Galanin pathogenic mutations in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment.

O perfil do médico em formação em radiologia e diagnóstico por imagem

OBJETIVO: Identificar diferenças no perfil psicossocial do especializando e médico residente em radiologia e diagnóstico por imagem, avaliar a aspiração profissional e as motivações internas que os influenciaram a escolher a especialidade radiologia e diagnóstico por imagem e se o nível de satisfação profissional melhora a relação médico-paciente. MATERIAIS E MÉTODOS: Foi aplicado um questionário com 26 perguntas que constava também do teste de auto-estima de Rosenberg. RESULTADOS: A auto-estima está acima da média para 39,6% dos médicos. Para 38,7% dos alunos, a escolha da medicina se deu por aptidão ou realizações pessoais. Para 50,9% dos médicos entrevistados, os clientes compreendem e assimilam as informações transmitidas. Apresentam condições para esclarecer as dúvidas dos pacientes 77,4% dos médicos. CONCLUSÃO: Não há diferença no perfil psicossocial do especializando e do médico residente em radiologia e diagnóstico por imagem. A aspiração profissional e as motivações internas dos médicos residentes e especializandos têm as mesmas influências na escolha da especialidade. Os médicos residentes estão mais preparados para o envolvimento na relação médico-paciente do que os especializandos.

Risk factors of postictal generalized EEG suppression in generalized convulsive seizures.

OBJECTIVE: To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). METHODS: We reviewed the video-EEG recordings of 417 patients included in the REPO2MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. RESULTS: A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p < 0.001) and lack of early administration of oxygen (p < 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). CONCLUSION: The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen.

Ninety-day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE)

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event

Theses

Painovuosi nimekkeestä.

Julkiset hankinnat: Case Helsingin seurakuntayhtymä

Tutkimuksen pääideana on tutkia miten julkisia hankintoja koskeva lainsäädäntö näkyy seurakuntayhtymän hankinnoissa. Julkisia hankintoja tutkitaan lakitekstien ja alan kirjallisuuden pohjalta sekä Helsingin seurakuntayhtymän työntekijän haastattelun pohjalta. Tutkielmassa käydään läpi muun muassa hankintalain mukaiset julkisten hankintojen pääperiaatteet ja hankintamenettelyt. Lisäksi työssä käydään läpi lyhyesti julkisten hankintojen hankintaprosessi. Työn loppuosa käsittelee Helsingin seurakuntayhtymää.

Historiallista sosiologiaa naisten mielisairaudesta

Kirjallisuusarvostelu

Kuva Raamatun maailmasta muuttuu

Kirjallisuusarvostelu

Integrating environmental aspects into product development process

Various regulations and customer requirements have made it necessary for Vacon Oyj to pay more attention to the environmental aspects in its processes. The main purpose of this master’s thesis project is to define how environmental aspects could be integrated into Vacon’s product development process. The aim is to find out the most important environmental aspects for the company to address, to examine how these could be taken into account during the development process and to map the critical factors that need consideration in order to ensure the successful integration of environmental aspects into the design process. Based on the customer requirements and evolving regulations the most important aspects for Vacon include minimizing the amount of harmful substances, improving the recyclability and energy efficiency of the product and moreover providing meaningful information related to these aspects. To tackle these issues, a new DfE process was developed, tasks in each phase were described and responsibilities were indicated. To ensure the success of the DfE process, management commitment, support of other processes and significant improvements in ways the information is managed are required. The developers should be provided with training and support. Environmental expertise and knowledge in-house should be developed and establishing meaningful environmental indicators is suggested.

Aarre saviastioissa on kaivattu johdanto Qumran-tutkimukseen

Kirjallisuusarvostelu

Hankintaprosessin optimaalinen toteutus: Case Medi-IT Oy

Tutkielman tavoitteena on löytää hankintaprosessin optimaalinen toteutustapa tutkimuksen kohdeyritykselle. Tutkielmassa kuvataan kohdeyrityksen hankintaprosessin kulku nykyisellään ja annetaan kehitysehdotuksia. Tutkielmassa pohditaan sitä, mitä osia kohdeyrityksen tulisi hankintaprosessissa suorittaa itse, ja mitä osia puolestaan tulisi ulkoistaa palveluntarjoajille. Tutkielmassa tutkitaan myös ICT-hankintoihin liittyviä erityispiirteitä ja haasteita. Lisäksi tutkielmassa käydään läpi toimittajien vertailussa käytettäviä kriteerejä. Myös hankintalain vaikutusta kohdeyrityksen toimintaan tarkastellaan lyhyesti. Tutkimuksen teoreettinen viitekehys koostuu neljästä teoria-alueesta, jotka ovat: ulkoistaminen, toimittajien luokittelu, toimittajien arviointi ja julkiset hankinnat. Teorian ja empirian välisen vuoropuhelun avulla esitetään ehdotus hankintaprosessin optimaaliseksi toteutustavaksi. Muutoksia ehdotetaan erityisesti toimijoiden väliseen roolijakoon hankintaprosessissa. Työ on luonteeltaan kvalitatiivinen tapaustutkimus. Teoriaosio perustuu kirjallisuuskatsaukseen ja empiriaosio perustuu lähinnä haastatteluihin.