Working memory updating training and the rehabilitation of goal management after brain injury

This thesis follows an interdisciplinary research approach employing methods from the fields of clinical neuropsychology and cognitive neuroscience to investigate the plastic changes following cognitive training. Disentangling the mechanism behind the training-induced cognitive and neural plastic changes can have a direct impact on the cognitive rehabilitation of individuals with long term cognitive impairments. Chapter one provides a brief overview of the executive function difficulties associated with acquired brain injury (ABI) and a description of the clinically evaluated goal management strategy-based training (Levine, Manly and Robertson, 2012). Process-based training paradigms and their implication for generalisation of learning are subsequently discussed together with the theoretical framework of adult plasticity proposed by Lövdén et al., (2010). The chapter discusses working memory processes, their relationship with executive functions and provides a description of the WM neural network involving fronto-parietal and striatal areas. At the end of this chapter, the development of a multidisciplinary intervention integrating goal management strategies and working memory process-based training in adults with ABI is described. Chapters two, three and four primarily focus on research in healthy adult populations and investigate the cognitive and neural changes following working memory updating (WMU) training. Chapter two is a meta-analysis of the training and transfer effects conducted together with a systematic review of the functional activity changes following WMU training. Existing work focuses mainly on healthy adults together with a small number of studies involving neurological populations. Chapters three and four investigate the grey matter volumetric changes and the task-based functional connectivity changes following adaptive working memory updating training in healthy young adults. These analyses are complementary to a previous fMRI analysis conducted by Flegal, Ragland and Ranganath (2019). Chapters five, six and seven focus on the transition from research with healthy adults to individuals with ABI and describes the development of an integrated goal management strategy and WMU process-based training protocol targeting executive dysfunction ABI. Chapter five is a critical review discussing key issues in the field of cognitive training with emphasis on WM protocols and highlights the importance of employing interdisciplinary methods from the field of cognitive neuroscience and clinical neuropsychology. Chapter six involves the detailed description of the integrated processes and strategies (iPRESS) training protocol combining the goal management training (GMT) (Levine, Manly and Robertson, 2012) with the adaptive WMU training protocol employed in Flegal, Ragland and Ranganath (2019). This chapter further describes the amendments put in place to allow for remote delivery of the iPRESS protocol due to COVID-19 constraints and disruptions. Chapter seven investigates the feasibility of running the remote version of iPRESS and to test the fMRI task protocol adapted for an individual with ABI. Chapter eight discusses the implications of the research conducted in this thesis involving a better understanding of the training-induced plastic changes as well as the development of interdisciplinary cognitive interventions. Finally, the chapter posits research questions to be addressed in the future

Η Αστική Ευθύνη των Δήμων κατά τα άρθρα 105-106 του Εισαγωγικού Νόμου του Αστικού Κώδικα. Η περίπτωση της εξωδικαστικής επίλυσης της διαφοράς

Το Δημόσιο και οι Οργανισμοί Τοπικής Αυτοδιοίκησης ευθύνονται σε αποζημίωση για παράνομες πράξεις, υλικές ενέργειες ή και παραλείψεις των οργάνων τους κατά την άσκηση των αρμοδιοτήτων που τους έχουν ανατεθεί. Η ευθύνη τους αυτή, που oνομάζεται «αστική», θεμελιώνεται στον Εισαγωγικό Νόμο του Αστικού Κώδικα και είναι αντικειμενική. Είναι δηλαδή ανεξάρτητη από την ύπαρξη ή μη υπαιτιότητας του οργάνου του Δημοσίου ή των ΟΤΑ, η πράξη, η παράλειψη ή υλική ενέργεια του οποίου προκάλεσε τη ζημιά. Όσοι υπέστησαν ζημία, εκ πράξεων ή παραλείψεων δηλαδή των οργάνων των ΟΤΑ, μπορούν να διεκδικήσουν την καταβολή αποζημίωσης από τα αρμόδια δικαστήρια. Οι αγωγές αποζημίωσης αυτές αφορούν κυρίως περιουσιακές ζημιές ή βλάβες της υγείας, που προήλθαν, από κακοτεχνίες του οδοστρώματος, από ελλιπή ή πλημμελή σήμανση ή φωτισμό των οδών, πτώση κλαδιών ή κορμών δένδρων, μετακινήσεις κάδων απορριμμάτων, τραυματισμό από αδέσποτο ζώο και άλλες παρεμφερείς αιτίες του πεδίου αρμοδιότητας των Δήμων. Παρατηρείται μάλιστα, ότι, τα τελευταία έτη, λόγω της παρατεταμένης οικονομικής κρίσης που επηρέασε τα ταμεία των Δήμων και «πάγωσε» τα έργα ανάπλασης των πόλεων, αλλά και λόγω των επιπτώσεων των έντονων φαινομένων της κλιματικής μεταβολής στις πόλεις, τα περιστατικά για τα οποία ευθύνονται οι Δήμοι σε αποζημίωση, έχουν αυξηθεί. Αντικείμενο της παρούσας εργασίας αποτελεί η περιγραφή της διαδικασίας καταβολής αποζημίωσης, για την αποκατάσταση αυτών των ζημιών, με σύναψη εξώδικου συμβιβασμού μεταξύ Δήμων και τρίτων που προβλέπει το άρθρο 72 παρ.1 περίπτωση ι ́ του Νόμου 3852/2010, αντί της προσφυγής στη δικαιοσύνη. Θα αναλυθούν οι προϋποθέσεις που πρέπει να συντρέχουν σωρευτικά, προκειμένου να «γεννηθεί» η αστική ευθύνη, όπως τις καθορίζει η νομολογία των ελληνικών δικαστηρίων, αλλά και η διαδικασία για να αποζημιωθεί κάποιος από έναν Δήμο με συμβιβασμό. Παρουσιάζονται ακόμα συνήθη περιστατικά που αντιμετωπίζουν οι Δήμοι, στα πλαίσια της αστικής ευθύνης τους, και ο ρόλος που διαδραμάτισε ο Συνήγορος του Πολίτη για την αναβίωση του θεσμού της εξωδικαστικής επίλυσης της διαφοράς. Σκοπός της παρούσας εργασίας είναι να συμβάλει, μέσα από την ανάλυση της θεωρίας, την επισκόπηση της νομολογίας και την εξέταση περιπτώσεων που αντιμετώπισαν οι Δήμοι, στην ορθή εφαρμογή του μηχανισμού της εξωδικαστικής αποζημίωσης εκ μέρους των υπηρεσιών των Δήμων με στόχο την αποκατάσταση του αισθήματος της εμπιστοσύνης του διοικούμενου στη διοίκηση.The State and Local Administration Organizations are liable for damages resulting of illegal act, or omission, or material action of governmental personnel in the exercise of powers assigned to them. Civil liability is established in the Introductory Law of the Civil Code and is objective. It is irrespective, in other words, of the existence or not of fault on the part of personnel of the State or Local Authorities, the act, or omission, or material action of which caused personal injury or damage to property. Those who have suffered damage or injury, caused by a negligent act or omission of personnel of local authorities, can claim compensation before the competent courts. These lawsuits principally concern personal injury or damage to property, which resulted of a highway or roadway defect, incomplete or defective road markings or roadway lighting, falling three branches or tree trunks, improper placing of waste bins, injury caused due to stray animals and other causes in the Municipality competence. In fact, it has been observed in recent years, due to the prolonged economic crisis that affected the funds of the Municipalities and halted urban regeneration projects, but also owing to the impacts of climate change in the cities, that the incidents for which the Municipalities are held liable in damages or injury have increased. The object of this study is to describe the procedure for payment of compensation for injury or damages, by concluding an out-of-court settlement between Municipalities and third parties, instead of going to court, under article 72 par. 1 case 10 of Law 3852/2010. The conditions that must be met cumulatively in order to engender civil liability, as defined by the case law of the Greek courts, will be analyzed, as well as the process for compensation by settlement from a Municipality. There are also common issues faced by Municipalities, in the context of civil liability, and the role of the Ombudsman for the revival of the institution of out-of-court dispute resolution. The purpose of the thesis is to contribute, through the analysis of theory and legislation and also case review to the correct application of the process of out-of-court settlement by the Municipalities in order to restore public confidence in the administration

Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma

The matrix protein osteopontin has been shown to be a marker of osteoclastic activity in multiple myeloma patients, as well as a regulator of angiogenesis. We measured serum levels of osteopontin in 50 untreated multiple myeloma patients (in 25, also after treatment) and examined the relation to markers of osteolytic and angiogenic activity. The median (range) of serum osteopontin was 85 (5-232) in the patient group vs. 36 (2-190) ng/ml in the control group. Serum osteopontin levels were significantly higher in patients with advanced stage or grade of myeloma disease. All patients with serum osteopontin levels >100 ng/ml had advanced stage (II or III) or high grade bone disease, whereas stage I or low grade patients had serum osteopontin levels <100ng/ml. Serum osteopontin levels significantly decreased after treatment. There was a positive correlation of osteopontin with the bone turnover marker N-terminal propeptide of procollagen type I (NTx) and the angiogenic markers vascular endothelial growth factor (VEGF) and bone marrow microvessel density (r: 0.35, 0.47 and 0.30 respectively, p < 0.05). These results support osteopontin as a dual marker of bone destruction and angiogenic activity in myeloma patients. Osteopontin represents a useful biomarker for monitoring myeloma disease activity

Peptide cell-display for selection of inhibitors against human glutathione transferase P1-1 (hGSTP1-1) allozymes

We developed a combinatorial strategy aiming at designing peptide inhibitors against the hGSTP1-1 isoenzyme involved in MDR. We developed a combinatorial strategy aiming at designing peptide inhibitors against the hGSTP1-1 isoenzyme. We employed a combinatorial peptide library featuring engineered E. coli cells harboring a plasmid able to express a fusion protein containing random 12peptides. After five selection rounds, clones were screened for hGSTP1-1 binding (dot blot hybridization) and those with the strongest signal were selected and sequenced. Sequence alignments showed a core binding sequence which, along with selected peptide fragments, were synthesized using the solid phase methodology . The synthetic peptides were studied for their inhibition potency against three human GSTP1-1 allozymes, A, B and

Combinatorial design, selection and synthesis of peptide inhibitors against human glutathione transferase p1-1

Certain glutathione S-transferase (GST) isoenzymes detoxify the cell from xenobiotics, thus becoming inhibition targets when overexpressed in various tumours leading to MDR. We developed a combinatorial strategy aiming at designing peptide inhibitors against the hGSTP1-1 isoenzyme involved in MDR. We employed a combinatorial peptide library featuring engineered E. coli cells harboring a plasmid able to express a fusion protein containing random 12 peptides which were inserted into the active loop of thioredoxin, which itself was inserted into the dispensable region of the flagellin gene. After five selection rounds, clones were screened for hGSTP1-1 binding and those with the strongest signal were selected and sequenced. Sequence alignments showed a core binding sequence which, along with selected peptide fragments, were synthesized using the solid phase methodology and Fmoc/tBu chemistry on 2-chlorotrityl chloride solid support. The four peptides were studied for their inhibition potency against hGSTP1-1 allozymes A, B and C

Transformation towards more sustainable soil management on Dutch arable farms

Currently a debate is ongoing in the Netherlands on how to increase soil sustainable management in general and specifically in short term lease. Sustainable practices may not be adopted by farmers because of an interplay between EU, national and provincial legislation, short-term land lease system, and social and economic aspects. Wageningen Plant Research requested students from Wageningen University to research this topic. The purpose of this project is to develop a Sustainable Soil Management Framework that integrates the legislation, economic and social factors, and Ecosystem Services in order to enable farmers to adopt sustainable soil management practices.Through a literature study key issues were collected on each of the aspects in the framework. Semi-structured interviews were conducted with farmers, land funds, provinces and experts. The interviewees provided additional key issues as well as input to potential solutions to those issues.The main key issues concern the absence of an evaluation and rewarding system of sustainable practices within lease agreements, the (short) duration of lease agreements, and insufficient knowledge transfer and exchange on soil sustainable management practices between farmers and other stakeholders. Based on these main key issues we propose a set of solutions for each aspect within the Sustainable Soil Management Framework

Synthesis of glutathione analogues and screening as substrates & inhibitors for human glutathione transferase p1‐1

A major detoxification mechanism of the cell involves the glutathione transferase (GST)‐catalyzed formation of glutathione (GSH) conjugates with various xenobiotics Based on the same mechanism, GST overexpression may lead to multidrug resistant phenotypes Therefore, several compounds with inhibitory potency against GSTs have been developed as potential tools fortackling GST-­‐attributed MDR. Several individual compounds and prodrugs have been proposed as GST‐inhibiting substances. In addition, GSH analogues have been considered as specific GST inhibitors, with particular attention been directed towards the synthesis of GSH analogues stable against γ‐glutamyltranspeptidase (γGT) and peptidases, as GST inhibitors

Marine-Derived Surface Active Agents: Health-Promoting Properties and Blue Biotechnology-Based Applications

Surface active agents are characterized for their capacity to adsorb to fluid and solid-water interfaces. They can be classified as surfactants and emulsifiers based on their molecular weight (MW) and properties. Over the years, the chemical surfactant industry has been rapidly increasing to meet consumer demands. Consequently, such a boost has led to the search for more sustainable and biodegradable alternatives, as chemical surfactants are non-biodegradable, thus causing an adverse effect on the environment. To these ends, many microbial and/or marine-derived molecules have been shown to possess various biological properties that could allow manufacturers to make additional health-promoting claims for their products. Our aim, in this review article, is to provide up to date information of critical health-promoting properties of these molecules and their use in blue-based biotechnology (i.e., biotechnology using aquatic organisms) with a focus on food, cosmetic and pharmaceutical/biomedical applications

Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities, July to October 2021

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.S