Untersuchung der Verläufe von Schwangerschaften nach Nierentransplantation unter besonderer Beachtung der maternalen und fetalen Komplikationen

Eine Nierentransplantation stellt keine Kontraindikation für eine Schwangerschaft dar. Aufgrund von Transplantatknappheit, medizinischer Vorgeschichte dieser Patientinnen, Immunsuppression und Begleiterkrankungen, gilt eine solche Schwangerschaft jedoch als Risikoschwangerschaft und kommt nur vereinzelt vor. Daher kann auch bei langfristigen Single-Center-Studien wie dieser stets nur ein kleines Kollektiv analysiert werden. Bei dieser Dissertation handelt es sich um eine retrospektive klinische Single-Center-Studie des Departments für Frauengesundheit der Universitätsklinik Tübingen. Analysiert wurden die Daten aller Patientinnen mit Nieren-(Pankreas-)transplantat, die dort im Zeitraum 2002 bis 2013 im Rahmen einer Schwangerschaft vorstellig wurden. Insgesamt waren elf Schwangerschaften bei neun Patientinnen dokumentiert. Hiervon endete eine mit intrauterinem Fruchttod. Aus den anderen gingen zehn lebende Neugeborene hervor, von denen eines in Folge extremer Frühgeburtlichkeit verstarb. Relevante maternale Begleiterkrankungen waren Hypertonie und Diabetes mellitus (bei sechs bzw. vier Schwangerschaften). Komplikationen, die im Rahmen der Schwangerschaften auftraten, waren eine schwangerschaftsinduzierte Hypertonie, fünf Fälle intrauteriner Wachstumsretardierung und zwei Fälle von Präeklampsie. Es traten vier fetale Infektionen, vier maternale Harnwegs- oder Vaginalinfekte und drei weitere maternale Infekte auf, darunter zwei Fälle von Amnioninfektionssyndrom und ein Zytomegalie-Primärinfekt während der Schwangerschaft. Die Schwangerschaften endeten per Sectio caesarea in Schwangerschaftswoche 31+6 (Median) und damit, mit nur einer Ausnahme, frühzeitig. Die Neugeborenen wiesen in Summe verringerte Körpermaße auf. Die Mediane von Körperlänge (40,5 cm), Gewicht (1535 g) und Kopfumfang (28,5 cm) bewegten sich entlang der 16. bis 20. Perzentile. Die Entwicklung der Kinder wurde ein und zwei Jahre postpartal dokumentiert. Die Immunsuppression wurde in allen Fällen auf die schwangerschaftskompatiblen Präparate Azathioprin, Cyclosporin A, Tacrolimus und (Methyl-)Prednisolon umgestellt. Ausschließlich gestillt werden konnte in keinem Fall, in wenigen Fällen wurde teilgestillt. Es fiel positiv auf, dass sich die Kinder motorisch und kognitiv altersgerecht entwickelten und sich auch hinsichtlich ihrer somatischen Entwicklung innerhalb der ersten beiden Lebensjahre der 50. Perzentile annäherten. Innerhalb des Kollektivs zeigte sich, dass eine stabile Transplantatfunktion der Mutter (gemessen am Kreatininwert) zu Beginn der Schwangerschaft mit einer günstigeren somatischen Entwicklung des Kindes intrauterin, einer längeren Schwangerschaftsdauer und einer besseren postpartalen Transplantatfunktion korrelieren. Es zeigte sich, dass die fetale körperliche Entwicklung bei Schwangerschaften während eines Zeitintervalls von zwei bis fünf Jahren nach Transplantation besonders günstig ist. Die Transplantatfunktion erwies sich im Kollektiv während der Schwangerschaft als etwas eingeschränkt, erkennbar an einer reduzierten glomerulären Filtrationsrate und erhöhten Kreatininwerten gegenüber den Ausgangswerten. Diese Werte hatten sich zwei Jahre nach Entbindung gebessert, aber nicht wieder bis auf Ausgangsniveau normalisiert. Akute Rejektionsereignisse oder die Notwendigkeit einer Hämodialyse traten während keiner Schwangerschaft auf. In der Langzeitbeobachtung (ein bis elf Jahre postpartal) kam es in einem Fall zu einem prolongierten Transplantatversagen mit Transplantatverlust ohne erkennbaren Zusammenhang zur vorausgegangenen Schwangerschaft. Hypertonus, Präeklampsie, Frühgeburt, Infektionen und eine Beeinträchtigung der Transplantatfunktion stellen ein reelles Risiko für Schwangere mit Nierentransplantat dar. Eine längerfristige Verschlechterung der Transplantatfunktion ist denkbar, ein Transplantatverlust nur vereinzelt zu befürchten. Die Risiken können durch eine exakte rechtzeitige Planung und engmaschige nephrologische und gynäkologische Kontrolle minimiert werden

Pregnancy following kidney transplantation - impact on mother and graft function and focus on childrens’ longitudinal development

BACKGROUND: Pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications. After careful patient selection successful pregnancies are described. Little is known about fetal outcomes and data is particularly scarce on childrens´ early development up to two years when born to kidney/-pancreas transplant recipients. Here, we analyzed maternal and fetal risk and evaluated graft function during pregnancy in transplanted women. We aimed to identify factors affecting the outcomes of mothers and their grafts during pregnancy and of children up to 2 years after delivery/ birth. METHODS: All consecutive pregnancies in kidney/ kidney-pancreas recipients with live-born children from 2002 to 2016 were evaluated in two transplant centers (Charité Berlin/ University Tuebingen). All data was gathered from medical records. Impact of pregnancy on obstetrical risks, graft function and fetal development was evaluated. Additionally, for the first time development of children, including physical examination and assessment of neurological function were evaluated at 12 and 24 months. RESULTS: Thirty-two pregnancies in 28 patients with a median duration of 34 gestational weeks (range, 24-38) were analyzed. 13 patients (46.4%) developed deterioration of kidney graft function > 10 ml/min during pregnancy. In majority, caesarean section was performed (75%). Twenty-five (78.1%) children were born prematurely, thereof (16%) < 28 weeks. Almost 70% had low birth weights (LBW) (< 2.500 g); median birth weight was 2.030 g. General health and physical constitution of children were unremarkable with normal development in 94% at 12 and 24 months of corrected age, respectively. CONCLUSION: Despite the high rate of preterm birth and LBW, development up to two years was age-appropriate in this cohort. Due to low absolute numbers, increasing efforts in centralized counseling, diagnostics and committed specialist support are required. Decisive treatment of these high-risk patients in specialized units leading to better performance of these patients (mother/ fetus) is deemed superior. In order to confirm this, prospective studies on neonatal and pediatric outcomes with a standard-of-care comparator arm will be conducted

From Winter to Late Summer in the Northwestern Barents Sea Shelf: Impacts of Seasonal Progression of Sea Ice and Upper Ocean on Nutrient and Phytoplankton Dynamics

Strong seasonality is a key feature of high-latitude systems like the Barents Sea. While the interannual variability and long-term changes of the Barents Sea are well-documented, the seasonal progression of the physical and biological systems is less known, mainly due to poor accessibility of the seasonally ice-covered area in winter and spring. Here, we use an extensive set of physical and biological in situ observations from four scientific expeditions covering the seasonal progression from late winter to late summer 2021 in the northwestern Barents Sea, from fully ice-covered to ice-free conditions. We found that sea ice meltwater and the timing of ice-free conditions in summer shape the environment, controlling heat accumulation, light and nutrient availability, and biological activity vertically, seasonally, and meridionally. In March and May, the ocean north of the Polar Front was ice-covered and featured a deep mixed layer. Chlorophyll-a concentrations increased from March to May along with greater euphotic depth, indicating the beginning of the spring bloom despite the absence of surface layer stratification. By July and in September, sea ice meltwater created a shallow low-density surface layer that strengthened stratification. In open water, chlorophyll-a maxima were found at the base of this layer as surface nutrients were depleted, while in the presence of ice, maxima were closer to the surface. Solar heating and the thickness of the surface layer increased with the number of ice-free days. The summer data showed a prime example of an Arctic-like space-for-time seasonal variability in the key physical and biological patterns, with the summer situation progressing northwards following sea ice retreat. The amount of sea ice melt (local or imported) has a strong control on the conditions in the northwestern Barents Sea, and the conditions in late 2021 resembled pre-2010 Arctic-like conditions with high freshwater content and lower ocean heat content.acceptedVersio

Panel-based Assessment of Ecosystem Condition of Norwegian Barents Sea Shelf Ecosystems - Appendices

publishedVersio

Panel-based Assessment of Ecosystem Condition of Norwegian Barents Sea Shelf Ecosystems - Appendices

Source at https://hi.no/hi

Panel-based Assessment of Ecosystem Condition of Norwegian Barents Sea Shelf Ecosystems

The System for Assessment of Ecological Condition, coordinated by the Norwegian Environment Agency, is intended to form the foundation for evidence-based assessments of the ecological condition of Norwegian terrestrial and marine ecosystems not covered by the EU Water Framework Directive. The reference condition is defined as “intact ecosystems”, i.e., a condition that is largely unimpacted by modern industrial anthropogenic activities. An ecosystem in good ecological condition is defined as a system that does not deviate substantially from this reference condition in structure, functions or productivity. This means that, in practice, what is assessed here is the extent to which an ecosystem is impacted by anthropogenic drivers. This report describes the first operational assessment of the ecological condition of Norwegian Arctic and Sub-Arctic marine shelf ecosystems in the Barents Sea. The assessment method employed is the Panel-based Assessment of Ecosystem Condition (PAEC1), and the current assessment has considered to what extent the Barents Sea shelf ecosystems deviate from the reference condition2 by evaluating change trajectories

Panel-based Assessment of Ecosystem Condition of Norwegian Barents Sea Shelf Ecosystems

The System for Assessment of Ecological Condition, coordinated by the Norwegian Environment Agency, is intended to form the foundation for evidence-based assessments of the ecological condition of Norwegian terrestrial and marine ecosystems not covered by the EU Water Framework Directive. The reference condition is defined as “intact ecosystems”, i.e., a condition that is largely unimpacted by modern industrial anthropogenic activities. An ecosystem in good ecological condition is defined as a system that does not deviate substantially from this reference condition in structure, functions or productivity. This means that, in practice, what is assessed here is the extent to which an ecosystem is impacted by anthropogenic drivers. This report describes the first operational assessment of the ecological condition of Norwegian Arctic and Sub-Arctic marine shelf ecosystems in the Barents Sea. The assessment method employed is the Panel-based Assessment of Ecosystem Condition (PAEC1), and the current assessment has considered to what extent the Barents Sea shelf ecosystems deviate from the reference condition2 by evaluating change trajectories.Panel-based Assessment of Ecosystem Condition of Norwegian Barents Sea Shelf EcosystemspublishedVersio

Deletion of the Huntingtin Polyglutamine Stretch Enhances Neuronal Autophagy and Longevity in Mice

Expansion of a stretch of polyglutamine in huntingtin (htt), the protein product of the IT15 gene, causes Huntington's disease (HD). Previous investigations into the role of the polyglutamine stretch (polyQ) in htt function have suggested that its length may modulate a normal htt function involved in regulating energy homeostasis. Here we show that expression of full-length htt lacking its polyglutamine stretch (ΔQ-htt) in a knockin mouse model for HD (Hdh140Q/ΔQ), reduces significantly neuropil mutant htt aggregates, ameliorates motor/behavioral deficits, and extends lifespan in comparison to the HD model mice (Hdh140Q/+). The rescue of HD model phenotypes is accompanied by the normalization of lipofuscin levels in the brain and an increase in the steady-state levels of the mammalian autophagy marker microtubule-associate protein 1 light chain 3-II (LC3-II). We also find that ΔQ-htt expression in vitro increases autophagosome synthesis and stimulates the Atg5-dependent clearance of truncated N-terminal htt aggregates. ΔQ-htt's effect on autophagy most likely represents a gain-of-function, as overexpression of full-length wild-type htt in vitro does not increase autophagosome synthesis. Moreover, HdhΔQ/ΔQ mice live significantly longer than wild-type mice, suggesting that autophagy upregulation may be beneficial both in diseases caused by toxic intracellular aggregate-prone proteins and also as a lifespan extender in normal mammals

Status for miljøet i norske havområder - Rapport fra Overvåkingsgruppen 2023

I denne rapporten gir Overvåkingsgruppen, for første gang, en felles vurdering av miljøtilstanden i Barentshavet og havområdene utenfor Lofoten, Norskehavet og Nordsjøen med Skagerrak. Det er også første rapport som bruker resultater fra det nylig utviklede fagsystemet for vurdering av økologisk tilstand. I denne rapporten dekkes to hovedtemaer: (1) Dominerende trekk i status og utvikling i økosystemet i alle tre havområdene, basert på vurderingene av økologisk tilstand, Overvåkingsgruppens rapport om forurensning fra 2022, indikatorer fra Overvåkingsgruppen som ikke er dekket under vurdering av økologisk tilstand, samt rapporter og annen relevant informasjon fra forskning, og (2) en vurdering av karbonbinding i marint plankton, marine vegetasjonstyper og marine sedimenter. I tillegg er det gitt en oppsummering for endringer i ytre påvirkning, vurdering av kunnskapsbehov samt en vurdering av indikatorverdier i forhold til referanseverdier og tiltaksgrenser. Vurderingen av dominerende trekk i utvikling og tilstand av miljøet som er gitt i kapittel 2, utgjør Overvåkingsgruppens bidrag til Faglig forums samlerapport om det faglige grunnlaget for revisjon og oppdatering av de helhetlige forvaltningsplanene for norske havområder.Status for miljøet i norske havområder - Rapport fra Overvåkingsgruppen 2023publishedVersio

Production de levains de tirage en champagne : influence de quelques variables opératoires

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