Verliebt – Verlobt – Verheiratet:Wandel der Hochzeit im 20. Jahrhundert

Die Entscheidung zu heiraten gilt heute als höchstpersönliche Angelegenheit des Brautpaares und Grundstein ihres individuellen Glücks. Doch wenn ein Paar heiratet, ist das nicht nur eine private Entscheidung. Die Brautleute sind immer auch Einflüssen aus Elternhaus, Kirche, Gesamtgesellschaft und Staat ausgesetzt und wirken ihrerseits mit ihrer Entscheidung auf diese Institutionen zurück. Änderungen im Heiratsverhalten stellen somit einen wichtigen Indikator für gesellschaftliche Entwicklungen dar. Um diese Entwicklungen erfassen und darstellen zu können, hat eine Gruppe von acht Teilnehmerinnen und Teilnehmern des Studiums im Alter an der Universität Münster, die Geschichte der Hochzeit im 20. Jahrhundert im Vergleich der Hochzeitsgenerationen der Studierenden (Heirat 1960-75), ihrer Eltern (Heirat 1930-45) und Großeltern (Heirat 1900-1915) untersucht. Hierzu recherchierte die Gruppe in Archiven und Bibliotheken und wertete 586 für das Projekt entwickelte, standardisierte Fragebögen aus

Accurate tumor purity determination is critical for the analysis of homologous recombination deficiency (HRD)

Homologous recombination deficiency (HRD) is a predictive marker for response to poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian carcinoma. HRD scores have entered routine diagnostics, but the influence of algorithms, parameters and confounders has not been analyzed comprehensively.A series of 100 poorly differentiated ovarian carcinoma samples was analyzed using whole exome sequencing (WES) and genotyping. Tumor purity was determined using conventional pathology, digital pathology, and two bioinformatic methods. HRD scores were calculated from copy number profiles determined by Sequenza and by Sclust either with or without fixed tumor purity. Tumor purity determination by digital pathology combined with a tumory purity informed variant of Sequenza served as reference method for HRD scoring.Seven tumors had deleterious mutations in BRCA1/2, 12 tumors had deleterious mutations in other homologous recombination repair (HRR) genes, 18 tumors had variants of unknown significance (VUS) in BRCA1/2 or other HRR genes, while the remaining 63 tumors had no relevant alterations. Using the reference method for HRD scoring, 68 tumors were HRD-positive. HRDsum determined by WES correlated strongly with HRDsum determined by single nucleotide polymorphism (SNP) arrays (R = 0.85). Conventional pathology systematically overestimated tumor purity by 8% compared to digital pathology. All investigated methods agreed on classifying the deleterious BRCA1/2-mutated tumors as HRD-positive, but discrepancies were observed for some of the remaining tumors. Discordant HRD classification of 11% of the tumors was observed comparing the tumor purity uninformed default of Sequenza and the reference method.In conclusion, tumor purity is a critical factor for the determination of HRD scores. Assistance by digital pathology helps to improve accuracy and imprecision of its estimation

Body growth, upper arm fat area, and clinical parameters in children with nephropathic cystinosis compared with other pediatric chronic kidney disease entities

Children with infantile nephropathic cystinosis (INC), an inherited lysosomal storage disease resulting in cystine accumulation in all body cells, are prone to progressive chronic kidney disease (CKD), impaired growth and reduced weight gain; however, systematic anthropometric analyses are lacking. In this prospective multicenter study we investigated linear growth, body proportion, body mass index (BMI), upper arm fat area (UFA) and biochemical parameters in 43 pediatric INC patients with CKD stages 1 to 5 and 49 age-matched CKD controls, with 193 annual measurements. INC patients showed more impaired height than CKD controls (-1.8 vs -0.7 z-score; P < .001), despite adequate cysteamine therapy, treatment for Fanconi syndrome and more frequent use of growth hormone. Only the youngest INC patients shared the same body pattern with CKD controls characterized by preferential impairment of leg length and rather preserved trunk length. In late-prepuberty, body pattern changed only in INC patients due to improved leg growth and more impaired trunk length. Mean UFA z-score in INC patients was slightly reduced in early childhood and progressively decreased thereafter reaching -0.8 z-score in adolescence, while CKD controls showed a steady increase in standardized BMI and UFA especially during adolescent age. Menarche in female INC patients was significantly delayed compared to CKD controls. Our data indicate that with age and progression of disease, pediatric INC patients undergo unique changes of body growth and fat stores that are distinct from those with CKD stemming from other causes, suggesting other factors apart from CKD to contribute to this development. Pediatric patients with infantile nephropathic cystinosis display more severe impaired linear growth than other peer CKD patients, despite of cysteamine treatment, supplementation for Fanconi syndrome, and more frequent use of growth hormone, with a distinct change of body proportions and overall lower body fat

Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo

Diverse death stimuli including anticancer drugs trigger apoptosis by inducing the translocation of cytochrome c from the outer mitochondrial compartment into the cytosol. Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. The results of this study show that on death induction by chemotherapeutic drugs, staurosporine and triggering of the death receptor CD95, cytochrome c not only translocates into the cytosol, but furthermore can be abundantly detected in the extracellular medium. The cytochrome c release from the cell Is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. Interestingly, elevated cytochrome c levels were observed in sera from patients with hematologic malignancies. In the course of cancer chemo-therapy, the serum levels of cytochrome c in the majority of the patients grew rapidly as a result of increased cell death. These data suggest that monitoring of cytochrome c In the serum of patients with tumors might serve as a useful clinical marker for the detection of the onset of apoptosis and cell turnover in vivo. (C) 2001 by The American Society of Hematology

Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases.

The major heat shock protein, Hsp70, is an effective inhibitor of apoptosis. To study its mechanism of action, we created tumor cell lines with altered Hsp70 levels. The expression levels of Hsp70 in the cells obtained correlated well with their survival following treatments with tumor necrosis factor, staurosporine and doxorubicin. Surprisingly, the surviving Hsp70-expressing cells responded to the apoptotic stimuli by activation of stress-activated protein kinases, generation of free radicals, early disruption of mitochondrial transmembrane potential, release of cytochrome c from mitochondria and activation of caspase-3-like proteases in a manner essentially similar to that of the dying cells with low Hsp70 levels. However, Hsp70 inhibited late caspase-dependent events such as activation of cytosolic phospholipase A2 and changes in nuclear morphology. Furthermore, Hsp70 conferred significant protection against cell death induced by enforced expression of caspase-3. Thus, Hsp70 rescues cells from apoptosis later in the death signaling pathway than any known anti-apoptotic protein, making it a tempting target for therapeutic interventions

The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions

Background: EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce. Patients and methods: We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.1. TP53 status was available for 88 cases. Results: Platinum doublets and chemoimmunotherapy showed similar response rates (20-25%), disease control rates (80%) and median progression-free survival (mPFS, asymptotic to 7 months), which were longer compared to monochemotherapy (9%, 59%, 4.1 months), EGFR inhibitors (0%, 46%, 3.0) and PD-(L)1 inhibitors (0%, 30%, 2.1; p 1 year) occasionally occurred under EGFR inhibitors for both 'near-' and 'far-loop' variants. Conclusions: Platinum doublets and chemoimmunotherapy have the highest activity with ORR of 20-25% and mPFS of approximately 7 months, regardless of the cytotoxic partner, while PD-(L)1 inhibitors show limited efficacy. TP53 mutations, brain metastases and a lower tumour CD8/Th1-cell ratio are independently associated with shorter survival. (C) 2022 Elsevier Ltd. All rights reserved