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The social aspects of medicine and medical education are more than imperative nowadays, given that several societal determinants, such as health care systems, political settings, unemployment, racial inequities, and exposure to chronic stress (Chrousos, 2009; Theoharides, 2020), could play a major role in public attitudes towards therapies or even change the course of medical decisions (Russell et al., 2004; McNeill et al., 2017; Nuwayhid and Zurayk, 2019; Ghilardi et al., 2020). It is now equally appreciated that the drug discovery processes (Kaitin and DiMasi, 2011), which may disproportionally focus on some fields (e.g., oncology), should take into account societal factors (e.g., access to medications) (Milne and Kaitin, 2019). Previous studies have shown that the quality of higher education (including medical schools) appeared suboptimal in terms of addressing the current needs of patients and the broader society (Kulasegaram et al., 2013; Bakoyiannis et al., 2017). Therefore, the need to familiarize medical doctors and, in particular, medical students to these societal concepts and aspects is more crucial than ever. Drugs are an undeniably chief tool for doctors in treating patients; however, the extent to which pharmacology courses address the ELSI (ethical, legal, and societal) aspects of pharmacology beyond providing strictly medical and scientific learning material (e.g., a drug’s mechanisms of action, its pharmacodynamics, pharmacokinetics, side effects) is largely explored, at least based on our experience at the National and Kapodistrian University of Athens Medical School. In general, a medical school curriculum consists of both basic and clinical medical science courses (e.g., biochemistry and surgery, respectively) which mostly focus on human physiology and diseases. We have also noticed, at least based on our experience, that in most courses, an underappreciated gap between pure biomedical and ELSI knowledge is present in medical education. This reflects the low exposure of students at medical schools, especially during their preclinical years of medical education, and students of pharmacy to societally- and humanities-focused courses, such as bioethics, health care, public health, health policy, medical history, or biomedical communications (Bell et al., 2008; Al-Haqwi and Al-Shehri, 2010; Westerhaus et al., 2015; Greenberg et al., 2016; Inerney, 2018). As a result, medical students and students of pharmacy may appear highly knowledgeable of drug-related mechanistic aspects but not significantly aware of societally-focused notions such as inappropriate prescription of drugs and/or the so-called medicamentation, which is defined as the use of drugs for social problems previously not requiring drug utilisation (e.g., ageing, loss of libido, etc.) (Mbongue et al., 2005). The above gap in education of students from schools of medicine and of pharmacy has been similarly observed in several other countries, implying it is a broader issue (Harding and Taylor, 2006; Hassali et al., 2011; Jaber et al., 2015; Makris et al., 2015; Mobrad et al., 2020; Góralska et al., 2021). Therefore, the lack of knowledge and skills in ELSI may, in turn, lead to suboptimal medical practice towards vulnerable groups. In fact, contemporary data on drug misuse (Culberson and Ziska, 2008), polypharmacy linked to multimorbidity (Blum et al., 2021), inappropriate and/or non-evidence-based self-medication (Yousef et al., 2008; Rather et al., 2017), misdosing (Nemati et al., 2016), inappropriate prescription trends (Hovstadius et al., 2014; Moriarty et al., 2015) (both hold true especially in the elderly), and mortality and morbidity outcomes in relation to drug overuse such as for opioids (Cheatle, 2015), alongside suboptimal medical practice (Ma et al., 2005; Massey et al., 2009), reinforce more than ever the call-to-action for developing Social Pharmacology courses to address these alarming issues. Social Pharmacology aims to bridge the gap between biomedical knowledge/drug innovation and implementation of pharmacology to daily life. Implementers and/or educators must take into consideration how drugs are connected to society, notably 1) how social determinants, beyond medical or scientific factors, affect the use of drugs, 2) the social effects of drug use, 3) how the different stakeholders such as the pharmaceutical industry, regulatory agencies, sponsors, payers/public and even non-traditional stakeholders, such as lawyers and media, can direct decisions that impact society (as illustrated in the COVID-19 pandemic), and 4) how the patient’s or physician’s personal and social factors (e.g., cultural background, depth of medical knowledge, or social status) can affect drug use (Montastruc, 2002). To our best knowledge, with regards to Pharmacology courses, there is a major overlapping between medical schools and schools of pharmacy in their approach and curricula. In regards to societal aspects of the course of Pharmacology, although several issues (e.g., dietary management, exercise, digital therapeutics, etc.) are neglected in both schools, the major concern is the financial burden of medications but from different aspects, i.e., medical schools focus on patient and the health systems, while pharmacy schools tend to focus more on how the pharmacist will effectuate the doctor’s prescription and be compensated (Hassali et al., 2011; Sheridan, 2015). Moreover, we feel that public health courses’ curriculum is already loaded with a whole range of topics (e.g., epidemiology, biostatistics, bioethics, history of public health, global health, infectious diseases) and, in doing so, may not provide the necessary time and niche for including and discussing Social Pharmacology topic. Hence, we opted to focus on Social Pharmacology for medical students as future drug prescribers, hoping that our Commentary will make a case for more wide-spread inclusion of courses...
Jannis S. Papadopulos; Alexios-Fotios A. Mentis; Charis Liapi. Social Pharmacology as an Underappreciated Field in Medical Education: A Single Medical School’s Experience. Frontiers in Pharmacology 2021, 12, 1 .
AMA StyleJannis S. Papadopulos, Alexios-Fotios A. Mentis, Charis Liapi. Social Pharmacology as an Underappreciated Field in Medical Education: A Single Medical School’s Experience. Frontiers in Pharmacology. 2021; 12 ():1.
Chicago/Turabian StyleJannis S. Papadopulos; Alexios-Fotios A. Mentis; Charis Liapi. 2021. "Social Pharmacology as an Underappreciated Field in Medical Education: A Single Medical School’s Experience." Frontiers in Pharmacology 12, no. : 1.
A three-dimensional graphic design representation of the potential role of meningeal vessels in Alzheimer disease. Although there are major differences between APOE4(+) and APOE4(−) Alzheimer disease cases (described in detail in the Comment article by Mentis and colleagues), the figure depicts the clearance of macromolecules and other solutes from meningeal lymphatic vessels. Cover image: Ella Maru Studio.
Zhangying Chen; Steven J. Schwulst; Alexios-Fotios A. Mentis. APOE4-mediated Alzheimer disease and “Vascular”—“Meningeal Lymphatic” components: towards a novel therapeutic era? 2021, 1 -3.
AMA StyleZhangying Chen, Steven J. Schwulst, Alexios-Fotios A. Mentis. APOE4-mediated Alzheimer disease and “Vascular”—“Meningeal Lymphatic” components: towards a novel therapeutic era? . 2021; ():1-3.
Chicago/Turabian StyleZhangying Chen; Steven J. Schwulst; Alexios-Fotios A. Mentis. 2021. "APOE4-mediated Alzheimer disease and “Vascular”—“Meningeal Lymphatic” components: towards a novel therapeutic era?" , no. : 1-3.
Myasthenia gravis (MG) is a typical B-cell-mediated neuromuscular junction disease that can be classified into seropositive and seronegative subtypes. Association of patients’ age at sampling and sex with the two major seropositive MG subcategories, i.e., MGs linked to antibodies directed against the acetylcholine receptor (AChRAb) and against the muscle-specific kinase (MuSKAb), has not been compared in a large population. We performed a retrospective analysis of samples from patients with MG in Greece who underwent neurochemical diagnostic evaluation between January 2, 2013, and August 31, 2016. Overall, 1,620 adult (623 male and 997 female patients; male-to-female ratio = 0.62) and 51 pediatric patients were found to be seropositive for MG. The distributions in both male and female patients were bimodal in the total and AChRAb MG cases but not in the total MuSKAb MG cases. Significant differences in the age at sampling distribution between the male and female adult patients were observed only in the AChRAb MG subtype. Significant differences between the AChRAb and MuSKAb MG categories were noted in the mean age values (60.10 and 51.49 years, respectively, for female and 65.69 and 56.19 years, respectively, for male adult patients). Our findings confirm an uneven profile of age at sampling and sex between the AChRAb and MuSKAb MG cases in a large population. Future mechanistic studies can elucidate the cause of these differences. Moreover, clinical studies can explore how such differences can affect MG treatment and prognosis.
Maria Belimezi; Antonios Kalliaropoulos; Juan Jiménez; Irene Garcia; Alexios-Fotios A. Mentis; George P. Chrousos. Age at sampling and sex distribution of AChRAb vs. MuSKAb myasthenia gravis in a large Greek population. Clinical Neurology and Neurosurgery 2021, 208, 106847 .
AMA StyleMaria Belimezi, Antonios Kalliaropoulos, Juan Jiménez, Irene Garcia, Alexios-Fotios A. Mentis, George P. Chrousos. Age at sampling and sex distribution of AChRAb vs. MuSKAb myasthenia gravis in a large Greek population. Clinical Neurology and Neurosurgery. 2021; 208 ():106847.
Chicago/Turabian StyleMaria Belimezi; Antonios Kalliaropoulos; Juan Jiménez; Irene Garcia; Alexios-Fotios A. Mentis; George P. Chrousos. 2021. "Age at sampling and sex distribution of AChRAb vs. MuSKAb myasthenia gravis in a large Greek population." Clinical Neurology and Neurosurgery 208, no. : 106847.
To assess the potential role of saffron in downregulating inflammation and cytokine storm during COVID-19. Three main compounds of saffron, i.e., crocetin esters, picrocrocin, and safranal, present strong antioxidant and anti-inflammatory action for several disease states (e.g., Alzheimer's, cancer, and depression) but have also been studied in COVID-19. In particular, based on our comprehensive review of both in vitro and in silico studies, saffron's essential oils and other constituents appear to have both immunomodulatory and anti-asthmatic actions; these actions can be particularly helpful to treat patients with respiratory symptoms due to COVID-19. Moreover, crocin appears to reduce the COVID-19-related cytokine cascade and downregulate angiotensin-converting enzyme 2 (ACE2) gene expression. Last, in silico studies suggest that saffron's astragalin and crocin could have inhibitory actions on SARS-CoV-2 protease and spike protein, respectively. Saffron represents a promising substance for toning down cytokine storm during COVID-19, as well as a potential preventive treatment for COVID-19. However, appropriate randomized clinical trials, especially those using biomarkers as surrogates to assess inflammatory status, should be designed in order to assess the clinical efficacy of saffron and allow its use as an adjunct treatment modality, particularly in resource-poor settings where access to drugs may be limited.
Alexios-Fotios A. Mentis; Maria Dalamaga; Cuncun Lu; Moschos G. Polissiou. Saffron for “toning down” COVID-19-related cytokine storm: Hype or hope? A mini-review of current evidence. Metabolism Open 2021, 11, 100111 -100111.
AMA StyleAlexios-Fotios A. Mentis, Maria Dalamaga, Cuncun Lu, Moschos G. Polissiou. Saffron for “toning down” COVID-19-related cytokine storm: Hype or hope? A mini-review of current evidence. Metabolism Open. 2021; 11 ():100111-100111.
Chicago/Turabian StyleAlexios-Fotios A. Mentis; Maria Dalamaga; Cuncun Lu; Moschos G. Polissiou. 2021. "Saffron for “toning down” COVID-19-related cytokine storm: Hype or hope? A mini-review of current evidence." Metabolism Open 11, no. : 100111-100111.
A bidirectional relationship appears to connect tension-type headache (TTH) and circadian dysregulation. The present systematic review examined the published evidence for melatonin (MT) supplementation in the prophylaxis of TTH. Initially, we reviewed case-control studies investigating nocturnal MT or 6-sulphatoxymelatonin (aMT6s, a urine-discarded metabolite) in TTH individuals and healthy controls (HC). Secondly, we reviewed studies appraising the use of MT in the prevention of TTH. The search strategy involved MEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar and OpenGrey. Case-control studies were appraised according to the Newcastle-Ottawa-Scale, whereas randomised controlled trials were assessed based on the risk-of-bias Cochrane tool. Infrequent, as well as frequent, episodic, and chronic TTH patients were evaluated separately in children and adults. Our search strategy yielded two case-control studies. One (high-quality) did not reveal any difference in morning salivary MT concentration between children with frequent episodic TTH and HC. The second (moderate-quality) was indicative of a disturbed nocturnal secretion pattern in adults with chronic TTH. For the second part, five uncontrolled studies were retrieved. In total, 94 adults with chronic TTH were assessed and results were suggestive of a beneficial effect of MT on headache frequency, intensity, induced disability, and induced analgesic consumption. However, the uncontrolled-unblinded designs may have induced an important placebo effect. Non-adult populations and frequent TTH were substantially understudied. There are not enough studies to designate the role of MT in the prevention of TTH. Given the disease's background, additional relevant research is warranted for chronic TTH.
I. Liampas; V. Siokas; A. Brotis; A.-F.A. Mentis; A.-M. Aloizou; M. Dastamani; Z. Tsouris; M. Lima; E. Dardiotis. Endogenous melatonin levels and therapeutic use of exogenous melatonin in tension type headache: A systematic review. Revue Neurologique 2021, 1 .
AMA StyleI. Liampas, V. Siokas, A. Brotis, A.-F.A. Mentis, A.-M. Aloizou, M. Dastamani, Z. Tsouris, M. Lima, E. Dardiotis. Endogenous melatonin levels and therapeutic use of exogenous melatonin in tension type headache: A systematic review. Revue Neurologique. 2021; ():1.
Chicago/Turabian StyleI. Liampas; V. Siokas; A. Brotis; A.-F.A. Mentis; A.-M. Aloizou; M. Dastamani; Z. Tsouris; M. Lima; E. Dardiotis. 2021. "Endogenous melatonin levels and therapeutic use of exogenous melatonin in tension type headache: A systematic review." Revue Neurologique , no. : 1.
Public health and city planning are highly interconnected; however, the nexus between the urban state of buildings and sidewalks and corresponding public and urban health issues is lacking in Greece. In a case study in Athens, Greece, we evaluated unsafe buildings, facades, balconies, and sidewalks during a 15-year follow-up. We manually inspected (a) if the building/location’s condition had worsened and (b) any effective intervention by the state. Of the 400 initially selected buildings, 251 nonoverlapping buildings were analyzed. Overall, ~20% of the buildings posed a subjectively perceived severe risk for collapse, 35% had near-to-fall objects, and 45% had other minor issues. Fifteen years later, ~85% of the buildings were at the same or higher risk of complete or partial fall, and in only 15% had the risk of collapse been reduced or removed by private or public intervention. We detected uneven and dangerous parts of sidewalks hindering walkability and increasing the risk of falling or tipping. Our assessment revealed that Athens’ historical center harbors plausible safety and health risks for pedestrians and dwellers due to entire or partial building collapse and poor-condition sidewalks, which can potentially act as stress factors. Collectively, the issue of near-collapse buildings and risky sidewalks as an urban health determinant appears neglected by municipal authorities in their urban planning priorities; thus, future studies are needed in the field.
Alexios-Fotios Mentis; Jannis Papadopulos. Near-Collapse Buildings and Unsafe Sidewalks as Neglected Urban & Public Health Issue: A Qualitative Study. Urban Science 2021, 5, 47 .
AMA StyleAlexios-Fotios Mentis, Jannis Papadopulos. Near-Collapse Buildings and Unsafe Sidewalks as Neglected Urban & Public Health Issue: A Qualitative Study. Urban Science. 2021; 5 (2):47.
Chicago/Turabian StyleAlexios-Fotios Mentis; Jannis Papadopulos. 2021. "Near-Collapse Buildings and Unsafe Sidewalks as Neglected Urban & Public Health Issue: A Qualitative Study." Urban Science 5, no. 2: 47.
Alexios-Fotios A. Mentis. What neurological and psychiatric effects does COVID-19 have on its survivors? BMC Medicine 2021, 19, 1 -3.
AMA StyleAlexios-Fotios A. Mentis. What neurological and psychiatric effects does COVID-19 have on its survivors? BMC Medicine. 2021; 19 (1):1-3.
Chicago/Turabian StyleAlexios-Fotios A. Mentis. 2021. "What neurological and psychiatric effects does COVID-19 have on its survivors?" BMC Medicine 19, no. 1: 1-3.
Differential diagnosis between bacterial and viral meningitis is crucial. In our study, to differentiate bacterial vs. viral meningitis, three machine learning (ML) algorithms (multiple logistic regression (MLR), random forest (RF), and naïve-Bayes (NB)) were applied for the two age groups (0–14 and >14 years) of patients with meningitis by both conventional (culture) and molecular (PCR) methods. Cerebrospinal fluid (CSF) neutrophils, CSF lymphocytes, neutrophil-to-lymphocyte ratio (NLR), blood albumin, blood C-reactive protein (CRP), glucose, blood soluble urokinase-type plasminogen activator receptor (suPAR), and CSF lymphocytes-to-blood CRP ratio (LCR) were used as predictors for the ML algorithms. The performance of the ML algorithms was evaluated through a cross-validation procedure, and optimal predictions of the type of meningitis were above 95% for viral and 78% for bacterial meningitis. Overall, MLR and RF yielded the best performance when using CSF neutrophils, CSF lymphocytes, NLR, albumin, glucose, gender, and CRP. Also, our results reconfirm the high diagnostic accuracy of NLR in the differential diagnosis between bacterial and viral meningitis.
Alexios-Fotios Mentis; Irene Garcia; Juan Jiménez; Maria Paparoupa; Athanasia Xirogianni; Anastasia Papandreou; Georgina Tzanakaki. Artificial Intelligence in Differential Diagnostics of Meningitis: A Nationwide Study. Diagnostics 2021, 11, 602 .
AMA StyleAlexios-Fotios Mentis, Irene Garcia, Juan Jiménez, Maria Paparoupa, Athanasia Xirogianni, Anastasia Papandreou, Georgina Tzanakaki. Artificial Intelligence in Differential Diagnostics of Meningitis: A Nationwide Study. Diagnostics. 2021; 11 (4):602.
Chicago/Turabian StyleAlexios-Fotios Mentis; Irene Garcia; Juan Jiménez; Maria Paparoupa; Athanasia Xirogianni; Anastasia Papandreou; Georgina Tzanakaki. 2021. "Artificial Intelligence in Differential Diagnostics of Meningitis: A Nationwide Study." Diagnostics 11, no. 4: 602.
Alexios-Fotios A. Mentis. Letter to my medical teacher: tolerating stress using happicles. Hormones 2021, 1 -2.
AMA StyleAlexios-Fotios A. Mentis. Letter to my medical teacher: tolerating stress using happicles. Hormones. 2021; ():1-2.
Chicago/Turabian StyleAlexios-Fotios A. Mentis. 2021. "Letter to my medical teacher: tolerating stress using happicles." Hormones , no. : 1-2.
The pervasive and frequently devastating nature of aggressive behavior calls for a collective effort to understand its psychosocial and neurobiological underpinnings. Regarding the latter, diverse brain areas, neural networks, neurotransmitters, hormones, and candidate genes have been associated with antisocial and aggressive behavior in humans and animals. This review focuses on the role of monoamine oxidases (MAOs) and the genes coding for them, in the modulation of aggression. During the past 20 years, a substantial number of studies using both pharmacological and genetic approaches have linked the MAO system with aggressive and impulsive behaviors in healthy and clinical populations, including the recent discovery of MAALIN, a long noncoding RNA (lncRNA) regulating the MAO-A gene in the human brain. Here, we first provide an overview of the MAOs and their physiological functions, we then summarize recent key findings linking MAO-related enzymatic and gene activity and aggressive behavior, and, finally, we offer novel insights into the mechanisms underlying this association. Using the existing experimental evidence as a foundation, we discuss the translational implications of these findings in clinical practice and highlight what we believe are outstanding conceptual and methodological questions in the field. Ultimately, we propose that unraveling the specific role of MAO in aggression requires an integrated approach, where this question is pursued by combining psychological, radiological, and genetic/genomic assessments. The translational benefits of such an approach include the discovery of novel biomarkers of aggression and targeting the MAO system to modulate pathological aggression in clinical populations.
Alexios-Fotios A. Mentis; Efthimios Dardiotis; Eleni Katsouni; George P. Chrousos. From warrior genes to translational solutions: novel insights into monoamine oxidases (MAOs) and aggression. Translational Psychiatry 2021, 11, 1 -11.
AMA StyleAlexios-Fotios A. Mentis, Efthimios Dardiotis, Eleni Katsouni, George P. Chrousos. From warrior genes to translational solutions: novel insights into monoamine oxidases (MAOs) and aggression. Translational Psychiatry. 2021; 11 (1):1-11.
Chicago/Turabian StyleAlexios-Fotios A. Mentis; Efthimios Dardiotis; Eleni Katsouni; George P. Chrousos. 2021. "From warrior genes to translational solutions: novel insights into monoamine oxidases (MAOs) and aggression." Translational Psychiatry 11, no. 1: 1-11.
Background The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases. Methods We performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified. Results We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia. Conclusions We identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).
Alexios-Fotios A. Mentis; Efthimios Dardiotis; Vasiliki Efthymiou; George P. Chrousos. Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews. BMC Medicine 2021, 19, 1 -28.
AMA StyleAlexios-Fotios A. Mentis, Efthimios Dardiotis, Vasiliki Efthymiou, George P. Chrousos. Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews. BMC Medicine. 2021; 19 (1):1-28.
Chicago/Turabian StyleAlexios-Fotios A. Mentis; Efthimios Dardiotis; Vasiliki Efthymiou; George P. Chrousos. 2021. "Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews." BMC Medicine 19, no. 1: 1-28.
Alexios-Fotios Mentis. Merging Helicobacter pylori eradication and family history-based genetic counseling in patients with gastric cancer: towards an overarching approach in clinical practice. Annals of Gastroenterology 2021, 34, 451 -452.
AMA StyleAlexios-Fotios Mentis. Merging Helicobacter pylori eradication and family history-based genetic counseling in patients with gastric cancer: towards an overarching approach in clinical practice. Annals of Gastroenterology. 2021; 34 (3):451-452.
Chicago/Turabian StyleAlexios-Fotios Mentis. 2021. "Merging Helicobacter pylori eradication and family history-based genetic counseling in patients with gastric cancer: towards an overarching approach in clinical practice." Annals of Gastroenterology 34, no. 3: 451-452.
In the frame of the coronavirus disease 2019 (COVID-19) pandemic, recent reports on SARS-CoV-2 potential neuroinvasion placed neurologists on increased alertness in order to assess early neurological manifestations and their potentially prognostic value for the COVID-19 disease. Moreover, the management of chronic neurological diseases, such as Multiple Sclerosis (MS), underwent guided modifications, such as an Extended Interval Dose (EID) of Disease-Modifying Treatment (DMT) administration, in order to minimize patients’ exposure to the health system, thus reducing the risk of SARS-CoV-2 infection. In this review, we summarize existing evidence of key immune pathways that the SARS-CoV-2 modifies during COVID-19 and the relevant implication for MS and other autoimmune diseases with associated demyelination (such as Systemic lupus erythematosus and Antiphospholipid syndrome), including the context of potential neuroinvasion by SARS-Cov-2 and the alterations that DMT induces to the immune system. Moreover we hereby aim to provide an overview of the possible consequences that COVID-19 may carry for the Central Nervous System (CNS) in People with MS (PwMS) and other demyelinating diseases, which are likely to pose challenges for treating Neurologists with respect to the long-term disease management of these diseases.
Marina Kleopatra Boziki; Alexios-Fotios A. Mentis; Maria Shumilina; Gleb Makshakov; Evgeniy Evdoshenko; Nikolaos Grigoriadis. COVID-19 Immunopathology and the Central Nervous System: Implication for Multiple Sclerosis and Other Autoimmune Diseases with Associated Demyelination. Brain Sciences 2020, 10, 345 .
AMA StyleMarina Kleopatra Boziki, Alexios-Fotios A. Mentis, Maria Shumilina, Gleb Makshakov, Evgeniy Evdoshenko, Nikolaos Grigoriadis. COVID-19 Immunopathology and the Central Nervous System: Implication for Multiple Sclerosis and Other Autoimmune Diseases with Associated Demyelination. Brain Sciences. 2020; 10 (6):345.
Chicago/Turabian StyleMarina Kleopatra Boziki; Alexios-Fotios A. Mentis; Maria Shumilina; Gleb Makshakov; Evgeniy Evdoshenko; Nikolaos Grigoriadis. 2020. "COVID-19 Immunopathology and the Central Nervous System: Implication for Multiple Sclerosis and Other Autoimmune Diseases with Associated Demyelination." Brain Sciences 10, no. 6: 345.
Myopathies represent a wide spectrum of heterogeneous diseases mainly characterized by the abnormal structure or functioning of skeletal muscle. The current paper provides a comprehensive overview of cognitive deficits observed in various myopathies by consulting the main libraries (Pubmed, Scopus and Google Scholar). This review focuses on the causal classification of myopathies and concomitant cognitive deficits. In most studies, cognitive deficits have been found after clinical observations while lesions were also present in brain imaging. Most studies refer to hereditary myopathies, mainly Duchenne muscular dystrophy (DMD), and myotonic dystrophies (MDs); therefore, most of the overview will focus on these subtypes of myopathies. Most recent bibliographical sources have been preferred.
Eleni Peristeri; Athina-Maria Aloizou; Paraskevi Keramida; Zisis Tsouris; Vasileios Siokas; Alexios-Fotios A. Mentis; Efthimios Dardiotis. Cognitive Deficits in Myopathies. International Journal of Molecular Sciences 2020, 21, 3795 .
AMA StyleEleni Peristeri, Athina-Maria Aloizou, Paraskevi Keramida, Zisis Tsouris, Vasileios Siokas, Alexios-Fotios A. Mentis, Efthimios Dardiotis. Cognitive Deficits in Myopathies. International Journal of Molecular Sciences. 2020; 21 (11):3795.
Chicago/Turabian StyleEleni Peristeri; Athina-Maria Aloizou; Paraskevi Keramida; Zisis Tsouris; Vasileios Siokas; Alexios-Fotios A. Mentis; Efthimios Dardiotis. 2020. "Cognitive Deficits in Myopathies." International Journal of Molecular Sciences 21, no. 11: 3795.
The potential existence and roles of the meningeal lymphatic system in normal and pathological brain function have been a long-standing enigma. Recent evidence suggests that meningeal lymphatic vessels are present in both the mouse and human brain; in mice, they seem to play a role in clearing toxic amyloid-beta peptides, which have been connected with Alzheimer disease (AD). Here, we review the evidence linking the meningeal lymphatic system with human AD. Novel findings suggest that the recently described meningeal lymphatic vessels could be linked to, and possibly drain, the efferent paravascular glial lymphatic (glymphatic) system carrying cerebrospinal fluid, after solute and immune cell exchange with brain interstitial fluid. In so doing, the glymphatic system could contribute to the export of toxic solutes and immune cells from the brain (an exported fluid we wish to describe as glymph, similarly to lymph) to the meningeal lymphatic system; the latter, by being connected with downstream anatomic regions, carries the glymph to the conventional cervical lymphatic vessels and nodes. Thus, abnormal function in the meningeal lymphatic system could, in theory, lead to the accumulation, in the brain, of amyloid-beta, cellular debris, and inflammatory mediators, as well as immune cells, resulting in damage of the brain parenchyma and, in turn, cognitive and other neurologic dysfunctions. In addition, we provide novel insights into APOE4—the leading genetic risk factor for AD—and its relation to the meningeal lymphatic system. In this regard, we have reanalyzed previously published RNA-Seq data to show that induced pluripotent stem cells (iPSCs) carrying the APOE4 allele (either as APOE4 knock-in or stemming from APOE4 patients) express lower levels of (a) genes associated with lymphatic markers, and (b) genes for which well-characterized missense mutations have been linked to peripheral lymphedema. Taking into account this evidence, we propose a new conceptual framework, according to which APOE4 could play a novel role in the premature shrinkage of meningeal lymphatic vessels (meningeal lymphosclerosis), leading to abnormal meningeal lymphatic functions (meningeal lymphedema), and, in turn, reduction in the clearance of amyloid-beta and other macromolecules and inflammatory mediators, as well as immune cells, from the brain, exacerbation of AD manifestations, and progression of the disease. Altogether, these findings and their potential interpretations may herald novel diagnostic tools and therapeutic approaches in patients with AD.
Alexios-Fotios A. Mentis; Efthimios Dardiotis; George P. Chrousos. Apolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework. Molecular Psychiatry 2020, 26, 1075 -1097.
AMA StyleAlexios-Fotios A. Mentis, Efthimios Dardiotis, George P. Chrousos. Apolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework. Molecular Psychiatry. 2020; 26 (4):1075-1097.
Chicago/Turabian StyleAlexios-Fotios A. Mentis; Efthimios Dardiotis; George P. Chrousos. 2020. "Apolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework." Molecular Psychiatry 26, no. 4: 1075-1097.
Circulating tumor cells (CTCs) are regarded as harbingers of metastases. Their ability to predict response to therapy, relapse, and resistance to treatment has proposed their value as putative diagnostic and prognostic indicators. CTCs represent one of the zeniths of cancer evolution in terms of cell survival; however, the triggers of CTC generation, the identification of potentially metastatic CTCs, and the mechanisms contributing to their heterogeneity and aggressiveness represent issues not yet fully deciphered. Thus, prior to enabling liquid biopsy applications to reach clinical prime time, understanding how the above mechanistic information can be applied to improve treatment decisions is a key challenge. Here, we provide our perspective on how CTCs can provide mechanistic insights into tumor pathogenesis, as well as on CTC clinical value. In doing so, we aim to (a) describe how CTCs disseminate from the primary tumor, and their link to epithelial–mesenchymal transition (EMT); (b) trace the route of CTCs through the circulation, focusing on tumor self-seeding and the possibility of tertiary metastasis; (c) describe possible mechanisms underlying the enhanced metastatic potential of CTCs; (d) discuss how CTC could provide further information on the tissue of origin, especially in cancer of unknown primary origin. We also provide a comprehensive review of meta-analyses assessing the prognostic significance of CTCs, to highlight the emerging role of CTCs in clinical oncology. We also explore how cell-free circulating tumor DNA (ctDNA) analysis, using a combination of genomic and phylogenetic analysis, can offer insights into CTC biology, including our understanding of CTC heterogeneity and tumor evolution. Last, we discuss emerging technologies, such as high-throughput quantitative imaging, radiogenomics, machine learning approaches, and the emerging breath biopsy. These technologies could compliment CTC and ctDNA analyses, and they collectively represent major future steps in cancer detection, monitoring, and management.
Alexios-Fotios A. Mentis; Petros D. Grivas; Efthimios Dardiotis; Nicholas A. Romas; Athanasios G. Papavassiliou. Circulating tumor cells as Trojan Horse for understanding, preventing, and treating cancer: a critical appraisal. Cellular and Molecular Life Sciences 2020, 77, 3671 -3690.
AMA StyleAlexios-Fotios A. Mentis, Petros D. Grivas, Efthimios Dardiotis, Nicholas A. Romas, Athanasios G. Papavassiliou. Circulating tumor cells as Trojan Horse for understanding, preventing, and treating cancer: a critical appraisal. Cellular and Molecular Life Sciences. 2020; 77 (18):3671-3690.
Chicago/Turabian StyleAlexios-Fotios A. Mentis; Petros D. Grivas; Efthimios Dardiotis; Nicholas A. Romas; Athanasios G. Papavassiliou. 2020. "Circulating tumor cells as Trojan Horse for understanding, preventing, and treating cancer: a critical appraisal." Cellular and Molecular Life Sciences 77, no. 18: 3671-3690.
The 2007–2008 economic crash has had long-lasting effects on Greece’s biomedical research landscape. It has exposed a gap in support for countries that are classified as high income but are living under austerity measures. A new model is needed for optimal utilization of the intellectual and natural resources that such countries can offer to improve the global research landscape.
George P. Chrousos; Alexios-Fotios A. Mentis; Efthimios Dardiotis. Biomedical research: lessons from the last decade’s crisis and austerity-stricken small countries for the current COVID-19-related crisis. Nature Medicine 2020, 26, 644 -646.
AMA StyleGeorge P. Chrousos, Alexios-Fotios A. Mentis, Efthimios Dardiotis. Biomedical research: lessons from the last decade’s crisis and austerity-stricken small countries for the current COVID-19-related crisis. Nature Medicine. 2020; 26 (5):644-646.
Chicago/Turabian StyleGeorge P. Chrousos; Alexios-Fotios A. Mentis; Efthimios Dardiotis. 2020. "Biomedical research: lessons from the last decade’s crisis and austerity-stricken small countries for the current COVID-19-related crisis." Nature Medicine 26, no. 5: 644-646.
Grounded in solid epidemiologic investigations and rigorous statistical approaches, Evidence‐based Medicine has now been widely recognized as the mainstream pathway leading correct clinical practice, development of guidelines and ensuring patient safety, while protecting society from medical misconceptions and malpractice. Over the last fifteen years, numerous studies have analyzed the standards and quality of scientific research −a field known as meta‐research to improve the rigor of Evidence‐based Medicine.
George P. Chrousos; Alexios-Fotios A. Mentis. Medical misinformation in mass and social media: An urgent call for action, especially during epidemics. European Journal of Clinical Investigation 2020, 50, e13227 .
AMA StyleGeorge P. Chrousos, Alexios-Fotios A. Mentis. Medical misinformation in mass and social media: An urgent call for action, especially during epidemics. European Journal of Clinical Investigation. 2020; 50 (5):e13227.
Chicago/Turabian StyleGeorge P. Chrousos; Alexios-Fotios A. Mentis. 2020. "Medical misinformation in mass and social media: An urgent call for action, especially during epidemics." European Journal of Clinical Investigation 50, no. 5: e13227.
An increase of multiple sclerosis (MS) incidence has been reported during the last decade, and this may be connected to environmental factors. This review article aims to encapsulate the current advances targeting the study of the gut–brain axis, which mediates the communication between the central nervous system and the gut microbiome. Clinical data arising from many research studies, which have assessed the effects of administered disease-modifying treatments in MS patients to the gut microbiome, are also recapitulated.
Marina Kleopatra Boziki; Evangelia Kesidou; Paschalis Theotokis; Alexios-Fotios A. Mentis; Eleni Karafoulidou; Mikhail Melnikov; Anastasia Sviridova; Vladimir Rogovski; Alexey Boyko; Nikolaos Grigoriadis. Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know. Brain Sciences 2020, 10, 234 .
AMA StyleMarina Kleopatra Boziki, Evangelia Kesidou, Paschalis Theotokis, Alexios-Fotios A. Mentis, Eleni Karafoulidou, Mikhail Melnikov, Anastasia Sviridova, Vladimir Rogovski, Alexey Boyko, Nikolaos Grigoriadis. Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know. Brain Sciences. 2020; 10 (4):234.
Chicago/Turabian StyleMarina Kleopatra Boziki; Evangelia Kesidou; Paschalis Theotokis; Alexios-Fotios A. Mentis; Eleni Karafoulidou; Mikhail Melnikov; Anastasia Sviridova; Vladimir Rogovski; Alexey Boyko; Nikolaos Grigoriadis. 2020. "Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know." Brain Sciences 10, no. 4: 234.
Background Helicobacter pylori (H. pylori) is a Gram‐negative bacterium, considered to trigger autoimmune gastrointestinal disorders. This pathogen has also been linked to the autoimmune sequelae in extra‐gastrointestinal diseases and peripheral neuropathies. Guillain‐Barré Syndrome (GBS) is a serious autoimmune demyelinating disorder of peripheral nerves, usually with a post‐infectious onset. About 30% of cases of GBS attributed to by Campylobacter jejuni, so, H. pylori, could be also involved. Growing evidence suggests the likely involvement of H. pylori infection in the development of GBS. The aim of the current study is to therefore estimate the prevalence of H. pylori antibodies in GBS. Methods A search of the literature was performed, using the PUBMED database, until December 2018. Data were extracted from six case‐control studies, and a stratification analysis was conducted according to cerebrospinal fluid (CSF) or serum detection material. Results Amongst 29 records found, 6 studies met in the inclusion criteria for the meta‐analysis. In the CSF subgroup, 105 participants were involved (40 GBS patients and 65 controls), while the serum subgroup included 325 participants (152 GBS and 173 controls). Data were combined using a fixed‐effects model. Anti‐ H. pylori IgG were significantly more prevalent in GBS patients compared to controls, in both CSF (95% CI: 9.66‐186.56, OR: 42.45, Pz<0.00001) and serum (95% CI: 1.30‐4.11, OR: 2.31, Pz: 0.004) subgroups. Conclusion The present meta‐analysis showed a strong association between GBS and the presence of H. pylori antibodies, especially in CSF, thereby suggesting a role of H. pylori infection in the pathophysiology of GBS.
Efthimios Dardiotis; Maria Sokratous; Zisis Tsouris; Vasileios Siokas; Alexios‐Fotios A. Mentis; Athina Maria Aloizou; Amalia Michalopoulou; Dimitrios P. Bogdanos; Georgia Xiromerisiou; Georgia Deretzi; Jannis Kountouras; Georgios M. Hadjigeorgiou. Association betweenHelicobacter pylori infection and Guillain‐Barré Syndrome: A meta‐analysis. European Journal of Clinical Investigation 2020, 50, e13218 .
AMA StyleEfthimios Dardiotis, Maria Sokratous, Zisis Tsouris, Vasileios Siokas, Alexios‐Fotios A. Mentis, Athina Maria Aloizou, Amalia Michalopoulou, Dimitrios P. Bogdanos, Georgia Xiromerisiou, Georgia Deretzi, Jannis Kountouras, Georgios M. Hadjigeorgiou. Association betweenHelicobacter pylori infection and Guillain‐Barré Syndrome: A meta‐analysis. European Journal of Clinical Investigation. 2020; 50 (5):e13218.
Chicago/Turabian StyleEfthimios Dardiotis; Maria Sokratous; Zisis Tsouris; Vasileios Siokas; Alexios‐Fotios A. Mentis; Athina Maria Aloizou; Amalia Michalopoulou; Dimitrios P. Bogdanos; Georgia Xiromerisiou; Georgia Deretzi; Jannis Kountouras; Georgios M. Hadjigeorgiou. 2020. "Association betweenHelicobacter pylori infection and Guillain‐Barré Syndrome: A meta‐analysis." European Journal of Clinical Investigation 50, no. 5: e13218.