Cancer incidence in urban, rural, and densely populated districts close to core cities in Bavaria, Germany.

OBJECTIVE: An ecologic study on the level of districts was performed to evaluate the possible association between district type and risk of cancer in Bavaria, Southern Germany. METHODS: Cancer incidence data for the years 2003-2012 were obtained from the population-based cancer registry Bavaria according to sex and cancer site. Data on district type, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption were obtained from publicly available sources. The possible association between district type and cancer risk adjusted for age, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption was evaluated using multivariable multi-level negative binomial regression. RESULTS: We found a significantly reduced cancer risk in densely populated districts close to core cities and/or rural districts compared to core cities with respect to the cancer sites mouth and pharynx (women only), liver (both sexes), larynx (both sexes), lung (both sexes), melanoma of the skin (both sexes), mesothelioma (men only), connective and soft tissue (both sexes), corpus uteri, other urinary tract (men only), urinary bladder (both sexes), and non-Hodgkin lymphoma (both sexes). CONCLUSION: Our findings require further monitoring. Since the apparently increased cancer risk in core cities may be related to lifestyle factors, preventive measures against lifestyle-related cancer could be specifically targeted at populations in deprived core cities.

[Data quality or differences in oncological care? - standards of reporting for cancer survival analyses based on registry data]. / Datenqualität oder Unterschiede in der onkologischen Versorgung? - Berichtsstandards für Überlebenszeitanalysen mit Krebsregisterdaten.

BACKGROUND: The results of population-based cancer survival analyses are essential criteria with regard to the evaluation of oncological care. Their use and their interpretation as such require knowledge and transparency with regard to the data basis in order to avoid inadequate conclusions. METHOD: The working group 'survival analysis' of the Association of Population-Based Cancer Registries in Germany (GEKID) has identified factors within cancer registration and data evaluation which may distort population-based cancer survival analyses to a relevant degree. Recommendations in terms of standards of reporting were developed by mutual consent following empirical studies and discussions within GEKID. RESULTS: We provide a list of 17 indicators to be taken into account and to be presented within the scope of population-based survival analyses. CONCLUSIONS: Referring to the "standards of reporting concerning population-based cancer survival analyses" introduced by GEKID there is a proposal on data transparency on hand, which might contribute substantially to the assessability of outcome quality in oncological care.

[Cancer survival analysis in Germany--heading towards representative and comparable findings]. / Überlebenschancen von Krebspatienten in Deutschland--auf dem Weg zu repräsentativen, vergleichbaren Aussagen.

Cancer is an important issue within the German health care system with an estimated annual number of 435 000 incident cases and almost 210 000 deaths. Data of population-based cancer registries enable us to identify improvements of survival in oncological patients due to progress in therapeutic care and secondary prevention, as well as to investigate regional and international differences of this outcome. Comparing cancer survival rates, however, requires considering the impact of both methodical approaches and data quality. Potential factors of influence like algorithms, reference population, completeness of case ascertainment and quality of follow-up are discussed. For the first time harmonized proceedings are recommended in order to achieve comparability of population-based cancer survival rates in Germany.

Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress.

The aim of this study was to investigate the effect of phosphatidylserine (PS) on cognition and cortical activity after mental stress. After familiarization, 16 healthy subjects completed cognitive tasks after induced stress in a test-re-test design (T1 and T2). Directly after T1, subjects were assigned double-blind to either PS or placebo groups followed by T2 after 42 days. At T1 and T2, cortical activity was measured at baseline and immediately after stress with cognitive tasks using electro-encephalography (EEG). EEG was recorded at 17 electrode positions and fast Fourier transforms (FFT) determined power at Theta, Alpha-1, Alpha-2, Beta-1 and Beta-2. Statistics were calculated using ANOVA (group x trial x time). The main finding of the study was that chronic supplementation of phosphatidylserine significantly decreases Beta-1 power in right hemispheric frontal brain regions (F8; P < 0.05) before and after induced stress. The results for Beta-1 power in the PS group were connected to a more relaxed state compared to the controls.

In vitro toxicity of nanoparticles in BRL 3A rat liver cells.

This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100 nm), molybdenum (MoO(3); 30, 150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe(3)O(4); 30, 47 nm), and titanium dioxide (TiO(2); 40 nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1 microm), manganese oxide (MnO(2); 1-2 microm), and tungsten (W; 27 microm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5-50 microg/ml. However, Fe(3)O(4), Al, MoO(3) and TiO(2) had no measurable effect at lower doses (10-50 microg/ml), while there was a significant effect at higher levels (100-250 microg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10-50 microg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100-250 microg/ml). In summary the Ag was highly toxic whereas, MoO(3) moderately toxic and Fe(3)O(4), Al, MnO(2) and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.

Prediction of halocarbon toxicity from structure: a hierarchical QSAR approach.

Mathematical structural invariants and quantum theoretical descriptors have been used extensively in quantitative structure-activity relationships (QSARs) for the estimation of pharmaceutical activities, biological properties, physicochemical properties, and the toxicities of chemicals. Recently our research team has explored the relative importance of various levels of chemodescriptors, i.e. topostructural (TS), topochemical (TC), geometrical (3D), and quantum theoretical descriptors, in property estimation. This study examines the contribution of chemodescriptors ranging from topostructural to quantum theoretic calculations, up to the Gaussian STO-3G level, in predicting the results of six indicators of oxidative stress for a set of 20 halocarbons. Using quantum theoretical calculations in this study is of particular interest as molecular energetics is related to the likelihood of electron attachment and free radical formation, the mechanism of toxicity for these chemicals and should aid in modeling their potential for oxidative stress.

QSAR modeling of oxidative stress in vitro following hepatocyte exposures to halogenated methanes.

Volatile halogenated aliphatic compounds are among those chemicals that can cause oxidative stress in vitro and in vivo. Relationships can be identified between the potential of these chemicals to elicit certain biological responses and their specific chemical descriptors, such as molecular orbital energies (LUMO) or partition coefficients (logP). A quantitative structure-activity relationship (QSAR) model has not been reported previously for the potential of a series of brominated and chlorinated methanes to induce oxidative stress in primary rat hepatocytes. By utilizing a novel in vitro methodology to expose cultures of rat primary hepatocytes to volatile chemicals, biological responses were assessed from exposures of hepatocytes to individual halogenated methanes. Indicators of lipid peroxidation, reactive oxygen species and cytotoxicity were measured. For the 10 brominated and chlorinated methanes tested, semi-empirical molecular orbital methods were used to calculate the physical/chemical descriptors used in the QSAR models. These models were used to explain the relative potential for a given halogenated methane to induce markers of oxidative stress or related damage in vitro. The results showed that certain descriptors, such as the molecular orbital energies, bond lengths, and lipophilicity are quantitatively correlated with induction of indicators for oxidative stress and cytotoxicity by halogenated methanes in primary rat hepatocytes.

Effect of JP-8 jet fuel on molecular and histological parameters related to acute skin irritation.

Organic chemicals such as jet fuels and solvents can cause skin irritation after dermal exposure. The molecular responses to these chemicals resulting in acute irritation are not understood well enough to establish safe exposure limits. Male F-344 rats were dermally exposed to JP-8 jet fuel for 1 h using Hill Top Chambers. Whole skin samples were collected at 0, 1, 2, 4, and 6 h after the beginning of the exposures, homogenized, and analyzed for interleukin (IL)-1alpha and inducible nitric oxide synthase (iNOS) protein and nitrite levels. IL-1alpha levels (determined by ELISA) ranged from approximately 11 to 34% above the 0-h samples over the observed time period. At 1 and 2 h, significantly higher (p < 0.05) levels of IL-1alpha were detected when compared to the 0-h samples. Western blot analysis revealed significantly higher (p < 0.05) levels of iNOS at 4 and 6 h compared to 0-h samples. Increases in IL-1alpha and iNOS expression were also observed in the skin immunohistochemically. Nitrite concentrations in skin samples were measured to estimate nitric oxide production. Although nitrite concentrations in the skin increased approximately 6-27% above the 0-h samples over the observed time period, no significant changes in nitrite levels were detected. Pathological changes in the skin following JP-8 exposure were evaluated histologically. Increased numbers of granulocytes were observed infiltrating the skin at 2 h and were more prominent by 6 h. These data show that a 1-h exposure to JP-8 results in a local inflammatory response, which can be detected by changes in molecular and histological parameters.

In vitro toxicities of experimental jet fuel system ice-inhibiting agents.

One research emphasis within the Department of Defense has been to seek the replacement of operational compounds with alternatives that pose less potential risk to human and ecological systems. Alternatives to glycol ethers, such as diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel system ice-inhibiting agents (FSIIs). This group of chemicals includes three derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M-27). In addition, M-DE was evaluated as a reference compound. Our approach was to implement an in vitro test battery based on primary rat hepatocyte cultures to perform initial toxicity evaluations. Hepatocytes were exposed to experimental chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity, glutathione level, and rate of protein synthesis as indicators of toxicity. Of the compounds tested, M-1, especially at the 10-mM dose, appeared to be more potent than the other chemicals, as measured by these toxicity assays. M-DE, the current FSII, elicited little response in the toxicity assays. Although some variations in toxicity were observed at the 10-mM dose, the in vitro toxicities of the chemicals tested (except for M-1) were not considerably greater than that of M-DE.

Effects of magnesium orotate on exercise tolerance in patients with coronary heart disease.

In a pilot study at 14 patients with coronary heart disease (CHD) and left-ventricular dysfunction (left ventricular enddiastolic volume [LVEDV] > or = 100 ml), who actively participated in an ambulatory cardiac sports group, left ventricular endsystolic volume (LVESV), LVEDV and duration of exercise were analyzed by echocardiographic and ergometric tests. An initial workup was followed by a 4 week double blind treatment phase, in which magnesium orotate 3 x 1 g or placebo was given additionally to medication taken prior to the study. At the end of this phase a concluding workup was performed. Magnesium orotate decreased significantly (p = 0.016) LVESV, increased significantly (p = 0.035) EF, decreased in tendency (p = 0.054) LVEDV and increased significantly (p = 0.011) exercise duration. The study gives references to favourable effects of oral magnesium orotate to left ventricular function and exercise tolerance in patients with CHD.

Selective transmission of variant genomes from mother to infant in neonatal fulminant hepatitis B.

Hepatitis B virus (HBV) nucleotide sequences isolated from mother/child pairs were analyzed in three cases of neonatal fulminant hepatitis B (FHB). Heterogeneous HBV sequences consistent with both adw2 and ayw subtype were found in all three mothers. In one case, in which the child survived, both subtypes were transmitted. By contrast, only the ayw subtype was present in the two other children with a fatal course of FHB. In one fatal case, studied in greater detail, multiple HBV variants (viral quasi-species) were identified in both mother and child. A direct sequence comparison showed that only a subfraction of the virus pool from the mother was transmitted and that multiple new mutations emerged in the child. These data suggest that a minor HBV subpopulation from the mother may prevail as the dominant species in the child and that neonatal FHB is associated with the selection of mutant strains.

Intron loss from the NADH dehydrogenase subunit 4 gene of lettuce mitochondrial DNA: evidence for homologous recombination of a cDNA intermediate.

The mitochondrial gene coding for subunit 4 of the NADH dehydrogenase complex I (nad4) has been isolated and characterized from lettuce, Lactuca sativa. Analysis of nad4 genes in a number of plants by Southern hybridization had previously suggested that the intron content varied between species. Characterization of the lettuce gene confirms this observation. Lettuce nad4 contains two exons and one group IIA intron, whereas previously sequenced nad4 genes from turnip and wheat contain three group IIA introns. Northern analysis identified a transcript of 1600 nucleotides, which represents the mature nad4 mRNA and a primary transcript of 3200 nucleotides. Sequence analysis of lettuce and turnip nad4 cDNAs was used to confirm the intron/exon border sequences and to examine RNA editing patterns. Editing is observed at the 5' and 3' ends of the lettuce transcript, but is absent from sequences that correspond to exons two, three and the 5' end of exon four in turnip and wheat. In contrast, turnip transcripts are highly edited in this region, suggesting that homologous recombination of an edited and spliced cDNA intermediate was involved in the loss of introns two and three from an ancestral lettuce nad4 gene.

The effect of a taurine-containing drink on performance in 10 endurance-athletes.

To determine the effect of a taurine-enriched drink "Red Bull" on performance, 10 endurance-athletes performed three trials. After 60 min. cycling at approximately 70% VO2 max, the subjects pedalled to exhaustion on a cycle ergometer. During each exercise, the subjects received 500 ml of a test-drink after 30 min. submaximal cycling: "Red Bull" without taurine, without glucuronolacton (U1), "Red Bull" without taurine, without glucuronolacton, without caffeine (U2) and "Red Bull" original drink containing taurine, glucuronolacton and caffeine (U3).The heart rate level was significantly lower in U3 (p = 0,0031) 15 min. after application. The plasma catecholamines increased slightly from begin of exercise to 15 min. after application of the drinks in all trials but remained on a significantly lower level in U3 (epinephrine (p = 0,0011) and norepinephrine (p = 0,0003). Endurance time was significantly longer with "Red Bull" original in U3 (p = 0,015). The results of this study show a positive effect of a taurine-containing drink on hormonal responses which leads to a higher performance.

Sensitivity and specificity of nuclear phase analysis versus ejection fraction in coronary artery disease.

Phase standard deviation (SD) and skew characteristics of the first Fourier harmonic of equilibrium radionuclide volume curves were examined and compared during rest and during supine bicycle exercise with ejection fraction (EF) changes and the development of ischemia in 17 control subjects and in 2 groups of patients (n = 57) with coronary artery disease (CAD). Group I comprised 37 patients with CAD; IA was a subgroup of 20 patients with previous myocardial infarction (MI) and IB a subgroup of 17 patients with CAD without MI (all with coronary stenosis greater than 75% diameter narrowing). Group II comprised 20 patients with CAD who had undergone coronary bypass surgery. In the Group I subjects, phase SD was the most sensitive indicator of CAD at rest (Group I, 56%; Group IA, 70%, and Group IB, 29%), and the EF was the most sensitive indicator at submaximal (Group I, 78%; Group IA, 86%, and Group IB, 64%) and maximal exercise (Group I, 70%; Group IA, 93%, and Group IB, 53%). When phase SD and skewness were combined with EF changes, little increase in sensitivity occurred in Group I (rest 61%, submaximal exercise 88% and maximal exercise 76%). The results from Group II subgroups were qualitatively similar to those observed with Group I subgroups. These data reveal a marginally improved sensitivity for detection of CAD during supine bicycle radionuclide ventriculography when phase measurements were added to changes in global EF values.