Δοσιμετρικοί υπολογισμοί Monte Carlo για δέσμες βαρέων ιόντων

Περίληψη Σκοπός: Σκοπό αυτής της διπλωματικής εργασίας αποτελεί η κατασκευή μεθόδων για την δημιουργία ευρείας καμπύλης (SOBP) βιολογικής δόσης βάθους με την χρήση του προγράμματος του Geant4 και η σύγκριση των μεθόδων με αντίστοιχες κατασκευασμένα για Fluka. Μέθοδοι: Δημιουργήθηκε μέθοδος κατασκευής μονοενεργειακής δέσμης βαρέων ιόντων σε κύβο νερού πλευράς 30 cm με μετατροπή σε υπάρχουσα εφαρμογή Geant4 (Hadrontherapy example [A] ) και δημιουργίας φυσικής καμπύλης δόσης Bragg. Επίσης δημιουργήθηκε φίλτρο διαπλάτυνσης δέσμης ιόντων (ridge) στο Geant4 με ιδιότητες αντίστοιχες μαθηματικού φίλτρου Fortan για το πρόγραμμα Fluka που εφαρμόστηκε στην δημοσίευση [B]. Πραγματοποιήθηκε σύγκριση των αποτελεσμάτων των προγραμμάτων Fluka και Geant4 για έλεγχο της ομοιότητας των καμπύλων φυσικών δόσεων των δύο προγραμμάτων και των δύο παρόμοιων φίλτρων για διαφορετικά βαρέα ιόντα. Oι ρυθμίσεις του Fluka ήταν σύμφωνες με την δημοσίευση [B]. Επίσης δημιουργήθηκαν καμπύλες δόσης βάθους για τα βαρέα ιόντα κάθετες στην δέσμη στο Geant4 για σύγκρισή των βαρέων ιόντων. Τέλος κατασκευάστηκε κώδικας C++ για την δημιουργία ευρείας καμπύλης φυσικής δόσης (SOBP). Λόγω περιορισμού χρόνου δεν ήταν δυνατή η κατασκευή μεθόδων που συνδέουν φυσική και βιολογική δόση. Αποτελέσματα: Υπάρχουν διαφορές στις καμπύλες δόσης βάθους χωρίς φίλτρο έως (6 %) που οφείλονται στις διαφορές των προγραμμάτων, οι διαφορές συνεχίζουν και στις μετρήσεις με φίλτρο που γίνονται πιο μεγάλες (10 %), με εξαίρεση το ήλιο-3 με διαφορά 20% και στις δύο περιπτώσεις. Δεν μπορεί να υπάρξει συμπέρασμα για τυχόν διαφορές των φίλτρων εφόσον υπάρχουν οι διαφορές των προγραμμάτων. Λόγω της κακής στατιστικής δεν μπορεί να υπάρξει επίσης αποτέλεσμα για ακριβείς διαφορές μεταξύ των βαρέων ιόντων ως προς την κάθετη κατανομή δόσης, αλλά υπάρχει η τάση όπου τα βαρύτερα ιόντα έχουν λιγότερη πλευρική απόκλιση από την δέσμη. Τέλος το πρόγραμμα κατασκευής ευρείας δέσμης έχει αρκετά καλή συμπεριφορά , αλλά ο περιορισμός της χρήσης αποκλειστικά μονο των κορυφών οδηγεί σε κυματισμό και επηρεασμό από την στατιστική διακύμανση των υπολογισμών. Συμπεράσματά: Παρ’ όλες τις διαφορές οι μετρήσεις είναι αρκετά κοντά και μπορούν να χρησιμοποιηθούν το ένα πρόγραμμα έναντι του άλλου, αλλά θέλουν προσοχή και εμπειρία στην χρήση τους και επιβεβαίωση με πειραματικά δεδομένα. To πρόγραμμα Fluka διατηρεί καλύτερη συμπεριφορά στα θραυσμάτα των ιόντων. Iόντα με μέσο ατομικό αριθμό όπως το λίθιο και το βόριο είναι καλές επιλογές για αδρονοθεραπεία, αν και χρειάζεται περισσότερη έρευνα για την απόδειξή τους. Με περαιτέρω βελτιώσεις του κώδικα δημιουργίας SOBP, δηλαδή χρήση δεδομένων εκτός κορυφών και καλύτερης στατιστικής των υπολογισμών θα βελτιωθεί η ποιότητα της SOBP. Σε αυτήν την διπλωματική έγινε σημαντικό πρόοδος για να ανοίξει ο δρόμος της χρήσης του Geant4 σε επόμενες εργασίες και ο στόχος της κατασκευής βιολογικής καμπύλης δόσης βάθους SOBP στο Geant4. A. G.A.P. Cirrone, L. Pandola, G. Petringa, F.Romano, hadrontherapy, available online: https://twiki.cern.ch/twiki/bin/view/Geant4/AdvancedExamplesHadrontherapy (last accessed on:11/5/2018). B. Ι.Kantemiris P.Karaiskos P.Papagiannis A.Angelopoulos (2011) Dose and dose averaged LET comparison of 1H, 4He, 6Li, 8Be, 10B, 12C, 14N, and 16O ion beams forming a spread-out Bragg peak. Med. Phys. 38,12 p6586.Abstract Purpose: The purpose of this master thesis is the construction of methods for the creation of spread out bragg peak (SOBP) dose-depth curve with the use of Geant4 program and the comparison with equivalent methods made for Fluka. Methods: Monoenergetic heavy ion Bragg peak dose-depth curves in water cube of 30 cm side were created with modifications in an existing Geant4 example (Hadrontherapy example (A)). Also a ridge flattening filter for Geant 4 was made that was modelled with the properties of a mathematical filter written in Fortran for Fluka, that was applied in a published research [B]. A comparison of the physical Βragg peak dose-depth curves between Fluka and Geant4 were made for the testing of the similarity between the different programs and the similar ridge filters for different heavy ions . The Fluka settings were in agreement with research [B]. Furthermore dose-side dispersion curves vertical to the beam direction in Geant4 for heavy ions were created for the comparison of heavy ions. Finally a C++ code for the creation of the speed out Bragg peak was written. Due to time limitations it was not possible to create a method for connecting biological and physical dose. Results: There are differences in the physical Βragg peak dose-depth curves without filter of 6 % that are caused due to the differences in the programs, the differences continue with filter the use of the filter and they become greater (10 %), with the exception of helium-3 with a difference of 20 % in both simulations. There cannot be a conclusion for potential differences between the ridge filters because there is the underlying difference in the programs. Due to the bad statistics in the vertical dose distribution, in perspective to the beam direction, there cannot be accurate results in the comparison of the heavy ions but there is a tendency where heavy ions have smaller lateral deviation from the beam. Finally the spread out Βragg peak creation program has a good behaviour, but the limitation of using only peaks leads to wave like patterns and influence from calculation statistics. Conclusions: Although the differences in the results it has been found that the two programs have similar behavior and they can be used interchangeably but they require attention and experience in their usage and validation with real data. Fluka code retains better behavior at ions fragments. Ions with medium atomic weight like lithium and boron are good options for hadrontherapy, but further research is needed for proving. With further improvement of the SOBP code as using data other than peaks and better calculation statistics the SOBP will be approached even further.In this master thesis important progress has been made to open the road towards Geant4 usage in future research and the target of creating biological dose spread out Βragg peaks in Geant4. A. G.A.P. Cirrone, L. Pandola, G. Petringa, F.Romano, hadrontherapy, available online: https://twiki.cern.ch/twiki/bin/view/Geant4/AdvancedExamplesHadrontherapy (last accessed on:11/5/2018). B. I.Kantemiris P.Karaiskos P.Papagiannis A.Angelopoulos (2011) Dose and dose averaged LET comparison of 1H, 4He, 6Li, 8Be, 10B, 12C, 14N, and 16O ion beams forming a spread-out Bragg peak. Med. Phys. 38,12 p6586

The effects of acute low-volume HIIT and aerobic exercise on leukocyte count and redox status

A single bout of exercise can result in inflammatory responses, increased oxidative stress and upregulation of enzymatic antioxidant mechanisms. Although low-volume high-intensity interval training (HIIT) has become popular, its acute responses on the above mechanisms have not been adequately studied. The present study evaluated the effects of HIIT on hematological profile and redox status compared with those following traditional continuous aerobic exercise (CET). Twelve healthy young men participated in a randomized crossover design under HIIT and CET. In HIIT session, participants performed four 30-sec sprints on a cycle-ergometer with 4 min of recovery against a resistance of 0.375 kg/kg of body mass. CET consisted of 30-min cycling on a cycle-ergometer at 70% of their VO2max. Blood was drawn at baseline, immediately post, 24h, 48h and 72h post-exercise and was analyzed for complete blood count and redox status (thiobarbituric acid reactive substances, [TBARS]; protein carbonyls, [PC]; total antioxidant capacity, [TAC]; catalase and uric acid). White blood cells (WBC) increased after both exercise protocols immediately post-exercise (HIIT: 50% and CET: 31%, respectively). HIIT increased (+22%) PC post-exercise compared to baseline and CET (p 0.05) for TBARS and catalase following either exercise protocol. Low-volume HIIT is associated with a greater acute phase leukocyte count and redox response than low-volume CET, and this should be considered when an exercise training program is developed and complete blood count is performed for health purposes

Disparate habitual physical activity and dietary intake profiles of elderly men with low and elevated systemic inflammation

The development of chronic, low-grade systemic inflammation in the elderly (inflammaging) has been associated with increased incidence of chronic diseases, geriatric syndromes, and functional impairments. The aim of this study was to examine differences in habitual physical activity (PA), dietary intake patterns, and musculoskeletal performance among community-dwelling elderly men with low and elevated systemic inflammation. Nonsarcopenic older men free of chronic diseases were grouped as ‘low’ (LSI: n = 17; 68.2 ± 2.6 years; hs-CRP: 1 mg/L) systemic inflammation according to their serum levels of high-sensitivity CRP (hs-CRP). All participants were assessed for body composition via Dual Emission X-ray Absorptiometry (DEXA), physical performance using the Short Physical Performance Battery (SPPB) and handgrip strength, daily PA using accelerometry, and daily macro- and micronutrient intake. ESI was characterized by a 2-fold greater hs-CRP value than LSI (p < 0.01). The two groups were comparable in terms of body composition, but LSI displayed higher physical performance (p < 0.05), daily PA (step count/day and time at moderate-to-vigorous PA (MVPA) were greater by 30% and 42%, respectively, p < 0.05), and daily intake of the antioxidant vitamins A (6590.7 vs. 4701.8 IU/day, p < 0.05), C (120.0 vs. 77.3 mg/day, p < 0.05), and E (10.0 vs. 7.5 mg/day, p < 0.05) compared to ESI. Moreover, daily intake of vitamin A was inversely correlated with levels of hs-CRP (r = −0.39, p = 0.035). These results provide evidence that elderly men characterized by low levels of systemic inflammation are more physically active, spend more time in MVPA, and receive higher amounts of antioxidant vitamins compared to those with increased systemic inflammation

Effects of cardiovascular, resistance and combined exercise training on cardiovascular, performance and blood redox parameters in coronary artery disease patients: An 8-month training-detraining randomized intervention

© 2021 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/antiox10030409It is well-documented that chronic/regular exercise improves the cardiovascular func-tion, decreases oxidative stress and enhances the antioxidant capacity in coronary artery disease (CAD) patients. However, there is insufficient evidence regarding the chronic effects of different types of training and detraining on cardiovascular function and the levels of oxidative stress and antioxidant status in these patients. Therefore, the present study aimed at investigating the effects of cardiovascular, resistance and combined exercise training followed by a three-month detraining period, on cardiovascular function, physical performance and blood redox status parameters in CAD patients. Sixty coronary artery disease patients were randomly assigned to either a cardiovascular training (CVT, N = 15), resistance training (RT, N = 11), combined cardiovascular and resistance training (CT, N = 16) or a control (C, N = 15) group. The training groups participated in an 8-month supervised training program (training three days/week) followed by a 3-month detraining period, while the control group participated only in measurements. Body composition, blood pressure, performance-related variables (aerobic capacity (VO2max ), muscle strength, flexibility) and blood redox status-related parameters (thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), reduced glutathione (GSH), oxidized glutathione (GSSG), catalase activity (CAT), protein carbonyls (PC)) were assessed at the beginning of the study, after 4 and 8 months of training as well as following 1, 2 and 3 months of detraining (DT). CVT induced the most remarkable and pronounced alterations in blood pressure (~9% reduction in systolic blood pressure and ~5% in diastolic blood pressure) and redox status since it had a positive effect on all redox-related variables (ranging from 16 to 137%). RT and CT training affected positively some of the assessed (TAC, CAT and PC) redox-related variables. Performance-related variables retained the positive response of the training, whereas most of the redox status parameters, for all training groups, restored near to the pre-exercise values at the end of the DT period. These results indicate that exercise training has a significant effect on redox status of CAD. Three months of detraining is enough to abolish the exercise-induced beneficial effects on redox status, indicating that for a better antioxidant status, exercise must be a lifetime commitment.This project was funded by the Cyprus Research Promotion Foundation, EPΥNE/0506/17Published versio

Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation

Circulating Sclerostin responses to acute weight and non weight bearing sport activity in pre adolescent males

Mechanical loading, i.e. physical activity and/or exercise, promotes bone formation during growth. Sclerostin, a glycoprotein, mediates osteocytes' response to mechanical loading by inhibiting the Wnt/lf-catenin pathway thereby inhibiting bone formation.Published versio

Recovery kinetics of knee flexor and extensor strength after a football match

© 2015 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0128072We examined the temporal changes of isokinetic strength performance of knee flexor (KF) and extensor (KE) strength after a football match. Players were randomly assigned to a control (N = 14, participated only in measurements and practices) or an experimental group (N = 20, participated also in a football match). Participants trained daily during the two days after the match. Match and training overload was monitored with GPS devices. Venous blood was sampled and muscle damage was assessed pre-match, post-match and at 12h, 36h and 60h post-match. Isometric strength as well as eccentric and concentric peak torque of knee flexors and extensors in both limbs (dominant and non-dominant) were measured on an isokinetic dynamometer at baseline and at 12h, 36h and 60h after the match. Functional (KFecc/KEcon) and conventional (KFcon/KEcon) ratios were then calculated. Only eccentric peak torque of knee flexors declined at 60h after the match in the control group. In the experimental group: a) isometric strength of knee extensors and knee flexors declined (P<0.05) at 12h (both limbs) and 36h (dominant limb only), b) eccentric and concentric peak torque of knee extensors and flexors declined (P<0.05) in both limbs for 36h at 60°/s and for 60h at 180°/s with eccentric peak torque of knee flexors demonstrating a greater (P<0.05) reduction than concentric peak torque, c) strength deterioration was greater (P<0.05) at 180°/s and in dominant limb, d) the functional ratio was more sensitive to match-induced fatigue demonstrating a more prolonged decline. Discriminant and regression analysis revealed that strength deterioration and recovery may be related to the amount of eccentric actions performed during the match and athletes' football-specific conditioning. Our data suggest that recovery kinetics of knee flexor and extensor strength after a football match demonstrate strength, limb and velocity specificity and may depend on match physical overload and players' physical conditioning level.Published versio

Lipids metabolism during resistance exercise

Η άσκηση με αντιστάσεις συστήνεται για την καταπολέμηση της παχυσαρκίας και του σακχαρώδη διαβήτη. Ωστόσο, δεν είναι γνωστή η επίδραση της άσκησης με αντιστάσεις στη δραστικότητα της λιπάσης των τριακυλογλυκερολών. Σκοπός της παρούσας διατριβής ήταν η διερεύνηση της λιπόλυσης στο λιπώδη ιστό κατά την άσκηση με αντιστάσεις σε άτομα φυσιολογικού βάρους (ΑΦΒ) και παχύσαρκα άτομα (ΠΑ). Εννέα ΑΦΒ και 8 ΠΑ (υγιείς άνδρες) πραγματοποίησαν μια προπονητική μονάδα μυϊκής ενδυνάμωσης με αντιστάσεις. Η άσκηση είχε τη μορφή της κυκλικής προπόνησης, όπου πραγματοποιήθηκαν 3 κύκλοι των 10 ασκήσεων με ένταση 70 - 75% της μιας μέγιστης επανάληψης. Δείγματα λιπώδους ιστού από την περιοχή του γλουτού, με σκοπό τη μέτρηση της δραστικότητας της λιπάσης των τριακυλογλυκερολών και δείγματα φλεβικού αίματος, με σκοπό τον προσδιορισμό των συγκεντρώσεων νορεπινφρίνης, επινεφρίνης, ινσουλίνης, κορτιζόλης, γλυκαγόνης, ελεύθερων λιπαρών οξέων (ΕΛΟ), γλυκερόλης, γλυκόζης και γαλακτικού οξέος, λήφθηκαν πριν την άσκηση, στα 5 λεπτά άσκησης, στο τέλος του 1ου, 2ου και 3ου κύκλου. Σε όλη τη διάρκεια της άσκησης πραγματοποιούνταν προσδιορισμός των αναπνευστικών αερίων. Από την ανάλυση των δεδομένων διαπιστώθηκε αυξημένη ενεργειακή δαπάνη άσκησης στα ΑΦΒ και τα ΠΑ (2.9 ± 0.5 2.6 ± 0.8 kcal kg-1 αντίστοιχα, p<0.05). Το αναπνευστικό πηλίκο κατά την άσκηση ήταν υψηλότερο στα ΠΑ έναντι των ΑΦΒ (0.98-1.03, 0.92-0.97 αντίστοιχα), υποδεικνύοντας χαμηλότερη οξείδωση λιπαρών οξέων στα ΠΑ. Η δραστικότητα της λιπάσης των τριακυλογλυκερολών αυξήθηκε 18 φορές στα 5 λεπτά άσκησης στα ΑΦΒ και 16 φορές στα ΠΑ στο τέλος του 1ου κύκλου και στη συνέχεια μειώθηκε παρά τη συνέχιση της άσκησης. Η καθυστερημένη λιπολυτική ανταπόκριση των ΠΑ διαπιστώθηκε και από τις συγκεντρώσεις των ΕΛΟ και της γλυκερόλης. Οι συγκεντρώσεις των κατεχολαμινών αυξήθηκαν και στις δύο ομάδες χωρίς να παρατηρηθούν διαφορές μεταξύ τους. Αντίθετα, η συγκέντρωση ινσουλίνης αυξήθηκε στα ΠΑ, όχι όμως και στα ΑΦΒ Από τα αποτελέσματα καθίσταται σαφές πως η άσκηση με αντιστάσεις αυξάνει το ρυθμό λιπόλυσης και την ενεργειακή δαπάνη και στις δύο ομάδες. Ακόμη, διαπιστώνεται καθυστερημένη λιπολυτική ανταπόκριση από τα ΠΑ, η οποία ενδεχομένως να οφείλεται στην αύξηση της ινσουλίνης και να ευθύνεται για τη μικρότερη χρήση λιπιδίωνResistance exercise is recommended for the treatment of obesity and diabetes. Its effect on triacylglycerol lipase activity in adipose tissue is not known. The aim of the present study was to investigate the effect of resistance exercise (RE) on lipid metabolism in lean and obese humans. Nine lean and 8 obese healthy men performed a 30-min circuit RE protocol (3 cycles of 10 exercises at 70-75% maximal strength). At baseline, 5 minutes, end of 1st, 2nd and 3rd cycle we sampled adipose tissue for triacylglycerol lipase assay; and blood for norepinephrine, epinephrine, insulin, glucagon, cortisol, non-esterified fatty acid (NEFA), glycerol, glucose and lactate determination. Respiratory gases were monitored throughout exercise. The analysis of data indicated that relative energy expenditure was higher in the lean (2.9 ± 0.5 vs. 2.6 ± 0.8 kcal kg-1, P < 0.05). Respiratory exchange ratio during exercise was higher in the obese (0.98-1.03 vs. 0.92-0.97), suggesting lower fat oxidation. Triacylglycerol lipase activity increased 18-fold at 5 min in the lean and 16-fold at approximately 10 min in the obese; thereafter it declined without reaching baseline. The delay in lipolytic activation in the obese was reflected in the NEFA and glycerol concentrations. Plasma catecholamines increased throughout exercise with no differences between groups. Plasma insulin increased in the obese but did not change in the lean. These findings show that RE upregulated adipose tissue lipolysis and enhanced energy expenditure in lean and obese men. Lipolytic activation in the obese displayed a delay which may be due to the hyperinsulinemic response and may be accountable for the lower fat utilizatio

Modern bioethical issues: Euthanasia, physician assisted suicide and abortion. Comparative study of attitudes between physicians and law professionals.

We aimed to examine and compare the attitudes of physicians and law professionals on modern bioethical issues. Euthanasia, physician assisted suicide and abortion were selected for this study, as they underline the conflict between human life as a fundamental value, and the individual&apos;s right to self-determination. The demand of euthanasia and physician assisted suicide services reflects each person&apos;s right to decide on the way their life will end, while the legalization of abortion determines the individual&apos;s right to self-determination. These are complex issues with moral, religious and social implications, and as such tend to divide public opinion. In order to investigate their attitudes, physicians of all specialties, as well as law professionals from all over Greece, were invited to participate in the study. In total, 220 professionals responded to the call and participated in the survey. The professionals involved showed fairly high rates of agreement in all the issues studied, but a significant difference in results was found when the occupation of participants was set as a criterion, with physicians being more negative to euthanasia, physician assisted suicide and abortion than lawyers. Religiousness, age and male sex were negatively correlated with &quot;positive&quot; attitudes towards euthanasia, physician assisted suicide and abortion. Moreover, participants&apos; attitudes towards euthanasia and physician assisted suicide were found to predict their attitudes towards abortion, indicating a single ideological direction of agreement or disagreement, accordingly. Individuals&apos; attitudes and opinions are complicated issues, not easy to be categorized. However, it is of scientific interest to shape a legislative framework that is close to the social consensus, ideological evolution and moral needs. This study tried to pave the way for a modern approach to the issues of euthanasia, physician assisted suicide and abortion