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

Herschel images of Fomalhaut An extrasolar Kuiper belt at the height of its dynamical activity

Context. Fomalhaut is a young (2 ± 1 × 108 years), nearby (7.7 pc), 2 M⊙ star that is suspected to harbor an infant planetary system, interspersed with one or more belts of dusty debris. Aims. We present far-infrared images obtained with the Herschel Space Observatory with an angular resolution between 5.7′′ and 36.7′′ at wavelengths between 70 μm and 500 μm. The images show the main debris belt in great detail. Even at high spatial resolution, the belt appears smooth. The region in between the belt and the central star is not devoid of material; thermal emission is observed here as well. Also at the location of the star, excess emission is detected. We aim to construct a consistent image of the Fomalhaut system. Methods. We use a dynamical model together with radiative-transfer tools to derive the parameters of the debris disk. We include detailed models of the interaction of the dust grains with radiation, for both the radiation pressure and the temperature determination. Comparing these models to the spatially resolved temperature information contained in the images allows us to place strong constraints on the presence of grains that will be blown out of the system by radiation pressure. We use this to derive the dynamical parameters of the system. Results. The appearance of the belt points toward a remarkably active system in which dust grains are produced at a very high rate by a collisional cascade in a narrow region filled with dynamically excited planetesimals. Dust particles with sizes below the blow-out size are abundantly present. The equivalent of 2000 one-km-sized comets are destroyed every day, out of a cometary reservoir amounting to 110 Earth masses. From comparison of their scattering and thermal properties, we find evidence that the dust grains are fluffy aggregates, which indicates a cometary origin. The excess emission at the location of the star may be produced by hot dust with a range of temperatures, but may also be due to gaseous free-free emission from a stellar wind

The Vega debris disc: A view from Herschel

We present five band imaging of the Vega debris disc obtained using the Herschel Space Observatory. These data span a wavelength range of 70–500 μm with full-width half-maximum angular resolutions of 5.6–36.9”. The disc is well resolved in all bands, with the ring structure visible at 70 and 160 μm. Radial profiles of the disc surface brightness are produced, and a disc radius of 11” (~85 AU) is determined. The disc is seen to have a smooth structure thoughout the entire wavelength range, suggesting that the disc is in a steady state, rather than being an ephemeral structure caused by the recent collision of two large planetesimals

Genetic identification of cytomegaloviruses in a rural population of Côte d'Ivoire.

BACKGROUND: Cytomegaloviruses (CMVs) are herpesviruses that infect many mammalian species, including humans. Infection generally passes undetected, but the virus can cause serious disease in individuals with impaired immune function. Human CMV (HCMV) is circulating with high seroprevalence (60-100 %) on all continents. However, little information is available on HCMV genoprevalence and genetic diversity in subsaharan Africa, especially in rural areas of West Africa that are at high risk of human-to-human HCMV transmission. In addition, there is a potential for zoonotic spillover of pathogens through bushmeat hunting and handling in these areas as shown for various retroviruses. Although HCMV and nonhuman CMVs are regarded as species-specific, potential human infection with CMVs of non-human primate (NHP) origin, shown to circulate in the local NHP population, has not been studied. FINDINGS: Analysis of 657 human oral swabs and fecal samples collected from 518 individuals living in 8 villages of Côte d'Ivoire with generic PCR for identification of human and NHP CMVs revealed shedding of HCMV in 2.5 % of the individuals. Determination of glycoprotein B sequences showed identity with strains Towne, AD169 and Toledo, respectively. NHP CMV sequences were not detected. CONCLUSIONS: HCMV is actively circulating in a proportion of the rural Côte d'Ivoire human population with circulating strains being closely related to those previously identified in non-African countries. The lack of NHP CMVs in human populations in an environment conducive to cross-species infection supports zoonotic transmission of CMVs to humans being at most a rare event

Benzoxazinoids in Root Exudates of Maize Attract Pseudomonas putida to the Rhizosphere

Benzoxazinoids, such as 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA), are secondary metabolites in grasses. In addition to their function in plant defence against pests and diseases above-ground, benzoxazinoids (BXs) have also been implicated in defence below-ground, where they can exert allelochemical or antimicrobial activities. We have studied the impact of BXs on the interaction between maize and Pseudomonas putida KT2440, a competitive coloniser of the maize rhizosphere with plant-beneficial traits. Chromatographic analyses revealed that DIMBOA is the main BX compound in root exudates of maize. In vitro analysis of DIMBOA stability indicated that KT2440 tolerance of DIMBOA is based on metabolism-dependent breakdown of this BX compound. Transcriptome analysis of DIMBOA-exposed P. putida identified increased transcription of genes controlling benzoate catabolism and chemotaxis. Chemotaxis assays confirmed motility of P. putida towards DIMBOA. Moreover, colonisation essays in soil with Green Fluorescent Protein (GFP)-expressing P. putida showed that DIMBOA-producing roots of wild-type maize attract significantly higher numbers of P. putida cells than roots of the DIMBOA-deficient bx1 mutant. Our results demonstrate a central role for DIMBOA as a below-ground semiochemical for recruitment of plant-beneficial rhizobacteria during the relatively young and vulnerable growth stages of maize

Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy: a medical hypothesis paper

Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention

Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations

A novel emergency department based prevention intervention program for people living with HIV: evaluation of early experiences

<p>Abstract</p> <p>Background</p> <p>HIV prevention is increasingly focused on people living with HIV (PLWH) and the role of healthcare settings in prevention. Emergency Departments (EDs) frequently care for PLWH, but do not typically endorse a prevention mission. We conducted a pilot exploratory evaluation of the first reported ED program to address the prevention needs of PLWH.</p> <p>Methods</p> <p>This retrospective observational cohort evaluation reviewed program records to describe the first six months of participants and programmatic operation. Trained counselors provided a risk assessment and counseling intervention combined with three linkage interventions: i) linkage to health care, ii) linkage to case management, and iii) linkage to partner counseling and referral.</p> <p>Results</p> <p>Of 81 self-identified PLWH who were approached, 55 initially agreed to participate. Of those completing risk assessment, 17/53 (32%, 95 CI 20% to 46%) reported unprotected anal/vaginal intercourse or needle sharing in the past six months with a partner presumed to be HIV negative. Counseling was provided to 52/53 (98%). For those requesting services, 11/15 (73%) were linked to healthcare, 4/23 (17%) were coordinated with case management, and 1/4 (25%) completed partner counseling and referral.</p> <p>Conclusion</p> <p>Given base resources of trained counselors, it was feasible to implement a program to address the prevention needs for persons living with HIV in an urban ED. ED patients with HIV often have unmet needs which might be addressed by improved linkage with existing community resources. Healthcare and prevention barriers for PLWH may be attenuated if EDs were to incorporate CDC recommended prevention measures for healthcare providers.</p

Packages of Care for Epilepsy in Low- and Middle-Income Countries

In the second in a series of six articles on packages of care for mental health disorders in low- and middle-income countries, Caroline Mbuba and Charles Newton discuss treatment for epilepsy

Herschel detects oxygen in the beta Pictoris debris disk

The young star β Pictoris is well known for its dusty debris disk produced through collisional grinding of planetesimals, kilometre-sized bodies in orbit around the star. In addition to dust, small amounts of gas are also known to orbit the star; this gas is likely the result of vaporisation of violently colliding dust grains. The disk is seen edge on and from previous absorption spectroscopy we know that the gas is very rich in carbon relative to other elements. The oxygen content has been more difficult to assess, however, with early estimates finding very little oxygen in the gas at a C/O ratio that is 20 × higher than the cosmic value. A C/O ratio that high is difficult to explain and would have far-reaching consequences for planet formation. Here we report on observations by the far-infrared space telescope Herschel, using PACS, of emission lines from ionised carbon and neutral oxygen. The detected emission from C+ is consistent withthat previously reported observed by the HIFI instrument on Herschel, while the emission from O is hard to explain without assuming a higher density region in the disk, perhaps in the shape of a clump or a dense torus required to sufficiently excite the O atoms. A possible scenario is that the C/O gas is produced by the same process responsible for the CO clump recently observed by the Atacama Large Millimeter/submillimeter Array in the disk and that the redistribution of the gas takes longer than previously assumed. A more detailed estimate of the C/O ratio and the mass of O will have to await better constraints on the C/O gas spatial distribution