Konstantinos Ε. Kouskoukis
Professor of Dermatology – Lawyer
President of the Hellenic Academy of Thermal Medicine, World President of World Academy of Chinese and Complementary Medicine
f. V. Rector – Gen. Secretary of the Ministry of National Education
Address: 42 Sofokleous Street, Voula 16673, Athens, Greece
Mob: 6944307423, E-mail: firstname.lastname@example.org
Professor of Dermatology
President Hellenic Academy of Thermal Medicine
President World Academy of Chinese & Complimentary Medicine
B’ Vice President GDHI
Scientifically Documented Thermal Medicine as Personalized Medicine
Thermal Medicine has a wide range of preventive and therapeutic applications using natural resources. It is not only for the elderly (babyboomers), as it could be established as a trend of young people for prevention (new lifestyle). Thermal Medicine includes activities in medi-spa and thalassotherapy centers for recreation and rejuvenation and plays, also, important role in cosmetology and cosmetics, dermatological products and spas.
Globally, current trends include combination of holidays and services for prevention, maintenance, or improvement of health through programs of rejuvenation and relaxation. Furthermore, Thermal Medicine is directed not only to patients, but also to their caregivers, as well as, to healthy people
Worldwide, life expectancy is increasing, the gap between male and female life expectancy is narrowing, while the period of healthy life expectancy is expanding. Moreover, the number of older tourists from existing markets in developed countries is getting larger, while older tourists want to have a younger outlook than previous generations
In most European countries, Medispas and spa facilities, treatment is paid by social/health insurance, while cross-border healthcare is mainly paid by patients/clients.
Thermal Medicine consists of Balneotherapy, Internal washes, Drinking therapy, Inhalation therapy, Mud therapy, Thalassotherapy and Cave-salt therapy. The basic therapeutic elements, which Thermal Medicine is based on, are inorganic elements and nonmetals (Cl–, SO42-, HCO3–, S, Br, I, F, NH3, NO3–, NO2–, PO43-, H2PO4–, HPO42-, CO2, O2, N2, H2, Se), microminerals (Na+, K+, Ca2+, Mg2+, Fe2+, Fe3+, Cu, Co, Zn, Ni, Mn, Li+, Al, Ba, Sr2+, Pb, As, B) and noble gases (Rn, He, Ne, Ar, Kr) and especially Sulfur (S).
It is evidenced based that Thermal Medicine can be used as therapeutical approach on myoskeletal, respiratory, cardiovascular, nervous, endocrinological, gastro-intestinal, urinary, dermatological, gynecological, allergic, ENT and periodontal diseases.
Vasileios Zogopoulos received his BSc in Computer Science and Biomedical Informatics from the University of Thessaly and his MSc in Bioinformatics from the University of Athens. He is currently part of Ioannis Michalopoulos Lab of Computational Biology and Bioinformatics as a PhD student in Bioinformatics at the Biomedical Research Foundation, Academy of Athens.
AI-based sparse biological data dimensionality reduction: Applications in single cell RNA-seq data
Zogopoulos, V.L.1,2, Tsotra, I.1,2, Iconomidou, V.A.2, and Michalopoulos, I.1,*
Single-cell RNA-Seq (scRNA-Seq) is an emerging RNA-Seq-based technology which studies the transcriptome of single cells. The gene count pipeline of scRNA-Seq data is similar to that of bulk RNA-Seq data. Nevertheless, since each scRNA-Seq sample corresponds to a single cell and tissues contain a large amount of cells, it is quite common to encounter datasets that include several hundred thousand samples, each containing expression values for tens of thousands of genes. Such high-dimensional data require an enormous amount of computational time for pre-processing and bioinformatics analysis. Furthermore, single-cell data are characterized by high sparsity, due to the appearance of a large amount of zero counts of genes (known as dropout events) that are truly expressed in other cells of the same type.
Dimensionality reduction is a Artificial Intelligence-based technique to handle high-dimensional data, aiming to transform the original space into a lower-dimensional space while retaining as much valuable information as possible. For example, scRNA-Seq sample data are projected onto a new subspace, either by selecting a subset of the original samples or by generating a smaller number of latent samples, both of which would be representative of the original data.
There are several Dimensionality Reduction implementations based in machine or deep learning, such as Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), Uniform Manifold Approximation and Projection (UMAP), Variational Autoencoders (VAEs), etc., which have been already successfully utilized in scRNA-Seq data analysis. Effective application of AI-based dimensionality reduction in scRNA-Seq data facilitates their downstream analysis by enabling the identification of detailed gene networks, as well as the discovery of new cell types. In the latter case, by studying the expression of single cells, drugs that target specific cell types or certain drug-resistant cell types may be discovered. In addition, the genetic variability and cellular heterogeneity which are observed through scRNA-Seq data can aid to the fine-tuning of precision medicine.
This talk aims to present the available dimensionality reduction methods in the context of scRNA-Seq data, as well as offer examples of such applications in pharmacogenomics.
H Ελένη Ντούμου είναι Μοριακή Βιολόγος-Γενετίστρια από το ΔΠΘ. Κάτοχος μεταπτυχιακού διπλώματος στις Εφαρμογές της Μοριακής Βιολογίας-Γενετικής και στους Διαγνωστικούς Δείκτες του Πανεπιστημίου Θεσσαλίας, με εξειδίκευση στη Φαρμακογενετική και διδακτορικό στην Επιγενετική ρύθμιση στην Οστεοαρθρίτιδα. Έχει δεκαπενταετή εργαστηριακή εμπειρία σε εργαστήρια της Ελλάδας και του Ηνωμένου Βασιλείου, ενώ υπήρξε Ερευνητικός επισκέπτης στο τμήμα Κυτταρικής και Αναπτυξιακής Βιολογίας του University College of London και στο Ινστιτούτο Kennedy του Πανεπιστημίου της Οξφόρδης. Είναι μέλος της FENS (Federation of European Neuroscience Societies). Στην παρούσα φάση εργάζεται στην εταιρεία iDNA, όπου πραγματοποιεί την εργαστηριακή και γενετική ανάλυση των δεδομένων, συμμετέχει στην ανάπτυξη νέων προϊόντων και είναι υπεύθυνη διαχείρισης ποιότητας της εταιρείας.
Amalia Papanikolopoulou MD, MSc, PhD & MPharm, MClinPharm
Is a Resident Doctor in Internal Medicine at GPP General Hospital of Chest Diseases “Sotiria”, Athens, Greece. She is also a Clinical Pharmacist and former Head of Clinical Pharmacology & Clinical Trials Dpt at Athens Medical Center, Athens, Greece. Her doctoral dissertation was on antimicrobial stewardship program in the hospital setting and the impact on antimicrobial resistance and nosocomial infections. Her research interests are focusing on infectious diseases, oncology and hematology.
Assistant Professor of Oncology at the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens,
I am a Medical Oncologist with a special interest in Gynecologic and Genitourinary Neoplasms. I work as an Assistant Professor at the Department of Clinical Therapeutics, NKUA, Alexandra Hospital, where I carry out my educational, clinical and research work.
I graduated with honors from the Medical School of Athens in 2002. I received my PhD with honors, titled “The Role of Oncogenes in the Induction of Cellular Senescence and Apoptosis in Cancer,” part of which was published in the journal Nature. I specialized in Medical Oncology at the Department of Clinical Therapeutics, Alexandra Hospital and obtained my specialty title in 2014. I continued working as a Locum Registrar and Registrar in the same department, participating in the clinical, educational, and research activities of the clinic.
So far, I have participated in 112 publications – original works, review articles, and clinical cases – in international scientific journals, many of which were published in high-quality journals such as Nature, Nature Cell Biology, Cancer Research, Journal of Clinical Oncology, Lancet Oncology, Annals of Oncology, among others. These publications have received 5421 citations, and my h-index is 29. In addition to my publications, I have given numerous lectures and presentations at national and international conferences. I hold the position of Editor in Chief at the Forum of Clinical Oncology journal, the official journal of the Hellenic Society of Medical Oncologists (HESMO), and I am a member of the Executive Committee of the Hellenic Genito-Urinary Cancer Group (HCUCG).
EVANGELOS J. GIAMARELLOS-BOURBOULIS, MD, PhD
He is Professor of Internal Medicine and Infectious Diseases at the Medical School of the National and Kapodistrian University of Athens since 2018. He was trained in the Immunology of Infections at the Department of Internal Medicine and Infectious Disease of Radboud University in the Netherlands. In 2012 and 2013 he served as guest Professor of the Department of Critical Care Medicine of Jena University Hospital in Germany. His main research contribution is immunomodulation in sepsis and in auto-inflammatory disorders for which he was awarded the Young Investigator Research Award by the European Society of Clinical Microbiology and Infectious Diseases. He has 513 publications in international peer-reviewed journals with more than 31,500 citations and h-index 86. He has contributed in the development of clarithromycin for immunomodulatory treatment of septic shock, the recognition of hidradenitis suppurativa (HS) as an auto-inflammatory disorder and in the licensing of adalimumab for treatment of (HS). He is the current chairman of the European Sepsis Alliance. His main achievement is the approval of anakinra for COVID-19 pneumonia in adults by the European Medicines Agency and the Food and Drug Administration through the phase 2 and 3 trials SAVE and SAVE-MORE that he designed and conducted.
National & Kapodistrian University of Athens
Director of the Laboratory of Pharmaceutical Technology and since 2008 he serves as President of the Hellenic Pharmaceutical Society (HPS). In 2018, was honored with an award by the Order of Sciences of the Academy of Athens for his scientific achievements in Pharmaceutical Nanotechnology. In 2021, Prof. Demetzos has been elected as Ordinary member in Class IV-Natural Sciences of the European Academy of Sciences and Arts (Academia Scientiarium et Artium Europaea). Since 2023 he acts as Associate Editor on the prestigious Journal of Liposome Research (Tayror & Francis).
http://demetzoslab.gr/; https://orcid.org/0000-0001-9771-4314; http://linkedin.com/in/costas-demetzos-76a651203
Complex nanomedicines and nanovaccines. Art and beauty at nanoscale.
Professor, School of Health Sciences, Department of Pharmacy, National & Kapodistrian University of Athens
email@example.com ; http://demetzoslab.gr/; https://orcid.org/0000-0001-9771-4314; http://linkedin.com/in/costas-demetzos-76a651203
Complex systems are defined as those containing many interdependent constitutes which interact nonlinearly (1). Nanotechnology in therapeutics is an attractive scientific field that provides innovative medicines and vaccines. More specifically, nanotechnology exhibits a tremendous potential for the diagnosis and treatment of several diseases, thus becoming an indispensable tool in several areas of medicine. Modern therapeutic and prophylactic products are based on the development of innovative nanodevices (Fig.1), that can deliver biomolecules to the injury tissues. The integration of Artificial Intelligence (AI) with nanotechnology will facilitate and optimize the development of nanomaterials and nanostructures, affecting several scientific fields and leading to a broad range of applications and smart conventional or nano formulations. The beauty of complex nanoparticles and their lyotropic properties (i.e., different organization of molecules in the bulk formulation) relate to their morphological characteristics and follow the order of the natural harmony.
Ref. (1). ‘Non extensive entropy. Interdisciplinary applications’, Ed. M. Gell-Mann and C. Tsallis, Santa Fe Institute, Studies in the Science of Complexity, Oxford University Press, 2004, p. 377.
Fig. 1. Comparison of different nanoscale biomolecules and nanoparticles.
Dr. Nikolaos Tsirikos-Karapanos is a Triple Board-Certified Pharmacist, Medical Doctor, and Cardiovascular Surgeon. He was born and studied Pharmacy and Medicine in Athens, Greece and moved to Rochester, Minnesota where he worked for five years at Mayo Clinic.
Dr. Tsirikos is the recipient of prestigious awards in Thoracic and Cardiovascular Surgery research, owner of several National and International Patents and the founder, owner, and President of Metron Nutraceuticals, an FDA Registered and FDA Inspected R&D company that produces its own patented dietary supplement formulations in Cleveland, Ohio, USA.
METABOLOMIC BIOMARKERS IN PSORIASIS: PRELIMINARY RESULTS FROM A CLINICAL TRIAL
Evangelia Sarandi1,2, Sabine Krueger-Krasagakis3, Dimitris Tsoukalas2,4, Aristidis Tsatsakis1
1Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece; firstname.lastname@example.org, email@example.com
2Metabolomic Medicine, Health Clinics for Autoimmune and Chronic Diseases, 10674 Athens, Greece
3Dermatology Department, University Hospital of Heraklion, 71500 Heraklion, Greece; firstname.lastname@example.org
4European Institute of Molecular Medicine, 00198 Rome, Italy; email@example.com
Introduction: Psoriasis, a chronic inflammatory skin disease, is associated with several metabolic complications that deteriorate patients’ quality of life (QoL). Altered metabolism plays a crucial role in psoriasis aetiopathogenesis offering novel insights in diagnosis and treatment. Materials and Methods: In this case-control study, a total of 93 participants (18-60 years old) were included to compare the baseline levels of plasma fatty acids of patients with psoriasis and healthy individuals using Gas-Chromatography Mass Spectrometry. The Mediterranean Diet Score (MDS) and the DLQI questionnaire assessed the participants’ diet and baseline disease-related QoL. Results: Values of Eicosapentaenoic acid, A-linolenic acid, Gamma-linolenic acid, Nervonic acid, Myristoleic acid, Lignocericc acid, Arachidonic acid/ Eicosapentaenoic acid ratio, and Saturated/Total fatty acids ratio were significantly altered in the group of psoriasis (n=32, 47%F) compared to the control (n=49, 57%F) (p<0.001 based on Bonferroni correction in age and sex-matched samples). No difference was observed between the two groups regarding the baseline adherence to MDS, alcohol consumption, smoking status, and exercise levels, while BMI was statistically significantly higher in patients with psoriasis compared to control (26.2 + 3.3 vs 23.9 + 2.5). Correlation analysis did not detect any association between fatty acid levels and population characteristics. Discussion and Conclusions: Lipid metabolism dysregulation is crucial in psoriasis progression due to specific cell substrate requirements and crosstalk with immune cells. Changes in plasma total fatty acid levels might serve as potential independent biomarkers of psoriasis early diagnosis with potential implications in targeted treatment.
Elisavet Stavropoulou is an Internal Medicine and Infectious Disease Specialist. She obtained her diploma in Medicine (2015) as well as a Master of Science in Hygiene and Occupational Health (2021) at Democritus University of Thrace and completed her medical specialty in Internal Medicine and Infectious Diseases at Lausanne University Hospital in Switzerland (2015-2023). She obtained a Doctorate (2023) at the University of Lausanne about the impact of regimen of antibiotic prophylaxis on surgical site infections. During the last years she particularly took care of patients in different states of immunosuppression (AIDS, leukemia with neutropenia, hematopoietic stem cell transplantation, solid organ transplantation) and infectious diseases such as invasive fungal diseases and has participated in scientific projects about invasive fungal infections, COVID-19 and infective endocarditis. She currently works for the National Office of Public Health as an infectious Disease consultant on antimicrobial resistance and hospital acquired infections. She is author or co-author of 53 publications in the field of Microbiology and Infectious Diseases.
Ioannis Axiotis-Zacharias – CV
Hydrogen Sulfide and Cardioprotection: Using mechanism-based combinations of H2S-donors to maximize the cardioprotective action of H2S
Ravani S 1,2, Chatzianastasiou A2, Papapetropoulos A 1,2
1 Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece, Athens Attiki, Greece
2 Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece, Athens Attiki, Greece
Introduction/Aim: H2S-donors are cardioprotective in ischemia/reperfusion (I/R) injury. Some H2S-donors exert their beneficial effects in a nitric oxide (NO)-dependent manner, while others act using NO-independent pathways. The aims of the present study were to (i) evaluate whether H2S-donors with distinct pharmacodynamic properties act synergistically in I/R injury and (ii) determine if H2S-donors remain cardioprotective in obese mice.
Methods: C57BL/6 mice were subjected to 30 min of ischemia followed by 120 min of reperfusion. Donors were administered intravenously at the end of ischemia (Na2S: 1 μmol/kg, GYY4137: 25 μmol/kg, AP39: 0,25 μmol/kg), while the 3-mercaptopyruvate sulfurtransferase (10 mg/kg) inhibitor was given intraperitonially 1h prior to ischemia. Infarct size was estimated by 2,3,5-triphenyltetrazolium staining, while the area at risk was calculated using Evans blue.
Results: All three donors reduced infarct size when administered as a sole treatment. Co-administration of Na2S/GYY4137, as well as Na2S/AP39 reduced further the I/R injury, beyond what was observed with each individual donor. Since inhibition of the H2S-producing enzyme 3-mercaptopyruvate sulfurtransferase is known to reduce infarct size, we co-administered C3 with Na2S to determine possible additive effects between the two agents. In this case, combination of C3 with Na2S did not yield superior results compared to the individual treatments. Similarly, to what was observed in healthy mice, administration of a H2S-donor (Na2S or AP39) reduced I/R injury in mice rendered obese by consumption of a high fat diet.
Conclusion: We conclude that combining a NO-dependent with a NO-independent H2S-donor leads to enhanced cardioprotection and that H2S-donors remain effective in obese animals.
Dr Sterghios A. Moschos is a Molecular Biologist (1999) with a Pharmaceutics PhD from University College London’s Centre for Drug Delivery Research (2002). His postdoctoral career at UCL and subsequently the National Heart and Lung Institute, Imperial College saw him become a world-recognised expert in RNA biotherapeutics and bioanalytics, particularly for lung diseases. Recruited to lead these areas at Pfizer, UK, his research influenced the strategic direction of the field for over a decade and culminated in first-in-man / phase IIb studies for DNA-directed RNAi. An academic since 2011, he explores modern multi-omic techniques for diagnostics and molecular therapy development for precision medicine.
Sofia Siest (Sophie Visvikis-Siest), PhD, is Director of Research in INSERM and has the direction of a Research Unit in Nancy, France: EA 1122; “Interactions Géne-Environement en Physiopathologie Cardio-Vasculaire” (IGE-PCV) at the University of Lorraine and of a Biological Resources Center (BRC): “Interactions Géne-Environement en Physiopathologie Cardio-Vasculaire” (IGE-PCV).
Dr Sofia Siest’s main research interests are in the domain of public health, personalised medicine, prevention, genetic epidemiology, genomics and pharmacogenomics, cardio-vascular diseases, VEGF and inflammation.
She has published more than 350 papers in international scientific committee journals (index h: 54, citations: 16064), 2 patents and gave more than 90 international conferences.
Professor Leonidas A. Phylactou
Leonidas Phylactou studied in UK and USA and then did a postdoc at the University of Oxford, where he set up a team working on gene therapy for Myotonic Dystrophy. In 1998, he established a research group at the Cyprus Institute of Neurology and Genetics (CING) working on the gene function and gene therapy. In 2005, he was appointed Head of the Department of Molecular Genetics, Function and Therapy. His research interests focus on the gene therapy for muscular dystrophy, the identification of biomarkers in Myotonic Dystrophy and the investigation of molecular causes for inherited diseases. Since November 2015, he is also the Chief Executive and Medical Director of CING and the Provost of the Cyprus School of Molecular Medicine at CING.
Nationality: Australian, Greek
Marital & Family status: Married, 8 children
Current work address: Genesis Athens Clinic, 14-16 Papanicoli street, Chalandri, Athens 152
32 Greece. Tel: +30 210 6894326; Fax: +30 210 6890897
Konstantinos Pantos was awarded his medical degree from the University of Athens in 1981. He specialized in Obstetrics – Gynecology at the University of Athens and in 1988 he was awarded the Doctorate in Medicine (PhD), University of Athens, Greece. He specialized in the field of medically assisted reproduction technology as a senior registrat in the Royal Women’s Hospital in Melbourne, Australia (1987-1989).
With nearly thirty years of experience in obstetrics and gynaecology and as an infertility specialist, Konstantinos Pantos is expert in all aspects of assisted reproduction treatment and technology. He is internationally renowned for its high quality of care and efficiency in proving patient care and couples seek for his service from 65 countries around the globe, including Europe, Australia and the United States. His is dedicated on research that has lead to successfully incorporating novel and pioneering technologies in patient care providing the best treatment, using custom-tailored technologies to optimize results for each individual. In addition to his extensive experience in practice, Dr. Pantos is the author or co-author of peer reviewed publications and a welcome speaker at numerous conferences reporting on his successful advances in the assisted reproduction field. He a member of international societies, including the European Society of Human Reproductions and Embryology (ESHRE), Fertility Society Australia (FSA), New York Academy of Science, American Society Reproductive Medicine (ASRM), as well as national scientific committees including the Hellenic Society of
Reproductive Medicine where he serves as the Secretary in the board. He is a member at the sector of Medical Tourism of the Institute of Scientific Research and member at the steering committee Greek Medical Tourism Council (Elitour). He also serves as a Vice President on the Board of Directors of International Health Tourism Center aiming at the organization, administration and efficient management of the high quality Health and Safety certified health product for all the stakeholders of its member countries. Currently, he is a Vice President of the Global Greek Doctors Institute with the scope to facilitate interconnection of all Greek physicians and Greek medical associations around the world for exchange of expertise, co-operation, professional development and creation of career
opportunities and incentives for the physicians to return and work at their home country.
TSOUKALAS DIMITRIOS, MD
Specialized in General & Family Medicine, Assoc. Member of the World Academy of Sciences, President of the European Institute of Nutritional Medicine
Dimitris Tsoukalas, a graduate of the Medical School of “Universita ‘degli Studi di Napoli Federico II” in Italy, completed his specialization in General & Family Medicine at the Hippocratic Hospital of Athens. He is an Associate Member of the World Academy of Sciences, Scientific Director of the Medical Group Metabolomic Medicine® Switzerland and President of the European Institute of Nutritional Medicine. He has been awarded the highest recognition and Honorable Mention by the Greek Ministry of Health for his contribution in primary health care and in 2017 was recognized as an outstanding reviewer by the scientific publishing organization ELSEVIER for contributing to the reviewing of scientific articles in Food and Chemical Toxicology. He collaborates with professor Tsatsakis at the Faculty of Medicine, University of Crete and researchers from international academic institutions such as the Stanford University, La Trobe, Melbourne, University of Brescia and Craiova Medical School in the clinical application of Precision Medicine, Metabolomics and telomere biology in autoimmune and chronic diseases.
Dr Alexander Haliassos, MD, PhD, EuSpLM
62 y.o., born in Athens (Greece), married, 4 adult children
Dr Alexander Haliassos is currently President and CEO of DIAMEDICA, a Greek reference laboratory specialized in Prenatal Diagnostics based in Athens since 2005. He also acts as Scientific Director of the Greek External Quality Assessment Scheme (ESEAP), a non-profit organization established by the Greek Ministry of Health as a spin-off of the Greek Society of Clinical Chemistry-Clinical biochemistry (GSCC-CB).
He obtained his MD diploma at the medical School of the University of Athens (1985). After his military service as medical doctor at the Greek Air Force (1985-1987), he obtained in 1991 his thesis (PhD) at the school of Medicine, National University of Athens, Greece. He pursued his scientific education at the Faculty of Medicine, Claude Bernard University, Lyon I (FR) where he obtained a thesis (DEA) on electronics applied to the medical field, and in addition one in human genetics in 1985. He completed his curriculum in France as post-doctoral fellow (1987-1991) at the Institute of Molecular Biology, Paris-Descartes University.
Dr Alexander Haliassos is registered as European Clinical Chemist (EurClinChem, now EurSpLM) since 2003. He fulfilled many responsibilities in teaching medical students at the National Research Foundation, Institute for Biological Research and Biotechnology, Athens (GR); in directing the core medical laboratory, including the Blood Bank of the Onassis Cardiac Surgery Center, the Athens Euroclinic and the Metropolitan Hospital at Athens (GR) and in participating in genetics research.
At the national level, Dr Haliassos has held a number of professional representative roles in Greece including GSCC-CB Executive Board member (1996-2003), GSCC-CB Scientific Secretary (2005-2011), General Secretary (2012-2017) and from 2017 until today President of the Greek society. Since 2011, he is a founding Member of the Scientific and Educational Committee of the GSCC-CB and a founding Member of the Greek National Registration Committee for Clinical Chemistry. He represents ESEAP at EQALM (the European Organization for External Quality Assurance Providers in Laboratory Medicine). He is an elected member of HellasLab Executive Board, the Greek section of EuroLab. On behalf of the Greek Society, he strengthened partnerships with multilateral agencies to promote the added value of laboratory medicine as a key factor to improve public health. Since 2005 he is the Greek IFCC National Representative.
At the international level, Dr Alexander Haliassos is the current Treasurer of IFCC (2021-2023) and re-elected for the next term (2024-2026). Within the federation, he served as member of the IFCC-WG on Standardization of Troponin I (WG-TNI) as well as member of the IFCC-Analytical Quality Committee (C-AQ). In 2014, he was appointed as Chair of the IFCC-Task Force on Proficiency Testing (TF-PT) that in 2017 evolved to the Committee on Proficiency Testing (C-PT), a multidisciplinary effort of IFCC in the analysis and the exploration of the Proficiency Testing and External Quality Control issues.
He intensified its engagements with the IFCC conferences and congresses acting as the Greek leader for the organization of the 10th IFCC-General Conference, at Corfu in 2010 and as Member of the EuroMedLab Paris 2015 Congress Organizing Committee (COC). As the President of EuroMedalb Athens 2017, he demonstrated an extensive experience and expertise in management, finance and institutional partnerships within the IVD industry. Considering the number of exhibitors, the number of received abstracts, the high participation at the conference and according to the IFCC survey, the overall satisfaction of Delegates and Exhibitors, EuroMedLab Athens 2017 was a great scientific congress and a very successful financial event for IFCC.
Dr Alexander Haliassos is member of the American Association of Clinical Chemistry (AACC) since 1993, and the leading Editor of the website www.labtestsonline.gr. During the last decade, he has been involved in various scientific and professional European committees and/or working groups. As member of the “EFCC-Distance Education Programs – E-Learning”, he organized the very first EFCC e-seminars. He was a member of the EFLM-TFG (task and finish group) on the “Continuous Professional Development [CPD] crediting rules harmonization in the European Union”.
Dr Alexander Haliassos published more than 65 papers in peer-reviewed scientific journals cited 1341 times, made more than 155 oral presentations in international congresses, participated in 195 posters in international meetings and chaired one international (the EuroMedLab Athens 2017), two national congresses and several seminars and webinars on laboratory medicine subjects.
Chremonidou 27-33, Athens, +30 6987167545, firstname.lastname@example.org
· Strategic planning
· Expertise in applied research in social and behavioral health
· Extensive knowledge of medications and their use
· Communication and collaboration skills
· Agile and adaptable
· Dedicated to provide first class services to customers, ensuring accuracy of advice offered.
National and Kapodistrian University of Athens, Athens 09/2019- 07/2022
Msc Department of Cosmetology and Dermopharmacology
Thesis: “The influence of genetics of cytokine diversity in the pathogenesis of psoriasis” Grade: 8.0 (Distinction)
Comenius University in Bratislava, Bratislava 09/2013- 06/2018
Department of Pharmacy
Thesis: “The impact of patient´s socio- demographic characteristics and comorbidities on their attitudes towards flu vaccination” Grade 8.5 (Distinction)
Long Beach City College, Long Beach, CA, USA, 09/2012- 06/2013
Grade: GPA 3, CUM Total 48
Omega Pharma Hellas – Perrigo, Athens 12/2022 – Present
Regulatory affairs, Quality assurance & Safety associate Greece/CY/ADR
Primeview Research and Consulting, Athens, 09/2021 – 08/2022
Qualitative Project Analyst,
INTERMED, Athens, 06/2020 – 07/2020
Internship in the QC & R&D Department
Wellness Pharmacy, Pharmacy Heirs of Aristides Zacharis, Thessaloniki, 12/2018- 04/2019
Assistant Pharmacist, London, UK, 2019, Internship at community pharmacy
Languages: Greek: native, English: fluent, Spanish: fair knowledge, Slovak: fair knowledge
Computer skills: ECDL 2019 (MS Office), IBM SPSS Statistics, CRM Software
International Diploma in Internet and Social Media Marketing: October 2022
VOLUNTEER EXPERIENCE OR LEADERSHIP
Date of birth: May 14th, 1993, Interests: Tennis, Horseback riding, Travelling, Acting (New York Film Academy, Spring/Summer 2012, Los Angeles, CA, USA)
Evangelia Charmandari, MD, MSc, PhD, MRCP(UK), CCST(UK)
Professor of Pediatrics – Pediatric and Adolescent Endocrinology
National and Kapodistrian University of Athens Medical School
‘Aghia Sophia’ Children’s Hospital, Athens, Greece
Evangelia Charmandari is a Professor of Pediatrics – Pediatric and Adolescent Endocrinology at the National and Kapodistrian University of Athens Medical School, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece. She is the Scientific Supervisor of the Division of Endocrinology and Metabolism, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. She is also the Director of the MSc Program entitled ‘General Pediatrics and Pediatric Subspecialties: Clinical Practice and Research’. She is the President of the Hellenic Society for Pediatric and Adolescent Endocrinology and a Μember of the ENDO-ERN Steering Committee.
Professor Charmandari graduated from the Aristotle University of Thessaloniki Medical School as a valedictorian of her class and completed her specialization in General Pediatrics in the UK. She was further subspecialized in Pediatric and Adolescent Endocrinology at Great Ormond Street Hospital for Children and University College Hospital in London, UK. She is a certified Pediatrician and Pediatric and Adolescent Endocrinologist by the Royal College of Pediatrics and Child Health, London, UK. She obtained a Master of Science in Clinical Pediatrics and a PhD in Pediatric and Adolescent Endocrinology, which were both awarded by the University College London (UCL), University of London, London, UK. She subsequently undertook a Postdoctoral Fellowship in Molecular Endocrinology and Cellular Biology at the National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA. She also worked as a Consultant in Pediatric and Adolescent Endocrinology at St. James’ University Hospital and Leeds General Infirmary, Leeds, UK.
Professor Charmandari’s research work has focused on the hypothalamic-pituitary-adrenal axis physiology, pathophysiology and its disorders, including Gushing’s disease, Congenital Adrenal Hyperplasia and Adrenal Insufficiency, the molecular mechanisms of glucocorticoid receptor action, the syndromes of Primary Generalized Glucocorticoid Resistance and Hypersensitivity, growth disorders, as well as childhood obesity.
She has more than 410 publications in SCI journals, books, and international conference proceedings (impact factor: 1603; Citations: 10,343 citations; h-index=47; i10-index: 106). She was awarded the ‘Henning Andersen Prize’ of the European Society of Pediatric Endocrinology (basic research), as well as several awards of the Hellenic Endocrine Society, Medical Society of Athens, Hellenic Society of Adolescent Medicine and Health Care Business Awards. She has been an invited speaker in more than 250 National and International Meetings. Finally, she has attracted approximately €3,200,000.00 research funding.
New Technologies in the Management of Childhood Obesity
Dr. Evangelia Charmandari, MD, PhD, Professor, Division of Endocrinology and Metabolism, First Department of Paediatrics, National and Kapodistrian University of Athens
Abstract: Obesity in childhood and adolescence represents a major health problem. Novel e-Health technologies have been developed in order to provide a comprehensive and personalized plan of action for the prevention and management of overweight and obesity in childhood and adolescence. We used information and communication technologies to develop a “National Registry and Guide for the Prevention and Management of Overweight and Obesity” in order to register online children and adolescents nationwide, and to guide pediatricians and general practitioners regarding the management of overweight or obese subjects. Furthermore, intelligent multi-level information systems and specialized artificial intelligence algorithms are being developed with a view to offering precision and personalized medical management to children with overweight or obesity. Moreover, the Big Data against Childhood Obesity platform records behavioral data objectively by using inertial sensors and Global Positioning System (GPS) and combines them with data of the environment, in order to assess the full contextual framework that is associated with increased BMI. These e-Health applications are expected to play an important role in the management of overweight and obesity in childhood and adolescence.
Genetic Polymorphisms in Transdermal Pharmacotherapy
Konstantinos Gogkas, MSc, Pharmacist, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, University of Athens
Alzheimer’s disease (AD) is an irreversible neurodegenerative disease of the central nervous system, which is characterized by progressive loss of memory, cognitive functions of daily life, changes in behavior and emotions and often leads to coma and death. Based on available data, APOE gene is the strongest genetic risk factor for the onset of Alzheimer’s disease. The APOE gene has four major isoforms: ε1. ε2, ε3 and ε4. Having at least one ε4 allele appears to triple the odds of developing AD. Allele combinations create three homozygous (APOE2/2, APOE3/3 and APOE4/4) and three heterozygous (APOE2/3, APOE2/4 and APOE3/4) genotypes. Cholinesterase inhibitors are mainly used to treat the disease. Rivastigmine, a carbamate-type acetyl- and butyrylcholinesterase inhibitor, ameliorates cholinergic-mediated cognitive deficits associated with Alzheimer’s disease.
The purpose of this study is to try to predict the response of AD patients to diadermal application of rivastigmine medication based on their genotype after comparing the genotypes of rs429358 and rs7412 polymorphisms of APOE gene between AD patients and controls. A total of 100 patients with confirmed Alzheimer’s disease and 100 unrelated controls participated, from whom DNA was isolated by DNA extraction. Then, real-time polymerase chain reaction was applied to detect the genotypes of polymorphisms in all individuals. Finally, the odds ratio and 95% confidence interval of each polymorphism were assessed between patients and controls.
The results of this study showed statistically significant differences between AD patients and controls for both polymorphisms: rs429358 (T:T/T:C+C:C, Odds Ratio=0.31, p-value=0.000629) and rs7412 (C:C/C:T+T:T, Odds Ratio=0.21, p-value=0.000679) at 95% confidence level.
Other studies and reports that have been performed to assess the response of AD patients to diadermal application of rivastigmine therapy based on ε4 allele carriers have not demonstrated any notable and clear difference. This fact may also indicate that genotype does not greatly influence treatment response and drug efficacy. Therefore, it is possible that neither dose adjustment is needed for the patients of the study, nor any other change in pharmacotherapy.
Precision Medicine in Invasive Fungal Infections
Dr. Elisavet Stavropoulou, MD, PhD, CHUV-Centre Hospitalier Universaire Vaudois
Invasive fungal infections (IFI) are a major cause of morbidity and mortality in immunocompromised individuals and are mentioned as one of the leading causes of death in hematopoietic stem cell transplant recipients. Recent advances in Immunology/Rheumatology and Hemato-Oncology have resulted in an increased and diverse population of immunocompromised patients at risk of IFI necessitating a move beyond the “one size fits all strategy” and highlighting the importance of Precision Medicine in diagnosis and treatment. This presentation will delve into the role of biomarkers in early and accurate IFI detection, offering the potential for improved outcomes as well as the transformative impact of genomic and molecular diagnostics, showcasing their ability to identify specific fungal strains. This becomes particularly relevant amid shifts in the epidemiologic landscape and the emergence of multi-resistant strains, as it enables targeted treatment strategies. Moreover, pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal drugs and the importance of therapeutic drug monitoring are going to be discussed. In conclusion, Precision Medicine and advanced diagnostics offer a tailored approach to IFI, optimizing detection and treatment. Embracing future research directions will continue to shape our strategies, ensuring resilience and improved outcomes against these complex challenges in immunocompromised patients.
Confirmation of Authenticity of Medicines in the Legal Distribution Chain
Dr. Artouros Isseyegh, PhD, Director of Cyprus Medicines Verification Organization, Nicosia, Cyprus
The Parliament and Council of the European Union have enforced a Directive on Falsified Medicines – 2011/62/EU and a Delegated Regulation (DR) – 2016/161(EU) for the safety features appearing on the packaging of prescription medicines for human use. The aim is to promote patient safety by minimizing the risk of falsified medicines infiltrating the legal supply chain. To achieve this scope, all stakeholders in the legal supply chain must fully comply to the provisions of the Directive and DR.
Stemming from the DR the European Medicines Verification System (EMVS) and the National Medicines Verification Systems have been established enabling the verification of the authenticity of medicines through an end-to-end verification process. Each country in this network connects to the EMVS through its NMVS. In Cyprus the NMVS is run by ΚΟΕΦ (see website: www.koef.org.cy for more details).
For the system to operate, manufacturers are required to print on the individual outer packaging of prescription medicines, a GS1 Data Matrix Code (DMC) which includes a Unique Identifier (UI) and to upload this information to the EMVS. The EMVS then distributes this information to the NMVS of all the markets involved. Furthermore, manufacturers are also required to incorporate an anti-tampering device on each individual pack, so that, any suspicious intervention on the pack is visually detectable.
Upon dispensing to the patient, the pack is examined visually for tampering and the DMC is scanned to verify its authenticity. If the UI on the pack matches the information in the EMVS/NMVS, the pack can be safely supplied to the patient. However, if the information does not match and the pack generates an Alert it is retained for potential falsification and an investigation procedure is initiated to determine the root cause. (technical, procedural or, a falsified pack).
Greece, having been granted a 6-year derogation period from February 2019, is obliged to establish an NMVS and become part of this network by February 2025.
FTIR spectroscopy and mathematical simulation of the increased risk of Covid-19 infection in cardiovascular diabetic patients.
E. Mylonas1, V. Mamareli2, J. Anastassopoulou2,3, I. Mamarelis4, T. Theophanides2, M. Filippakis
1Department of Digital Systems, University of Piraeus, Piraeus, Greece, 2National Technical University of Athens, Radiation Chemistry & Biospectroscopy, Zografou Campus, 15780, Athens, 3 International Institute of Anticancer Research, 1st Km Kapandriti, Attiki, 4401 Military General Hospital, Cardiology Department, Athens, Greece
Patients with TypeII diabetes and cardiovascular diseases were found to be more susceptible to COVID-19 infection. However, the patients who used metformin antidiabetic drug experienced lower rates of hospitalization and mortality. To assess the risk of morbidity and mortality from COVID-19 in diabetic patients based on their antidiabetic medication. For this study, FT-IR spectra of 35 calcified coronary arteries from patients who underwent CABG were recorded and were compared among COVID-19-infected TypeII diabetic patients who used metformin, insulin, and thiazolidinediones as treatments. The number of infected patients was obtained from the National Health Organization (NHO).
FT-IR spectral “marker bands” at 1742 cm-1, and between 200-1000 cm-1, due to oxidative stress and advanced end glycation (AEGs)/phosphorylation products, respectively, were less pronounced in patients medicated with metformin (Figure 1). By using Susceptible Infected Recovered (SIR) model it was demonstrated that patients medicated with metformin had a lower probability of infection compared to those receiving insulin and thiazolidinediones (Figure 2). The mathematical model was found to be in full agreement with the experimental and clinical data, which is also supported by existing literature.
We suggested the hypothesis that the AGEs are the key targets of COVID-19 spike protein binding through -OH and -NH groups (Figure 3). Metformin can interact through -NH directly with COVID-19 spike, inhibiting its entry into the cells, and indirectly by regulating the ATPases activity reducing the oxidative stress and immune response. In contrast, thiazolidinediones act on cytochrome P450, which supports electron transfer reactions, altering the redox potential of the cells.
Impact of MC4R, DRD2 and DRD3 gene polymorphisms in genetic susceptibility to vitiligo in a Caucasian population of Southeastern Europe.
1 Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens; 2 1st Department of Dermatology‑Venereology, Faculty of Medicine, National and Kapodistrian University of Athens, 3 Department of Dermatology‑Venereology, ‘A. Sygros’ Hospital for Skin and Venereal Diseases, 16121 Athens, Greece; 3. Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece 4. General Hospital G. Gennimatas.
Vitiligo, a common depigmenting skin disorder, is characterized by non-scaly, chalky-white amelanotic macules resulting from selective loss of functional melanocytes. Multiple genes have been associated with the onset of the disease, strengthening the hypothesis that vitiligo has an important genetic background. In this regard, the melanocortin system, an important regulator of melanogenesis and melanocyte survival, has been implicated/is of interest in vitiligo pathogenesis. In fact, decreased melanocortin receptor (MCR) expression in vitiligo-affected skin has already been reported. To date, however, the associations between MCR single nucleotide polymorphisms (SNPs) and risk of vitiligo remain largely unknown. Moreover, the dopamine pathway may be involved in the depigmentation process. The catecholamine neurotransmitter dopamine has been shown to interfere with melanocytes by inhibiting melanogenesis and inducing melanocyte apoptosis. Since the dopamine receptors (DR) DRD1 – DRD5 mediate all the biological functions of dopamine, the DR family might thus represent susceptibility genes for vitiligo. The present study investigated the possible association of polymorphisms rs11782312 T>C and rs489693 C>A of the melanocortin receptor 4 gene (MC4R), polymorphisms rs1800497 C>T and rs1799978 A>G of the dopamine receptor 2 gene (DRD2) and polymorphism rs963468 G>A of the dopamine receptor 3 gene (DRD3), with the susceptibility and clinical aspects of vitiligo in a Southeastern European Caucasian population. The aim of the study was to find the distribution of these gene polymorphisms in the population studied as well as to compare these results with the distribution frequencies of the same genotypes in healthy controls. A total of 152 unrelated vitiligo cases and 235 general population controls were enrolled in the stydy. Genomic DNA was extracted from whole blood after de identification and anonymization of the samples and genotyped for the selected polymorphisms by qPCR (endpoint genotyping). MC4R and DRD3 allelic frequency distribution did not differ significantly between patients and controls (p > 0.05) indicating that comparisons between the case and control groups showed no evidence to support an association between susceptibility to vitiligo and MC4R and DRD3 polymorphisms in this cohort. However, the proportion of the mutated T allele for rs1800497 C>T was significantly higher in patients than in controls and at a statistically significant level (T = 72% for patients and T = 23% for controls, pT could be considered as a possible biomarker for the onset of vitiligo. Finally, regarding the polymorphism rs17799978 A>G, the proportion of the mutated G allele was statistically significantly higher in controls than in vitiligo patients (G= 28% for patients and T = 38% for controls, p<0.0001). In conclusion, the presence of the G allele could be considered to have a protective role for the onset of vitiligo. Further research with larger sample sizes should be conducted to confirm these findings.
CYP2C9, CYP1A2 and ESR1 gene polymorphisms association with leflunomide (ARAVA) therapy efficacy
Dorothea Ntikou, MSc, Pharmacist, Clinical Pharmacology and Pharmacogenomics Research Group, Department of Pharmacology, National and Kapodistrian University of Athens
Leflunomide is known under the brand name ARAVA. It is an anti-rheumatic drug and belongs to the DMARDs. It is used in active moderate to severe rheumatoid arthritis (RA) and psoriatic arthritis. It is an inhibitor of the biosynthesis of pyrimidine, acts by inhibiting dihydrohydrogen dehydrogenase, and is a derivative of isoxazole with immunomodulatory activity. LEF is structurally and pharmacologically different from other immunomodulatory agents used in the treatment of rheumatic diseases. The frequency of distribution of each polymorphism and genotypes in all five populations was plotted using diagrams. Then, using other diagrams, the distribution of genotypes in the populations was compared in order to find the international differences in the administration of leflunomide. The polymorphisms in the CYP2C9 gene were found to not significantly affect the leflunomide response. Regarding the rs762551 polymorphism (CYP1A2), it was found that the presence of the A allele is associated with a better response to LEF compared to the presence of the C allele. Finally, two polymorphisms were identified in the ESR1 gene. In rs9340799, it appears that the presence of the A allele is associated with an excellent response to LEF therapy. Numerous studies have shown that gene mapping of patients with the mutations under study plays a key role in achieving maximum LEF efficacy. Adjusting the recommended dose of LEF in different populations “brings to the fore” the need for individualized treatment in most diseases and the administration of the appropriate dose of drug in the presence of a mutation. In conclusion, although studies have been performed on Leflunomide and its therapeutic activity in the presence of polymorphisms, there is still much room for future research on both the genes and populations examined and on a variety of others.
Digital imaging analysis: An innovative and non-invasive approach for studying the skin irradiation effects
Athina Markouizou1, Michail-Christou Rallis2, Jane Anastassopoulou3, Christina Mamareli3, Theo Theophanides3, Dimitriοs Sgouros3, Sotiris Mentonis2
1Department of Radiation Oncology, Metaxa Cancer Hospital, Piraeus, 2School of Health Sciences, Section of Pharmaceutical Technology, National and Kapodistrian University of Athens, 3National Technical University of Athens, Radiation Chemistry & Biospectroscopy, Zografou Campus, 15780, Athens, Greece
The last years the scientists try to develop in digital form rapid non-destructive and non-invasive techniques for early diagnosis, to increase the image resolution and minimize the number of biopsies. Imaging infrared or analysis. In this research we support the infrared spectroscopy in combination with ImageJ analysis software to record and discriminate the local biochemical changes at a molecular and macromolecular level caused by the diseases. Here, we emphasize the effect of ionizing radiation on skin during breast cancer radiotherapy, as well as the UV-skin interaction and cancer development. Both methods are non-destructive and are easy to be used to follow the disease as well as the curing effect of the therapeutic scheme. From our experience it was documented that the lipophilic products and aggregates are expressed as craters, while the mineralized areas appear as bumps (hill-like). Figure shows the BCC produced on mice skin and the FT-IR spectra upon skin cancer radiotherapy.
Artificial intelligence in external quality assessment schemes (EQA) in Laboratory Medicine.
Dr Alexander Haliassos
MD, PhD, EurSpLM
External Quality Assessment (EQA) schemes used to address only the analytical procedures of the medical laboratories. It is important to consider that every EQA scheme introduces some limitations and that it is not appropriate to use them as the sole means of evaluating laboratory quality.
They provide scientific evidence of laboratory competence for Patients, Accrediting Bodies, and Regulatory Agencies, and serve as a unique source of information that is not obtainable in other ways.
Computer science defines Artificial intelligence (AI) research as the study of “intelligent agents“. The Artificial intelligence, or machine intelligence, is intelligence demonstrated by machines, in contrast to the natural intelligence displayed by humans. Intelligent agent is any device that perceives its environment and takes actions that maximize its chance of successfully achieving its goals. Alternatively, the term artificial intelligence is often used to describe machines (or computers) that mimic “cognitive” functions that humans associate with the human mind, such as “learning” and “problem solving”. Machine capabilities generally classified as AI include successfully understanding human speech, competing at the highest level in strategic game systems, autonomously operating cars, intelligent routing in content delivery networks, and military simulations.
The Artificial intelligence can be used in EQA schemes mainly for the:
But also can be used for the automated and enhanced detection of Errors in EQA testing as the: Non-analytical errors and Analytical errors as the EQA materials can exhibit a matrix effect in the examination system used by a participating laboratory (Non commutable materials) or any other sources of analytical problems from reagents, instruments, test methods, calibrations and calculations.
Internet of things is the interconnection via the Internet of computing devices embedded in everyday objects, enabling them to send and receive data and can be involved in EQA schemes for the efficient Temperature tracking of control materials, the Sample Identification and the detection of Filling levels (reconstitution accuracy of samples).
The use of Artificial intelligence along with Internet of Things technologies in the field of external quality assessment schemes in Laboratory Medicine can:
leading to the improvement of the overall quality of participating laboratories by empowering their staff and giving them a measurable way of testing their individual proficiency.
Efficacy evaluation of Citrus aurantium, Cistus creticus and Olea europaea leaves extract combination on the lipid profile of individuals with marginally elevated lipid levels.
Natalia Papakonstantinou, Biomedical scientist, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy,
School of Health Sciences, National and Kapodistrian University of Athens, Greece
INTRODUCTION: Two forms of lipids that combine with lipoproteins in plasma are cholesterol and triglycerides. Two major types of cholesterol in plasma are HDL and LDL. The imbalance of these factors can lead to dyslipidemia which involves increased levels of total cholesterol, LDL, and triglycerides and/or decreased levels of HDL. Also, dyslipidemia is highly related to cardiovascular mortality. The main treatment that is administered is statins, but in specific clinical situations non-statin therapies are considered more useful such as flavonoids and polyphenols which decrease the oxidative stress as well as fasting dyslipidemia. Bitter orange, Rock rose and Olive leaves extracts have been highlighted for their antioxidant and lipid- lowering properties in numerous studies.
AIM: The aim of this pilot observational study was to evaluate the synergistic effect of a standardized, rich in polyphenols and flavonoids food supplement containing a blend of Citrus aurantium, Olea europaea leaf, and Cistus creticus extracts, chromium, and vitamin B complex, on its potential to lower cardiovascular risk.
MATERIALS AND METHODS: In this study, 20 individuals with mild dyslipidemia were treated with two capsules daily for 12 weeks. For statistical analysis IBM SPSS software was used.
RESULTS: The rate of triglycerides at 12 weeks was significantly decreased. Although there was no statistically significant difference in LDL, HDL, or total cholesterol, there was a tendency for improvement in their rates.
DISCUSSION: The findings support a significant decrease in triglycerides and an increase in HDL, promoting further evaluation of this supplement to a larger study population.
FREQUENCY DISTRIBUTION STUDY OF POLYMORPHISMS
rs1799963, rs6025, rs1801133, rs1801131
ASSOCIATED WITH THROMBOPHILIA
Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Greece
INTRODUCTION Thrombophilia is a medical state characterized by an increased propensity to develop venous thromboembolic disease due to genetic, acquired or combination of these factors. It’s important to note that thrombophilia is not a disease, but rather a risk factor for thrombosis. Genetic polymorphisms such as rs1799963 in the prothrombin gene, rs6025 in the factor v-leiden gene and rs1801133 and rs1801131 in the MTHFR gene may be linked to inherited thrombophilia.
PURPOSE The objective of this study is to ascertain the distribution frequency of these polymorphisms within a Caucasian sample from Southeastern Europe. The relationship between allele frequency and gender was examined. The findings were also set against other European populations for comparison.
METHODS The research involved 860 volunteers from the southeastern Caucasian population, both men and women. DNA was extracted from whole blood samples of these individuals, whose ages ranged from 18 to 89 years. Genotyping was performed using Real time PCR. The study focused on analyzing the genotype and allele frequency distribution of these polymorphisms. Statistical analysis was conducted to the data results.
RESULTS AND DISCUSSION The findings indicated that there is no statistically significant difference in the allelic distribution of all the studied polymorphisms between male and female volunteers. These results align with previous research on the frequency distribution of these polymorphisms. In this study, for the polymorphisms rs1799963 and rs6025 most of the volunteers were homozygous for the normal allele, indicating a low likelihood of thrombosis. Regarding MTHFR mutations, this study suggests higher prevalence in the southern Caucasian subpopulation, but their association with thrombosis risk requires further investigation.
FREQUENCY DISTRIBUTION STUDY OF POLYMORPHIMS rs1799752, rs699, rs4762, rs1800562 ASSOCIATED WITH HEART FAILURE OCCURRENCE
Christina Ioannou, Panagiotis Tradalis, Annia Tsolakou, Dr. Nikolaos Drakoulis
Heart failure is the pathological entity in which the heart is unable to maintain sufficient cardiac output to irrigate tissues due to systolic or diastolic dysfunction. Gene variants such as rs1799752 of ACE gene, rs699 and rs4762 of AGT gene, rs1800562 of HFE have been shown to be associated with the predisposition and therapeutic response of heart failure.
Through this study we aim to study the frequency distribution of these polymorphisms in a sample of southeastern Caucasians and then compare the findings with data from other populations. In addition, the risk of heart failure from the cumulative effect of the genes is determined. The aim of this study is to highlight the role of gene variants involved in the process of developing or treating heart failure, in the context of individualized treatment of heart failure, in different population groups. Samples were collected and studied from 1084 southeastern Caucasian volunteers, 457 men and 627 women, aged 1 to 89 years with a mean age of 37 years and a median age of 38. DNA was extracted and followed by genotyping using the Competitive Allele Specific PCR (KASP) method. Finally, the frequencies of genotype and allele distribution in the sample and total genotypic risk (TGS) were calculated, and x2 – analysis was used to investigate the association of alleles and TGS with gender. There is no statistically significant difference in the allelic distribution of the studied polymorphisms between male and female volunteers in the different population groups tested.
Total Genotype Score (TGS) was calculated and correlated with various parameters. Individuals with TGS<50 (5.0%) may have increased genetic risk of heart failure, whereas individuals with TGS>50 (78.5%) may have a decreased genetic risk of heart failure. Individuals with TGS=50 have a normal risk of developing heart failure. For rs1799752 and rs699 polymorphisms individually, it is shown that the South Eastern European Caucasian population appears to be at increased risk of heart failure, whereas for rs4762 and rs1800562 polymorphisms they are at reduced risk. However, in combination, the TGS calculation shows that the Southeast European Caucasian population has a reduced risk of heart failure.
These results are in agreement with previous studies on the frequency of allele distribution of these polymorphisms.
VEGF-A a potential biomarker for personalised medicine in cardiovascular diseases
EA_1122- IGE-PCV, University of Lorraine, Nancy France
Vascular endothelial growth factor–A (VEGF–A) is implicated in angiogenesis, lymphangiogenesis, vascular permeability, and haematopoiesis. It is associated with numerous pathologies including cardiovascular diseases.
We specifically developed an integrative systems biology strategy for clinical improvement of this biomarker.
A high heritability of this trait, 60%, was estimated in the STANISLAS cohort.
We then searched, by a Genome Wide Association Study (GWAS), the VEGF–A genetic variants and the inter-connexions of these biomarkers with other cardiovascular diseases-associated molecules in healthy populations.
The GWAS was performed in 3,527 healthy participants (Framingham Heart Study) and the most significant results (P <5×10-8) were replicated in 1,727 individuals (STANISLAS Family Study, PIVUS study).
Four polymorphisms (rs6921438, rs4416670, rs6993770, rs10738760) explaining ~50% of VEGF–A heritability were identified. A further meta-GWAS identified 6 additional rs explaining VEGF–A levels variability.
VEGF-A related variants, directly or via gene x gene x environment interactions had significant effects on HDL, LDL, TNF-a, IL-6, E selectin and ICAM-1 plasma levels. Furthermore, associations between VEGF–A and blood lipids were assessed in a discovery (n=1,006) and in a replication population (n=1,145) of healthy individuals.
More recently, in a case-control population with atherosclerosis (n=402), we found that VEGF-A related SNPs were associated with leukocyte and muscle telomere length.
Ongoing investigations focus on clinical implementation of the ‘–omics’ determinants of this biomarker.
VEGF-A gene polymorphisms in a female, general population of Southeastern European Caucasian origin and their association with miscarriages
Marianna Bokou, Kiriaki Bougia, Pharmacists, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens
Studying the prevalence of polymorphisms of the vascular endothelial growth factor A (VEGF-A) gene among the general Southeastern European Caucasian female population and their correlation with recurrent miscarriages. Recurrent Pregnancy Loss (RPL), defined as two or more consecutive pregnancy losses before the 20th week of gestation, poses a significant challenge to couples of childbearing age. Genetic factors have emerged as a key area of investigation in understanding RPL, with the Vascular Endothelial Growth Factor A (VEGFA) gene garnering attention for its role in pregnancy-related angiogenesis. This study examined the frequency and the impact of three specific Single Nucleotide Polymorphisms (SNPs) (rs2010963, rs1570360, rs699947) of the gene encoding the VEGFA protein on RPL within 407 Southeast European Caucasian (SEC) females, while comparing our findings with existing data from other populations. For the rs699947 variant, despite the presence of the mutant allele A, there was no correlation in increasing the risk of RPL in SEC women, consistent with existing literature. Conversely, for the rs1570360, SEC women carrying the mutant allele A exhibited a potentially heightened risk of RPL, aligning with previous research. Lastly, for the rs2010360, SEC women with the mutant allele C faced an elevated risk of RPL, despite some inconsistencies in existing literature. This research sheds valuable light on the role of VEGFA gene polymorphisms in RPL within the SEC population. These findings contribute to our understanding of the intricate factors involved in recurrent pregnancy loss and hold the potential to guide future research and interventions in this crucial field.
The effect of COL1A1, MMP1 and VDR genes on skin aging
Angeliki Asimakopoulou, Chemist, Pharmacist, MSc, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens
Skin aging is classified into two types: intrinsic and extrinsic aging. Extrinsic aging is accelerated by environmental factors including ultraviolet (UV) radiation, ambient pollutants, and smoking. Intrinsic aging is described as a result of genetic factors. The aim of this study was to evaluate the contribution of COL1A1 (rs1800012), MMP1 (rs1799750) and VDR (rs2228570, rs1544410, rs731236) genes on skin aging. A total of 735 volunteers of Southeastern European Caucasian (SEC) ancestry were recruited, of which 360 are men and 375 are women aged between 18 and 85. For DNA extraction, buccal epithelial cells were collected from each volunteer, using buccal swabs. Competitive allele specific PCR was used for DNA amplification. The results from SEC population were statistically processed and compared with the allele frequency and genotype distribution of American, non-SEC European, African, and Asian populations. We found that in general the genotype distribution of the polymorphisms rs1800012, rs1799750, rs2228570, rs1544410, rs731236 of the SEC population is similar to that of the non-SEC European population. It is documented that the rs1800012 of COL1A1 is involved in the type I collagen turnover and rs1799750 of MMP1 is connected with skin elasticity. Also, rs2228570 (T:C), and rs1544410 (AG+AA) are associated with susceptibility to melanoma. The heterozygous genotype Tt of rs731236 is associated with protection of developing solar keratosis. In conclusion, individuals carrying the T:T genotype of rs1800012 are expected to have an increased predisposition to reduced collagen remodeling in their skin. The (2G:2G) genotype of rs1799750 is related with increased expression of MMP1, which leads to higher levels or rates of collagen breakdown, resulting in loss of skin elasticity. More studies are needed for the effect of VDR SNPs on skin aging.
THE INFLUENCE OF GENETICS OF CYTOKINE DIVERSITY IN PATHOGENESIS OF PSORIASIS
Ioanna Chatzianastasiadou, Pharmacist, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens
Psoriasis is a chronic autoimmune disease characterized by skin inflammation and is known to have a strong genetic component. This study aimed to investigate the association between specific genetic polymorphisms and psoriasis susceptibility, as well as their potential impact on disease characteristics. The primary focus was on the IL-23R, IL-12B, Interleukin 6 (IL-6), and Interleukin 23 (IL-23) genes. A case-control study design was employed, including 102 unrelated psoriasis patients and 136 healthy controls. The patients were diagnosed with different types and severities of psoriasis, and their demographic and clinical data were collected. The results revealed a significant association between the rs1004819 polymorphism of the IL-23 gene and psoriasis susceptibility. Patients carrying the CT and TT genotypes showed a significantly higher risk of developing psoriasis. Additionally, the IL-6 gene polymorphism (rs1800795) did not demonstrate a statistically significant association with psoriasis. Furthermore, correlations were explored between genetic polymorphisms and various disease characteristics, such as psoriatic arthritis, onychia psoriatic, and disease onset.
VEGF gene polymorphisms association with diabetic foot ulcers
Marilena Andreopoulou Pharmacist MSc, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens
Diabetes is a serious condition that can cause life-threatening complications affecting multiple organs and systems if not properly managed. Diabetic foot ulcers represent significant complications of diabetes that may lead to lower extremity amputations. One critical protein involved in wound healing is vascular endothelial growth factor (VEGF), which stimulates angiogenesis and promotes tissue repair. However, several studies have reported that VEGFA expression and function can be influenced by genetic variations, including polymorphisms in the VEGFA gene. For instance, the A allele of rs1570360 has been associated with decreased VEGF expression and activity, which could result in impaired angiogenesis and delayed wound healing. Similarly, the A allele of rs699947 has been linked with reduced VEGFA expression and the C allele of rs2010963 has been associated with increased VEGF expression and activity which can result in faster wound healing. To investigate the potential impact of VEGFA polymorphisms on diabetic foot ulcer healing, a study was conducted in a total population of 70 individuals with diabetic foot ulcers. Blood samples were collected, and genomic DNA was extracted from peripheral blood leukocytes. The VEGFA polymorphisms rs1570360, rs699947, and rs2010963 were genotyped using Real- Time Polymerase Chain Reaction. For each patient, data on the area of diabetic foot ulcers have been collected 1,3 and 6 months after the initial appointment. Finally,the different VEGFA polymorphisms and their combination were correlated with the extent of diabetic foot ulcer healing. For data evaluation SPSS was used. Results showed for the rs1570360 polymorphism that 8.6% of individuals are homozygous for the mutation, 42.9% are heterozygous and 48,6% are homozygous for the wild type. For the rs2010963 polymorphism, 17,1% are homozygous for the mutation, 54,3% are heterozygous and 28,6% are homozygous for the wild type. Finally, for the rs699947 polymorphism, 14,3% are homozygous for the mutation, 51,4% are heterozygous and 34,3% are homozygous for the wild type. The AG/GG/AA genotype combination represents the quickest mean foot ulcer healing time haplotype, followed by AG/GG/CC and CG/CC/CC. Fifteen patients (21,43%) carried the AG/GG/AA haplotype which is the quickest mean foot ucler healing time haplotype, ten patients(14,27%) carried the AG/GG/AA, 3 patients (4,3%) carried the GG/CG/CC and 8 patients carried the GG/CC/CC haplotype. The probably dominant wild type G allele of rs1570360 and C allele of rs6999470 and the mutant C allele of rs2010963 may accelerate wound healing, providing better oxygenation of the wound, thus optimizing ulcer healing time. Understanding the effects of VEGF polymorphisms on the healing of diabetic foot ulcers may have significant implications for developing personalized therapies for individuals with diabetes.
Extemporaneous preparations as a valuable tool for precision medicine
Dr. Andreas Vitsos, Ass. Prof Dr. Paraskevas Dallas
National and Kapodistrian University of, Athens, School of Pharmacy, Department of Pharmaceutical Technology, Panepistimioupolis Zografou, Athens, Greece.
Precision medicine has revolutionized healthcare by tailoring medical treatment to individual patients based on their genetic, environmental, and lifestyle factors. In the quest for optimized therapeutic outcomes, a significant component often overlooked is the role of extemporaneous preparations. These preparations, encompassing the on-demand compounding and customization of pharmaceuticals, hold immense potential as a vital tool for precision medicine. This presentation explores the critical nexus between extemporaneous preparations and precision medicine, highlighting their role in personalizing treatment regimens for a wide range of patient populations.
The evolving landscape of precision medicine requires a comprehensive understanding of individual patient needs, and extemporaneous preparations offer the flexibility to formulate precise drug dosages, combinations, and delivery methods that align with a patient’s unique genomic and clinical profile. These preparations empower healthcare providers to address the specific requirements of patients who do not respond optimally to commercially available medications, such as pediatric, geriatric and rare disease populations.
We will delve into the key considerations and challenges associated with extemporaneous preparations in the context of precision medicine, including regulatory and quality assurance aspects, safety, and the integration of advanced technologies. Moreover, this presentation will showcase real-world examples of successful extemporaneous preparations, underscoring their impact on improving therapeutic outcomes, minimizing adverse effects, and enhancing patient adherence.
As the field of precision medicine continues to advance, this presentation underscores the importance of recognizing extemporaneous preparations as an invaluable tool in the pursuit of truly personalized healthcare. By embracing and harnessing the potential of extemporaneous preparations, we can bridge the gap between standardized medicine and precision medicine, ultimately contributing to better patient care and clinical outcomes.
Keywords: Extemporaneous Preparations, Precision Medicine, Personalized Healthcare, Therapeutic Outcomes, Pharmacogenomics, Pharmaceutical Compounding, Patient-Centric Care, Drug Customization.
Unlocking RNA viruses’ secret targets
Dr. Urania Georgopoulou, Research Director, Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece
Human innate cellular defense pathways have evolved to sense and eliminate pathogens including viruses that are considered to be of the most dangerous. Their simple structure makes the identification of RNA viral invasion a difficult task for cells. Viral genomes are one of the strongest and reliable early identifiers of infection and RNA sensing is the central mechanism in innate immunity and is crucial for triggering an appropriate antiviral response. The repertoire of viral evasion strategies is extremely wide, ranging from masking pathogenic RNA through manipulating host epigenetic routes to deceive host cellular RNA degrading enzymes, and hijacking the most basic cellular immunometabolic pathways. In this review, we aim to dissect RNA viruses’ secret targets such as, Lysine-specific demethylase 1 (LSD1) which is an epigenetic controller of critical cellular functions crucial for antiviral immune defenses, as well as extracellular vesicles mediation, on the establishment and progression of viral diseases. We propose that understanding the fate of viral RNA upon infection and detailing the molecular mechanisms behind virus-host interactions, may be helpful for developing more effective antiviral strategies.
Human Genetic Susceptibility Factors to COVID-19 Severity: A literature review
Ioannis Axiotis – Zacharias, Maria Zacharioudaki
The rapid spread of the new coronavirus SARS-CoV-2, which causes the disease COVID-19, has triggered an unprecedented global public health crisis. SARS-CoV-2 has turned the scientific community towards a massive and coordinated effort to investigate both the virus itself and the disease it causes, with the aim of combating it. The individual’s genetic makeup is well known to have an impact on susceptibility to infection and disease, which can be either protective or deleterious. This study focuses on collecting the most significant findings from current literature, regarding genetic polymorphisms that appear to influence both susceptibility to infection from SARS-CoV-2 and disease severity, with the aim of outlining a genetic profile to help interpret the variability of response to infection and illness. We conducted a comprehensive search from January 2020 to July 2021 across multiple databases, including PubMed, Scopus, Google Scholar, and Science Direct, to identify single nucleotide polymorphisms (SNPs) with a Minor Allele Frequency (MAF) greater than 1% that are investigated for their potential impact on susceptibility to infection and course of disease. Data extraction and analysis were performed using Microsoft Excel. Additionally, genetic information from databases such as Ensembl, GeneCards, dbSNP, gnomAD, and the Allele Frequency Net Database was integrated to enhance our understanding of the identified SNPs and their potential implications. There was no restriction in terms of study design; hence, both cohort and in-silico studies were included. The identified polymorphisms were classified into two broad categories: those that are believed to impact susceptibility to infection and those that are believed to impact the disease course. Regardless of their effect mechanism, the identified SNPs varied in terms of type (missense, intron) and effect, as some seemed to have a protective effect, while others a deleterious one. Polymorphisms belonging to the first category mainly regarded the genetic locus of ACE2, TMPRSS2/MX1 and PCSK3. Some deleterious SNPs from these loci are rs2106806, rs6629110, rs2285666 and rs469390. Protective SNPs were also identified for these 3 genes (rs35803318, rs464397, rs2070788, rs383510, rs4702). Of the SNPs with an impact on disease course, those on the genetic loci of IFIH1, IFITM3, CCR5 and HLA are suggestive of altering the immune responsiveness to the virus. On these locus, some SNPs (rs6598045, rs12252) were found to be deleterious while others (rs1990760, rs333) seemed to have a protective effect. Evidence indicates that SNPs on the genetic loci of ACE1, GC, DBP, SIGMAR1, DPP4, APOE, BIN1, LZTFL1 and ABO may also influence the disease course indirectly. Various SNPs on the aforementioned genetic loci have been suggested to have a direct or indirect impact on susceptibility to infection, COVID-19 complications and mortality risk. On the other hand, a few SNPs on the same genetic locus seem to have a protective effect. These findings may promote the development of optimized clinical management of patients under the scope of personalized medicine; however, a subsequent systematic literature review would be necessary to validate and evaluate the robustness of this preliminary evidence.
Association between consumption of antibiotics, infection control interventions and Clostridioides difficile infections: Analysis of six-year time-series data in a tertiary-care hospital in Greece
Dr. Amalia Papanikolopoulou, MD, PhD, Resident Doctor of Internal Medicine at “Sotiria” General Hospital of Chest Diseases, National and Kapodistrian University of Athens
Background: To investigate the association between Clostridioides difficile infection (CDI), antibiotic use, and infection control interventions, during an antibiotic stewardship program (ASP) implemented in a tertiary-care hospital in Greece from 2013 to 2018.
Methods: Analysis was applied for the following monthly indices: 1. consumption of antibiotics; 2. use of hand hygiene disinfectant solutions; 3. percentage of isolations of patients either with multidrug-resistant (MDR) bacteria, or CDI, or admitted from another hospital; and 4. percentage of patients with CDI divided into two groups: community-acquired CDI (CACDI) and hospital-associated CDI (HACDI) (onset <72 h and >72 h after admission, respectively).
Results: During the study, a significant reduction in CACDI rate from 0.3%/admissions [95% CI 0.1-0.6] to 0.1%/admissions [95%CI 0.0-0.3] (p-value=0.035) was observed in adults ICU, while CDI rates were stable in the rest of the hospital. Antibiotic consumption showed a significant reduction in total hospital, from 91.7DDDs [95%CI 89.7-93.7] to 80.1DDDs [95%CI 79.1-81.1] (p-value<0.001), except adults ICU. Non-advanced antibiotics correlated with decreased CDI rates in Adults Clinic Departments and ICU. Isolation of patients one and two months earlier correlated with decreased CACDI rates per 20% [95%CI 0.64-1.00, p- value=0.046] and HACDI per 23% [95%CI 0.60-1.00, p-value=0.050] in Adults Clinic Departments. Consumption of disinfectant solutions current month correlated with decreased rate for CACDI per 33% [95%CI 0.49-0.91, p-value=0.011] and HACDI per 38% [95%CI 0.40-0.98, p-value=0.040] in total Hospital Clinics.
Conclusion: Rational antibiotic prescribing during ASP along with multipronged intervention strategy focusing on hand hygiene and patient isolation measures prevent and control CDI outbreaks in the hospital setting
Study Of Single Nucleotide Polymorphisms In Patients With Multiple Sclerosis
Stavrianna Pariou, BSc Chemist, MSc Pharmacy, Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Greece
Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease characterized by neuronal demyelination affecting the function of the Central Nervous System (CNS). The etiology of MS remains unknown, although current scientific data suggest an association between environmental factors and common genetic variants, which may determine susceptibility to the disease. At least 200 Single Nucleotide Polymorphisms (SNPs) have been identified, which appear to be associated with the risk of MS. In the present study, in which 200 volunteer patients with MS and 207 volunteer controls from the general population of Southeast European Caucasian origin took part, the incidence of a total of three single nucleotide polymorphisms (SNPs) in genes (1) rs1800795-IL6, (2) rs1800629-TNFa, (3) rs6265-BDNF associated with inflammation, were investigated in order to examine their association or not with the disease onset. The participants’ blood samples were collected and the genetic material (DNA) was isolated. The identification of the genotypes for the under investigation genetic polymorphisms was conducted by KASP PCR method and then the statistical analysis of the results was carried out. The statistical analysis of the results was divided into two parts. A statistical analysis of the distribution of genotypes for the studied polymorphisms was first performed between the patient and control populations in which no statistically significant effect has been shown (p value>0.05). Subsequent analysis in subgroups of patients showed a statistically significant difference in the distribution of genotypes between patients who had motor problems as a disease onset symptom compared to patients without motor problems as a disease onset symptom for the rs1800795 polymorphism in IL6 gene. Further studies, with a larger sample size, are required to confirm the findings of the present study and to provide additional information about the role of the studied polymorphisms in the occurrence of MS, taking into account interactions between other related genes and between related genes and the environment.
Genetic polymorphisms in COMT, BDNF KAI ANKK1 genes in the treatment of patients with lithium-containing preparations
Antria Michael, MSc, Clinical Pharmacology & Pharmacogenomics Research Group, Department of Pharmacology, Frederick University, Cyprus
Lithium and specifically lithium salts are widely used as mood stabilizers, mainly in psychiatric diseases such as bipolar disorder. As proved, bipolar disorder is an inherited disease. The manifestation of the disorder and the appearance of affective disorders are closely related to the inheritance of several genes that exhibit polymorphisms and are responsible for the specific disorder. In this review a brief description of the definition of genetic polymorphisms and their importance in the treatment of diseases and in the development of new targeted therapies is provided. The following is a historical review concerning lithium, a description of the mechanism of action, the pharmacokinetic properties, the therapeutic indications and the dosage of lithium. Also, the properties of three genes (COMT, BDNF and ANKK1), as well as the main polymorphisms of a nucleotide (SNPs) that occur in them, are described in detail. The purpose of this paper was to study the role of genetic polymorphisms in COMT, BDNF and ANKK1 genes in the treatment of patients with lithium-containing formulations. A literature review was conducted on the electronic databases and datas on the frequency of distribution of polymorphisms in different populations came from the’ 1000 Genomes project ‘ and were analyzed in detail. Research shows that the correlation between the polymorphisms of these genes and the response to lithium treatment is inconsistent.
While studies show a correlation between genetic variants mainly of the COMT and BDNF gene and response to lithium therapy for patients with bipolar disorder, research remains inconclusive regarding recommendations to be made regarding therapeutic interventions based on the results of pharmacogenetic trials.
Single nucleotide polymorphisms in vitamin D receptor (VDR) gene and Alzheimer’s disease in the Greek population.
Dr. Timos Dimitrakis, Pharmacist MSc, MBA, PhD. University General Hospital “ATTIKON” National & Kapodistrian University of Athens
Vitamin D has been studied extensively in the past few years in order to describe its effects in neurodegenerative disorders and Alzheimer’s disease (AD). Data from in vitro and in vivo AD experimental models have provided a lot of information suggesting a beneficial role of vitamin D for neural cells in regards to neuroprotection, neuroinflammation, amyloid-β (Aβ) clearance and neurotoxicity. In parallel a number of clinical studies have described the association between low blood levels of 25(OH)D3 and dementia or AD. Clinical studies have reported lower levels of 25(OH)D3 in AD patients and lower performance in cognitive tests suggesting and increased risk for dementia or AD when vitamin D insufficiency is present. In parallel a small number of studies have provided information regarding the key protein that mediates vitamin D effects, the vitamin D receptor (VDR) and the respective gene (VDR). These studies have been focused on the single nucleotide polymorphisms (SNPs) and haplotypes of VDR gene and have reported potential associations with AD. However, the reported so far associations of AD with VDR SNPs and haplotypes were not consistent and seem to be highly affected by the ethnic population studied. In the present article the association of specific VDR SNPs and haplotypes with late onset Alzheimer’s disease (LOAD) are presented from two studies conducted with samples from the Greek population belonging to the Southeastern European Caucasian (SEC) population. SNPs that have been studied were TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570). The TaqI TT genotype has been associated with 1.86‑fold higher risk for AD in the SEC population (OR, 1.86; 95% CI, 1.04‑3.32; P=0.035), while the TaqI C allele may act protectively, with a 46% lower risk of developing the disease (OR, 0.54; 95% CI, 0.30‑0.96; P=0.035). The TAC (TaqI, BsmI and FokI) haplotype was associated with an ~6‑fold greater risk of developing AD (OR, 6.19; 95% CI, 1.91‑20.13; P=0.0028) while the CAC (TaqI, BsmI and FokI) haplotype was found to be associated with a 53% lower risk of developing AD (OR,0.47; 95% CI, 0.23‑0.96; P=0.04) in the SEC cohort studied. Moreover, female SEC subjects carrying the TAC haplotype had a ~9‑fold greater risk of developing AD in comparison to female control subjects (OR, 9.27; 95% CI, 1.86‑46.28; P<0.05). Overall, it has been concluded that vitamin D utilization in the SEC population is negatively affected by specific VDR SNPs increasing the risk for LOAD.
Small extracellular vesicles encapsulating muscle-specific miRNAs in Myotonic Dystrophy type 1
Small extracellular vesicles (small EVs) are membranous nanosized particles naturally secreted by various cell types and tissues. They have been detected in most of the biological fluids, like serum and urine, carrying proteins, lipids, nucleic acids from their host cells. Small EVs are currently gaining an emerging interesting for their use for gene therapy and clinical biomarkers. Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adults primarily affecting skeletal muscle tissue. In particular, DM1 is characterized by muscle wasting and weakness. We have reported that small EVs isolated from serum samples of DM1 patients contain elevated levels of the four muscle-specific miRNAs, miR-1, miR-133a, miR-133b, and miR-206, compared to healthy participants. Importantly, the levels of the four muscle-specific miRNAs encapsulated within the small EVs were found to be associated with the progression of muscle wasting in DM1 patients. Furthermore, we showed that the levels of the four muscle-specific miRNAs were also elevated in small EVs circulating in the serum of the DM1 animal model, DMSXL mice. We next investigated the possibility that muscle tissues communicate between them through small EVs and the delivery of their miRNA cargo. We showed that downregulation of miR-133a and miR-133b in the tibialis anterior (TA) skeletal muscle of mice resulted in reduction of the levels of the two miRNAs in muscle-derived small EVs and in small EVs circulating in the blood circulation. Furthermore, the levels of the two miRNAs were found to be reduced in other skeletal muscles of close proximity. All the above results suggest that small EVs have a role to play in the communication between tissues and in the pathogenesis of DM1. Moreover, they could be developed in such a way to identify useful clinical biomarkers and therapeutic targets for the disease.
CEO and Medical Director
The Cyprus Institute of Neurology & Genetics
Exploiting interrelated genomic, biochemical, nutritional, and pathophysiological data to optimize athletic performance.
Department of Forensic Sciences and Toxicology, School of Medicine, University of Crete, 71003 Heraklion, Greece
This work presents a multidimensional approach to enhance athletic performance through the integration of innovative and interrelated methodologies. In this respect, telomere dynamics, genotyping/phenotype analysis, metabolomics, biochemical tests, essential elements quantitation, echocardiography, and burnout testing are jointly employed to provide a comprehensive assessment of athlete health wellness and longevity. Telomere analysis as a biomarker of effect offers novel insights into cellular dynamics, aging, and adaptability, elucidating the impact of training on cellular well-being. Genotype/phenotype analysis reveals genetic variances related to athletic performance (i.e., strength, flexibility, endurance, power, VO2max), injury predisposition, and recovery needs, facilitating the customization of training programs and interventions. Metabolomics provides a detailed overview of low-molecular weight metabolites, revealing pivotal metabolic pathways and responses to exercise. Biochemical tests critically evaluate markers associated with energy metabolism, inflammation, and recovery, offering crucial information for tailored performance optimization. Essential elements quantitation assesses micronutrient status, a vital factor for sustained peak performance. Echocardiography enables assessments of cardiac structure and function, fine-tuning cardiovascular performance for superior athletic output and for early detection of underlying abnormalities. Burnout testing evaluates psychological stress, fatigue levels, and readiness for optimal performance, ensuring holistic well-being. By integrating these advanced scientific methodologies, this approach yields a comprehensive understanding of athlete health. This, in turn, informs personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness. Through evidence-based, personalized strategies, this rigorous scientific framework holds significant promise in advancing athletic performance and longevity, propelling the field of sports performance optimization, and unlocking athletic excellence.
Athlegenetics: Athletic characteristics and musculoskeletal diseases.
Athlegenetics, an emerging field in sports sciences, explores the intricate interplay between genetic variations, phenotypic traits, and athletic performance. Utilizing the advancements in systems biology, researchers investigate how genetic variants, especially single nucleotide polymorphisms (SNPs), play a pivotal role in shaping endurance, strength, power, and other athletic attributes. Genotyping and phenotypic analysis in sports medicine have unveiled over 250 potential genetic markers associated with endurance, strength, and power. Personalized genetic profiles empower athletes by highlighting strengths and pinpointing areas for improvement, guiding customized training and recovery plans.
Furthermore, specific genetic markers are associated with an increased susceptibility to musculoskeletal diseases like osteoarthritis and osteoporosis, shedding light on the genetic underpinnings of these conditions. Despite challenges, particularly in understanding gene-environment interactions, this integrated methodology promises personalized interventions, ranging from optimizing athletic performance to injury prevention strategies.
To sum up, the convergence between the fields of genetics, sports science, and personalized medicine is reshaping our understanding of athletic capabilities and health optimization. Athlegenetics paves the way for a future where individualized interventions, based on genetic insights, promote not only peak athletic performance but also long-term musculoskeletal health.
The importance of telomeres and telomerase enzyme activity in athletes.
Telomeres are repetitive DNA sequences at the end of linear chromosomes which along with associated proteins (shelterin complex) form protective structures at chromosome ends, preserving genetic integrity and protecting chromosomes from fusion or degradation. With each cell division, telomeres shorten, eventually leading to cellular senescence or apoptosis when telomeric attrition reaches the Hayflick limit. Lifestyle factors and oxidative stress influence the rate of telomere shortening, contributing to an individual’s biological age, which may deviate from their chronological age. Telomerase is an RNA-dependent DNA polymerase that counteracts telomere shortening and features prominently in maintaining genomic integrity. Telomere analysis, which considers telomere length, rate of attrition, and telomerase activity can provide insights into cellular aging and adaptive responses. Hence, telomere characteristics can serve as a biomarker of effect considering the impact of environmental factors and lifestyle in overall wellness. For example, physical exercise has been associated with increased telomerase activity and longer telomeres, underscoring their potential significance in monitoring cellular aging, and indicating implications for improved performance and longevity in sports. Athletes typically exhibit longer telomeres, indicating improved tolerance in oxidative stress and inflammation, along with increased shelterin expression and telomerase activity. Therefore, telomere dynamics offer a novel approach to analyse athletes’ cellular health and longevity. As further research uncovers innovative approaches in athletes, the incorporation of telomere analysis can provide personalized strategies to optimize training, recovery, and injury prevention serving as a valuable tool to predict athletes’ longevity in their sport.
METABOLOMICS, MITOCHONDRIA AND CELLULAR ENERGY: THE ROLE OF DIET AND EXERCISE
Dimitris Tsoukalas1,2, Evangelia Sarandi2,3, Aristidis Tsatsakis3
1European Institute of Molecular Medicine, 00198 Rome, Italy; email@example.com
2Metabolomic Medicine, Health Clinics for Autoimmune and Chronic Diseases, 10674 Athens, Greece
3Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece; firstname.lastname@example.org, email@example.com
Mitochondria are responsible for cellular energy production, redox and calcium homeostasis and cellular apoptosis. Complex mechanisms regulate mitochondrial activity to maintain metabolic and cellular homeostasis. Dysfunctional mitochondria are a major contributing factor in aging and associated diseases due to increased oxidative stress and tissue inflammation.
Hormesis, exposure to low-dose stressful triggers (e.g. moderate exercise), and nutrient fluctuations promote adaptative responses that lead to mitochondrial biogenesis and improved capacity. However, during intense exercise, managing metabolic shifts is crucial to avoid excessive production of ROS and toxic byproducts while also meeting the energy and macro/micronutrient demands. In prolonged exercise-driven stress, cortisol and adrenaline secretion promote protein catabolism, mitochondrial dysfunction and glucose intolerance. Circulating factors that are secreted in response to unresolved stress (metabolic or mechanic) upregulate pro-inflammatory signaling pathways, increasing the risk for disease. Monitoring these metabolic events is crucial for the early detection and management of mitochondrial and cellular impairment and their complications. Quantification of metabolites through metabolomics provides a personalized map to evaluate metabolic health, mitochondrial function and micronutrient requirements. Targeted restoration of identified metabolic blocks can improve the efficacy and capacity of mitochondria while promoting biogenesis and clearance of dysfunctional organelles. Ultimately, combinatorial interventions based on personalized metabolic requirements can improve the body’s performance and cellular energy levels, thereby increasing cells’ capacity to withstand greater stress.