Clinical profile and treatment of infantile spasms using vigabatrin and ACTH - a developing country perspective

Background: Infantile spasms represent a serious epileptic syndrome that occurs in the early infantile age. ACTH and Vigabatrin are actively investigated drugs in its treatment. This study describes the comparison of their efficacy in a large series of Patients with infantile spasms from Pakistan. Methods: All Patients with infantile spasms who presented to Aga Khan University Hospital, Karachi, Pakistan from January, 2006 to April, 2008 were included in this study. Inclusion criteria were clinical symptoms of infantile spasms, hypsarrythmia or modified hyparrythmia on electroencephalography, at least six months of follow-up period and receipt of any of the two drugs mentioned above. The type of drug distribution was random according to the availability, cost and ease of administration. Results: Fifty six cases fulfilled the inclusion criteria. 62.5% were males. Mean age at onset of seizures was 5 +/- 1.4 months. Fifty two (92.8%) Patients demonstrated hypsarrythmia on electroencephalography. 64.3% cases were identified as symptomatic while 19.6% were cryptogenic and 16.1% were idiopathic. Eighteen Patients received ACTH while 38 Patients received Vigabatrin as first line therapy. Initial response to first line therapy was similar (50% for ACTH and 55.3% for Vigabatrin). Overall, the symptomatic and idiopathic groups responded better to Vigabatrin. The relapse rate was higher for ACTH as compared to Vigabatrin (55.5% vs. 33.3%) when considering the first line therapy. Four Patients evolved to Lennox-Gastaut variant, all of these Patients had initially received Vigabatrin and then ACTH. Conclusion: Vigabatrin and ACTH showed no significant difference in the initial treatment of infantile spasms. However, Patients receiving ACTH were 1.2 times more likely to relapse as compared to the Patients receiving Vigabatrin when considering monotherapy. We suggest that Vigabatrin should be the initial drug of choice in Patients presenting with infantile spasms. However, larger studies from developing countries are required to validate the therapeutic trends observed in this study

Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: Study protocol for a randomised controlled trial

© The Author(s). 2017. Background: Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE. Methods/design: This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up. Discussion: This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting

One-year molecular survey of astrovirus infection in turkeys in Poland

The presence of turkey astrovirus (TAstV) was monitored in meat-type turkey flocks in Poland in 2008. Clinical samples (10 individual faecal swabs/flock) from 77 flocks aged 1-19 weeks were collected from different regions of the country. RT-PCR experiments were performed for detection and molecular characterization of TAstV using four sets of primers within the RdRp gene (ORF1b). The prevalence of astrovirus was 34/77 (44.15%) in the flocks tested. TAstV type 2 was associated with 30 of 77 infections (38.9%), either alone or in mixed infections; TAstV type 1 was detected in 9 of 77 flocks (11.6%), either alone or in mixed infections; ANV was detected only in one flock (1.29%) by sequence analysis during this study. Phylogenetic analysis revealed genetic variability in the TAstV strains that were isolated. Some of Polish TAstV-2 strains were genetically related to the North American isolates; however, most of them formed a distinct subgroup of “European” isolates, suggesting their separate origin or evolution. Additionally, due to the high variability of the TAstV sequences, the most suitable method for TAstV typing seems to be sequencing

Stable Isotope Evidence for Dietary Overlap between Alien and Native Gastropods in Coastal Lakes of Northern KwaZulu-Natal, South Africa

Tarebia granifera (Lamarck, 1822) is originally from South-East Asia, but has been introduced and become invasive in many tropical and subtropical parts of the world. In South Africa, T. granifera is rapidly invading an increasing number of coastal lakes and estuaries, often reaching very high population densities and dominating shallow water benthic invertebrate assemblages. An assessment of the feeding dynamics of T. granifera has raised questions about potential ecological impacts, specifically in terms of its dietary overlap with native gastropods.A stable isotope mixing model was used together with gut content analysis to estimate the diet of T. granifera and native gastropod populations in three different coastal lakes. Population density, available biomass of food and salinity were measured along transects placed over T. granifera patches. An index of isotopic (stable isotopes) dietary overlap (IDO, %) aided in interpreting interactions between gastropods. The diet of T. granifera was variable, including contributions from microphytobenthos, filamentous algae (Cladophora sp.), detritus and sedimentary organic matter. IDO was significant (>60%) between T. granifera and each of the following gastropods: Haminoea natalensis (Krauss, 1848), Bulinus natalensis (Küster, 1841) and Melanoides tuberculata (Müller, 1774). However, food did not appear to be limiting. Salinity influenced gastropod spatial overlap. Tarebia granifera may only displace native gastropods, such as Assiminea cf. ovata (Krauss, 1848), under salinity conditions below 20. Ecosystem-level impacts are also discussed.The generalist diet of T. granifera may certainly contribute to its successful establishment. However, although competition for resources may take place under certain salinity conditions and if food is limiting, there appear to be other mechanisms at work, through which T. granifera displaces native gastropods. Complementary stable isotope and gut content analysis can provide helpful ecological insights, contributing to monitoring efforts and guiding further invasive species research

University student engagement inventory (USEI): psychometric properties

Academic engagement describes students’ investment in academic learning and achievement and is an important indicator of students’ adjustment to university life, particularly in the first year. A tridimensional conceptualization of academic engagement has been accepted (behavioral, emotional and cognitive dimensions). This paper tests the dimensionality, internal consistency reliability and invariance of the University Student Engagement Inventory (USEI) taking into consideration both gender and the scientific area of graduation. A sample of 908 Portuguese first-year university students was considered. Good evidence of reliability has been obtained with ordinal alpha and omega values. Confirmatory factor analysis substantiates the theoretical dimensionality proposed (second-order latent factor), internal consistency reliability evidence indicates good values and the results suggest measurement invariance across gender and the area of graduation. The present study enhances the role of the USEI regarding the lack of consensus on the dimensionality and constructs delimitation of academic engagement.Jorge Sinval received funding from the William James Center for Research, Portuguese Science Foundation (FCT UID/PSI/04810/2013). Leandro S. Almeida and Joana R. Casanova received funding from CIEd – Research Centre on Education, projects UID/CED/1661/2013 and UID/CED/1661/2016, Institute of Education, University of Minho, through national funds of FCT/MCTES-PT. Joana R. Casanova received funding from the Portuguese Science Foundation (FCT) as a Doctoral Grant, under grant agreement number SFRH/BD/117902/2016.info:eu-repo/semantics/publishedVersio

Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

<p>Abstract</p> <p>Background</p> <p>Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.</p> <p>Methods</p> <p>Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.</p> <p>Results</p> <p>In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).</p> <p>Conclusions</p> <p>The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.</p

Synthetic biology to access and expand nature's chemical diversity

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology — including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits — and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products

A Research Agenda for Helminth Diseases of Humans: Basic Research and Enabling Technologies to Support Control and Elimination of Helminthiases

Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vectors. This will depend largely on updated knowledge of relevant and fundamental parasite biology. There is a need, therefore, to exploit and apply new knowledge and techniques in order to make significant and novel gains in combating helminthiases and supporting the sustainability of current and successful mass drug administration (MDA) programmes. Among the fields of basic research that are likely to yield improved control tools, the Disease Reference Group on Helminth Infections (DRG4) has identified four broad areas that stand out as central to the development of the next generation of helminth control measures: 1) parasite genetics, genomics, and functional genomics; 2) parasite immunology; 3) (vertebrate) host–parasite interactions and immunopathology; and 4) (invertebrate) host–parasite interactions and transmission biology. The DRG4 was established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR). The Group was given the mandate to undertake a comprehensive review of recent advances in helminthiases research in order to identify notable gaps and highlight priority areas. This paper summarises recent advances and discusses challenges in the investigation of the fundamental biology of those helminth parasites under the DRG4 Group's remit according to the identified priorities, and presents a research and development agenda for basic parasite research and enabling technologies that will help support control and elimination efforts against human helminthiases