<p>Om närstående ska orka leva tillsammans med en yngre demenssjuk partner behöver de erbjudas stöd som är utformat utifrån deras situation och behov. Syftet var att i samarbete med närstående till personer vars demenssjukdom debuterat före 65 års ålder planera ett närståendestöd. Metoden som användes var Participatory Action Research (PAR), en interaktiv forskningsmetod som innefattar reflektion, analys och handling. Fokusgruppssamtal genomfördes med två fokusgrupper vid vardera tre tillfällen. Samtliga deltagare var make eller maka som levde tillsammans med en yngre demenssjuk partner. Studien visade att närstående genomgår en process som har stora likheter med och följer den transitionsprocess som personen med demenssjukdom går igenom. Initialt upplevde närstående oro, ovisshet,ensamhet och osäkerhet och man upplevde brist på stöd. För att lindra dessa upplevelser krävs indirekt stöd riktat mot den sjuke och direkt stöd riktat mot den närstående. Tidigt i sjukdomsförloppet behövs individuellt anpassat stöd som bör förändras i takt med att sjukdomsprocessen fortskrider. Att ha tillgång till en person som kan fungera som lots mellan de olika övergångar närstående går igenom var betydelsefullt.</p> / <p>Living together with a younger spouse who is suffering from dementia requires that relatives are offered support. The aim of this Participatory Action Research (PAR) project was to, in collaboration with relatives, plan support for relatives to persons with dementia below 65 years of age. PAR is an interactive research method based on reflection, analysis and action. Two groups of relatives participated in focus groups at three occasions and data were content analysed. Relatives were wives or husbands to a younger person with dementia. Findings showed that relatives pass through a similar transition process as the person. It is important to offer individualized support initially, support that needs to be changed as the disease proceeds. Furthermore, the study showed that if relatives shall manage their own anxiety, uncertainty, and feelings of loneliness, emotional support is necessary. However, it is impossible to just offer direct support to the relatives without considering the sick persons’ needs. Finally, a personal guide that could follow the couple trough the entire process would be of importance.</p>

Om närstående ska orka leva tillsammans med en yngre demenssjuk partner behöver de erbjudas stöd som är utformat utifrån deras situation och behov. Syftet var att i samarbete med närstående till personer vars demenssjukdom debuterat före 65 års ålder planera ett närståendestöd. Metoden som användes var Participatory Action Research (PAR), en interaktiv forskningsmetod som innefattar reflektion, analys och handling. Fokusgruppssamtal genomfördes med två fokusgrupper vid vardera tre tillfällen. Samtliga deltagare var make eller maka som levde tillsammans med en yngre demenssjuk partner. Studien visade att närstående genomgår en process som har stora likheter med och följer den transitionsprocess som personen med demenssjukdom går igenom. Initialt upplevde närstående oro, ovisshet,ensamhet och osäkerhet och man upplevde brist på stöd. För att lindra dessa upplevelser krävs indirekt stöd riktat mot den sjuke och direkt stöd riktat mot den närstående. Tidigt i sjukdomsförloppet behövs individuellt anpassat stöd som bör förändras i takt med att sjukdomsprocessen fortskrider. Att ha tillgång till en person som kan fungera som lots mellan de olika övergångar närstående går igenom var betydelsefullt. / Living together with a younger spouse who is suffering from dementia requires that relatives are offered support. The aim of this Participatory Action Research (PAR) project was to, in collaboration with relatives, plan support for relatives to persons with dementia below 65 years of age. PAR is an interactive research method based on reflection, analysis and action. Two groups of relatives participated in focus groups at three occasions and data were content analysed. Relatives were wives or husbands to a younger person with dementia. Findings showed that relatives pass through a similar transition process as the person. It is important to offer individualized support initially, support that needs to be changed as the disease proceeds. Furthermore, the study showed that if relatives shall manage their own anxiety, uncertainty, and feelings of loneliness, emotional support is necessary. However, it is impossible to just offer direct support to the relatives without considering the sick persons’ needs. Finally, a personal guide that could follow the couple trough the entire process would be of importance.

Bakgrund: En psykos innebär att tappa fotfästet i verkligheten. Risken för att drabbas av försämrad livskvalitet med stort lidande är hög. Tidigt insatta interventioner hos personer med nydebuterad psykos kan hindra ett ogynnsamt sjukdomsförlopp men forskning av nyinsjuknade genererar sällan kunskap gällande omvårdnad. Patienters symptombild med starka vanföreställningar och oro komplicerar ofta försök att interagera och en gynnsam vårdrelation kan vara svår att utveckla i och med patienternas speciella tillstånd. Syfte: Att beskriva hur personalen kan skapa en vårdprocessfrämjande relation med personen som drabbats av nydebuterad psykos på en slutenvårdsavdelning. Metod: Systematisk litteraturöversikt inkluderat femton artiklar med kvalitativt perspektiv för att besvara syftet. Data har analyserats med hjälp av kvalitativ metasummering. Resultat: Resultatet antyder på fördelar med att skapa tillit på ett tidigt stadium med hjälp av vårdrelationen. I och med ökande tillit till omgivningen ökar också behovet av att ha personalen som stöd med kunskap och förståelse för att kunna lösa problem i ett ömsesidigt samarbete. Personalen bör vara tillgänglig, vänlig, kunnig, tydlig, empatisk, flexibel med positiv hållning för gynnsamt skapande av hälsoprocessfrämjande omvårdnad.  Diskussion: I den optimala vårdrelationen sker ett samarbete runt mål och hälsoprocessfrämjande interventioner där personalen stöttar patienternas val med kunskap, uppmuntran och positiv feedback. Att få patienten att acceptera sin situation, att det kanske aldrig blir som förr och att leda in patienten på nya realistiska banor som inger livsmod och hopp kan vara en av personalens största utmaningar. / Background: A psychosis brings a lost sense of reality and generates a high risk of impaired quality of life with great suffering. Research shows that early intervention can prevent a disadvantageous health course whilst seldom generates knowledge regarding nursing as such. The nurse patient relationship is essential but often complicated by lack of trust due to symptoms such as strong delusions and anxiety. Aim: To describe how staff can create a care process promoting relationship with persons affected by recent-onset psychosis at an inpatient ward. Methods: Systematic literature review based on fifteen articles with a qualitative perspective. A qualitative meta-summary was chosen as method for synthesizing and analyzing the findings. Results: The result shows that the caring relationships focus may be on gaining trust at an early stage. As the patient gains trust in the surrounding environment the need for support from staff increases. Problem solving, together with staff, becomes more appreciated as symptoms fade away. Staff who are accessible, friendly, knowledgeable, clear, empathetic, flexible with a positive attitude are beneficial in creating a healthy process of promoting nursing. Discussions: Optimal nurse patient relationship interacts around goals and health process promotion interventions where staff supports the patients’ choices with the use of knowledge, encouragement and positive feedback. Getting the patient to accept their situation, making them realize that life may never be the same, leading them onto new realistic paths inspiring courage and hope, can be one of the staff's greatest challenges.

Text in English / Two consecutive referrals of early onset (symptom onset at 11 years) anorexia nervosa (restricting sub-type) to an inpatient eating disorders unit in a psychiatric hospital, will be described. Within both cases, there was a history of sequential mother-daughter dieting prior to the daughter's onset of anorexic symptoms. This pattern will be viewed from the perspective of systemic theory, with reference to the cybernetic processes implicated in the onset and maintenance of symptoms. Structural systemic interpretations, in terms of exchangeable senses of self within the mother-daughter pairs, will also be considered. A brief comment will be made about the symmetry which underlies the choreography of anorexia nervosa when viewed from the perspective of communication theory. The implications for intervention will be addressed. In conclusion, the nature of the intergenerational transmission of disordered eating behaviours, will be considered with reference to the nature-nurture debate. / Clinical Psychology / M.A. (Clinical Psychology)

Orientador: Maria Terezinha Serrão Peraçoli / Resumo: Introdução: A pré-eclâmpsia (PE) é uma patologia obstétrica e uma das principais causas de morbimortalidade materna e fetal. Na PE ocorre um estado de má adaptação da tolerância imunológica, caracterizada por ativação anormal do sistema imune inato e adaptativo. As células T reguladoras (Treg) representam uma população de linfócitos T responsáveis pela manutenção da tolerância e controle da inflamação, enquanto células Th17 medeiam diferentes tipos de reações inflamatórias. Portanto, o balanço entre células Treg e Th17 pode ser crítico para a tolerância ao feto e prevenção da PE. Objetivo: Avaliar as subpopulações de células T CD4+ (Th1, Th2, Th17 e Treg) e o perfil de citocinas produzido por essas células, em gestantes portadoras de pré-eclâmpsia, classificadas em PE precoce e PE tardia. Métodos: Foram estudadas 60 gestantes, sendo 20 normotensas e 40 portadoras de PE, pareadas pela idade gestacional. As gestantes com PE foram classificadas de acordo com o aparecimento das manifestações clínicas em PE precoce (< 34 semanas de gestação; n=20) e PE tardia (≥ 34 semanas de gestação; n=20). Células mononucleares do sangue periférico (PBMCs), obtidas das gestantes foram avaliadas quanto à produção de citocinas pró e anti-inflamatórias e à expressão de fatores de transcrição envolvidos na caracterização das subpopulações de células T CD4+. A expressão dos fatores de transcrição intracitoplasmáticos de células Th1 (T-bet), Th2 (GATA-3), Th17 (RORc) e Treg (FoxP3) foi avaliada por c... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

OBJECTIVES: The aim of our study was to assess clinical presentation of early-onset schizophrenia spectrum disoders (EO-SSD), the time to first improvement and efficacy associated with selected atypical (AAPs) and typical (TAPs) antipsychotics, as well as two main side effects - weight gain and treatment-emergent extrapyramidal symptoms (EPSs) during the treatment in patients with EO-SSD. METHODS: This was a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs (risperidone, olanzapine, ziprasidone, quetiapine and clozapine) and TAPs (haloperidol, perphenazine and sulpiride), for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 173 patients (85 males, 88 females; mean age 15.8±1.6 years); their treatment included 297 treatment trials. Data on premorbid adjustment, prodromal symptoms and psychopathology at admission, as well as comorbidity were evaluated based on the patients' medical records. The time to first improvement could be estimated in 258 treatment trials; of these, 195 (76%) comprised AAPs and 63 (24%) TAPs. The time to first improvement was assessed in agreement with the methodology established for retrospective studies as the number of treatment days prior to the first record of improvement...

Objective: Mutations in the parkin (PARK2) gene have been associated with autosomal recessive early-onset Parkinson's disease (EOPD) with various frequencies in different populations. The aim of the study is to describe phenotypic characteristics of Czech EOPD patients, to evaluate the influence of environmental risk factors, and to determine the frequency of parkin allelic variants in patients and healthy controls. Methods: A total of 70 EOPD patients (age at onset ≤ 40 years) and 75 controls were phenotyped and screened for the sequence variants and exon rearrangements in the parkin gene. Results: The main features in the phenotype of the patients' sample were: the absence of cognitive deficit, high occurrence of dystonia, depression, hyperhidrosis, an excellent response to dopaminergic therapy, early onset of dyskinesia and motor fluctuation. Patients with mutations in the parkin gene had significantly lower age at onset. The agricultural occupation and work with chemicals increased the risk of EOPD, however the coffee drinking appeared to be a protective factor. Parkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous...

Les Encéphalopathies Épileptiques Précoces sont des pathologies rares et sévères caractérisées par des crises fréquentes commençant dans les trois premiers mois de vie accompagnées d’un EEG intercritique altéré et un pronostic très défavorable. Au cours de la caractérisation génétique d’une cohorte de 402 patients, nous avons mis en évidence une délétion de 19,9 kb localisée en Xp11.23 chez un garçon et 34 mutations de novo du gène KCNQ2. La première partie de mon projet a consisté en l’étude de la pathogénicité de la délétion Xp11.23, qui implique trois gènes dont WDR45. Les mutations de WRD45 ont été décrites dans une dégénérescence neuronale avec accumulation de fer et presque exclusivement chez des patients de sexe féminin. Le diagnostic initial, chez ce patient, montre une IRM normale avec un phénotype d'EEP et l'accumulation de fer a été détectée à partir de 5 ans. Ce travail m’a permis de décrire le premier patient atteint d’EEP porteur d’une délétion de WDR45. La deuxième partie de mon projet a concerné le gène KCNQ2. Nos résultats ont montré que les mutations sont impliquées dans deux mécanismes physiopathologiques, une délocalisation subcellulaire et un gain de fonction. Ces résultats ouvrent de nouvelles perspectives en terme de compréhension de la pathologie et de thérapies qui peuvent être proposées. Une dernière partie de ce projet a consisté en l’élaboration de nouveaux modèles in vitro, j’ai mis au point des lignées stables exprimant KCNQ2 qui permettront le criblage de molécules thérapeutiques à haut-débit, ainsi que des progéniteurs neuronaux différenciés à partir de cellules iPS issues de la reprogrammation de fibroblastes de patients. / Early onset epileptic encephalopathies are rare and severe disorders, characterized by frequent motor seizures occurring before three months of age associated with an altered interictal EEG pattern. The prognosis is poor. During the course of the genetic characterization of a cohort of 402 EOEE patients, we identified a de novo deletion located at Xp11.23 in a male patient and 34 KCNQ2 de novo mutations. The first part of my project consisted in the study of the pathogenicity of the Xp11.23 deletion that encompasses three genes including WDR45. Mutations in the WDR45 gene been have recently identified in patients suffering from neurodegeneration with brain iron accumulation. WDR45 mutations have been almost exclusively found in females. Our patient with the Xp11.23 deletion presented a normal MRI and the EOEE phenotype was predominant. Iron accumulation began only at 5 years. My work reveals that deletions of WDR45 are viable in males and can be diagnosed as EOEE. The second part of my project was aimed at the functional study of two KCNQ2 gene mutations. During this work, my results showed that those mutations were involved in new pathological mechanisms, namely a mislocalization or gain of function. Those results provide new perspectives in term of disease knowledge and therapy. The last part of my project consisted in the development of two new in vitro models for the study of KCNQ2 mutations: stable cell lines expressing the Kv7.2 channel for high-throughput screening of drugs and the production of neurons from induced pluripotent stem cells arising from reprogrammed patient fibroblasts.

Introduction : La variabilité du rythme cardiaque est étudiée à partir des variations de durée des cycles cardiaques (intervalle R-R de l’électrocardiogramme). Ces variations peuvent être analysées par des méthodes linéaires (temporelles et fréquentielles) et non linéaires (théorie de l’information ou des fractales) de quantifications mathématiques et statistiques qui donnent des informations innovantes sur les signaux analysés. L’application de ces méthodes d’étude en néonatologie a démontré un intérêt pour le diagnostique précoce de l’infection néonatale tardive du prématuré mais n’avait pas été étudié dans l’infection néonatale précoce du nouveau-né à terme, dans le contexte des évènements cardio-respiratoires suivant la primo-vaccination des prématurés ou pour évaluer un effet neurologique de l’hyperbilirubinémie dans l’ictère néonatal. Notre hypothèse dans ce travail était qu’il était possible de : (i) caractériser la variabilité du rythme cardiaque en cas d’infection materno fœtale ou de méningite néonatale, (ii) mettre en évidence des facteurs prédisposant à la survenue d’évènements cardio-respiratoires post-vaccinaux, (iii) Identifier un éventuel retentissement neurologique de l’ictère néonatal par étude de la variabilité du rythme cardiaque. / The heart rate variability measures permitted to evaluate equilibrium state and perturbation in the regulation of cardio-vascular system.  These tools, based on heart rate variability analysis, helped to recognize associated disease state as early onset neonatal sepsis and non-infectious inflammatory response induced to immunization. An increase in global variability (SD), long term variability (SD, LF) and low approximated entropy (ApEn) were observed in the proven-sepsis full term infants. Importance of decrease in ApEn was correlated to the severity of sepsis assessed by blood markers. These suggest an association of sepsis with uncoordinated sympatho-vagal coactivation together with loss of adaptability. In premature infants, the risk of increase in cardio-respiratory events after the first immunization was associated with a specific pre-immunization profile: sympathetic predominance in heart rate control (high LF/HF ratio), abnormal oversimplification of heart rate variability and persistence rhythm control immaturity. Increased ApEn after immunization reflects a marginal result from adaptability of the heart rate to environmental changes without possibility to reserve in case of severe infection.

Objective: Mutations in the parkin (PARK2) gene have been associated with autosomal recessive early-onset Parkinson's disease (EOPD) with various frequencies in different populations. The aim of the study is to describe phenotypic characteristics of Czech EOPD patients, to evaluate the influence of environmental risk factors, and to determine the frequency of parkin allelic variants in patients and healthy controls. Methods: A total of 70 EOPD patients (age at onset ≤ 40 years) and 75 controls were phenotyped and screened for the sequence variants and exon rearrangements in the parkin gene. Results: The main features in the phenotype of the patients' sample were: the absence of cognitive deficit, high occurrence of dystonia, depression, hyperhidrosis, an excellent response to dopaminergic therapy, early onset of dyskinesia and motor fluctuation. Patients with mutations in the parkin gene had significantly lower age at onset. The agricultural occupation and work with chemicals increased the risk of EOPD, however the coffee drinking appeared to be a protective factor. Parkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous...