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Development of the rodent somatosensory cortex is well characterised and involves activity-dependent mechanisms that occur during the first postnatal week. Glutamate is a key neurotransmitter responsible for signalling events that result in formation of cortical barrels - aggregates of cells in the cortex corresponding to whiskers on the face pad. The molecular mechanisms that occur downstream of glutamate signalling are not fully understood and data here contributes to the unveiling of some of these mechanisms. Transgenic mice with deletions of genes that encode members of the post-synaptic complex associated with NMDARs were used to understand the role of individual genes in the formation of barrels. SynGAP, a ras GTPase activating protein (GAP) that negatively regulates the ERK-MAPK pathway downstream of NMDARs is required for the formation of barrels and data here agrees with other findings that the ras GAP NF1 has a similar role. Examination of RICS, a RhoGAP and Dusp6 - a phosphatase that inactivates ERK reveals that neither are necessary for the formation of barrels. This finding adds to previous data postulating that barrels form in an ERK-independent manner (Watson et al., 2006, Barnett et al., 2006). MAGUKs are important scaffolding molecules in the PSD and bind NMDARs to downstream signalling molecules such as SynGAP. Two of these MAGUKs SAP102 and PSD-95 have roles in hippocampal plasticity, and learning and memory and Sap102 mutations result in a form of X-linked human retardation (Tarpey et al., 2004). Deletion of either gene does not cause defects in the development of barrels, perhaps due to compensation mechanisms already described in hippocampus (Vickers et al., 2006 Cuthbert et al., 2007). Double knockout mice die by P3 and analysis of all other mutants revealed a defect in the formation of barrels and segregation of TCAs in Sap102-/y Psd-95+/-. Surprisingly this defect was not seen in Sap102+/- Psd-95-/- mice, agreeing with previous findings that SAP102 is better able to compensate for loss of PSD-95 (is up-regulated) than PSD-95 is for SAP102. An explanation for this effect may lie with the fact that Sap102 is X-linked and therefore females that are heterozygote for Sap102 are mosaic with a population of cells expressing SAP102 and a population not expressing SAP102. Using β-Galactosidase antibody to label one population of cells, female mice that had two populations of cells were examined. In these mice one population of cells were Sap102-Psd-95+/-, and did not previously segregate into normal barrels and the other population were Sap102+Psd-95+/- and should segregate normally. Both populations of cells segregated normally, indicating that the cells expressing SAP102 were rescuing the cells not expressing SAP102 by a cell non-autonomous mechanism. The final part of this thesis focuses on the role of glutamate-dependent signalling pathways in the regulation of CSPGs- key extracellular matrix proteoglycans that regulate the termination of the sensitive period. Analysis of 3 overlapping but distinct subsets of chondroitin-sulphate proteoglycans (CSPGs) reveals that expression of each of the three is different throughout development. After 2-3 weeks perineuronal nets (PNNs) labelled with Cat-315 and Cat-316 are visible and locate to specific regions within the cortical barrel-field. To determine whether the formation of PNNs is regulated by proteins involved in glutamate signalling, expression of the three CSPG subsets was analysed in mice with barrel defects due to mutations of Plcβ1, Mglur5, Syngap and Prkar2b. Interestingly, Prkar2b mutant adults but no other mutants have reduced Cat-315-PNNs, indicating that PKARIIβ regulates pathways that lead to formation of Cat-315-PNNs in adulthood. Cat-315 has previously been found to be regulated in the cortex of visually deprived cats and the cortex of whisker-trimmed mice, indicating that specific subsets of CSPGs are regulated by neuronal activity. Molecular pathways that lead to expression of Cat-315 positive PNNs involve PKARIIβ and the formation of PNNs may be an important step in the plasticity of circuits in barrels. Taken together, these results demonstrate that an important part of molecular signalling downstream of glutamate enabling barrels to form is played by molecules that maintain structure inside the synapse and outside the cell.

The purpose of this study is to add to the body of knowledge concerning intelligence, self-concept, and social competency as related to the habilitation of retardates by investigating the following problem: what is the relationship between intelligence, self-concept, and social competency among the mentally retarded?

Este estudo teve o objetivo de analisar a durabilidade de restaurações confeccionadas pela técnica de Tratamento Restaurador Atraumático (ART), realizadas em associação ou não ao emprego do Carisolv® em pacientes com deficiência mental. O protocolo foi aprovado pelo Comitê de Ética local e obteve-se o consentimento livre e esclarecido dos responsáveis. Dos 26 pacientes com deficiência mental que participaram desta pesquisa, 14 eram do sexo masculino e 12 do feminino; tinham entre oito a dezesseis anos (mediana e semi-amplitude interquartílica de 12 anos ± 1,50). As condições dentais e de higiene bucal puderam ser avaliadas pelos índices CPO-D, que foi igual a 6,27 (desvio padrão de 3,26); e IPV (índice de placa gengival) com resultado de 57,30 (desvio padrão de 25,79). Cada paciente selecionado recebeu pelo menos uma restauração da técnica ART (controle) e outra modificada em associação com Carisolv®, aleatoriamente escolhidas para tratamento. O número de dentes tratados foi 52 sendo 26 com a técnica ART (T1) e 26 com a técnica ART associada a Carisolv® (T2). Este grupo de pacientes com deficiência mental precisou de uma média de duas sessões de condicionamento cada. Quanto à profundidade cavitária, apenas dois dentes do total analisado foram considerados com cavidades profundas, os quais foram restaurados coincidentemente com a mesma técnica (T1), as outras cavidades se distribuíram igualmente entre rasas e médias. Quanto à dificuldade encontrada pelo operador no momento da remoção do tecido cariado, considerando-se as duas técnicas (T1 e T2) os registros foram muito próximos, isto é, a técnica de remoção mecânica do tecido cariado (T1) e a técnica de remoção química-mecânica (T2) apresentaram o mesmo grau de dificuldade. Como cada paciente foi submetido às duas técnicas, foi possível avaliar o grau de dificuldade sentida pela profissional, entre elas, no mesmo paciente. Em 80,77% dos casos as respostas foram coincidentes. Dos 26 pacientes, apenas cinco não foram capazes de relatar o grau de desconforto sentido no momento da remoção do tecido cariado. A maioria dos pacientes (44,23%) não sentiu desconforto durante o procedimento. Comparando as respostas do mesmo paciente diante de cada uma das técnicas, obteve-se 85,72% de respostas coincidentes. O tempo operacional das restaurações foi somado, respeitandose as técnicas. As 26 restaurações pela técnica T1 resultaram em 1005 minutos e as 26 da T2 em 1070 minutos. A diferença é de 65 minutos a mais para a T2 que, se dividido pelo número de restaurações (26), obtém-se um acréscimo de 2,5 min. a mais para cada procedimento. Os escores utilizados para avaliação clínica das restaurações após 6 e 12 meses foram os preconizados para a técnica por Frencken de 0 a 9, sendo escores: 0, 1 e 7 sucesso; escores 2, 3, 4 e 8 falha e escores 5,6 e 9 excluídas restaurações do estudo. Aos 6 meses apenas duas restaurações foram excluídas do trabalho; porém, aos 12 meses este item foi de 21 restaurações, 18 destas pela impossibilidade de diagnóstico por ausência do paciente para avaliação. Os escores obtidos nas avaliações aos 6 e 12 meses classificados como sucessos foram: aos 6 meses, T1-76,92%, T2-84,62%; aos 12 meses T1-53,84%, T2-57,69%. Aqueles classificados como falhas foram aos 6 meses T1-19,23%, T2-11,53%; aos 12 meses T1-3,84%, T2-3,84%. Já as restaurações com escores de excluídas representaram aos 6 meses T1-3,84%, T2-3,84% e aos 12 meses T1-42,30%, T2-38,46% do total de restaurações que compunham a amostra. Se não forem computadas como falha todas aquelas restaurações classificadas com escore 9, ou seja, aquelas pertencentes aos pacientes que não foi possível examinar, as porcentagens se alteram; os escores obtidos serão então classificados como sucesso: aos 6 meses, T1-80,00%, T2-88,00%; aos 12 meses T1-82,36 % e T2-88,24%. Em todas variáveis estudadas: profundidade, dificuldade, desconforto, tempo operatório, avaliação clínica aos 6 e 12 meses não se observou diferença estatisticamente significante entre as técnicas T1 e T2 (teste estatístico de Wilconxon (P-value > 0,05). / This study analyzes the durability of restorations accomplished by the Atraumatic Restorative Technique (ART), with or without utilization of Carisolv® in patients with mental impairment. The study design was approved by the local Institutional Review Board and the caretakers of patients signed an informed consent term. Among the 26 patients with mental impairment included in this study, 14 were males and 12 were females; patients were aged 8 to 16 years (median and interquartile semi-amplitude 12 years ± 1.50). The dental and oral hygiene status were evaluated by the DMFT index, which revealed a mean value of 6.27 (standard deviation 3.26); and GPI (gingival plaque index) with a mean value of 57.30 (standard deviation 25.79). Each patient received at least one restoration by the ART technique (control) and another restoration by the modified technique associated with Carisolv®, randomly selected for treatment. Overall, 52 teeth were treated, being 26 by the ART technique (T1) and 26 by the ART technique associated with Carisolv® (T2). This group of patients with mental impairment required a mean of two sessions of psychological preparation in the dental clinic each. With regard to the cavity depth, only two teeth were considered as deep cavities, which coincidently were restored by the same technique (T1); the other cavities were equally distributed among shallow and medium depth. Concerning the difficulty experienced by the operator for removal of carious tissue, considering the two techniques (T1 and T2), the records were very close, i.e. the mechanical technique (T1) and the chemicalmechanical technique (T2) for removal of carious tissue presented the same degree of difficulty. Since each patient was submitted to both techniques, it was possible to evaluate the degree of difficulty experienced by the professional between both techniques in the same patient. Responses were coincident in 80.77% of cases. Among the 26 patients, only five were unable to report the degree of discomfort felt during removal of carious tissue. Most patients (44.23%) did not feel any discomfort during the procedure. Comparison of the responses of the same patient for each technique revealed 85.72% of coincident responses. The chair time of restorations was added, according to the techniques. The 26 restorations performed by the T1 technique required 1,005 minutes, compared to 1,070 minutes for the 26 restorations performed by the T2 technique. The 65-minute difference for T2, divided by the number of restorations (26), revealed an increase of 2.5 minutes for each procedure. Clinical evaluation of restorations after 6 and 12 months was scored by the Frencken technique, from 0 to 9, as follows: 0, 1 and 7, success; scores 2, 3, 4 and 8, failure; and scores 5, 6 and 9, restorations excluded from the study. At six months, only two restorations were excluded; however, at 12 months, this score was assigned to 21 restorations, 18 of which due to the impossibility of diagnosis because the patient was not available for evaluation. The following percentages of restorations were scored as success: at 6 months, T1 76.92%, T2 84.62%; at 12 months, T1 53.84%, T2 57.69%. The percentages of restorations scored as failures were as follows: at 6 months, T1 19.23%, T2 11.53%; at 12 months, T1 3.84%, T2 3.84%. The percentage of restorations excluded was T1 3.84%, T2 3.84% at 6 months and T1 42.30%, T2 38.46% at 12 months. No statistically significant differences were found between the T1 and T2 techniques for any study variable (depth, difficulty, discomfort, chair time, clinical evaluation at 6 and 12 months) (Wilcoxon statistical test , p value > 0.05).

Thesis (M.A. (Psychology)) --University of Limpopo, 2013 / This study explored the phenomenological experiences of mothers of children with mental retardation in two special schools (i.e. Fulufhelo and Pfunanani). The former is in Vhembe while the later is situated in Mopani district in Limpopo province. A qualitative approach was followed and participants were selected using purposive sampling. The sample consisted of 24 members (12 for individual interviews and 12 for focus group) whose children were diagnosed with mental retardation at the time of the study. Data were collected through unstructured interviews and analysed using interpretative phenomenological analysis. The following psychological themes emerged from the study: mothers’ subjective understanding of mental retardation; mothers’ understanding of the causes of mental retardation; living with a mental retarded child; psychological reactions of mothers to a diagnosis of mental retardation and mothers’ causal explanation of mental retardation. The present study discovered that all families with mentally retarded children are directly or indirectly affected by this condition.

<p>Denna litteraturöversikt visar att det finns en hel del litteratur och forskning inom området föräldrar med förståndshandikapp. Den forskning som gjorts är till största delen internationell, men de resultat denna studie kommit fram till bör kunna vara användbara under svenska förhållanden. Syftet var att belysa ett antal bestämda faktorer som kan påverka insatsers effektivitet, bland annat attityder, sociala nätverk och handikappmedvetandet. Resultatet visar att förmågan hos många av föräldrarna kan förbättras med hjälp av träning och utbildning. Studien har sin utgångspunkt i systemteori och visar att insatsers effektivitet påverkas av olika system runt den förståndshandikappade föräldern, där även föräldern själv ingår som ett system.</p>

The loss of expression of the fragile X mental retardation protein (FMRP) leads to fragile X syndrome. Fragile X syndrome is the most prevalent inheritable mental retardation. FMRP has two types of RNA binding domains, two K-homology domains and an arginine-glycine-glycine box domain, and is proposed to act as a translation regulator of specific mRNA. Despite extensive research, the mechanism by which FMRP loss leads to the fragile X syndrome remains unclear. Thus, there is high interest to produce sufficient quantities of pure recombinant FMRP for biochemical and biophysical studies of the protein function. However, the recombinant bacterial expression of FMRP has had limited success, and subsequent recombinant eukaryotic and in vitro systems may produce FMRP which is posttranslationally modified, as phosphorylation and arginine methylation have been shown to occur on FMRP. In this study, we have successfully isolated the conditions for recombinant expression, purification and dialysis of full-length FMRP using Escherichia coli, with a high yield. The expression of FMRP using E. coli renders the protein devoid of the posttranslational modifications of phosphorylation and arginine methylation, allowing for the further study of the direct effects of these modifications individually and simultaneously. Additionally, FMRP has been shown to undergo alternative splicing, with one of the splicing sites in close proximity to the FMRP domain shown to be involved in binding G quadruplex mRNA with high affinity and specificity. We have analyzed how naturally occurring truncations in the FMRP sequence affect its RNA binding affinity, by applying the expression, purification and dialysis process to the second and third longest FMRP isoforms, followed by subsequent analysis of the G quadruplex mRNA binding properties by fluorescence spectroscopy. Our results show that as FMRP gets truncated by alternative splicing, its mRNA binding affinity increases. To test a model we proposed for FMRP translation regulation activity, we developed a luciferase reporter gene construct that contains the G quadruplex structure in the mRNA 5���-untranslated region. Using luminescence spectroscopy to analyze luciferase translation, we showed that low levels of full-length FMRP reduces luciferase translation, and as the concentration of full-length FMRP increases the luciferase translation increases. / Bayer School of Natural and Environmental Sciences / Chemistry and Biochemistry; / PhD; / Dissertation;

This retrospective study investigated the incidence, characteristics, and risk factors of bone fracture among a group of 518 adults with severe mental retardation between 25 and 75 years old. Data were collected from a large state developmental center in the Western United States between April 1, 1991 and March 31, 1996. Ninety-six of 271 males and 133 of 247 females experienced 291 fractures during the study period. Relative risk of fracture for all males was .658 compared to 1.540 for females. Menopausal status did not significantly influence the risk of fractures among females. Risk of fracture by self-feeding ability ranged from 1.675 for individuals who were tube fed to .343 for those requiring no assistance during meals. As a group, individuals with a body mass index (BMI) less than 20 were at the greatest risk of fracture (RR=2.416). Males with BMI values between 20-25 (RR=.560) and greater than 25 (RR=.373) had a decreased risk of fracture. Ambulatory males and females had a significantly decreased risk of fracture (RR=.356 and .559 respectively). Rib, femur, vertebrae, and radial fractures accounted for nearly 60% of all fractures. The etiology of the 41% of fractures was of unknown origin. Transfers by developmental training personnel (10.3%), falls to the ground (15.8%), and accidents (32.6%) were also frequently related to fracture cause. Logistic regression analysis revealed the occurrence of any fracture was significantly associated with ambulation, calcium intake, body weight, self-feeding ability, and body mass index. / Graduation date: 1997

Denna litteraturöversikt visar att det finns en hel del litteratur och forskning inom området föräldrar med förståndshandikapp. Den forskning som gjorts är till största delen internationell, men de resultat denna studie kommit fram till bör kunna vara användbara under svenska förhållanden. Syftet var att belysa ett antal bestämda faktorer som kan påverka insatsers effektivitet, bland annat attityder, sociala nätverk och handikappmedvetandet. Resultatet visar att förmågan hos många av föräldrarna kan förbättras med hjälp av träning och utbildning. Studien har sin utgångspunkt i systemteori och visar att insatsers effektivitet påverkas av olika system runt den förståndshandikappade föräldern, där även föräldern själv ingår som ett system.

Changes in health care and increasing provision of community services have resulted in an increased number of community dwelling older adults with intellectual disabilities (ID), leading to questions about future planning for service delivery. Although selected aspects of functioning have been explored in various research studies, less longitudinal information pertaining to broad aspects of health is available to planners. This longitudinal project was designed over 10 years ago with the primary purpose of exploring individual and systemic issues in the health needs of this challenging population, leading to improved service planning.<p>Cross-sectional and longitudinal health data were collected from 360 adults with intellectual disabilities (ID) recruited from social services agencies from across the province of Saskatchewan. Data collection included caregiver information, chart information and directly administered tests of selected aspects of cognitive functioning. Formal data-collection occurred every second year for a maximum of four test times, and was supplemented by follow-up phone calls.<p>Analysis of study results showed that young, rather than older people without DS had a greater severity of health needs related to their underlying conditions, and more problematic behavioral and mental health issues. The reason for this was likely the increased survival of multiply handicapped young people, and the increasing trend for these people to be maintained in the community rather than in large institutions. This population was more likely to receive psychotropic medications, both for underlying problems such as seizure disorders, but also for difficult behaviors such as aggression.<p>On the other hand, adults with DS had relatively fewer problems in their younger adult years, but had increasing problems as they aged. Most aspects of functioning were decreased in the older compared to the younger cohorts, which was consistent with the longitudinal, individual level data showing yearly declines in most measured skills. These declines were greater than those found in adults without DS. Although yearly declines were noted in most age cohorts, the largest declines were noted in the oldest age groups, 50 years and over, suggesting that, while aging related decline was present from an early age, declines severe enough to suggest a dementing process probably do not start until after middle age. Declines in visual memory appear to precede those in praxis.<p>Mortality was increased with age, lower baseline functioning, DS, male gender, and baseline depressive symptoms.<p>The use of aging programs did not change much during the course of the study, but interesting differences in service use between people with and without DS were noted. Adults with DS were more likely than those without DS to participate in generic aging services, which was thought to be due to people with DS presenting with more typical, Alzheimer type behaviors, rather than severe behaviors such as aggression.