Assessment of bulbar function in amyotrophic lateral sclerosis: validation of a self-report scale (Center for Neurologic Study Bulbar Function Scale).

BACKGROUND AND PURPOSE: Impaired bulbar functions of speech and swallowing are among the most serious consequences of amyotrophic lateral sclerosis (ALS). Despite this, clinical trials in ALS have rarely emphasized bulbar function as an endpoint. The rater-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) or various quality-of-life measures are commonly used to measure symptomatic benefit. Accordingly, we sought to evaluate the utility of measures specific to bulbar function in ALS. METHODS: We assessed bulbar functions in 120 patients with ALS, with clinicians first making direct observations of the degree of speech, swallowing and salivation impairment in these subjects. Clinical diagnosis of bulbar impairment was then compared with ALSFRS-R scores, speech rate, time to swallow liquids and solids, and scores obtained when patients completed visual analog scales (VASs) and the newly-developed 21-question self-administered Center for Neurologic Study Bulbar Function Scale (CNS-BFS). RESULTS: The CNS-BFS, ALSFRS-R, VAS and timed speech and swallowing were all concordant with clinician diagnosis. The self-report CNS-BFS and ALSFRS-R bulbar subscale best predicted clinician diagnosis with misclassification rates of 8% and 14% at the optimal cut-offs, respectively. In addition, the CNS-BFS speech and swallowing subscales outperformed both the bulbar component of the ALSFRS-R and speech and swallowing VASs when correlations were made between these scales and objective measures of timed reading and swallowing. CONCLUSIONS: Based on these findings and its relative ease of administration, we conclude that the CNS-BFS is a useful metric for assessing bulbar function in patients with ALS

Categorization of regional and foreign accent in 5- to 7-year-old British children

This study examines children's ability to detect accent-related information in connected speech. British English children aged 5 and 7 years old were asked to discriminate between their home accent from an Irish accent or a French accent in a sentence categorization task. Using a preliminary accent rating task with adult listeners, it was first verified that the level of accentedness was similar across the two unfamiliar accents. Results showed that whereas the younger children group behaved just above chance level in this task, the 7-year-old group could reliably distinguish between these variations of their own language, but were significantly better at detecting the foreign accent than the regional accent. These results extend and replicate a previous study (Girard, Floccia, & Goslin, 2008) in which it was found that 5-year-old French children could detect a foreign accent better than a regional accent. The factors underlying the relative lack of awareness for a regional accent as opposed to a foreign accent in childhood are discussed, especially the amount of exposure, the learnability of both types of accents, and a possible difference in the amount of vowels versus consonants variability, for which acoustic measures of vowel formants and plosives voice onset time are provided. © 2009 The International Society for the Study of Behavioural Development

Spatiotemporal distribution of the seismicity along the Mid-Atlantic Ridge north of the Azores from hydroacoustic data: Insights into seismogenic processes in a ridge-hot spot context

The seismicity of the North Atlantic was monitored from May 2002 to September 2003 by the 'SIRENA array' of autonomous hydrophones. The hydroacoustic signals provide a unique data set documenting numerous low-magnitude earthquakes along the section of the Mid-Atlantic Ridge (MAR) located in a ridge-hot spot interaction context. During the experiment, 1696 events were detected along the MAR axis between 40 degrees N and 51 degrees N, with a magnitude of completeness level of m(b) approximate to 2.4. Inside the array, location errors are in the order of 2 km, and errors in the origin time are less than 1 s. From this catalog, 15 clusters were detected. The distribution of source level (SL) versus time within each cluster is used to discriminate clusters occurring in a tectonic context from those attributed to non-tectonic (i.e. volcanic or hydrothermal) processes. The location of tectonic and non-tectonic sequences correlates well with regions with positive and negative Mantle Bouguer Anomalies (MBAs), indicating the presence of thinner/colder and thicker/warmer crust respectively. At the scale of the entire array, both the complete and declustered catalogs derived from the hydroacoustic signals show an increase of the seismicity rate from the Azores up to 43 degrees 30'N suggesting a diminishing influence of the Azores hot spot on the ridge-axis temperature, and well correlated with a similar increase in the along-axis MBAs. The comparison of the MAR seismicity with the Residual MBA (RMBA) at different scales leads us to think that the low-magnitude seismicity rates are directly related to along-axis variations in lithosphere rheology and temperatures.info:eu-repo/semantics/publishedVersio

Kinase/phosphatase overexpression reveals pathways regulating hippocampal neuron morphology

Kinases and phosphatases that regulate neurite number versus branching versus extension are weakly correlated.The kinase family that most strongly enhances neurite growth is a family of non-protein kinases; sugar kinases related to NADK.Pathway analysis revealed that genes in several cancer pathways were highly active in enhancing neurite growth

Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

Comparing phoneme frequency, age of acquisition, and loss in aphasia:Implications for phonological universals

Phonological complexity may be central to the nature of human language. It may shape the distribution of phonemes and phoneme sequences within languages, but also determine age of acquisition and susceptibility to loss in aphasia. We evaluated this claim using frequency statistics derived from a corpus of phonologically transcribed Italian words (phonitalia, available at phonitalia,org), rankings of phoneme age of acquisition (AoA) and rate of phoneme errors in patients with apraxia of speech (AoS) as an indication of articulatory complexity. These measures were related to cross-linguistically derived markedness rankings. We found strong correspondences. AoA, however, was predicted by both apraxic errors and frequency, suggesting independent contributions of these variables. Our results support the reality of universal principles of complexity. In addition they suggest that these complexity principles have articulatory underpinnings since they modulate the production of patients with AoS, but not the production of patients with more central phonological difficulties

Assessment of Narrow-Body Transport Airplane Evacuation by Numerical Simulation

This paper presents the results obtained with a new agent-based computer model that can simulate the evacuation of narrow-body transport airplanes in the conditions prescribed by the airworthiness regulations for certification. The model, described in detail in a former paper, has been verified with real data of narrow-body certification demonstrations. Numerical simulations of around 20 narrow-body aircraft, representative of current designs in various market segments, show the capabilities of the model and provide relevant information on the relationship between cabin features and emergency evacuation. The longitudinal location of emergency exits seems to be even more important than their size or the overall margin with respect to the prescribed number and type of exits indicated by the airworthiness requirement

Autism spectrum disorder is related to endoplasmic reticulum stress induced by mutations in the synaptic cell adhesion molecule, CADM1

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown molecular pathogenesis. A recent molecular focus has been the mutated neuroligin 3, neuroligin 3(R451C), in gain-of-function studies and for its role in induced impairment of synaptic function, but endoplasmic reticulum (ER) stress induced by mutated molecules also deserves investigation. We previously found two missense mutations, H246N and Y251S, in the gene-encoding synaptic cell adhesion molecule-1 (CADM1) in ASD patients, including cleavage of the mutated CADM1 and its intracellular accumulation. In this study, we found that the mutated CADM1 showed slightly reduced homophilic interactions in vitro but that most of its interactions persist. The mutated CADM1 also showed morphological abnormalities, including shorter dendrites, and impaired synaptogenesis in neurons. Wild-type CADM1 was partly localized to the ER of C2C5 cells, whereas mutated CADM1 mainly accumulated in the ER despite different sensitivities toward 4-phenyl butyric acid with chemical chaperone activity and rapamycin with promotion activity for degradation of the aggregated protein. Modeling analysis suggested a direct relationship between the mutations and the conformation alteration. Both mutated CADM1 and neuroligin 3(R451C) induced upregulation of C/EBP-homologous protein (CHOP), an ER stress marker, suggesting that in addition to the trafficking impairment, this CHOP upregulation may also be involved in ASD pathogenesis

Absence of Ca2+-stimulated adenylyl cyclases leads to reduced synaptic plasticity and impaired experience-dependent fear memory

Ca2+-stimulated adenylyl cyclase (AC) 1 and 8 are two genes that have been shown to play critical roles in fear memory. AC1 and AC8 couple neuronal activity and intracellular Ca2+ increases to the production of cyclic adenosine monophosphate and are localized synaptically, suggesting that Ca2+-stimulated ACs may modulate synaptic plasticity. Here, we first established that Ca2+-stimulated ACs modulate protein markers of synaptic activity at baseline and after learning. Primary hippocampal cell cultures showed that AC1/AC8 double-knockout (DKO) mice have reduced SV2, a synaptic vesicle protein, abundance along their dendritic processes, and this reduction can be rescued through lentivirus delivery of AC8 to the DKO cells. Additionally, phospho-synapsin, a protein implicated in the regulation of neurotransmitter release at the synapse, is decreased in vivo 1 h after conditioned fear (CF) training in DKO mice. Importantly, additional experiments showed that long-term potentiation deficits present in DKO mice are rescued by acutely replacing AC8 in the forebrain, further supporting the idea that Ca2+-stimulated AC activity is a crucial modulator of synaptic plasticity. Previous studies have demonstrated that memory is continually modulated by gene–environment interactions. The last set of experiments evaluated the effects of knocking out AC1 and AC8 genes on experience-dependent changes in CF memory. We showed that the strength of CF memory in wild-type mice is determined by previous environment, minimal or enriched, whereas memory in DKO mice is unaffected. Thus, overall these results show that AC1 and AC8 modulate markers of synaptic activity and help integrate environmental information to modulate fear memory

Synaptic Vesicle Docking: Sphingosine Regulates Syntaxin1 Interaction with Munc18

Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation. Consistently, electron microscopy revealed reduced number of docked vesicles. Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1 conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle docking in primary neurons and increases paired-pulse facilitation when added to wt hippocampal slices. These data provide with a novel mechanism for synaptic vesicle control by sphingolipids and could explain cognitive deficits of NPA patients