Studienprotokoll: Register zur Prognose akut-symptomatischer Anfälle (PROSA-Register) – eine prospektive multizentrische Beobachtungsstudie

Background: Acute symptomatic epileptic seizures occur in close temporal relation to an acute disturbance of brain function. They are associated with a low risk of subsequent unprovoked seizures; thus, current guidelines recommend not to administer a long-term antiseizure medication; however, in clinical practice long-term secondary seizure prophylaxis is frequently initiated. The seizure prognosis after guideline-conform untreated or only briefly treated acute symptomatic seizures, is so far unknown. Hypothesis: Following an acute symptomatic first epileptic seizure of structural etiology, the 1-year risk of subsequent unprovoked seizures is not higher than 25%, even if antiseizure medication was not applied or for a short period only. Methods: The PROSE register is a single-arm, open, prospective, multicenter observational study. A total of 115 subjects aged 18 years or older with an acute symptomatic first epileptic seizure of structural etiology will be included if the seizure was not a status epilepticus. Intrahospital follow-up will be based on the hospital records. Telephone follow-up interviews will be conducted 3, 6, and 12 months after the acute symptomatic seizure. Discussion: The PROSE register will shed light on current treatment practice of acute symptomatic seizures and the actual seizure outcome within 1 year. The results are assumed to support the current evidence that giving antiseizure medication for a longer period of time exceeding the acute phase of the underlying condition is unnecessary

Einfluss der Transkriptionsfaktoren STAT3 und AP-1 auf die Expression der Matrixmetalloproteinase 1 in Zellen des kolorektalen Karzinoms

In vorangegangenen Arbeiten konnte eine Koinzidenz zwischen der Protease Matrixmetalloproteinase 1 (MMP-1) und der malignen Progression des kolorektalen Karzinoms aufgezeigt werden. Als wichtiger Induktor des Enzyms wird der Signal Transducer and Activator of Transcription (STAT) 3 angesehen. Ziel war es, die Expressionskontrolle von MMP-1 durch STAT3 unter Einbezug des Transkriptionsfaktors Activator Protein (AP-)1 näher zu untersuchen. Dabei wurde u.a. ein bestimmter Abschnitt des MMP-1- Promoters fokussiert, welcher eine STAT3- und eine AP-1- Bindungsstelle besitzt. Reportergen- Analysen mit diesem 0,6kb- Fragment stellten zum einen AP-1 als dominierenden Faktor bezüglich der transkriptionellen Aktivierung heraus. Zum anderen lieferten sie den Hinweis auf eine expressionswirksame Kooperation zwischen den beiden Faktoren, welche durch DNA- Bindungsassays (ABCD) im Sinne einer Komplexbildung erhärtet wurden. In Real Time PCR- Versuchen zeigte sich der beobachtete additive Effekt als Ausdruck einer Kooperation nicht, was sich eventuell durch STAT3- inhibierende Mechanismen am Volllängenpromoter begründen lässt. Jedoch führte die artifizielle Suppression des intrazellulären STAT3- Levels zu einer Reduktion der basalen MMP-1- Expression, was die Bedeutung von unphosphoryliertem STAT3 zur Diskussion stellt. Mit Hilfe einer Kernfraktionierung gelang der Nachweis von im Zellkern lokalisiertem inaktivem STAT3, sodass eine derartige Einflussnahme auf die MMP-1 Expression möglich scheint. Neben diesem offenbarten die Ergebnisse der Real Time PCR- Versuche einen potentiellen Beitrag des als Tumorsuppressor bekannten Mediators STAT1. In zusammenfassender Betrachtung der Ergebnisse erscheint die Kooperation zwischen diesen Transkriptionsfaktoren als möglicher essentieller Mechanismus bezüglich der Expressionkontrolle von MMP-1

Results of a survey (1998 - 2000) on women in childbed in the Old and New Federal States of Germany

Titelblatt und Inhaltsverzeichnis Einleitung und Zielstellung Material und statistische Auswertung Ergebnisse Diskussion Zusammenfassung LiteraturverzeichnisAuch heute noch fallen die Ansichten bezüglich Familie und Beruf in beiden Teilen Deutschlands sehr unterschiedlich aus. Frauen aus den neuen Bundesländern haben sowohl allgemein als auch persönlich eine positivere Einstellung zur Vereinbarkeit von Beruf und Familie. Sie finden es leichter möglich beides zu vereinbaren als Frauen aus den alten Bundesländern, da sie die Vereinbarkeit durch ihre höhere Erwerbsbeteiligung auch häufiger praktizieren. Frauen aus den neuen Bundesländern verfügen jedoch auch über ein gut ausgebautes Netz von Kinderbetreuungseinrichtungen. In den alten Bundesländern hingegen stellt die Kinderbetreuung weiterhin ein großes Problem dar. Für Kinder unter 3 und über 6 Jahren gibt es kaum Angebote, so dass eine Berufstätigkeit der Mutter nur durch aufwendig organisierte private Betreuung oder gar nicht möglich ist. Für Kinder von 3 bis 6 Jahren gibt es zwar überwiegend flächendeckende Betreuungsmöglichkeiten, doch bei einem Anteil von Ganztagsplätzen von unter 25% ist selbst die Ausübung einer Teilzeitberufstätigkeit deutlich erschwert und Vollzeitarbeit kaum möglich. In den neuen Bundesländern stehen in allen Altersgruppen genügend Ganztagsplätze zur Verfügung, so dass die Kinderbetreuung hier zur Vereinbarung von Beruf und Familie beiträgt. Ostdeutsche Mütter arbeiten daher häufiger Vollzeit als westdeutsche und scheiden nach Geburt eines Kindes nur für kurze Zeit aus dem Beruf aus. Frauen aus den neuen Bundesländern sind ebenfalls wesentlich seltener zur Aufgabe ihres Berufes bereit, auch bei ausreichend hohem Einkommen des Mannes. Des Weiteren teilen sich Mütter und Väter aus den neuen Bundesländern die Kindererziehung partnerschaftlicher als in den alten Bundesländern. Hier hingegen ist die Mutter häufiger allein für die Erziehung der Kinder verantwortlich. Dagegen verfügen Familien aus den alten Bundesländern weiterhin über ein höheres Haushaltseinkommen und haben einen besseren Lebensstandard. Die vorliegende Arbeit konnte somit zeigen, dass die Unterschiede zwischen den alten und neuen Bundesländern auch über ein Jahrzehnt nach der Wiedervereinigung weiter bestehen, auch bei Frauen, die sich gerade für ein Kind entschieden haben. Diese Unterschiede bleiben auch bei Berücksichtigung des Schulabschlusses der Wöchnerinnen, dem Nettoeinkommen, der Zahl der Kinder, dem Lebensstandard und der beruflichen Stellung der Wöchnerinnen sowie ihrer Partner größtenteils bestehen. Lediglich bei Untergruppen mit kleinen Fallzahlen sind die Unterschiede nicht immer signifikant.People in Eastern and Western Germany still have different views on family and career. Women from the New Laender think more positive of the compatibility of family and career in general and personally. They think it is easier to combine both, because of their higher labor participation, they more often practice compatibility. They are also in advantage of childcare possibilities contrary to women in the Old Laender. There are only few offers for childcare for children under the age of 3 and above 6. In between there are area-wide kindergartens, but less than 25% offer full time care. So it is almost impossible for mothers to work at full time jobs. The New Federal States offer full time care for almost all ages. So women there work more often in full time jobs and start working earlier after birth of a child. They are also often not willing to stay at home if the husband s income is adequate for the family s needs. Breeding and education of children is more often part of both parents in Eastern than in Western Germany, where women are more the only responsible parent. In contrast, family income and standard of living are still higher in the Old Federal States. This survey points out that differences still resume even ten years after reunification of both German countries. These differences are not significantly constrained by graduation level, family income, number of children, standard of living and professional qualification of the examined women in childbed and their partners

Fallstudie: Antibiotika in der Palliativmedizin

The paper at hand explores medical decision-making in instances where a decision on the continuance or withdrawal of the antibiotic therapy of a palliative patient is required. Representatives of hospices, palliative care institutions and oncologic and geriatric clinics were interviewed on the issue of decisions related to a specific therapy and the decision-making criteria which are to be fulfilled. Important criteria were identified to be the achievable quality of life, the prospect of success and patient wishes. Decisions were most frequently justified on the basis of the necessity of symptom monitoring and the statement that therapy is worthwhile. The most frequent reasons for the rejection of therapy were incorrect indication, malignant underlying disease or statements in advance patient directives which declined invasive, life-prolonging treatments. The “urinary tract infection” and “pneumonia” scenarios highlighted concurrences in the assessments given by representatives of various specialisations. Decision-making was shown to be more difficult in the “sepsis” scenario. The case of a young patient exhibiting acute deterioration in their previously good overall health was described and considered. Short- and long-term prognoses were difficult to establish. Age and family situation had differing impacts on the decision. There were also discrepancies between declarations made in the patient’s advanced directive and the wishes of his wife. The majority of oncologic and geriatric clinics support therapy in such cases. The opinion of representatives of hospices and palliative care institutions was shown to be divided. In the majority of cases, hospices, palliative care institutions and geriatric clinics found justification for the rejection of treatment in the instructions set out by the patient in their advanced directive. Hospices and palliative care institutions rejected treatment in instances where the underlying disease was malignant and the prognosis was poor. On the other hand, geriatric and oncologic clinics were found to opt for therapy on a more regular basis, with the patient’s wish to receive treatment the most common justification. The paper at hand identifies variations in approach from specialisation to specialisation. This indicates that in-depth discussion of related issues and the education of doctors in palliative care are both sensible and necessary where the legal and ethical assessment of therapy decisions is concerned

Fallstudie: Antibiotika in der Palliativmedizin

The paper at hand explores medical decision-making in instances where a decision on the continuance or withdrawal of the antibiotic therapy of a palliative patient is required. Representatives of hospices, palliative care institutions and oncologic and geriatric clinics were interviewed on the issue of decisions related to a specific therapy and the decision-making criteria which are to be fulfilled. Important criteria were identified to be the achievable quality of life, the prospect of success and patient wishes. Decisions were most frequently justified on the basis of the necessity of symptom monitoring and the statement that therapy is worthwhile. The most frequent reasons for the rejection of therapy were incorrect indication, malignant underlying disease or statements in advance patient directives which declined invasive, life-prolonging treatments. The “urinary tract infection” and “pneumonia” scenarios highlighted concurrences in the assessments given by representatives of various specialisations. Decision-making was shown to be more difficult in the “sepsis” scenario. The case of a young patient exhibiting acute deterioration in their previously good overall health was described and considered. Short- and long-term prognoses were difficult to establish. Age and family situation had differing impacts on the decision. There were also discrepancies between declarations made in the patient’s advanced directive and the wishes of his wife. The majority of oncologic and geriatric clinics support therapy in such cases. The opinion of representatives of hospices and palliative care institutions was shown to be divided. In the majority of cases, hospices, palliative care institutions and geriatric clinics found justification for the rejection of treatment in the instructions set out by the patient in their advanced directive. Hospices and palliative care institutions rejected treatment in instances where the underlying disease was malignant and the prognosis was poor. On the other hand, geriatric and oncologic clinics were found to opt for therapy on a more regular basis, with the patient’s wish to receive treatment the most common justification. The paper at hand identifies variations in approach from specialisation to specialisation. This indicates that in-depth discussion of related issues and the education of doctors in palliative care are both sensible and necessary where the legal and ethical assessment of therapy decisions is concerned

Treatment of established status epilepticus in the elderly - a study protocol for a prospective multicenter double-blind comparative effectiveness trial (ToSEE)

Background!#!Status epilepticus (SE) is a common neurological emergency condition that especially affects the elderly and old population. Older people with SE frequently have non-convulsive SE (NCSE) and are also at special risk of suffering a poor outcome. The application of benzodiazepines fails to control SE in about one third of the cases. For benzodiazepine refractory SE (BRSE) in elderly, there is little evidence that would justify the choice of one of the commonly used antiepileptic drugs. The present study aims to generate evidence for the treatment of BRSE in this age group.!##!Methods!#!We will conduct a prospective, randomized, double-blind comparative effectiveness study in more than twenty hospitals in Germany over a four-year period. Four hundred and seventy-seven elderly patients (≥ 65 years old) diagnosed with BRSE will be allocated by 1:1 randomization to receive either levetiracetam or valproate. All types of SE will be considered. For the diagnosis NCSE a verification by EEG is required. Levetiracetam or valproate will be administered in one single infusion. The primary endpoint is the stable cessation of ictal activity 15 min after the start of infusion persisting for the following 45 min of observation. EEG recording is maintained over the whole observation period, clinical examinations are conducted in predefined intervals. In case of treatment success patients and study staff remain blinded until 60 min after the start of the infusion. Adverse events will be recorded until the end of the study. EEG data will be reviewed by two external independent experts. To obtain data about the further treatment of SE, intrahospital complications and the functional outcome in the short term the study participants will be observed until the day of discharge or day 30 whichever is earliest.!##!Discussion!#!ToSEE is the first study which shall deliver evidence for the SE-therapy in the elderly and old population in a controlled prospective comparator study. By design it also shall collect information about therapy regimes and outcome aspects of this disease.!##!Trial registration!#!The trial has been registered at the German Clinical Trials Register on 3 July, 2020 ( DRKS00022308 ,  https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022308 )

Metabolic Long-Term Monitoring of Transcorneal Electrical Stimulation in Retinitis Pigmentosa

Introduction!#!Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyze oxygen saturation in retinal vessels and has shown promising short-term results as a therapy monitoring tool for TES. The aim of our study was to measure the long-term effects of TES on RO parameters over a period of 3 years (3Y).!##!Methods!#!A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0-1.5 optic-disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V SO2) were measured and their difference (A-V SO2) was calculated. In addition, we recorded the diameters in the main arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were employed for statistical analysis using SPSS®.!##!Results!#!After 3Y of TES treatment both the mean A-SO2 (from 96.35 ± 12.76% to 100.89 ± 5.87%, p = 0.22) and V SO2 (from 62.20 ± 11.55% to 64.55 ± 8.24%, p = 0.77) increased slightly. The A-V SO2, which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance (p = 0.27). TES also did not appear to alter the vascular diameter parameters, D-A and D-V (p > 0.05).!##!Conclusion!#!Our long-term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow-up study and to confirm this trend reflecting a possible benefit of TES for RP

Untersuchung von ScAlN für piezoelektrische und ferroelektrische Anwendungen

ScxAl1-xN ist ein vielversprechendes Material, da Scandium unter Beibehaltung der kristallinen Wurtzitstruktur die piezoelektrischen Konstanten gegenüber reinem AlN stark erhöht. In dieser Arbeit wird ein stationäres reaktives Puls-Magnetron-Sputtern zur Abscheidung von Funktionsschichten mit einem Scandiumgehalt x = 0… 0,44 eingesetzt. Die Schichtmorphologie, die piezoelektrische Eigenschaften als auch die Durchbruchspannung werden untersucht. XRD Messungenzeigen, dass ein hoher Scandiumgehalt zu einer schwächer ausgeprägten Wurtzitbildung führt. Die vom Parameterx abhängige Gitterkonstante wurde auf der Basis von XRD-Daten berechnet. Die resultierende Kurvencharakteristik stimmt mit der Dichtefunktionaltheorie überein. Der höchste piezoelektrische Koeffizient d33 wurde bei einem Scandiumgehalt von 36,6% beobachtet, er beträgt 27,5 pC / N. Parallele Kondensatorstrukturen wurden durch chlorbasiertes ICP-Ätzen und Lift-Off-Strukturierung der oberen Elektroden erzeugt. Die technologischen Details des Strukturierungsprozesses werden vorgestellt. Die Ätzrate von ScxAl1-xN hängt dabei stark vom Scandiumgehalt ab. Anhand der Teststrukturen wurde die Permittivität bestimmt. Sie nimmt mit zunehmendem Scandiumgehalt signifikant zu. Es wurden hohe Kapazitätswerte bis zu 7,4 nF gemessen. Die adäquate Durchbruchspannung von 51 V für Scandiumkonzentrationen von x = 0,22 oder höher legt nahe, dass solche Schichten neben den bewährten piezoelektrischen Anwendungen für integrierteDünnschichtkondensatoren verwendet werden können