Identifying dyspepsia in the Greek population: translation and validation of a questionnaire

BACKGROUND: Studies on clinical issues, including diagnostic strategies, are considered to be the core content of general practice research. The use of standardised instruments is regarded as an important component for the development of Primary Health Care research capacity. Demand for epidemiological cross-cultural comparisons in the international setting and the use of common instruments and definitions valid to each culture is bigger than ever. Dyspepsia is a common complaint in primary practice but little is known with respect to its incidence in Greece. There are some references about the Helicobacter Pylori infection in patients with functional dyspepsia or gastric ulcer in Greece but there is no specific instrument for the identification of dyspepsia. This paper reports on the validation and translation into Greek, of an English questionnaire for the identification of dyspepsia in the general population and discusses several possibilities of its use in the Greek primary care. METHODS: The selected English postal questionnaire for the identification of people with dyspepsia in the general population consists of 30 items and was developed in 1995. The translation and cultural adaptation of the questionnaire has been performed according to international standards. For the validation of the instrument the internal consistency of the items was established using the alpha coefficient of Chronbach, the reproducibility (test – retest reliability) was measured by kappa correlation coefficient and the criterion validity was calculated against the diagnosis of the patients' records using also kappa correlation coefficient. RESULTS: The final Greek version of the postal questionnaire for the identification of dyspepsia in the general population was reliably translated. The internal consistency of the questionnaire was good, Chronbach's alpha was found to be 0.88 (95% CI: 0.81–0.93), suggesting that all items were appropriate to measure. Kappa coefficient for reproducibility (test – retest reliability) was found 0.66 (95% CI: 0.62–0.71), whereas the kappa analysis for criterion validity was 0.63 (95% CI: 0.36–0.89). CONCLUSION: This study indicates that the Greek translation is comparable with the English-language version in terms of validity and reliability, and is suitable for epidemiological research within the Greek primary health care setting

Sol–Gel Synthesis and Characterization of YSZ Nanofillers for Dental Cements at Different Temperatures

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-26, pub-electronic 2021-10-29Publication status: PublishedFunder: The project is co-financed by Greece and the EuropeanUnion (European Social Fund-ESF) by the Operational Program Human Resources Development,Education and Lifelong Learning 2014–2020.; Grant(s): MIS5047876Background: Yttria-stabilized zirconia nanoparticles can be applied as fillers to improve the mechanical and antibacterial properties of luting cement. The aim of this study was to synthesize yttria-stabilized zirconia nanoparticles by the sol–gel method and to investigate their composition, structure, morphology and biological properties. Methods: Nanopowders of ZrO2 7 wt% Y2O3 (nY-ZrO) were synthesized by the sol–gel method and were sintered at three different temperatures: 800, 1000 and 1200 °C, and their composition, size and morphology were investigated. The biocompatibility was investigated with human gingival fibroblasts (hGFs), while reactive oxygen species (ROS) production was evaluated through fluorescence analysis. Results: All synthesized materials were composed of tetragonal zirconia, while nanopowders sintered at 800 °C and 1000 °C additionally contained 5 and 20 wt% of the cubic phase. By increasing the calcination temperature, the crystalline size of the nanoparticles increased from 12.1 nm for nY-ZrO800 to 47.2 nm for nY-ZrO1200. Nano-sized particles with good dispersion and low agglomeration were received. Cell culture studies with human gingival fibroblasts verified the nanopowders’ biocompatibility and their ROS scavenging activity. Conclusions: the obtained sol–gel derived nanopowders showed suitable properties to be potentially used as nanofillers for dental luting cement

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

The protein C system and genetic of thrombophilia

The protein C pathway plays an important role in the regulating of formation of fibrin. The normal blood flow depends on the precise binding on the surface of endothelial cells of thrombin (T), thrombomodulin (TM), protein C (PC) and (endothelial receptor protein C) EPCR. Thrombomodulin is an important cofactor in the protein C pathway and an endothelial receptor for thrombin which plays an important role in the regulation of blood clotting, reducing the activity of thrombin and enhancing the activation of protein C. Scanning of thrombomodulin gene in patients who had one or more thrombotic episodes in young age has revealed several mutations and/or polymorphisms , some of which are associated with venous thrombosis (VTE). Endothelial receptor protein C is a transmembrane protein, which is expressed in the endothelium of large vessels, binds protein C (PC) and enhances its activation. The involvment of EPCR in hemostasis suggests a possible role in the pathogenesis of VTE. Genetic abnormalities affecting the gene of thrombomodulin and th endothelial protein C receptor may be associated with disturbances in the protein C pathway and therefore associated with an increased risk for thrombotic events.The purpose of this study was to investigate the appearance of 127G/A and 1456G/T mutations in the TM gene and the appearance of the two most common polymorphisms in the EPCR gene, 4600A/G in exon 4 that predicts a substitution of Ser219 by Gly in the transmembrane region of EPCR and 4678G/C in the 3’-UT region, in young patients with thrombosis as well as their impact on the risk of VTE, on the age of the first thrombotic episode and recurrence. We recruited 84 patients aged 22-83, as well as a control group of 100 healthy individuals matched for age and sex. All individuals were Caucasians and completed a detailed questionnaire including data of personal and family history of thrombosis, malignancy and drug intake. The study was approved by the local ethics committee and all the subjects gave their informed consent. Real-time polymerase chain reaction (RT-PCR) was used for the identification of 127G/A and 1456G/T mutations in the TM gene and the 4600A/G and 4678G/C polymorphisms in EPCR gene (LightCycler 2.0 Instrument, Roche Diagnostics GmbH). Patients were also studied for hereditary thrombophilia [FV Leiden and FII G20210A, deficiency of natural inhibitors of coagulation (PrC, PrS, and AT)].The FV Leiden and FII G20210A mutations were assessed by PCR and reverse hybridization that concurrently detects these two mutations (FV-PTH SripAssay, VIENNALAB, AUSTRIA). Automated hemostasis analyzer BCS System (Siemens GmbH) was used to determine the activity of natural inhibitors of coagulation.In our study, it appears that 127G/A and 1456G/T mutations is not a common risk factor of VTE in the Greek population. As far as, EPCR polymorphisms is regarded, frequency of the EPCR 4600A/G and 4678G/C genotype was comparable in patients and controls (p=0.7 and p=0.5 respectively). However, in a subset analysis we observed that the EPCR 4600A/G genotype was more prevalent (69.3%) in patients who developed VTE earlier (<35) compared to older age groups. Moreover, the EPCR 4678C/C genotype confers a protective advantage for VTE in terms of age of first thrombotic manifestation.The insights gained from studies that evaluate the involvement of EPCR polymorphisms in the risk of VTE may not only elucidate underlying pathophysiological mechanisms but also their clinical significance and the interplay between these polymorphisms and other congenital and/or epigenetic risk factors. Further studies including larger number of patients as well as detection of EPCR levels are required in order to clarify the implication, if any, of these polymorphisms in the pathogenesis of VTE.Το μονοπάτι της πρωτεΐνη C παίζει σημαντικό ρόλο στη ρύθμιση του σχηματισμού ινώδους. Η ομαλή ροή εξαρτάται από την ακριβή δέσμευση, στην επιφάνεια των ενδοθηλιακών κυττάρων, της θρομβίνης (T), της θρομβομοντουλίνης (TM), της πρωτεΐνης C (PC) και του ενδοθηλιακού υποδοχέα της πρωτεΐνης C (EPCR). Η ΤΜ αποτελεί έναν σημαντικό συμπαράγοντα στο μονοπάτι της πρωτεΐνης C, καθώς είναι ενδοθηλιακός υποδοχέας της θρομβίνη που διαδραματίζει σημαντικό ρόλο στη ρύθμιση της πήξης του αίματος, μειώνοντας την δραστηριότητα της θρομβίνης και ενισχύοντας την ενεργοποίηση της PC. Η σάρωση του γονίδιου της TM σε ασθενείς που έχουν παρουσιάσει ένα ή περισσότερα θρομβωτικά επεισόδια έχει αποκαλύψει αρκετές μεταλλάξεις και/ή πολυμορφισμούς, μερικοί από τους οποίους σχετίζονται με φλεβική θρόμβωση. Ο EPCR είναι μια διαμεμβρανική πρωτεΐνη που εκφράζεται στο ενδοθήλιο των μεγάλων αγγείων, δεσμεύει την PC και ενισχύει την ενεργοποίηση της. Η εμπλοκή του EPCR στον μηχανισμό της αιμόστασης υποδηλώνει έναν πιθανό ρόλο στην παθογένεια της φλεβικής θρόμβωσης (ΦΘΕ). Γενετικές ανωμαλίες που επηρεάζουν το γονίδιο της ΤΜ και του EPCR ενδεχομένως να σχετίζονται με διαταραχές στο μονοπάτι της PC και κατά συνέπεια να συνδέονται με αυξημένο κίνδυνο για θρομβωτικά επεισόδια.Ο σκοπός της παρούσας μελέτης ήταν να διερευνηθεί η παρουσία των μεταλλάξεων 127G/A και 1456G/T στο γονίδιο της TM και των δύο πιο κοινών πολυμορφισμών στο γονίδιο του EPCR (του πολυμορφισμού 4600A/G στο εξώνιο 4 που οδηγεί σε υποκατάσταση Ser219Gly στην διαμεμβρανική περιοχή του EPCR και του πολυμορφισμού 4678G/C στην 3' μη μεταφραζόμενη περιοχή του EPCR σε ασθενείς που έχουν παρουσιάσει μια ή/και περισσότερες θρομβοεμβολικές επιπλοκές όπως Πνευμονική Εμβολή, εν τω βάθει φλεβική θρόμβωση, αγγειακό εγκεφαλικό επεισόδιο και έμφραγμα του μυοκαρδίου σε νεαρή ηλικία με τελικό στόχο τη διερεύνηση της μοριακής βάσης θρομβοφιλικής διάθεσης άγνωστης μέχρι στιγμής αιτιολογίας, καθώς επίσης εκτίμηση του κινδύνου εμφάνισης φλεβικής θρομβοεμβολής σε άτομα τα οποία φέρουν αυτές τις μεταλλάξεις σε συνδυασμό με ήδη γνωστές μεταλλάξεις ή/ και άλλους παράγοντες κινδύνου. Διεξήχθη μελέτη στην οποία συμπεριλαμβάνονταν 84 ασθενείς και 100 υγιή άτομα ως ομάδα ελέγχου. Για την ανίχνευση των παραπάνω μεταλλάξεων και πολυμορφισμών στον ελληνικό πληθυσμό εφαρμόστηκε η αλυσιδωτή αντίδραση πολυμεράσης πραγματικού χρόνου (Real-Time PCR). Με την τεχνική αυτή, μας δίνεται η δυνατότητα προσδιορισμού της παρουσίας ή απουσίας μεταλλάξεων με απώτερο σκοπό τη διερεύνηση της μοριακής βάσης θρομβοφιλικής διάθεσης άγνωστης μέχρι στιγμής αιτιολογίας. Επίσης, έγινε συγκριτικός έλεγχος του προσδιορισμού των πολυμορφισμών 4600A/G και 4678G/C στο γονίδιο του EPCR με τη μέθοδο του ανάστροφου υβριδισμού.Πραγματοποιήθηκε, ακόμη, προσδιορισμός των κύριων μεταλλάξεων που σχετίζονται με εμφάνιση φλεβικής θρόμβωσης, της μετάλλαξης FVLeiden και του πολυμορφισμού G20210A στο γονίδιο της προθρομβίνης (FII), στους ασθενείς και στην ομάδα ελέγχου, με τη μέθοδο του ανάστροφου υβριδισμού, με σκοπό την διερεύνηση της παρουσίας γενετικής προδιάθεσης και εκτίμησης του κινδύνου ΦΘΕ σε άτομα τα οποία φέρουν αυτές τις μεταλλάξεις σε συνδυασμό με νέες μεταλλάξεις/πολυμορφισμούς. Τέλος, διεξήχθη προσδιορισμός δραστικότητας των φυσικών ανασταλτών της πήξης, πρωτεϊνών C, S και AT, στο δείγμα των ασθενών, με τον αυτοματοποιημένο αναλυτή πήξη BCS System, έτσι ώστε να γίνει έλεγχος θρομβοφιλικής προδιάθεσης στα πλαίσια διερεύνησης της μοριακής βάσης συγγενούς ανεπάρκειας των παραπάνω παραγόντων του μονοπατιού της πρωτεΐνης C και του μονοπατιού της πήξης. Παρατηρήθηκε ότι οι μεταλλάξεις 127G/A και 1456G/T δεν είναι συχνές στον ελληνικό πληθυσμό και ως εκ τούτου δεν είναι πιθανό να αποτελούν συνήθεις παράγοντες κινδύνου για φλεβική θρόμβωση. Η συχνότητα του γονότυπου EPCR 4600A/G και 4678G/C βρέθηκε συγκρίσιμη στην ομάδα ασθενών και στην ομάδα ελέγχου (ρ=0.7 και ρ=0.5 αντίστοιχα). Ωστόσο, σε μια υπό-ανάλυση παρατηρήθηκε ότι ο γονότυπος EPCR 4600A/G ήταν πιο συχνός (69,3%) σε ασθενείς που ανέπτυξαν ΦΘΕ σε νεαρή ηλικία (<35) σε σύγκριση με τις μεγαλύτερες ηλικιακές ομάδες (p=0.001). Επιπλέον, ο γονότυπος EPCR 4678C/C φαίνεται ότι προσδίδει προστατευτικό πλεονέκτημα έναντι ΦΘΕ όσον αφορά την ηλικία εμφάνισης πρώτου επεισοδίου. Οι περιορισμοί που σχετίζονται από τον μικρό αριθμό ασθενών δεν μας επιτρέπουν να προβούμε σε οριστικά αποτελέσματα αλλά μόνο να προτείνουμε πιθανές αλληλεπιδράσεις. Περισσότερες μελέτες που να αφορούν ένα μεγαλύτερο αριθμό ασθενών, καθώς και ανίχνευση των επιπέδων του sEPCR απαιτούνται προκειμένου να αποσαφηνιστεί η επίπτωση, εάν και εφόσον υπάρχει, αυτών των πολυμορφισμών στην παθογένεια της ΦΘΕ

Omics Approaches to Assess Flavor Development in Cheese

Cheese is characterized by a rich and complex microbiota that plays a vital role during both production and ripening, contributing significantly to the safety, quality, and sensory characteristics of the final product. In this context, it is vital to explore the microbiota composition and understand its dynamics and evolution during cheese manufacturing and ripening. Application of high-throughput DNA sequencing technologies have facilitated the more accurate identification of the cheese microbiome, detailed study of its potential functionality, and its contribution to the development of specific organoleptic properties. These technologies include amplicon sequencing, whole-metagenome shotgun sequencing, metatranscriptomics, and, most recently, metabolomics. In recent years, however, the application of multiple meta-omics approaches along with data integration analysis, which was enabled by advanced computational and bioinformatics tools, paved the way to better comprehension of the cheese ripening process, revealing significant associations between the cheese microbiota and metabolites, as well as their impact on cheese flavor and quality

eNOS Gene Variants and the Risk of Premature Myocardial Infarction

BACKGROUND: Endothelial nitric oxide synthase (eNOS) as well as nitric oxide play an important role in the regulation of cardiovascular function. There are limited and controversial data regarding the impact of polymorphisms of eNOS gene that is implicated in the vasoconstrictive properties of the endothelium in the pathogenesis of premature myocardial infarction (MI)

Towards Robustifying Image Classifiers against the Perils of Adversarial Attacks on Artificial Intelligence Systems

Adversarial machine learning (AML) is a class of data manipulation techniques that cause alterations in the behavior of artificial intelligence (AI) systems while going unnoticed by humans. These alterations can cause serious vulnerabilities to mission-critical AI-enabled applications. This work introduces an AI architecture augmented with adversarial examples and defense algorithms to safeguard, secure, and make more reliable AI systems. This can be conducted by robustifying deep neural network (DNN) classifiers and explicitly focusing on the specific case of convolutional neural networks (CNNs) used in non-trivial manufacturing environments prone to noise, vibrations, and errors when capturing and transferring data. The proposed architecture enables the imitation of the interplay between the attacker and a defender based on the deployment and cross-evaluation of adversarial and defense strategies. The AI architecture enables (i) the creation and usage of adversarial examples in the training process, which robustify the accuracy of CNNs, (ii) the evaluation of defense algorithms to recover the classifiers&rsquo; accuracy, and (iii) the provision of a multiclass discriminator to distinguish and report on non-attacked and attacked data. The experimental results show promising results in a hybrid solution combining the defense algorithms and the multiclass discriminator in an effort to revitalize the attacked base models and robustify the DNN classifiers. The proposed architecture is ratified in the context of a real manufacturing environment utilizing datasets stemming from the actual production lines