Die vorliegende Arbeit überprüft die Entlassungsbriefe des ersten Halbjahres 2011 der Medizinischen Klinik II des Klinikums Aschaffenburg – Alzenau. Ziel der Arbeit ist es zu erfassen, wie viele Patienten mit einer PPI-Medikation aus der stationären Behandlung entlassen wurden und in wie vielen Fällen diese Behandlung indikations-, zeit- und dosisgerecht war. Es sollte damit auch überprüft werden, ob in Entlassungsbriefen einer gastroenterologischen Fachabteilung ein höheres Bewusstsein für eine leitlinienkonforme PPI-Empfehlung vorliegt. / This thesis examines the discharge letters of the first semester 2011 of the Medical Clinic II of the Aschaffenburg - Alzenau Hospital. The aim of this study is to record how many patients with PPI medication were discharged from inpatient treatment and in how many cases this treatment was appropriate for indication, time and dose. It should also be used to check whether discharge letters from a gastroenterological department are more aware of a guideline-compliant PPI recommendation.

Introduction Social and emotional functions play a key role in schizophrenia. Both positive symptoms, such as hallucinations and persecutory delusions, as well as negative symptoms such as social withdrawal, and flattened affect impact socioemotional function. These functions involve distributed brain networks. The ‘Disconnection Hypothesis’, a plausible unifying theory of schizophrenia, proposes connectivity within such networks as a core pathological feature of schizophrenia. Connectivity is also related to specific genetic risk factors. Therefore the present project addresses the hypothesis that individuals with schizophrenia might show disconnection within socio-emotional brain networks, and examines the effects of a functional polymorphism of the BDNF gene on connectivity within these networks. Methods Here I examined the brain activation and connectivity for implicit emotional reaction and social judgment in schizophrenia, as well as with variation in the val66met polymorphism of BDNF. Brain activation was examined with functional magnetic resonance imaging, and effective connectivity was estimated using psycho-physiological interactions, from the bilateral amygdala to the whole brain (using a facial image paradigm for explicit approachability judgement and implicit fear response respectively). Results Individuals with schizophrenia showed reduced activation in the right lingual gyrus, right superior temporal gyrus and left amygdala during fear processing, as well as reduced connectivity from the left amygdala to the right temporo-parietal junction and precuneus. During approachability judgments, patients overactivated the right inferior frontal gyrus and right precuneus and showed reduced connectivity from the bilateral amygdala to the right inferior frontal gyrus. Met allele carriers of the BDNF val66met polymorphism showed overactivation in the medial anterior cingulate cortex, and bilateral insula, as well as reduced connectivity between the anterior cingulate cortex and hippocampus. For approachability judgment, met carriers overactivated the middle occipital gyrus, and showed reduced connectivity from the left amygdala to the right parahippocampal gyrus and medial frontal gyrus, as well as the left posterior cingulate gyrus, pre and post central gyrus, middle temporal gyrus and cerebellum. Conclusion In conclusion, connectivity between the amygdala and brain regions associated with a range of socially relevant functions were found to be reduced in both patients, and met allele carriers of the BDNF val66met SNP. Given the key role of the amygdala in affective processing this diffuse disconnection in networks for socio-emotional functions might mediate the aberrant emotional and social behavior seen in individuals with schizophrenia.

År 2011 utlämnades recept på PPI-preparat (protonpumpshämmare) till 790 000 personer i Sverige, varav 59 % var kvinnor. Omeprazol (Losec®) är det preparat som helt dominerar förskrivningen. Den förskrivna volymen motsvarar 174 miljoner DDD (Definierade Dygns Doser), vilket är en mängd som räcker till att behandla ovannämnda personer i genomsnitt 220 dagar med en dos på 20 mg/dag. Behandling med PPI-preparat kan vara svårt att sätta ut på grund av att utsättning leder till återkomst av syrahypersekretion. Syftet med detta arbete är att lyfta fram den problematik som finns vid utsättning av PPI. Som metod har litteraturstudie valts för att besvara frågeställningen. Resultatet i studierna har visat på ökade chromogranin A-(CgA-) och gastrinvärden i plasma under en PPI-behandling. I en av studierna var S-gastrinvärdena före behandlingen 31,2 pmol/l och 54,8 pmol/l i slutet av behandlingen (p< 0.01), d.v.s. nästan en fördubbling, för att 2 veckor efter utsättning återgå till startvärdena 31,7 pmol/l. P-CgA värdena var före behandling 16.7 u/l, och 37.5 u/l i slutet (p< 0.01), vilket visar på en ökning med över 200%, för att 2 veckor efter utsättning återgå till att likna startvärdena 17.7 u/l. Av patienter som behandlats under en längre tid för syrarelaterade symptom med PPI-preparat klarade 14 -27 % att avsluta behandlingen utan att utveckla utsättningssymptom. 31 % klarade av att avsluta behandlingen utan utsättningssymptom då man trappade ner dosen. I två av studierna redovisas att 27 % klarar av att avsluta behandlingen efter långtidsanvändning av PPI. I tre studier visades att personer, som inte led av gastroesofageal refluxsjukdom (GERD), fick 44 – 52 % utsättnings symptom efter att ha konsumerat PPI-preparat i mer än fyra veckor. Slutsats: Resultaten tyder på att det är lättare att avluta behandlingen hos dem som behandlades med låga PPI-doser och hos de patienter som trappade ner dosen. Hos individer som varken led av magsår eller gastroesofageal refluxsjukdom, utvecklade nästan varannan person dyspeptiska symptom t.ex. halsbränna, sura uppstötningar och magkatarr efter utsättningen. Patienterna hade haft en daglig användning av PPI- preparat under fyra till åtta veckor.

Yes / This paper reflects Alzheimer Europe’s position on PPI (patient and public involvement) in the context of dementia research and highlights some of the challenges and potential risks and benefits associated with such meaningful involvement. The paper was drafted by Alzheimer Europe in collaboration with members of INTERDEM and the European Working Group of People with Dementia. It has been formally adopted by the Board of Alzheimer Europe and endorsed by the Board of INTERDEM and by the JPND working group ‘Dementia Outcome Measures - Charting New Territory’. Alzheimer Europe is keen to promote the involvement of people with dementia in research, not only as participants but also in the context of PPI, by generating ideas for research, advising researchers, being involved in consultations and being directly involved in research activities. This position paper is in keeping with this objective. Topics covered include, amongst others, planning involvement, establishing roles and responsibilities, training and support, managing information and input from PPI, recognising the contribution of people with dementia involved in research in this way, promoting and protecting the rights and well-being of people with dementia, training and support, and promoting an inclusive approach and the necessary infrastructure for PPI in dementia research. / European Union's Health Programme (2014-2020), grant number 707934. This work received funding under an operating grant from the European Union's Health Programme (2014-2020), grant number 707934. / European Union's Health Programme (2014–2020), grant number 707934.

Darbe tirta Co6Om (m=0-9) nanodalelių ir PPI dendrimerų optinės savybės, siekiant nustatyti ar PPI dendrimerai galėtų būti naudojami dirbtinių neuroninių tinklų, skirtų aptikti Co nanodaleles, kūrimui. Tyrimo rezultatai yra: 1) Co6Om (m=0-9) nanodalelių absorbcijos spektrų tyrimai parodė, kad absorbcijos intensyvumas 500-700 nm intervale mažėja, kai deguonies atomų skaičius didinamas iki 5. Absorbcijos intensyvumas vėl pradeda didėti, kai deguonies atomų skaičius tampa 6. 2) Teoriškai ir eksperimentiškai ištirta glikodendrimero su triptofano molekulėmis spektro prigimtis 200 - 400 nm intervale. Nustatyta, kad minėtame bangų ilgių diapazone stebimas triptofano molekulės π→π* sužadinimas. 3) Tirti PPI dendrimerai galėtų būti naudojami kaip neuroniniai tinklai, skirti aptikti Co nanodaleles. / In this research our aim was to investigate possibilities to use PPI dendrimers as a neural network for detecting Co nanoparticles. Our investigation results are: 1) Intensity of absorption of the Co6Om (m=0-9) particles should decrease in the 500-700 nm region with increasing of oxygen number till 5, and should increase again when number of oxygen atom is 6; 2) Nature of spectrum of PPI dendrimers with Tryptophan molecule in 200-400 nm range was investigated both theoretically and experimentally. It is obtained, that in above mentioned wavelength region absorption is due to π→π* excitation of tryptophan units; 3) Investigated PPI dendrimers could be used as an artificial neural network for detecting Co nanoparticles.

Examensarbetet har gjorts utifrån Arkitektkopia AB:s vägnar för att undersöka gränsvärden för bildupplösning inom digi-taltryck med bibehållen bildkvalitet. Detta för att om möjligt höja produktionshastigheten då en lägre bildupplösning ger en mindre filstorlek som går fortare att cmykseparera i RIP:en. Dessutom behövde Arkitektkopia AB en korrigering och uppdatering av sin dåvarande tabell för kundrekommendationer beträffande bildupplösning för olika format och betrakt-ningsavstånd. En visuell undersökning med Arkitektkopias kunder och privatpersoner har gjorts för att kunna fastställa riktvärden för bildupplösning och utröna toleransen för en godtagbar bildkvalitet. Resultaten utifrån kundundersökningen har legat till grund för den nya tabellen med kundrekommendationer som examensarbetet resulterat i. Undersökningen omfattade tre provgrupper i formaten A4, 70x100cm och 70x100cm (motsv. 135x180cm) med betrakt-ningsavstånden 30cm, 2m och 5m. Dessutom innefattade de tre provgrupperna två olika typer av bildmotiv. Endast färg-bilder ingick i undersökningen.Resultaten utifrån undersökningen visar på att bildupplösningen kan sänkas avsevärt jämfört med tidigare kundrekommen-dationer. Störst variationer återfanns för formatet A4 med ett betraktningsavstånd på 30cm (läsavstånd). Där var toleransen för en godtagbar bildkvalitet något högre för privatpersonerna än för kundgruppen.

The thesis focus on the availibility of the time series of producer price index (PPI) in the selected countries from Eastern Europe. The PPI time series are necessary for assets price estimation. The aim of the thesis is to proove if there could be a "converter" between the PPI total and PPI for individual activity which could be used for creating time series in countries where the data are not available.

Bovine Infected Cell Protein 0 (bICP0) is an immediate-early protein encoded by Bovine Herpesvirus-1 that modulates host immune response, activates transcription for all viral promoters, and causes ubiquitin-dependent degradation of proteins. Presented herein is a bICP0 protein-protein interaction (PPI) profile, consisting of 98 cellular and 15 viral proteins, generated through co-immunoprecipitation of bICP0 and its binding partners. The PPI profile was analyzed computationally to identify potential sites of interaction with bICP0 and any cellular pathways that may be influenced by bICP0. Some interactors fall in conjunction with bICP0’s known roles during infection, and others are consistent with known associations of bICP0 homologs. However, some proteins in the PPI profile are involved in apoptosis signaling and mRNA spicing—processes both significant during viral infection and novel to the known functions of bICP0 and its homologs. The interaction and co-localization of some of these proteins with bICP0 was further examined.

This observational study compared bone health biomarkers, bone mineral density (BMD),dietary habits, and physical activity levels of men (n=31) and non-estrogen supplementing postmenopausal women (n=23) divided according to duration of proton pump inhibitor (PPI) therapy; more than 5 years (n=16), less than 5 years (n=15), and no PPI therapy (n=23). The shortest duration of PPI therapy was 2 months and the longest duration of PPI therapy was 25 years with a mean duration of 7.5 years. No significant differences were found between measures of spine BMD, urinary deoxypyridinoline (bone resorption), urinary calcium and magnesium, serum osteocalcin (bone formation), serum parathyroid hormone, serum magnesium, serum 25 hydroxyvitamin D3, dietary and supplement intake, or physical activity levels. However, mean hip BMD was higher in females than in males in participants who took PPI therapy for any duration. In the no PPI therapy group, hip BMD was not significantly different between genders. These results suggest that there may be no measurable or clinically significant negative effects of long term PPI therapy on bone health. However, men may be at higher risk of hip fracture when taking long-term PPI therapy than women.

O Transtorno de Déficit de Atenção e Hiperatividade (TDAH) é a doença do neurodesenvolvimento mais comum na infância, afetando cerca de 5,8% de crianças e adolescentes no mundo. Muitos estudos vêm tentando investigar a suscetibilidade genética em TDAH, mas sem muito sucesso. Este estudo teve como objetivo analisar variantes raras e comuns contribuindo para a arquitetura genética do TDAH. Foram gerados os primeiros dados de exoma de TDAH de 30 trios brasileiros em que o filho foi diagnosticado com TDAH esporádico. Foram analisados tanto variações de único nucleotídeo (ou SNVs, single-nucleotide variants) quanto variações de número de cópias (ou CNVs, copy-number variants), tanto nesses trios quanto em outros conjuntos de dados, incluindo uma amostra brasileira de 503 crianças/adolescentes controles, bem como resultados previamente publicados em quatro estudos com variação de número de cópias e uma meta-análise de estudos de associação ao longo do genoma. Tanto os trios quanto os controles fazem parte da Coorte de Escolares de Alto Risco para o desenvolvimento de Psicopatologia e Resiliência na Infância do Instituto Nacional de Psiquiatria do Desenvolvimento (INPD). Os resultados de trios brasileiros mostraram três padrões marcantes: casos com variações herdadas e somente SNVs de novo ou CNVs de novo, e casos somente com variações herdadas. Embora o tamanho amostral seja pequeno, pudemos ver que diferentes comorbidades são mais frequentes em casos somente com variações herdadas. Após explorarmos a composição de variações nos probandos brasileiros, foram selecionados genes recorrentes entre amostras do nosso estudo ou em bancos de dados públicos. Além disso, usando somente genes expressos no cérebro (amostras pós-mortem dos projetos Brain Atlas e Genotype-Tissue Expression), construímos uma rede de interação proteína-proteína \"in silico\" com interações físicas confirmadas por pelo menos duas fontes. Análises topológicas e funcionais dos genes da rede mostraram genes relacionados a sinapse, adesão celular, vias glutamatérgicas e serotonérgicas, o que confirma achados de trabalhos independentes na literatura indicando ainda novos genes e variantes genéticas nessas vias. / Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neuro-developmental disorder in children, affecting 5.8% of children and adolescents in the world. Many studies have attempted to investigate the genetic susceptibility of ADHD without much success. The present study aimed to analyze rare and common variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios where the children were diagnosed with sporadic ADHD. We analyzed both single-nucleotide variants (SNVs) and copy-number variants (CNVs) in these trios and across multiple datasets, including a Brazilian sample of 503 children/adolescent controls from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of four CNV studies of ADHD involving children/adolescent Caucasian samples. The results from the Brazilian trios showed 3 major patterns: cases with inherited variations and de novo SNVs or de novo CNVs and cases with only inherited variations. Although the sample size is small, we could see that various comorbidities are more frequent in cases with only inherited variants. After exploring the rare variant composition in our 30 cases we selected genes with variations (SNVs or located in CNV regions) in our trio analysis that are recurrent in the families analyzed or in public data sets. Moreover, using only genes expressed in brain (post-mortem samples from Brain Atlas and The Genotype-Tissue Expression project), we constructed an in silico protein-protein interaction (PPI) network, with physical interactions confirmed by at least two sources. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.