Cold dark matter in brane cosmology scenario

We analyze the dark matter problem in the context of brane cosmology. We investigate the impact of the non-conventional brane cosmology on the relic abundance of non-relativistic stable particles in high and low reheating scenarios. We show that in case of high reheating temperature, the brane cosmology may enhance the dark matter relic density by many order of magnitudes and a stringent lower bound on the five dimensional scale is obtained. We also consider low reheating temperature scenarios with chemical equilibrium and non-equilibrium. We emphasize that in non-equilibrium case, the resulting relic density is very small. While with equilibrium, it is increased by a factor of O(10^2) with respect to the standard thermal production. Therefore, dark matter particles with large cross section, which is favored by detection expirements, can be consistent with the recent relic density observational limits.Comment: 14 pages, 1 figur

Zonisamide (CI-912) and Cognition: Results from Preliminary Study

Nine patients with refractory partial seizures were evaluated in a pilot study of a new anticonvulsant compound, zonisamide (l,2-benzisoxazole-3-methane-sulfonamide; CI-912). Cognitive functioning was evaluated prior to treatment with zonisamide and repeated after 12 and 24 weeks of treatment with zonisamide. At minimum steady-state plasma concentrations >30 jjug/ml, zonisamide appeared to affect specific cognitive functions such as acquisition and consolidation of new information. Previously learned material, such as vocabulary, and psychomotor performance were not affected. Verbal learning was affected, while visual-perceptual learning was unimpaired. These cognitive effects were observed in the absence of the usual clinical signs and symptoms of toxicity. A linear relationship was found between impairment of cognitive abilities and the minimum plasma concentration (r = -0.73; p < 0.05). Findings also suggest the development of tolerance to the adverse cognitive effects. RESUMEN En un estudio piloto realizado para valorar la eficacia de la zonisamida (1,2-Bencisoxazol-melanosulfonamida [CI-912]), un nuevo compuesto anticonvulsive se han evaluado unos 9 pa-cientes con ataques parciales refractarios al tratamiento. Se de-terminÓ la capacidad cognitiva anterior al tratamiento y se re-pitio 12 y 24 semanas despuÉs del tratamiento con zonisamida. Con concentraciones plasmÁticas mÍnimas estables per encima de 30 mcg/ml, la zonisamida afectÓ las funciones cognitives especÍficas tales como la adquisiciÓn y consolidaciÓn de nueva informaciÓn. El material aprendido previamente, tal como el vo-cabulario, y las funciones psicomotoras no se afectaron. El aprendizaje verbal se modificÓ mientras que el aprendizaje visuo-perfectivo no se modificÓ. Estos efectos cognitivos se ob-servaron en ausencia de los habituales signos y sÍntomas clÍnicos de toxicidad. Se encontrÓ una relaciÓn lineal entre la alteraciÓn de las posibilidades cognitivas y la concentraciÓn plasmÁtica mÍnima (r = -0.73, p < 0.05). Estos hallazgos tambiÉn sugieren el desarrollo de una tolerancia a los efectos cognitivos adversos. ZUSAMMENFASSUNG 9 Patienten mit rezidivierenden Partial-AnfÄllen wurden in einer Pilotstudie mit einer neuen antiepileptischen Substanz: Zonisamide untersucht. Die kognitiven Funktionen wurden vor der Behandlung mit Zonisamide geprtÜft und nach 12 und 24 Therapiewochen mit Zonisamide wiederholt. Bei einem Min-destplasmaspiegel von 30 mcg/ml schien Zonisamide spezifische kognitive FÄhigkeiten wie Aufnahme und Speicherung neuer In-formationen zu beeintrÄchtigen. Vorher gelernte Inhalte wie sprachliche und psychomotorische Fertigkeiten wurden nicht beeinflußt. Verbales Lernen war ebenfalls betroffen, wÄhrend visuell, perzeptives Lernen nicht verschlechtert war. Diese BeeintrÄchtigung kognitiver Funktionen wurde bei fehlenden klinischen Intoxikationszeichen beobachtet. Eine lineare Bezie-hung zwischen Verschlechterung kognitiver FÄhigkeiten und Mindest-Plasmaspiegel konnte hergestellt werden (r = -0,73; p < 0,05). Allerdings lassen die Ergebnisse auch auf eine GewÖhnung an diese unerwÜnschten Nebenwirkungen schließen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65995/1/j.1528-1157.1987.tb03624.x.pd

Pilot Study of Zonisamide (1,2-Benzisoxazole-3-methanesulfonamide) in Patients with Refractory Partial Seizures

A new anticonvulsant compound, zonisamide (1,2 benzioxazole-methanesulfonamide), was studied in 10 adults with medically refractory partial seizures. Following a single oral dose of 400 mg, peak plasma levels occurred an average of 2.8 h after dosing, and the mean clearance from plasma was 2.34 L/h. Whole blood concentrations were high than plasma concentrations because of red blood cell binding. steady-state plasma concentrations were high than predicted from a linear kinetic model. In most patients, seizure frequency was reduced after zonisamide was substituted for a standard antiepileptic drug. Dose-related reversible side effects in the central nervous and gastrointestinal system were observed. Most patients tolerated doses between 5.2 and 12.5 mg/kg/day. RÉSUMÉ Un nouveau produit anticonvulsivant, le zonisamide (1,2 benziosoxazole-methylsulfonamide) a ÉtÉ administrÉÀ 10 adultes atteints de crises partielles non contrÔlÉes par le traitement mÉdical. AprÈs une dose unique orale de 400 mg, le pic du taux plasmatique survient en moyenne 2 h 1/2 aprÉs l'ingestion, et la clairance plasmatique moyenne est de 2,34 litres par heure. les concentrations sanguines totales sont plus ÉlevÉes que les concentrations plasmatiques, en raison de la liaison aux globules rouges, les concentrations plasmatiques À l'État d'equilibre sont plus ÉlevÉes que celles que l'on peut dÉdurie d'un modÈle de cinÉtique linÉaire. Chez la plupart des patients, la frÉquence des crises a ÉtÉrÉduite par la substitution du zonisamide au traitement antiÉpileptique standard. Des effets secondaires doses-dÉpendants et rÉversibles ont ÉtÉ observÉs au niveau du systÈme nerveux central et du tube digestif. La plupart des patients ont tolÉrÉ des doses entre 5,2 et 12,5 mg/kg de poids par jour. RESUMEN En 10 adultos con ataques parciales refractarios a1 tratamiento mÉdico, se ha estudiado la acciÓn de un nuevo compuesto anticonvulsivo, la zonisamida (1,2 benzisoxazol-metanosulfonamida). Tras la ingestiÓn de una sola dosis oral de 400 mg., se alcanzaron los niveles pico en plasma en un promedio de 2.8 horas desputs de la dosis y el aclaramiento medio del plasma fuÉ de 2, 34 litros/hora. Las concentraciones en sangre fueron mÁs altas que las plasmÁticas debido a que la medicaciÓn se ligaba a los hematies. Las concentraciones plasmÁticas estables fueron mÁs altas que las previsibles de un modelo cinÉtico lineal. En la mayorÍa de los pacientes la frecuencia de los ataques se redujo despuÉs de cambiar la medicaciÓn antiepilÉptica standard por la zonisamida. TambiÉn se observaron los efectos colaterales sobre el tracto gastrointestinal y el sistema nervioso central que estaban relacionadas con la dosis y eran reversibles. La mayor parte de los pacientes tolerÓ dosis que oscilaban entre 5.2 y 12.5 mg/kg/dÍa. ZUSAMMENFASSUNG Ein neues Antikonvulsivum, Zonisamid (1,2 Benzisoxazol-Methansulfonamid) wurde bei 10 Envachsenen mit therapieresistenten PartialanfÄllen gesucht. Nach einer oralen Einzeldosis von 400 mg wurden Plasmaspitzenwerte im Durchschnitt nach 2, 8 Stunden erreicht. Die mittlere Clearance aus dem Plasma betrug 2, 34 L/Stunde. Ganzblutkonzentrationen waren hÖher als Plasmakonzentrationen aufgrund der Bindung an die roten BlutkÖrperchen. Die steady-state Plasmakonzentrationen waren hÖher als bei einem linearen kinetischen Modell zu envarten. Bei den meisten Patienten konnte die Anfallsfrequenz nach Substitution eines Standardantiepileptikums durch Zonisamid reduziert werden. Es bestanden dosisabhÄngige, reversible, zentral-nervÖse und gastrointestinale Nebenwirkungen. Die meisten Patienten tolerierten Dosen zwischen 5, 2 und 12, 5 mg/kg/Tag.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65938/1/j.1528-1157.1985.tb05407.x.pd

Dramatic outcomes in epilepsy: depression, suicide, injuries, and mortality

In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report to their treating physician any change in their mood and existence of suicidal ideation. The risk of injuries for the general epilepsy population is increased only moderately. The risk is higher in selected populations attending epilepsy clinics and referral centers. This being said, there are PWE that may suffer frequent, severe, and sometimes even life-threatening seizure-related injuries. The most obvious way to reduce risk is to strive for improved seizure control. Finally, PWE have a 2–3 times higher mortality rate than the general population. Deaths in PWE may relate to the underlying cause of epilepsy, to seizures (including sudden unexpected death in epilepsy [SUDEP] and seizure related injuries) and to status epilepticus, as well as to other conditions that do not appear directly related to epilepsy. Improving seizure control and patient education may be the most important measures to reduce epilepsy related mortality in general and SUDEP in particular

A comparison of the mismatch negativity (MMN) event-related potential to tone and speech stimuli in normal and aphasic adults

We evaluated the mismatch negativity (MMN) event-related potential (ERP) in normal and aphasic adults to tone and speech stimuli to determine aphasic patients' auditory discrimination and the relationship between MMN measures and severity of aphasia. MMNs were present in 89 % of normal subjects and 79 % of aphasic subjects to tone stimuli. MMNs were present in 100% of normal subjects and 54 % of aphasic subjects to speech stimuli. The duration of the MMN ERP to speech stimuli was significantly related to severity of aphasia on the Western Aphasia Battery, Porch Index of Communicative Ability, and the Token Test. Thus, not all aphasic people show an early, preconscious orientation response to tone and speech stimuli. However, the duration of this response, when present, to speech stimuli appears to be related to the severity of aphasia

Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy

The Msx1 Homeoprotein Recruits G9a Methyltransferase to Repressed Target Genes in Myoblast Cells

Although the significance of lysine modifications of core histones for regulating gene expression is widely appreciated, the mechanisms by which these modifications are incorporated at specific regulatory elements during cellular differentiation remains largely unknown. In our previous studies, we have shown that in developing myoblasts the Msx1 homeoprotein represses gene expression by influencing the modification status of chromatin at its target genes. We now show that genomic binding by Msx1 promotes enrichment of the H3K9me2 mark on repressed target genes via recruitment of G9a histone methyltransferase, the enzyme responsible for catalyzing this histone mark. Interaction of Msx1 with G9a is mediated via the homeodomain and is required for transcriptional repression and regulation of cellular differentiation, as well as enrichment of the H3K9me2 mark in proximity to Msx1 binding sites on repressed target genes in myoblast cells as well as the developing limb. We propose that regulation of chromatin status by Msx1 recruitment of G9a and other histone modifying enzymes to regulatory regions of target genes represents an important means of regulating the gene expression during development

Phenotyping male infertility in the mouse: how to get the most out of a ‘non-performer’

BACKGROUND: Functional male gametes are produced through complex processes that take place within the testis, epididymis and female reproductive tract. A breakdown at any of these phases can result in male infertility. The production of mutant mouse models often yields an unexpected male infertility phenotype. It is with this in mind that the current review has been written. The review aims to act as a guide to the 'non-reproductive biologist' to facilitate a systematic analysis of sterile or subfertile mice and to assist in extracting the maximum amount of information from each model. METHODS: This is a review of the original literature on defects in the processes that take a mouse spermatogonial stem cell through to a fully functional spermatozoon, which result in male infertility. Based on literature searches and personal experience, we have outlined a step-by-step strategy for the analysis of an infertile male mouse line. RESULTS: A wide range of methods can be used to define the phenotype of an infertile male mouse. These methods range from histological methods such as electron microscopy and immunohistochemistry, to hormone analyses and methods to assess sperm maturation status and functional competence. CONCLUSION: With the increased rate of genetically modified mouse production, the generation of mouse models with unexpected male infertility is increasing. This manuscript will help to ensure that the maximum amount of information is obtained from each mouse model and, by extension, will facilitate the knowledge of both normal fertility processes and the causes of human infertility