p-Nitrophenol and glutathione response in medaka (Oryzias latipes) exposed to MX,a drinking water carcinogen

When chlorine is introduced into public drinking water for disinfection, it can react with organic compounds in surface waters to form toxic by-products such as 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX). We investigated the effect of exposure to MX on cytochrome P450 2E1 (CYP2E1)-like activity and total glutathione (GSH) in the liver of the small fish model, medaka (Oryzias latipes). The multi-site carcinogen methylazoxymethanol acetate (MAMAc) was the positive control compound. Both medaka liver microsome preparations and S-9 fractions catalyzed the hydroxylation of p-nitrophenol (PNP), suggesting CYP2E1-like activity in the medaka. Male medaka exposed for 96 h to the CYP2E1 inducers ethanol and acetone under fasted conditions showed significant increases in PNP-hydroxylation activity. Furthermore, total reduced hepatic GSH was reduced in fish fasted for 96 h, indicating that normal feeding is a factor in maintaining xenobiotic defenses. Exposure to MX and MAMAc induced significant increases in hepatic CYP2E1-like activity, however MX exposure did not alter hepatic GSH levels. These data strengthen the role of the medaka as a suitable species for examining cytochrome P450 and GSH detoxification processes and the role these systems play in chemical carcinogenesis.     

Cognitive impairments among older drivers: medical examination and driving test

The aim of this study was to gain insight in the prevalence of cognitive impairments among active older drivers and in driving performance of cognitively impaired ones. The study was implemented in the existing Dutch relicensing procedure for older drivers and consisted of three evaluation moments: a medical screening (for all subjects), a neuropsychological assessment and a test-drive (for candidates with cognitive impairments). In total, 2992 drivers were medically evaluated. In 4% of cases indications for impaired cognitive functioning were observed that could be evaluated and confirmed with neuropsychological tests. Eighty subjects performed an on-road test. Of these subjects, 57% were allowed to renew their driver's license, while in the remaining 43% no new licenses or restricted licenses were issued. During the test-drive, slow reactions and attention deficits were the most important causes for impaired fitness to drive.     

A genome-wide screening in Saccharomyces cerevisiae for genes that confer resistance to the anticancer agent cisplatin

Cisplatin is a potent DNA-damaging agent that has demonstrated anticancer activities against several tumors. However, manifestation of cellular resistance is a major obstacle in anticancer therapy that severely limits the curative potential of cisplatin. Therefore, understanding the molecular basis of cisplatin resistance could significantly improve the clinical efficacy of this anticancer agent. Here, we employed Saccharomyces cerevisiae as a model organism to study cisplatin resistance mechanisms and describe a one-step cisplatin selection to identify and characterize novel cisplatin resistance genes. Screening a multicopy yeast genomic library enabled us to isolate several yeast clones for which we could confirm that the cisplatin resistance phenotype was linked to the introduced fragment. In a first attempt, a number of open reading frames could be identified. Among these genes, PDE2 and ZDS2 were repeatedly identified as genes whose overexpression confers cellular resistance to cisplatin. PDE2, encoding cAMP-phosphodiesterase 2, is of particular interest because the overexpression of this yeast gene is known to induce cisplatin resistance in mammalian cells as well, providing proof of the principle of our experimental approach. In addition, the identification of PDE2 shows that our yeast screening system can directly be informative for drug resistance in mammalian cells.     

The Effects of Compensatory Scanning Training on Mobility in Patients with Homonymous Visual Field Defects: A Randomized Controlled Trial

IntroductionHomonymous visual field defects (HVFD) are a common consequence of postchiasmatic acquired brain injury and often lead to mobility-related difficulties. Different types of compensatory scanning training have been developed, aimed at decreasing consequences of the HVFD by changing visual scanning.AimThe aim of the present study is to examine the effects of a compensatory scanning training program using horizontal scanning on mobility-related activities and participation in daily life.MethodThe main interest of this study is to assess the effectiveness of training on mobility-related activities and participation in daily life. Visual scanning tests, such as dot counting and visual search, and control measures for visual functions and reading have been included as well. First, it is examined how performance on scanning and mobility-related measures is affected in patients with HVFD by comparing scores with scores of a healthy control group (n = 25). Second, the effect of training is assessed using an RCT design, in which performance of 26 patients before and after training is compared to performance of 23 patients in a waiting list control group.ResultsSelf-reported improvements after training were found, accompanied by improvements in detecting peripheral stimuli and avoiding obstacles during walking, especially in dual task situations in which a second task limits the attentional capacity available for compensatory scanning. Training only improved mobility-related activities in which detection of peripheral stimuli is important, while no improvement was found on tests that require other visual skills, such as reading, visual counting and visual search.ConclusionThis is the first RCT to evaluate the effects of a compensatory scanning training that is based on a systematic horizontal scanning rhythm. This training improved mobility-related activities. The results suggest that different types of compensatory scanning strategies are appropriate for different types of activities.

Trial Registration

ISRCTN Registry ISRCTN16833414     

Streptococcus suis Meningitis: A Systematic Review and Meta-analysis

Background

Streptococcus suis is the most common cause of meningitis in pork consuming and pig rearing countries in South-East Asia. We performed a systematic review of studies on S. suis meningitis to define the clinical characteristics, predisposing factors and outcome.

Methodology

Studies published between January 1, 1980 and August 1, 2015 were identified from main literature databases and reference lists. Studies were included if they were written in West-European languages and described at least 5 adult patients with S. suis meningitis in whom at least one clinical characteristic was described.

Findings

We identified 913 patients with S. suis meningitis included in 24 studies between 1980 and 2015. The mean age was 49 years and 581 of 711 patients were male (82%). Exposure to pigs or pork was present in 395 of 648 patients (61%) while other predisposing factors were less common. 514 of 528 patients presented with fever (97%), 429 of 451 with headache (95%), 462 of 496 with neck stiffness (93%) and 78 of 384 patients (20%) had a skin injury in the presence of pig/pork contact. The case fatality rate was 2.9% and hearing loss was a common sequel occurring in 259 of 489 patients (53%). Treatment included dexamethasone in 157 of 300 (52%) of patients and was associated with reduced hearing loss in S. suis meningitis patients included in a randomized controlled trial.

Conclusion

S. suis meningitis has a clear association with pig and pork contact. Mortality is low, but hearing loss occurs frequently. Dexamethasone was shown to reduce hearing loss.     

Serosurvey of Brucella spp. infection in the Kafue lechwe (Kobus leche kafuensis) of the Kafue flats in Zambia

One of the diseases of veterinary and public health importance affecting the Kafue lechwe (Kobus leche kafuensis) on the Kafue flats is brucellosis, for which only scant information is available. During the 2003 (October), 2004 (December), and 2008 (July-December) hunting seasons in the Kafue flats, we conducted a study to determine the seroprevalence of Brucella spp. in the Kafue lechwe and to evaluate serologic tests for detection of Brucella spp. antibodies in lechwe. The Rose Bengal Test (RBT), competitive enzyme-linked immunosorbent assay (cELISA), and fluorescence polarization assay (FPA) were used. A total of 121 Kafue lechwe were hunted for disease investigations in 2003, 2004, and 2008 in the Kafue Flat Game Management Area. Of these, 21.6%, (95% confidence interval [CI]: 14.2-29.1%) had detectable antibodies to Brucella spp. The Kafue lechwe in Lochnivar National Park had higher antibody results than those in Blue Lagoon National Park (odds ratio=3.0; 95% CI: 0.94-9.4). Infection levels were similar in females (21.6%) and males (21.7%). Results were similar among RBT, FPA, cELISA tests, suggesting that these could effectively be used in diagnosing brucellosis in the Kafue lechwe. Our study demonstrates the presence of Brucella infections in the Kafue lechwe in two national parks located in the Kafue flats and further highlights the suitability of serologic assays for testing the Kafue lechwe. Because the Kafue lechwe is the most hunted wildlife species in Zambia, hunters need to be informed of the public health risk of Brucella spp. infection.