A Universal Tumor-Specific Promoter for Cancer Gene Therapy.

An artificial double tandem tumor-specific promoter based on survivin and human telomerase reverse transcriptase gene promoters was constructed. Studies in in vitro and ex vivo therapeutic systems showed that the designed promoter exhibits a high activity in tumor cells, which is comparable to the activity of the CMV constitutive promoter.

Enhanced Vector Design for Cancer Gene Therapy with Hierarchical Enhancement of Therapeutic Transgene Expression.

A set of vectors for Cre recombinase-dependent expression of the hybrid suicidal FCU1 transgene was constructed, including a two-plasmid system wherein the FCU1 and Cre transgenes reside in separate vectors, and single-plasmid variants in which a single plasmid bears both transgenes. To improve the safety profile and specificity in cancer gene therapy applications, as well as to ensure stable propagation of plasmids in bacterial cells, the Cre/LoxP system components were optimized. A bicistronic vector with the Cre expression cassette placed between the LoxP sites unidirectionally with FCU1 cDNA resulted in higher therapeutic efficiency compared with the double-plasmid system in an enzyme-prodrug suicide cancer gene therapy scheme. Therefore, the feasibility of a single-plasmid approach in the development of cancer gene therapy with hierarchical enhancement of therapeutic transgene expression has been demonstrated.

[Health status of people with a migrant background and impact of socio-economic factors: First results of the German Health Interview and Examination Survey for Adults (DEGS1)]. / Die gesundheitliche Lage von Menschen mit Migrationshintergrund und die Bedeutung des sozioökonomischen Status : Erste Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1).

People with a migrant background (PMB) have specific health-related risk factors and resources compared to the non-migrant population (NMP). The analysis focuses on the relationship between migrant background and health and health-related behavior. Moreover, the study analyses whether socio-economic status (SES) contributes to the explanation of differences between PMB and the NMP. The research is based on the German Health Interview and Examination Survey for Adults (DEGS1) (2008-2012, n = 8151). The population for cross-sectional analyses contains 1107 PMB (weighted 19.8 %). The research question is addressed on the basis of nine exemplary health outcomes. All analyses are gender specific and make a distinction between first and second generation PMB. Logistic regression is calculated adjusting for age and SES. The results reveal clear gender-specific patterns: For women, differences are statistically significant mainly for first generation PMB. Compared to the NMP their self-assessed health status is lower, they are less physically active, consume less alcohol, feel less informed about cancer screening programs and make less use of preventive health services. However, daily smoking is more prevalent in second generation women. For men, differences are statistically significant for first and second generation PMB. Men with a migrant background show more symptoms of depression, consume less alcohol and feel less informed about cancer screening programs. After adjusting for SES the impact of migrant background on health status and health-related behavior largely remains stable. The study shows that the DEGS1 data offers valuable results and new insights into the health status of people with a migrant background. The use of this data for further research requires a differentiated approach to the concept of migrant background and a careful interpretation of results.

Inconsistencies and misleading information in officially approved prescribing information from three major drug markets.

The summary of product characteristics (SPC) should provide information for the safe prescription and use of a drug. We evaluated the consistency of critical interaction warnings, the quality of presentation of undesirable effects as well as concordance of critical information of representative drugs marketed in the United States, the UK, and Germany. Reciprocal warnings regarding drug-drug interactions that constitute contraindications were frequently missing in the SPCs of the drugs concerned (all countries >40%). Most SPCs did not explicitly exclude adverse reactions considered not reasonably attributable to the use of the drug. Comparing SPCs of different generic brands of the same drug, only 60, 10, and 20% of the US, UK, and German SPCs, respectively, provided identical contraindications. Current SPCs contain inconsistencies and misleading data that are not compatible with the purpose of SPCs, which is to provide a basis for the safe prescription and use of drugs.

[Unintentional injuries in the German adult population. Results of the "German Health Update" survey 2010]. / Das Unfallgeschehen bei Erwachsenen in Deutschland. Ergebnisse der Befragung "Gesundheit in Deutschland aktuell" 2010.

In Germany, more than 20,000 people were killed in accidents and 8.7 million people suffered nonfatal unintentional injuries (UI) in 2011. This report gives an overview of the occurrence of nonfatal UI in the German adult population. The representative health survey "German Health Update" 2010 (phone survey) collected data on nonfatal accidents in the adult population within a recall period of 12 months (n = 22,050). Interviewees reporting medically treated UI responded to 19 further questions about accident locations, accident mechanisms, injuries, and consequences of up to three UI within 1 year. Overall, detailed data on 2,117 UI were collected. About 7.9 % of the German adult population suffers at least one medically treated UI within 1 year. Men are more often affected than women and young people more frequently than older people. The majority of all UI occurs at home or during leisure-time activities. One in five UI results from accidents on public footways, roads, and squares. Falls account for almost every third UI and about one in five accidents causes fractures. Two thirds of all UI require inpatient treatment. Two in three UI lead to temporary sick leave averaging 29.7 days of absenteeism. Among UI at home and in leisure-time activities, falls have particularly serious consequences. Moreover, falls play an important role in UI among pedestrians and cyclists. UI affect large parts of the German adult population and are clearly patterned by gender, age, and accident location. Therefore, prevention activities should consider target group-specific needs and setting-specific circumstances of UI.

[Unintentional injuries among children and adolescents in Germany. Data sources and results]. / Das Unfallgeschehen bei Kindern und Jugendlichen in Deutschland. Datenquellen und Ergebnisse.

Compared to adults, children and adolescents run a considerably higher risk of suffering unintentional injuries (UI). To prevent UI, detailed knowledge of the overall accident occurrence and the determinants of UI is needed. This article gives an overview of the data sources covering the occurrence of UI among children and adolescents in Germany. According to the Robert Koch Institute's German Health Interview and Examination Survey for Children and Adolescents (KiGGS), approximately 15.3 % of children and adolescents (1-17 years) in Germany suffer at least one UI within 12 months. Most accidents (60.7 %) occur at home or during leisure-time activities. In 2011, the German Statutory Accident Insurance (DGUV) registered more than 1.4 million accidents among children in day-care facilities and students in educational institutions. According to official statistics, in the same year, more than 50,000 children and adolescents were injured in traffic accidents. Moreover, the Federal Statistical Office registered 260,534 hospital admissions due to injuries and poisonings among children and adolescents. All data sources revealed age- and sex-specific differences. Boys suffer UI more frequently than girls do and they show higher injury rates in adolescence than during childhood. While UI among children mostly happen at home, road traffic and leisure-time accidents increase in occurrence during adolescence. In Germany, there are numerous initiatives dedicated to the prevention of UI in children and adolescents. The creation of target group-specific prevention measures is complicated by the fact that the methodological approaches of existing data sources differ considerably.

[Expression of sphingomyelin synthase 1 (SGMS1) gene varies in human lung and oesophagus cancer].

The investigation of molecular mechanisms contributing to cancer progression is the burning problem ofcurrent research. Considerable attention has been given to the study of gene expression in cancer cells. Sphingomyelin synthase 1 gene (SGMS1) is one of the genes whose expression can be altered in cancer. SMS1 enzyme, encoded by this gene, catalyzes the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide. SMS1 may maintain the balance between cell death and survival by regulating the formation of the pro-apoptotic mediator ceramide and anti-apoptotic mediator diacylglycerol. In addition, the changes in sphingomyelin level and sphingomyelin synthase activity have been observed in cancers of many tissues. However the peculiarities of SGMS1 gene transcription have been insufficiently explored. In this work the expression of transcripts of SGMS1 has been investigated by the method of Real Time PCR in matched pairs of samples of human lung and oesophagus cancer and adjacent tissues without pathology. A significant decrease in SMS1 transcripts expression has been found in samples of human lung cancer. At the same time, in the samples of human oesophagus cancer and adjacent tissue, expression of SMS1 transcripts varies insignificantly: it is increased in 7 and decreased in 5 of 15 samples. The obtained results indicate that SGMS1 gene is differently expressed in cancers of different genesis.

The effect of cationic microbicide exposure against Burkholderia cepacia complex (Bcc); the use of Burkholderia lata strain 383 as a model bacterium.

AIM: The extensive use of microbicides in a wide range of applications has been questioned with regard to their role in the development of bacterial resistance to antimicrobials. This study aims to measure the phenotypic and genotypic changes in Burkholderia lata strain 383 exposed to chlorhexidine gluconate (CHG) and benzalkonium chloride (BZC), two commonly used cationic microbicides. METHODS AND RESULTS: The susceptibility of B. lata strain 383 to CHG and BZC and a range of antibiotics was determined using standardized MIC, MBC and antibiotic susceptibility testing protocols before and after short-term exposure to a low microbicide concentration. Measurements were performed on four separate occasions over a 1-year period. Changes in gene expression were investigated using quantitative real-time PCR. Although the susceptibility profile to CHG and BZC was not altered, a change in antibiotic susceptibility profile was observed for ceftazidime, and for imipenem and ciprofloxacin in 2/4 repeats. An outer membrane protein and ABC transporter were found to be significantly upregulated following treatment with BZC and CHG, respectively. CONCLUSIONS: The comparison of MIC and MBC results following microbicide exposure with baseline data offered a prospective protocol to quantify any change in bacterial susceptibility profile. However, the use of a standardized antibiotic susceptibility protocol with B. lata strain 383 showed some inconsistencies in results between repeats. SIGNIFICANCE AND IMPACT OF THE STUDY: With ever-increasing interest in the impact of microbicides on emerging antimicrobial resistance in bacteria growing, this study demonstrated that comparing susceptibility profile obtained after exposure to microbicides with baseline susceptibility values could play a role in establishing the potential risk of microbicide resistance and cross-resistance development and also in the development of a protocol that allows the prediction of microbicide resistance.

[Participation in cancer screening in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)]. / Inanspruchnahme von Krebsfrüherkennungsuntersuchungen: Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1).

A growing number of people in Germany participate in the cancer screening services offered by statutory health insurance. Using data from the first wave of the German Health Interview and Examination Survey for Adults (DEGS1), current levels of participation in cancer screening services were determined. DEGS1 (2008-2011) permits representative cross-sectional analyses to be performed. In DEGS1, persons who were entitled to different cancer screening services were interviewed on their awareness, participation and regular utilisation of cancer screening for different types of cancer. Overall, 67.2% of women and 40.0% of men participate regularly. Participation rates fluctuate to a great extent for individual types of cancer screening. Women participate in cancer screening more frequently than men do. For women, a better socioeconomic status was associated with higher participation rates. Participation rates improve with increasing age, meaning that the difference in participation rates between women and men becomes smaller. The current analyses present information on specifically targeted population groups to promote informed decision-making about cancer screening, so that participation rates can be improved further. The analyses thus provide an important basis for health policy measures. An English full-text version of this article is available at SpringerLink as supplemental.

[National health target "healthy ageing". Medical, psychosocial and nursing care for elderly people]. / Nationales Gesundheitsziel "Gesund älter werden". Handlungsfeld II: Medizinische, psychosoziale und pflegerische Versorgung älterer Menschen.

What kind of health targets should be pursued concerning the health care of elderly people? What kind of activities should be implemented to ensure good health care with regard to future challenges? The Association for the Continuous Development of the National Health Target Process, health-targets.de, deals with these issues under the new national health target "Healthy Ageing". We develop concrete objectives and proposals for practical implementation in the areas of "outpatient and inpatient care", "nursing" and "rehabilitation in old age". health-targets.de supports a common health target process and initiates interventions in the field of health care for elderly people.

[Comparative analysis of herpes simplex virus thymidine kinase gene expression potentiation via HIV-1 Tat-TAR-system and cancer-specific promoters in p53(+) and p53(-) cells].

Tumor-specific promoters are predominantly active and ensure expression of the gene under control exclusively in cancer cells. However, a low activity of the promoters is an essential disadvantage for their therapy usage. To achieve a higher expression level of the therapeutic gene, herpes simplex virus thymidine kinase (HSV-tk), the Tat-TAR-system being utilized by HIV-1 for increasing own gene expression was developed. A potentiating activity of tat gene under control of two different cancer-specific gene (human survivin gene and human telomerase reverse transcriptase) promoters for increasing of the HSV-tk gene expression being regulated by TAR-element was evaluated, and activity of the cancer-specific promoters in the Tat-TAR-system was compared. Co-transfection of the cells with the both constructions led to the tat protein synthesis and its affect the HIV-1 TAR-element. An expression level of HSV-tk gene ensured by the both promoters in the binary system was close to that for strong non-specific cytomegalovirus (CMV) promoter. Enzymatic activity of HSV-tk protein in cells having both elements of Tat-TAR-system was two orders of magnitude higher than that in the cells transfected with HSV-tk gene under control of the cancer-specific promoter. Notably, the effect was independent of p53-status of transfected cells: HSV-tk expression level was almost the same in p53(+) and p53(-) cells. The obtained results show that system may be used for therapy of different cancer types both p53-defective and p53-positive ones inhibiting cancer-specific promoters activity.

[Health and old age: taking stock from the perspective of health reporting]. / Alter und Gesundheit: Eine Bestandsaufnahme aus Sicht der Gesundheitsberichterstattung.

With advancing age, there is a significant increase in the number of health problems; at the same time, the complexity of the existing impairments increases. In addition to the diagnosed somatic and psychological illnesses, functional disorders and disabilities as well as the self-assessed health of the individual play an important role. Health in old age is an important individual and societal topic today and in the future. In order to plan health politics, mapping of morbidity and prognosis are important. They require representative, valid, current, and comparable data over time. Databases of the health reporting in the area of senior citizens have improved in recent years. However, data are still missing, for example, in the area of not being able to fully take part in daily life. Research is needed, because of the specificity of health problems in the elderly, including the survey methodology and the selection of suitable indicators.

Identification of some human genes oppositely regulated during esophageal squamous cell carcinoma formation and human embryonic esophagus development.

Here we directly compared gene expression profiles in human esophageal squamous cell carcinomas and in human fetal esophagus development. We used the suppression subtractive hybridization technique to subtract cDNAs prepared from tumor and normal human esophageal samples. cDNA sequencing and reverse transcription polymerase chain reaction (RT-PCR) analysis of RNAs from human tumor and the normal esophagus revealed 10 differentially transcribed genes: CSTA, CRNN, CEACAM1, MAL, EMP1, ECRG2, and SPRR downregulated, and PLAUR, SFRP4, and secreted protein that is acidic and rich in cysteine upregulated in tumor tissue as compared with surrounding normal tissue. In turn, genes up- and downregulated in tumor tissue were down- and upregulated, respectively, during development from the fetal to adult esophagus. Thus, we demonstrated that, as reported for other tumors, gene transcriptional activation and/or suppression events in esophageal tumor progression were opposite to those observed during development from the fetal to adult esophagus. This tumor 'embryonization' supports the idea that stem or progenitor cells are implicated in esophageal cancer emergence.

[gesundheitsziele.de. Results of criteria analysis to select a new health target in Germany]. / gesundheitsziele.de. Ergebnisse der Kriterienanalyse für die Auswahl eines neuen Gesundheitsziels in Deutschland.

In 2008 the forum gesundheitsziele.de selected "Healthy aging" as a new health target. Besides "Healthy aging" three other targets were considered: chronic back pain, myocardial infarction, and vaccination. This paper describes the selection process for all four health targets which followed several criteria: mortality, morbidity, prevalence, burden of disease, economic impact, potential for improvement, equity in health, empowerment of and priorities in the population. The analysis particularly focused on assessment of feasibility and readiness of stakeholders to participate in the development and implementation of the health target.

[Increase of BIRC5 gene expression in non-small cell lung cancer and esophageal squamous cell carcinoma does not correlate with expression of genes SMAC/DIABLO and PML encoding its inhibitors].

Survivin (BIRC5) is one of the members of IAP-family apoptosis inhibitors. The BIRCS gene is expressed in most human embryonic tissues and malignant tumors but not in normal differentiated tissues of adult human. It was suggested that BIRC5 proteins inhibit apoptosis and play an essential role in tumorigenesis, makings surviving an attractive target for anticancer therapy. The mechanisms regulating level of survivin are not completely understood. It was supposed that natural inhibitors of survivin, namely SMAC and PML, play an important role in these processes. Using RT-PCR and immunoblotting we analyzed the transcription level of BIRC5, SMAC and PML genes and content of corresponding proteins in normal and tumor human tissues in non-small cell lung cancer and esophageal squamous cell carcinoma. It was demonstrated that BIRC5 is transcribed only in tumor tissues, whereas expression levels of SMAC and PML are the same in normal and tumor tissues. The contents of proteins correspond to levels of mRNA of the respective genes. Thus the increase of level of survivin in tumor tissues is not the result of decrease in content of its inhibitors SMAC and PML, as their content in tumor and normal cells is the same.

A new tool to monitor training and performance of sport horses using global positioning system (GPS) with integrated GSM capabilities.

Global Positioning Systems (GPS) are considered suitable to monitor the position and velocity of horses during cross-country competition or in training. Furthermore, simultaneous recording of life data such as heart rate could be useful to assess the horse's condition during exercise. To test the suitability and reliability of a commercially available GPS system with integrated heart rate recording system and with built in GSM for data transmission, the Fidelak Equipilot Type EP-2003-15/G-2.11 (EP-15/G) was evaluated first for reliability of pulse recording from a pulse generator within the physiological range of horses; furthermore distance, velocity and heart rate recordings were carried out on a standard 1000 m field track with five repetitions. Agreement (% deviation from actually measured distance and from stopwatch-distance based velocity calculations) and variability (Coefficient of Variation for distance, velocity, heart rate) were calculated. From the results it was safe to assume that the heart rate sensor recorded horse heart rates at a high degree of accuracy. Overall distances and velocities are in high agreement with actually measured values. However, overall variability expressed in terms of relative variability (C.V.) is smaller for distance recording (C.V. 0.68%) when compared to velocity (C.V. 1.01%). The system tested is suitable and reliable for simultaneously recording of distance, velocity and heart rates for horses during cross country exercise. GPS-based monitoring of movement along with simultaneous recording of physiological data and the possibility to call upon data will not only be of benefit for training horses or for surveillance during competition, it may also be suitable for distant patient monitoring and in behavioural studies as well as in veterinary medicine in general.

[Regulatory potential of S/MAR elements in transient expression].

S/MARs (scaffold/matrix attachment regions) are the DNA regions that are involved in the interaction with the nuclear matrix and are identified by in vitro methods. According to the available information, S/MARs possess an insulating activity, i.e., the ability to block the interaction between the enhancer and promoter in vivo, and are, probably, intact insulators or their fragments. Nevertheless, there is still no direct proof for this correspondence. To obtain additional information on the insulator activity of S/MARs, we selected five DNA fragments of different lengths and affinities for the nuclear matrix from the previously constructed library of S/MARs and tested their ability to serve as insulators. Two of five elements exhibited an insulator (enhancer-blocking) activity upon the transient transfection of CHO cells. None of the S/MARs displayed either promoter or enhancer/silencer activities in these cells.

Microbial communities in the chemocline of a hypersaline deep-sea basin (Urania basin, Mediterranean Sea).

The Urania basin is a hypersaline sulfidic brine lake at the bottom of the eastern Mediterranean Sea. Since this basin is located at a depth of approximately 3,500 m below the sea surface, it receives only a small amount of phytoplankton organic carbon. In the present study, the bacterial assemblages at the interface between the hypersaline brine and the overlaying seawater were investigated. The sulfide concentration increased from 0 to 10 mM within a vertical interval of 5 m across the interface. Within this chemocline, the total bacterial cell counts and the exoenzyme activities were elevated. Employing 11 cultivation methods, we isolated a total of 70 bacterial strains. The 16S ribosomal DNA sequences of 32 of the strains were identical to environmental sequences detected in the chemocline by culture-independent molecular methods. These strains were identified as flavobacteria, Alteromonas macleodii, and Halomonas aquamarina. All 70 strains could grow chemoorganoheterotrophically under oxic conditions. Sixty-six strains grew on peptone, casein hydrolysate, and yeast extract, whereas only 15 strains did not utilize polymeric carbohydrates. Twenty-one of the isolates could grow both chemoorganotrophically and chemolithotrophically. While the most probable numbers in most cases ranged between 0.006 and 4.3% of the total cell counts, an unusually high value of 54% was determined above the chemocline with media containing amino acids as the carbon and energy source. Our results indicate that culturable bacteria thriving at the oxic-anoxic interface of the Urania basin differ considerably from the chemolithoautotrophic bacteria typical of other chemocline habitats.