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Guangzhou, China

Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is one of the more common forms of chronic epilepsy. Its aetiology is unknown, though an early developmental insult is thought by some to be an important trigger. There is not a strong genetic predisposition; gene-environment interactions are more significant considerations. Environmental risk factors for TLE-HS are under-researched. Domoic acid (DA) is an environmental neurotoxin of algal origin that can contaminate marine food webs. DA can cross the placenta, is significantly more toxic to the developing brain compared to the adult brain, and has affected humans and marine wildlife through mass poisonings. DA coincidentally has a decades-long history of use as a chemical model of temporal lobe epilepsy, along with its close structural analogue kainic acid (also of algal origin). The principal hypothesis presented here is that dietary exposure to doses of DA that are sub-clinical in pregnant women may be sufficient to damage the foetal hippocampus and initiate epileptogenesis. The hypothesis could be tested both experimentally by in vivo proof-of-concept animal studies that expand on current knowledge of prenatal susceptibility to DA neurotoxicity, and by epidemiological investigations directed towards dietary exposure to marine food products. If only a small proportion of the attributable risk for TLE-HS is found to be due to gestational exposure to DA, the public health implications would still be of great significance, as this would represent a potentially preventable exposure.Other potent neurotoxins are produced by marine microalgae and freshwater cyanobacteria. These structurally and mechanistically diverse toxins can also contaminate water supplies, seafood and shellfish. Several operate by modulating ion channels, so may also be of interest to epilepsy researchers.DA is also the subject of preliminary scrutiny in strandings involving odontocete cetaceans. The implications of such work are discussed here. © 2009. Source

Kiri V.A.,University of Limerick | Kiri V.A.,39 Health
Drug Safety | Year: 2012

Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of drugs but not necessarily so for drug safety where inadequate power to detect either multiple or rare adverse events is a major handicap. Furthermore, the conditions under which drugs are approved for market use are often different from the settings in actual use. Indeed, with their control mechanisms, trials are by design largely inadequate for the identification of potential safety signals, especially of the rare type, hence the value of postmarketing surveillance and risk management plan-based activities.Today, clinical trials constitute only a part of the research that goes into assessing the safety of drugs. Observational studies, where the investigators merely collect data on treatments received by patients and their health status in routine clinical practice are increasing in uptake because they reflect the real-life utility of drugs, despite the absence of random treatment assignment. Although such studies generally provide less compelling evidence than RCTs, they can be far more useful to drug safety assessment activities than generally acknowledged.An increasing number of post-authorization safety studies (PASS) within the European Medicines Agencys jurisdiction are of the observational type considered perhaps as more appropriate vehicles for exploring and documenting how products perform in the real world. A similar trend is emerging in the US following the FDA Amendments Act of 2007; since early 2010, an increasing number of post-approval commitments mandated by the FDA include observational studies. However, despite this pattern, not much is known about ongoing efforts to address many of the recognized inadequacies associated with existing methodologies and practices currently adopted in observational PASS. This current opinion presents an overview of some of the main challenges we face in prospective observational PASS, mainly from practical experience, and proposes certain steps for improvement. © 2012 Springer International Publishing AG. All rights reserved. Source

Hershko C.,39 Health | Camaschella C.,Vita-Salute San Raffaele University
Blood | Year: 2014

Endoscopic gastrointestinal workup fails to establish the cause of iron deficiency anemia (IDA) inasubstantial proportion of patients. In patients referred for hemato-logic evaluation with unexplained or refractory IDA, screening for celiac disease, autoimmune gastritis, Helicobacter pylori, and hereditary forms of IDA is recommended. About 4% to 6% of patients with obscure refractory IDA have celiac disease, and autoimmune gastritis is encountered in 20% to 27% of patients. Stratification by age cohorts in autoimmune gastritis implies a disease presenting as IDA many years before the establishment of clinical cobalamin deficiency. Over 50% of patients with unexplained refractory IDA have active H pylori infection and, after excluding all other causes of IDA, 64% to 75% of such patients are permanently cured by H pylori eradication. In young patients with a history suggestive of hereditary iron deficiency with serum ferritin higher than expected for IDA, mutations involving iron trafficking and regulation should be considered. Recognition of the respective roles of H pylori, autoimmune gastritis, celiac disease, and genetic defects in the pathogenesis of iron deficiency should have a strong impact on the current diagnostic workup and management of unexplained, or refractory, IDA. © 2014 by The American Society of Hematology. Source

Varnik P.,39 Health | Varnik P.,Tallinn University
International Journal of Environmental Research and Public Health | Year: 2012

Introduction: Over the past 20 years the WHO has considerably improved world mortality data. There are still shortcomings but more countries now report data and world-wide estimates are regularly made. Methods: Data about mortality have been retrieved from the WHO world database. Worldwide injury mortality estimates for 2008 as well as trends of the suicide rate from 1950 to 2009 were analysed. Results: Suicides in the world amount to 782 thousand in 2008 according to the WHO estimate, which is 1.4% of total mortality and 15% of injury mortality. The suicide rate for the world as a whole is estimated at 11.6 per 100,000 inhabitants. The male-female rate ratio of suicide is estimated to be highest in the European Region (4.0) and the lowest in the Eastern Mediterranean region (1.1). Among males the highest suicide rate in the 15-29 age group is in the SE Asian region, in the 45-59 age group in European males and for ages above 60 in the Western Pacific region. Females from SE Asia have a remarkably high suicide rate among 15-29-year-olds and from age 45 in the Western Pacific region. The leading country is currently Lithuania, with a suicide rate of 34.1 per 100,000 inhabitants. Also among males the suicide rate is the highest in Lithuania at 61.2. Among females South Korea with 22.1 is at the top of world suicide rates. Conclusions: During the past six decades, according to the WHO Japan, Hungary, and Lithuania have topped the list of world countries by suicide rate, but if the current trends continue South Korea will overtake all others in a few years. The heart of the problem of suicide mortality has shifted from Western Europe to Eastern Europe and now seems to be shifting to Asia. China and India are the biggest contributors to the absolute number of suicides in the world. © 2012 by the authors; licensee MDPI, Basel, Switzerland. Source

Wallace J.D.,39 Health
Health Physics | Year: 2012

Ion Chambers have a generally flat energy response with some deviations at very low (<100 keV) and very high (>2 MeV) energies. Some improvements in the low energy response can be achieved through use of high atomic number gases, such as argon and xenon, and higher chamber pressures. This work looks at the energy response of high pressure xenon-filled ion chambers using the MCNP Monte Carlo package to develop geometric models of a commercially available high pressure ion chamber (HPIC). The use of the F6 tally as an estimator of the energy deposited in a region of interest per unit mass, and the underlying assumptions associated with its use are described. The effect of gas composition, chamber gas pressure, chamber wall thickness, and chamber holder wall thicknesses on energy response are investigated and reported. The predicted energy response curve for the HPIC was found to be similar to that reported by other investigators. These investigations indicate that improvements to flatten the overall energy response of the HPIC down to 70 keV could be achieved through use of 3 mm-thick stainless steel walls for the ion chamber. © 2012 Health Physics Society. Source

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