Interleukin-8 is the single most up-regulated gene in whole genome profiling of H. pylori exposed gastric epithelial cells

<p>Abstract</p> <p>Background</p> <p>The association between <it>Helicobacter pylori </it>infection and upper gastrointestinal disease is well established. However, only a small fraction of <it>H. pylori </it>carriers develop disease, and there are great geographical differences in disease penetrance. The explanation to this enigma lies in the interaction between the bacterium and the host. <it>H. pylori </it>Outer Membrane Phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 h of <it>H. pylori </it>exposure, and to study the inflammatory response to OMPLA⁺and OMPLA^-<it>H. pylori </it>variants.</p> <p>Results</p> <p>Interleukin-8 was the most significantly up-regulated gene and appears to play a paramount role in the epithelial cell response to <it>H. pylori </it>infection and in the pathological processes leading to gastric disease. MAPK and NF-kappaB cellular pathways were powerfully activated, but did not seem to explain the impressive <it>IL-8 </it>response. There was marked up-regulation of <it>TP53BP2</it>, whose corresponding protein ASPP2 may interact with <it>H. pylori </it>CagA and cause marked p53 suppression of apoptosis. Other regulators of apoptosis also showed abberant regulation. We also identified up-regulation of several oncogenes and down-regulation of tumor suppressor genes as early as during the first 24 h of infection. <it>H. pylori </it>OMPLA phase variation did not seem to influence the inflammatory epithelial cell gene response in this experiment.</p> <p>Conclusion</p> <p>In whole genome analysis of the epithelial response to <it>H. pylori </it>exposure, <it>IL-8 </it>demonstrated the most marked up-regulation, and was involved in many of the most important cellular response processes to the infection. There was dysregulation of apoptosis, tumor suppressor genes and oncogenes as early as in the first 24 h of <it>H. pylori </it>infection, which may represent early signs of gastric tumorigenesis. OMPLA^+/-did not affect the acute inflammatory response to <it>H. pylori</it>.</p

The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes Differs between Rectal and Colon Carcinoma

The E-cadherin-catenin complex provides cell-cell adhesion. In order for a carcinoma to metastasize, cancer cells must let go of their hold of neighboring cells in the primary tumor. The presence of components of the E-cadherin-catenin complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and compared to their presence in 219 colon carcinomas. The expression data were correlated to clinical information from the patients' records. There were statistically significant differences in protein expression between the rectal and the colon carcinomas regarding membranous β-catenin, γ-catenin, p120-catenin, and E-cadherin, as well as nuclear β-catenin. In the rectal carcinomas, there was a significant inverse association between the expression of p120-catenin in cell membranes of the primary tumors and the occurrence of local recurrence, while membranous protein expression of β-catenin was inversely related to distant metastases

Differences in Protein Expression and Gene Amplification of Cyclins between Colon and Rectal Adenocarcinomas

Adenocarcinomas of rectum and colon may be different with regard to the cellular biological basis for cancer development. A material of 246 rectal cancers removed surgically at Akershus University Hospital in the years 1992–2000 was investigated and was compared to a material of 219 colon cancers operated on at Akershus University Hospital during the years 1988, 1990 and 1997–2000. There were highly significant differences between the rectal and the colon cancers in the protein expression of cyclin D1, cyclin D3, cyclin E, nuclear β-catenin, and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and cyclin E. Gene amplification and protein expression in the rectal cancers correlated significantly for the cyclins B1, D3, and E. A statistically significant relation was observed between overexpression of cyclin A2 and local relapse of rectal carcinomas, as higher expression of cyclin A2 was associated with lower local recurrence rate

Karst i Elgfjellet, Lomsdal-Visten nasjonalpark: Strukturgeologi og grottearkitektur i Gråryggen

Postponed access: the file will be accessible after 2021-06-16Ei grotte kan definerast som eit naturleg holrom stort nok til at eit menneske kan kome seg inn (Ford og Williams, 2007). Om ei grotte er danna i oppløyseleg kalkstein eller marmor, omtalast holrommet som ei karstgrotte. For at ei karstgrotte skal kunne utformast, er ei av dei naudsynte faktorane eit samanhengande sprekkesystem. Grottepassasjar utviklast frå pre-eksisterende sprekkar, som kan knyttast opp mot det relevante området si tektoniske historie. Det strukturgeologiske aspektet rundt grottedanning står dermed svært sentralt for å kunne forstå utviklinga. Denne masteroppgåva utgjer ei av totalt fem masteroppgåver (Jenssen, 2020; Krossøy, 2020; Remmen, 2020; Torstad, 2020), som inngår i forskingsarbeidet tilknytta Elgfjellprosjektet, SA i Lomsdal-Visten nasjonalpark. Gråryggen omfattar eit området på A sida av Elgfjellet, beståande av eit marmorbelte av særs homogen og rein kalkspatmarmor. Denne oppgåva har som føremål å gjennom kartlegging og strukturelle målingar, gjennomført både på overflata og undergrunnen tilhøyrande Gråryggen, kunne belyse innverknaden den lokale og regionale strukturgeologien har hatt for utviklinga av dei aktuelle grottene. Revidert kartlegging har resultert i ei total passasjelengd på 1,2 km, fordelt på fire grottesystem lokalisert på Gråryggen. Grottene strekk seg i NA – SV til NV – SA retning, der dei i hovudsak er utvikla i skjeringslinjen mellom foliasjon og avlastingssprekker. Passasjemorfologi er styrt av hydrauliske årsaker, med berre få, lokale modifikasjonar. Det er føreslått at grottearkitektur er påverka av ei open synklinal fald, der ei tidlegare samankopling mellom to system er sannsynleg. Det er også identifisert sterk stratigrafisk kontroll på grottene si plassering, der både løyslegheit, sprekketettleik og den litologiske kontakten spelar inn. Det antas at løyslegheit utgjer den dominerande kontrollerande faktoren. Det er ikkje funne bevis for neotektonisk rørsle for feltområdet, der framlagte bevis frå tidlegare arbeid forklarast gjennom differensiell korrosjon. Hydrotermale mineralfyllingar antyder at sprekkar er eldre enn grotten, og kan tilskrivast prosessar knytt til den kaledonske orogonese i sein silur til tidleg devon eller opninga av Norskehavet i neogen. Gjennom ei kryssingsanalyse er føreseiing av passasjeretning forsøkt, der resultat i beste fall visar sannsynleg utstrekking.Masteroppgåve i geovitskapGEOV399MAMN-GEO

Usefulness of a national parent experience survey in quality improvement: views of paediatric department employees

Objectives\ud \ud This study presents results from an electronic survey among paediatric department employees, addressing employees' attitudes and use of results from a national parent experience survey carried out in 2005.\ud \ud Methods\ud \ud Electronic questionnaire survey of employees from each of the 20 paediatric departments included in the national survey, with a response rate of 87%.\ud \ud Results\ud \ud The employees had favourable opinions of user experience surveys, and the results from the national survey were well known among both managers and other personnel. User experience surveys were considered important, and 56% reported that they had implemented improvement actions addressing problems identified in the national survey. Managers reported more often than staff without managerial responsibility that the results had been informally discussed, and that the survey was useful for their own department. Department leaders were more positive to the usefulness of the survey than non-leaders. Significant differences in attitudes were found between physicians and other health personnel.\ud \ud Conclusion\ud \ud Employees in the paediatric departments were positive to user experience surveys, and the surveys have a potential to be actively used in quality improvement actions. Effects of the quality improvement initiatives should be assessed in future parent experience surveys

Exotoxin-encoding gene content in community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus

AbstractReports of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) causing hospital infections are increasing, and it is questionable whether the existing molecular definition of CA-MRSA is suitable for the characterization of all strains involved. The 821 methicillin-resistant S. aureus (MRSA) isolates recovered from patients in Health Region East, Norway during the period 1991—2006 were characterized by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) gene typing, and their content of exotoxin-encoding genes. Cluster analysis based on exotoxin-encoding gene content was performed to separate the MRSA isolates into valid clusters with respect to microbiological characteristics. The analysis gave a four-cluster structure, and the four toxin clusters differed in the genetic lineages they included and in the diversity of the genetic lineages. A few genetic lineages were present in several toxin clusters. These results support the theory that mobile genetic elements encoding virulence genes do not move randomly among genetic lineages, but are restricted by the clonal lineages’ genetic background. Using the molecular criteria, MLST type, SCCmec type and the presence of the lucS/F-Panton–Valentine leukocidin (PVL) gene to define a CA-MRSA isolate, it was found that the CA-MRSA isolates mainly grouped together in two toxin clusters with a low prevalence of exotoxin-encoding genes. Statistical analyses supported the conclusion that toxin clusters with CA-MRSA genetic lineages were characterized by a low prevalence of exotoxin-encoding genes, whereas toxin clusters with hospital-acquired MRSA genetic lineages were characterized by a higher prevalence of exotoxin-encoding genes

Patients Who Die by Suicide: A Study of Treatment Patterns and Patient Safety Incidents in Norway

Underlying patterns and factors behind suicides of patients in treatment are still unclear and there is a pressing need for more studies to address this knowledge gap. We analysed 278 cases of suicide reported to The Norwegian System of Patient Injury Compensation, drawing on anonymised data, i.e., age group, gender, diagnostic category, type of treatment provided, inpatient vs. outpatient status, type of treatment facility, and expert assessments of medical errors. The data originated from compensation claim forms, expert assessments, and medical records. Chi-square tests for independence, multinominal logistic regression, and Bayes factors for independence were used to analyse whether the age group, gender, diagnostic category, inpatient/outpatient status, type of institution, and type of treatment received by patients that had died by suicide were associated with different types of medical errors. Patients who received medication tended to be proportionally more exposed to an insufficient level of observation. Those who received medication and psychotherapy tended to be proportionally more exposed to inadequate treatment, including inadequate medication. Inpatients were more likely to be exposed to inappropriate diagnostics and inadequate treatment and follow up while outpatients to insufficient level of observation and inadequate suicide risk assessment. We conclude that the patients who had received medication as their main treatment tended to have been insufficiently observed, while patients who had received psychotherapy and medication tended to have been provided insufficient treatment, including inadequate medication. These observations may be used as learning points for the suicide prevention of patients in treatment in Norwegian psychiatric services

Compensation claims in pediatric orthopedics in Norway between 2012 and 2018: a nationwide study of 487 patients

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Intratumoural mRNA expression of genes from the oestradiol metabolic pathway and clinical and histopathological parameters of breast cancer

INTRODUCTION: The expression of the oestrogen receptor (ER) is one of the more important clinical parameters of breast cancer. However, the relationship between the ER and its ligand, oestradiol, and the enzymes that synthesise it are not well understood. The expression of mRNA transcripts of members of the oestradiol metabolic and signalling pathways including the ER was studied in detail. METHOD: mRNA transcripts for aromatase (CYP19), 17-β-hydroxysteroid dehydrogenase I, 17-β-hydroxysteroid dehydrogenase II, ERα, ERβ, steroid sulfatase (STS), oestradiol sulfotransferase (EST), cyclin D(1 )(CYCLD1) and ERBB2 were fluorometrically quantified by competitive RT-PCR using an internal standard in 155 breast carcinomas. In addition, the transcripts of CYP19 were analysed for alternative splicing/usage of exon 1 and an alternative poly A tail. RESULTS: A great variability of expression was observed, ranging from 0 to 2376 amol/mg RNA. The highest levels were observed for STS and EST, and the lowest levels (close to zero) were observed for the 17-β-hydroxysteroid dehydrogenase isoenzymes. The levels of mRNA expression were analysed with respect to clinical and histopathological parameters as well as for disease-free survival. High correlation of the mRNA expression of STS, EST and 17-β-hydroxysteroid dehydrogenase in the tumours suggested a common regulation, possibly by their common metabolite (oestradiol). Hierarchical clustering analysis in the 155 patients resulted in two main clusters, representing the ERα-negative and ERα-positive breast cancer cases. The mRNA expression of the oestradiol metabolising enzymes did not follow the expression of the ERα in all cases, leading to the formation of several subclasses of tumours. Patients with no expression of CYP19 and patients with high levels of expression of STS had significantly shorter disease-free survival time (P > 0.0005 and P < 0.03, respectively). Expression of ERβ mRNA was a better prognostic factor than that of ERα in this material. CONCLUSION: Our results indicate the importance of CYP19 and the enzymes regulating the oestrone sulfate metabolism as factors of disease-free survival in breast cancer, in addition to the well-known factors ER and ERBB2

The Terra-scandal: For municipalities the road to hell is paved with good intentions

Mastergradsoppgave MPA, 2013. Ordinær master, 45 st.p.I løpet av oktober 2007 blei det kjent at fire Helgeland kommunar og fire Vestland kommunar hadde gått på store tap. Ti norske kommunar hadde i åra 2001 – 2003 gjort investeringar i amerikanske finansprodukt formidla av meklarfirmaet Terra Securities. To av kommunane kom seg ut utan tap. Saman med bustyret i Terra Securities tok sju kommunar ut søksmål mot bankgruppa Citigroup etter at Terra Securities blei slegen konkurs 29.november 2007. No vel seks år seinare og med vel 90 millionar brukt på advokatar håpar framleis dei råka norske kommunane å komma sigrande ut av eit rettsoppgjer i New York mot den amerikanske finansgiganten Citigroup, ein av verda sin mektigaste bankar. Like før påske i 2013 blei saka forkasta i det amerikanske rettsapparatet. Men det er kjent at det framleis ligg eit håp om at saka kan prøvast på nytt att. Det er krise når små kommunar taper hundrevis av millionar. Det er det vårt prosjekt ønskjer å sjå nærare på. Me har prøvd å gjera ein kontekstualisert rekonstruksjon å finne ut kva val gjorde dei kommunane som takka nei til Terra. Kva slags faktorar i dei ulike kontekstane på nasjonalt nivå – lokalt nivå – individ nivå har gjort at dei fleste norske kommunar avstod tilbodet frå Terra og kvifor inngjekk nokre få kommunar ein avtale. Det er kjent at dei fleste av dei ti kommunane som investerte i Terra sine produkt var kommunar med høge konsesjonskraftinntekter per innbyggjar. Me har valt at dei inngår i utvalet vårt til den komparative analysen. I tillegg har me valt oss ut ti andre kommunar med nokså store konsesjonskraftinntekterper innbyggjar som også er med i utvalet til den komparative analysen. Vårt utgangspunkt til forsking på Terra er at det er skreve ein master om kva som skjedde i dei ti Terra-råka kommunane og at det føreligg rapportar frå Riksrevisjon, Fylkesmenn og granskingsrapportar bestilt av det enkelte kontrollutval i kommunane. Vårt arbeid har difor vorte å framskaffe datamateriell i frå nei-kommunane. Me har brukt ein referansekommune for å kartleggje. I analysearbeidet har me støtta oss på Blumer og Hoonard, Sensitizing Consepts. Funna i referansekommunen har ein kategorisert og deretter operasjonalisert for vidare bruk i den komparative analysen. Utgangspunktet for desse 20 kommunane er at dei er heilt like. Dei har store konsesjonskraft inntekter pr. innbyggjar og dei har alle fått eit tilbod frå Terra. Me nytta analyseverktøyet ”most similar systems ” og har funne ein kritisk variabel som skil dei . Våre funn visar at den kritiske variabelen er intern ekspertise.Engelsk sammendrag (abstract): During October 2007 it was announced that four Helgeland municipalities and four Western municipalities had gone to great losses. Ten Norwegian municipalities had in the years 2001 - 2003 made investment in U.S. Treasury products conveyed by broker firm Terra Securities. Two of the municipalities came out without loss. Along with bankruptcy board of Terra Securities took seven municipalities proceedings against banking group Citigroup after Terra Securities went bankrupt on 29 November 2007. Now, over six years later and with well 90 million used on lawyers still hope the Norwegian municipalities that were hit to get victorious from a legal settlement in New York against the U.S. financial giant Citigroup, one of the world s most powerful banks. Just before Easter in 2013, the case was dismissed in U.S. courts. But it is known that there is still a hope that the case can be tried again. It is a crisis when small municipalities are losing hundreds of millions. That is what our project would like to look into. We have attempted to make a contextualized reconstruction to determine which choice was made by the local authorities refused to Terra. What factors in the different contexts at the national level - local level - individual level has meant that the vast majority of Norwegian municipalities ceded an offer from Terra and why signed a few municipalities that kind of deal. It is known that most of the ten municipalities that invested in Terra’s products were municipalities with high concessionary income per capita. We have chosen them to be part of our selection in the comparative analysis. In addition, we have chosen us out ten other municipalities with relatively large concessionary income per capita which is also included in the sample for the comparative analysis. Our starting point in research on Terra is that it is written a master of what happened in the ten Terra-affected municipalities and that there are reports from the Auditor General, Region Men and investigation reports commissioned by the individual Scrutiny in municipalities. Our work has therefore been to obtain data from the no-municipalities. We have used a local reference to map. In the analyzes, we have relied on Blumers and Hoonards Sensitizing Concepts. The findings of the reference municipality has categorized and then operationalized for further use in the comparative analysis. The basis for these 20 municipalities is that they are completely equal. We used analysis tool “most similar systems” and our findings show that the critical variable is internal expertise