[Loneliness in Bavaria before and during the COVID-19 pandemic].

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).

[Establishing Prevention Reporting in Bavaria - Concept, Implementation and First Results].

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.

Inhibition of hepatitis C virus RNA translation by antisense bile acid conjugated phosphorothioate modified oligodeoxynucleotides (ODN).

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.

Inhibition of hepatitis C virus gene expression by adenoviral vectors encoding antisense RNA in vitro and in vivo.

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.

Plasminogen derivatives encoding kringles 1-4 and kringles 1-5 exert indirect antiangiogenic and direct antitumoral effects in experimental lung cancer.

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.

CD40ligand-expressing dendritic cells induce regression of hepatocellular carcinoma by activating innate and acquired immunity in vivo.

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.

Liver resection or combined chemoembolization and radiofrequency ablation improve survival in patients with hepatocellular carcinoma.

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).

[Evidence and evaluation in health promotion and prevention: the example of the health promotion initiative "healthy living in Bavaria"].

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.

Induction of interleukin-6 by hepatitis C virus core protein in hepatitis C-associated mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma.

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.

Induction of murine liver damage by overexpression of CD40 ligand provides an experimental model to study fulminant hepatic failure.

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.

Plasminogen fragment K1-5 improves survival in a murine hepatocellular carcinoma model.

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.

Patient-derived dendritic cells transduced with an a-fetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells.

Background/aims: Breaking immunologic tolerance towards the hepatocellular carcinoma (HCC)-associated alpha-fetoprotein (AFP) antigen is possible. The use of this potential for the treatment of immunocompromised HCC patients is limited. In this study, we analyzed whether dendritic cells (DCs) from HCC patients transduced with a human AFP (hAFP)-expressing adenovirus and co-cultured with cytokine-induced killer (CIK) cells can induce a strong specific immune response against HCC-cells.

Hammerhead ribozymes with cleavage site specificity for NUH and NCH display significant anti-hepatitis C viral effect in vitro and in recombinant HepG2 and CCL13 cells.

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.

Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers.

Chronic alcohol consumption is associated with an increased risk for upper aerodigestive tract cancer and hepatocellular carcinoma. Increased acetaldehyde production via alcohol dehydrogenase (ADH) has been implicated in the pathogenesis. The allele ADH1C*1 of ADH1C encodes for an enzyme with a high capacity to generate acetaldehyde.

Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice.

Aim: Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor (VEGF) via stimulating endothelial cell proliferation, migration, and survival. Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities. Here, we tested a recombinant adenovirus, AdsFlt1-3, that encodes an antagonistically acting fragment of the VEGF receptor 1 (Flt-1), for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice.

Effective angiostatic treatment in a murine metastatic and orthotopic hepatoma model.

Vascular endothelial growth factor (VEGF) activity is correlated with a progressive tumor disease in patients with hepatocellular carcinoma (HCC). In spite of the well-recognized role of VEGF in HCC, there are few data available regarding therapeutic strategies to block VEGF activity. Therefore, we employed a recombinant adenoviral vector encoding a soluble dominant negative fragment of VEGF receptor 2 (Flk-1), AdsFlk-1, to control pre-established murine orthotopic and metastatic hepatomas.

Effective antitumour mono- and combination therapy by gene delivery of angiostatin-like molecule and interleukin-12 in a murine hepatoma model.

Methods: We applied an experimental approach employing two recombinant adenoviral vectors (Ad) that express interleukin-12 (IL-12) and angiostatin-like molecule (K1-3) respectively to a subcutaneous hepatoma model in mice.

Results: Injection of AdK1-3 into tumour nodules established by subcutaneous (s.c.

Altered expression of TGF-beta receptors in hepatocellular carcinoma--effects of a constitutively active TGF-beta type I receptor mutant.

Background/aims: Hepatocellular carcinomas (HCC) often show resistance to the effects of transforming growth factor-beta (TGF-beta). This study focuses on molecular mechanisms of this resistance to explore ways to overcome it.

Methods: Transcription and protein expression of TGF-beta type I and type II receptors (TGF-betaRI/RII) were analyzed in clinical HCCs and the human hepatoma cell lines HuH-7 and HepG2.

Accumulation of 8-hydroxy-2'-deoxyguanosine adducts in HBx recombinant HepG2 cells and HBx transgenic mice.

Background/aims: Transgenic mice overexpressing hepatitis B x protein (HBx) show an increased susceptibility to mutations if exposed to mutagens. Also involved in HBx signalling, reactive oxygen intermediates (ROI) can induce DNA adducts such as 8-hydroxy-2'-deoxyguanosine that can in turn lead to G/T transversion mutations. Therefore, we investigated whether HBx expression increases the level of the mutational precursor 8-hydroxy-2'-deoxyguanosine in hepatocellular DNA.

Molecular profiling of human hepatocellular carcinoma defines mutually exclusive interferon regulation and insulin-like growth factor II overexpression.

Molecular subtyping of human hepatocellular carcinoma (HCC) with potential mechanistic and therapeutic impact has not been achieved thus far. We have analyzed the mRNA expression patterns of 43 different human HCC samples and 3 HCC cell lines in comparison with normal adult liver using high-density cDNA microarrays. Two main groups of HCC, designated group A (65%) and group B (35%), were distinguished based on clustering of the most highly varying genes.

Does intubation really equal death in cirrhotic patients? Factors influencing outcome in patients with liver cirrhosis requiring mechanical ventilation.

Objective: It is not known whether the poor outcome of ventilated cirrhotic patients is related to the severity of the underlying liver disease or to the severity of the acute illness for which ICU care is required. This study examines parameters both of chronic liver disease and of acute illness with regard to their influence on outcome in mechanically ventilated cirrhotic patients.

Design And Setting: Retrospective observational case series in a 9-bed medical ICU in an academic tertiary care center.

Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma.

Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2'-deoxyguanosine (8-oxo-dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C --> T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine DNA glycosylase (hOGG1) and human MutY homolog (hMYH).

Establishment of an orthotopic tumour model for hepatocellular carcinoma and non-invasive in vivo tumour imaging by high resolution ultrasound in mice.

Background/aims: In this study we established an orthotopic tumour model for hepatocellular carcinoma and evaluated a non-invasive high resolution ultrasound technique for diagnosis and follow-up of intrahepatic HCC.

Methods: Orthotopic liver tumours were induced by intrahepatic tumour cell injection of 10(5) Hepa129 hepatoma cells. Tumour establishment and growth were assessed by explorative laparotomy, ultrasound technique and hepatectomy one and two weeks after tumour cell implantation.

An independent evaluation of modern prognostic scores in a central European cohort of 120 patients with hepatocellular carcinoma.

Background And Objectives: Hepatocellular carcinoma (HCC) is a common cancer worldwide. As prognosis of HCC patients depends not only on tumour extension but also on liver function, TNM staging of HCC is of limited value. The Okuda score incorporating the variables of liver function and tumour extension is used widely.

Requirements for adeno-associated virus-derived non-viral vectors to achieve stable and site-specific integration of plasmid DNA in liver carcinoma cells.

Background And Aims: Adeno-associated virus (AAV) is the only known virus capable of site-specific genomic integration in human cells. Thus, AAV-based vectors may be an attractive option to achieve prolonged transgene expression in human cells. We therefore studied the minimal elements of gene therapy vectors necessary for stable integration and tested the effectiveness of this approach in hepatoma cells.