<p> Fragile X Syndrome (FXS) is the most common inherited disease of mental impairment, typically caused by a mutation in the Fragile X mental retardation 1 (FMRJ) gene. The clinical features are thought to result from abnormal neurobiology due to a lack of the Fragile X mental retardation protein (FMRP). Previously, it was thought that FMRP was confined exclusively to neurons; however, our laboratory recently discovered that astrocytes also express FMRP. Consequently, it is possible that astrocytes also suffer abnormalities as a result of a lack of FMRP. Astrocytes play integral roles in the development and maintenance of communication in the central nervous system. Therefore, it is now important to determine the contribution of astrocytes to the abnormal neuronal phenotype seen in FXS. In these experiments, neurons and astrocytes were independently isolated from wild type (WT) or FMRJ null mice and grown in a coculture. Neurons were evaluated using immunocytochemistry in combination with computer-aided morphometric and synaptic protein analyses. The findings presented here provide convincing evidence that Fragile X astrocytes contribute to the abnormal neurobiology seen in FXS . Fragile X astrocytes alter the dendrite morphology and excitatory synaptic protein expression of WT neurons in culture; and, importantly, when Fragile X neurons are grown with WT astrocytes these changes are prevented. Interestingly, the Fragile X astrocytes appear to act by causing a delay in development; even WT neurons grown in the presence of Fragile X astrocytes, that displayed an abnormal phenotype at 7 days in culture, exhibited nearly normal dendrite morphology and expression of excitatory synapses at 21 days. Furthermore, the results suggest that the dendritic abnormalities induced by the Fragile X astrocytes specifically target neurons with a spiny stellate morphology. This research establishes a role for astrocytes in the development of the abnormal neurobiology seen in FXS, and as such, the results presented here have significant implications for Fragile X research. The novel prospect that astrocytes are key contributing components in the development of FXS provides an exciting new direction for investigations into the mechanisms underlying FXS, with many unexplored avenues for potential treatment strategies. </p> / Thesis / Doctor of Philosophy (PhD)

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В настоящем исследовании сравнивается зрительное восприятие детей 7–12 лет с аутизмом и легкой умственной отсталостью с учетом их системы сенсорной интеграции. В этом исследовании использовались 3 теста сенсорной интеграции SIPT, SPM2, Сенсорный профиль и Зрительно-моторный Гештальт-тест Бендера (всего 4 теста). При общем сравнении и сравнении случаев были указаны три теста SIPT, SPM2, Сенсорный профиль относительно эффективности для тестируемой группы детей (аутизм и умственная отсталость), слабые и сильные стороны этих тестов. Гештальт-тест Бандера дал нам хорошую информацию о различиях в зрительном восприятии и различиях в вводе визуальной информации в двух тестируемых группах. В тестах на рисование и копирование дети с аутизмом показали лучшие результаты (ближе к нормальному диапазону успеваемости). По результатам можно утверждать, что у детей-аутистов нет проблем в процессе зрительного восприятия и обработки, а разница может заключаться в том, как зрительная информация поступает в их систему зрительной обработки, тогда как у умственно отсталых детей наблюдаются нарушения в зрительной системе. система обработки восприятия. / The present study compares visual perception between 7-12-year-old children with autism and mild mental retardation, considering their sensory integration system. In this research, 3 sensory integration tests SIPT, SPM2, sensory profile and Visual-motor Bender Gestalt test were used (total 4 tests). In the overall comparison and the case comparison, the three SIPT, SPM2, Sensory profile tests were stated regarding the effectiveness for the tested group of children (autism and mental retardation), the weaknesses and strengths of these tests. Bander Gestalt test gave us good information about the differences in visual perception and differences in the input of visual information in the two tested groups. In the drawing and copying tests, autistic children obtained better results (closer to the normal performance range). According to the results, it can be claimed that autistic children do not have problems in the process of visual perception and processing, and the difference can be in the way visual information enters their visual processing system, while mentally retarded children have disorders in the visual perception processing system.

The study aimed at giving a thick description of African families' experiences, views, cultural beliefs and interpretations of traumatic brain injury (TBI), and making recommendations for rehabilitation. It was conducted from the qualitative research paradigm, adopting a phenomenological research method. Twenty-two pairs of participants (patients and their caregivers )were interviewed about their perception of TBI. The semi-structured interviews were conducted at the participants' homes in Sesotho, and where necessary in their home languages. The consequences of TBI were found to follow universal trends (Oddy, 1984). However, participants' perceptions, as shaped by their experiences, views and cultural beliefs, were found to be unique. On analysing the gathered data, using inductive data analysis, it was found that African families' interpretations of TBI were based on beliefs about witchcraft, thwasa, Satanism, ancestral anger and God's wish. Based on these findings, rehabilitation services in the form of education, advocacy, networking and family therapy are recommended. / Psychology / M.A.(Clinical Psychology)

Syftet med denna studie är att bidra med en fördjupad förståelse av och kunskap om hur interaktionen mellan en matematiklärare och en högstadieelev på grundsärskolan gestaltar sig när eleven löser problemlösningsuppgifter. Studien har ett sociokulturellt perspektiv. Studiens metod är videoinspelade klassrumsobservationer på en grundsärskolas högstadium. Studiens observationer fokuserar på interaktionen mellan läraren och en specifik elev under matematiklektionerna där fler elever varit närvarande. Frågeställningarna handlar om talutrymme, initiativtagande, hur eleven visar sin matematiska förståelse, lärarens kommunikationsanpassningar utifrån elevens matematiska förståelse och lärarens språkanvändning som ett verktyg respektive hinder för elevens matematiklärande. Studiens resultat visar att både elev och lärare bidrar till formandet av undervisningen. Eleven visar sin förståelse genom att ställa specifika matematiska frågor, att be om bekräftelse, att be om lotsning/vägledning, att vara helt tyst, att svara på ett osäkert sätt, att svara på ett säkert sätt, att instruera sig själv och att ställa nyfikna frågor. I interaktionen anpassar matematikläraren sitt kommunikationssätt efter elevens matematiska förståelse. Lärarens kommunikationssätt är att med vägledande/lotsande frågor, slutna frågor, bekräftelse, beröm och specifika matematiska frågor stödja elevens lärande i matematik.   Denna studie kan bidra till att öka förståelsen för hur interaktionen mellan matematikläraren och enskild elev – i klassrummet med fler elever närvarande är en viktig undervisningsform där läraren får möjlighet att möta den enskilda eleven utifrån elevens individuella kunskaper. / The purpose of this study is to provide in-depth understanding and knowledge of interaction between math teacher and a junior high student at a special education school when the student works on problem solving tasks. The study has a socio-cultural perspective.   The method for the study consists of video recorded observations from the classroom at a junior high special education school. The observations focus on interaction between the teacher and a specific student during math classes where several students are present.   The questions concern the opportunity to speak, initiative, how the student shows his/hers understanding of mathematics, the teacher´s modifications of the communication based on the student´s understanding of mathematics and how the teacher´s use of the language functions of mathematics as a toll or becomes an obstacle for the student´s learning of mathematics.   The student results shows his/her understanding by asking open questions, requesting confirmation, asking for guidance, remaining totally quiet, answering in an insecure or a confident manner, instructing himself/herself an being curious. The math teacher adjusts his/her mode of communication to the student´s understanding of mathematics during the interaction. The teacher´s mode of communication is to support the student´s learning of mathematics through guiding questions, closed questions, confirmation, praise and specific math questions.   This study can contribute to an increased understanding of how the interaction between the math teacher and a single student – with several students present in the classroom – provides an important form of teaching where the teacher has an opportunity to approach the single student baser on that student´s individual knowledge.

Η Αυξητική ορμόνη παίζει σημαντικό ρόλο στη μεταγεννητική κατά μήκος αύξηση, στη σκελετική ανάπτυξη, στο μεταβολισμό των πρωτεϊνών, των λιπών και των υδατανθράκων, στην οστική ανακύκλωση και την ανοσιακή λειτουργία. Διαταραχή στην έκκριση ή στη δράση της ορμόνης στα παιδιά προκαλεί, μεταξύ άλλων, ανεπάρκεια αύξησης. Έχουν περιγραφεί αρκετές κλινικές οντότητες ανεπάρκειας αύξησης, που οφείλονται κυρίως σε διαταραχές στην υποφυσιακή έκκριση GH, στην 24ωρη αυθόρμητη έκκριση της GH, στον αριθμό ή τη λειτουργία των υποδοχέων GHR, στη μετά τον υποδοχέα μεταβίβαση του σήματος της GH και στη σύνθεση ή δράση του IGF-I. Η παρούσα μελέτη εξέτασε έναν ασθενή με Διαταραχή στη Μεταγωγή του Σήματος της GH (Growth Hormone Transduction Defect/GHTD). Η οντότητα αυτή χαρακτηρίζεται από σοβαρό κοντό ανάστημα με φυσιολογικές δοκιμασίες φαρμακολογικής πρόκλησης, φυσιολογικές τιμές 24ωρης έκκρισης GH, χαμηλά επίπεδα IGF-I, διαταραχή στη φωσφορυλίωση του μεταγραφικού παράγοντα STAT3 και υπερέκφραση του αναστολέα του κυτταρικού κύκλου p21. Επιπλέον, οι ασθενείς με GHTD παρουσιάζουν σημαντικά αυξημένα επίπεδα IGF-I μετά από επαγωγή με hGH κατά τo IGF-I generation test και σημαντική αναπλήρωση αύξησης μετά από θεραπεία με hGH. Επίσης, χαρακτηρίζονται από απουσία μεταλλάξεων στην πρωτεΐνη STAT3, στον υποδοχέα GHR και στο γονίδιο GH1. Χρησιμοποιήθηκαν πρωτογενείς καλλιέργειες ινοβλαστών από ούλα του προς μελέτη ασθενή κι ενός μάρτυρα. Μελετήθηκαν σηματοδοτικά μόρια του μεταγωγικού μονοπατιού της GH και του μονοπατιού αρνητικής ρύθμισης, και διερευνήθηκε ο ρόλος της πρωτεΐνης CIS στην παθολογική μεταβίβαση του σήματος της GH στον ασθενή, καθώς και η επίδραση της καταστολής του γονιδίου CIS στη σηματοδότηση της GH. Επίσης, διερευνήθηκε η πιθανή διασυνομιλία ανάμεσα στα σηματοδοτικά μονοπάτια της GH και του EGF, καθώς και ο ρόλος της διασυνομιλίας αυτής στην αποκατάσταση της φυσιολογικής σηματοδότησης της GH και, κατ’επέκταση, στην κλινική ανταπόκριση μετά από θεραπεία με εξωγενώς χορηγούμενη ανθρώπινη βιοσυνθετική ορμόνη, παιδιών με GHTD. Η πρωτεϊνική έκφραση των μελετηθέντων πρωτεϊνών μελετήθηκε με ανοσοαποτύπωση κατά Western, η κυτταρική εντόπισή τους με ανοσοφθορισμό και η διαντίδραση ορισμένων από τις πρωτεΐνες με ανοσοσυγκατακρήμνιση. Τα ευρήματα της εργασίας στοιχειοθετούν την αρχική υπόθεση ότι η διαταραγμένη μεταβίβαση του σήματος της GH στα παιδιά με GHTD διαμεσολαβείται μέσω της υπερέκφρασης της ουβικουιτινυλιωμένης μορφής της πρωτεΐνης CIS, η οποίθα προκαλεί ραγδαία και εκσεσημασμένη μεταφορά του GHR στο πρωτεάσωμα για αποδόμηση. Τα αποτελέσματα επίσης έδειξαν ότι η αποκατάσταση της φυσιολογικής σηματοδότησης της GH μετά τη σίγαση του γονιδίου CIS περιλαμβάνει την επαναφορά του GHR στην κυτταροπλασματική μεμβράνη για φυσιολογική ενεργοποίηση από την GH, καθώς και την ενεργοποίηση του σηματοδοτικού μονοπατιού του EGFR. Επιπροσθέτως, υπάρχει έντονη διασυνομιλία μεταξύ των σηματοδοτικών μονοπατιών της GH και του EGF κατά τη χορήγηση εξωγενούς hGH στα παιδιά με GHTD, με αποτέλεσμα την επιτάχυνση της αύξησης που παρατηρείται στα παιδιά αυτά μετά από θεραπεία με hGH. / Growth Hormone (GH) plays an important role in postnatal linear growth, skeletal development, protein, lipid and carbohydrate metabolism, bone turnover and immune function. Defects in the GH secretion and function in children can cause growth retardation. Several clinical entities of growth retardation have been described, including defects in pituitary GH secretion, spontaneous 24h GH secretion, GH receptor number or function, post-receptor signaling and IGF-I synthesis or function. In this study, one patient with Growth Hormone Transduction Defect (GHTD) was studied. GHTD is characterized by severe short stature with normal provoked and spontaneous GH secretion, low IGF-I concentrations, impaired phosphorylation of the transcriptional factor STAT3 and overexpression of the cyclin-dependent kinase inhibitor, p21. Furthermore, GHTD patients have significantly increased IGF-I concentrations after induction with hGH during the IGF-I generation test, and significant ‘catch-up’ growth after hGH therapy. No mutations were found in STAT3, GHR and GH1 gene in the GHTD patients. Primary fibroblast cultures were established from gingival biopsies obtained from the GHTD patient and one control. The GH signaling molecules and the negative regulators of GH were studied, as well as the role of protein CIS in the impaired GH signaling and the effect of CIS silencing on GH signaling. Furthermore, the possible crosstalk between the GH and EGF signaling cascades was examined, as well as its role in the restoration of the impaired GH signaling and the clinical response after therapy with exogenous hGH. The protein expression of the studied molecules was studied by Western Immunoblotting, their cellular localization by Immunofluoresence and the protein-protein interactions by Co-immunoprecipitation. The results of this study support the hypothesis that impaired GH signaling in GHTD children is mediated by the overexpression of ubiquitinated CIS, which causes rapid and excessive translocation of the GHR to the proteasomes for degradation. The results also showed that the restoration of physiological GH signaling after the silencing of CIS involves the restoration of the GHR to the plasma membrane for normal activation by GH, as well as the activation of the EGFR pathway. In addition, there is vigorous crosstalking between the GH and EGF signaling pathways during exogenous hGH treatment in the GHTD children, resulting in the accelerated growth seen in these children after hGH therapy.

I have sought to discover genetic causes of neuroanatomical defects by conducting N-ethyl-N-nitrosourea mutagenesis and transgenic knock out screens in mice. The rationale behind this is that mutations causal to structural defects will be informative about developmental neurobiology and the biological basis of behaviour. Direct screening for behavioural abnormalities in mice has historically been arduous and yielded few findings due to small effect sizes and limited statistical power. My approach sought to bypass these problems by screening for highly penetrant morphological phenotypes. This thesis details my screens and the histological, genetic and behavioural characterisation of lines of interest. These include models of hydrocephalous, pyramidal cell layer ectopia, abnormal neurogenesis, corpus callosum agenesis, hippocampal enlargement, elevated cell death and hypomyelination. Whilst N-ethyl-N-nitrosourea mutagenesis screening has been conducted since the twilight of the 20^th century, systematic transgenic knock out screening is currently in its infancy. By discovering gene-phenotype associations through both approaches, I have been able to compare the relative yields, strengths and weaknesses of the two screening methods. Additionally, I have discussed the significant of the gene-phenotype associations produced from both screens.

Syfte: Syftet med denna uppsats är att undersöka och jämföra mängden och nivån på fysisk aktivitet under skoldagen, där även lektioner i idrott och hälsa ingår, hos elever på gymnasie- och gymnasiesärskolan. Metod: Målgruppen utgjordes av en klass från gymnasiesärskolan bestående av sex elever och45 elever från fyra klasser från årskurs 1–3 i gymnasieskolan. För att undersöka mängden och nivån av den fysiska aktiviteten användes som mätinstrument stegräknare och pulsmätare. Undersökningen pågick under två skoldagar som inkluderade lektioner i idrott och hälsa. Som teoretiskt ramverk kommer uppsatsen utgå från begreppet fysisk aktivitet, indelat i nivå och mängd, vilket kommer analyseras utifrån begreppet moderate to vigorous physical activity (MVPA) samt hälsorekommendationerna gällande antal steg per dag. Resultat: Undersökningen visade att eleverna i gymnasiesärskolan och gymnasieskolan i genomsnitt ackumulerade ungefär lika många steg under en skoldag. Det var däremot signifikant skillnad när det gällde hur många av skoldagens steg som utfördes under lektionen i idrott och hälsa. Eleverna i gymnasiesärskolan gick ca 34 procent av skoldagens totala antal steg under lektionen i idrott och hälsa medan eleverna i gymnasieskolan gick ca 50 procent. Det var också signifikant skillnad gällande vilken nivå av fysisk aktivitet eleverna låg på under lektionen i idrott och hälsa. Eleverna i gymnasiesärskolan spenderade ca 33 procent av lektionen i MVPA medan motsvarande var 70 procent av lektionen för eleverna gymnasieskolan.    Slutsats: Resultatet gällande total fysisk aktivitet under skoldagen indikerar att eleverna i gymnasiesärskolan har en mer fysisk aktiv skoldag utöver lektionerna i idrott och hälsa än eleverna på gymnasieskolan. Detta eftersom resultatet visar att de kommer upp i liknande antal steg över en hel skoldag, trots att de har färre antal steg på lektionen i idrott och hälsa än eleverna på gymnasieskolan. Beträffande nivån på fysisk aktivitet under lektionen i idrott och hälsa visade resultaten signifikanta skillnader gällande tid spenderad i MVPA mellan grupperna. Eleverna i gymnasiesärskolan spenderade mindre än hälften av lektionstiden i MVPA jämfört med eleverna i gymnasieskolan. En förklaring till det skulle kunna var olika lektionsinnehåll eller problematiken kring utvecklingsstörning. / Purpose: The main purpose of this study was to examine and compare amount and level of physical activity during the school day, which also include a physical education lesson, among pupils in upper secondary school with and without mental retardation. Method: The target group of this study composed of six high school students from one class from special school and 45 students from four classes of first to third grade in the upper secondary school. In order to examine the amount and level of physical activity, the study used pedometers and heart rate monitors. The survey of this study lasted two whole school days which included physical education lessons. As for theoretical framework, this study presupposes from the concept physical activity which is divided into level and amount of physical activity. It will be analyzed with the concept moderate to vigorous physical activity (MVPA)and the recommendation of health regarding steps taken per day. Results: The study showed that students from the special school and upper secondary school on average accumulated the same amount of steps during one school day. There was however a significant difference in how much of the total steps of the school day that was accumulated during the physical education lesson. For the students in the special school about 34 percent of the steps taken during the school day came from the physical education lesson and equal result for the students in upper secondary school was about 50 percent. There were also significant differences regarding the level of physical activity among the students during the lesson in physical education. Students in special school spent about 33 percent of the lesson in MVPA while the students in upper secondary school spent 70 percent of the lesson in MVPA. Conclusion: The result indicates that the students in special school overall have a more active schoolday beyond the lessons in physical education than the students in upper secondary school. This is because the results show that they have the same amount of steps during the whole school day, despite the fact that they have fewer steps than the students in upper secondary school during the lesson in physical education. Regarding the level of physical activity during the lesson in physical education the result showed significant difference between the study groups. The students in the special school spent less than half the time in MVPA compared with the students in upper secondary school. An explanation to that could be different lesson content or the complex of problems regarding intellectual disabilities.

The thesis focuses mostly on discovering unrevealed causes of pathologic phenotype symptoms of patients with whom no pathologic changes in genetic material were detected by common cytogenetic methods. All samples were examined by a chip method array-CGH (comparative genomic hybridization) which detects aberrant spots without any knowledge of where they are located in the genome. In some cases the method was used to verify or specify the finding that was diagnosed during previous genetic testing. The patients were examined by this method in an accredited genetics laboratory GENvia, s.r.o. in 2013 and partly also in 2014. The theoretical part of the thesis focuses on the role of the common cytogenetic method and its diagnostic use. I also describe the basic principle of the array-CGH method and its use in prenatal and postnatal diagnostics. The practical part of the thesis describes results of all examined patients. But mostly it focuses on pediatric patients where the diagnosis correlates with their clinical symptoms. All the results were verified by another method used for the particular diagnosis. Some results were verified by FISH (fluorescence in situ hybridization) method, other ways of the results verification are described as well. In total 8 pathologic findings were discovered in patients up to 12...

This thesis is devoted to the history of Children's Psychiatric Hospital, which was founded in the South Bohemian Opařany in 1887 as a branch of the Prague Institute for the Mentally Ill. For a deeper understanding of the topic, the thesis focuses more on the importance and appreciation of selected personalities who dedicated themselves to people with learning disabilities and psychiatric conditions. In the introductory part, the thesis focuses on the presentation of the field of psychopaedia and the individual selected concepts / definitions that are competently explained using appropriate terminology. It also contains the biography of selected representatives of the field who have contributed to the development of the paradigm of the psychopaedic care. The current specialisation of Opařany hospital and its therapeutic possibilities are particularly discussed, with particular emphasis on the comprehensive component and selected therapeutic methods in special education - art therapy, music therapy, occupational therapy.The work seeks to provide a comprehensive account of the history of the Opařany Institute and of the related topics in the field of the psychopaedic care. Keywords Children's Psychiatric Hospital Opařany The history of special education Mental disorder Mental retardation Psychopaedia...