Posterior reversible encephalopathy syndrome and other severe central nervous system adverse events in the NOPHO ALL2008 protocol : clinical and radiological findings, genetic risk factors and prognosis

Background: The advances in the therapeutic protocols for pediatric acute lymphoblastic leukemia (ALL) have led to a current survival rate of more than 90% in developed countries. Treatment periods are, however, long and marked by complications and toxicity that may challenge treatment outcomes and quality of life for patients. Central nervous system (CNS) toxicity is common during pediatric ALL treatment and may implicate treatment postponement as well as long-term adverse effects. The aim of this thesis was to map CNS toxicities in pediatric ALL in patients treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Methods: Patients aged 1 to 17.9 years at diagnosis of B-cell-precursor and T-cell ALL who were treated according to the NOPHO ALL2008 protocol between 2008 and 2015 were included. Detailed data on CNS toxicity were collected from the NOPHO ALL2008 registry with seven participating countries and a complementary questionnaire addressing phenotypical and work-up details. Genome-wide association studies (GWAS) and candidate single nucleotide polymorphism (SNP) analyses were performed. A validation study of significant findings from GWAS and candidate SNP analyses was made in an independent Australian cohort of pediatric ALL patients (n=797) including patients with diverse CNS toxicities (n=103) and methotrexate-related CNS-toxicity (n=48). The role of minimal CNS leukemia in CNS toxicity risk was further examined by detecting leukemic blasts in cerebrospinal fluid (CSF) by flow cytometric immunophenotyping (FCI) in addition to cytomorphological analysis (CM), which is the CSF examination method specified in the NOPHO ALL2008 protocol. Results: 1464 patients were included in the study of whom 52 (3.8%) had posterior reversible encephalopathy syndrome (PRES), and 135 (9.2%) had at least one form of CNS toxicity. Overall, 82/135 patients had at least one seizure episode (60.7%). PRES was the most common form of CNS toxicity in this cohort (38.5%). Older age, defined as each extra year of age and/or as patient group >10 years of age was a significant risk factor for PRES, seizures, and all CNS toxicities. T-cell immunophenotype was significant risk factor for PRES in univariate analysis and after adjustment for age. Leukemic blasts in CSF by CM were significantly related to PRES during induction and high-risk block treatment was related to PRES after induction. Minimal CNS leukemia, detected by FCI, was a significant risk factor for PRES, seizures, and all CNS toxicities in patients without CNS leukemia by CM in univariate analyses and for PRES and seizures after adjusting for induction therapy. Genome-wide association studies did not demonstrate any significant associations with CNS toxicities, but candidate SNP analyses showed that the ATXN1rs68082256 SNP, related to epilepsy, was associated with seizures in patients <10 years. ATXN1rs68082256 was replicated in the Australian cohort in the patient group with diverse CNS toxicities. At the last follow-up, 11.7% of survivors (12/103) who had displayed CNS toxicity were reported to have had an epilepsy diagnosis. Clinical suspicion of neurocognitive impairment was reported for 10.9% of survivors (12/110) with CNS toxicity at their last follow-up, but neuropsychiatric testing was performed in only two cases. Conclusion: Central nervous system toxicity was common during pediatric ALL treatment and PRES was the most common form of CNS toxicity in this cohort. Older patients had a greater risk of CNS toxicity as well as patients with minimal CNS leukemia. The role of ATXN1rs68082256 SNP in CNS toxicity warrants further studies. Epilepsy is rather common in ALL survivors, while the neurocognitive outcome warrants more systematic follow-up

A deep Chandra observation of the interacting star-forming galaxy Arp 299

We present results from a 90 ks Chandra ACIS-S observation of the X-ray luminous interacting galaxy system Arp 299 (NGC 3690/IC 694). We detect 25 discrete X-ray sources with luminosities above 4.0x10^38 erg s^-1 covering the entire Ultra Luminous X-ray source (ULX) regime. Based on the hard X-ray spectra of the non-nuclear discrete sources identified in Arp 299, and their association with young, actively star-forming region of Arp 299 we identify them as HMXBs. We find in total 20 off-nuclear sources with luminosities above the ULX limit, 14 of which are point-like sources. Furthermore we observe a marginally significant deficit in the number of ULXs, with respect to the number expected from scaling relations of X-ray binaries with the star formation rate (SFR). Although the high metalicity of the galaxy could result in lower ULX numbers, the good agreement between the observed total X-ray luminosity of ULXs, and that expected from the relevant scaling relation indicates that this deficit could be the result of confusion effects. The integrated spectrum of the galaxy shows the presence of a hot gaseous component with kT = 0.72+-0.03 keV, contributing 20% of the soft (0.1-2.0 keV) unabsorbed luminosity of the galaxy. A plume of soft X-ray emission in the west of the galaxy indicates a large scale outflow. We find that the AGN in NGC 3690 contributes only 22% of the observed broad-band X-ray luminosity of Arp 299.Comment: 20 pages, 14 figures, 9 tables. Accepted for publication in MNRA

Διαχείριση αποβλήτων ηλεκτρικού και ηλεκτρονικού εξοπλισμού (Α.Η.Η.Ε) σε Ελλάδα και Ευρώπη

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Περιβάλλον και Ανάπτυξη

Osteoporosis in Men

Osteoporosis is a chronic, progressive disease characterized by low bone mass, bone deterioration, and decreased bone strength resulting in bone fragility and increased fracture risk. 1 Osteoporosis increasingly is being recognized as an important cause of morbidity and mortality in older men. Approximately 2 million men in the United States have osteoporosis, 2 and 1.5 million of these men are over the age of 65 years. 3 The risk of osteoporosis increases with age but develops in men approximately 5 to 10 years later than in women. 4 The estimated lifetime risk of developing an osteoporotic fracture after the age of 50 years is 13 % for men versus 40 % for women. 5 Between 25% and 35 % of hip fractures occur in men. 6 For reasons that are unclear, the mortality associated with hip fractures is higher in men than in women. 7 Men are twice as likely to die in the hospital following a hip fracture (14 % versus 6 % for women), 7 and it is estimated that 31 % of men with hip fracture die within 1 year of the fracture versus 17 % of women. 8 Although osteoporosis is recognized as a debilitating condition in older men and a cause of significant morbidity and mortality, it remains poorly understood and is frequently overlooked in clinical practice. As the population of men over age 65 years continues to grow, physicians in various settings are increasingly likely to encounter male patients with or at risk for osteoporosis. Early recognition of these patients is essential to achieving better outcomes of care in men with osteoporosis. This article provides an overview of osteoporosis in men, with a focus on causes and risk factors, use of dual-energy x-ray absorptiometry (DXA) for screening and diagnosis, and treatment options

Φυτοχημική Aνάλυση Aιθερίων Eλαίων : 7 Ελληνικών Yβριδίων Citrus sp. (Περικαρπίων, Φύλλων) και Επιλεγμένων Δειγμάτων Pimpinella anisum

1. Η συγκριτική μελέτη της χημικής σύστασης των αιθέριων ελαίων επτά (7) ταυτοποιημένων υβριδίων εσπεριδοειδών που καλλιεργούνται στον Δενδροκομικό Σταθμό Πόρου που αποτελεί πρότυπο κέντρο καλλιέργειας εσπεριδοειδών της χώρας, καθώς και η αξιολόγηση των βιολογικών τους δράσεων με δυνητική περαιτέρω χρήση τους στη βιομηχανία τροφίμων. Citrus paradisi cv Star Ruby x νερατζιά (Citrus aurantium L.) Citrus sinensis cv New Hall x citrumelo (Poncirus trifoliata x Citrus paradisi) Citrus sinensis cv New Hall x trifoliata Citrus sinensis cv Oval Valencia Πόρου x citrumelo Citrus sinensis cv Oval Valencia Πόρου x trifoliata Citrus grandis cv Cuba Shaddock x trifoliata Citrus reticulata cv Tangelo Minneola x trifoliata Όλα τα αιθέρια έλαια παραλήφθηκαν με ψυχρή έκθλιψη από τα περικάρπια και με υδραπόσταξη από τα φύλλα των εσπεριδοειδών και υποβλήθηκαν σε αναλύσεις με αέρια χρωματογραφία συζευγμένη με φασματομετρία μάζας (GC-MS). Πραγματοποιήθηκε επίσης, απομόνωση δευτερογενών μεταβολιτών τους, πολυμεθοξυφλαβονοειδών από τα Citrus reticulata cv Tangelo Minneola x trifoliata και Citrus sinensis cv Oval Valencia Πόρου x citrumelo, ενώ από το δεύτερο απομονώθηκε και ένα λιπαρό οξύ. Παρατηρήθηκε ότι τα πτητικά συστατικά που ανιχνεύθηκαν βρίσκονται σε συμφωνία με βιβλιογραφικά δεδομένα που αφορούν άλλα είδη του γένους Citrus. Στα 7 περικάρπια που μελετήθηκαν φυτοχημικά ταυτοποιήθηκε μεγάλο ποσοστό τερπενίων. Έχουν αναλυθεί 45 συστατικά μέσω αέριας χρωματογραφίας συζευγμένης με φασματομετρία μάζας (GC-MS) από τα οποία το λιμονένιο βρίσκεται στη μεγαλύτερη συγκέντρωση, ακολουθούμενο από τα β-πινένιο, μυρκένιο, γ-τερπινένιο και βαλενσένιο. Επίσης παρατηρήθηκε η ύπαρξη κουμαρινών (auraptene, 7-methoxy-8-(2-oxo-3-methylbutyl) coumarin και osthole) από περικάρπια συγκεκριμένων υβριδίων καθώς επίσης και πολυμεθοξυφλαβονών στα 5 από τα 7 δείγματα Citrus που μελετήθηκαν εκτός των Citrus sinensis cv New Hall x trifoliata και Citrus grandis cv Cuba Shaddock x trifoliata. Έγινε επίσης απομόνωση και φασματοσκοπική ταυτοποίηση φλαβονοειδών και ειδικότερα πολυμεθοξυφλαβονοειδών (sinensetin, nobiletin και μεθόξυ παράγωγά τους) από τα περικάρπια των υβριδιών Citrus sinensis cv Oval Valencia Πόρου x citrumelo και Citrus reticulata cv Tangelo Minneola x trifoliata. Επιλέχθηκαν τα παραπάνω υβρίδια λόγω επαρκούς ποσότητας αιθερίου ελαίου (30.5 mg και 15.1 mg αντίστοιχα). 2. Επίσης, έγινε χημική ανάλυση με ανάλογη μέθοδο (GC-MS) των αιθερίων ελαίων τριών (3) ελληνικών δειγμάτων γλυκανίσου (Pimpinella anisum) Λισβορίου (Λέσβου), Βόλου (Θεσσαλίας) και Λιβαδειάς (Βοιωτίας) και ενός δείγματος της ελληνικής αγοράς, Τούρκικης προέλευσης. Τα αιθέρια έλαια παραλήφθηκαν με υδραπόσταξη από νωπά σπέρματα των δειγμάτων κονιοποιημένων πριν την απόσταξη. Στα πλαίσια των ελέγχων βέλτιστης απόδοσης και ποιότητας του αιθερίου ελαίου, ποσότητες γλυκανίσου από το Λισβόρι Λέσβου υποβλήθηκαν σε υδραπόσταξη σε τρείς διαφορετικούς χρόνους (1h, 2h και 3h αντίστοιχα). Προσδιορίσθηκε, ως βέλτιστη, η 1 ώρα απόσταξης στην οποία η απόδοση του ελαίου ήταν και η μεγαλύτερη (80ml/kg). Μετά την διατήρηση των δειγμάτων γλυκανίσου Λισβορίου σε θερμοκρασία δωματίου για ένα έτος, επαναλήφθηκαν οι αποστάξεις και προσδιορίσθηκε η μείωση της απόδοσής τους. Ο συνολικός αριθμός συστατικών στα δείγματα αιθερίων ελαίων που αναλύθηκαν κυμάνθηκε από 18-38, στο αιθέριο έλαιο γλυκάνισου Λιβαδειάς βρέθηκαν 38 συστατικά, στα δείγματα από το Λισβόρι Λέσβου (19-26), του Βόλου (18) και της Τουρκίας (30). Επιπλέον, από το δείγμα αιθερίου ελαίου Λισβορίου απομονώθηκαν και ταυτοποιήθηκαν φασματοσκοπικά οι δυο κύριες ενώσεις trans-ανηθόλη και γ-himachalene σε μίγμα με α- και β-himachalene.In the framework of our studies on Greek Citrus hybrids, we report here in the chemical analyses of the essential oils from cold pressed peels and hydrostillated leaves of 7 selected Greek Citrus hybrids as referred below: one grapefruit [Citrus paradisi cv Star Ruby x Citrus aurantium], four oranges [Citrus sinensis cv Newhall x citrumelo, C. sinensis cv Newhall x trifoliata, C. sinensis cv Valencia Porou x citrumelo, C. sinensis cv Valencia Porou x trifoliata], one pomelo [C. grandisi cv Cuban shaddock x trifoliata] and one mandarin [Citrus reticulata cv Τangelo Minneola x trifoliata] All cultivated in the Arboricultural Station of Poros island, which to our knowledge (international literature) have never been studied before. All volatiles have been analyzed through GC-MS and 45 constituents were identified among which limonene appeared as the most abundant compound, followed by: β-pinene, myrcene, γ-terpinene and valencene. Moreover, from the endemic orange hybrids Citrus reticulata cv Tangelo Minneola x trifoliata και Citrus sinensis cv Oval Valencia Πόρου x citrumelo, several polymethoxyflavones (sinensetin, nobiletin and their methoxy derivatives) were isolated and structurally determined by modern spectral means. 2. Chemical analyses were carried out (GC-MS) on the essential oils of three Greek anise samples (Pimpinella anisum) from Lisvori (Lesvos island), Volos (Thessaly) and Livadia (Viotia) in comparison with a sample of the Greek market of Turkish origin. The essential oils were obtained by hydrostillation from the fresh seed samples, comminuted just before distillation. Samples (same quantity) of Lesvos samples were distilled at three different duration time (1h, 2h and 3h respectively), in order to compare and find out the optimal time of distillation according to the oil yield. It has been proposed as optimal, 1 hour distillation where the oil yield was 80ml/kg. Moreover, from the oil sample of Lesvos the two most important compounds trans-anethole and γ-himachalene in a mixture with α- and β-himachalene were isolated and structurally determined by modern spectral means