Foramen ovale electrodes in the preoperative evaluation of temporal lobe epilepsy in children

Purpose:  Foramen ovale electrodes (FOEs) can localize the epileptogenic zone in adults with mesial temporal lobe epilepsy (TLE). Our aim was to investigate the feasibility and safety of using FOEs to investigate refractory TLE in children.
Methods:  Thirty-eight children with seizure semiology and video-EEG (electroencephalography) consistent with medically refractory TLE, and/or the presence of a lesion in the temporal lobe, had FOEs inserted. Complications occurring during the monitoring and up to 3 months after surgery and the long-term seizure outcome were registered.
Results:  Forty electrodes were placed in 38 patients. The mean age of the patients was 9.8 years (range 2.3–15.4 years). FOEs confirmed a unilateral mesial temporal lobe seizure onset in 14 patients, onset in both FOEs and lateral electrodes in two patients, and onset in the anterior temporal electrodes in only one patient. Six patients had seizures recorded but were not considered surgical candidates; four patients had no seizures recorded, and 11 patients were further investigated with depth electrodes. One patient (2.6%) developed a hematoma in the cheek, and in two patients the electrodes were extracranial but could still be used for recording. Twenty-eight children had a temporal resection; 25 were Engel class I at follow-up.
Discussion:  FOEs are safe to use in children and provide valuable information on the mesial temporal lobe structures in the preoperative investigation of pediatric TLE. Patient selection for FOE investigation is, however, essential for a conclusive result.     

Intra-specific variation in nitrate tolerance in tadpoles of the Natterjack toad

Anthropogenic sources of nitrogen that pollute bodies of water can have toxic and sub-lethal effects on amphibians. It has been hypothesized that such exposure may promote local adaptation, that is, selection for higher tolerance in individuals in populations exposed to pollutants. We tested this hypothesis with respect to the Natterjack toad (Bufo calamita Laurenti, 1768), by comparing the nitrate dose response of tadpoles from eight populations (doses: 0, 50, 100, 500 and 1000 mg/l nitrate) from relatively unpolluted and intensively farmed environments. We evaluated the effect of nitrate exposure by observing the behavior (movements) of tadpoles exposed to different concentrations of nitrates. Exposure to high nitrate levels did not cause tadpole mortality in the populations used in our experiments; however, we did observe changes in activity for all populations, with these changes being either dose-related responses (decreased activity after exposure to 500 or 1000 mg/l), or more complex responses (increased activity when exposed to 50 or 100 mg/l nitrate, followed by decreased activity at higher concentrations). Natterjack toad tadpoles exhibited variable behavioural responses among the tested populations. Although these populations were selected on the basis of their potential agrochemical contamination, the observed variation in population tolerance was not related to the parameters used to estimate this contamination in these breeding sites. Possible explanations for this apparent lack of local adaptation in B. calamita tadpoles include inadequate estimates of the toads’ actual nitrate exposure in the field, and the biological characteristics of B. calamita, which may limit the effects of exposure or favor phenotypic plasticity.     

Compared ability of garlic (Allium sativum) extract or α-tocopherol + magnesium association to reduce metabolic disorders and oxidative stress in diabetic rats

Since some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the protective effects of (1) a garlic (Allium sativum) aqueous extract or (2) a combination of α-tocopherol and magnesium were investigated comparatively in alloxan-diabetic rats. Garlic extract (1 mL of extract corresponding to 300 mg fresh garlic/kg) or α-tocopherol (100 mg/kg) + MgCl(2) (200 mg/kg body weight) were i.p. injected to rats, once a day for 4 weeks. Lipid peroxidation levels and the activities of superoxide-dismutase, catalase and glutathione peroxidase were then measured in liver and pancreas. Under our experimental conditions, garlic extract or α-tocopherol + Mg were found to (1) significantly reduce the plasma levels of glucose, total cholesterol and triglyceride and (2) lactate dehydrogenase, alkaline phosphatase and transaminase activities in blood of diabetic animals. In addition, treatment with garlic extract or α-tocopherol + magnesium appeared to exert an antioxidative activity demonstrated (1) by the increase of catalase, superoxide-dismutase and glutathione-peroxidase activities in liver and pancreas, and (2) a lowering of lipid peroxidation level in these organs. In conclusion, both garlic extract and α-tocopherol + magnesium association were found to alleviate diabetes-associated metabolic disorders and oxidative stress in rats.     

Infection with versus Exposure to Taenia solium: What Do Serological Test Results Tell Us?

Taenia solium cysticercosis is an endemic zoonosis in many developing countries. Serological tests are the most appropriate diagnostic tools to understand the transmission dynamics of the parasite, but the performances of these methods in such a setting are not known. A south Ecuadorian human population living in an endemic area was tested using three common serological tests. Because none of them is a gold standard, a Bayesian Latent Class analysis was used to estimate the test characteristics. Two definitions of a case were considered to differentiate between prevalence of current infection and prior exposure to the parasite. Differences between the performances of the same test in function of the definition of a case were observed. This study shows that test results and prior information should be interpreted carefully in a Bayesian analysis framework, particularly when the latter is based on clinical studies.     

Neurobehavioral effect of chronic and bolus doses of methylmercury following prenatal exposure in C57BL/6 weanling mice

Several studies with animals have shown that even low and medium prenatal and postnatal exposure to methylmercury (MeHg) can result in locomotor, motor coordination and learning deficits. However, some behavioural effects of MeHg remain controversial and the methods to model human MeHg exposure in animal still remain to be optimized. We investigated the neurobehavioral effects of two different patterns of MeHg exposure. MeHg was given mixed in palatable food that mice readily ate. For the first pattern (chronic group), C57BL/6 mice dams were given 1.4 μg/g body weight (BW)/day (n = 20) throughout gestation mixed in palatable food. For the second pattern (bolus) dams were given 6.0 μg/g BW/day mixed in palatable food on gestation day 12 and 16 together with a lower chronic dose of 0.85 μg/g BW/day mixed in palatable food on all remaining gestation days (n = 20). Day 12 and 16 were chosen because neuron proliferation and the start of migration for many brain regions occur during that period. Behavioural testing on weanling animals started at 8 weeks. Both the chronic and bolus groups showed an impairment of working memory and visual spatial ability in the radial arm maze task. Other tests did not provide clear evidence that methylmercury exposure had significant adverse effects on locomotor activity, motor coordination or emotional reactivity. However, the chronic groups had a tendency for lower performance in most tests including activity in Skinner box and open field trials, as well as a higher number of anxiety-like behaviors. Chronic exposure to lower levels of MeHg combined to acute exposure with high levels of a few days during gestation appears to be less damaging than chronic exposure to slightly higher levels without acute MeHg exposure even though, equal amounts were administered during gestation. Possibly, as indicated by preliminary data, the relatively larger impact of chronic administration of a higher daily dose could be the consequence of a higher brain MeHg burden in pups compared to brain MeHg levels in the pups from dams receiving a smaller daily dose with 2 large doses on gestation day 12 and 16. Alternatively, bolus MeHg could have had a larger impact if administered on different gestation days when some neural development processes are more sensitive to MeHg.     

Developing a model of recovery in mental health

Background

Vast quantities of electronic data are collected about patients and service users as they pass through health service and other public sector organisations, and these data present enormous potential for research and policy evaluation. The Health Information Research Unit (HIRU) aims to realise the potential of electronically-held, person-based, routinely-collected data to conduct and support health-related studies. However, there are considerable challenges that must be addressed before such data can be used for these purposes, to ensure compliance with the legislation and guidelines generally known as Information Governance.

Methods

A set of objectives was identified to address the challenges and establish the Secure Anonymised Information Linkage (SAIL) system in accordance with Information Governance. These were to: 1) ensure data transportation is secure; 2) operate a reliable record matching technique to enable accurate record linkage across datasets; 3) anonymise and encrypt the data to prevent re-identification of individuals; 4) apply measures to address disclosure risk in data views created for researchers; 5) ensure data access is controlled and authorised; 6) establish methods for scrutinising proposals for data utilisation and approving output; and 7) gain external verification of compliance with Information Governance.

Results

The SAIL databank has been established and it operates on a DB2 platform (Data Warehouse Edition on AIX) running on an IBM 'P' series Supercomputer: Blue-C. The findings of an independent internal audit were favourable and concluded that the systems in place provide adequate assurance of compliance with Information Governance. This expanding databank already holds over 500 million anonymised and encrypted individual-level records from a range of sources relevant to health and well-being. This includes national datasets covering the whole of Wales (approximately 3 million population) and local provider-level datasets, with further growth in progress. The utility of the databank is demonstrated by increasing engagement in high quality research studies.

Conclusion

Through the pragmatic approach that has been adopted, we have been able to address the key challenges in establishing a national databank of anonymised person-based records, so that the data are available for research and evaluation whilst meeting the requirements of Information Governance.     

Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets

Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to investigate the effects of IL-7 therapy on lymphocytes in vivo. rhIL-7 induced in vivo T cell cycling, bcl-2 up-regulation, and a sustained increase in peripheral blood CD4(+) and CD8(+) T cells. This T cell expansion caused a significant broadening of circulating T cell receptor (TCR) repertoire diversity independent of the subjects' age as naive T cells, including recent thymic emigrants (RTEs), expanded preferentially, whereas the proportions of regulatory T (T reg) cells and senescent CD8(+) effectors diminished. The resulting composition of the circulating T cell pool more closely resembled that seen earlier in life. This profile, distinctive among cytokines under clinical development, suggests that rhIL-7 therapy could enhance and broaden immune responses, particularly in individuals with limited naive T cells and diminished TCR repertoire diversity, as occurs after physiological (age), pathological (human immunodeficiency virus), or iatrogenic (chemotherapy) lymphocyte depletion.