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Die Rolle des intraoperativen Neuromonitorings bei der Behandlung von zerebrovaskulären Erkrankungen und infratentoriellen Tumoren
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Treatment outcome and survival analysis of Ebola patients receiving treatment in Sierra Leone
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Ebola Virus Disease (EVD) was first discovered in 1976 in Zaire along Ebola River affecting more than 250 people and had a mortality rate of 53%. Currently, there are five (Zaire ebolavirus, Reston ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus and Bundibugyo ebolavirus) strains of Ebola Virus. The Zaire ebolavirus has the highest (88%) mortality rate; Reston ebolavirus was discovered in Reston, Virginia, USA in 1989 in imported monkeys from Mindanao, Tai Forest ebolavirus was accidently discovered in 1994 in Tai Forest, Cote d'Ivoire. In 2005, the first direct evidence implicating bats as reservoir host for Ebola Virus emerged. EVD has various symptoms including fever, hemorrhage, myalgia, and diarrhea. There were more than 8,000 confirmed EVD cases and more than 4,000 EVD-related deaths were reported in Sierra Leone during the 2013 - 2016 West Africa EVD outbreak.
Method
We anonymized and later separately analysed the medical records of laboratory-confirmed pediatric, adult EVD patients, and a mixed cohort of EVD cases who received treatment at the 34 Military Hospital and the Police Training School ETCs in Sierra Leone; we also analysed the anonymized medical records of mixed cohort of laboratory-confirmed EVD cases who received treatment at the Kenema Government Hospital ETC (KGHETC).
Results
Majority of the 139 paediatric EVD cases in our study reported anorexia (99.1%), chest pain (98.6%), muscle pain (97.8%), headache (95.0%), fever (82.7%),
diarrhoea (71.3%), fatigue (67.0%), had Stage 2 EVD infection (64.0%) upon admission at the 34 Military Hospital ETC. The associations between the Case Fatality Rate (CFR), sex, age groups and occupational levels for our adult EVD cases admitted at the 34 Military Hospital were all statistically significant. Our predictive EVD patients mortality risk score for our mixed cohort of 1077 EVD patients admitted at the 34 Military Hospital shows that, those EVD patients who had an in-facility risk score of 12 had in 100% of cases a fatal outcome. The CFR for the 205 EVD patients treated at KGHETC was lower for those EVD patients who came from outside Kenema District compared to those who were admitted directly from within Kenema.
Conclusion
Based on the findings of our studies we recommend an adaptation of current EVD case definitions. We were able to identify a range of characteristics of EVD patients that were associated with adverse treatment outcomes. However, as both setting and virus strains may be different in future situations, the adoption of our model in future outbreak situations has to be taken with caution
Optical single-molecule biosensors assembled by DNA origami
Get PDFOptical biosensing with single-molecule sensitivity requires high performant fluorescent probes. Many different functionalities have to be combined into small chemical entities. In this thesis, the DNA origami technique was used to tailor single-molecule biosensors according to their diverse needs as it offers a modular probe development with straightforward iteration possibilities. The focus was on a nucleic acid detection assay for future in vitro diagnostic applications and on voltage sensors to be applied to cell membranes.
Particularly, for the nucleic acid detection assay, a silver nanoparticle was bound to a DNA origami pillar yielding a so-called nanoantenna which enhances the fluorescence of a dye in close proximity through plasmonic field interaction. This phenomenon was used to increase the optical signal released from a single DNA hairpin equipped with a dye-quencher pair. In the presence of a specific target nucleic acid, the hairpin’s secondary structure was broken and a fluorescence signal was observed. Using a hairpin sensing Zika specific sequences, the assay was characterized in terms of hairpin opening yield and fluorescence enhancement as well as single-nucleotide variation sensitivity and multiplexing ability. Further, diagnostic conditions were imitated by enriching heat-inactivated human serum with target DNA and using RNA targets. The presented detection assay yielded promising results for further development and future application in in vitro diagnostic assays at the point-of-care.
In addition, two single-molecule biosensors for electrical membrane potentials were developed; one sensor for transmembrane potentials and a second one for membrane surface charges of lipid head groups. Both sensors translated the voltage into Förster Resonance Energy Transfer (FRET) signals. A rectangular DNA origami was used as an assembly platform with different optional modifications, i.e. for membrane targeting, surface immobilization and voltage sensing. In both sensors, the sensing unit protruding from the origami plate, consisted of DNA and carried a FRET-compatible dye pair. The red dye anchored the sensing unit to the membrane and provided a stable FRET acceptor. A green dye was placed on DNA between the membrane and the DNA origami plate and flexibly changed its conformation in response to the voltages which resulted in the desired FRET change. For both, the transmembrane and the surface charge sensor, the sensing unit’s chemical structure was adapted to meet the different requirements.
The functionality of the transmembrane potential sensor was tested using liposomes with defined electrical potentials. It was shown that changes in the transmembrane potential were translated into different single-molecule FRET signals. Further, by introducing small chemical variations in the molecular structure of the sensing unit, the biosensor’s sensitivity was changed to respond either to de- or hyperpolarized membranes. Also, the membrane charge sensor yielded promising results; changes in the amounts of anionic lipids in liposomes resulted in different FRET signals. These findings suggested a quantitative translation of membrane surface charges into optical signals and were read out on the level of single sensors. Both sensing mechanisms were further characterized with molecular dynamic (MD) simulations for the transmembrane potential sensor and with fluorescence correlation spectroscopy (FCS) for the membrane surface charge sensor.
Overall, three different biosensors with optical single-molecule read-out were introduced in this thesis using DNA origami as an assembly platform. The sensors were examined for potential diagnostic applications and future in vivo voltage imaging. The presented results underline the potential of DNA origami for further single-molecule biosensors beyond the ones investigated within this thesis
Die Erwartungshaltung des Patienten beeinflusst die Rekonvaleszenz nach Major Leberresektion
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Placeboeffekte existieren auf allen Gebieten der Medizin und werden vom Arzt-Patienten-Verhältnis beeinflusst. Eine Reihe an Studien suggeriert einen bedeutenden Einfluss der Patientenerwartung als Teil des Placeboeffekts. Wir stellten daher die Hypothese auf, dass die präoperative Patientenerwartung an die postoperative Verweildauer Marker physischer Erholung nach Leberresektion beeinflusst.
Methoden
33 Patienten mit Leberresektion (≥4 Segmente) wurden nach Randomisierung über ein standardisiertes Video präoperativ entweder eine erwartete postoperative Verweildauer von 7-10 (kurzer Arm) oder 12- 16 Tagen (langer Arm) genannt und bezüglich psychologischer Merkmale befragt. Darüber hinaus blieb die perioperative Behandlung unverändert. Primärer Endpunkt war das Erreichen vordefinierter objektiver Entlasskriterien (orale Analgetika, intakte Stuhlpassage, Kostaufbau, Mobilisierung, keine Komplikationen). Ergebnisse Patienten im kurzen Arm erreichten die objektiven Entlasskriterien nach 7,94 (SD 3,21) und im Patienten im langen Arm nach 14,00 (SD 5,92) Tagen (p=0,002). Die tatsächliche Verweildauer betrug im kurzen Arm 12,0 (IQR 8-16) und im langen Arm 19,3 (IQR 14-26) Tage (p=0.008). Eine stärkere Selbstwirksamkeitsüberzeugung der Patienten korrelierte dabei mit schnellerem Erreichen der objektiven Entlasskriterien (p=0,04).
Schlussfolgerung
Die Erwartung einer kürzeren Aufenthaltsdauer resultiert in einer schnelleren physischen Erholung der Patienten nach Leberresektion. Weiterhin kann diese Erwartung moduliert und im Sinne des Patienten für verbesserte Ergebnisse genutzt werde
