Καρκίνος στην παιδική ηλικία. Επιπτώσεις στην εικόνα σώματος και τη σεξουαλικότητα στην εφηβεία

Στην παρούσα πτυχιακή εργασία γίνεται προσπάθεια να εξετασθούν οι επιπτώσεις του καρκίνου στην παιδική ηλικία, στο τότε αναπτυσσόμενο σώμα και ψυχισμό, στην εικόνα σώματος και τη στάση του ατόμου απέναντι στη σεξουαλικότητα στην εφηβεία. Το κεντρικό επιχείρημα που θα αναπτυχθεί θα είναι βασισμένο πάνω σε κλινικό υλικό έφηβης που στην παιδική ηλικία εμφάνισε καρκίνο. Θα γίνει αναφορά στην επανεμφάνιση στην εφηβεία, ίσως και με μεγαλύτερη ένταση ή με άλλη μορφή των εκδηλώσεων της συμπτωματολογίας του καρκίνου (χωρίς να ξανανοσήσει), που αντιμετώπισε το άτομο ως παιδί (απώλεια κιλών, πτώση μαλλιών κ.α.). Η μελέτη αυτή θα αφορά κυρίως στη σφαίρα των ψυχικών εκδηλώσεων και ειδικότερα σε φαινόμενα της συμπεριφοράς και των σωματοποιήσεων, στις αντικειμενότροπες σχέσεις, και στην επίδραση των τραυματικών εμπειριών, που σχετίζονται με τις ανεπάρκειες της ψυχικής λειτουργίας και την εμφάνιση της παθολογίας. Έμφαση δίνεται στην προσπάθεια διερεύνησης της παθολογίας του Εγώ, διερευνώντας τα πρώιμα ψυχικά τραύματα, τους πρώιμους μηχανισμούς άμυνας, τις καθηλώσεις, τα ναρκισσιστικά ελλείμματα και την επανεμφάνιση των ελλειμμάτων αυτών στην εφηβεία. Επίσης σημαντική είναι η αναφορά στην παλινδρόμηση της λίμπιντο που συνδέεται με την παιδική παντοδυναμία. Ακόμα θα αναφερθούν οι ψυχικές άμυνες σε διαδικασίες απώλειας και πένθους και οι θεραπευτικές παρεμβάσεις που έγιναν ώστε να κρατηθεί το νόημα των αντικειμένου. Η μεθοδολογία της έρευνας που θα χρησιμοποιηθεί είναι η Μελέτη Περίπτωσης. Το σκεπτικό της εργασίας αφορά κυρίως στην κλινική παρατήρηση για την κατανόηση και την ερμηνεία του υλικού (συνειδητού και ασυνείδητου) που μας παρέχει η ασθενής. Στόχος είναι η εμβάθυνση και κατανόηση των κλινικών φαινομένων η προσπάθεια αναλυτικής αναφοράς της περίπτωσης που μελετάται, της προσωπικότητάς της, της αλληλουχίας των γεγονότων, των συγκρούσεων κ.α. Σημαντική θα είναι η αναφορά στην πολύ καθοριστική συμβολή της ψυχοδυναμικής ψυχοθεραπείας στην βαθύτερη κατανόηση της σχέσης των αναπτυξιακών σταδίων και των εκδηλώσεων στην σωματική και ψυχοσεξουαλική ανάπτυξη του ατόμου. Σκοπός: Επιδιώκεται λοιπόν, η σύνδεση, η μελέτη και η ερμηνεία των εκδηλώσεων μιας τραυματικής εμπειρίας στην παιδική ηλικία (καρκίνος), με την ψυχοσεξουαλική ανάπτυξη και την εικόνα σώματος του ατόμου στην εφηβεία.The primary goal of this Master’s Thesis is to examine the consequences of cancer in childhood, in the then developing body and psyche, along with the body image and the attitude of the child towards sexuality in adolescence. The study will elaborate on clinical material related to a female teenager who was diagnosed with cancer in her early childhood. Reference will be made to the reappearance of the disease in adolescence, perhaps with even greater intensity or by another form of the manifestations of the cancer symptoms (without ailing again), which the individual confronted as a child (weight loss, hair loss etc.). This research is focused on the field of manifestations and more specifically on phenomena related to the behavior and the somatizations, the object relations, and on the influence of traumatic experiences related to the deficiencies of the psychological function and the appearance of pathology. Emphasis is given on the attempt to explore the pathology of the “Ego” by examining the early psychological traumas, the early mechanisms of defense, the restrains, the narcissist deficits, and their reappearance in adolescence. It is also worthy to mention the functional properties of thought and the regression of libido which is associated with childhood omnipotence. Moreover, the psychological defense mechanisms used in the coping process of loss and mourning will be reported as well as the therapeutic interventions made to keep the meaning of the object. The rationale for the study is mainly about the clinical observation for the understanding and interpretation of the material (both conscious and subconscious) that is provided by the patient. More specifically, the aim of this research is to deepen and understand the clinical phenomena, to thoroughly report on the case study, and especially, to examine her personality, the sequence of the events, the conflicts she faced and so on. Additionally, there is a significant reference on the crucial contribution of the psychodynamic psychotherapy sessions to the deeper understanding of the relationship between developmental stages and manifestations in somatic and psychosexual development of the individual. In summary, this study aims to link, study and interpret the events of a traumatic experience in childhood in childhood (cancer) in relation to the psychosexual development and body image in adolescence

GNG5 Controls the Number of Apical and Basal Progenitors and Alters Neuronal Migration During Cortical Development

Cortical development is a very complex process in which any temporal or spatial alterations can give rise to a wide range of cortical malformations. Among those malformations, periventricular heterotopia (PH) is characterized by clusters of neurons that do not migrate to the correct place. Cerebral organoids derived from patients with mutations in DCHS1 and FAT4, which have been associated with PH, exhibit higher levels of GNG5 expression in a patient-specific cluster of neurons. Here we investigate the role of GNG5 during the development of the cerebral cortex in mice and human cerebral organoids. GNG5, highly expressed in progenitors and downregulated in neurons, is critical for controlling the number of apical and basal progenitors and neuronal migration. Moreover, forced expression of GNG5 recapitulates some of the alterations observed upon downregulation of Dchs1 and Fat4 in mice and human cerebral organoids derived from DCHS1 and FAT4 patients, suggesting a critical role of GNG5 in cortical development

Water Quality modelling of the Southern North sea using TELEMAC-3D coupled with AED2

Hydrodynamic

Large Eddy Simulations of sediment entrainment induced by a lock-exchange gravity current

Large Eddy simulations of lock-exchange gravity currents propagating over a mobile reach are presented. The numerical setting allows to investigate the sediment pick up induced by the currents and to study the underlying mechanisms leading to sediment entrainment for different Grashof numbers and grain sizes. First, the velocity field and the bed shear-stress distribution are investigated, along with turbulent structures formed in the flow, before the current reaches the mobile bed. Then, during the propagation of the current above the erodible section of the bed the contour plots of the entrained material are pre- sented as well as the time evolution of the areas covered by the current and by the sediment at this section. The numerical outcomes are compared with experimental data showing a very good agreement. Overall, the study confirms that sediment pick up is prevalent at the head of the current where the strongest turbulence occurs. Further, above the mobile reach of the bed, settling process seems to be of minor importance, with the entrained material being advected downstream by the current. Additionally, the study shows that, although shear stress is the main mechanism that sets particles in motion, turbu- lent bursts as well as vertical velocity fluctuations are also necessary to counteract the falling velocity of the particles and maintain them into suspension. Finally, the analysis of the stability conditions of the current shows that, from one side, sediment concentration gives a negligible contribution to the stability of the front of the current and from the other side, the stability conditions provided by the current do not allow sediments to move into the ambient fluid

Non-cell-autonomous regulation of interneuron specification mediated by extracellular vesicles

Disruption in neurogenesis and neuronal migration can influence the assembly of cortical circuits, affecting the excitatory-inhibitory balance and resulting in neurodevelopmental and neuropsychiatric disorders. Using ventral cerebral organoids and dorsoventral cerebral assembloids with mutations in the extracellular matrix gene LGALS3BP, we show that extracellular vesicles released into the extracellular environment regulate the molecular differentiation of neurons, resulting in alterations in migratory dynamics. To investigate how extracellular vesicles affect neuronal specification and migration dynamics, we collected extracellular vesicles from ventral cerebral organoids carrying a mutation in LGALS3BP, previously identified in individuals with cortical malformations and neuropsychiatric disorders. These results revealed differences in protein composition and changes in dorsoventral patterning. Proteins associated with cell fate decision, neuronal migration, and extracellular matrix composition were altered in mutant extracellular vesicles. Moreover, we show that treatment with extracellular vesicles changes the transcriptomic profile in neural progenitor cells. Our results indicate that neuronal molecular differentiation can be influenced by extracellular vesicles

NUMERICAL SIMULATION OF SEDIMENT ENTRAINMENT BY LOCK-EXCHANGE GRAVITY CURRENTS

Gravity currents are flows driven by buoyancy differences between two contacting fluids caused by differences in temperature, salinity, or by the presence of suspended particles. Such flows can reach high velocities near the bed, especially on the area behind the front of the current. As a result, rapid morphological changes may take place in river and estuarine beds due to the passage of these flows. Essential to determine the erosion induced by the current, are the spatial and temporal distributions of the bed shear stress. However, these are troublesome to measure in laboratory or in the field. To bridge this difficulty, the eddy-solving numerical simulations may be used. This study presents here the three-dimensional numerical simulations of lock-exchange salinity currents flowing over a mobile bed. It is aimed at the characterization of the sediment entrainment capacity of the current. The large eddy simulation technique is employed for analyzing the evolution and the structure of the current. For the sediment simulation, an Euler-Euler methodology based on a single phase approach is used. The main features of the current are compared with experimental data obtained in the laboratory. Velocity fields and bed shear stress distributions for different initial current densities are analyzed and linked to entrainment scenarios. The influence of small variations in particle size of the mobile bed is also discussed

Mcidas mutant mice reveal a two-step process for the specification and differentiation of multiciliated cells in mammals

Motile cilia on multiciliated cells (MCCs) function in fluid clearance over epithelia. Studies with Xenopus embryos and individuals with the congenital respiratory disorder reduced generation of multiple motile cilia (RGMC), have implicated the nuclear protein MCIDAS (MCI), in the transcriptional regulation of MCC specification and differentiation. Recently, a paralogous protein, geminin coiled-coil domain containing (GMNC), was also shown to be required for MCC formation. Surprisingly, in contrast to the presently held view, we find that Mci mutant mice can specify MCC precursors. However, these precursors cannot produce multiple basal bodies, and mature into single ciliated cells. We identify an essential role for MCI in inducing deuterosome pathway components for the production of multiple basal bodies. Moreover, GMNC and MCI associate differentially with the cell-cycle regulators E2F4 and E2F5, which enables them to activate distinct sets of target genes (ciliary transcription factor genes versus basal body amplification genes). Our data establish a previously unrecognized two-step model for MCC development: GMNC functions in the initial step for MCC precursor specification. GMNC induces Mci expression that drives the second step of basal body production for multiciliation

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy

Progressive myoclonus epilepsy (PME) of Unverricht-Lundborg type (EPM1) is an autosomal recessive neurodegenerative disorder with the highest incidence of PME worldwide. Mutations in the gene encoding cystatin B (CSTB) are the primary genetic cause of EPM1. Here, we investigate the role of CSTB during neurogenesis in vivo in the developing mouse brain and in vitro in human cerebral organoids (hCOs) derived from EPM1 patients. We find that CSTB (but not one of its pathological variants) is secreted into the mouse cerebral spinal fluid and the conditioned media from hCOs. In embryonic mouse brain, we find that functional CSTB influences progenitors' proliferation and modulates neuronal distribution by attracting interneurons to the site of secretion via cell-non-autonomous mechanisms. Similarly, in patient-derived hCOs, low levels of functional CSTB result in an alteration of progenitor's proliferation, premature differentiation, and changes in interneurons migration. Secretion and extracellular matrix organization are the biological processes particularly affected as suggested by a proteomic analysis in patients' hCOs. Overall, our study sheds new light on the cellular mechanisms underlying the development of EPM1

Mob2 Insufficiency Disrupts Neuronal Migration in the Developing Cortex

Disorders of neuronal mispositioning during brain development are phenotypically heterogeneous and their genetic causes remain largely unknown. Here, we report biallelic variants in a Hippo signaling factor-MOB2-in a patient with one such disorder, periventricular nodular heterotopia (PH). Genetic and cellular analysis of both variants confirmed them to be loss-of-function with enhanced sensitivity to transcript degradation via nonsense mediated decay (NMD) or increased protein turnover via the proteasome. Knockdown of Mob2 within the developing mouse cortex demonstrated its role in neuronal positioning. Cilia positioning and number within migrating neurons was also impaired with comparable defects detected following a reduction in levels of an upstream modulator of Mob2 function, Dchs1, a previously identified locus associated with PH. Moreover, reduced Mob2 expression increased phosphorylation of Filamin A, an actin cross-linking protein frequently mutated in cases of this disorder. These results reveal a key role for Mob2 in correct neuronal positioning within the developing cortex and outline a new candidate locus for PH development