How to create ball lightning

Procedures are given on how to produce ball lightning. Necessary equipment includes a transformer of 150,000 watts capable of providing approximately 10,000 amperes at 15 volts, 60 cycles; thick one inch cables of stranded wire leading into a 3 by 4 by 1 foot plastic tank; a quarter inch thick 4 by 6 inch aluminum plate to be used as one of the discharge electrodes; and another electrode of heavy copper wire with the insulation stripped back 6 inches

Population toxicokinetics of ethylene - Calibration and preceding investigations

A basic step in the risk assessment of potential carcinogens is the determination of toxicokinetic parameters. The present approach is part of a strategy to determine the processes of uptake, elimination, and metabolism of the gas ethylene, an important industrial chemical, which is classified in category 3 of carcinogenic substances in the German list of MAK- and BAT-values. This paper deals with the calibration, which is indispensable to determine the decline of atmospheric concentrations of ethylene within a broad range of initial concentrations applied in an inhalation experiment

The influence of glutathione S­-transferases M1 and M3 on the development of bladder cancer

Problem: Cigarette smoking is the most important risk factor of transitional cell carcinoma of the urinary bladder. The effect of the glutathione S­transferases M1 (GSTM1) and M3 (GSTM3) on the influence of this risk factor was investigated. Methods: A total of 293 bladder cancer patients from Dortmund and Wittenberg as well as 176 surgical patients without any malignancy from Dortmund were genotyped for GSTM1 und GSTM3 according to standard PCR/RFLP methods. Smoking habits were also qualified by a standardized interview. Results: The percentage of GSTM1 negative cases was 63 % in the entire bladder cancer patient group compared to 50 % in the control group. GSTM3*A/*A genotype was 76 % in the entire group of bladder cancer cases and 74 % in controls. Smokers and ex­smokers were overrepresented in the bladder cancer patient group. A significant association between smoking status and GSTM1 or GSTM3 genotype could not be revealed. Conclusion: The elevated percentage of GSTM1 negative bladder cancer cases shows the important effect of this polymorphic enzyme on the development of bladder cancer. In contrast to some other studies, an influence of GSTM1 on the risk due to cigarette smoking could not be observed

Biomarkers in drug hypersensitivity

Biomarkers, especially those based on pharmacogenomics testing, have proved to be extremely useful for type A adverse drug reactions. Clinical practice guidelines based on biomarker testing are presently being developed and updated for type A adverse drug reactions. In contrast, little attention has been paid to the potential use of biomarkers in type B adverse reactions, characterized by the occurrence of reactions not directly related to the pharmacological properties of the drug. Drug-induced hypersensitivity belongs to those type B reactions. Drug-induced hypersensitivity reactions involve complex mechanisms that include, among others, the metabolic activation and haptenization of drug metabolites. Hence, factors that influence the pharmacokinetics of drug and metabolites may contribute to the development of some drug-induced hypersensitivity reactions. This implies that processes such as ADME (absorption, distribution, metabolism and excretion) that are typically involved in type A adverse drug reactions, may have a role in hypersensitivity reactions too. In addition to metabolic activation, several signal transduction pathways participate and modulate the development and the clinical presentation of drug hypersensitivity. The diverse mechanisms underlying such drug-hypersensitivity reactions lead to four major groups of reactions according to the Gell and Coombs classification: immediate, cytotoxic, immune complex and delayed. The enormous complexity of drug-hypersensitivity reactions is a consequence of the variety of mechanisms involved, which may be related, among others, to drug metabolism, generation of antigenic signals, stimulation and maturation of dendritic cells, presentation of haptens and mechanisms of cytotoxicity. In addition, a plethora of possible clinical presentations exists, including urticaria, angioedema, anaphylaxis, cytopenias, nephritis, serum sickness, vasculitis, contact dermatitis, drug rash, eosinophilia and systemic symptoms, Stevens–Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. The rapid progress in the field in recent years indicates that the combination of several disciplines is essential to understand the mechanisms involved in this particular, and not completely understood, type of adverse drug reactions. The objective of this Research Topic is to present insights obtained from both basic and clinical scientists, which may include studies related to the identification, validation, refinement and clinical implementation of biomarkers for drug-induced hypersensitivity. The Topic aims to include recent findings related, but not limited to, potential phenomic, genomic, proteomic, metabolomic and signal transduction biomarkers. These biomarkers could eventually be used in clinical practice and/or these might contribute, as a proof of concept, to our understanding of the complex events leading to drug hypersensitivity reactions. In addition the Topic will cover recent developments and methodological advances in the diagnosis, prevention and therapeutic management of drug-induced hypersensitivity

Genetic determinants of steatosis and fibrosis progression in paediatric non‐alcoholic fatty liver disease

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents today. In comparison with adult disease, paediatric NAFLD may show a periportal localization, which is associated with advanced fibrosis. This study aimed to assess the role of genetic risk variants for histological disease pattern and severity in childhood NAFLD. METHODS: We studied 14 single nucleotide polymorphisms (SNP) in a cohort of 70 adolescents with biopsy-proven NAFLD. Genotype was compared to an adult control cohort (n = 200) and analysed in relation to histological disease severity and liver tissue proteomics. RESULTS: Three of the 14 SNPs were significantly associated with paediatric NAFLD after FDR adjustment, rs738409 (PNPLA3, P = 2.80 × 10-06 ), rs1044498 (ENPP1, P = 0.0091) and rs780094 (GCKR, P = 0.0281). The severity of steatosis was critically associated with rs738409 (OR=3.25; 95% CI: 1.72-6.52, FDR-adjusted P = 0.0070). The strongest variants associated with severity of fibrosis were rs1260326, rs780094 (both GCKR) and rs659366 (UCP2). PNPLA3 was associated with a portal pattern of steatosis, inflammation and fibrosis. Proteome profiling revealed decreasing levels of GCKR protein with increasing carriage of the rs1260326/rs780094 minor alleles and downregulation of the retinol pathway in rs738409 G/G carriers. Computational metabolic modelling highlighted functional relevance of PNPLA3, GCKR and UCP2 for NAFLD development. CONCLUSIONS: This study provides evidence for the role of PNPLA3 as a determinant of portal NAFLD localization and severity of portal fibrosis in children and adolescents, the risk variant being associated with an impaired hepatic retinol metabolism

Biomarker Testing to Estimate Under-Reported Heavy Alcohol Consumption by Persons with HIV Initiating ART in Uganda

Alcohol affects the transmission and treatment of HIV, yet may be under-reported in resource-limited settings. We compared self-reported alcohol consumption with levels of plasma carbohydrate-deficient transferrin (%CDT), a biomarker of heavy alcohol consumption, in persons initiating antiretroviral therapy in Uganda. Almost seven percent (6.7%) of persons reporting abstaining and 10% reporting consuming 1–40 drinks in the prior month tested positive for %CDT, and actual under-report may be higher due to low sensitivity of %CDT. These results suggest likely under-report in those reporting abstaining and current drinking. Improved identification of heavy alcohol consumption is needed for research and clinical purposes