Depressive Störungen im mittleren Erwachsenenalter : die Bedeutung distaler und proximaler Belastungen und positiver Faktoren

Viele Studien zeigen Zusammenhänge zwischen depressiven Störungen und distalen sowie proximalen belastenden Lebensereignissen. Bisher fehlen jedoch Untersuchungen, die a) die Wirkung belastender distaler und proximaler Ereignisse gleichzeitig analysieren, b) den Einfluss dieser Ereignisse auf unterschiedliche Verlaufsformen depressiver Störungen untersuchen und c) die Rolle positiver Faktoren berücksichtigen. Basierend auf Daten von 349 Personen (geb. 1950-52), die an den ersten beiden Messzeitpunkten der Interdisziplinären Längsschnittstudie des Erwachsenenalters (ILSE) teilnahmen (T1-T2: 4.1 Jahre), wird der Einfluss von distalen und proximalen Lebensereignissen auf den weiteren Verlauf von minorer und Major Depression analysiert sowie die Rolle positiver Faktoren untersucht. Ausgehend von ILSE-T2 stehen 227 psychisch immer gesunden Teilnehmern, 78 remittierte Depressive (dies sind Probanden, die bis zu T1 irgendwann im Laufe ihres Lebens eine depressive Episode erlitten hatten, aber nicht mehr in den vier Erhebungszwischenjahren), 23 Depressive mit einem Rückfall und 21 späte neuerkrankte Depressive gegenüber. Die psychiatrischen Diagnosen wurden mit dem Strukturierten klinischen Interview für DSM-III-R erhoben. Belastende Kindheitsereignisse (0 bis 16. Lebensjahr) wurden zu T1 im Rahmen eines halbstrukturierten Interviews, anhand offener Fragen zur Kindheit, Situation in der Familie etc. erhoben und anhand einer qualitativen Inhaltsanalyse 20 Kategorien aus den Bereichen Verlust- Trennungsereignisse, Psychopathologie eines Elternteils, Traumatisierung durch andere und weitere Widrigkeiten (disharmonische Familienverhältnisse, eigene chronische Erkrankung) zugeordnet. Die zeitnahen Ereignisse wurden zu T2 anhand eines halbstrukturierten Interviews (offene Fragen zu Veränderungen in den vorausgegangenen vier Jahren) erhoben und 34 Kategorien aus den Bereichen Beruf, Gesundheit, Wohnen, Finanzen, Justiz, Partnerschaft, soziales Umfeld, Tod zugeordnet. Basierend auf einer Hauptkomponentenanalyse wurden die folgenden fünf positiven Faktoren aufgebaut: 1) Ausgedehnter Lebensraum/stützendes familiäres Umfeld, 2) hohe Selbstwirksamkeit, 3) hohe Integration in Peergruppen, 4) hohes Selbstwertgefühl/positives Selbstbild in der Jugend und 5) hohe kognitive Befähigung. Es zeigen sich im Vergleich mit der gesunden Kontrollgruppe bei remittierten, wieder erkrankten und neu erkrankten Personen a) mehr kritische Lebensereignisse, b)differenzielle Einflüsse der Ereignisse auf Inzidenz und Verlauf einer Depression und c) protektive Effekte von persönlichen und sozialen Ressourcen auf spezifische Lebensereignisse

Genomic Potential and Virulence Mechanisms of Paenibacillus larvae

Paenibacillus larvae, a Gram positive bacterial pathogen, causes American Foulbrood (AFB), which is the most serious infectious disease of honey bees. In order to investigate the genomic potential of P. larvae, two strains belonging to two different genotypes were sequenced and used for comparative genome analysis. The complete genome sequence of P. larvae strain DSM 25430 (genotype ERIC II) consisted of 4,056,006 bp and harbored 3,928 predicted protein-encoding genes. The draft genome sequence of P. larvae strain DSM 25719 (genotype ERIC I) comprised 4,579,589 bp and contained 4,868 protein- encoding genes. Both strains harbored a 9.7 kb plasmid and encoded a large number of virulence-associated proteins such as toxins and collagenases. In addition, genes encoding large multimodular enzymes producing nonribosomally peptides or polyketides were identified. In the genome of strain DSM 25719 seven toxin associated loci were identified and analyzed. Five of them encoded putatively functional toxins. The genome of strain DSM 25430 harbored several toxin loci that showed similarity to corresponding loci in the genome of strain DSM 25719, but were non-functional due to point mutations or disruption by transposases. Although both strains cause AFB, significant differences between the genomes were observed including genome size, number and composition of transposases, insertion elements, predicted phage regions, and strain-specific island-like regions. Transposases, integrases and recombinases are important drivers for genome plasticity. A total of 390 and 273 mobile elements were found in strain DSM 25430 and strain DSM 25719, respectively. Comparative genomics of both strains revealed acquisition of virulence factors by horizontal gene transfer and provided insights into evolution and pathogenicity

Child Sexual Abuse by Catholic Priests, Deacons, and Male Members of Religious Orders in the Authority of the German Bishops’ Conference 1946–2014

This study explores the extent of sexual abuse of minors by members of the Catholic Church in Germany. It is the first comprehensive study to examine this extent in a European country. The goals of this study are as follows: (a) to analyze whether the extent and characteristics of sexual abuse in a European country are comparable to those in the United States and Australia and (b) how discrepancies can be explained. The personnel files of 38,156 Catholic Priests, deacons, and male members of religious orders in the authority of the German Bishops’ Conference were analyzed. The study period lasted from 1946 to 2014. All 27 German dioceses took part in this study. A total of 4.4% of all clerics (N = 1,670) from 1946 to 2014 were alleged to have committed sexual abuse, and 3,677 children or adolescents were identified as victims. These results are similar to those from comparable studies in the United States. Sexual abuse of minors within the authority of the Catholic Church seems to be a worldwide phenomenon

Molecular matched targeted therapies for primary brain tumors—a single center retrospective analysis

PURPOSE: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy. METHODS: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected. RESULTS: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI. CONCLUSION: A broad range of actionable alterations was targeted with available molecular therapeutics. However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-022-04049-w