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Background: Loneliness represents a significant health risk and is associated with numerous mental and physical conditions. The aim of this paper was to describe the prevalence of loneliness in Bavaria before and during the COVID-19 pandemic with respect to socio-demographic attributes., Methods: Data sources were the German Ageing Survey (DEAS) and the Socio-Economic Panel (SOEP). Univariate statistical analyses were carried out for different socio-demographic attributes, such as age, gender, type of household, education, and financial resources., Results: According to the SOEP, the proportion of adults who are often or very often lonely increased from 2.3% in 2017 to 16.2% in 2021. In 2021, women had a higher prevalence of loneliness than men (21.0% vs. 11.3%), and younger adults had the highest prevalence of loneliness (18 to 25 years: 31.7%) compared to the other age groups., Discussion and Conclusions: During the COVID-19 pandemic, loneliness increased in almost every population subgroup in Bavaria. Further studies are needed to examine whether this development is temporary or represents a long-term effect even after the measures to prevent the spread of COVID-19 have been lifted., (© 2024. Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature.)

Background: Bavaria is currently embarking on the endeavour of building up systematic prevention reporting. Prevention reporting is meant to support the implementation of the Bavarian Prevention Plan and the German Prevention Law and to further the ongoing development in the field of health promotion and health-related prevention in Bavaria., Goals: Prevention reporting in Bavaria aims to draw on general health reporting and complement it with specific prevention-related data taking into special consideration the Bavarian Prevention Plan. Particularly, data on prevention-amenable health determinants, prevention interventions, prevention spending and on indicators related to the targets of the Bavarian Prevention Plan are meant to be included. Periodic reporting will allow ongoing monitoring and the observation of trends. The reporting system will encompass shorter publications for the general public as well as more extensive reports for an expert audience. Where possible, data will be reported not only Bavaria wide but also on a smaller regional level to support local action., Implementation and First Results: An extensive stocktaking of prevention and health promotion activities in Bavaria in 2014/2015 as well as a survey of the partner organisations in the Bavarian Prevention Alliance in 2016 presented an overview of the prevention scene in Bavaria. A core indicator set to support the implementation of the Bavarian Prevention Plan was developed in 2016 and a first short data brochure for the public was published. A comprehensive compilation of prevention-related data and a Bavarian prevention report are planned for 2017 and 2018., Conclusions: Like health reporting, prevention reporting, as conceptualised in Bavaria, presents overview data and thus allows a monitoring of prevention. For specific planning or evaluation purposes, it needs to be supplemented by more in-depth analyses. Current challenges include the development of valid, prevention-specific indicators, the generation of an empiric database and the attempt of a coordinated approach amongst the federal states within Germany., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Health promotion and prevention are key elements of Bavarian health policy and are currently being re-oriented along the framework of the "Bavarian Prevention Plan". In this context, a stock taking of prevention and health promotion in Bavaria was conducted with the aim to contribute to the continued strategic and quality-orientated development of this field. Methods: The investigation was restricted to activities of primary prevention and health promotion with a focus on the action areas of the Bavarian Prevention Plan. The prevention actors, not projects, were the smallest units that were surveyed. During the 3-month field phase in 2014/2015, 595 prevention players were contacted and asked to complete an online questionnaire on their activities and target groups as well as quality and structural aspects. In addition, 9 expert interviews were conducted in an urban and a rural area in order to explore the field of small commercial and civic prevention actors. Results: 135 prevention players took part in the survey (return rate 23%). The most commonly cited themes of activities are health literacy (62% of players) and mental health (58%). The target groups are often broadly defined, gender specific measures and those for socially disadvantaged groups are comparatively rare. Provision of health-related information is the most commonly used approach (58-69% of players depending on the action area), least used are community work approaches (9-12%). 77% of the respondents state to use models of best practice and 55% scientific results in the development of measures; 43% conduct outcome evaluations and 80% take part in committee work and networks. The latter are mainly used to exchange information (90% of actors), 55 and 54% state to use them for joint planning and delivery of interventions, respectively. Conclusions: The most important prevention players took part in the survey. Methodologically it proved difficult to achieve a meaningful depiction of central aspects of the prevention scene via a quantitative survey approach. There is a lack of well-tried instruments and approaches for such cross-agency surveys. Nevertheless, the study allows trend statements on the spectrum, structure and quality of prevention in Bavaria. Thus, a starting line for the implementation of the Bavarian Prevention Plan as well as the basis of prevention reporting as intended by the new national prevention law could be established., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The 5'-noncoding region (5'NCR) of the HCV-genome comprises an internal ribosome entry site essential for HCV-translation/replication. Phosphorothioate oligodeoxynucleotides (tS-ODN) complementary to this region can inhibit HCV-translation in vitro. In this study, bile acid conjugated tS-ODN were generated to increase cell-selective inhibition of 5'NCR-dependent HCV-translation., Methods: Different bile acid conjugated tS-ODN complementary to the HCV5'NCR were selected for their inhibitory potential in an in vitro transcription/translation assay. To analyze OATP (organic anion transporting polypeptides)-selective uptake of bile acid conjugated ODN, different hepatoma cells were stably transfected with the OATP1B1-transporter and primary human hepatocytes were used. An adenovirus encoding the HCV5'NCR fused to the luciferase gene (Ad-GFP-NCRluc) was generated to quantify 5'NCR-dependent HCV gene expression in OATP-overexpressing hepatoma cells and in vivo., Results: A 17mer phosphorothioate modified ODN (tS-ODN4_13) complementary to HCV5'NCR was able to inhibit 5'NCR-dependent HCV-translation in an in vitro transcription/translation test system by more than 90% and it was also effective in Huh7-cells containing the HCV subgenomic replicon. Conjugation to taurocholate (tS-ODN4_13T) significantly increased selective ODN uptake by primary human hepatocytes and by OATP1B1-expressing HepG2-cells compared to parental HepG2-cells. Correspondingly, tS-ODN4_13T significantly inhibited HCV gene expression in liver-derived OATP1B1-expressing HepG2- or CCL13-cells up to 70% compared to unconjugated tS-ODN and compared to mismatch taurocholate coupled tS-ODN. In vivo, tS-ODN4_13T showed also a trend to block 5'NCR-dependent HCV gene expression., Conclusions: The tested taurocholate conjugated 17mer antisense ODN complementary to HCV5'NCV showed an increased and selective uptake by hepatocytes and liver-derived cells through OATP-mediated transport resulting in enhanced specific inhibition of HCV gene expression in vitro and in vivo. Thus, this novel approach may represent a promising strategy to improve antisense approaches with ODN in the control of hepatitis C infection., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background & Aims: In this study, adenoviral vectors encoding an antisense RNA complementary to the 5' non-coding region (5'NCR) of the HCV-genome were generated to inhibit HCV-RNA gene expression in cell culture and in vivo., Methods: First and second-generation (with E4-deletion) adenoviruses encoding the HCV5'NCR in antisense direction (Ad-NCRas and Ad-E4del-NCRas) were generated. Inhibition of HCV gene expression was analyzed in hepatoma cells stably transfected with the HCV5'NCR cDNA fused to the firefly luciferase gene (NCRluc), as well as in the HCV subgenomic replicon (genotypes 1b and 2a) and the fully infectious HCV JFH-1 cell culture systems. For in vivo experiments, an adenovirus encoding the NCRluc-gene was injected intravenously to achieve a NCR-dependent luciferase-expression in the liver of C3H/HeNcrl-mice., Results: Forty eight hours after transduction with GFP-encoding adenoviruses, >85% of HepG2-, CCL13-and Huh7-cells expressed GFP. Surprisingly, GFP-expression of E4-deleted adenoviruses was considerably reduced at the same MOI. Using antisense first-generation adenoviruses (Ad-NCRas), a significant inhibition of the 5'NCR-dependent HCV-gene expression (54±19% in HepG2-cells and 66.2±15% in Huh7-cells) was achieved 48h after transduction. In Huh7-cells containing the HCV subgenomic replicons and in infectious HCV JFH-1 cell cultures, adenovirus-mediated transcription of antisense 5'NCR significantly blocked HCV-replication (40% and 76%, respectively). Corresponding to low transgene expression, the maximal inhibition reached with Ad-delE4-NCRas was 30%. In vivo, antisense adenoviral vectors also showed a significant inhibition (40%) of NCR-dependent luciferase expression compared to control adenoviruses (p<0.05)., Conclusions: The data indicate that HCV gene expression can be inhibited by antisense RNA encoding adenoviruses in the tested settings., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

For a large territorial state like Bavaria only a decentralised cancer registration structure promises successful results: in the form of regional clinical cancer registries and--using the clinical registration as a base--one population-based registry. After ten years of epidemiological cancer registration in Bavaria it can now be shown that the chosen registration concept has proved itself. Currently the completeness of cancer notifications exceeded the international recommended threshold of 90%. A largely complete data stock is available for the years of diagnosis from 2004 to 2005. The task sharing between clinical and population-based cancer registries avoids double registration of data. Both types of registries are supporting physicians and hospitals with a wide palette of services. Together they enable transparency of cancer occurrence as well as transparency of health care for tumour patients.

Unlabelled: Dendritic cells (DCs) are professional antigen-presenting cells able to prime T-cells against tumor-associated antigens (TAA), but their potential to induce hepatocellular carcinoma (HCC) regression is still limited. CD40/CD40L interaction is essential for DC activation and induction of antigen-specific T-cells. In this study, transduction of TAA-pulsed DC with a CD40L-encoding adenovirus (Ad-CD40L) was used to improve the immune response induced by DC toward HCC. Bone marrow-derived DC from C3H/HeNcrl mice were cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6, tumor-lysate pulsed DCs were infected with adenoviruses. HCCs were induced by inoculation of mice with Hepa129-cells subcutaneously. When tumor-volume was 100 to 400 mm(3), DCs were injected intratumorally, subcutaneously, or intravenously. Ad-CD40L transduction exerted CD40/CD40L interactions between DCs, increasing DC immunostimulation with up-regulation of CD80/CD86- and interleukin-12 (IL-12) expression. Intratumoral injection of CD40L-DC was superior to intravenous or subcutaneous treatments, yielding tumor elimination in almost 70% of mice. Moreover, all tumor-free animals were protected against hepatic tumor cell rechallenge. In a preventive setting, subcutaneous injection of CD40L-expressing DCs protected 50% of mice for more than 3 months toward tumor cell challenge. The induced immune response seemed to be dependent on cross-priming with Th1-lymphocytes in the lymph nodes, because transduced DCs were redetected in lymphoid tissues. In addition, immunohistochemistry of tumors indicated a significant tumor infiltration with CD4+, CD8+ T cells and natural killer (NK) cells. Tumor-infiltrating lymphocytes were tumor-specific, as shown in interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot and T-cell proliferation assays., Conclusion: Transduction of DCs with Ad-CD40L increases significantly the stimulatory capacity of DCs. Intratumoral injection of DCs activates both acquired and innate immunity, inducing complete regression of established tumors and long-term immunity against tumor recurrence. This approach improves the antitumoral potential of DCs.

Recently, increasing evidence has been found demonstrating direct effects of angiostatin on tumor cells themselves. We have applied the plasminogen derivatives K1-4 and K1-5 to a lung cancer model to analyse indirect angiostatic effects against endothelial and direct effects against tumor cells. In accordance with preceding findings both derivatives inhibited endothelial cell functions in vitro. Additionally K1-4 and K1-5 have also shown substantial anti-proliferative and pro-apoptotic effects in tumor cells and have inhibited tumor growth. In addition our data supports the recent conclusion that plasminogen derivatives have a dual antitumor mechanism affecting both tumor angiogenesis and tumor cells.

Objectives: There are regional differences in mortality in Bavaria. Although these regional dif-ferences in mortality were associated with behavioural risk factors and socioeconomic factors in a study conducted for this reason, the quantitative effect of behavioural risk factors and socio-economic factors as well as the regional structure on the individual health as a predictor of mortality were not known., Methods: Persons between the age of 18 and 80 were interviewed with the Behavioral Risk Factor Surveillance System (BRFSS) in two Bavarian regions with high mortality, two Bavarian regions with low mortality and in the capital of Bavaria, Munich. For regional structural data, the INKAR database was used. Data were analysed descriptively, with a multivariable-adjusted logistic regression and with a multilevel analysis., Results: There were lower proportions of persons with a good or very good state of health as well as adverse results for overweight/adipositas, the behavioural risk factors for doing sports, smoking and consuming fruits and vegetables and the socioeconomic factors education and unemployment in the two regions with high mortality "Ostbayerische Grenzregion" and "Oberfranken". In a multivariable adjusted logistic regression, the body mass index, smoking, doing sports, climbing stairs, consuming alcohol, being satisfied with the job and the interaction between education and marital status were found to have an influence on the individual health. The small remaining regional component could be explained in the multilevel analysis by different variables which describe the economical situation of the regions., Conclusions: In accordance with the study hypotheses, a consistency between behavioural risk factors and regional differences in mortality could be observed. Socioeconomic influences and a small regional component are involved. In addition to specific prevention programmes for the target groups, structural support is also meaningful with regard to its potential health impact.

Background: The prognosis of patients with hepatocellular carcinoma (HCC) remains poor, and new alternative treatments are needed., Aims: To comparatively test the angiostatic and antitumour effects of adenoviral gene transfer of angiostatin (PlgK1-4, amino acids 1-440) and full kringles 1-5 (PlgK1-5, amino acids 1-546) in a model of subcutaneously transferred HCC in mice., Methods: PlgK1-4 and PlgK1-5 were generated from human WtPlg cDNA and used for adenovirus construction. Vector function and angiostatic effects were confirmed in vitro and in vivo. Antitumoral efficacies of intratumoral vector injections were studied in a model of subcutaneously transferred HCC model., Results: Cell supernatants containing PlgK1-4 and PlgK1-5 reduced endothelial tube formation in vitro by about 30%, whereas WtPlg exerted no inhibitory effect. Endothelial cell infiltration in vivo was decreased by about 60%, but not in AdWtPlg-treated animals. Intratumoral treatment of subcutaneous HCC tumours inhibited growth by 40% for AdPlgK1-4 and 63% for AdPlgK1-5 in surviving mice 12 days after initiation of treatment, whereas treatment with AdWtPlg even led to accelerated growth. Although PlgK1-4 and PlgK1-5 have similar inhibitory effects on intratumoral microvessels, PlgK1-5 markedly improved the survival time compared with PlgK1-4., Conclusion: PlgK1-5 and PlgK1-4 effectively inhibited HCC growth. As PlgK1-5 could also prolong the survival time, inducing complete tumour elimination in half of the AdPlgK1-5-treated mice, PlgK1-5 might be the most potential plasminogen fragment for treatment of experimental HCC.

Background/aims: To evaluate the long-term outcome of surgical and non-surgical local treatments of patients with hepatocellular carcinoma (HCC)., Methods: We stratified a cohort of 278 HCC patients using six independent predictors of survival according to the Vienna survival model for HCC (VISUM-HCC)., Results: Prior to therapy, 224 HCC patients presented with VISUM stage 1 (median survival 18 months) while 29 patients were classified as VISUM stage 2 (median survival 4 months) and 25 patients as VISUM stage 3 (median survival 3 months). A highly significant (p < 0.001) improved survival time was observed in VISUM stage 1 patients treated with liver resection (n = 52; median survival 37 months) or chemoembolization (TACE) and subsequent radiofrequency ablation (RFA) (n = 44; median survival 45 months) as compared to patients receiving chemoembolization alone (n = 107; median survival 13 months) or patients treated by tamoxifen only (n = 21; median survival 6 months). Chemoembolization alone significantly (p < or = 0.004) improved survival time in VISUM stage 1-2 patients but not (p = 0.341) in VISUM stage 3 patients in comparison to those treated by tamoxifen., Conclusion: Both liver resection or combined chemoembolization and RFA improve markedly the survival of patients with HCC., (2007 S. Karger AG, Basel)

Background: The use of evidence and evaluation is rapidly gaining importance in the field of health promotion and prevention. The evidence base, evaluation methods as well as the capacity and required competencies among practitioners are still being developed., Aims: Beyond its specific health-related targets, the health promotion initiative "Healthy Living in Bavaria" aims to integrate the use of evidence and evaluation as key components into project funding as part of a total quality management concept. Another objective is the creation of new evidence for the field of health promotion and prevention., Approach: A core element of the quality management concept is the initiative's multistage evidence and evaluation model which embraces the initiative as a whole as well as the individual projects. The model is operationalized through a set of matching instruments for application, reporting, evaluation, and appraisal., Conclusion: Nationally as well as internationally, evidence and evaluation stand out as central aspects of quality improvement instruments in health promotion and prevention. Characteristic of Bavaria's quality improvement approach is the seamless process from the application to the evaluation under consideration of scientific as well as pragmatic aspects.

Objective: In completion of a decision of the Bavarian Parliament we examined the regional mortality differences within Bavaria., Data: The analysis was based on the number of deaths in Bavaria in the years of 2000-2002. Data on regional demographic and socioeconomic indicators were used to identify potential associations., Methods: Deaths were analysed by cause of death and region. Crude and age standardised mortality rates were calculated. Additionally, we assessed the potential years of life lost in order to obtain some indication of the potential effects of preventive action. The association with likely explanatory factors was investigated on an ecological level., Results: The regional mortality differences in Bavaria show a northeast-southwest gradient favouring the southwest, which reflects the socioeconomic situation within Bavaria. This may be due to the economic disadvantage northeast Bavaria had to endure as a result of its marginal location within a divided Europe. We found strong bivariate correlations of the mortality rate with individual socioeconomic factors (e. g. with available income: -0.582; with unemployment: +0.416; with the immigration rate: -0.473). Exploratory analysis suggest that about 50 % of the regional variation in mortality could be explained by socioeconomic factors., Discussion: The results for cause of death indicate that behavioural factors in relation to socioeconomic aspects may well play a role in the mortality gradient. This will be the focus of a future piece of research of our unit.

Inhibition of vascular endothelial growth factor (VEGF) by gene transfer techniques was effectively applied to control experimental tumor growth, whereas effects on systemic VEGF levels had not been investigated. Therefore, we evaluated the effect of VEGF inhibition by adenoviral-mediated gene delivery of a dominant-negative soluble fragment of FLK-1 (sFlk-1) on systemic VEGF levels, organ-specific VEGF-RNA expression and antitumor efficacy in a murine colorectal cancer (CRC) tumor model. Vector function of AdsFlk-1 was shown by Western blot analysis and transgene expression was documented over a time period of 42 days in the serum of treated mice. Although cell supernatant of CT26 cells contained considerable levels of VEGF, systemic VEGF levels in the serum of tumor-bearing mice remained unaffected. Interestingly, mice that were systemically treated with AdsFlk-1 showed a strong upraise of circulating VEGF, whereas VEGF remained at background levels in the control. Vascular endothelial growth factor was increased not only in tumor bearing but also in healthy, tumor-free mice. Vascular endothelial growth factor determination in liver tissue homogenates showed a 16.5-fold upraise in AdsFlk-1-treated animals as compared to the AdLacZ control. Consecutively, systemic small interfering RNA injection targeted against VEGF reverted elevated VEGF levels almost back to normal levels. In spite of elevated VEGF levels, AdsFlk-1 administration showed significant antitumor effects in a subcutaneous metastatic CRC tumor model. There was no significant correlation between antitumour treatment response and VEGF levels in this model. Collectively, we conclude that the systemic administration of AdsFlk-1 had significant inhibitory effects on metastatic CRC tumor growth in spite of elevated systemic VEGF levels and that VEGF serum concentrations did not correlate to tumor burden and antitumor treatment response in this model.

Purpose: Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non-Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL., Experimental Design: Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA., Results: HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14(+) cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P < 0.05)., Conclusions: Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C-associated MC and B-NHL.

Previously, we demonstrated that intrahepatic upregulation of the immunoactivating molecules CD40 and CD40 ligand (CD40L) are early mechanisms for liver cell damage in human and murine fulminant hepatic failure (FHF). In the present study, we investigated the functional effects of intrahepatic overexpression of CD40L by adenoviral-mediated gene transfer (AdCD40L) in mice. AdCD40L injection induced severe liver cell damage, which was associated with increased alanine aminotransferase (ALT) levels peaking at day 5 after vector administration (AdCD40L, 1,707 +/- 279 U/L; AdLacZ, 213 +/- 25 U/L) and with lethality in half of the mice. Except for mild splenomegaly, no organs other than the liver were involved in inflammatory reactions. CD40-CD40L interaction was mandatory for liver damage, because CD40(-/-) mice were completely protected. Furthermore, CD40L-induced FHF depended on competent lymphocytes, because inflammatory reactions were strongly decreased in SCID and Rag1(-/-) mice. In contrast, neither natural killer T (NKT) cells nor Kupffer cells relevantly influenced histology as shown in NKT cell-deficient CD1d(-/-) mice and by gadolinium depletion of Kupffer cells. Furthermore, immunosuppression by dexamethasone and cyclosporin A was not sufficient to block CD40L damage. In conclusion, we present a model of FHF with strong similarities to human FHF with respect to time course and histological changes. This model suggests involvement of the CD40-CD40L system in FHF and might have important implications for future pathophysiological studies of this condition.

Background/aims: Four different ribozymes (Rz) targeting the hepatitis C virus (HCV) 5'-non-coding region (NCR) at nucleotide (nt) positions GUA 165 (Rz1), GUC 270 (Rz2), GUA 330 (Rz3) and GCA 348 (Rz1293) were compared for in vitro cleavage using a 455 nt HCV RNA substrate. The GUA 330 (Rz3) and GCA 348 (Rz1293) ribozymes, both targeting the HCV loop IV region, were found to be the most efficient, and were further analyzed in an in vitro translation system., Methods: For this purpose RNA transcribed from a construct encoding a HCV-5'-NCR-luciferase fusion protein was used. Cleavage-inactive (Rz1426), mismatch (Rz1293m) or unrelated ribozymes (Rz1437) were synthesized as controls for Rz-1293. HCV specificity was analysed by competition experiments using sense and mismatch oligodeoxynucleotides HCVrzCI and HCVrzMM, respectively., Results: A chemically modified nuclease-resistant variant of the GCA 348 cleaving ribozyme was selected for cell culture experiments using recombinant HepG2 or CCL13 cell lines stably transfected with a HCV-5'-NCR-luciferase target construct., Conclusions: This ribozyme (Rz1293) showed an inhibitory activity of translation of more than 70% thus verifying that the GCA 348 cleavage site in the HCV loop IV is an accessible target site in vivo and may be suitable for the development of novel optimized hammerhead structures.