Sodium channel alpha 1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms

Background: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS(+)). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS(+) in a significant proportion of patients with SMEI Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. Method: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. Results: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. Conclusions: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS(+) could interact with other loci to cause SMEI in cases with a family history of GEFS(+). This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.

Towards a History didactics definition

This paper aims to define history didactics along the lines of the current German literature, which conceives it to be closer to history than to education. Associated to the word Geschichtsdidaktik, this definition is opposed to the concepts of history didactics as the art of teaching - Lehrkunst - history or as a collection of methods used both in the teaching of history and in the teaching of other school subjects - Unterrichtsmethoden. In opposition to these two definitions, this paper discusses German, French and Brazilian literatures to propose a conception of history didactics as a subarea of history, once it does not encompass only history teaching, but all history elaborations without a scientific form - nicht- wissenschaftsformigen Geschichtsverarbeitungen.

History of vegetation and habitat change in the Austral-Asian region

Over 1000 marine and terrestrial pollen diagrams and Some hundreds of vertebrate faunal sequences have been studied in the Austral-Asian region bisected by the PEPII transect, from the Russian arctic extending south through east Asia, Indochina, southern Asia, insular Southeast Asia (Sunda), Melanesia, Australasia (Sahul) and the western south Pacific. The majority of these records are Holocene but sufficient data exist to allow the reconstruction of the changing biomes over at least the past 200,000 years. The PEPII transect is free of the effects of large northern ice caps yet exhibits vegetational change in glacial cycles of a similar scale to North America. Major processes that can be discerned are the response of tropical forests in both lowlands and uplands to glacial cycles, the expansion of humid vegetation at the Pleistocene-Holocene transition and the change in faunal and vegetational controls as humans occupy the region. There is evidence for major changes in the intensity of monsoon and El Nino-Southern oscillation variability both on glacial-interglacial and longer time scales with much of the region experiencing a long-term trend towards more variable and/or drier climatic conditions. Temperature variation is most marked in high latitudes and high altitudes with precipitation providing the major climate control in lower latitude, lowland areas. At least some boundary shifts may be the response of vegetation to changing CO2 levels in the atmosphere. Numerous questions of detail remain, however, and current resolution is too coarse to examine the degree of synchroneity of millennial scale change along the transect. (C) 2003 Elsevier Ltd and INQUA. All rights reserved.

The Development of Science Education Research in Brazil and Contributions from the History and Philosophy of Science

Over the last 50 years a new research area, science education research, has arisen and undergone singular development worldwide. In the specific case of Brazil, research in science education first appeared systematically 40 years ago, as a consequence of an overall renovation in the field of science education. This evolution was also related to the political events taking place in the country. We will use the theoretical work of Rene Kaes on the development of groups and institutions as a basis for our discussion of the most important aspects that have helped the area of science education research develop into an institution and kept it operating as such. The growth of this area of research can be divided into three phases: The first was related to its beginning and early configurations; the second consisted of a process of consolidation of this institution; and the third consists of more recent developments, characterised by a multiplicity of research lines and corresponding challenges to be faced. In particular, we will analyse the special contributions to this study gleaned from the field known as the history and philosophy of science.

ICRAM (the International Campaign to Revitalise Academic Medicine): Agenda setting

Following die launch by the BMJ and others of the campaign to promote academic medicine, a working party of 20 medical academics from all over the world was convened to develop a plan of action.

Evolutionary History of Arabidopsis thaliana Aminoacyl-tRNA Synthetase Dual-Targeted Proteins

Aminoacyl-transfer RNA (tRNA) synthetases (aaRS) are key players in translation and act early in protein synthesis by mediating the attachment of amino acids to their cognate tRNA molecules. In plants, protein synthesis may occur in three subcellular compartments (cytosol, mitochondria, and chloroplasts), which requires multiple versions of the protein to be correctly delivered to its proper destination. The organellar aaRS are nuclear encoded and equipped with targeting information at the N-terminal sequence, which enables them to be specifically translocated to their final location. Most of the aaRS families present organellar proteins that are dual targeted to mitochondria and chloroplasts. Here, we examine the dual targeting behavior of aaRS from an evolutionary perspective. Our results show that Arabidopsis thaliana aaRS sequences are a result of a horizontal gene transfer event from bacteria. However, there is no evident bias indicating one single ancestor (Cyanobacteria or Proteobacteria). The dual-targeted aaRS phylogenetic relationship was characterized into two different categories (paralogs and homologs) depending on the state recovered for both dual-targeted and cytosolic proteins. Taken together, our results suggest that the dual-targeted condition is a gain-of-function derived from gene duplication. Selection may have maintained the original function in at least one of the copies as the additional copies diverged.

A history of agricultural production at Neolithic Catalhoyuk East, Turkey

A history of agricultural production is proposed for Neolithic Catalhoyuk East, central Turkey, using archaeobotanical, environmental, population and settlement studies. In the aceramic early phase of site occupation, intensive strategies developed as changes in population and environment caused stress on food supplies produced within a limited territory. Food exchange may have been part of the social means by which Catalhoyuk and nearby contemporary settlements amalgamated into the single site of the main occupation phase. Population change, inherited territories and continuing environmental impact led to the development of an extensive system of agriculture using widely dispersed dry soils, with an intensive regime applied to nearby alluvial soils. Social tensions caused by the evolution of this system contributed to the fissioning of the site by the Chalcolithic.

History teaching today: wanderings, gains and losses

This article analyzes traditions of debate about the teaching of history in Brazil since the 1964-1984 dictatorship. It discusses the changes, continuities, achievements and losses in the history of the discipline. It emphasizes the importance of school culture, the necessary continuity of the school as an institution and dialogue with non-school forms of education.

ACHIEVEMENTS AND CHALLENGES OF ISPRM

This paper describes the history of the International Society of Physical and Rehabilitation Medicine (ISPRM) Past achievements. and current challenges are outlined ISPRM has been successful In setting up a central office. attracting individual and national members,. holding International congresses, and establishing relations with the Journal of Rehabilitation Medicine (JRM) as the organization`s official journal ISPRM is currently; In official relations with the World Health Organization (WHO) and collaborates closely, with WHO`s Disability and Rehabilitation team ISPRM, however also faces challenges with regard to its growth and the realization of its goals These Include boundaries of voluntary leadership. limited economic resources, the need for enhancing the central office. variations in membership. limits of the current congress bidding system and structure, relations with regional societies, and the need to further develop policies within the field of Physical and Rehabilitation Medicine (PRM) and In relation to WHO and the United Nations system is concluded that ISPRM must evolve from an organization, of which the main activities ay-e to hold a biennial congress hosted by a member nation and to provide input to WHO on request. Into a professional non-governmental organization (NGO) ISPRA should embark on assuming, a leadership role at the further development of PRM within the broader area of human functioning and rehabilitation

Cardiac MRI for Detection of Unrecognized Myocardial Infarction in Patients With End-Stage Renal Disease: Comparison With ECG and Scintigraphy

OBJECTIVE. The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI. SUBJECTS AND METHODS. We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI. RESULTS. Fifty-six patients (78%) were men ( mean age, 56.2 +/- 9.4 years) and 16 (22%) were women ( mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% ( not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis. CONCLUSION. Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.

Exploring the use of Viagra in place of animal and plant potency products in traditional Chinese medicine

Recently, conservationists have debated whether consumers of animal and plant potency products used to treat erectile dysfunction (ED) in traditional Chinese medicine (TCM) might be switching to Viagra, consequently consuming fewer of these animals and plants. To address this question, a survey examined the medical decisions of male consumers of TCM in Hong Kong who were over the age of 50. As predicted, these consumers reported selectively switching to Western medicines to treat ED, but not to treat other health ailments. These findings provide support for the possibility that Viagra may have conservation benefits for certain species.

Prevalence and Risk of Asthma Symptoms Among Firefighters in Sao Paulo, Brazil: A Population-Based Study

The firefighters are at increased risk of respiratory disease as a result of exposure to smoke and dust. The aim of this study was to determine the prevalence and risk associated with respiratory symptoms among city firefighters in Sao Paulo, Brazil. Methods A cross-sectional study utilizing the European Community Respiratory Health Survey (ECRHS) questionnaire was administered to firefighters and police officers, in order to evaluate their respiratory symptoms. Results Complete respiraton, data were obtained from 1,235 firefighters and 1,839 police officers. Among the firefighters, there were 55.5% never-smokers, 22.4% current smokers and 18.2% former smokers (P < 0.05). Among the police officers, there were 63.4%, 18.6%, and 9.6% who were never-smokers, current smokers and former smokers (P < 0.05), respectively. Compared to police, firefighters experienced an increase in wheezing [OR = 1.63 (95% CI: 1.43-1.87)], wheezing with breathlessness [OR = 1.34 (95% CI: 1.10-1.64)], wheezing without a cold [OR = 1.60 (95% CI: 1.32-1.95)], waking with tightness in the chest [OR = 1.20 (95% CI: 1.02-1.42)], and rhinitis [OR = 1.12 (95% CI: 1.03-1.22)]. The prevalence of adult-onset asthma in never-smokers was 9.3% and 6.7% for firefighters and police officers [OR = 1.23 (95% CI: 1.01-1.56)]. All independent association was observed between years employed, smoking, history of rhinitis, and work as a firefighter and respiratory, and nasal symptoms. We observed a high prevalence of asthma-like symptoms in firefighters who presented respiratory symptoms beginning immediately after firefighting. Conclusion These results suggest that the prevalence of respiratory symptoms and asthma in firefighters is higher than those in police officers. Work-as a firefighter, rhinitis and vears employed were risk factors for respiratory,symptoms of asthma. Am. J. Ind. Med. 52:261 269, 2009. (C) 2008 Wiley-Liss, Inc.

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50). Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. Funding Bristol-Myers Squibb.