"Der schwarze Donnerstag"

Die Massenmedien sind in der modernen, funktional differenzierten Gesellschaft allgegenwärtig. Wie eine Gesellschaft, wie Politik verfasst ist, hängt zentral mit den Kommunikationsleistungen des Mediensystems zusammen. Aus diesem Grund kann die moderne Gesellschaft als „Mediengesellschaft“ bezeichnet werden. So werden nicht nur alle gesellschaftlichen Bereiche von den Medien durchdrungen, auch die Vermittlungsgeschwindigkeit und -leistung hat sich enorm ausgeweitet. Die politischen Akteure haben auf diese Entwicklungen mit einer Orientierung an der Medienlogik reagiert. So wurden nicht nur die Kommunikationsstrategien medial ausgerichtet auch die PR-Abteilungen wurden ausgebaut und professionalisiert. Ein Ereignis, das im Jahr 2010 nicht nur bundesweit große Aufmerksamkeit erregt hatte, war der Polizeieinsatz im Stuttgarter Schlossgarten am 30. September 2010. Die Eskalation im Stuttgarter Schlossgarten – von den Medien als „schwarzer Donnerstag“ bezeichnet – war trauriger Höhepunkt einer Auseinandersetzung um das Bahnprojekt „Stuttgart 21“, bei dem mehr als hundert Menschen verletzt wurden. Zum ersten Mal seit 40 Jahren setzte die Polizei Wasserwerfer gegen Demonstranten ein, die die Baumfällaktionen zu verhindern versuchten. Ziel dieser Arbeit war es einerseits die Begründungen der baden-württembergischen Landesregierung inhaltsanalytisch zu identifizieren. Andererseits wurde die Berichterstattung von vier regionalen und überregionalen Qualitätszeitungen über die Ereignisse dahingehend inhaltsanalytisch analysiert, inwieweit die Kommunikationsziele der badenwürttembergischen Landesregierung übernommen wurden. Um den Stellenwert der Medien in der modernen Gesellschaft zu verdeutlichen, wurde neben den Funktionen der Massenmedien und der Verfasstheit des Mediensystems auch die Entwicklung hin zur Mediengesellschaft näher beleuchtet. Dabei wurde neben dem gesellschaftlichen Wandel, auch der ökonomische Wandel sowie der Wandel des Mediensystems dargestellt. Ein weiterer Punkt legt das Forschungsgebiet der „Politischen Kommunikation“ dar, welches sich damit befasst, wie die gesellschaftliche Kommunikation Prozesse und Strukturen der Politik bedingt und wie Politik gesellschaftliche Kommunikation bedingt und bestimmt. Die Reaktion der Politik wird in einem weiteren Kapitel über politische PR näher beleuchtet, gefolgt von einem Kapitel über die Methode sowie Fakten zum Bahnprojekt Stuttgart 21

Barrieren von Frauen mit Lernschwierigkeiten beim Übergang von berufsvorbereitenden Maßnahmen in den ersten Arbeitsmarkt

Am Weg zur beruflichen Teilhabe müssen Frauen mit Lernschwierigkeiten zahlreiche Barrieren überwinden. Die Barrieren, die sich den Frauen beim Übergang an der zweiten Schwelle, das heißt dem Übergang von berufsvorbereitenden Maßnahmen in den ersten Arbeitsmarkt stellen, sind bis dato allerdings kaum erforscht. Darum soll in der vorliegenden Diplomarbeit der Frage nachgegangen werden „Welche Barrieren erfahren Frauen mit Lernschwierigkeiten beim Übergang von berufsvorbereitenden Maßnahmen in den allgemeinen Arbeitsmarkt?“ Diesbezüglich wird der berufliche Verlauf von sechs jungen Frauen mit Lernschwierigkeiten in den ersten drei Jahren nach Beendigung des Projekts Prima Donna herangezogen und aus deren Perspektive nachgezeichnet. Das qualitative Forschungsdesign setzt sich aus einer Kombination von problemzentriertem Interview nach Witzel (2000) und der Grounded Theory nach Glaser und Strauss (1998) zusammen. Es gab zwei Erhebungsphasen, wobei die zweite dazu diente, bereits vorliegende Ergebnisse abzusichern bzw. genauer nach zu fragen. Zur Auswertung, die sich sehr aufwändig gestaltete, wurde das Programm ATLAS.TI herangezogen. Aus den Ergebnissen geht hervor, dass die Frauen im Rahmen ihrer beruflichen Teilhabe auf zahlreiche Barrieren stoßen, die in einem komplexen Gefüge miteinander verstrickt sind

DHTKD1 Mutations Cause 2-Aminoadipic and 2-Oxoadipic Aciduria

Abnormalities in metabolite profiles are valuable indicators of underlying pathologic conditions at the molecular level. However, their interpretation relies on detailed knowledge of the pathways, enzymes, and genes involved. Identification and characterization of their physiological function are therefore crucial for our understanding of human disease: they can provide guidance for therapeutic intervention and help us to identify suitable biomarkers for monitoring associated disorders. We studied two individuals with 2-aminoadipic and 2-oxoadipic aciduria, a metabolic condition that is still unresolved at the molecular level. This disorder has been associated with varying neurological symptoms. Exome sequencing of a single affected individual revealed compound heterozygosity for an initiating methionine mutation (c.1A>G) and a missense mutation (c.2185G>A [p.Gly729Arg]) in DHTKD1. This gene codes for dehydrogenase E1 and transketolase domain-containing protein 1, which is part of a 2-oxoglutarate-dehydrogenase-complex-like protein. Sequence analysis of a second individual identified the same missense mutation together with a nonsense mutation (c.1228C>T [p.Arg410∗]) in DHTKD1. Increased levels of 2-oxoadipate in individual-derived fibroblasts normalized upon lentiviral expression of the wild-type DHTKD1 mRNA. Moreover, investigation of L-lysine metabolism showed an accumulation of deuterium-labeled 2-oxoadipate only in noncomplemented cells, demonstrating that DHTKD1 codes for the enzyme mediating the last unresolved step in the L-lysine-degradation pathway. All together, our results establish mutations in DHTKD1 as a cause of human 2-aminoadipic and 2-oxoadipic aciduria via impaired turnover of decarboxylation 2-oxoadipate to glutaryl-CoA

Cross-sectional observational study of 208 patients with non-classical urea cycle disorders.

Urea cycle disorders (UCDs) are inherited disorders of ammonia detoxification often regarded as mainly of relevance to pediatricians. Based on an increasing number of case studies it has become obvious that a significant number of UCD patients are affected by their disease in a non-classical way: presenting outside the newborn period, following a mild course, presenting with unusual clinical features, or asymptomatic patients with only biochemical signs of a UCD. These patients are surviving into adolescence and adulthood, rendering this group of diseases clinically relevant to adult physicians as well as pediatricians. In preparation for an international workshop we collected data on all patients with non-classical UCDs treated by the participants in 20 European metabolic centres. Information was collected on a cohort of 208 patients 50% of which were ≥ 16 years old. The largest subgroup (121 patients) had X-linked ornithine transcarbamylase deficiency (OTCD) of whom 83 were female and 29% of these were asymptomatic. In index patients, there was a mean delay from first symptoms to diagnosis of 1.6 years. Cognitive impairment was present in 36% of all patients including female OTCD patients (in 31%) and those 41 patients identified presymptomatically following positive newborn screening (in 12%). In conclusion, UCD patients with non-classical clinical presentations require the interest and care of adult physicians and have a high risk of neurological complications. To improve the outcome of UCDs, a greater awareness by health professionals of the importance of hyperammonemia and UCDs, and ultimately avoidance of the still long delay to correctly diagnose the patients, is crucial

Etiology and Outcome of Adult and Pediatric Acute Liver Failure in Europe

Acute liver failure (ALF) is rare but life-threatening. Common causes include intoxications, infections, and metabolic disorders. Indeterminate etiology is still frequent. No systematic data on incidence, causes, and outcome of ALF across Europe are available. Via an online survey we reached out to European Reference Network Centers on rare liver diseases. Numbers and etiology of ALF cases during 2020 were retrieved and diagnostic and treatment availabilities assessed. In total, 455 cases (306 adult, 149 pediatric) were reported from 36 centers from 20 countries. Intoxication was the most common cause in adult and pediatric care. The number of cases with indeterminate etiology is low. Diagnostic tools and specific treatment options are broadly available within this network. This is the first approach to report on etiology and outcome of ALF in the pediatric and adult population in Europe. High diagnostic yield and standard of care reflects the expert status of involved centers.</p

Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta

Background Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1 in 15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcome and patient benefit. Report Whole exome sequencing in patients with OI identified, in two patients with a multi-system phenotype, compound heterozygous variants in NBAS (neuroblastoma amplified sequence). Patient 1: NBAS c.5741G > A p.(Arg1914His); c.3010C > T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G > A p.(Arg1914His); c.2032C > T p.(Gln678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency. Discussion Homozygous missense NBAS variants cause SOPH syndrome (short stature; optic atrophy; Pelger-Huet anomaly), the same missense variant was found in our patients on one allele and a nonsense variant in the other allele. Recent literature suggests a multi-system phenotype. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from ‘Classical’ OI. Conclusions Here we report on variants in NBAS, as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS. We explore the mechanism underlying NBAS and the striking skeletal phenotype in our patients

Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy

Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever

Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders

Inherited methylation disorders are a group of rarely reported, probably largely underdiagnosed disorders affecting transmethylation processes in the metabolic pathway between methionine and homocysteine. These are methionine adenosyltransferase I/III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. This paper provides the first consensus recommendations for the diagnosis and management of methylation disorders. Following search of the literature and evaluation according to the SIGN-methodology of all reported patients with methylation defects, graded recommendations are provided in a structured way comprising diagnosis (clinical presentation, biochemical abnormalities, differential diagnosis, newborn screening, prenatal diagnosis), therapy and follow-up. Methylation disorders predominantly affect the liver, central nervous system and muscles, but clinical presentation can vary considerably between and within disorders. Although isolated hypermethioninemia is the biochemical hallmark of this group of disorders, it is not always present, especially in early infancy. Plasma S-adenosylmethionine and S-adenosylhomocysteine are key metabolites for the biochemical clarification of isolated hypermethioninemia. Mild hyperhomocysteinemia can be present in all methylation disorders. Methylation disorders do not qualify as primary targets of newborn screening. A low-methionine diet can be beneficial in patients with methionine adenosyltransferase I/III deficiency if plasma methionine concentrations exceed 800 μmol/L. There is some evidence that this diet may also be beneficial in patients with S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies. S-adenosylmethionine supplementation may be useful in patients with methionine adenosyltransferase I/III deficiency. Recommendations given in this article are based on general principles and in practice should be adjusted individually according to patient's age, severity of the disease, clinical and laboratory findings

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke