bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin analogues in children with Type 1 diabetes: a 52‐week randomized clinical trial
Authors: Thalange N. , Bereket A. , Larsen J. , Hiort L. C. , Peterkova V. 
Published: October 2012

AbstractAimsThis 52‐week, randomized, multinational, open‐label, parallel‐group, non‐inferiority trial investigated the efficacy and safety of basal–bolus treatment with insulin detemir vs. NPH (neutral protamine Hagedorn) insulin, in combination with insulin aspart, in subjects aged 2–16 years with Type 1 diabetes mellitus.MethodsOf the 347 randomized and exposed subjects, 177 received insulin detemir and 170 NPH insulin, both administered once or twice daily in combination with mealtime insulin aspart. Glycaemic measurements and weight were followed over 52 weeks.ResultsAfter 52 weeks, insulin detemir was shown to be non‐inferior to NPH insulin with regard to HbA1c [mean difference insulin detemir–NPH: 1.30 mmol/mol, 95% CI –1.32 to 3.92 (0.12%, 95% CI –0.12 to 0.36) in the full analysis set and 1.41 mmol/mol, 95% CI –1.26 to 4.08 (0.13%, 95% CI –0.12 to 0.37) in the per protocol analysis set]. Hypoglycaemic events per subject‐year of exposure of 24‐h and nocturnal hypoglycaemia were significantly lower with insulin detemir than with NPH insulin (rate ratio 0.76, 95% CI 0.60–0.97, P = 0.028 and 0.62, 95% CI 0.47–0.84, P = 0.002, respectively). Weight standard deviation (sd) scores (body weight standardized by age and gender) decreased with insulin detemir, but increased slightly with NPH insulin (change: –0.12 vs. 0.04, P < 0.001). At end of the trial, median insulin doses were similar in both treatment groups.ConclusionsInsulin detemir was non‐inferior to NPH insulin after 52 weeks' treatment of children and adolescents aged 2–16 years, and was associated with a significantly lower risk of hypoglycaemia, together with significantly lower weight sd score when compared with NPH insulin.
Cytoarchitectural, behavioural and neurophysiological dysfunctions in theBCNU‐treated rat model of cortical dysplasia
Authors: Inverardi Francesca , Chikhladze Maia , Donzelli Andrea , Moroni Ramona Frida , Regondi Maria Cristina , Pennacchio Paolo , Zucca Ileana , Corradini Irene , Braida Daniela , Sala Mariaelvina , Franceschetti Silvana , Frassoni Carolina 
Published: October 2012

AbstractCortical dysplasias (CDs) include a spectrum of cerebral lesions resulting from cortical development abnormalities during embryogenesis that lead to cognitive disabilities and epilepsy. The experimental model ofCDobtained by means ofin uteroadministration ofBCNU(1‐3‐bis‐chloroethyl‐nitrosurea) to pregnant rats on embryonic day 15 mimics the histopathological abnormalities observed in many patients. The aim of this study was to investigate the behavioural, electrophysiological and anatomical profile ofBCNU‐treated rats in order to determine whether cortical and hippocampal lesions can directly lead to cognitive dysfunction. TheBCNU‐treated rats showed impaired short‐term working memory but intact long‐term aversive memory, whereas their spontaneous motor activity and anxiety‐like response were normal. The histopathological and immunohistochemical analyses, made after behavioural tests, revealed the disrupted integrity of neuronal populations and connecting fibres in hippocampus and prefrontal and entorhinal cortices, which are involved in memory processes. An electrophysiological evaluation of theCA1 region ofin vitrohippocampal slices indicated a decrease in the efficiency of excitatory synaptic transmission and impaired paired pulse facilitation, but enhanced long‐term potentiation (LTP) associated with hyperexcitability inBCNU‐treated rats compared with controls. The enhancedLTP, associated with hyperexcitability, may indicate a pathological distortion of long‐term plasticity. These findings suggest that prenatal developmental insults at the time of peak cortical neurogenesis can induce anatomical abnormalities associated with severe impairment of spatial working memory in adultBCNU‐treated rats and may help to clarify the pathophysiological mechanisms of cognitive dysfunction that is often associated with epilepsy in patients withCD.
Novel approaches to epilepsy treatment
Authors: Sørensen Andreas T. , Kokaia Merab 
Published: October 2012

SummaryThe aim of epilepsy treatment is to achieve complete seizure freedom. Nonetheless, numerous side effects and seizure resistance to antiepileptic drugs (AEDs) affecting about 30–40% of all patients are main unmet needs in today’s epileptology. For this reason, novel approaches to treat epilepsy are highly needed. Herein, we highlight recent progress in stem‐cell–based and gene transfer–based therapies in epilepsy according to findings in animal models and address their potential clinical application. Multiple therapeutic targets are described, including neuropeptides, neurotrophic factors, and inhibitory neurotransmitters. We also address new molecular‐genetic approaches utilizing optogenetic technology. The therapeutic strategies presented herein are predominately aimed toward treatment of partial/focal epilepsies, but could also be envisaged for targeting key seizure propagation areas in the brain. These novel strategies provide proof‐of‐principle for developing effective treatments for refractory epilepsy in the foreseeable future.
Magnetic source imaging and ictal SPECT in MRI‐negative neocortical epilepsies: Additional value and comparison with intracranial EEG
Authors: Schneider Felix , Irene Wang Z. , Alexopoulos Andreas V. , Almubarak Salah , Kakisaka Yosuke , Jin Kazutaka , Nair Dileep , Mosher John C. , Najm Imad M. , Burgess Richard C. 
Published: October 2012

SummaryPurpose:  To investigate the utility of magnetic source imaging (MSI) and ictal single photon emission computed tomography (SPECT), each compared with intracranial electroencephalography (EEG) (ICEEG), to localize the epileptogenic zone (EZ) and predict epilepsy surgery outcome in patients with nonlesional neocortical focal epilepsy.Methods:  Studied were 14 consecutive patients with nonlesional neocortical epilepsy who underwent presurgical evaluation including ICEEG, positive MSI, and localizing subtraction Ictal SPECT coregistered to MRI (SISCOM) analysis. Follow‐up after epilepsy surgery was ≥24 months. ICEEG, MSI, and SPECT results were classified using a sublobar classification.Key Findings:  Of 14 patients, 6 (42.9%) became seizure‐free after surgery. Sublobar ICEEG focus was completely resected in 11 patients; 5 (45.5%) of them became seizure‐ free. Concordance of ICEEG and MSI and complete focus resection was found in 5 (35.7%) patients; 80% of them became seizure‐free. Sublobar ICEEG‐MSI concordance and complete focus resection significantly increased the chance of seizure freedom after epilepsy surgery (p = 0.038). In contrast, of the 6 patients (42.9%) with concordant ICEEG and SISCOM and complete focus resection, only 66.7% became seizure‐free (p = 0.138). Assuming concordant results, the additive value to ICEEG alone for localizing the EZ is higher with ICEEG‐MSI (odds ratio 14) compared to ICEEG‐SISCOM (odds ratio 6).Significance:  This study shows that combination of MSI and/or SISCOM with ICEEG is useful in the presurgical evaluation of patients with nonlesional neocortical epilepsy. Concordant test results of either MSI or SISCOM with ICEEG provide useful additive information for that provided by ICEEG alone to localize the EZ in this most challenging group of patients. When sublobar concordance with ICEEG is observed, MSI is more advantageous compared to SISCOM in predicting seizure‐free epilepsy surgery outcome.
Association between epilepsy and cysticercosis and toxocariasis: A population‐based case–control study in a slum in India
Authors: Singh Gagandeep , Bawa Jasleena , Chinna Deepinder , Chaudhary Anurag , Saggar Kavita , Modi Manish , Sander Josemir W. 
Published: October 2012

SummaryPurpose:  To assess the association between epilepsy and exposure to the parasites, Toxocara canis and Taenia solium in a slum‐community in India.Methods:  A door‐to‐door survey to determine the prevalence of epilepsy was carried out by trained field workers. For every case, one age‐ and gender‐matched control was selected from the same community. Serologic evaluation was carried out to detect antibodies against T. canis and T. solium.Key Findings:  The crude prevalence of active epilepsy was 7.2 per 1,000. We enrolled 114 people with active epilepsy and 114 controls. The prevalence of antibodies to T. canis was similar in people with active epilepsy (4.7%; 5 of 106 people) and in controls (5.7%; 6 of 106 people). The prevalence of antibodies to T. solium was 25.5% (27 of 106) in people with active epilepsy, significantly higher than in controls (12.3%; 13 of 106 cases; p = 0.02). Adjusted conditional (fixed‐effects) logistic regression estimated an odds ratio of 2.8 (95% confidence interval 1.2–6.8) for detection of T. solium antibodies. Nineteen people with active epilepsy demonstrated evidence of neurocysticercosis (NCC) on magnetic resonance imaging (MRI), including 7 (36.5%) with solitary cysticercus granuloma.Significance:  Our findings do not support an association between epilepsy and exposure to T. canis in the community studied. A significant association between T. solium exposure and epilepsy was observed. Of those with active epilepsy and evidence of NCC on MRI, a large proportion demonstrated solitary cysticercus granuloma.
Posthemispherectomy hydrocephalus: Results of a comprehensive, multiinstitutional review
Authors: Lew Sean M. , Matthews Anne E. , Hartman Adam L. , Haranhalli Neil ,   on behalf of the Post‐Hemispherectomy Hydrocephalus Workgroup
Published: October 2012

SummaryPurpose:  Hemispherectomy surgery for medically intractable epilepsy is known to cause hydrocephalus in a subset of patients. Existing data regarding the incidence of, and risk factors for, developing posthemispherectomy hydrocephalus have been limited by the relatively small number of cases performed by any single center. Our goal was to better understand this phenomenon and to identify risk factors that may predispose patients to developing hydrocephalus after hemispherectomy surgery.Methods:  Fifteen pediatric epilepsy centers participated in this study. A retrospective chart review was performed on all available patients who had hemispherectomy surgery. Data collected included surgical techniques, etiology of seizures, prior brain surgery, symptoms and signs of hydrocephalus, timing of shunt placement, and basic demographics.Key Findings:  Data were collected from 736 patients who underwent hemispherectomy surgery between 1986 and 2011. Forty‐six patients had preexisting shunted hydrocephalus and were excluded from analysis, yielding 690 patients for this study. One hundred sixty‐two patients (23%) required hydrocephalus treatment. The timing of hydrocephalus ranged from the immediate postoperative period to 8.5 years after surgery, with 43 patients (27%) receiving shunts >90 days after surgery. Multivariate regression analysis revealed anatomic hemispherectomies (odds ratio [OR] 4.1, p < 0.0001) and previous brain surgery (OR 1.7, p = 0.04) as independent significant risk factors for developing hydrocephalus. There was a trend toward significance for the use of hemostatic agents (OR 2.2, p = 0.07) and the involvement of basal ganglia or thalamus in the resection (OR 2.2, p = 0.08) as risk factors.Significance:  Hydrocephalus is a common sequela of hemispherectomy surgery. Surgical technique and prior brain surgery influence the occurrence of posthemispherectomy hydrocephalus. A significant portion of patients develop hydrocephalus on a delayed basis, indicating the need for long‐term surveillance.
What determines the climatic niche width of species? The role of spatial and temporal climatic variation in three vertebrate clades
Authors: Quintero Ignacio , Wiens John J. 
Published: October 2012

AbstractAimClimatic niche breadth (the range of climatic conditions that a species experiences over space and time) is a fundamental topic in ecology, biogeography and evolution. But what determines the climatic niche width of species? In 1967, Janzen suggested that climatic niche widths for temperature were determined by levels of seasonal fluctuation in temperature at each locality, such that niche breadths are narrow in tropical species and broad in temperate species. However, it is unclear whether climatic niche breadths of species are determined more by seasonal variability within sites as opposed to climatic variation between sites across the species’ range. We address this question here.LocationGlobal.MethodsWe analysed three vertebrate clades (plethodontid salamanders, hylid frogs and phrynosomatid lizards) for which we had phylogenetic information and climatic data from localities throughout each species’ geographic range, collectively including 409 species. We tested how climatic niche breadths of localities (i.e. temporal variation) are related to overall species climatic niche breadths (i.e. temporal and spatial variation) using phylogenetic comparative methods, focusing both on temperature extremes and precipitation.ResultsAcross the three clades, we find that niche breadths for single localities generally span most of the species’ climatic niche breadth, and are strongly correlated with overall species niche breadths. However, species with wider climatic niches also tend to show greater climatic divergence between localities.Main conclusionsThe extent to which the climatic niche breadths of species are determined by variation within localities versus spatial variation between localities has been largely unexplored. Our results suggest that within‐locality seasonal variation explains most variation in climatic niche breadths among species. However, between‐locality variation and local adaptation may also play some role. These results require more general testing, but have several important implications.
Beta‐diversity patterns elucidate mechanisms of alien plant invasion in mountains
Authors: Marini Lorenzo , Bertolli Alessio , Bona Enzo , Federici Germano , Martini Fabrizio , Prosser Filippo , Bommarco Riccardo 
Published: October 2012

AbstractAimOur aims were: (1) to separately evaluate the elevational patterns of β‐diversity for nestedness, species richness difference and replacement, (2) to identify the drivers of β‐diversity patterns by testing the effect of geographical and environmental distance (human population, temperature and land‐use), and (3) to compare the response on native versus alien species to elucidate mechanisms of community assembly along elevational gradients.LocationTwo mountain regions (Bergamo‐Brescia and Trento) in the Italian Alps.MethodsWe used two floristic datasets in which species composition was sampled within two regular grids. First, we extracted species elevational range and quantified species composition nestedness along the elevational gradient. Second, we partitioned β‐diversity into its species richness difference and replacement components and tested drivers using regression on distance matrix and hierarchical partitioning. All analyses were performed on natives and aliens, separately.ResultsFor aliens, we found lack of mountain specialists (i.e. species with a distribution range restricted to high elevations), large nestedness, large species richness difference and low species replacement between low and high elevations. All findings point in the same direction: a great majority of alien species were introduced to the lowlands and only a subset of this community spread up the mountains. Both human pressures and temperature selection were important processes underpinning the observed filtering, while geographical and land‐use distances were not important. Natives present contrasting patterns with large replacement along the elevation gradients indicating different mechanisms of community assembly.Main conclusionsThe relatively large alien species replacement in the lowlands indicated the presence of a pool of species that may potentially invade the temperate mountains in the future. Investigations of the identity of alien species occurring in the lowlands and their climatic pre‐adaptation might provide tools to prevent invasions in the mountains by predicting the potential invaders and their future elevational distribution.
Metabolic analysis of the cutaneous fungi Malassezia globosa and M. restricta for insights on scalp condition and dandruff
Authors: Gordon James A. , Abraham Karen H. , Cox Diana S. , Moore Alison E. , Pople Jennifer E. 
Published: October 2012

SynopsisDandruff is a global consumer problem, characterized by flaking and scaling of the scalp, accompanied by itch and irritancy. However, the aetiology of the condition remains poorly understood, although there is a strong consensus that the cutaneous fungi Malassezia globosa and M. restricta are a major contributory factor. Although there is a paucity of understanding on how these commensal microorganisms adopt a pathogenic phenotype, a rich source of potential insights now exists in the shape of the recently published whole‐genome sequence of M. globosa, a functional annotation and metabolic reconstruction of which is freely accessible via the integrated microbial genomes (IMG) online community resource (http://www.hmpdacc-resources.org/cgi-bin/imgm_hmp/main.cgi). In these studies, we have taken a combined in‐silico and in‐vitro approach to investigate aspects of lipid and amino acid metabolism by M. globosa and M. restricta that have the potential to impact on scalp condition and dandruff. The IMG platform was employed to analyse the metabolism of triacylglycerols and fatty acids, as well as the aromatic amino acid tryptophan, by M. globosa, to investigate pro‐inflammatory pathways linked in the literature to dandruff and pityriasis versicolour, respectively. Results were equivocal, leaving question marks over the ability of M. globosa to fully degrade unsaturated fatty acids and metabolize tryptophan to indole‐3‐pyruvic acid. In‐vitro assay systems were then developed to study the biotransformation of these metabolites by both M. globosa and M. restricta, as well as their effect on human keratinocytes, and the results here indicated that neither unsaturated fatty acids nor indole derivatives are likely to be major aetiological factors in dandruff.
Neuropsychological profile in adults with neurofibromatosis type 1 compared to a control group
Authors: Descheemaeker M.‐J. , Plasschaert E. , Frijns J.‐P. , Legius E. 
Published: October 2012

AbstractBackgroundNeurofibromatosis type 1 (NF1) is a common inherited autosomal dominant condition, characterised by multiple café‐au‐lait macules, axillary and/or inguinal freckling, iris Lisch nodules and tumours of the nervous system such as neurofibromas and optic pathway gliomas. At the same time, NF1 is frequently associated with intellectual disabilities across several neuropsychological domains. Existing neuropsychological data in NF1 adults are limited and sometimes contradictory. Moreover, most studies use a non‐IQ‐controlled norm group for comparison. This study sought to investigate specific neuropsychological characteristics in intellectual abilities unrelated to the global intellectual capacity.MethodTwenty NF1 adults and an IQ‐, age‐ and gender‐matched control group completed a comprehensive neuropsychological test battery composed of specific cognitive tests investigating visual‐spatial abilities and memory, auditory memory, selective and sustained attention and executive functioning. A short version of the Wechsler Adult Intelligence Scale – III was also administered to both groups.ResultsNorm comparison showed that both groups perform poorly on most neuropsychological functions, except for sustained attention. However, comparison with the IQ‐matched control group showed significantly lower scores on visual‐spatial abilities and memory, on auditory working memory and on tests for cognitive flexibility in NF1 adults. Nevertheless, as the significant difference in average estimated IQ score between the NF1 group and the selected control group almost reaches the 5% significance level, further analysis is needed to include IQ as a covariate. Eventually, problems in visual‐spatial skills and auditory long‐term memory seem to be specific NF1‐related deficits, while problems in attention and executive functioning are particularly related to their general lowered intellectual abilities.ConclusionTaking into account that primary visual perception problems could be part of a more general central coherence deficit while interpreting auditory memory problems as possibly related to deficits in language use and comprehension, this idea also fits with the observation of several problems in social information processing and functioning of NF1 persons.
Lipaemic plasma induces haemolysis in resuspended red cell concentrate
Authors: Bashir S. , Wiltshire M. , Cardigan R. , Thomas S. 
Published: October 2012

Introduction  We investigated whether haemolysis in red cells suspended in plasma was affected by the lipid content and/or methylene blue (MB) treatment of fresh‐frozen plasma (FFP). We also investigated whether haemolysis was affected by the conditions under which lipaemic plasma was stored.Methods  Study 1: Visibly lipaemic (n = 22) or nonlipaemic FFP (n = 24) units were thawed, pooled and split into identical pairs, one of which was MB treated. These units were used to resuspend red cell concentrates (RCC) and tested for haemolysis immediately and after 24 and 48 h of storage at 2–6°C. Study 2: Fresh plasma was aliquoted into 15‐ml tubes and stored in one of four ways as follows: room temperature; 2–6°C; frozen and thawed; or twice frozen and thawed. A sample of RCC was resuspended in each of these plasmas and haemolysis measured after 2 h. Study 3: Plasma was divided into 15‐ml tubes and stored as in study 2 followed by storage left standing upright in a refrigerator (2–6°C) for 24 h (with the exception of the room temperature sample). Plasma was separated into top, middle and bottom fractions and used to resuspend RCC that were assessed for haemolysis after 2 h.Results  The levels of haemolysis in RCC were immediately greater when suspended in lipaemic plasma (0·70 ± 0·53% v 0·05 ± 0·06% for nonlipaemic plasma), which increased further on subsequent storage for 48 h (1·22 ± 0·40% v 0·15 ± 0·14% for nonlipaemic plasma). This was irrespective of whether plasma was MB treated. Lipaemic plasma stored frozen and then thawed resulted in the greatest haemolysis. In lipaemic plasma stored at 2–6°C, the chylomicron‐rich top fraction caused the highest level of haemolysis.Conclusion  Haemolysis in red cells is increased in those suspended in lipaemic plasma and is dependent upon the storage conditions of that plasma prior to suspension. These data are relevant to the choice of plasma used to suspend red cells for neonatal exchange transfusion.