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The long-term follow-up of patients with bronchial carcinoma treated by surgery is presented. Of 471 patients who underwent thoracotomy, the tumour could not be resected in 38 (8%). Sixty-three (13.4%) died within the first four weeks; 125 (28.9%) survived more than five years. A high percentage developed either late metastases, late recurrences, or a second primary lung carcinoma. The results of surgical resection for bronchial carcinoma cannot be considered satisfactory, although resection remains the best treatment even in those patients with an apparently unfavourable prognosis. In spite of reservations regarding retrospective studies, conclusions can be drawn regarding diagnosis, therapy, and prognosis. Questions concerning histological type, size, and site of tumour, and tumour stage can be answered only after an adequate postoperative interval. Five years after operation the patient who has apparently been successfully treated may die from a second primary carcinoma. [ABSTRACT FROM PUBLISHER]

After a primary operation for bronchial carcinoma, 17 patients underwent reoperation for local recurrence or intrathoracic metastasis (nine squamous cell, five alveolar cell, and three adenocarcinomas). The average interval between the first and second operation was 23 months (range: six to 48 months). Twelve patients had a pneumonectomy after an initial ipsilateral lobectomy. Five patients underwent contralateral wedge excision after initial lobectomy or wedge excision. Three patients died within 30 days of the reoperation. Eight of the remaining 14 patients died subsequently, the time of survival averaging 18 months (range: three to 54 months). Six patients are still alive, two having survived their reoperation for more than five years. Reoperation for recurrent bronchial carcinoma is rarely performed, but it should be considered in all cases where patients survive operation for lung cancer if the primary operation was thought to be radical. [ABSTRACT FROM PUBLISHER]

We apply improved nucleon-nucleon potentials up to fifth order in chiral effective field theory, along with a new analysis of the theoretical truncation errors to study nucleon-deuteron (Nd) scattering and selected low-energy observables in ³H,4He, and 6Li. Calculations beyond second order differ from experiment well outside the range of quantified uncertainties, providing truly unambiguous evidence for missing three-nucleon forces within the employed framework. The sizes of the required three-nucleon-force contributions agree well with expectations based on Weinberg's power counting. We identify the energy range in elastic Nd scattering best suited to study three-nucleon-force effects and estimate the achievable accuracy of theoretical predictions for various observables. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by genomic aberrations in oncogenes, cytogenetic abnormalities, and an aberrant epigenetic landscape. Nearly 50% of AML cases will relapse with current treatment. A major source of therapy resistance is the interaction of mesenchymal stroma with leukemic cells resulting in therapeutic protection. We aimed to determine pro-survival/anti-apoptotic protein networks involved in the stroma protection of leukemic cells. Proteomic profiling of cultured primary AML (n = 14) with Hs5 stroma cell line uncovered an up-regulation of energy-favorable metabolic proteins. Next, we modulated stroma-induced drug resistance with an epigenetic drug library, resulting in reduced apoptosis with histone deacetylase inhibitor (HDACi) treatment versus other epigenetic modifying compounds. Quantitative phosphoproteomic probing of this effect further revealed a metabolic-enriched phosphoproteome including significant up-regulation of acetyl-coenzyme A synthetase (ACSS2, S30) in leukemia-stroma HDACi treated cocultures compared with untreated monocultures. Validating these findings, we show ACSS2 substrate, acetate, promotes leukemic proliferation, ACSS2 knockout in leukemia cells inhibits leukemic proliferation and ACSS2 knockout in the stroma impairs leukemic metabolic fitness. Finally, we identify ACSS1/ACSS2-high expression AML subtype correlating with poor overall survival. Collectively, this study uncovers the leukemia-stroma phosphoproteome emphasizing a role for ACSS2 in mediating AML growth and drug resistance., (© 2024. The Author(s).)

The IL-6-gp130-STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function mutations in STAT3 (STAT3 GOF ) are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis. To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, the gp130-JAK-STAT3 axis was constitutively activated using a transgene, L-gp130 , specifically targeted to T cells. Activating gp130 signaling in T cells in vivo resulted in fatal, early onset, multi-organ autoimmunity in mice that resembled human STAT3 GOF disease. Female mice had more rapid disease progression than male mice. On a cellular level, gp130 signaling induced the activation and effector cell differentiation of T cells, promoted the expansion of T helper type 17 (T H 17) cells, and impaired the activity of regulatory T cells. Transcriptomic profiling of CD4 + and CD8 + T cells from these mice revealed commonly dysregulated genes and a gene signature that, when applied to human transcriptomic data, improved the segregation of patients with transcriptionally diverse STAT3 GOF mutations from healthy controls. The findings demonstrate that increased gp130-STAT3 signaling leads to T H 17-driven autoimmunity that phenotypically resembles human STAT3 GOF disease.

Proteasome inhibition is a highly effective treatment for multiple myeloma (MM). However, virtually all patients develop proteasome inhibitor resistance, which is associated with a poor prognosis. Hyperactive small ubiquitin-like modifier (SUMO) signaling is involved in both cancer pathogenesis and cancer progression. A state of increased SUMOylation has been associated with aggressive cancer biology. We found that relapsed/refractory MM is characterized by a SUMO-high state, and high expression of the SUMO E1-activating enzyme (SAE1/UBA2) is associated with poor overall survival. Consistently, continuous treatment of MM cell lines with carfilzomib (CFZ) enhanced SUMO pathway activity. Treatment of MM cell lines with the SUMO E1-activating enzyme inhibitor subasumstat (TAK-981) showed synergy with CFZ in both CFZ-sensitive and CFZ-resistant MM cell lines, irrespective of the TP53 state. Combination therapy was effective in primary MM cells and in 2 murine MM xenograft models. Mechanistically, combination treatment with subasumstat and CFZ enhanced genotoxic and proteotoxic stress, and induced apoptosis was associated with activity of the prolyl isomerase PIN1. In summary, our findings reveal activated SUMOylation as a therapeutic target in MM and point to combined SUMO/proteasome inhibition as a novel and potent strategy for the treatment of proteasome inhibitor-resistant MM., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Justice evaluations are proposed to provide a link between the objective level of inequality and the consequences at the individual and societal level. Available instruments, however, focus on the subjective perception of inequality and income distributions. In light of findings that subjective perceptions of inequality and income levels can be biased and subject to method effects, we present the newly developed Justice Evaluation of the Income Distribution (JEID) Scale, which captures justice evaluations of the actual earnings distribution. JEID comprises five items that provide respondents with earnings information for five groups at different segments along the distribution of earnings in a given country. We provide a German-language and an English-language version of the scale. The German-language version was developed and validated based on three comprehensive heterogeneous quota samples from Germany; the translated English-language version was validated in one comprehensive heterogeneous quota sample from the UK. Using latent profile analysis and k-means clustering, we identified three typical response patterns, which we labeled "inequality averse," "bottom-inequality averse," and "status quo justification." JEID was found to be related to normative orientations in the sense that egalitarian views were associated with stronger injustice evaluations at the bottom and top ends of the earnings distribution. With a completion time of between 1.50 and 2.75 min, the JEID scale can be applied in any self-report survey in the social sciences to investigate the distribution, precursors, and consequences of individuals' subjective evaluations of objective differences in earnings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nießen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

FAT atypical cadherin 1 (FAT1), a transmembrane protein, is frequently mutated in various cancer types and has been described as context-dependent tumor suppressor or oncogene. The FAT1 gene is mutated in 12-16% of T-cell acute leukemia (T-ALL) and aberrantly expressed in about 54% of T-ALL cases contrasted with absent expression in normal T-cells. Here, we characterized FAT1 expression and profiled the methylation status from T-ALL patients. In our T-ALL cohort, 53% of patient samples were FAT1 positive (FAT1pos) compared to only 16% FAT1 positivity in early T-ALL patient samples. Aberrant expression of FAT1 was strongly associated with FAT1 promotor hypomethylation, yet a subset, mainly consisting of TLX1-driven T-ALL patient samples showed methylation-independent high FAT1 expression. Genes correlating with FAT1 expression revealed enrichment in WNT signaling genes representing the most enriched single pathway. FAT1 knockdown or knockout led to impaired proliferation and downregulation of WNT pathway target genes (CCND1, MYC, LEF1), while FAT1 overexpressing conveyed a proliferative advantage. To conclude, we characterized a subtype pattern of FAT1 gene expression in adult T-ALL patients correlating with promotor methylation status. FAT1 dependent proliferation and WNT signaling discloses an impact on deeper understanding of T-ALL leukemogenesis as a fundament for prospective therapeutic strategies., (© 2023. The Author(s).)

History-graded increases in older adults' levels of cognitive performance are well documented, but little is known about historical shifts in within-person change: cognitive decline and onset of decline. We combined harmonized perceptual-motor speed data from independent samples recruited in 1990 and 2010 to obtain 2,008 age-matched longitudinal observations ( M = 78 years, 50% women) from 228 participants in the Berlin Aging Study (BASE) and 583 participants in the Berlin Aging Study II (BASE-II). We used nonlinear growth models that orthogonalized within- and between-person age effects and controlled for retest effects. At age 78, the later-born BASE-II cohort substantially outperformed the earlier-born BASE cohort ( d = 1.20; 25 years of age difference). Age trajectories, however, were parallel, and there was no evidence of cohort differences in the amount or rate of decline and the onset of decline. Cognitive functioning has shifted to higher levels, but cognitive decline in old age appears to proceed similarly as it did two decades ago.

Pre-vaccine SARS-CoV-2 seroprevalence data from Germany are scarce outside hotspots, and socioeconomic disparities remained largely unexplored. The nationwide representative RKI-SOEP study (15,122 participants, 18-99 years, 54% women) investigated seroprevalence and testing in a supplementary wave of the Socio-Economic-Panel conducted predominantly in October-November 2020. Self-collected oral-nasal swabs were PCR-positive in 0.4% and Euroimmun anti-SARS-CoV-2-S1-IgG ELISA from dry-capillary-blood antibody-positive in 1.3% (95% CI 0.9-1.7%, population-weighted, corrected for sensitivity = 0.811, specificity = 0.997). Seroprevalence was 1.7% (95% CI 1.2-2.3%) when additionally correcting for antibody decay. Overall infection prevalence including self-reports was 2.1%. We estimate 45% (95% CI 21-60%) undetected cases and lower detection in socioeconomically deprived districts. Prior SARS-CoV-2 testing was reported by 18% from the lower educational group vs. 25% and 26% from the medium and high educational group (p < 0.001, global test over three categories). Symptom-triggered test frequency was similar across educational groups. Routine testing was more common in low-educated adults, whereas travel-related testing and testing after contact with infected persons was more common in highly educated groups. This countrywide very low pre-vaccine seroprevalence in Germany at the end of 2020 can serve to evaluate the containment strategy. Our findings on social disparities indicate improvement potential in pandemic planning for people in socially disadvantaged circumstances., (© 2022. The Author(s).)

Background: Evidence on the relationship between socioeconomic position (SEP) and infections with SARS-CoV-2 is still limited as most of the available studies are ecological in nature. This is the first German nationwide study to examine differences in the risk of SARS-CoV-2 infections according to SEP at the individual level., Methods: The 'CORONA-MONITORING bundesweit' (RKI-SOEP) study is a seroepidemiological survey among a dynamic cohort of the German adult population (n=15 122; October 2020-February 2021). Dried blood samples were tested for SARS-CoV-2 antibodies and oral-nasal swabs for viral RNA. SEP was measured by education and income. Robust logistic regression was used to examine adjusted associations of SARS-CoV-2 infections with SEP., Results: 288 participants were seropositive, PCR positive or self-reported a previous laboratory-confirmed SARS-CoV-2 infection. The adjusted odds of SARS-CoV-2 infection were 1.87-fold (95% CI 1.06 to 3.29) higher among low-educated than highly educated adults. Evidence was weaker for income differences in infections (OR=1.65; 95% CI 0.89 to 3.05). Highly educated adults had lower odds of undetected infection., Conclusion: The results indicate an increased risk of SARS-CoV-2 infection in low-educated groups. To promote health equity in the pandemic and beyond, social determinants should be addressed more in infection protection and pandemic planning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The SARS-CoV-2 coronavirus has spread rapidly across Germany. Infections are likely to be under-recorded in the notification data from local health authorities on laboratory-confirmed cases since SARS-CoV-2 infections can proceed with few symptoms and then often remain undetected. Seroepidemiological studies allow the estimation of the proportion in the population that has been infected with SARS-CoV-2 (seroprevalence) as well as the extent of undetected infections. The 'CORONA-MONITORING bundesweit' study (RKI-SOEP study) collects biospecimens and interview data in a nationwide population sample drawn from the German Socio-Economic Panel (SOEP). Participants are sent materials to self-collect a dry blood sample of capillary blood from their finger and a swab sample from their mouth and nose, as well as a questionnaire. The samples returned are tested for SARS-CoV-2 IgG antibodies and SARS-CoV-2 RNA to identify past or present infections. The methods applied enable the identification of SARS-CoV-2 infections, including those that previously went undetected. In addition, by linking the data collected with available SOEP data, the study has the potential to investigate social and health-related differences in infection status. Thus, the study contributes to an improved understanding of the extent of the epidemic in Germany, as well as identification of target groups for infection protection., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

HBV-DNA levels are low or even undetectable in the majority HDV-infected patients. The impact of PEG-IFNα on HBV-DNA kinetics in HDV-infected patients has not been studied in detail. We analysed data of a prospective treatment trial where 120 HDV-RNA-positive patients were randomized to receive PEG-IFNα-2a plus tenofovir-disoproxil-fumarate (PEG-IFNα/TDF, n = 59) or placebo (PEG-IFNα/PBO; n = 61) for 96 weeks. At week 96, HBV-DNA was still quantifiable in 71% of PEG-IFNα/PBO-treated patients but also in 76% of PEG-IFNα/TDF-treated patients, despite low HBV-DNA baseline values. Surprisingly, a transient HBV-DNA increase between weeks 12 and 36 was observed in 12 in PEG-IFNα/TDF-treated and 12 PEG-IFNα/PBO-treated patients. This increase was positively associated with HBsAg loss [(P = 0.049, odds ratio (OR) 5.1] and HDV-RNA suppression (P = 0.007, OR 4.1) at week 96. Biochemical markers of cell death (M30 and ALT) were higher during the HBV-DNA peak but no distinct systemic immune pattern could be observed by screening 91 soluble inflammatory markers. In conclusion, an early increase in HBV-DNA during PEG-IFNα-2a therapy occurred in more than 20% of patients, even in TDF-treated patients. This transient HBV-DNA rise may indicate PEG-IFNα-induced cell death and lead to long-term HDV-RNA suppression and HBsAg loss., (© 2020 John Wiley & Sons Ltd.)

Introduction: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH., Methods: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls., Results: K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH cases. K18-M30 and M65 were associated with 90-day mortality, independent of age and Model for End-stage Liver Disease score in untreated patients. The association for K18-M65 was independent of both age and Model for End-stage Liver Disease in prednisolone-treated patients. Modelling of the effect of prednisolone on 90-day mortality as a function of pretreatment serum K18 levels indicated benefit in those with high serum levels of K18-M30. At low pretreatment serum K18 levels, prednisolone was potentially harmful. A threshold of K18-M30 5 kIU/L predicted therapeutic benefit from prednisolone above this level (odds ratio: 0.433, 95% confidence interval: 0.19-0.95, P = 0.0398), but not below (odds ratio: 1.271, 95% confidence interval: 0.88-1.84, P = 0.199). Restricting prednisolone usage to the former group would have reduced exposure by 87%., Discussion: In a large cohort of patients with severe AH, serum K18 strongly correlated with histological severity, independently associated with 90-day mortality, and predicted response to prednisolone therapy. Quantification of serum K18 levels could assist in clinical decision-making.

Amiodarone is a widely used antiarrhythmic drug that can cause the development of steatohepatitis as well as liver fibrosis and cirrhosis. The molecular mechanisms of amiodarone-mediated liver injury remain largely unknown. We therefore analyzed amiodarone-mediated hepatocellular injury in patients with chronic heart failure, in primary hepatocytes and HepG2 cells. We found that amiodarone-treated patients with chronic heart failure revealed significantly higher serum levels of caspase-cleaved keratin-18, an apoptosis biomarker, compared to healthy individuals or patients not receiving amiodarone. Furthermore, amiodarone treatment of hepatocytes resulted in apoptosis associated with lipid accumulation and ER-stress induction. Liver cell steatosis was accompanied by enhanced de novo lipogenesis which, after reaching peak levels, declined together with decreased activation of ER stress. The decline of amiodarone-mediated lipotoxicity was associated with protective autophagy induction. In contrast, in hepatocytes treated with the autophagy inhibitor chloroquine as well as in autophagy gene (ATG5 or ATG7)-deficient hepatocytes, amiodarone-triggered toxicity was increased. In conclusion, we demonstrate that amiodarone induces lipid accumulation associated with ER stress and apoptosis in hepatocytes, which is mirrored by increased keratin-18 fragment serum levels in amiodarone-treated patients. Autophagy reduces amiodarone-mediated lipotoxicity and could provide a therapeutic strategy for protection from drug-induced liver injury.

Non-alcoholic fatty liver disease (NAFLD) shows an increasing prevalence and is associated with the development of liver fibrosis and cirrhosis as the major risk factors of liver-related mortality in this disease. The therapeutic possibilities are limited and restricted to life style intervention, since specific drugs for NAFLD are unavailable so far. TNFα has been implicated as a major pathogenic driver of NAFLD. TNFα-mediated liver injury occurs mainly via TNF-receptor-1 (TNFR1) signaling, whereas TNFR2 mediates protective pathways. In this study, we analyzed the therapeutic effects of a novel antibody, which selectively inhibits TNFR1 while retaining protective TNFR2 signaling in a high-fat diet (HFD) mouse model of NAFLD. Mice were fed with HFD for 32 weeks and treated with anti-TNFR1-antibody or control-antibody for the last 8 weeks. We then investigated the mechanisms of TNFR1 inhibition on liver steatosis, inflammatory liver injury, insulin resistance and fibrosis. Compared to control-antibody treatment, TNFR1 inhibition significantly reduced liver steatosis and triglyceride content, which was accompanied by reduced expression and activation of the transcription factor SREBP1 and downstream target genes of lipogenesis. Furthermore, inhibition of TNFR1 resulted in reduced activation of the MAP kinase MKK7 and its downstream target JNK, which was associated with significant improvement of insulin resistance. Apoptotic liver injury, NAFLD activity and alanine aminotransferase (ALT) levels, as well as liver fibrosis significantly decreased by anti-TNFR1 compared to control-antibody treatment. Thus, our results suggest selective TNFR1 inhibition as a promising approach for NAFLD treatment.

Objectives: Nonalcoholic steatohepatitis (NASH) and fibrosis play critical roles for the prognosis of patients with nonalcoholic fatty liver disease (NAFLD). Identification of patients at risk of NASH and fibrosis is therefore critical for disease management. NAFLD Fibrosis Score (NFS) and transient elastography (TE) have been suggested to exclude advanced fibrosis. However, there is increasing evidence that also patients with NASH and early fibrosis are at risk of disease progression and complications, emphasizing the need for improved noninvasive risk stratification in NAFLD., Methods: Because hepatocyte apoptosis plays an early role in NASH pathogenesis, we evaluated whether the apoptosis biomarker M30 might identify NAFLD patients who are at risk of NASH and fibrosis despite low NFS or TE values. Serum M30 levels were assessed by enzyme-linked immunosorbent assay in combination with NFS and/or TE in an exploration (n = 103) and validation (n = 100) cohort of patients with biopsy-proven NAFLD., Results: Most patients with low NFS (cutoff value < -1.455) revealed increased M30 levels (>200 U/L) in the exploration (62%) and validation (67%) cohort, and more than 70% of them had NASH, mostly with histological fibrosis. Vice versa, most patients with NFS < -1.455 but nonelevated M30 levels showed no NASH. NASH was also detected in most patients with indeterminate NFS (-1.455 to 0.676) but elevated M30 levels, from which ∼90% showed fibrosis. Similar results were obtained when using TE instead of NFS., Discussion: The combination of the M30 biomarker with NFS or TE enables a more reliable identification of patients with an increased risk of progressed NAFLD and improves patient stratification.

Blood-sucking leeches like the medicinal leech, Hirudo medicinalis, have been used for medical purposes since ancient times. During feeding, medicinal leeches transfer a broad range of bioactive substances into the host's wound to prevent premature hemostasis and blood coagulation. Hirudin is probably the best known of these substances. Despite its long history of investigation, recombinant production and clinical use, there still exist conflicting data regarding the primary structure of hirudin. Entirely unclear is the potential biological significance of three different subtypes and many isoforms of hirudins that have been characterized so far. Furthermore, there is only incomplete information on their cDNA sequences and no information at all on gene structures and DNA sequences are available in the databases. Our efforts to fill these gaps revealed the presence of multiple hirudin-encoding genes in the genome of Hirudo medicinalis. We have strong evidence for the expression of all three subtypes of hirudin within individual leeches and for the expression of additional hirudins or hirudin-like factors that may have different biological functions and may be promising candidates for new drugs.

Modifying the chromatin structure and interacting with non-histone proteins, histone deacetylases (HDAC) are involved in vital cellular processes at different levels. We here specifically investigated the direct effects of HDAC5 in macrophage activation in response to bacterial or cytokine stimuli. Using murine and human macrophage cell lines, we studied the expression profile and the immunological function of HDAC5 at transcription and protein level in over-expression as well as RNA interference experiments. Toll-like receptor-mediated stimulation of murine RAW264.7 cells significantly reduced HDAC5 mRNA within 7 hrs but presented baseline levels after 24 hrs, a mechanism that was also found for Interferon-γ treatment. If treated with lipopolysaccharide, RAW264.7 cells transfected for over-expression only of full-length but not of mutant HDAC5, significantly elevated secretion of tumour necrosis factor α and of the monocyte chemotactic protein-1. These effects were accompanied by increased nuclear factor-κB activity. Accordingly, knock down of HDAC5-mRNA expression using specific siRNA significantly reduced the production of these cytokines in RAW264.7 or human U937 cells. Taken together, our results suggest a strong regulatory function of HDAC5 in the pro-inflammatory response of macrophages., (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Chylous ascites is a rare complication following pancreaticoduodenectomy. We report on a case of chylous ascites following pancreaticoduodenectomy in a 76-year-old patient diagnosed with pancreatic cancer. There are various known conservative management strategies, including dietary measures or total parenteral nutrition. Unfortunately, conservative treatment-with total parenteral nutrition and fasting over a period of 4 weeks-was not successful in the present case. The daily output volume of chylous ascites was up to 2500 ml/day. Based on clinical experiences with successfully treated lymphocutaneous fistulas, low-dose radiotherapy was initiated. External beam radiotherapy comprising a total dose of 8.0 Gy to the paraaortic lymph node region was administered in daily single fractions of 1.0 Gy (five fractions/week). Throughout the course of external beam radiotherapy, the secretion of abdominal ascites rapidly decreased, resulting in complete resolution after 2 weeks. There was no clinical evidence of chylous ascites on follow-up. As a result of this experience, we believe that external beam radiotherapy should be considered as an alternative therapy in refractory cases of chylous ascites.

Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aims: The study aimed to investigate (a) the association between low to moderate prenatal alcohol exposure (PAE) and the use of alcohol, tobacco and illicit drugs in adolescence and (b) whether the associations are modified by gender and ethnicity., Methods: The subjects of the study were 5922 children and adolescents, aged from 11 to 17 years, enrolled in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents (the KiGGS study). Information on PAE is based on parental self-report questionnaires. Use of alcohol, tobacco and illicit drugs was assessed through self-report questionnaires for adolescents., Results: Low to moderate PAE was associated with an increased risk of drinking alcohol (adjusted odds ratio (OR) 1.73, 95% confidence interval (CI) 1.34, 2.18) and also of illicit drug use (adjusted OR 1.62, 95% CI 1.23, 2.14). The associations between PAE and the use of alcohol, tobacco and illicit drugs differed according to gender and ethnicity. Gender-stratified analyses resulted in adverse effects of PAE on drinking alcohol, smoking and illicit drug use in females; however, in German males, the associations disappeared. Stronger associations between PAE and the outcome measures were found in non-Germans., Conclusions: Our findings indicate that low to moderate levels of maternal alcohol intake during pregnancy are a risk factor for use of alcohol, tobacco and illicit drugs by the offspring, with stronger associations in females and non-Germans.

People differ systematically in their vulnerability to injustice. We present two-item scales for the efficient measurement of justice sensitivity from 4 perspectives (victim, observer, beneficiary, perpetrator). In Study 1 using a quota-based sample of German adults, a latent state-trait analysis revealed the factorial validity and high reliabilities of the scales. In Study 2 employing a large random sample, we tested for measurement invariance of the items within the context of our short 2-item scales compared to the original 10-item scales. Multigroup confirmatory factor analyses confirmed that the validity of the indicators and the internal structure of the assessed constructs did not change across item contexts. In both studies, correlations with personality dimensions and life satisfaction provide evidence for the validity of our scales. With the presented instrument, future research can extend scientific knowledge regarding the role of individual differences in reactions to injustice for the explanation of well-being and physical health.

Carbon anions in solution: C(2)(2-) dumbbells are well-known in solid-state compounds. The crystallization of the title compounds now shows that acetylide ions are existent in solution and therefore chemistry with small dissolved carbon anions may be within reach., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Anxiety, depression and impaired health-related quality of life (HRQoL) are commonly reported in patients with multiple sclerosis (MS) and are of great interest for therapeutic approaches. Based on regional differences a quantitative assessment of these factors in comparison to the general population, and the consideration of demographic cofactors, would be useful when designing specific interventions. We adopted such an approach in a German cohort of MS patients. Anxiety, depression (HADS) and HRQoL (SF-36) were measured in 49 consecutive outpatients with MS and compared to age- and gender-adjusted control groups (n=1330 for HADS; n=5087 for SF-36) extracted from German National Health Surveys. Patients with MS showed significantly increased levels of anxiety and depression as well as decreased HRQoL with the exception of mental health; the effect sizes ranged from 0.39 (depression) to 1.06 (physical functioning). As could be expected, MS patients with relapsing-remitting clinical course had better physical functioning than patients with secondary progressive MS. There were strong relations between anxiety and depression (r=0.54; P<0.01), and between neurological impairment (EDSS) and physical functioning (r=-0.80; P<0.001) as well as depression (r=0.48; P<0.05). This investigation of MS patients confirms the prevalence and impact of anxiety, depression and most of the HRQoL dimensions in MS patients and provides evidence for the usefulness of a quantitative comparison to a region-specific general population as a starting point for therapeutic approaches.

Background and Objective: Osteoporosis is thought to be one possible side-effect of oral anticoagulant therapy, especially after long-term treatment. Nevertheless, data concerning this problem only exist from earlier years. Therefore, we decided to look for the incidence of osteoporosis in patients under long-term oral anticoagulant treatment., Patients and Methods: 30 patients (15 female, 15 male) - age between 38 and 77 years (average age 65,1+/-11,2 years) were examined. Group A: 10 patients with a capture time between 0,5 - 5 years, Group B: 10 patients with a capture time between 6 - 11 years, Group C: 10 patients with a capture time more than 11 years. The control group consisted 30 healthy persons - age between 39 and 81 years (18 female, 12 male, average age 61,5 +/- 12 years)., Results: In 21 out of 30 patients (9 female, 12 male) osteoporosis was found due to results of x-ray and bone-density-measurements. In 9 patients (6 female, 3 male) no osteoporosis was detected. No correlation between appearance of osteoporosis and duration of oral anticoagulant treatment was detected. Nevertheless, the number of patients presenting with osteoporosis in comparison with the control group was highly unexpected and astonishing., Conclusion: While treating patients with oral anticoagulants the possibility of appearing osteoporosis should be kept in view. In those circumstances the therapy should be supported by calcium and vitamin D.

Thoracic endometriosis is characterised by recurring pulmonary symptoms in association with the menstrual period. Pleural endometriosis manifests itself as recurring pneumothorax or hematothorax while pulmonary endometriosis is characterized by hemoptysis. The pathogenetic mechanism is not completely understood but it appears that hematogenous and lymphangitic embolization of endometrial tissue may play a significant part in parenchymal and pleural endometriosis respectively. Clinical symptoms begin with ovulation. Hemoptysis is explained by sloughing off of decidual tissue and an increased capillary fragility during menstruation. Rupture of pleurally based alveoli in the vicinity of endometrial tissue or necrosis of the diaphragm at the side of diaphragmatic endometrial implants might be causative for the development of a pneumothorax. Therapy of both forms of thoracic endometriosis consists in hormonal suppression but in some cases surgical intervention might become necessary.

Arteriovenous fistulas of the lung occur as a disease limited to the lung, or as a pulmonary manifestation of hereditary Rendu-Osler-Weber's disease. Typical complications are haemoptysis, haemothorax and cerebral embolism. We report on 3 patients in whom arteriovenous fistulas of the lung were removed by wedge excision or lobectomy. One of them had already suffered cerebral infarction. The indication for operative removal of single lesions is always given with respect to the severe complications of this disease. Decrease of the right-to-left shunt volume can usually be achieved.

201 adults with non-specific pleural empyema (58 women, 143 men) had suction drainage. Most of the patients were aged 61-70 years. In the 47 patients who had not had antibiotic therapy before admission the main causal micro-organisms were staphylococci, pneumococci and streptococci; in the 149, who had had antibiotic therapy outside, micro-organisms such as Pseudomonas, Esch. coli and Proteus predominated. Suction drainage had to be kept up for a remarkably long time: for 4-8 weeks in 36% of the cases and for more than 8 weeks in 8%. 31 patients died, but only 17 of them as a direct result of the pleural empyema. They had all been "high risk" cases on account of age (average 67.7 years), type of bacteria (59%), serious primary or complicating disease (59%), duration of the pleural empyema (76%). Suction drainage succeeded in 140 patients in clearing the infection; but marked adhesions were demonstrable in 27% of the patients when they were discharged from hospital.