Nutrigenomics: a controversy

Nutrigenomics is an emerging science which investigates a certain area of nutrition that uses molecular tools to search access and understand the several responses obtained through a certain diet applied between individual and population groups. The increased need for the use of personalised nutrition in patients is increasing and research is being made on its possible effects. However, research on nutrigenomics and in particular, obesity is still ongoing. Following a current metanalysis on thirty-eight nutrigenomics genes, it seems that a definite association between the genes usually examined in nutrigenomics testing and several diet-related diseases is lacking, even though there is a limited number of studies associating them. In 2014, literature search results in a great number of studies on several polymorphisms. This heterogeneity could only show the way towards new research aims. Nutrigenomics was born due to the need to move from Epidemiology and Physiology to Molecular Biology and Genetics. Currently, there are steps that need to be considered in order for nutrigenomics to be applied: the genes, the gene/protein network, and the strategy towards the determination of the nutrients' influence on gene/protein expression. It is certainly an interesting evolving science with many areas to be investigated further and from different perspectives, as it involves ethics, medicine, genetics and nutritio

Δημιουργική λογιστική στην Ελλάδα στα χρόνια των μνημονίων.

Είναι κοινά αποδεκτό ότι το φαινόμενο της παραποίησης των οικονομικών καταστάσεων έχει λάβει τα τελευταία χρόνια ανησυχητικές διαστάσεις, αποτελώντας πλέον, το σύγχρονο πρόβλημα της διεθνούς οικονομίας. Ως εκ τούτου, όλο και περισσότερα κρούσματα λογιστικών σκανδάλων και ατασθαλιών έρχονται στο προσκήνιο, τα οποία κλονίζουν την παγκόσμια αγορά. Στη χρήση, λοιπόν, της «δημιουργικής λογιστικής» οφείλεται η διαστρεβλωμένη εικόνα των οικονομικών δεδομένων, η οποία έχει αρνητικές συνέπειες για την ίδια την επιχείρηση μακροπρόθεσμα, καθώς δημιουργείται ένα κλίμα δυσπιστίας και εξαπάτησης στα εμπλεκόμενα μέρη και περισσότερο στους επενδυτές. Οι επενδυτές δυσκολεύονται να διακρίνουν αν τα δημοσιευμένα οικονομικά στοιχεία απεικονίζουν ή όχι την πραγματική οικονομική θέση της επιχείρησης. Η λανθασμένη αποτύπωση των χρηματοοικονομικών καταστάσεων και της απόδοσης της επιχείρησης έχει όμως και σοβαρές κοινωνικές επιπτώσεις, καθώς παραπλανεί την κοινωνία και μεταφέρει πλούτο από τους μικροεπενδυτές στους μεγαλομετόχους . Αυτή η διενέργεια των οικονομικών ατασθαλιών έχει ως στόχο να εξυπηρετήσει τα συμφέροντα της κάθε οικονομικής οντότητας και των άμεσα ενδιαφερομένων μερών. Η οικονομική κρίση, οι αυξανόμενες καθημερινές υποχρεώσεις των οικονομικών μονάδων καθώς και οι συνεχείς απαιτήσεις της κεφαλαιαγοράς, έχουν οδηγήσει πολλές φορές τις επιχειρήσεις, τόσο στη Ελλάδα όσο και στον υπόλοιπο κόσμο, σε εφαρμογή πρακτικών και μεθόδων που συμβάλλουν στην παρουσίαση μιας παραπλανητικής εικόνας σε σχέση με την αληθινή οικονομική θέση της επιχείρησης. Είναι αναγκαίο κατά συνέπεια, να πραγματοποιείται έλεγχος από τους αρμόδιους ελεγκτές των οικονομικών οντοτήτων, προκειμένου να εντοπιστούν, να αποκαλυφθούν και να αντιμετωπιστούν τα φαινόμενα της λογιστικής απάτης. Συνεπώς, κρίνεται απαραίτητο ένα αποτελεσματικό σύστημα εσωτερικού και εξωτερικού ελέγχου, για την πρόληψη τυχόν εκούσιων ή ακούσιων λαθών στις οικονομικές καταστάσεις και τη μείωση της παρεχόμενης δόλιας χρηματοοικονομικής πληροφόρησης προς τους χρήστες των καταστάσεων. Στην παρούσα διπλωματική εργασία περιγράφεται το φαινόμενο της «ωραιοποίησης» των λογιστικών καταστάσεων, που είναι ιδιαίτερα διαδεδομένο και έχει απασχολήσει έντονα μεγάλο αριθμό ερευνητών, οικονομικών αναλυτών, επαγγελματιών της αγοράς, επενδυτών κ.ά. Εκτός από την εννοιολογική οριοθέτηση του ζητήματος της Δημιουργικής Λογιστικής, στα πλαίσια της εργασίας αυτής, συζητείται ειδικότερα η παραποίηση των οικονομικών καταστάσεων κατά τη διάρκεια της οικονομικής κρίσης στην Ελλάδα και της επιβολής των μνημονίων. Μελετώνται επίσης οι οικονομικές καταστάσεις μη εισηγμένων εταιρειών στο Χρηματιστήριο Αξιών Αθηνών του κλάδου των supermarket, προκειμένου να εντοπίσουμε επιχειρήσεις που ενδεχομένως να έχουν παραποιήσει τα οικονομικά τους στοιχεία κατά την προαναφερόμενη περίοδο.It is commonly accepted that the phenomenon of counterfeiting of financial statements has received enormous dimensions in recent years, becoming the modern problem of the international economy. As a result, more and more cases of accounting scandals and irregularities are emerging to the foreground, which unsettle the global market. Therefore, the use of "creative accounting" is due to the distorted report of economic data, which has negative implications on the business itself in the long run, as it creates a climate of mistrust and deception for the parties involved and more for the investors. The investors have great difficulty distinguishing whether the published economic data show or not the real financial position of the firm. However, the misrepresentation of the financial statements and the false depiction of the performance of the business has also serious social impacts, because these distorted data mislead the society and the wealth is distributed from small investors to large shareholders. The purpose of this financial distortion is to serve the interests of each economic entity and of the parties directly concerned. The economic crisis, the increasing daily obligations of the financial entities, as well as the continuous demands of the capital market, have often led companies, both in Greece and in the rest of the world, to apply practices and methods that contribute to the presentation of a misleading depiction in relation to the actual economic performance of the entities. Consequently, the auditing is necessary to be conducted by the auditors of the firms, in order to identify, detect and deal with the cases of accounting fraud. As a consequence, an effective internal and external control system is required to prevent intentional and unintentional errors in the financial statements and to reduce the deceitful financial information, which is provided to the users of the statements. This dissertation describes the phenomenon of "idealization" of financial statements, which is quite widespread and concerns many people, such as researchers, financial analysts, professionals, investors and others. In this thesis, apart from the conceptual approach of the issue of Creative Accounting, we discuss the phenomenon of misrepresentation of financial statements, during the financial crisis in Greece and the imposition of memorandums. We also study the financial statements of unlisted companies in the Athens Stock Exchange in the super market sector, in order to identify companies that may have distorted their financial information during the aforementioned period

Nutrigenomics 2.0: The Need for Ongoing and Independent Evaluation and Synthesis of Commercial Nutrigenomics Tests' Scientific Knowledge Base for Responsible Innovation

Nutrigenomics is an important strand of precision medicine that examines the bidirectional interactions of the genome and nutritional exposures, and attendant health and disease outcomes. This perspectives article presents the new concept of "Nutrigenomics 2.0," so as to cultivate and catalyze the next generation research and funding priorities for responsible and sustainable knowledge-based innovations. We further contextualize our recent study of the 38 genes included in commercially available nutrigenomics tests, and offer additional context in relation to the 2014 American Academy of Nutrition and Dietetics position. Finally, we make a call in the best interest of the nutrigenomics science community, governments, global society, and commercial nutrigenomics test providers that new evidence evaluation and synthesis platforms are created concerning nutrigenomics tests before they become commercially available. The proposed assessment and synthesis of nutrigenomics data should be carried out on an ongoing dynamic basis with periodic intervals and/or when there is a specific demand for evidence synthesis, and importantly, in ways that are transparent where conflict of interests are disclosed fully by the involved parties, be they scientists, industry, governments, citizens, social scientists, or ethicists. We submit that this will cultivate responsible innovation, and business models that are sustainable, robust, and stand the test of time and context

In vivo characterisation of a therapeutically relevant self-assembling 18 F-labelled β-sheet forming peptide and its hydrogel using positron emission tomography

Positron emission tomography (PET) and fluorescence labelling have been used to assess the pharmacokinetics, biodistribution and eventual fate of a hydrogel-forming nonapeptide, FEFKFEFKK (F9) in healthy mice, using 18F-labelled and fluoresceinisothiocyanate (FITC) - labelled F9 analogues. F9 was site-specifically radiolabelled with 2-[18F]fluoro-3-pyridinecarboxaldehyde ([18F]FPCA) via oxime bond formation. [18F]FPCA-F9 in vivo fate was evaluated both as a solution, following intravenous administration, and as a hydrogel when subcutaneously injected. The behaviour of FITC-F9 hydrogel was assessed following subcutaneous injection. [18F]FPCA-F9 demonstrated high plasma stability and primarily renal excretion; [18F]FPCA-F9 when in solution and injected into the bloodstream displayed prompt bladder uptake (53.4 ± 16.6 SUV at 20 minutes post injection) and rapid renal excretion, whereas [18F]FPCA-F9 hydrogel, formed by co-assembly of [18F]FPCA-F9 monomer with unfunctionalised F9 peptide and injected subcutaneously, showed gradual bladder accumulation of hydrogel fragments (3.8 ± 0.4 SUV at 20 minutes post injection), resulting in slower renal excretion. Gradual disaggregation of the F9 hydrogel from the site of injection was monitored using FITC-F9 hydrogel in healthy mice (60 ± 3 over 96 hours), indicating a biological half-life between 1-4 days. The in vivo characterisation of F9, both as a gel and a solution highlights its potential as a biomaterial

Meta-analysis of genes in commercially available nutrigenomic tests denotes lack of association with dietary intake and nutrient-related pathologies

Nutrigenomics is an emerging discipline that aims to investigate how individual genetic composition correlates with dietary intake, as well as how nutrition influences gene expression. Herein, the fundamental question relates to the value of nutrigenomics testing on the basis of the currently available scientific evidence. A thorough literature search has been conducted in PubMed scientific literature database for nutrigenomics research studies on 38 genes included in nutrigenomics tests provided by various private genetic testing laboratories. Data were subsequently meta-analyzed to identify possible associations between the genes of interest and dietary intake and/or nutrient-related pathologies. Data analysis occurred according to four different models due to data sparsity and inconsistency. Data from 524,592 individuals (361,153 cases and 163,439 controls) in a total of 1,170 entries were obtained. Conflicting findings indicated that there was a great incompatibility regarding the associations (or their absence) identified. No specific-and statistically significant-association was identified for any of the 38 genes of interest. In those cases, where a weak association was demonstrated, evidence was based on a limited number of studies. As solid scientific evidence is currently lacking, commercially available nutrigenomics tests cannot be presently recommended. Notwithstanding, the need for a thorough and continuous nutrigenomics research is evident as it is a highly promising tool towards precision medicine

Variants in TPMT, ITPA, ABCC4 and ABCB1 genes as predictors of 6-mercaptopurine induced toxicity in children with acute lymphoblastic leukemia

Uvod: Akutna limfoblastna leukemija je najčešća maligna bolest decjeg doba. Optimalna upotreba antileukemijskih lekova dovela je do smanjenja toksičnosti i neželjenih događaja, kao i do povećanja stope preživljavanja. Tiopurinski lekovi, uključujući 6-merkaptopurin, predstavljaju najčešće korišćene antileukemijske lekove u lečenju dece obolele od akutne limfoblastne leukemije, koji se koriste u toku faze održavanja. Persona lizovana terapija 6-merkaptopurinom, prilagođena TPMT genotipu svakog pacijenta, već je implementirana u terapijske protokole. Cilj ove studije je bio da ispita ulogu varijanti u genima TPMT, ITPA, ABCC4 i ABCB1 kao prediktora ishoda i toksičnosti uzrokovane 6-merkaptopurinom u toku faze održavanja u lečenju pedijatrijske akutne limfoblastne leukemije. Metode: U studiju je bilo uključeno 68 dece obolele od akutne limfoblastne leukemije. Pacijenti su lečeni primenom A LL IC-BFM 2002 ili A LL IC-BFM 2009 protokola. Toksičnost i neželjeni događaji su posmatrani i beleženi upotrebom surogat markera (broj nedelja bez terapije, broj epizoda leukopenije i prosecna doza 6-merkaptopurina) a probabilisticki modeli su korišćeni za predikciju ukupne toksicnosti uzrokovane primenom 6-merkaptopurina. Rezultati: Studija je potvrdila da pacijenti oboleli od akutne limfoblastne leukemije koji imaju neaktivni TPMT alel zahtevaju redukciju doze 6-merkaptopurina. Varijante u genima ITPA i ABCC4 nisu bile povezane sa toksicnošću koja je uzrokovana primenom 6-merkaptopurina u toku faze održavanja. Nosioci varijante u genu ABCB1 su ispoljili veću hepatotoksicnost. Probabilisticki model Neural net kojim su posmatrane sve analizirane genske varijante se pokazao kao najbolji predikcioni model. Primenom ovog modela bilo je moguće razlikovati A LL pacijente sa lošom i dobrom tolerancijom 6-merkaptopurina u 71% slucajeva (AUC=0,71). Zaključak: Ova studija doprinosi dizajniranju panela farmakogenetskih markera koji bi se koristili za predikciju toksicnosti uzrokovane primenom tiopurinskih lekova kod dece obolele od akutne limfoblastne leukemije.Background: Acute lymphoblastic leukemia is the most common childhood malignancy. Optimal use of anti leukemic drugs has led to less toxicity and adverse reactions, and a higher survival rate. Thiopurine drugs, including 6-mercaptopurine, are mostly used as antileukemic medications in the maintenance phase of treatment for children with acute lymphoblastic leukemia. For those patients, TPMT genotype-tailored 6-mercaptopurine therapy is already implemented in the treatment protocols. We investigated the role of TPMT, ITPA, ABCC4 and ABCB1 genetic variants as predictors of outcome and 6-mercaptopurine induced toxicity during the maintenance phase of treatment in pediatric acute lymphoblastic leukemia. Methods: Sixty-eight children with acute lymphoblastic leukemia were enrolled in this study. Patients have been treated according to A LL IC-BFM 2002 or ALL IC-BFM 2009 protocols. Toxicity and adverse events have been monitored via surrogate markers (off-therapy weeks, episodes of leukopenia and average 6-mercaptopurine dose) and a probabilistic model was employed to predict overall 6-mercaptopurine related toxicity. Results: We confirmed that patients with acute lymphoblastic leukemia that carry inactive TPMT allele(s) require 6mercaptopurine dose reduction. ITPA and ABCC4 genetic variants failed to show an association with 6-mercapto - purine induced toxicity during the maintenance phase. Carriers of ABCB1 variant allele experienced greater hepatotoxicity. The probabilistic model Neural net which considered all the analysed genetic variants was assessed to be the best prediction model. It was able to discriminate ALL patients with good and poor 6-mercaptopurin tolerance in 71% of cases (A U C = 0 .7 l). Conclusions: This study contributes to the design of a panel of pharmacogenetic markers for predicting thiopurineinduced toxicity in pediatric ALL

Liposomal encapsulation enhances and prolongs the anti-inflammatory effects of water-soluble dexamethasone phosphate in experimental adjuvant arthritis

Introduction The objective of this study was to evaluate the efficacy of intravenous (i.v.) injection of liposomally encapsulated dexamethasone phosphate (DxM-P) in comparison to free DxM-P in rats with established adjuvant arthritis (AA). This study focused on polyethylene glycol (PEG)-free liposomes, to minimize known allergic reactions caused by neutral PEG-modified (PEG-ylated) liposomes. Methods Efficacy was assessed clinically and histologically using standard scores. Non-specific and specific immune parameters were monitored. Activation of peritoneal macrophages was analyzed via cytokine profiling. Pharmacokinetics/biodistribution of DxM in plasma, synovial membrane, spleen and liver were assessed via mass spectrometry. Results Liposomal DxM-P (3 × 1 mg/kg body weight; administered intravenously (i.v.) on Days 14, 15 and 16 of AA) suppressed established AA, including histological signs, erythrocyte sedimentation rate, white blood cell count, circulating anti-mycobacterial IgG, and production of interleukin-1beta (IL-1β) and IL-6 by peritoneal macrophages. The suppression was strong and long-lasting. The clinical effects of liposomal DxM-P were dose-dependent for dosages between 0.01 and 1.0 mg/kg. Single administration of 1 mg/kg liposomal DxM-P and 3 × 1 mg/kg of free DxM-P showed comparable effects consisting of a partial and transient suppression. Moreover, the effects of medium-dose liposomal DxM-P (3 × 0.1 mg/kg) were equal (in the short term) or superior (in the long term) to those of high-dose free DxM-P (3 × 1 mg/kg), suggesting a potential dose reduction by a factor between 3 and 10 by liposomal encapsulation. For at least 48 hours after the last injection, the liposomal drug achieved significantly higher levels in plasma, synovial membrane, spleen and liver than the free drug. Conclusions This new PEG-free formulation of macrophage-targeting liposomal DxM-P considerably reduces the dose and/or frequency required to treat AA, with a potential to enhance or prolong therapeutic efficacy and limit side-effects also in the therapy of rheumatoid arthritis. Depot and/or recirculation effects in plasma, inflamed joint, liver, and spleen may contribute to this superiority of liposomally encapsulated DxM-P

Genomic medicine without borders: which strategies should developing countries employ to invest in precision medicine? A new "fast-second winner" strategy

Genomic medicine has greatly matured in terms of its technical capabilities, but the diffusion of genomic innovations worldwide faces significant barriers beyond mere access to technology. New global development strategies are sorely needed for biotechnologies such as genomics and their applications toward precision medicine without borders. Moreover, diffusion of genomic medicine globally cannot adhere to a “one-size-fits-all-countries” development strategy, in the same way that drug treatments should be customized. This begs a timely, difficult but crucial question: How should developing countries, and the resource-limited regions of developed countries, invest in genomic medicine? Although a full-scale investment in infrastructure from discovery to the translational implementation of genomic science is ideal, this may not always be feasible in all countries at all times. A simple “transplantation of genomics” from developed to developing countries is unlikely to be feasible. Nor should developing countries be seen as simple recipients and beneficiaries of genomic medicine developed elsewhere because important advances in genomic medicine have materialized in developing countries as well. There are several noteworthy examples of genomic medicine success stories involving resource-limited settings that are contextualized and described in this global genomic medicine innovation analysis. In addition, we outline here a new long-term development strategy for global genomic medicine in a way that recognizes the individual country's pressing public health priorities and disease burdens. We term this approach the “Fast-Second Winner” model of innovation that supports innovation commencing not only “upstream” of discovery science but also “mid-stream,” building on emerging highly promising biomarker and diagnostic candidates from the global science discovery pipeline, based on the unique needs of each country. A mid-stream entry into innovation can enhance collective learning from other innovators' mistakes upstream in discovery science and boost the probability of success for translation and implementation when resources are limited. This à la carte model of global innovation and development strategy offers multiple entry points into the global genomics innovation ecosystem for developing countries, whether or not extensive and expensive discovery infrastructures are already in place. Ultimately, broadening our thinking beyond the linear model of innovation will help us to enable the vision and practice of genomics without borders in both developed and resource-limited settings

Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnic mutation databases, all built around Microsoft’s PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The above mentioned updates further enhance the impact of FINDbase, as a key resource for Genomic Medicine applications

Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach

Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic variants have been previously reported to be causative of, or associated with, an increased risk for various types of cancer. Here, we adopted a next-generation sequencing approach in 11 members of two families of Greek descent to identify all genomic variants with the potential to predispose family members to cancer. Cross-comparison with data from the Human Gene Mutation Database identified a total of 571 variants, from which 47 % were disease-associated polymorphisms, 26 % disease-associated polymorphisms with additional supporting functional evidence, 19 % functional polymorphisms with in vitro/laboratory or in vivo supporting evidence but no known disease association, 4 % putative disease-causing mutations but with some residual doubt as to their pathological significance, and 3 % disease-causing mutations. Subsequent analysis, focused on the latter variant class most likely to be involved in cancer predisposition, revealed two variants of prime interest, namely MSH2 c.2732T>A (p.L911R) and BRCA1 c.2955delC, the first of which is novel. KMT2D c.13895delC and c.1940C>A variants are additionally reported as incidental findings. The next-generation sequencing-based family genomics approach described herein has the potential to be applied to other types of complex genetic disorder in order to identify variants of potential pathological significance