Isolierung und Identifizierung lipolytischer Substanzen und ihre Charakterisierung in 3T3-L1 Adipozyten

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Fetal cardiac magnetic resonance imaging of the descending aorta in suspected left-sided cardiac obstructions

BackgroundSevere left-sided cardiac obstructions are associated with high morbidity and mortality if not detected in time. The correct prenatal diagnosis of coarctation of the aorta (CoA) is difficult. Fetal cardiac magnetic resonance imaging (CMR) may improve the prenatal diagnosis of complex congenital heart defects. Flow measurements in the ascending aorta could aid in predicting postnatal CoA, but its accurate visualization is challenging.ObjectivesTo compare the flow in the descending aorta (DAo) and umbilical vein (UV) in fetuses with suspected left-sided cardiac obstructions with and without the need for postnatal intervention and healthy controls by fetal phase-contrast CMR flow. A second objective was to determine if adding fetal CMR to echocardiography (echo) improves the fetal CoA diagnosis.MethodsProspective fetal CMR phase-contrast flow in the DAo and UV and echo studies were conducted between 2017 and 2022.ResultsA total of 46 fetuses with suspected left-sided cardiac obstructions [11 hypoplastic left heart syndrome (HLHS), five critical aortic stenosis (cAS), and 30 CoA] and five controls were included. Neonatal interventions for left-sided cardiac obstructions (n = 23) or comfort care (n = 1 with HLHS) were pursued in all 16 fetuses with suspected HLHS or cAS and in eight (27%) fetuses with true CoA. DAo or UV flow was not different in fetuses with and without need of intervention. However, DAo and UV flows were lower in fetuses with either retrograde isthmic systolic flow [DAo flow 253 (72) vs. 261 (97) ml/kg/min, p = 0.035; UV flow 113 (75) vs. 161 (81) ml/kg/min, p = 0.04] or with suspected CoA and restrictive atrial septum [DAo flow 200 (71) vs. 268 (94) ml/kg/min, p = 0.04; UV flow 89 vs. 159 (76) ml/kg/min, p = 0.04] as well as in those without these changes. Adding fetal CMR to fetal echo predictors for postnatal CoA did not improve the diagnosis of CoA.ConclusionFetal CMR-derived DAo and UV flow measurements do not improve the prenatal diagnosis of left-sided cardiac obstructions, but they could be important in identifying fetuses with a more severe decrease in blood flow across the left side of the heart. The physiological explanation may be a markedly decreased left ventricular cardiac output with subsequent retrograde systolic isthmic flow and decreased total DAo flow

Population divergence in East African coelacanths

The coelacanth, Latimeria chalumnae, occurs at the Eastern coast of Africa from South Africa up to Kenya. It is often referred to as a living fossil mainly because of its nearly unchanged morphology since the Middle Devonian. As it is a close relative to the last common ancestor of fish and tetrapods, molecular studies mostly focussed on their phylogenetic relationships. We now present a population genetic study based on 71 adults from the whole known range of the species. Despite an overall low genetic diversity, there is evidence for divergence of local populations. We assume that originally the coelacanths at the East African Coast derived from the Comoros population, but have since then diversified into additional independent populations: one in South Africa and another in Tanzania. Unexpectedly, we find a split of the Comoran coelacanths into two sympatric subpopulations. Despite its undeniably slow evolutionary rate, the coelacanth still diversifies and is therefore able to adapt to new environmental conditions

Investigations on the importance of socio-economic factors and promoter polymorphisms of interleukin 10 and tumor necrosis factor alpha for malaria in the first year of life in Ghana

Titelblatt und Inhaltsverzeichnis Einleitung Material und Methoden Ergebnisse Diskussion Zusammenfassung Literaturverzeichnis</aDie Anfälligkeit für die Plasmodium falciparum-Infektion und ihre klinische Manifestation sind interindividuell verschieden und von genetischen und nicht- genetischen Einflüssen abhängig. Promoterpolymorphismen von Tumornekrosefaktor alpha (TNF-α 308G/A) und Interleukin 10 (IL-10 1082G/A) weisen hohe Genfrequenzen im subsaharischen Afrika auf. Es bestehen z.T. widersprüchliche auf einen hinsichtlich der Malaria disponierenden Effekt der Variante TNF-α -308A und auf eine eher protektive Wirkung des IL-10 -1082A-Allels. Da nach Rückgang des Nestschutzes die Anfälligkeit für Malaria am größten und der Effekt protektiver oder disponierender genetischer Varianten am stärksten ausgeprägt ist, wählten wir als Untersuchungszeitraum das erste Lebensjahr. Einhundertvierzig Neugeborenen wurden von Januar 2000 bis Juli 2001 in vierwöchentlichen Intervallen und bei akuter Erkrankung außerhalb des regulären Termins bis zum Erreichen der 52. Lebenswoche verfolgt und klinisch, hämatologisch und parasitologisch untersucht. Besuche in den Wohnstätten der Kinder und eine Befragung der Eltern dienten der Erfassung sozioökonomischer Faktoren. Die Promoterpolymorphismen und sozioökonomischen Faktoren wurden zu den Parametern Infektion, Parasitendichte, klinische Malaria und Malaria- Anämie in Bezug gesetzt. Für die untersuchten Promoterpolymorphismen zeigte sich kein signifikanter Zusammenhang mit dem Auftreten einer P. falciparum- Infektion oder der Höhe der Parasitendichte im ersten Lebensjahr. In der univariaten Analyse wiesen Kinder mit homozygotem IL-10 1082A-Allel eine verminderte Zahl von Episoden klinischer Malaria und schwerer Malaia-Anämie auf. Dieser protektive Einfluss auf die Manifestation der Malaria verlor sich nach Adjustierung für sozioökonomische Faktoren, was deren größere Bedeutung in diesem Zusammenhang unterstreicht. In der vorliegenden Arbeit ergaben sich keine Hinweise auf einen Einfluss des TNF-α 308A-Allels auf die Malaria im ersten Lebensjahr. Sozioökonomische Faktoren besaßen einen deutlichen Einfluss auf alle Basisparameter. So wiesen Kinder, die nicht vor Moskitos geschützt waren, im Regenwald lebten oder deren Mütter nicht lesen konnten, ein signifikant erhöhtes Risiko für eine P. falciparum-Infektion und klinische Manifestation auf.The susceptibility to Plasmodium falciparum infection and the clinical manifestation of malarial disease differ between human beings and depend on host genetics and non-genetic influences. Promoter polymorphisms of tumor necrosis factor alpha (TNF-α-308G/A) and interleukin 10 (IL-10-1082G/A) show high gene frequencies in Sub-Saharan Africa. The dispositional effect of the TNF-α-308A allele and a more protecting effect of the IL-10-1082A allele with respect to clinical malaria are controversially discussed. After loss of the innate protection at birth the susceptibility to malaria is highest and the influence of protecting and dispositional genetic variants strongest. Therefore, we chose the first year of life for our investigations. We surveyed 140 newborns until the age of 52 weeks every 4th week, and additionally when showing any acute disease, from January 2000 until July 2001. The children were examined clinically, hematologically and parasitologically. For collecting socio-economic factors we visited their homes and questioned their parents. These factors and the two promoter polymorphisms were investigated and compared regarding their influences on P. falciparum infection, parasite density, clinical malaria manifestation and malarial anemia. There was no significant dependency between the two promoter polymorphisms and the P. falciparum infection or the parasite density in the first year of life. The univariate analysis resulted in less episodes of clinical malaria und severe malarial anemia for children with homozygous IL-10-1082A allele. This protecting influence on disease severity is not observed when taking socio- economic factors into account, thus emphasizing their importance. We demonstrated that there is no significant relation between the TNF-α-308A- allele and malaria in the first year of life. Socio-economic factors have a strong influence on infection, parasite density and the clinical manifestation of malaria. Children without any mosquito protection, living in the rain forest, and having illiterate mothers, have a significant higher risk of P. falciparum infections and clinically manifested malaria

Fetal Echocardiographic Dimension Indices: Important Predictors of Postnatal Coarctation

The aim of the study is to identify reliable quantitative fetal echocardiographic predictors for postnatal development of coarctation (CoA). In this retrospective study, we included 65 fetuses with a prenatally suspected, isolated CoA, born 2010–2018. Dimensions of the cardiac structures, aortic, and ductal arches expressed as ratios and Z-scores were analyzed in relation to outcome. Fetuses that developed CoA postnatally (34%) exhibited significantly smaller Z-scores of left cardiac structures from the mitral valve to the aortic isthmus. The most sensitive and specific predictors were a carotid-subclavian artery index (CSAI) of < 0.78 (92.3% sensitivity, 96.8% specificity) or a product of isthmus-to-duct ratio in the three-vessel trachea view (3VT) and the mitral-to-tricuspid valve ratio (I/D3VTxMV/TV) of < 0.37 (100% sensitivity, 94.6% specificity). When comparing different Z-score datasets, we observed large and highly significant differences. Postnatal CoA can be predicted with high accuracy during fetal life using CSAI or I/D3VTxMV/TV. The latter may be particularly useful if adequate sagittal aortic arch images cannot be obtained. As significant and clinically unacceptable differences in Z-scores were observed for the same measurements, this calls for a large multi-center collaboration to generate reliable fetal echocardiographic Z-scores

Utility of Fetal Cardiovascular Magnetic Resonance for Prenatal Diagnosis of Complex Congenital Heart Defects

Importance: Prenatal diagnosis of complex congenital heart defects reduces mortality and morbidity in affected infants. However, fetal echocardiography can be limited by poor acoustic windows, and there is a need for improved diagnostic methods.Objective: To assess the clinical utility of fetal cardiovascular magnetic resonance imaging in cases in which fetal echocardiography could not visualize all relevant anatomy.Design, Setting, and Participants: This cohort study was conducted between January 20, 2017, and June 29, 2020, at Skåne University Hospital (Lund, Sweden), a tertiary center for pediatric cardiology and thoracic surgery. Participants were fetuses referred for fetal cardiovascular magnetic resonance examination by a pediatric cardiologist after an inconclusive echocardiograph.Exposures: Fetal cardiovascular magnetic resonance examination requested by the patient's pediatric cardiologist.Main Outcomes and Measures: Any change in patient management because of diagnostic information gained from fetal cardiovascular magnetic resonance imaging.Results: A total of 31 fetuses underwent cardiovascular magnetic resonance examination at a median gestational age of 36 weeks (range, 31-39 weeks). Overall, fetal cardiovascular magnetic resonance imaging had clinical utility, affecting patient management and/or parental counseling in 26 cases (84%). For aortic arch anatomy including signs of coarctation (20 fetuses), fetal cardiovascular magnetic resonance imaging added diagnostic information in 16 cases (80%). For assessment of univentricular vs biventricular outcome in borderline left ventricle, unbalanced atrioventricular septal defect, and pulmonary atresia with intact ventricular septum (15 fetuses), fetal cardiovascular magnetic resonance imaging visualized intracardiac anatomy and ventricular function, allowing assessment of outcome in 13 cases (87%). In 4 fetuses with hypoplastic left heart syndrome, fetal cardiovascular magnetic resonance imaging helped delivery planning in 3 cases (75%). Finally, fetal cardiovascular magnetic resonance imaging provided valuable information for parental counseling in 21 cases (68%).Conclusions and Relevance: In this cohort study, fetal cardiovascular magnetic resonance imaging added clinically useful information to what was available from echocardiography. These findings suggest that fetal CMR has the potential to affect clinical decision-making in challenging cases of congenital heart defects with inconclusive data from echocardiography. Fetal cardiovascular magnetic resonance imaging showed an association with clinical decision-making, including mode of delivery and early postnatal care, as well as with parental counseling

Comparison of 2D and 4D Flow MRI in Neonates Without General Anesthesia

BackgroundNeonates with critical congenital heart disease require early intervention. Four-dimensional (4D) flow may facilitate surgical planning and improve outcome, but accuracy and precision in neonates are unknown.PurposeTo 1) validate two-dimensional (2D) and 4D flow MRI in a phantom and investigate the effect of spatial and temporal resolution; 2) investigate accuracy and precision of 4D flow and internal consistency of 2D and 4D flow in neonates; and 3) compare scan time of 4D flow to multiple 2D flows.Study TypePhantom and prospective patients.PopulationA total of 17 neonates with surgically corrected aortic coarctation (age 18 days [IQR 11–20]) and a three-dimensional printed neonatal aorta phantom.Field Strength/SequenceA 5 T, 2D flow and 4D flow.AssessmentIn the phantom, 2D and 4D flow volumes (ascending and descending aorta, and aortic arch vessels) with different resolutions were compared to high-resolution reference 2D flow. In neonates, 4D flow was compared to 2D flow volumes at each vessel. Internal consistency was computed as the flow volume in the ascending aorta minus the sum of flow volumes in the aortic arch vessels and descending aorta, divided by ascending aortic flow.Statistical testsBland–Altman plots, Pearson correlation coefficient (r), and Student's t-tests.ResultsIn the phantom, 2D flow differed by 0.01 ± 0.02 liter/min with 1.5 mm spatial resolution and −0.01 ± 0.02 liter/min with 0.8 mm resolution; 4D flow differed by −0.05 ± 0.02 liter/min with 2.4 mm spatial and 42 msec temporal resolution, −0.01 ± 0.02 liter/min with 1.5 mm, 42 msec resolution and −0.01 ± 0.02 liter/min with 1.5 mm, 21 msec resolution. In patients, 4D flow and 2D flow differed by −0.06 ± 0.08 liter/min. Internal consistency in patients was −11% ± 17% for 2D flow and 5% ± 13% for 4D flow. Scan time was 17.1 minutes [IQR 15.5–18.5] for 2D flow and 6.2 minutes [IQR 5.3–6.9] for 4D flow, P < 0.0001.Data ConclusionNeonatal 4D flow MRI is time efficient and can be acquired with good internal consistency without contrast agents or general anesthesia, thus potentially expanding 4D flow use to the youngest and smallest patients.Evidence Level1Technical EfficacyStage

A quantitative real-time polymerase chain reaction assay for the seagrass pathogen Labyrinthula zosterae

The protist Labyrinthula zosterae (Phylum Bigyra, sensu Tsui et al. 2009) has been identified as a causative agent of wasting disease in eelgrass (Zostera marina), of which the most intense outbreak led to the destruction of 90% of eelgrass beds in eastern North America and western Europe in the 1930s. Outbreaks still occur today, albeit at a smaller scale. Traditionally, L. zosterae has been quantified by measuring the necrotic area of Z. marina leaf tissue. This indirect method can however only lead to a very rough estimate of pathogen load. Here, we present a quantitative real-time polymerase chain reaction (qPCR) approach to directly detect and quantify L. zosterae in eelgrass tissue. Based on the internal transcribed spacer (ITS) sequences of rRNA genes, species-specific primers were designed. Using our qPCR, we were able to quantify accurately and specifically L. zosterae load both from culture and eelgrass leaves using material from Europe and North America. Our detection limit was less than one L. zosterae cell. Our results demonstrate the potential of this qPCR assay to provide rapid, accurate and sensitive molecular identification and quantification of L. zosterae. In view of declining seagrass populations worldwide, this method will provide a valuable tool for seagrass ecologists and conservation projects

Impact of Left Ventricular Morphology on Adverse Outcomes Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome : 20 Years of National Data From Sweden

BACKGROUND: Hypoplastic left heart syndrome is associated with significant morbidity and mortality. We aimed to assess the influence of left ventricular morphology and choice of shunt on adverse outcome in patients with hypoplastic left heart syndrome and stage 1 palliation. METHODS AND RESULTS: This was a retrospective analysis of patients with hypoplastic left heart syndrome with stage 1 palliation between 1999 and 2018 in Sweden. Patients (n=167) were grouped based on the anatomic subtypes aortic-mitral atresia, aortic atresia-mitral stenosis (AA-MS), and aortic-mitral stenosis. The left ventricular phenotypes including globular left ventricle (Glob-LV), miniaturized and slit-like left ventricle (LV), and the incidence of major adverse events (MAEs) including mortality were assessed. The overall mortality and MAEs were 31% and 41%, respectively. AA-MS (35%) was associated with both mortality (all other subtypes versus AA-MS: interstage-I: hazard ratio [HR], 2.7; P=0.006; overall: HR, 2.2; P=0.005) and MAEs (HR, 2.4; P=0.0009). Glob-LV (57%), noticed in all patients with AA-MS, 61% of patients with aortic stenosis-mitral stenosis, and 19% of patients with aortic atresia-mitral atresia, was associated with both mortality (all other left ventricular phenotypes versus Glob-LV: interstage-I: HR, 4.5; P=0.004; overall: HR, 3.4; P=0.0007) and MAEs (HR, 2.7; P=0.0007). There was no difference in mortality and MAEs between patients with AA-MS and without AA-MS with Glob-LV (P&gt;0.15). Patients with AA-MS (35%) or Glob-LV (38%) palliated with a Blalock-Taussig shunt had higher overall mortality compared with those palliated with Sano shunts, irrespective of the stage 1 palliation year (AA-MS: HR, 2.6; P=0.04; Glob-LV: HR, 2.1; P=0.03). CONCLUSIONS: Glob-LV and AA-MS are independent morphological risk factors for adverse short-and long-term outcome, especially if a Blalock-Taussig shunt is used as part of stage 1 palliation. These findings are important for the clinical management of patients with hypoplastic left heart syndrome