Visual word form processing deficits driven by severity of reading impairments in children with developmental dyslexia.

The visual word form area (VWFA) in the left ventral occipito-temporal (vOT) cortex is key to fluent reading in children and adults. Diminished VWFA activation during print processing tasks is a common finding in subjects with severe reading problems. Here, we report fMRI data from a multicentre study with 140 children in primary school (7.9-12.2 years; 55 children with dyslexia, 73 typical readers, 12 intermediate readers). All performed a semantic task on visually presented words and a matched control task on symbol strings. With this large group of children, including the entire spectrum from severely impaired to highly fluent readers, we aimed to clarify the association of reading fluency and left vOT activation during visual word processing. The results of this study confirm reduced word-sensitive activation within the left vOT in children with dyslexia. Interestingly, the association of reading skills and left vOT activation was especially strong and spatially extended in children with dyslexia. Thus, deficits in basic visual word form processing increase with the severity of reading disability but seem only weakly associated with fluency within the typical reading range suggesting a linear dependence of reading scores with VFWA activation only in the poorest readers.

Implementation of OIE international standards: challenges and opportunities for monitoring.

The World Organisation for Animal Health (OIE) is a major actor in international cooperation to improve animal health and welfare throughout the world. The OIE sets international standards to support Member Countries in their efforts to prevent and control animal diseases, strengthen Veterinary Services and Aquatic Animal Health Services, and facilitate safe international trade. Member Countries face many challenges in the implementation of OIE standards. Poor governance and a lack of resources and technical capacity are often major constraints. Trade concerns raised at the World Trade Organization (WTO) can also be a signal that countries are experiencing difficulties in implementing international standards. In May 2018, the World Assembly of OIE Delegates adopted a resolution recommending the establishment of an observatory to monitor the implementation of OIE standards. This monitoring mechanism will help the OIE to improve its international standard-setting process and identify the capacity-building needs of Member Countries. Monitoring implementation will be challenging as the OIE does not prescribe a specific procedure for implementing OIE standards. World Organisation for Animal Health Member Countries use a range of approaches to implement OIE standards, because of differences in animal health situations, legal frameworks and procedures, trade profiles, and acceptable levels of risk. Given this complexity, this article proposes a 'cross-over' approach to monitoring implementation that would require the collection of information from various trusted sources, such as the World Animal Health Information System (WAHIS), the OIE Performance of Veterinary Services (PVS) Pathway mission reports and the WTO Sanitary and Phytosanitary Information Management System database. This approach aims to document what is currently happening and to identify potential patterns in Member Country practices when implementing OIE standards.

L'Organisation mondiale de la santé animale (OIE) est un acteur majeur de la coopération internationale oeuvrant à l'amélioration de la santé et du bien-être animal dans le monde. L'OIE élabore des normes internationales visant à soutenir les efforts déployés par ses Membres pour prévenir et lutter contre les maladies animales, renforcer les Services vétérinaires et les Services chargés de la santé des animaux aquatiques, et faciliter un commerce international sûr. Les Membres rencontrent de nombreuses difficultés lors de la mise en oeuvre des normes de l'OIE. Une mauvaise gouvernance et l'insuffisance des ressources et des capacités techniques constituent souvent des contraintes majeures. Les préoccupations commerciales soulevées au sein de l'Organisation mondiale du commerce (OMC) sont également révélatrices des difficultés rencontrées par les pays pour mettre en oeuvre les normes internationales. En mai 2018, l'Assemblée mondiale des Délégués de l'OIE a adopté une résolution recommandant la création d'un observatoire destiné à assurer le suivi de la mise en oeuvre des normes de l'OIE. Grâce à ce mécanisme de suivi, l'OIE sera à même d'améliorer le processus d'élaboration de ses normes internationales et d'identifier les besoins de ses Membres en matière de renforcement des capacités. Le suivi de la mise en oeuvre ne sera pas une tâche facile, dans la mesure où l'OIE ne prescrit pas de procédure spécifique pour appliquer ses normes. Les Membres de l'OIE recourent à diverses approches pour mettre en oeuvre les normes de l'OIE, dictées par des différences dans les situations zoosanitaires, les cadres et procédures juridiques, les profils commerciaux et les niveaux de risque considérés comme acceptables. Face à une telle complexité, les auteurs proposent une méthode transversale de suivi de la mise en oeuvre, qui passe par la collecte d'informations auprès de diverses sources fiables telles que le Système mondial d'information sanitaire de l'OIE (WAHIS), les rapports de mission du Processus de l'OIE pour évaluer la Performance des Services vétérinaires (Processus PVS) et la base de données de l'OMC de gestion des renseignements sanitaires et phytosanitaires. Cette approche vise à documenter ce qui se fait actuellement et à identifier d'éventuelles tendances dans les pratiques des Membres en matière de mise en oeuvre des normes de l'OIE.

La Organización Mundial de Sanidad Animal (OIE) es uno de los actores principales de la cooperación internacional para mejorar la sanidad y el bienestar animales en todo el mundo. La OIE elabora normas internacionales destinadas a apoyar el esfuerzo de los Países Miembros por prevenir y combatir las enfermedades animales, fortalecer los Servicios Veterinarios y los Servicios de sanidad de los animales acuáticos y facilitar un comercio internacional seguro. Los Países Miembros afrontan numerosos desafíos a la hora de implementar las normas de la OIE. La insuficiencia de mecanismos de gobernanza y la falta de recursos y capacidad técnica constituyen a menudo obstáculos de gran calado. Las preocupaciones comerciales expresadas ante la Organización Mundial del Comercio (OMC) también pueden ser una señal de las dificultades que afrontan los países para implementar las normas internacionales. En mayo de 2018, la Asamblea Mundial de Delegados de la OIE aprobó una resolución en la que recomendaba la creación de un observatorio para el seguimiento de la implementación de las normas de la OIE. Este mecanismo ayudará a la OIE a mejorar su proceso de elaboración de normas internacionales y a identificar las necesidades de capacidades específicas de los Países Miembros. El seguimiento de la implementación no será fácil, pues la OIE no prescribe ningún procedimiento específico para poner en práctica sus normas. Los Países Miembros utilizan modalidades distintas debido a las diferencias en cuanto a situaciones zoosanitarias, ordenamiento y procedimientos jurídicos, perfiles comerciales y niveles de riesgo aceptables. Teniendo en cuenta esta compleja situación, los autores proponen aquí un enfoque «transversal¼ de seguimiento de la implementación de las normas, que requeriría reunir información de diversas fuentes fidedignas, como el Sistema Mundial de Información Zoosanitaria (WAHIS), los informes de las misiones de evaluación de las prestaciones de los Servicios Veterinarios (Proceso PVS) de la OIE y la base de datos del sistema de la OMC de gestión de información relativa a las medidas sanitarias y fitosanitarias. Tal enfoque tiene por objetivo documentar lo que está ocurriendo actualmente e identificar posibles patrones en las prácticas de los Países Miembros al implementar las normas de la OIE.

International regulatory cooperation: contribution of the OIE and the WTO Agreement on the Application of Sanitary and Phytosanitary Measures and SPS Committee.

The World Trade Organization (WTO) and the World Organisation for Animal Health (OIE) play an important role in supporting efforts to facilitate the safe trade of animals and animal products by promoting international regulatory cooperation among their Members. International regulatory cooperation is embedded in the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement) and is an integral part of the work of the Sanitary and Phytosanitary Committee. The OIE plays a crucial part in this cooperation, as the OIE is the WTO reference organisation for international standards related to animal health and zoonoses. The SPS Agreement encourages governments to apply national sanitary measures that are consistent with OIE standards, particularly when making decisions on the importation of animals and animal products. This principle of harmonisation is key to integrating the reference frameworks of the WTO SPS Agreement and the OIE standards. This paper describes international regulatory cooperation, the principle of harmonisation and its expressions, and, finally, the various ways in which the WTO and the OIE cooperate towards the achievement of their goals.

L'Organisation mondiale du commerce (OMC) et l'Organisation mondiale de la santé animale (OIE) jouent un rôle majeur dans les efforts déployés pour faciliter des échanges internationaux sûrs d'animaux et de produits d'origine animale en encourageant leurs Membres à faire appel à la coopération réglementaire internationale. La coopération réglementaire internationale s'inscrit dans l'Accord sur l'application des mesures sanitaires et phytosanitaires (Accord SPS) de l'OMC et fait partie intégrante des travaux du Comité des mesures sanitaires et phytosanitaires. L'OIE est un acteur essentiel de cette coopération, étant reconnue par l'OMC comme l'organisation de référence pour les normes internationales en lien avec la santé animale et les zoonoses. L'Accord SPS encourage les gouvernements à faire en sorte que les mesures sanitaires nationales qu'ils appliquent soient conformes aux normes de l'OIE, en particulier lorsqu'il s'agit de décisions relatives aux importations d'animaux et de produits d'origine animale. Ce principe d'harmonisation est essentiel pour intégrer les cadres de référence que constituent à la fois l'Accord SPS de l'OMC et les normes de l'OIE. Cet article décrit la coopération réglementaire internationale, le principe d'harmonisation et ses traductions concrètes, et, enfin, les diverses modalités de la coopération entre l'OMC et l'OIE en vue de réaliser leurs objectifs.

La Organización Mundial del Comercio (OMC) y la Organización Mundial de Sanidad Animal (OIE), al promover la cooperación internacional entre sus Miembros sobre cuestiones ligadas a la reglamentación, cumplen una importante función de apoyo para facilitar el comercio seguro de animales y productos de origen animal. La cooperación internacional sobre temas de reglamentación, inscrita en el Acuerdo sobre la Aplicación de Medidas Sanitarias y Fitosanitarias (Acuerdo MSF), forma parte integrante de la labor del Comité de Medidas Sanitarias y Fitosanitarias (Comité MSF). La intervención de la OIE es fundamental en esta cooperación, puesto que es la organización de referencia para la OMC en cuanto a la normativa internacional sobre sanidad animal y zoonosis. El Acuerdo MSF promueve que los gobiernos apliquen medidas sanitarias nacionales acordes con las normas de la OIE, especialmente al adoptar decisiones sobre la importación de animales y productos de origen animal. Este principio de armonización es clave para integrar los marcos de referencia que constituyen tanto el Acuerdo MSF de la OMC como las normas de la OIE. Las autoras describen la cooperación internacional en materia de reglamentación, el principio de armonización y sus aplicaciones prácticas y, por último, las diversas maneras en que la OMC y la OIE colaboran entre sí para cumplir sus objetivos.

Trade of aquatic animals and aquatic animal products: the use of OIE international standards for devising sanitary measures.

The World Organisation for Animal Health (OIE) develops international standards for the prevention, detection and control of aquatic animal diseases as well as the safe international trade of amphibians, crustaceans, fish, molluscs and their products. The Competent Authorities of importing and exporting countries should implement the OIE international standards by adopting the required legislation as this provides the basis for setting sanitary measures that ensure safe international trade, while avoiding unjustified sanitary barriers to trade. Based on an analysis of legislation notified by countries to the World Trade Organization (WTO) in the context of the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement), the authors explore how and to what extent Member Countries use the OIE international standards when developing sanitary measures. The study develops an analytical framework for collecting and presenting countries' legislation to determine if a direct link can be demonstrated between national legislation and OIE international standards. Results show that OIE international standards are implemented through different categories of legislation which range from more general (those providing a general sanitary framework) to more specific (those setting requirements for the import of aquatic animals and aquatic animal products). However, the study illustrates the difficulty of identifying direct links between countries' legislation and OIE international standards. Nonetheless, this study is the first step in the design of an approach to better understand how OIE international standards are used by Member Countries to devise sanitary measures in the context of international trade. It further notes that increased transparency of national sanitary legislation can facilitate efforts to improve knowledge on the implementation of OIE international standards.

L'Organisation mondiale de la santé animale (OIE) prépare et publie des normes internationales relatives à la prévention, la détection et le contrôle des maladies des animaux aquatiques et à la sécurité sanitaire des échanges internationaux d'amphibiens, crustacés, poissons, mollusques et produits issus de ces espèces. Les Autorités compétentes des pays importateurs et exportateurs doivent procéder à la mise en œuvre de ces normes par le biais d'une législation appropriée, celle-ci fournissant la base pour élaborer des mesures sanitaires destinées à garantir la sécurité sanitaire des échanges internationaux et à éviter l'imposition d'obstacles injustifiés au commerce. À partir d'une analyse des notifications adressées par les pays à l'Organisation mondiale du commerce (OMC) concernant les dispositions de leur législation relevant de l'Accord sur l'application des mesures sanitaires et phytosanitaires (Accord SPS), les auteurs explorent comment et dans quelles mesures les Pays membres utilisent les normes internationales de l'OIE pour développer des mesures sanitaires. Un cadre analytique a été élaboré pour les besoins de cette étude afin de recueillir et de traiter les données relatives à la législation des pays en vue de déterminer l'existence ou non d'un lien direct entre la législation nationale et les normes internationales de l'OIE. Les résultats montrent que la mise en œuvre des normes internationales de l'OIE fait appel à diverses catégories d'instruments législatifs qui vont du plus général (ceux qui fournissent un cadre sanitaire général) au plus spécifique (dispositions relatives aux importations d'animaux aquatiques et de leurs produits). Cette étude fait néanmoins état des difficultés à déceler un lien direct entre la législation d'un pays et les normes internationales de l'OIE. Malgré tout, cette étude marque une première étape dans l'élaboration d'une approche destinée à mieux comprendre comment les Pays membres utilisent les normes internationales de l'OIE lorsqu'ils instaurent des mesures sanitaires dans le contexte des échanges internationaux. Elle fait également ressortir que l'amélioration de la transparence de la législation sanitaire d'un pays est un élément facilitateur pour mieux comprendre tous les aspects de la mise en œuvre des normes internationales de l'OIE.

La Organización Mundial de Sanidad Animal (OIE) elabora normas internacionales que regulan la prevención, la detección y el control de las enfermedades de los animales acuáticos, así como la seguridad del comercio internacional de anfibios, crustáceos, peces y moluscos y los productos derivados de ellos. Las autoridades competentes de los países importadores y exportadores deben aplicar las normas internacionales de la OIE adoptando la legislación necesaria, pues esta sienta las bases para establecer medidas sanitarias que garanticen un comercio internacional seguro, evitando a la vez toda barrera sanitaria al comercio que no esté justificada. Los autores, partiendo del análisis de los textos legislativos comunicados por los países a la Organización Mundial del Comercio (OMC) como parte del Acuerdo sobre la Aplicación de Medidas Sanitarias y Fitosanitarias (Acuerdo MSF), explican cómo y en qué medida los Países Miembros utilizan las normas internacionales de la OIE al definir medidas sanitarias. Como parte del estudio se elaboró un marco analítico destinado a recopilar y presentar la legislación de los países y a determinar, a partir de ahí, si existe un nexo directo entre la legislación nacional y las normas internacionales de la OIE. Los resultados demuestran que las normas internacionales de la OIE se implementan mediante diferentes categorías de instrumentos legales, que van desde lo más genérico (textos que sientan un marco sanitario general) hasta lo más específico (textos que establecen requisitos para importar animales acuáticos y sus derivados). Sin embargo, el estudio evidencia también la dificultad de encontrar nexos directos entre la legislación de los países y las normas internacionales de la OIE. Con todo, el estudio aquí presentado supone el primer paso hacia la concepción de un método que ayude a comprender mejor el modo en que los Países Miembros utilizan las normas internacionales de la OIE para definir medidas sanitarias que se apliquen al comercio internacional. Además, pone de manifiesto que un mayor grado de transparencia de la legislación sanitaria nacional puede facilitar los esfuerzos por conocer con mayor profundidad la forma en que se aplican las normas internacionales de la OIE.

Multicolor flow cytometric analysis of cryopreserved bovine sperm: A tool for the evaluation of bull fertility.

The study aimed at the analysis of the functional status of cryopreserved bovine sperm using multicolor flow cytometry. The value of sperm functional traits as predictors of bull fertility was further evaluated through a retrospective fertility study. For this purpose, 20 Holstein-Friesian bulls serving as mature sperm donors in an artificial insemination (AI) center were selected based on their annual 56-d non-return rate (%) after at least 1,000 AI, and were accordingly classified as high (HF; nHF = 10 bulls) or low fertility bulls (LF; nLF = 10 bulls). Four to 5 cryopreserved ejaculates per bull (91 ejaculates in total) were examined immediately after thawing (0 h) and after a 3-h incubation at 38°C (3 h). A panel of 5 fluorochromes including calcein violet, propidium iodide, pycoerythrin-conjugated lectin of Arachis hypogea, Fluo-4, and cyanine dye DiIC1(5) was configured by means of a 3-laser flow cytometer, to simultaneously assess sperm esterase activity, plasma membrane integrity, acrosomal status, intracellular Ca2+ levels, and mitochondrial membrane potential, respectively. The % relative size of 18 sperm sub-populations showing 2 or more of a combination of the following features was determined: high esterase activity (Cpos), intact plasma membrane (PIneg), unstained acrosome (PNAneg), low intracellular Ca2+ levels (Fneg), and high mitochondrial membrane potential (Mpos). In both fertility groups, Mpos cells comprised more than 90 and 84% of PInegPNAneg sperm at 0 and 3 h, respectively. The percentage of CposPInegPNAnegFnegMpos sperm did not differ between HF and LF ejaculates; however, the percentage of Fneg cells within the PInegPNAneg and PInegMpos sperm populations at 0 h was higher in the HF than in the LF bulls. Applying the random forest ensemble learning method, approximately two-thirds of ejaculates could be correctly assigned to their fertility group. The fraction of Fneg sperm within the PInegMpos population at 0 h was the most important fertility predictor among the 18 defined sperm populations. In conclusion, multicolor flow cytometry offered an insight into the functional heterogeneity of cryopreserved bovine sperm. Indeed, the ability of viable sperm to retain low Ca2+ levels differed between bulls of diverse fertility. A classifier based on selected sperm populations assessed through multicolor flow cytometry could contribute to the prognosis of bull fertility after AI.

The need for repeated dental care under general anaesthesia in children.

AIM: Though the use of advanced behaviour management may facilitate dental treatment in children, some patients still require comprehensive care under general anaesthesia (GA). This is especially true for young children and/or medically compromised children. Thus, this study aimed to provide information about children undergoing GA with regard to age, sex and medical conditions (ICD-10), repeated treatments, dental procedures and recall. MATERIALS AND METHODS: A total of 464 medically compromised children treated under GA in a dental university clinic between 2004 and 2012 were included. Patients` records were analysed retrospectively using SPSS (Version 21.0) and R for statistical analysis. RESULTS: More than 75% of the patients were younger than six years when receiving initial GA. The proportion of children subjected to repeated treatments was low, at 11% for a second and <2% for a third round of GA. The greatest proportion of dental care consisted of restorative therapy and tooth extractions. The recall behaviour observed between the first and second GA revealed no significant influence on the time elapsed in between events (p>0.05). CONCLUSION: Oral care in children with medical conditions is mostly caries-related, and repeated treatment may be necessary, though it was generally uncommon in this university-based study population.

Better Understanding of Phosphoinositide 3-Kinase (PI3K) Pathways in Vasculature: Towards Precision Therapy Targeting Angiogenesis and Tumor Blood Supply.

The intracellular PI3K-AKT-mTOR pathway is involved in regulation of numerous important cell processes including cell growth, differentiation, and metabolism. The PI3Kα isoform has received particular attention as a novel molecular target in gene therapy, since this isoform plays critical roles in tumor progression and tumor blood flow and angiogenesis. However, the role of PI3Kα and other class I isoforms, i.e. PI3Kß, γ, δ, in the regulation of vascular tone and regional blood flow are largely unknown. We used novel isoform-specific PI3K inhibitors and mice deficient in both PI3Kγ and PI3Kδ (Pik3cg(-/-)/Pik3cd(-/-)) to define the putative contribution of PI3K isoform(s) to arterial vasoconstriction. Wire myography was used to measure isometric contractions of isolated murine mesenteric arterial rings. Phenylephrine-dependent contractions were inhibited by the pan PI3K inhibitors wortmannin (100 nM) and LY294002 (10 µM). These vasoconstrictions were also inhibited by the PI3Kα isoform inhibitors A66 (10 µM) and PI-103 (1 µM), but not by the PI3Kß isoform inhibitor TGX 221 (100 nM). Pik3cg(-/-)/Pik3cd(-/-)-arteries showed normal vasoconstriction. We conclude that PI3Kα is an important downstream element in vasoconstrictor GPCR signaling, which contributes to arterial vasocontraction via α1-adrenergic receptors. Our results highlight a regulatory role of PI3Kα in the cardiovascular system, which widens the spectrum of gene therapy approaches targeting PI3Kα in cancer cells and tumor angiogenesis and regional blood flow.

CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense.

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases.

Occlusal caries extension in relation to visual and radiographic diagnostic criteria: results from a microcomputed tomography study.

OBJECTIVE: This in vitro study aimed to evaluate occlusal caries extension in relation to visual and radiographic diagnostic criteria and their clinical value to indicate operative or preventive dental care. METHODS: A total of 196 third molars with clinically sound occlusal fissures or noncavitated lesions were collected. Before microcomputed tomography (µCT) investigation, each tooth was examined visually and radiographically. Kühnisch's µCT-based caries-extension index (CE index) was used to determine the caries depth on a numeric scale (0 = sound; 0.01-0.99 = enamel caries; 1.0-1.99 = dentin caries). Sensitivities (SEs), specificities (SPs), and area under the receiver operating characteristic curve (Az value) were also calculated. RESULTS: Based on µCT data, the following mean CE index values and standard deviations (SDs) were documented according to the visual criteria: sound = 0.6 (0.4); first visible signs = 0.9 (0.4); established lesions = 1.3 (0.3); microcavities = 1.4 (0.2); dentin exposure = 1.5 (0.2); and large cavities = 1.5 (0.3). The radiographic categories according to Marthaler (enamel caries [D0-2], caries in the outer half of dentin [D3], and caries in the inner half of dentin [D4]) were related to CE index values of 0.9 (0.4), 1.4 (0.2) and 1.6 (0.4), respectively. Caries detected visually or radiographically showed an SE of 84% and an SP of 85% (Az = 0.85). When both methods were used to predict dentin involvement simultaneously, SE = 27%, SP = 100%, and Az = 0.63; this combined visual and radiographic approach was associated with a perfect specificity and no false-negative decisions. The proportion of false-positive diagnoses was moderately high, and lesion extension in these cases was mainly limited to the outer 20% of the dentin. CONCLUSIONS: Our results might be useful for differentiating between preventive and operative dental care for pits and fissures.

Irregularities below the enamel-dentin junction may predispose for fissure caries.

This study investigated the structure of the fissure fundus on occlusal surfaces with respect to the detection of possible irregularities below the enamel-dentin junction (EDJ). Occlusal surfaces were examined by micro-computed tomography (µCT). In total, 203 third molars with clinically sound occlusal fissures or non-cavitated lesions were selected. All specimens were scanned with µCT. Subsequently, each tooth was sectioned, and each slice was investigated by stereomicroscopy. In 7 of 203 molars (3.4%), demarcated radiolucencies below the EDJ were detected by µCT. These defects were obviously of non-carious origin, because the µCT images revealed no gradient of demineralization in the dentin. In all cases, a direct pathway between the oral cavity and the dentin was evident. The comparison of the µCT sites with conventional histological images also revealed defects in the dentin. These results demonstrate that demarcated radiolucencies below the EDJ may not necessarily be caries lesions according to µCT images and may be classified as possible developmental irregularities. To avoid misinterpreting µCT data, dental researchers should carefully consider this condition when analyzing µCT images. The clinical significance of this finding is that these defects may predispose molar teeth to early-onset caries in occlusal pits and fissures.

Does greater low frequency EEG activity in normal immaturity and in children with epilepsy arise in the same neuronal network?

Greater low frequency power (<8 Hz) in the electroencephalogram (EEG) at rest is normal in the immature developing brain of children when compared to adults. Children with epilepsy also have greater low frequency interictal resting EEG activity. Whether these power elevations reflect brain immaturity due to a developmental lag or the underlying epileptic pathophysiology is unclear. The present study addresses this question by analyzing spectral EEG topographies and sources for normally developing children and children with epilepsy. We first compared the resting EEG of healthy children to that of healthy adults to isolate effects related to normal brain immaturity. Next, we compared the EEG from 10 children with generalized cryptogenic epilepsy to the EEG of 24 healthy children to isolate effects related to epilepsy. Spectral analysis revealed that global low (delta: 1-3 Hz, theta: 4-7 Hz), medium (alpha: 8-12 Hz) and high (beta: 13-25 Hz) frequency EEG activity was greater in children without epilepsy compared to adults, and even further elevated for children with epilepsy. Topographical and tomographic EEG analyses showed that normal immaturity corresponded to greater delta and theta activity at fronto-central scalp and brain regions, respectively. In contrast, the epilepsy-related activity elevations were predominantly in the alpha band at parieto-occipital electrodes and brain regions, respectively. We conclude that lower frequency activity can be a sign of normal brain immaturity or brain pathology depending on the specific topography and frequency of the oscillating neuronal network.

Learning to appreciate others: neural development of cognitive perspective taking.

Neuroimaging studies have thoroughly investigated brain regions that are recruited when we put ourselves in another person's shoes. Taking a third-person perspective (3PP) as opposed to a first-person perspective (1PP) has been associated with brain activation in the inferior parietal cortex, the medial posterior cortex and the prefrontal cortex. Here we investigate for the first time the development of the neural network that yields cognitive perspective taking. Twelve adults (aged 25-32 years) and twelve school-aged children (aged 8-10 years) were investigated using functional magnetic resonance imaging (fMRI). Behaviorally, we found a decrease of reaction time differences between 3PP and 1PP with age indicating that adults were more efficient in processing a 3PP. Despite the reaction time differences both groups were equally accurate in their judgments. Brain imaging data indicated neural activity in the left inferior parietal cortex and precuneus for adults during 3PP as compared with 1PP judgments. Children additionally showed enhanced activity in the dorsolateral prefrontal cortex and the right inferior perietal cortex. We found a significant interaction between groups and brain activation in the right dorsolateral prefrontal cortex and in the right inferior parietal cortex. These results suggest that the development of the ability to reason about another person's mind accompanies a shift in activity from frontal to posterior brain regions and from bilateral to unilateral left inferior parietal cortex.

In vivo anti-malarial effect of the beta-amino alcohol 1t on Plasmodium berghei.

Glycerol derivatives are a class of compounds, which are easy and inexpensive to produce with potent anti-malarial activities against blood stages of Plasmodium falciparum in vitro. In the present study, one of these compounds, termed 1t, which had the lowest IC(50) values, was assessed in a murine malarial model. Nuclear magnetic resonance imaging and Balb/c mice infected with Plasmodium berghei ANKA strain were treated in a 4-day suppressive test. Mice received a once-daily intraperitoneal administration of 50 mg/Kg of the drug for 4 days. Although no parasitaemia clearance was reached, a slower parasite proliferation and a slightly longer survival time compared with the placebo group were observed.

Clinical performance of a new laser fluorescence device for detection of occlusal caries lesions in permanent molars.

OBJECTIVES: To determine the clinical performance of a laser fluorescence device (DIAGNOdent pen, KaVo) to discriminate between different occlusal caries depths (D(0)-D(1-4); D(0-2)-D(3,4)) in permanent molars. METHODS: In this prospective, randomized two-centre-study 120 sound/uncavitated carious sites in 120 patients were measured after visual and radiographic caries assessment. In cases of operative intervention (n=86), the lesion depths after caries removal were recorded (reference). In cases of preventive intervention (n=34), the sites were reassessed visually/radiographically after 12 months to verify the status assessed before (reference). The discrimination performance was determined statistically (Mann-Whitney test, Spearman's rho coefficient, and areas under the receiver operating characteristic curves (AUCs)). Sensitivities (SE) and specificities (SP) were plotted as a function of the measured values and cut-off values for the mentioned thresholds suggested. RESULTS: Sound sites (n=13) had significantly minor fluorescence values than carious sites (n=107) (P<0.0001) as had sites with no/enamel caries (n=63) compared to dentinal caries (n=57). The AUCs for the same discriminations were 0.92 and 0.78 (P<0.001). For the D(0)-D(1-4) threshold, a cut-off at a value of 12 (SE: 0.88, SP: 0.85) and for the D(0-2)-D(3,4) threshold at 25 (SE: 0.67, SP: 0.79) can be suggested. A moderate positive correlation between the measurements and the caries depths was calculated (rho=+0.57, P=0.01). CONCLUSION: Within this study, the device's discrimination performance for different caries depths was moderate to very good and it may be recommended as adjunct tool in the diagnosis of occlusal caries.

Frequency of non-carious triangular-shaped radiolucencies on bitewing radiographs.

OBJECTIVES: The assessment of bitewing radiographs requires knowledge of radiographic anatomy and pathology, and the comprehension of possible effects of superposition which may lead to false positive diagnoses. Based on a clinical case report in which non-carious radiolucencies were discovered on the mesial surfaces of upper molars, this phenomenon, which has not been reported before, was explained. Due to the anatomical characteristics of the rhombic tooth, in particular the crown's receding mesial surface from the mesiobuccal towards the distopalatal side, which is combined with an often prominent palatal cusp and a smaller mesiodistal diameter at the cervical neck, radiolucencies - normally typical caries indicators - can sometimes be observed on the mesial surfaces of upper primary and first permanent molars on bitewings. These triangular-shaped radiolucencies (TSRs) can therefore be attributed to the effects of superposition. The aim of the present epidemiological study was to assess the radiographic frequency of TSRs. METHODS: As part of a clinical-radiographic follow-up examination involving 11-12 year old children (n = 113), both the caries status (World Health Organization (WHO) standard) and the frequency of TSRs were recorded. RESULTS: TSRs were most frequently present on upper second primary molars (60.3%). 35.5% of the upper first primary molars and 24.8% of the upper first permanent molars displayed TSRs. However, none of the lower primary and/or permanent molars displayed this phenomenon. CONCLUSION: In the mesial surface of upper primary and permanent molars where the frequency of TSRs was fairly high, it may be essential to distinguish this change from approximal caries.

Influence of ovarian steroid hormones or platelet-activating factor on mRNA of platelet-activating factor receptor in endometrial explant perfusion cultures from ovariectomized bovine.

Platelet-activating factor (PAF) and its receptors are involved in inflammatory-like processes of the uterus associated with increased vascular permeability. PAF is supposed to be influenced by ovarian steroid hormones. The present study was undertaken to examine whether progesterone (P(4)), estradiol (E(2)) or PAF influence the PAF receptor gene expression in perfused endometrial explants derived from ovariectomized bovine. Furthermore, we identified the cell types in which the PAF receptor gene and protein are expressed. In endometrial explants, applications of 10 nM P(4) or 10nM P(4) plus 10 nM E(2) for 24 h induced elevated transcript levels of PAF receptor in comparison to the controls or after treatment with 1 nM E(2). When explants were administered 10 nM E(2), a slight decrease in the transcript level was recorded. After treatment of explants with PAF, no significant changes in PAF receptor mRNA expression was observed compared to the control group. We demonstrate that PAF receptor immunoreactivity and mRNA are detected mainly in the luminal epithelium, epithelial cells of the superficial glands and to a lesser degree in stroma. Levels of PAF receptor mRNA in bovine endometrial explants were correlated with PAF receptor protein localization assessed by immunohistochemistry. The regulation of PAF receptor by progesterone in bovine endometrial explants suggests that PAF is involved in the physiological process of reproduction.

[Does weather modify headaches? An empirical evaluation of bio-weather categorization]. / Hat das Wetter Einfluss auf Kopfschmerzen? Eine Evaluation der Biowetterklassen.

BACKGROUND: Headache patients frequently refer to the weather as a triggering factor for their headaches. Apart from a literature review, we tested empirically the generally used classification of weather epochs into a so called bio-weather categorization. METHOD: Headache diary data (frequency, duration, intensity) of 98 patients in a headache trial were correlated with the concurrent bio-weather classification. RESULTS: Correlations were small and significant only for the summer-half of the year (contingency coefficients between 0.04 and 0.06). The classification of certain types of weather as headache prone as used in the current bio-weather classification could only partly be verified. CONCLUSION: There is a clear but small correlation between headache and weather. More, and more fine-grained, studies are warranted, especially for identifying those patients at risk for weather prone headaches. Clinically more important is the weather as a source of causal attributions.

The T cell oncogene Tal2 is necessary for normal development of the mouse brain.

Transcription factors are commonly involved in leukemia by activation through chromosomal translocations and normally function in cell type(s) that differ from that of the tumor. TAL2 is a member of a basic helix-loop-helix gene family specifically involved in T cell leukemogenesis. Null mutations of Tal2 have been made in mice to determine its function during development. Tal2 null mutant mice show no obvious defects of hematopoiesis. During embryogenesis, Tal2 expression is restricted to the developing midbrain, dorsal diencephalon, and rostroventral diencephalic/telencephalic boundary, partly along presumptive developing fiber tracts. The null mutant mice are viable at birth but growth become progressively retarded and they do not survive to reproductive age. Tal2-deficient mice show a distinct dysgenesis of the midbrain tectum. Due to loss of superficial gray and optical layers, the superior colliculus is reduced in size and the inferior colliculus is abnormally rounded and protruding. Death is most likely due to progressive hydrocephalus which appears to be caused by obstruction of the foramen of Monro (the connection between the ventricles of the forebrain). Thus, in addition to its oncogenicity when ectopically expressed, Tal2 normally plays a pivotal role in brain development and without this gene, mice cannot survive to maturity.

Winter mortality in relation to climate.

We report further details of the Eurowinter survey of cold related mortalities and protective measures against cold in seven regions of Europe, and review these with other evidence on the relationship of winter mortality to climate. Data for the oldest subject group studied, aged 65-74, showed that in this vulnerable group, high levels of protection against indoor and outdoor cold at given outdoor temperatures were found mainly in countries with cold winters, and were associated with low levels of excess mortality at a given level of outdoor cold. Regions such as London that had poor protection against cold and/or high baseline mortalities had higher levels of winter excess mortality than expected for the coldness of their winters.