31(4):378-381. Epub 2020 Dec 28.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, University General Hospital of Larissa, Larissa, Greece.

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http://dx.doi.org/10.31138/mjr.31.4.378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841100PMC
December 2020

and Polymorphisms as Risk Factors for Parkinson's Disease.

J Clin Med 2021 Jan 20;10(3). Epub 2021 Jan 20.

Laboratory of Neurogenetics, Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.

Background: Parkinson's disease (PD) is the second commonest neurodegenerative disease. The genetic basis of PD is indisputable. Both and have been linked to PD, to some extent, but the exact role of those polymorphisms in PD remains controversial.

Objective: We assessed the role of and on PD risk.

Methods: We genotyped 358 patients with PD and 358 healthy controls for and . We also merged and meta-analyzed our data with data from previous studies, regarding these two polymorphisms and PD.

Results: No significant association with PD was revealed ( > 0.05), for either or , in any of the examined genetic model of inheritance. In addition, results from meta-analyses yield negative results.

Conclusions: Based on our analyses, it appears rather unlikely that or is among the major risk factors for PD, at least in Greek patients with PD.
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http://dx.doi.org/10.3390/jcm10030381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864159PMC
January 2021

Low FODMAP Diet for Functional Gastrointestinal Symptoms in Quiescent Inflammatory Bowel Disease: A Systematic Review of Randomized Controlled Trials.

Nutrients 2020 Nov 27;12(12). Epub 2020 Nov 27.

Department of Rheumatology and Clinical Immunology, School of Health Sciences, Faculty of Medicine, University of Thessaly, Biopolis, GR-41334 Larissa, Greece.

A low FODMAP diet (LFD) has been hypothesized to relieve symptoms of functional gastrointestinal disorders (FGD) in patients with inflammatory bowel disease (IBD). The aim of the study was to systematically review the literature for randomized controlled trials (RCTs) assessing the effectiveness of the LFD in patients with IBD and FGD. Four databases were searched, but a meta-analysis was not performed due to methodological and outcomes heterogeneity. Four RCTs fulfilled the criteria, with three having some concerns in their risk of bias assessment. All interventions compared the LFDs against a "typical" or sham diet, spanning in duration from 21 days to 6 weeks. Quality of life was improved in two RCTs, while revealing inconsistent findings in the third trial, based on different assessment tools. The fecal assays revealed non-significant findings for most variables (fecal weight, pH, water content, gene count, and gut transit time) and inconsistent findings concerning stool frequency and short-chain fatty acids concentration. Levels of fecal calprotectin, CRP, or T-cell phenotype did not differ between intervention and comparator arms. Two RCTs reported a reduction in abdominal pain, while results concerning pain duration and bloating were inconsistent. In one trial, energy intake was considerably reduced among LFD participants. Regarding gut microbiota, no differences were noted. A considerable degree of methodological and outcome heterogeneity was observed, paired with results inconsistency. The available data are not sufficient to justify the claim that an LFD induces relief of FGD symptoms, although it may pave the way to a placebo response.
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http://dx.doi.org/10.3390/nu12123648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760970PMC
November 2020

The role of MiRNA-21 in gliomas: Hope for a novel therapeutic intervention?

Toxicol Rep 2020 6;7:1514-1530. Epub 2020 Nov 6.

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.

Gliomas are the most common primary brain tumors in adults. They are generally very resistant to treatment and are therefore associated with negative outcomes. MicroRNAs (miRNAs) are small, non-coding RNA molecules that affect many cellular processes by regulating gene expression and, post-transcriptionally, the translation of mRNAs. MiRNA-21 has been consistently shown to be upregulated in glioma and research has shown that it is involved in a wide variety of biological pathways, promoting tumor cell survival and invasiveness. Furthermore, it has been implicated in resistance to treatment, both against chemotherapy and radiotherapy. In this review, we gathered the existent data on miRNA-21 and gliomas, in terms of its expression levels, association with grade and prognosis, the pathways it involves and its targets in glioma, and finally how it leads to treatment resistance. Furthermore, we discuss how this knowledge could be applied in clinical practice in the years to come. To our knowledge, this is the first review to assess in extent and depth the role of miRNA-21 in gliomas.
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http://dx.doi.org/10.1016/j.toxrep.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677650PMC
November 2020

Multiple Sclerosis: Shall We Target CD33?

Genes (Basel) 2020 Nov 12;11(11). Epub 2020 Nov 12.

Laboratory of Neurogenetics, Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Myeloid lineage cells (microglia and macrophages) may participate in the pathogenic mechanisms leading to MS. CD33 is a transmembrane receptor, mainly expressed by myeloid lineage cells. CD33 rs3865444 is a promoter variant previously associated with Alzheimer's disease, whose role in MS remains obscure.

Objective: To assess the role of CD33 rs3865444 in MS risk.

Methods: We genotyped 1396 patients with MS and 400 healthy controls for the presence of the CD33 rs3865444 variant. Odds ratios (ORs) with the respective 95% confidence intervals (CIs), were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant, and log-additive), with the G allele as the reference allele. The value of 0.05 was set as the threshold for statistical significance.

Results: CD33 rs3865444 was associated with MS risk in the dominant (GG vs. GT + TT; OR (95% C.I.) = 0.79 (0.63-0.99), = 0.041) and the over-dominant (GG + TT vs. GT; OR (95% C.I.) = 0.77 (0.61-0.97), = 0.03) modes of inheritance. Given that the GG genotype was more frequent and the GT genotype was less frequent in MS patients compared to controls-while the observed frequency of the TT genotype did not differ between the two groups-the observed difference in MS risk may be stemming from either the GG (as a risk factor) or the GT (as a protective factor) genotype of CD33 rs3865444.

Conclusions: Our preliminary results suggest a possible contribution of CD33 rs3865444 to MS. Therefore, larger multiethnic studies should be conducted, investigating the role of CD33 rs3865444 in MS.
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http://dx.doi.org/10.3390/genes11111334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696272PMC
November 2020

Kawasaki Disease and COVID-19.

Mediterr J Rheumatol 2020 Sep 21;31(Suppl 2):268-274. Epub 2020 Sep 21.

Department of Rheumatology and Clinical Immunology, Faculty of medicine, School of Health Sciences, University of Thessaly, Larissa.

The recent passing away of Dr. Tomisaku Kawasaki, who first described what is now known as Kawasaki Disease (KD), and recent reports of a multisystem inflammatory disease in children associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (MIS-C), makes a review on KD and MIS-C timely. Kawasaki Disease is a systemic vasculitis with predilection for coronary arteries occurring mostly in early childhood. The main features are high fever, extensive skin rash, cheilitis with red, cracking, bleeding lips and strawberry tongue, conjunctivitis, erythema and induration of hands and feet, subsiding with periungual peeling, cervical lymphadenopathy, and coronary artery dilation/aneurysms. Treatment consists of intravenous (IV) immunoglobulin (Ig) plus acetylsalicylic acid. MIS-C is considered a cytokine storm with high fever, inflammation, multi-organ dysfunction, that shares features with KD, toxic shock, and macrophage activation syndrome. Many children require admission to paediatric intensive care units for circulatory support. Bacterial sepsis, staphylococcal toxic shock syndrome, and enterovirus-causing myocarditis should be excluded. Treatment is not standardized and includes IVIg, IV methylprednisolone and IL-6 and IL-1 inhibitors.
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http://dx.doi.org/10.31138/mjr.31.3.268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656130PMC
September 2020

Effectiveness of oral vitamin D supplementation in lessening disease severity among patients with psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Nutrition 2021 02 18;82:111024. Epub 2020 Sep 18.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Objective: Many treatment modalities have been used to manage psoriasis; however, there is, to our knowledge, no pooled estimate for the effectiveness of oral vitamin D supplements in patients with psoriasis. Hence, the aim of the present study was to systematically review and meta-analyze the efficacy of oral vitamin D supplementation in lessening disease severity of patients with psoriasis.

Methods: A systematic literature review was performed on the electronic databases PubMed, Embase, and Cochrane Central and the gray literature for retrieving randomized controlled trials comparing oral vitamin D supplementation with placebo. The primary outcome was the change of Psoriasis Area and Severity Index (PASI) score. We used the random effects model for synthesizing the evidence.

Results: Of the total 5018 search results, 4 studies were included in the qualitative and 3 studies in quantitative analysis. Vitamin D supplementation was effective in ameliorating the PASI score after 6 mo of intervention (mean difference [MD] = -0.92, 95% confidence interval [CI] = -1.72 to -0.11). However, after the Hartung-Knapp adjustment, the results became non-significant (MD = -0.92, 95% CI = -2.21 to 0.38).

Conclusions: A favorable effect of oral vitamin D supplementation in patients with psoriasis could not be verified. More randomized controlled trials with larger sample sizes are needed to produce robust results.
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http://dx.doi.org/10.1016/j.nut.2020.111024DOI Listing
February 2021

Arthritis and Myositis in a Patient Treated with Programmed Cell Death-1 (PD-1) Inhibitor Pembrolizumab for Lung Cancer.

Mediterr J Rheumatol 2020 Sep 30;31(3):355-357. Epub 2020 Sep 30.

Department of Rheumatology and Clinical Immunology and.

Immune checkpoint inhibitors (ICIs) are a new class of drug that have demonstrated efficacy across many cancer types. Because of their nature and mode of action, ICIs unleash immune activation raising concerns as to whether they can be used in patients with concomitant autoimmune or auto-inflammatory diseases. Their usage can lead to the development of autoimmune phenomena known as immune related adverse events (irAEs), virtually affecting every organ. As the use of ICIs is drastically increasing, evidence of irAEs has been accumulating. Herein, we report a case of inflammatory myositis and arthritis 6 months after pembrolizumab therapy, an anti-programmed death-1 (PD1) ICI in a patient with lung cancer, aiming at raising awareness of the diagnostic and clinical challenges clinicians may face when checkpoint inhibitors-related rheumatologic irAEs are developed.
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http://dx.doi.org/10.31138/mjr.31.3.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641028PMC
September 2020

Let Food Be Thy Medicine: The Case of The Mediterranean Diet in Rheumatoid Arthritis.

Mediterr J Rheumatol 2020 Sep 30;31(3):325-329. Epub 2020 Sep 30.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

The role of diet in rheumatoid arthritis (RA) has been the topic of extensive research. The present review aimed to present and appraise the studies assessing adherence to the Mediterranean diet (MD) and the primary/secondary prevention of rheumatoid arthritis. Based on the available studies, the evidence appears low and adherence to the MD does not appear to affect RA indices.
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http://dx.doi.org/10.31138/mjr.31.3.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641021PMC
September 2020

Dietary Factors and Supplements Influencing Prostate Specific-Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Analysis Review Based on Randomized Controlled Trials.

Nutrients 2020 Sep 29;12(10). Epub 2020 Sep 29.

Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-56429 Thessaloniki, Greece.

The quest for dietary patterns and supplements efficient in down-regulating prostate-specific antigen (PSA) concentrations among men with prostate cancer (PCa) or increased PCa risk has been long. Several antioxidants, including lycopene, selenium, curcumin, coenzyme Q10, phytoestrogens (including isoflavones and flavonoids), green tea catechins, cernitin, vitamins (C, E, D) and multivitamins, medicinal mushrooms (), fruit extracts (saw palmetto, cranberries, pomegranate), walnuts and fatty acids, as well as combined supplementations of all, have been examined in randomized controlled trials (RCTs) in humans, on the primary, secondary, and tertiary PCa prevention level. Despite the plethora of trials and the variety of examined interventions, the evidence supporting the efficacy of most dietary factors appears inadequate to recommend their use.
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http://dx.doi.org/10.3390/nu12102985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600271PMC
September 2020

Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System.

Curr Treat Options Neurol 2020 25;22(11):37. Epub 2020 Sep 25.

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.

Purpose Of Review: To describe the possible neuroinvasion pathways of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemic.

Recent Findings: We present data regarding the family of Coronaviruses (CoVs) and the central nervous system (CNS), and describe parallels between SARS-CoV-2 and other members of the family, which have been investigated in more depth and combine these findings with the recent advancements regarding SARS-CoV-2.

Summary: SARS-CoV-2 like other CoVs is neuroinvasive, neurotropic and neurovirulent. Two main pathways of CNS penetration seem to be the strongest candidates, the hematogenous and the neuronal. Τhe olfactory route in particular appears to play a significant role in neuroinvasion of coronaviruses and SARS-CoV-2, as well. However, existing data suggest that other routes, involving the nasal epithelium in general, lymphatic tissue and the CSF may also play roles in SARS-CoV-2 invasion into the CNS.
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http://dx.doi.org/10.1007/s11940-020-00647-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515807PMC
September 2020

Genetic Risk Factors for Essential Tremor: A Review.

Tremor Other Hyperkinet Mov (N Y) 2020 06 11;10. Epub 2020 Jun 11.

Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Greece, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GR.

Highlights: In the current review, we thoroughly reviewed 74 identified articles regarding genes and genetic loci that confer susceptibility to ET. Over 50 genes/genetic loci have been examined for possible association with ET, but consistent results failed to be reported raising the need for collaborative multiethnic studies.

Background: Essential tremor (ET) is a common movement disorder, which is mainly characterized by bilateral tremor (postural and/or kinetic) in the upper limbs, with other parts of the body possibly involved. While the pathophysiology of ET is still unclear, there is accumulating evidence indicating that genetic variability may be heavily involved in ET pathogenesis. This review focuses on the role of genetic risk factors in ET susceptibility.

Methods: The PubMed database was searched for articles written in English, for studies with humans with ET, controls without ET, and genetic variants. The terms "essential tremor" and "polymorphism" (as free words) were used during search. We also performed meta-analyses for the most examined genetic variants.

Results: Seventy four articles concerning and and genes, and ETM genetic loci were included in the current review. Results from meta-analyses revealed a marginal association for the STK32B rs10937625 and a marginal trend for association (in sensitivity analysis) for the LINGO1 rs9652490, with ET.

Discussion: Quite a few variants have been examined for their possible association with ET. LINGO1 rs9652490 and STK32B rs10937625 appear to influence, to some extent, ET susceptibility. However, the conflicting results and the lack of replication for many candidate genes raise the need for collaborative multiethnic studies.
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http://dx.doi.org/10.5334/tohm.67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394223PMC
June 2020

Parkinson's disease and pesticides: Are microRNAs the missing link?

Sci Total Environ 2020 Nov 29;744:140591. Epub 2020 Jun 29.

Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, Greece, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Parkinson's disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and decline in the quality of life. It develops due to loss of dopaminergic neurons in the substantia nigra pars compacta, and among its pathogenic factors oxidative stress plays a critical role in disease progression. Pesticides are a broad class of chemicals widely used in agriculture and households for the protection of crops from insects and fungi. Several of them have been incriminated as risk factors for PD, but the underlying mechanisms have yet to be fully understood. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in regulating mRNA translation and protein synthesis. miRNA levels have been shown to be affected in several diseases as well. Since the studies on the association between pesticides and PD have yet to reach definitive conclusions, here we review recent evidence on deregulated microRNAs upon pesticide exposure, and attempt to find an overlap between miRNAs deregulated in PD and pesticides, as a missing link between the two, and enhance future research in this direction.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140591DOI Listing
November 2020

Adrenocorticotropic hormone: an effective "natural" biologic therapy for acute gout?

Rheumatol Int 2020 Dec 26;40(12):1941-1947. Epub 2020 Jul 26.

Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Patras, Greece.

Treatment of acute gout consists of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and steroids. However, the typical patient with gout has multiple comorbidities such as cardiovascular disease, hypertension, renal dysfunction or diabetes/metabolic syndrome that represent contraindications to these therapeutic options. The aim of this study is to review the available evidence regarding the use of ACTH as an alternative therapeutic option for acute gout and explore potential mechanisms of action. We performed an electronic search (MEDLINE, Scopus and Web of Science) using the keywords ACTH or adrenocorticotropic hormone combined with gout or crystal-induced arthritis. ACTH appears suitable for patients with many comorbidities due to its good safety profile. Clinical evidence shows that ACTH is at least as effective as classic agents. The mechanism of action of ACTH in gout is not entirely known. Robust experimental evidence points to the direction that ACTH does not act solely by triggering the release of endogenous steroids but also appears to downregulate inflammatory responses by activating melanocortin receptors on innate immune cells, such as macrophages. Moreover, indirect evidence indicates that ACTH may have an IL-1 antagonistic effect. We propose that ACTH may be an alternative therapeutic option for gout in patients with multiple comorbidities. Large-scale studies assessing the efficacy and safety of ACTH compared to classic therapeutic options are needed.
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http://dx.doi.org/10.1007/s00296-020-04659-5DOI Listing
December 2020

Autoantibodies against specific nuclear antigens are present in psoriatic disease and are diminished by secukinumab.

Clin Chim Acta 2020 Nov 23;510:400-407. Epub 2020 Jul 23.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larisa, Greece. Electronic address: http://www.autorheumatology.com.

Anti-nuclear antibodies (ANA) are frequently detected in patients with psoriasis (Ps) and psoriatic arthritis (PsA), but their target autoantigens remain unknown. We assessed antibody (ab) reactivity against 23 known nuclear antigens in patients with Ps and PsA and assess the effects of secukinumab (anti-IL17A) treatment on ANA levels. A total of 201 patients, 101 with Ps and 100 with PsA, and 50 ANA-negative healthy controls (HCs) were tested for ANAs by a line immunoassay testing reactivity to 23 nuclear antigens. Ab reactivity to at least 1 antigen was found in 20.4% psoriatic disease patients (25.7% Ps and 15% PsA) compared to 8% HCs (p = ns), the most frequent being against dense fine speckled 70 (DFS70) (6.5%). In Ps and PsA patients with secukinumab-induced remission, anti-DFS70 and other antigen-specific autoantibodies were diminished over time. No decline was noted for IgG abs against antigens from pathogens such as cytomegalovirus, Epstein-Barr virus and Helicobacter pylori. Autoantibody decrease was associated with significant reduction of plasmablasts, follicular B and follicular T cells. In conclusion, one third of antigen-specific ANA patients with psoriatic disease recognize DFS70. Secukinumab decreases nuclear antigen autoreactivity, plasmablasts, follicular B and follicular T cells, highlighting a new mechanism of its action.
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http://dx.doi.org/10.1016/j.cca.2020.07.037DOI Listing
November 2020

A study of antigen-specific anti-cytomegalovirus antibody reactivity in patients with systemic sclerosis and concomitant anti-Ro52 antibodies.

Rheumatol Int 2020 Oct 17;40(10):1689-1699. Epub 2020 Jul 17.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Βiopolis, 40500, Larissa, Thessaly, Greece.

Anti-Ro52 autoantibody (autoAb), highly prevalent in Sjogren's syndrome (SjS) and systemic lupus erythematosus (SLE), is also frequent in systemic sclerosis (SSc). Viral agents, such as human cytomegalovirus (HCMV), have been considered as a trigger for SSc and SSc-associated autoAbs. To seek for antigen-specific anti-HCMV associations with anti-Ro52, we assessed the dominant anti-HCMV ab responses in anti-Ro52 antibody (ab)-positive and -negative patients with SSc and compared them with those in SLE and SjS. 116 Anti-HCMV ab(+) sera were analyzed, including 70 from anti-Ro52(+) patients (29 SSc, 23 SLE and 18 SjS) and 46 from anti-Ro52(-) patients (29 with SSc, 9 with SLE and 8 with SjS) as negative controls. Abs against specific HCMV pp130/UL57, pp65/UL83, pp55/UL55, pp52/UL44, p38 and pp28/UL99 antigens were tested by immunoblotting. Anti-Ro52(+) SSc patients reacted more frequently against pp52/UL44 and p38 compared to anti-Ro52(-) [(13/29, 44.8%; 95% CI 26.7-62.9% vs. 1/29, 3.4%; 95% CI 0-10%, p < 0.001, and 9/29, 31.0%; 95% CI 14.2-47.8% vs. 2/29, 6.9%; 95% CI 0-16.1%, p = 0.041, respectively]. No such differences were noted between anti-Ro52(+) and anti-Ro52(-) SLE or SjS patients. Also, antibody titres against HCMV pp65/UL83, pp52/UL44 and p38 antigens were higher in anti-Ro52(+) than anti-Ro52(-) SSc patients (p < 0.01). Ab responses against specific HCMV antigens differ among anti-Ro52 ab-positive and -negative patients with SSc (as well as between SSc and SLE or SjS), but whether these differences are epiphenomenal remains to be seen.
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http://dx.doi.org/10.1007/s00296-020-04643-zDOI Listing
October 2020

2020 international consensus on ANCA testing beyond systemic vasculitis.

Autoimmun Rev 2020 Sep 12;19(9):102618. Epub 2020 Jul 12.

Laboratory Medicine, University Hospitals Leuven, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.
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http://dx.doi.org/10.1016/j.autrev.2020.102618DOI Listing
September 2020

SLC2A3 rs12842 polymorphism and risk for Alzheimer's disease.

Neurol Res 2020 Oct 4;42(10):853-861. Epub 2020 Jul 4.

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa , Larissa, Greece.

Background: Many studies support the hypothesis that brain glucose dysregulation contributes to neurodegeneration and disease progression. The SLC2A3 gene encodes the Neuronal Glucose Transporter 3 (GLUT3), a critical molecule for glucose transport into the neuron. The GLUT3 rs12842 polymorphism has been associated with an increased risk for attention-deficit/hyperactivity disorder (ADHD). Epidemiological and genetic studies have reported a link between antecedent ADHD and Alzheimer's disease (AD), as both share a dysregulation of brain glucose.

Aim: This study aimed to explore the possible correlation of the SLC2A3 rs12842 polymorphism with susceptibility towards AD.

Methods: We genotyped 327 patients with AD and 327 controls for the GLUT3 rs12842. : Rs12842 was associated with a decreased risk of developing AD in the co-dominant [Odds Ratio (OR) (95% confidence interval (CI) = 0.67 (0.45-0.99)), p = 0.039], dominant [OR (95% CI) = 0.64 (0.44-0.93), p = 0.019] and log-additive modes [OR (95% CI) = 0.65 (0.46-0.91), p = 0.012].

Conclusions: Our results suggest a significant, inverse association between SLC2A3 rs12842 and the risk of AD.
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http://dx.doi.org/10.1080/01616412.2020.1786973DOI Listing
October 2020

To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease.

Adv Nutr 2020 11;11(6):1583-1602

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Alzheimer disease (AD) is a global health concern with the majority of pharmacotherapy choices consisting of symptomatic treatment. Recently, ketogenic therapies have been tested in randomized controlled trials (RCTs), focusing on delaying disease progression and ameliorating cognitive function. The present systematic review aimed to aggregate the results of trials examining the effects of ketogenic therapy on patients with AD/mild cognitive impairment (MCI). A systematic search was conducted on PubMed, CENTRAL, clinicaltrials.gov, and gray literature for RCTs performed on adults, published in English until 1 April, 2019, assessing the effects of ketogenic therapy on MCI and/or AD compared against placebo, usual diet, or meals lacking ketogenic agents. Two researchers independently extracted data and assessed risk of bias with the Cochrane tool. A total of 10 RCTs were identified, fulfilling the inclusion criteria. Interventions were heterogeneous, acute or long term (45-180 d), including adherence to a ketogenic diet, intake of ready-to-consume drinks, medium-chain triglyceride (MCT) powder for drinks preparation, yoghurt enriched with MCTs, MCT capsules, and ketogenic formulas/meals. The use of ketoneurotherapeutics proved effective in improving general cognition using the Alzheimer's Disease Assessment Scale-Cognitive, in interventions of either duration. In addition, long-term ketogenic therapy improved episodic and secondary memory. Psychological health, executive ability, and attention were not improved. Increases in blood ketone concentrations were unanimous and correlated to the neurocognitive battery based on various tests. Cerebral ketone uptake and utilization were improved, as indicated by the global brain cerebral metabolic rate for ketones and [11C] acetoacetate. Ketone concentrations and cognitive performance differed between APOE ε4(+) and APOE ε4(-) participants, indicating a delayed response among the former and an improved response among the latter. Although research on the subject is still in the early stages and highly heterogeneous in terms of study design, interventions, and outcome measures, ketogenic therapy appears promising in improving both acute and long-term cognition among patients with AD/MCI. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019128311.
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http://dx.doi.org/10.1093/advances/nmaa073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666893PMC
November 2020

CYP1A2 rs762551 polymorphism and risk for amyotrophic lateral sclerosis.

Neurol Sci 2021 Jan 26;42(1):175-182. Epub 2020 Jun 26.

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, Faculty of Medicine, University Hospital of Larissa, Larissa, Greece.

Background: Genetic variability is considered to confer susceptibility to amyotrophic lateral sclerosis (ALS). Oxidative stress is a significant contributor to ALS-related neurodegeneration, and it is regulated by cytochromes P450 (CYPs), such as CYP1A2; these are responsible for the oxidative metabolism of both exogenous and endogenous substrates in the brain, subsequently impacting ALS. The function of CYP1A2 is largely affected by genetic variability; however, the impact of CYP1A2 polymorphisms in ALS remains underinvestigated.

Objective: This study aims to examine the possible association of ALS with the CYP1A2 rs762551 polymorphism, which codes for the high inducibility form of the enzyme.

Methods: One hundred and fifty-five patients with sporadic ALS and 155 healthy controls were genotyped for the CYP1A2 rs762551. Statistical testing for the association of CYP1A2 rs762551 with risk for ALS was performed using SNPstats.

Results: The CYP1A2 rs762551 C allele was associated with a decreased risk of ALS development. In the subgroup analysis according to the ALS site of onset, an association between CYP1A2 rs762551 and limb and bulbar onset of ALS was shown. Cox proportional-hazard regression analyses revealed a significant effect of the CYP1A2 rs762551 on the age of onset of ALS.

Conclusions: Based on our results, a primarily potential link between the CYP1A2 rs762551 polymorphism and ALS risk could exist.
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http://dx.doi.org/10.1007/s10072-020-04535-xDOI Listing
January 2021

When there is a pandemic there is no time to waste: should we have hydroxychloroquine in our armoury against COVID-19 infected patients?

Mediterr J Rheumatol 2020 Mar 31;31(1):94-97. Epub 2020 Mar 31.

Department of Rheumatology and Clinical Immunology.

The current use of chloroquine and/or hydroxychloroquine, a drug currently used to treat autoimmune rheumatic diseases, in treating severe acute respiratory syndrome caused by coronavirus 2 (SARSCoV-2) or COVID-19-infected patients with pneumonia is a matter of intense consideration. We wish to enter the ongoing debate as to whether this well-known drug must be given to Greek COVID-19-infected patients, especially those with pneumonia. Our arguments are based on the existing data and the capacity of the Greek health system to afford potent anti-viral treatments, which are under immense investigation. We propose several suggestions related to treatment of COVID-19 pneumonia with chloroquine/hydroxychloroquine that we think must be taken into consideration to fit the evolving situation of the pandemic in Greece.
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http://dx.doi.org/10.31138/mjr.31.1.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219635PMC
March 2020

A Bioinformatics Analysis Reveals Novel Pathogens as Molecular Mimicry Triggers of Systemic Sclerosis.

Mediterr J Rheumatol 2020 Mar 31;31(1):50-70. Epub 2020 Mar 31.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, University of Thessaly, Larissa, Greece.

A recent bioinformatic analysis revealing dominant B cell epitopes of systemic sclerosis-specific autoantibodies, including anti-centromere B, anti-topoisomerase I and anti-fibrillarin, has demonstrated the existence of several in silico antigenic mimics of pathogens that could act as triggers of the respective dominant autoepitopes. Based on those findings, the aim of the present study was to use a more comprehensive bioinformatic analysis. We demonstrated the presence of a plethora of novel microbial mimics, unnoticed by the studies so far conducted, which share remarkable amino acid similarities with the respective autoantigenic epitopes. This bioinformatic approach coupled by in vitro testing of the homologous self/non-self-mimics in serum samples from patients with systemic sclerosis may provide novel evidence of immunological cross-reactivity, implicating currently ignored or overlooked pathogens, which may indeed play a role in the induction of SSc-specific autoantibodies and assist efforts to understand the pathogenesis of this enigmatic disease.
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http://dx.doi.org/10.31138/mjr.31.1.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219639PMC
March 2020

AMY1 diploid copy number among end-stage renal disease patients.

Hormones (Athens) 2020 Sep 14;19(3):369-376. Epub 2020 May 14.

Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Purpose: The salivary amylase gene (AMY1) copy number variation (CNV) is increased as a human adaptation to starch-enriched nutritional patterns. The purpose of this study was to evaluate the relationship between AMY1 CNV, dietary starch consumption, and anthropometric indices among a known population with elevated cardiovascular risk, being end-stage renal disease (ESRD) patients.

Methods: A total of 43 ESRD patients were recruited based on the following inclusion criteria: being (1) adults, (2) on hemodialysis for more than 3 months, (3) able to communicate effectively, and (4) willing to participate. Anthropometric measurements were performed, dietary intake was recorded via food-frequency questionnaires, and AMY1 CNV was quantified in blood samples DNA via real-time PCR.

Results: Median AMY1 CNV was 4.0 (2.0-17.0). A total of 21 patients had an even, and 22 had an odd AMY1 copy number (CN). Independent samples t tests revealed that AMY1-odd diploid CN is associated with increased body weight, waist and hip circumferences, and fat mass compared to the respective even diploid CN carrier group. No differences were observed for BMI or nutritional intake. Multiple regression analysis revealed that AMY1-odd diploid CN was positively associated with increased hip circumference (ß = 7.87, 95% CI = 0.34 to 15.39) and absolute fat mass (ß = 6.66, 95% CI = 0.98 to 12.34); however, after applying the Bonferroni correction for multiplicity, all regression analyses lost their significance.

Conclusions: AMY1-odd diploid CN appears to be associated with selected adiposity variables among hemodialysis patients. However, more research is needed to verify this finding in this population with known increased cardiovascular risk.
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http://dx.doi.org/10.1007/s42000-020-00199-6DOI Listing
September 2020

A comprehensive analysis of antigen-specific autoimmune liver disease related autoantibodies in patients with multiple sclerosis.

Auto Immun Highlights 2020 Dec 10;11(1). Epub 2020 Apr 10.

2Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa 40500 Greece.

Introduction: Abnormal liver function tests are frequently seen in patients with multiple sclerosis (MS) and their origin at times is attributed to the possible co-occurrence or the de novo induction of autoimmune liver diseases (AILD), namely autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but comprehensive analysis of AILD-related autoantibody has not been carried out.

Aim: To assess the presence of AILD-related autoantibodies in a well-defined cohort of MS patients, and to assess their clinical significance.

Materials And Methods: 133 MS (93 female) patients (102 RRMS, 27 SPMS, and 5 PPMS), mean age 42.7 ± 11.9 SD years, mean duration of disease 11.2 ± 7.2 years were studied. 150 age and sex-matched healthy individuals were tested as normal controls (NCs).Autoantibody testing was performed by indirect immunofluorescence (IF) using triple tissue and HEp-2, a multiparametric line immunoassay detecting anti-LKM1(anti-CYP2D6), anti-LC1(anti-FTCD), soluble liver antigen/liver-pancreas(anti-SLA/LP), AMA-M2, and AMA-MIT3 (BPO), PBC-specific ANA (anti-gp210, anti-sp100 and anti-PML), and ELISA for anti-F-actin SMA and anti-dsDNA antibodies.

Results: Reactivity to at least one autoantibody was more frequent in MS patients compared to NCs (30/133, 22.6% vs 12/150, 8%) NCs (p = 0.00058). SMAs by IIF were more frequent in MS patients (18/133, 13.53%) compared to NCs (6/150, 4%, p = 0.002%). The AIH-1 related anti-F-actin SMA by ELISA were present in 21 (15.8%), at relatively low titres (all but three of the SMA-VG pattern by IF); anti-dsDNA in 3 (2.3%), and anti-SLA/LP in none; AIH-2 anti-LKM1 autoantibodies in 1 (0.8%, negative by IF), and anti-LC1 in none; PBC-specific AMA-M2 in 2 (1.5%, both negative for AMA-MIT3 and AMA by IF) and PBC-specific ANA anti-PML in 6 (4.5%), anti-sp100 in 1 (0.8%) and anti-gp210 in 1 (0.8%). Amongst the 30 MS patients with at least one autoantibody positivity, only 4 (3%) had overt AILD (2 AIH-1 and 2 PBC). Autoantibody positivity did not differ between naïve MS patients and patients under treatment.

Conclusions: Despite the relatively frequent presence of liver autoantibodies, tested either by IF or molecular assays, overt AILD is rather infrequent discouraging autoantibody screening strategies of MS patients in the absence of clinical suspicion.
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http://dx.doi.org/10.1186/s13317-020-00130-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147023PMC
December 2020

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options.

Auto Immun Highlights 2019 Dec 10;10(1). Epub 2019 Aug 10.

1Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, Biopolis, Mezourlo Hill, 41100 Larissa, Greece.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by focal or diffuse inflammation, demyelination, axonal loss and neurodegeneration. Brain atrophy can be seen in the earliest stages of MS, progresses faster compared to healthy adults, and is a reliable predictor of future physical and cognitive disability. In addition, it is widely accepted to be a valid, sensitive and reproducible measure of neurodegeneration in MS. Reducing the rate of brain atrophy has only recently been incorporated as a critical endpoint into the clinical trials of new or emerging disease modifying drugs (DMDs) in MS. With the advent of easily accessible neuroimaging softwares along with the accumulating evidence, clinicians may be able to use brain atrophy measures in their everyday clinical practice to monitor disease course and response to DMDs. In this review, we will describe the different mechanisms contributing to brain atrophy, their clinical relevance on disease presentation and course and the effect of current or emergent DMDs on brain atrophy and neuroprotection.
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http://dx.doi.org/10.1186/s13317-019-0117-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065319PMC
December 2019