Department of Internal Medicine, Section of Vascular Medicine, Diabetes and Endocrinology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Mesial temporal lobe epilepsy (MTLE) is one of the most common types of the intractable epilepsies and is most often associated with hippocampal sclerosis (HS), which is characterized by pronounced loss of hippocampal pyramidal neurons. microRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE and HS.
miRNA expression was quantified in hippocampal specimens from human patients using miRNA microarray and quantitative real-time polymerase chain reaction RT-PCR, and by RNA-seq on fetal brain specimens from domestic pigs. In situ hybridization was used to show the spatial distribution of miRNAs in the human hippocampus. The potential effect of miRNAs on targets genes was investigated using the dual luciferase reporter gene assay.
miRNA expression profiling showed that 25 miRNAs were up-regulated and 5 were down-regulated in hippocampus biopsies of MTLE/HS patients compared to controls. We showed that miR-204 and miR-218 were significantly down-regulated in MTLE and HS, and both were expressed in neurons in all subfields of normal hippocampus. Moreover, miR-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a direct target of miR-204.
miR-204 and miR-218 are developmentally regulated in the hippocampus and may contribute to the molecular mechanisms underlying the pathogenesis of MTLE and HS.
Ablation trumps meds for atrial fibrillation treatment. Catheter ablation provides better long-term relief from atrial fibrillation than medication, but surgical ablation is best, a second study concludes.
This selective report notes recent events relating to pregnancy termination in the U.S., France, England, Italy, East and West Germany, Norway, Sweden, and the Netherlands. Due to the Supreme Court decision in January 1973, abortion is now legal in the U.S. Although abortions is illegal in France, an estimated 400,000-1,000,000 clandestine abortions occur each year. Although abortions are legal in Britain, the ease with which they can be obtained varies regionally. As of March 1973, contraceptives are part of Britain's National Health Service. In Italy, a bill to legalize abortion has been introduced in Parliament, though there is little likelihood of its passing. In East Germany, abortion can be granted for medical or social reasons, while in West Germany, the governmental policies are more conservative, resulting in an abundance of illegal abortions performed by physicians. There is a trend toward easier abortion laws in Norway and Sweden. Little is happening in the Netherlands as far as liberalizing the abortion laws. Rather liberal grounds for pregnancy termination exist in China (though emphasis is on contraception), India, Russia, and Eastern Europe (with the exception of Romania). Abortion is frowned upon in Africa, Latin America, and the Middle East resulting in a large number of illegal abortions. It is concluded that there is liberalized abortion in communist bloc countries, there is trend toward liberalizing abortion in a large group of western countries, and tradition and religion are responsible for conservative abortion laws in a third group of countries.
The purpose of this study was to conduct a comparison, using qualitative analytic methodology, of perceptions concerning abortion among health care providers and administrators, along with politicians and anti-abortion activists (total n = 75) in Great Britain, Sweden, The Netherlands, and the United States. In none of these countries was there consensus about abortion prior to legalization, and, in all countries, public discussion continues to be present. In general, after legalization of abortion has no longer made it a volatile issue European countries have refocused their energy into providing family planning services, education, and more straightforward access to abortion compared with similar activities in the United States.
Currently, researchers have to apply separately to individual biobanks if they want to carry out studies that use samples and data from multiple biobanks. This article analyzes the access governance arrangements of the original five biobank members of the Biobank Standardisation and Harmonisation for Research Excellence in the European Union (BioSHaRE-EU) project in Finland, Germany, the Netherlands, Norway, and the United Kingdom to identify similarities and differences in policies and procedures, and consider the potential for internal policy "harmonization." Our analysis found differences in the range of researchers and organizations eligible to access biobanks; application processes; requirements for Research Ethics Committee approval; and terms of Material Transfer Agreements relating to ownership and commercialization. However, the main elements of access are the same across biobanks; access will be granted to bona fide researchers conducting research in the public interest, and all biobanks will consider the scientific merit of the proposed use and it's compatibility with the biobank's objectives. These findings suggest potential areas for harmonization across biobanks. This could be achieved through a single centralized application to a number of biobanks or a system of mutual recognition that places a presumption in favor of access to one biobank if already approved by another member of the same consortium. Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortia (BBMRI-ERIC), a European consortium of biobanks and bioresources with its own ethical, legal, and social implications (ELSI) common service, could provide a platform by developing guidelines for harmonized internal processes.
Two large prospective cohort studies of childhood epilepsy (Nova Scotia and the Netherlands) each developed a statistical model to predict long-term outcome. We sought to evaluate the accuracy of a prognostic model based on the two studies combined.
Analyses with classification tree models and stepwise logistic regression produced predictive models for the combined dataset and the two separate cohorts. The resulting models were then externally validated on the opposite cohort. Remission was defined as no longer receiving daily medication for any length of time at the end of follow-up.
The combined cohorts yielded 1,055 evaluable patients. At the end of follow-up (>or=5 years in >96%), 622 (59%) were in remission. By using the combined data, the classification tree model and the logistic regression model predicted the outcome correctly in approximately 70%. The classification tree model split the data on epilepsy type and age at first seizure. Predictors in the logistic regression model were: seizure number before treatment, age at first seizure, absence seizures, epilepsy types of symptomatic generalized and symptomatic partial, preexisting neurologic signs, intelligence, and the combination of febrile seizures and cryptogenic partial epilepsy. When the prediction models from each cohort were cross-validated on the opposite cohort, the outcome was predicted slightly less accurately than did the model from the combined data.
Based on currently available clinical and EEG variables, predicting the outcome of childhood epilepsy may be difficult and appears to be incorrect in about one of every three patients.
Quantitative analysis of threshold limit levels of UV-irradiation in the workroom environment established in USA, Netherlands and Russia was made. Comparison of its results with modern information about effective doses and action spectra of UV-radiation biological action allowed to reveal essential differences in the approach to rate setting and in some cases presence of internal contradictions and exceeding of threshold limit levels of UV irradiation above biologically effective values. The possibility of workroom UV standards utilisation for regulation of nature UV-radiation exposures was considered.
An ongoing outbreak of Cryptococcus gattii-caused infections, which emerged on Vancouver Island and the Pacific Northwest, has affected more than 200 of the islands' residents, of whom eight died. While C. gattii infections are rarely described in travelers, we report a case of cryptococcosis caused by C. gattii in a patient treated with high dose corticosteroids for systemic lupus erythematosus induced autoimmune hemolytic anemia. She acquired the disease during a visit to Vancouver Island one year before the onset of the symptoms. This indicates that C. gattii may cause a dormant infection that can be activated during treatment with corticosteroids.
