Zgon w przebiegu kleszczowego zapalenia mózgu – opis serii przypadków

Tick-borne encephalitis (TBE) is a disease which may present as meningitis, encephalomeningitis and myeloencephalomeningitis. The course of the disease is usually mild although it may result in the patient's death in 1–4% of cases. Patients with myeloencephalomeningitis are the most endangered group, but also encephalomeningitis may have a fatal outcome. There are many risk factors which influence the severity of TBE, including patient's age, immunosuppression and concomitant diseases. We present four cases of patients who died because of TBE. The aim of the paper was to underline that in elderly patients or patients suffering from chronic diseases and additional infections, special attention should be paid to their treatment, including mechanical ventilation and steroid use.Kleszczowe zapalenie mózgu (KZM) może przebiegać pod trzema postaciami: zapalenia opon mózgowo-rdzeniowych, zapalenia mózgu i opon mózgowo-rdzeniowych oraz zapalenia rdzenia, mózgu i opon mózgowo-rdzeniowych. Przebieg choroby jest zazwyczaj łagodny, jednak w przypadku 1–4% pacjentów choroba może zakończyć się zgonem. Grupami najbardziej narażonymi na zgon są pacjenci z zapaleniem rdzenia, mózgu i opon mózgowo-rdzeniowych oraz z zapaleniem mózgu i opon mózgowo-rdzeniowych. Istnieje wiele czynników wpływających na ciężkość KZM, m.in. wiek pacjentów, upośledzenie układu odpornościowego i współistnienie innych chorób. W pracy zaprezentowano opisy czterech przypadków pacjentów, którzy zmarli z powodu KZM. Celem pracy jest podkreślenie, iż w przypadku starszych pacjentów lub pacjentów z chorobami przewlekłymi czy z innymi zakażeniami towarzyszącymi, chorujących na KZM należy zwrócić uwagę na leczenie, w tym respiratoro- i steroidoterapię

Neuroborelioza

Borelioza wywołana przez krętka Borrelia burgdorferi s.l. (B. burgdorferi s.l.) jest chorobą, która może się rozwinąć w kompleks zaburzeń wieloukładowych. Neuroborelioza to postać boreliozy z Lyme, której objawy dotyczą układu nerwowego. Jej symptomatologia wynika z możliwości lokalizacji procesu chorobowego w każdym miejscu układu nerwowego. Za najwcześniejszy zespół objawów uważa się zapalenie opon mózgowo-rdzeniowych, przebiegające z porażeniem nerwów czaszkowych, najczęściej VII. Zapalenie mózgu i rdzenia kręgowego jest najcięższą postacią neuroboreliozy. Częstość oceniana jest na 0,1% zakażonych B. burgdorferi i może się pojawić w każdym okresie zapalenia opon mózgowo-rdzeniowych. Encefalopatie bardzo często mają niewyjaśnioną przyczynę, występują tylko u niektórych pacjentów z boreliozą i przebiegają dość łagodnie. W chorobie z Lyme obserwuje się szerokie spektrum zaburzeń dotyczących nerwów obwodowych, takich jak: pojedyncze lub mnogie neuropatie czaszkowe, radikulopatie z zespołem bólowym lub rozlane polineuropatie, traktowane często jako mnogie mononeuropatie. Z chorobą z Lyme wiąże się również szerokie spektrum objawów psychicznych. Do grupy zaburzeń związanych z układem nerwowym należy tak zwany post Lyme syndrome stanowiący trudny problem kliniczny. Rozpoznanie neuroboreliozy opiera się na symptomatologii neurologicznej. Równie istotny jest wywiad, uwzględniający pobyt na terenie endemicznym z możliwością ekspozycji na ukłucie przez kleszcze. Potwierdzeniem rozpoznania jest wykrycie przeciwciał przeciw B. burgdorferi we krwi i płynie mózgowo-rdzeniowym w badaniach wykonanych za pomocą metody ELISA, a potwierdzonych metodą Western-blot. Badania elektroencefalograficzne (EEG), elektromiograficzne (EMG), potencjały wywołane, tomografia komputerowa (CT, computed tomography), rezonans magnetyczny (MRI, magnetic resonance imaging) i tomografia emisyjna pojedynczego fotonu (SPECT, single-photon emission computed tomography) są badaniami uzupełniającymi. W leczeniu stosuje się antybiotyki. Lekiem z wyboru jest cefalosporyna III generacji, na przykład ceftriakson w dawce 2-4 g na dobę przez okres przynajmniej 1 miesiąca

Equivalence of ELISpot Assays Demonstrated between Major HIV Network Laboratories

The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-γ) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates.We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study.Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (-1.5%, 1.5%) and CEF (-0.4%, 7.8%) responses, were both contained in the pre-specified equivalence margin of interval [-15%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study.The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories

«Det vestlandske» i moderne norsk prosa: en analyse av språk, sted og identitet i verkene til Erlend Nødtvedt, Frode Grytten og Marit Eikemo

Denne oppgaven er en analyse av hvordan begrepene språk, sted og identitet blir brukt for å uttrykke den vestlandske væremåten og utforme den «typisk vestnorske skrivestilen» i tre nåtidsprosaverk fra området: Erlend Nødtvedts Vestlandet, Frode Gryttens Bikubesong og Hardanger av Marit Eikemo. Målet er å avgjøre om man kan snakke om en enhetlig vestlandsk skrivestil i moderne litteratur. Jeg forsøker å finne svaret ved å identifisere hvordan de ovennevnte begrepene blir tolket i hvert av prosastykkene. I tillegg undersøker jeg hvilke litterære grep som blir brukt i verkene ansees for å være «typisk vestnorske» av sentrale vestlandsforskere. Avgjørelsen om en enhetlig, vestlandsk skrivestil eksisterer blir trukket gjennom en sammenligning av hvordan begrepene og ideen om det typisk vestlandske blir anvendt og skildret i Vestlandet, Bikubesong og Hardanger. Den teoretiske bakgrunnen for diskusjonen av de tre begrepene tar utgangspunkt i Johan Gottfried von Herder, Arne Garborg, Georg Arnestad og Sigrid Bø Grønstøl for språkbegrepet, Thomas Hylland-Eriksen og Narve Bjørgo for identitetsbegrepet, og Dan Ringgaard samt Per Thomas Andersen for stedsbegrepet. For vestlandsspesifikk teori benytter jeg meg av Sigrid Bø Grønstøls og Narve Bjørgos kapitler fra flerbindsverket Vestlandets historie og Georg Arnestads artikkel Vestlendingen – finst ho eller han og eventuelt kvar helst?. Avhandlingen konkluderes med en påstand at man ikke kan snakke om en bestemt vestlandsk skrivemåte, da steds- og identitetsbegrepene er meget subjektive størrelser med stor påvirkning på språk og litteratur. I tillegg kan de trekkene som ble identifisert som «typisk vestlandske» i analyse- og syntesedelen bli anvendt i litterære verk fra andre land og områder uten at identitetsperspektivet forskyves, noe som videre avkrefter muligheten for en enhetlig vestlandsk skrivestil

“The western Norwegian” mythos in modern Norwegian prose: an analysis of language, location and identity in the works of Erlend Nødtvedt, Frode Grytten and Marit Eikemo.

Denne oppgaven er en analyse av hvordan begrepene språk, sted og identitet blir brukt for å uttrykke den vestlandske væremåten og utforme den «typisk vestnorske skrivestilen» i tre nåtidsprosaverk fra området: Erlend Nødtvedts Vestlandet, Frode Gryttens Bikubesong og Hardanger av Marit Eikemo. Målet er å avgjøre om man kan snakke om en enhetlig vestlandsk skrivestil i moderne litteratur. Jeg forsøker å finne svaret ved å identifisere hvordan de ovennevnte begrepene blir tolket i hvert av prosastykkene. I tillegg undersøker jeg hvilke litterære grep som blir brukt i verkene ansees for å være «typisk vestnorske» av sentrale vestlandsforskere. Avgjørelsen om en enhetlig, vestlandsk skrivestil eksisterer blir trukket gjennom en sammenligning av hvordan begrepene og ideen om det typisk vestlandske blir anvendt og skildret i Vestlandet, Bikubesong og Hardanger. Den teoretiske bakgrunnen for diskusjonen av de tre begrepene tar utgangspunkt i Johan Gottfried von Herder, Arne Garborg, Georg Arnestad og Sigrid Bø Grønstøl for språkbegrepet, Thomas Hylland-Eriksen og Narve Bjørgo for identitetsbegrepet, og Dan Ringgaard samt Per Thomas Andersen for stedsbegrepet. For vestlandsspesifikk teori benytter jeg meg av Sigrid Bø Grønstøls og Narve Bjørgos kapitler fra flerbindsverket Vestlandets historie og Georg Arnestads artikkel Vestlendingen – finst ho eller han og eventuelt kvar helst?. Avhandlingen konkluderes med en påstand at man ikke kan snakke om en bestemt vestlandsk skrivemåte, da steds- og identitetsbegrepene er meget subjektive størrelser med stor påvirkning på språk og litteratur. I tillegg kan de trekkene som ble identifisert som «typisk vestlandske» i analyse- og syntesedelen bli anvendt i litterære verk fra andre land og områder uten at identitetsperspektivet forskyves, noe som videre avkrefter muligheten for en enhetlig vestlandsk skrivestil.This thesis seeks to analyse how the concepts of language, location and identity are being employed to express the western Norwegian character and create the “typically western Norwegian” writing style in three modern works of prose from the area: Erlend Nødtvedts Vestlandet, Frode Gryttens Bikubesong and Marit Eikemos Hardanger. The aim is to determine whether one can identify a cohesive, “typically western Norwegian” writing style in modern literature. I attempt to find the answer by identifying how the aforementioned concepts are being interpreted in each work of prose, and which literary devices that are deemed “typically western Norwegian” by the most prominent scholars on western Norwegian culture, are being put to use in these works. I try to determine if one can speak of a cohesive western Norwegian writing style through the comparison of how the three concepts, along with the notion of what is western Norwegian, are being depicted in Vestlandet, Bikubesong and Hardanger. The theoretical background for the discussion of the three concepts consists of Johann Gottfried von Herder, Arne Garborg, Georg Arnestad and Sigrid Bø Grønstøl for language, Thomas Hylland-Eriksen and Narve Bjørgo for identity, and Dan Ringgaard and Per Thomas Andersen for the concept of location. For western Norway-specific theory, I’ve turned to Sigrid Bø Grønstøls and Narve Bjørgos chapters in the three-tome work Vestlandets historie and Georg Arnestads article Vestlendingen – finst ho eller han og eventuelt kvar helst?. The thesis concludes by asserting that there is no such thing as one specific western Norwegian way of writing, as the concepts of location and identity are principally subjective in their nature while having great influence on language and literature. Furthermore, the literary devices deemed “typically western Norwegian” in the analysis and synthesis part of the thesis can successfully be used in literary works outside of the region without shifting their identity profile, which further dispels any hopes of a singular, western Norwegian writing style.Mastergradsoppgåve i nordisk språk og litteraturMAHF-NORDMAHF-LÆNONOLISP35

Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope

The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the target of three of the five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have determined crystal structures of the antigen-binding fragment for one of these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41 membrane-proximal region, at 2.0-, 2.1-, and 2.2-Å resolutions, respectively. The structures reveal an extended gp41 conformation, which stretches over 30 Å in length. Contacts are made with five complementarity-determining regions of the antibody as well as with nonpolymorphic regions. Only one exclusive charged face of the gp41 epitope is bound by 2F5, while the nonbound face, which is hydrophobic, may be hidden due to occlusion by other portions of the ectodomain. The structures reveal that the 2F5 antibody is uniquely built to bind to an epitope that is proximal to a membrane surface and in a manner mostly unaffected by large-scale steric hindrance. Biochemical studies with proteoliposomes confirm the importance of lipid membrane and hydrophobic context in the binding of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody that recognizes the membrane-proximal region of gp41. Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed