The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study

AIMS: Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF.METHODS AND RESULTS: Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N=299024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1000000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1mmHg increase, 95% confidence interval (CI): 1.012-1.024, P<0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P<0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P=0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded.CONCLUSIONS: The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population

The Gifted Rating Scales - School Form in Greek elementary and middle school learners: a closer insight into their psychometric characteristics

The Gifted Rating Scales - School Form (GRS-S), an evaluation tool for the identification of gifted elementary and middle school children, was the subject of the current study, which focused on its psychometric features (internal consistency reliability and structural validity). Four hundred and eighty-nine teachers (342 women, 139 men, and 8 without gender declaration) used the GRS-S to estimate the dimensions of giftedness in their students for the current study. Particularly, 489 children (253 girls and 236 boys) were evaluated by their teachers. Eight elementary and middle school classes and sixteen 6-month age bands were used to stratify the student population. The scales’ outstanding internal consistency and good factorial validity were revealed by statistical analyses (EFA, CFA, and Cronbach’s coefficients). According to the current research findings, the GRS-S as a reliable and valid assessment tool for identifying gifted students (by their teachers) within the Greek cultural environment

Association between genetic variants and risk of melanoma

The development of melanoma is a complex process involving the interplay of environmental, phenotypic and genetic risk factors. Novel findings of predisposing genetic variants for melanoma risk may result to deeper understanding of its pathophysiology and to evaluating melanoma cases based on their genetic profile, toward more precise disease risk prediction. In the current thesis, we first attempt to validate an extensive set of SNPs previously associated with melanoma risk in an independent sample of melanoma patients and healthy controls from Greece. In addition, we assessed the cumulative impact of the genetic variants on melanoma risk prediction by calculating a weighted genetic risk score (GRS). Fifteen independent SNPs were significantly associated with melanoma (P<0.05). GRS was strongly associated with melanoma risk, but achieves a modest improvement in risk prediction when added to a phenotypic risk model. We next tried to establish novel susceptibility genetic variants for melanoma by assessing candidate genes in the largest GWAS for melanoma up to date. For our selected genetic variant, no genome-wide significant estimates were obtained (P=1.95x10-5) despite the large number of melanoma cases used in the analysis (Ν=16,534). Next, we examined the role of sun exposure in individuals with higher risk of melanoma incidence based on genetic predisposition within UK Biobank. A weighted GRS was calculated based on previously reported genetic variants that achieved genome-wide significance in their association with melanoma and we divided the population sample in groups of high and low genetic risk. GRS and sun exposure were strongly associated with the risk of melanoma. Among participants at high genetic risk, every additional hour of sun exposure increases the risk of melanoma incidence by 4%. Those results reinforce precision medical practices with the aim of preventing melanoma, especially in individuals at higher genetic risk. Finally, in the current thesis, we performed Mendelian Randomization to test the possible causal relationship between genetically predicted dietary factors and melanoma. We used summary statistics from the largest GWASs up to date for coffee consumption, beta-carotene intake, retinol intake, and serum vitamin D and from UK Biobank for melanoma. The results showed that there is no significant causal relationship between the selected dietary factors and risk of melanoma. As a next step in this analysis, new data on melanoma cases will be added by the MelaNostrum consortium, which investigates the risk of melanoma in the Mediterranean countries.Η ανάπτυξη του μελανώματος είναι σύνθετη και περιλαμβάνει την αλληλεπίδραση φαινοτυπικών χαρακτηριστικών, περιβαλλοντικών εκθέσεων και γενετικών παραγόντων. Η εύρεση γενετικών τόπων που σχετίζονται με το μελάνωμα οδηγεί σε μεγαλύτερη κατανόηση της παθοφυσιολογίας του και επιτρέπει την αξιολόγηση των ασθενών βάση του γενετικού τους προφίλ, ενισχύοντας τις πρακτικές ιατρικής ακριβείας με στόχο την πρόληψή του. Στην παρούσα διατριβή, αρχικά αξιολογήθηκε η επίδραση γνωστών γενετικών παραγόντων που έχουν συσχετιστεί με τον κίνδυνο ανάπτυξης μελανώματος σε έναν ανεξάρτητο ελληνικό πληθυσμό ώστε να επικυρωθεί η σημαντικότητα τους. Επιπλέον αξιολογήθηκε η προβλεπτική ικανότητα των γενετικών αυτών παραγόντων ως προς τον κίνδυνο ανάπτυξης μελανώματος, δημιουργώντας ένα γενετικό δείκτη κινδύνου (ΓΔΚ). 15 από τους γνωστούς αυτούς γενετικούς παράγοντες συσχετίστηκαν σημαντικά με τον κίνδυνο ανάπτυξης μελανώματος στον ελληνικό πληθυσμό. Η προσθήκη του ΓΔΚ σε ένα φαινοτυπικό μοντέλο πρόβλεψης βελτίωσε οριακά, όχι όμως σημαντικά την προγνωστική ικανότητα του μοντέλου. Στη συνέχεια της διατριβής έγινε προσπάθεια να ανακαλυφθούν και να ταυτοποιηθούν νέοι γενετικοί τόποι που σχετίζονται με τον κίνδυνο ανάπτυξης μελανώματος, αξιολογώντας την ήδη υπάρχουσα πληροφορία από την μεγαλύτερη GWAS που έχει πραγματοποιηθεί έως σήμερα για το μελάνωμα. Ο υποψήφιος πολυμορφισμός στον οποίο κατέληξε η διαδικασία αξιολόγησης δεν έδειξε σημαντική σχέση σε ευρυ-γονιδιωματικό επίπεδο με τον κίνδυνο ανάπτυξης μελανώματος (P=1.95x10-5) παρά τον μεγάλο αριθμό περιστατικών μελανώματος που χρησιμοποιήθηκαν στην ανάλυση (Ν=16,534). Στη συνέχεια εξετάστηκε κατά πόσο η αλληλεπίδραση της έκθεσης στην ηλιακή ακτινοβολία με τη γενετική προδιάθεση μεταβάλλει τον κίνδυνο ανάπτυξης μελανώματος στον πληθυσμό της βιοτράπεζας UK Biobank. Κατασκευάστηκε ένας ΓΔΚ με βάση γονίδια που σχετίζονται ισχυρά με τον κίνδυνο ανάπτυξης μελανώματος και ο πληθυσμός της μελέτης χωρίστηκε σε ομάδες υψηλού και χαμηλού γενετικού κινδύνου. Τα αποτελέσματα της ανάλυσης έδειξαν πως ο ΓΔΚ και η έκθεση στην ηλιακή ακτινοβολία σχετίζονται ισχυρά με τον κίνδυνο ανάπτυξης μελανώματος. Επιπλέον στην ομάδα υψηλού ΓΔΚ, κάθε επιπλέον ώρα έκθεσης στην ηλιακή ακτινοβολία αυξάνει τον σχετικό κίνδυνο ανάπτυξης μελανώματος κατά ~4%. Τα αποτελέσματα αυτά ενισχύουν πρακτικές ιατρικής ακριβείας με στόχο την πρόληψη του μελανώματος, ιδιαίτερα σε άτομα τα οποία φέρουν επιβεβαρυμένο γενετικό φορτίο. Τέλος, διερευνήθηκε η αιτιώδης σχέση μεταξύ επιλεγμένων διατροφικών παραγόντων και κινδύνου ανάπτυξης μελανώματος με τη χρήση της μεθόδου της Μεντελιανής τυχαιοποίησης. Χρησιμοποιήθηκαν συγκεντρωτικά στοιχεία από τις μεγαλύτερες GWAS που έχουν πραγματοποιηθεί μέχρι σήμερα για κατανάλωση καφέ, λήψη β-καροτένης και ρετινόλης, καθώς και συγκέντρωση βιταμίνης D, ενώ τα δεδομένα για την εμφάνιση μελανώματος συγκεντρώθηκαν από τη βιοτράπεζα της UK Biobank. Τα αποτελέσματα έδειξαν πως δεν υπάρχει σημαντική αιτιώδης σχέση μεταξύ των επιλεγμένων διατροφικών παραγόντων και κινδύνου ανάπτυξης μελανώματος. Σαν επόμενο βήμα αυτής της ανάλυσης, θα προστεθούν νέα δεδομένα για τα περιστατικά μελανώματος από τον συνασπισμό MelaNostrum, ο οποίος ερευνά την ανάπτυξη του μελανώματος στις μεσογειακές χώρες

Association between genetic variants and risk of melanoma

The development of melanoma is a complex process involving the interplay of environmental, phenotypic and genetic risk factors. Novel findings of predisposing genetic variants for melanoma risk may result to deeper understanding of its pathophysiology and to evaluating melanoma cases based on their genetic profile, toward more precise disease risk prediction. In the current thesis, we first attempt to validate an extensive set of SNPs previously associated with melanoma risk in an independent sample of melanoma patients and healthy controls from Greece. In addition, we assessed the cumulative impact of the genetic variants on melanoma risk prediction by calculating a weighted genetic risk score (GRS). Fifteen independent SNPs were significantly associated with melanoma (P<0.05). GRS was strongly associated with melanoma risk, but achieves a modest improvement in risk prediction when added to a phenotypic risk model. We next tried to establish novel susceptibility genetic variants for melanoma by assessing candidate genes in the largest GWAS for melanoma up to date. For our selected genetic variant, no genome-wide significant estimates were obtained (P=1.95x10-5) despite the large number of melanoma cases used in the analysis (Ν=16,534). Next, we examined the role of sun exposure in individuals with higher risk of melanoma incidence based on genetic predisposition within UK Biobank. A weighted GRS was calculated based on previously reported genetic variants that achieved genome-wide significance in their association with melanoma and we divided the population sample in groups of high and low genetic risk. GRS and sun exposure were strongly associated with the risk of melanoma. Among participants at high genetic risk, every additional hour of sun exposure increases the risk of melanoma incidence by 4%. Those results reinforce precision medical practices with the aim of preventing melanoma, especially in individuals at higher genetic risk. Finally, in the current thesis, we performed Mendelian Randomization to test the possible causal relationship between genetically predicted dietary factors and melanoma. We used summary statistics from the largest GWASs up to date for coffee consumption, beta-carotene intake, retinol intake, and serum vitamin D and from UK Biobank for melanoma. The results showed that there is no significant causal relationship between the selected dietary factors and risk of melanoma. As a next step in this analysis, new data on melanoma cases will be added by the MelaNostrum consortium, which investigates the risk of melanoma in the Mediterranean countries.Η ανάπτυξη του μελανώματος είναι σύνθετη και περιλαμβάνει την αλληλεπίδραση φαινοτυπικών χαρακτηριστικών, περιβαλλοντικών εκθέσεων και γενετικών παραγόντων. Η εύρεση γενετικών τόπων που σχετίζονται με το μελάνωμα οδηγεί σε μεγαλύτερη κατανόηση της παθοφυσιολογίας του και επιτρέπει την αξιολόγηση των ασθενών βάση του γενετικού τους προφίλ, ενισχύοντας τις πρακτικές ιατρικής ακριβείας με στόχο την πρόληψή του. Στην παρούσα διατριβή, αρχικά αξιολογήθηκε η επίδραση γνωστών γενετικών παραγόντων που έχουν συσχετιστεί με τον κίνδυνο ανάπτυξης μελανώματος σε έναν ανεξάρτητο ελληνικό πληθυσμό ώστε να επικυρωθεί η σημαντικότητα τους. Επιπλέον αξιολογήθηκε η προβλεπτική ικανότητα των γενετικών αυτών παραγόντων ως προς τον κίνδυνο ανάπτυξης μελανώματος, δημιουργώντας ένα γενετικό δείκτη κινδύνου (ΓΔΚ). 15 από τους γνωστούς αυτούς γενετικούς παράγοντες συσχετίστηκαν σημαντικά με τον κίνδυνο ανάπτυξης μελανώματος στον ελληνικό πληθυσμό. Η προσθήκη του ΓΔΚ σε ένα φαινοτυπικό μοντέλο πρόβλεψης βελτίωσε οριακά, όχι όμως σημαντικά την προγνωστική ικανότητα του μοντέλου. Στη συνέχεια της διατριβής έγινε προσπάθεια να ανακαλυφθούν και να ταυτοποιηθούν νέοι γενετικοί τόποι που σχετίζονται με τον κίνδυνο ανάπτυξης μελανώματος, αξιολογώντας την ήδη υπάρχουσα πληροφορία από την μεγαλύτερη GWAS που έχει πραγματοποιηθεί έως σήμερα για το μελάνωμα. Ο υποψήφιος πολυμορφισμός στον οποίο κατέληξε η διαδικασία αξιολόγησης δεν έδειξε σημαντική σχέση σε ευρυ-γονιδιωματικό επίπεδο με τον κίνδυνο ανάπτυξης μελανώματος (P=1.95x10-5) παρά τον μεγάλο αριθμό περιστατικών μελανώματος που χρησιμοποιήθηκαν στην ανάλυση (Ν=16,534). Στη συνέχεια εξετάστηκε κατά πόσο η αλληλεπίδραση της έκθεσης στην ηλιακή ακτινοβολία με τη γενετική προδιάθεση μεταβάλλει τον κίνδυνο ανάπτυξης μελανώματος στον πληθυσμό της βιοτράπεζας UK Biobank. Κατασκευάστηκε ένας ΓΔΚ με βάση γονίδια που σχετίζονται ισχυρά με τον κίνδυνο ανάπτυξης μελανώματος και ο πληθυσμός της μελέτης χωρίστηκε σε ομάδες υψηλού και χαμηλού γενετικού κινδύνου. Τα αποτελέσματα της ανάλυσης έδειξαν πως ο ΓΔΚ και η έκθεση στην ηλιακή ακτινοβολία σχετίζονται ισχυρά με τον κίνδυνο ανάπτυξης μελανώματος. Επιπλέον στην ομάδα υψηλού ΓΔΚ, κάθε επιπλέον ώρα έκθεσης στην ηλιακή ακτινοβολία αυξάνει τον σχετικό κίνδυνο ανάπτυξης μελανώματος κατά ~4%. Τα αποτελέσματα αυτά ενισχύουν πρακτικές ιατρικής ακριβείας με στόχο την πρόληψη του μελανώματος, ιδιαίτερα σε άτομα τα οποία φέρουν επιβεβαρυμένο γενετικό φορτίο. Τέλος, διερευνήθηκε η αιτιώδης σχέση μεταξύ επιλεγμένων διατροφικών παραγόντων και κινδύνου ανάπτυξης μελανώματος με τη χρήση της μεθόδου της Μεντελιανής τυχαιοποίησης. Χρησιμοποιήθηκαν συγκεντρωτικά στοιχεία από τις μεγαλύτερες GWAS που έχουν πραγματοποιηθεί μέχρι σήμερα για κατανάλωση καφέ, λήψη β-καροτένης και ρετινόλης, καθώς και συγκέντρωση βιταμίνης D, ενώ τα δεδομένα για την εμφάνιση μελανώματος συγκεντρώθηκαν από τη βιοτράπεζα της UK Biobank. Τα αποτελέσματα έδειξαν πως δεν υπάρχει σημαντική αιτιώδης σχέση μεταξύ των επιλεγμένων διατροφικών παραγόντων και κινδύνου ανάπτυξης μελανώματος. Σαν επόμενο βήμα αυτής της ανάλυσης, θα προστεθούν νέα δεδομένα για τα περιστατικά μελανώματος από τον συνασπισμό MelaNostrum, ο οποίος ερευνά την ανάπτυξη του μελανώματος στις μεσογειακές χώρες

The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study

Aims Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF. Methods and results Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including &gt;1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012-1.024, P &lt; 0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P &lt; 0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P = 0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded. Conclusions The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population

Measuring Impulsivity in Greek Adults: Psychometric Properties of the Barratt Impulsiveness Scale (BIS-11) and Impulsive Behavior Scale (Short Version of UPPS-P)

Introduction: The aim of the present study was to validate the Barratt Impulsiveness Scale (BIS-11th version) scale as well as the short version of the Impulsive Behavior Scale (UPPS-P) in a population of Greek young adults. Secondly, we aimed at validating the BIS-11 in older adults. Methods: 167 (Group 1) university students completed the Greek version of the BIS-11 (BIS-11-G) and the UPPS (UPPS-P-G) scales. Additionally, BIS-11-G was also administered to 167 (Group 2) cognitively intact older adults, to identify whether it could be used to measure impulsivity in an older adult population. Results: Both scales had satisfactory internal reliability and test–retest reliability, as well as convergent validity in the young adult population. In regard to the factor structure, a principal component analysis (PCA) extracted two factors for the BIS-11-G in the young adult population and three factors in older adults, as well as three factors for the short UPPS-P-G in young adults. Conclusions: The BIS-11-G and the UPPS-P-G scales can be used to measure different aspects of impulsivity in the Greek population of different ages in research and clinical practice

An Investigation of Working Memory Profile and Fluid Intelligence in Children With Neurodevelopmental Difficulties

The present study aims to evaluate the distinct patterns of working memory (WM) capacity of children with Developmental Language Disorder (DLD), High-functioning children with Autism Spectrum Disorder (ASD) and children with Down syndrome (DS). More specifically, the current study investigates the complex relationship of fluid intelligence and WM between 39 children with DLD, 20 High-functioning children with ASD, and 15 children with DS. All children were evaluated in different measures of Phonological Working Memory, Visual-spatial Working Memory whereas Fluid Intelligence was measured with Raven Progressive Matrices. The result analysis revealed a significant difference among the three groups, both among each function separately and the correlations among them, as well. The results revealed that the DLD groups and High-functioning ASD group exhibited a common picture or an overlap of performances in all Phonological and Visuo-spatial working memory measures, except Backward Digit Recall task. As for the DS group research findings revealed different and unique working memory patterns in comparison to DLD group and High-functioning ASD. Their differences have been studied and further conclusions have been drawn about the different patterns of working memory among the three clinical groups. The implications of these findings are discussed in light of support for learning. The common profile that characterize the two developmental conditions and the distinct pattern of working memory performance in DS group underlies the need for further research in the field

The Role of Digital Tools in the Timely Diagnosis and Prevention of Acute Exacerbations of COPD: A Comprehensive Review of the Literature

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways and lung parenchyma with multiple systemic manifestations. Exacerbations of COPD are important events during the course of the disease, as they are associated with increased mortality, severe impairment of health-related quality of life, accelerated decline in lung function, significant reduction in physical activity, and substantial economic burden. Telemedicine is the use of communication technologies to transmit medical data over short or long distances and to deliver healthcare services. The need to limit in-person appointments during the COVID-19 pandemic has caused a rapid increase in telemedicine services. In the present review of the literature covering published randomized controlled trials reporting results regarding the use of digital tools in acute exacerbations of COPD, we attempt to clarify the effectiveness of telemedicine for identifying, preventing, and reducing COPD exacerbations and improving other clinically relevant outcomes, while describing in detail the specific telemedicine interventions used

Rotationplasty outcomes assessed by gait analysis following resection of lower extremity bone neoplasms: a systematic review and meta-analysis

Aims: The standard of surgical treatment for lower limb neoplasms had been characterized by highly interventional techniques, leading to severe kinetic impairment of the patients and incidences of phantom pain. Rotationplasty had arisen as a potent limb salvage treatment option for young cancer patients with lower limb bone tumours, but its impact on the gait through comparative studies still remains unclear several years after the introduction of the procedure. The aim of this study is to assess the effect of rotationplasty on gait parameters measured by gait analysis compared to healthy individuals. Methods: The MEDLINE, Scopus, and Cochrane databases were systematically searched without time restriction until 10 January 2022 for eligible studies. Gait parameters measured by gait analysis were the outcomes of interest. Results: Three studies were eligible for analyses. Compared to healthy individuals, rotationplasty significantly decreased gait velocity (-1.45 cm/sec; 95% confidence interval (CI) -1.98 to -0.93; p < 0.001), stride length (-1.20 cm; 95% CI -2.31 to -0.09; p < 0.001), cadence (-0.83 stride/min; 95% (CI -1.29 to -0.36; p < 0.001), and non-significantly increased cycle time (0.54 sec; 95% CI -0.42 to 1.51; p = 0.184). Conclusion: Rotationplasty is a valid option for the management of lower limb bone tumours in young cancer patients. Larger studies, with high patient accrual, refined surgical techniques, and well planned rehabilitation strategies, are required to further improve the reported outcomes of this procedure. Cite this article: Bone Jt Open 2023;4(11):817–824

The Gifted Rating Scales-Preschool/Kindergarten Form (GRS-P): A Preliminary Examination of Their Psychometric Properties in Two Greek Samples

The present paper is based on data of two samples concerning the Gifted Rating Scales-Preschool/Kindergarten Form (GRS-P) that aimed to gain insight into the psychometric properties (internal consistency reliability, structural and convergent validity) of the Greek version of the GRS-P. In both studies, teachers estimated their students&rsquo; giftedness with the GRS-P and executive functions with the Childhood Executive Functioning Inventory (Study 1). In Study 2, kindergarteners were examined in cognitive measurements which included the colored progressive matrices, the children category test, the Athena test, and the mini-mental state examination. Statistical analyses (EFA, CFA, Cronbach&rsquo;s &alpha;, and Pearson&rsquo;s r coefficients) revealed the excellent internal consistency of the scales as well as their good factorial and convergent/discriminant validity. In relation to the children&rsquo;s cognitive ability measures, it emphasized the fact that the GRS-P is a reliable and valid tool for teachers to assess their gifted students in a Greek cultural context