To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question

Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors – the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic drugs) is necessary to answer the title question

Componentes lipofílicos y evaluación de las actividades citotóxicas y antioxidantes de Impatiens glandulifera Royle e Impantiet noli-tangere L. (Balsaminaceae)

The chemical composition of the lipophilic fractions of Impatiens glandulifera Royle and I. noli-tangere L. were analyzed by gas chromatography-mass spectrometry (GC-MS)., The study focused on the fatty acids, triterpenoids and sterols in the leaves, roots and seeds. Most of the identified compounds are new for these species. a-linolenic, oleic and palmitic acids were the most abundant in the fatty acid fractions, β-amyrin and 5a-lup-20(29)-en-3β-ol in the triterpenoid fractions, and β-sitosterol, spinasterol and chondrillasterol in the sterol fractions. The fatty acid and triterpenoid fractions showed strong antioxidant activity, similar to positive controls. Moreover, the triterpenoid fraction from I. noli-tangere seeds significantly inhibited HL-60 human leukemia cells. Other fractions showed moderate cytotoxicity. The present study suggests that I. glandulifera and I. noli-tangere are good source of omega-3 fatty acids, and they might be considered as antioxidant and chemopreventive agents.La composición química de las fracciones lipofílicas, centrada en los ácidos grasos, triterpenoides y esteroles de las partes aéreas, raíces y semillas de Impatiens glandulifera Royle e Impatient. noli-tangere L. se analizaron por cromatografía de gases-espectrometría de masas (GC-MS). La mayoría de los compuestos identificados son nuevos para estas especies. Los ácidos a-linolénico, oleico y palmítico fueron los más abundantes en las fracciones de ácidos grasos, β-amirina y 5a-lup-20 (29)-en-3β-ol en las fracciones triterpenoides, y β-sitosterol, espinasterol y condriplasterol en las fracciones de esteroles. Las fracciones de ácidos grasos y triterpenos mostraron una fuerte actividad antioxidante, similar a los controles positivos. Además, la fracción triterpenoidea de las semillas de I. noli-tangere inhibió significativamente las células de leucemia humana HL-60. Otras fracciones mostraron citotoxicidad moderada. El presente estudio sugiere que I. glandulifera e I. noli-tangere son la buena fuente de ácidos grasos omega-3, y podrían considerarse antioxidantes y agentes quimiopreventivos

Der diskrete Charme der Bourgeoisie - Ein Beitrag zur Soziologie des modernen Wirtschaftsbürgertums

Entgegen der These der Auflösungserscheinungen des Bürgertums stellt der Autor die Annahme auf den Prüfstand, dass wir es nach wie vor mit gesellschaftlichen Fraktionierungen bürgerlicher Lebensweisen zu tun haben. Am Beispiel autobiographischer Schriften von deutschen Topmanagern stellt der Text ein modernes Verständnis des Wirtschaftsbürgertums vor, das organisational (durch die Karrieremechanismen der Organisation) und institutionell (im Feld der Wirtschaft) verankert ist. Die moderne Sozialformation des Wirtschaftsbürgertums ist nur noch auf der Grundlage von Organisationen denkbar. Sie lässt sich, jenseits von Klasse und Stand, als Positionselite beschreiben. Anhand der Autobiographien lässt sich die Reproduktion dieser Elite auf Basis einer engen Verknüpfung zwischen familialer Herkunft, an organisationale Karrieren gebundene Leistungsbereitschaft und hoher formaler Bildung nachzeichnen. Die Abgrenzung in der Statusreproduktion zwischen Bildungs- und Wirtschaftsbürgertum weist der Autor am jeweiligen Verhältnis zur Bildung nach; zwar können beide einen hohen Bildungsgrad in Form von Bildungspatenten nachweisen, doch im Falle des Wirtschaftsbürgertums herrscht ein instrumentelles Verhältnis zur Bildung vor. Der hohe Bildungsgrad folgt hier dem Bedürfnis, den Status mittels formaler Bildung abzusichern und damit die Gefahr der eigenen Austauschbarkeit - als Personal der Organisation - zu kompensieren. Der Text macht außerdem generationale Effekte sichtbar; insbesondere indem er darlegt, inwieweit der "moderne Manager" einerseits in der Betonung seines Status seinen Vorgängern gleicht und sich doch gleichzeitig in der Art der Unternehmensführung abgrenzt - indem er bspw. die Managementkonzepte seiner Zeit aufgreift

Transcendental-Phenomenological Proof and Descriptive Metaphysics

Following P.F. Strawson's reading of Kant, the majority of the literature on transcendental arguments seeks to divorce such arguments from their original Kantian context. This thesis is concerned with Mark Sacks's recent defence of transcendental arguments, which takes a different approach. A critique is given of Sacks's work and extensions and modifications of his approach are recommended. It is proposed that certain difficulties encountered by Kant's transcendentally-ideal approach can be overcome with Hegelian solutions

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Evolutionary approaches for the reverse-engineering of gene regulatory networks: A study on a biologically realistic dataset

<p>Abstract</p> <p>Background</p> <p>Inferring gene regulatory networks from data requires the development of algorithms devoted to structure extraction. When only static data are available, gene interactions may be modelled by a Bayesian Network (BN) that represents the presence of direct interactions from regulators to regulees by conditional probability distributions. We used enhanced evolutionary algorithms to stochastically evolve a set of candidate BN structures and found the model that best fits data without prior knowledge.</p> <p>Results</p> <p>We proposed various evolutionary strategies suitable for the task and tested our choices using simulated data drawn from a given bio-realistic network of 35 nodes, the so-called insulin network, which has been used in the literature for benchmarking. We assessed the inferred models against this reference to obtain statistical performance results. We then compared performances of evolutionary algorithms using two kinds of recombination operators that operate at different scales in the graphs. We introduced a niching strategy that reinforces diversity through the population and avoided trapping of the algorithm in one local minimum in the early steps of learning. We show the limited effect of the mutation operator when niching is applied. Finally, we compared our best evolutionary approach with various well known learning algorithms (MCMC, K2, greedy search, TPDA, MMHC) devoted to BN structure learning.</p> <p>Conclusion</p> <p>We studied the behaviour of an evolutionary approach enhanced by niching for the learning of gene regulatory networks with BN. We show that this approach outperforms classical structure learning methods in elucidating the original model. These results were obtained for the learning of a bio-realistic network and, more importantly, on various small datasets. This is a suitable approach for learning transcriptional regulatory networks from real datasets without prior knowledge.</p