Effects of the T-type calcium channel CaV3.2 R1584P mutation on absence seizure susceptibility in GAERS and NEC congenic rats models.

RATIONALE: Low-voltage-activated or T-type Ca2+ channels play a key role in the generation of seizures in absence epilepsy. We have described a homozygous, gain of function substitution mutation (R1584P) in the CaV3.2 T-type Ca2+ channel gene (Cacna1h) in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The non-epileptic control (NEC) rats, derived from the same original Wistar strains as GAERS but selectively in-breed not to express seizures, are null for the R1584P mutation. To study the effects of this mutation in rats who otherwise have a GAERS or NEC genetic background, we bred congenic GAERS-Cacna1hNEC (GAERS null for R1584P mutation) and congenic NEC-Cacna1hGAERS (NEC homozygous for R1584P mutation) and evaluated the seizure and behavioral phenotype of these strains in comparison to the original GAERS and NEC strains. METHODS: To evaluate seizure expression in the congenic strains, EEG electrodes were implanted in NEC, GAERS, GAERS-Cacna1hNEC without the R1584P mutation, and NEC-Cacna1hGAERS with the R1584P mutation rats. In the first study, continuous EEG recordings were acquired from week 4 (when seizures begin to develop in GAERS) to week 14 of age (when GAERS display hundreds of seizures per day). In the second study, the seizure and behavioral phenotype of GAERS and NEC-Cacna1hGAERS strains were evaluated during young age (6 weeks of age) and adulthood (16 weeks of age) of GAERS, NEC, GAERS-Cacna1hNEC and NEC-Cacna1hGAERS. The Open field test (OFT) and sucrose preference test (SPT) were performed to evaluate anxiety-like and depressive-like behavior, respectively. This was followed by EEG recordings at 18 weeks of age to quantify the seizures, and spike-wave discharge (SWD) cycle frequency. At the end of the study, the whole thalamus was collected for T-type calcium channel mRNA expression analysis. RESULTS: GAERS had a significantly shorter latency to first seizures and an increased number of seizures per day compared to GAERS-Cacna1hNEC. On the other hand, the presence of the R1584P mutation in the NEC-Cacna1hGAERS was not enough to generate spontaneous seizures in their seizure-resistant background. 6 and 16-week-old GAERS and GAERS-Cacna1hNEC rats showed anxiety-like behavior in the OFT, in contrast to NEC and NEC-Cacna1hGAERS. Results from the SPT showed that the GAERS developed depressive-like in the SPT compared to GAERS-Cacna1hNEC, NEC, and NEC-Cacna1hGAERS. Analysis of the EEG at 18 weeks of age showed that the GAERS had an increased number of seizures per day, increased total seizure duration and a higher cycle frequency of SWD relative to GAERS-Cacna1hNEC. However, the average seizure duration was not significantly different between strains. Quantitative real-time PCR showed that the T-type Ca2+ channel isoform CaV3.2 channel expression was significantly increased in GAERS compared to NEC, GAERS-Cacna1hNEC and NEC-Cacna1hGAERS. The presence of the R1584P mutation increased the total ratio of CaV3.2 + 25/-25 splice variants in GAERS and NEC-Cacna1hGAERS compared to NEC and GAERS-Cacna1hNEC. DISCUSSION: The data from this study demonstrate that the R1584P mutation in isolation on a seizure-resistant NEC genetic background was insufficient to generate absence seizures, and that a GAERS genetic background can cause seizures even without the mutation. However, the study provides evidence that the R1584P mutation acts as a modulator of seizures development and expression, and depressive-like behavior in the SPT, but not the anxiety phenotype of the GAERS model of absence epilepsy.

Assessment of the Use of Multi-Channel Organic Electrodes to Record ENG on Small Nerves: Application to Phrenic Nerve Burst Detection.

Effective closed-loop neuromodulation relies on the acquisition of appropriate physiological control variables and the delivery of an appropriate stimulation signal. In particular, electroneurogram (ENG) data acquired from a set of electrodes applied at the surface of the nerve may be used as a potential control variable in this field. Improved electrode technologies and data processing methods are clearly needed in this context. In this work, we evaluated a new electrode technology based on multichannel organic electrodes (OE) and applied a signal processing chain in order to detect respiratory-related bursts from the phrenic nerve. Phrenic ENG (pENG) were acquired from nine Long Evans rats in situ preparations. For each preparation, a 16-channel OE was applied around the phrenic nerve's surface and a suction electrode was applied to the cut end of the same nerve. The former electrode provided input multivariate pENG signals while the latter electrode provided the gold standard for data analysis. Correlations between OE signals and that from the gold standard were estimated. Signal to noise ratio (SNR) and ROC curves were built to quantify phrenic bursts detection performance. Correlation score showed the ability of the OE to record high-quality pENG. Our methods allowed good phrenic bursts detection. However, we failed to demonstrate a spatial selectivity from the multiple pENG recorded with our OE matrix. Altogether, our results suggest that highly flexible and biocompatible multi-channel electrode may represent an interesting alternative to metallic cuff electrodes to perform nerve bursts detection and/or closed-loop neuromodulation.

Audiogenic seizure as a model of sudden death in epilepsy: A comparative study between four inbred mouse strains from early life to adulthood.

OBJECTIVE: Mouse models of sudden unexpected death in epileptic patients (SUDEP) using audiogenic seizures (AGS) are valuable because death can occur following a sound-induced seizure in the absence of any pharmacologic or electric component. However, only a few strains of mice are AGS prone, and the vast majority of studies involve DBA/2 or DBA/1 inbred strains. With the goal of characterizing the variation of AGS susceptibility with age, and of offering a larger panel of mice available for AGS studies, we performed a comparative study of the variability in AGS responses. METHODS: The variation of AGS with age was determined in two classically used inbred strains of mice, DBA/2 and DBA/1, and two additional strains, BALB/c and 129/SvTer. As AGS-stimulated tonic seizures can be lethal or nonlethal, even in the same inbred strain, in a second experiment, we addressed whether there is an innate capacity to reproduce the same response after a tonic AGS, referred to as "determinism," in the DBA/2J, DBA/1J, and 129/SvTer mouse strains. RESULTS: Results show that the 129/SvTer mouse is a more versatile model of SUDEP due to its wider age range of susceptibility compared to the DBA/2J and DBA/1J mouse strains. In addition, we show that determinism is not consistently evident in DBA/2J and 129/SvTer strains after AGS. Hence, one cannot be certain that a lethal AGS will always be lethal in successive testing after resuscitation and vice versa in these two mouse strains. SIGNIFICANCE: These studies highlight the phenotypic variability of AGS in different mouse strains, show the value of an additional mouse strain, 129/SvTer, for studies using AGS, and thus provide valuable information for future studies of AGS and SUDEP.

COMP Report: A survey of radiation safety regulations for medical imaging x-ray equipment in Canada.

X-ray regulations and room design methodology vary widely across Canada. The Canadian Organization of Medical Physicists (COMP) conducted a survey in 2016/2017 to provide a useful snapshot of existing variations in rules and methodologies for human patient medical imaging facilities. Some jurisdictions no longer have radiation safety regulatory requirements and COMP is concerned that lack of regulatory oversight might erode safe practices. Harmonized standards will facilitate oversight that will ensure continued attention is given to public safety and to control workplace exposure. COMP encourages all Canadian jurisdictions to adopt the dose limits and constraints outlined in Health Canada Safety Code 35 with the codicil that the design standards be updated to those outlined in NCRP 147 and BIR 2012.

Long-term negative impact of an inappropriate first antiepileptic medication on the efficacy of a second antiepileptic medication in mice.

Childhood absence epilepsy (CAE) is one of the most frequent epilepsies in infancy. The first-line recommended therapy for CAE is based on the prescription of the narrow-spectrum ethosuximide and the broad-spectrum valproic acid, which have similar efficacy in the first 12 months. Nevertheless, some antiepileptic drugs (AEDs) may worsen seizure duration and type in this syndrome. In line with this, we have encountered a case of identical twins with CAE and early exposure to different antiseizure drugs leading to divergent outcomes. From this, we hypothesized that the first AED to treat CAE may determine the long-term prognosis, especially in the developing brain, and that some situations leading to drug resistance may be explained by use of an inappropriate first AED. Therefore, we investigated this hypothesis by using a genetic mouse model of absence epilepsy (BS/Orl). Mice received a first appropriate or inappropriate AED followed by the same appropriate AED. Our data demonstrate that an inappropriate first AED has a negative impact on the long-term efficacy of a second appropriate AED. This work supports the necessity to effectively diagnose epileptic syndromes prior to medication use, particularly in children, in order to prevent the deleterious effects of an inappropriate initial AED.

Glutamatergic neuron-targeted loss of LGI1 epilepsy gene results in seizures.

Leucin-rich, glioma inactivated 1 (LGI1) is a secreted protein linked to human seizures of both genetic and autoimmune aetiology. Mutations in the LGI1 gene are responsible for autosomal dominant temporal lobe epilepsy with auditory features, whereas LGI1 autoantibodies are involved in limbic encephalitis, an acquired epileptic disorder associated with cognitive impairment. We and others previously reported that Lgi1-deficient mice have early-onset spontaneous seizures leading to premature death at 2-3 weeks of age. Yet, where and when Lgi1 deficiency causes epilepsy remains unknown. To address these questions, we generated Lgi1 conditional knockout (cKO) mice using a set of universal Cre-driver mouse lines. Selective deletion of Lgi1 was achieved in glutamatergic pyramidal neurons during embryonic (Emx1-Lgi1cKO) or late postnatal (CaMKIIα-Lgi1cKO) developmental stages, or in gamma amino butyric acidergic (GABAergic) parvalbumin interneurons (PV-Lgi1cKO). Emx1-Lgi1cKO mice displayed early-onset and lethal seizures, whereas CaMKIIα-Lgi1cKO mice presented late-onset occasional seizures associated with variable reduced lifespan. In contrast, neither spontaneous seizures nor increased seizure susceptibility to convulsant were observed when Lgi1 was deleted in parvalbumin interneurons. Together, these data showed that LGI1 depletion restricted to pyramidal cells is sufficient to generate seizures, whereas seizure thresholds were unchanged after depletion in gamma amino butyric acidergic parvalbumin interneurons. We suggest that LGI1 secreted from excitatory neurons, but not parvalbumin inhibitory neurons, makes a major contribution to the pathogenesis of LGI1-related epilepsies. Our data further indicate that LGI1 is required from embryogenesis to adulthood to achieve proper circuit functioning.

Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg.

OBJECTIVE: Originally derived from a Wistar rat strain, a proportion of which displayed spontaneous absence-type seizures, Genetic Absence Epilepsy Rats from Strasbourg (GAERS) represent the most widely utilized animal model of genetic generalized epilepsy. Here we compare the seizure, behavioral, and brain morphometric characteristics of four main GAERS colonies that are being actively studied internationally: two from Melbourne (MELB and STRAS-MELB), one from Grenoble (GREN), and one from Istanbul (ISTAN). METHODS: Electroencephalography (EEG) recordings, behavioral examinations, and structural magnetic resonance imaging (MRI) studies were conducted on GAERS and Non-Epileptic Control (NEC) rats to assess and compare the following: (1) characteristics of spike-and-wave discharges, (2) anxiety-like and depressive-like behaviors, and (3) MRI brain morphology of regions of interest. RESULTS: Seizure characteristics varied between the colonies, with MELB GAERS exhibiting the least severe epilepsy phenotype with respect to seizure frequency, and GREN GAERS exhibiting four times more seizures than MELB. MELB and STRAS-MELB colonies both displayed consistent anxiety and depressive-like behaviors relative to NEC. MELB and GREN GAERS showed similar changes in brain morphology, including increased whole brain volume and increased somatosensory cortical width. A previously identified mutation in the Cacna1h gene controlling the CaV 3.2 T-type calcium channel (R1584P) was present in all four GAERS colonies, but absent in all NEC rats. SIGNIFICANCE: This study demonstrates differences in epilepsy severity between GAERS colonies that were derived from the same original colony in Strasbourg. This multi-institute study highlights the potential impact of environmental conditions and/or genetic drift on the severity of epileptic and behavioral phenotypes in rodent models of epilepsy.

Two polygenic mouse models of major depressive disorders identify TMEM161B as a potential biomarker of disease in humans.

Treatments are only partially effective in major depressive disorders (MDD) but no biomarker exists to predict symptom improvement in patients. Animal models are essential tools in the development of antidepressant medications, but while recent genetic studies have demonstrated the polygenic contribution to MDD, current models are limited to either mimic the effect of a single gene or environmental factor. We developed in the past a model of depressive-like behaviors in mice (H/Rouen), using selective breeding based on behavioral reaction after an acute mild stress in the tail suspension test. Here, we propose a new mouse model of depression (H-TST) generated from a more complex genetic background and based on the same selection process. We first demonstrated that H/Rouen and H-TST mice had similar phenotypes and were more sensitive to glutamate-related antidepressant medications than selective serotonin reuptake inhibitors. We then conducted an exome sequencing on the two mouse models and showed that they had damaging variants in 174 identical genes, which have also been associated with MDD in humans. Among these genes, we showed a higher expression level of Tmem161b in brain and blood of our two mouse models. Changes in TMEM161B expression level was also observed in blood of MDD patients when compared with controls, and after 8-week treatment with duloxetine, mainly in good responders to treatment. Altogether, our results introduce H/Rouen and H-TST as the two first polygenic animal models of MDD and demonstrate their ability to identify biomarkers of the disease and to develop rapid and effective antidepressant medications.

Distinct hyperexcitability mechanisms underlie fast ripples and epileptic spikes.

OBJECTIVE: In partial epilepsies, interictal epileptic spikes (IESs) and fast ripples (FRs) represent clinically relevant biomarkers characteristic of epileptogenic networks. However, their specific significance and the pathophysiological changes leading to either FRs or IESs remain elusive. The objective of this study was to analyze the conditions in which hyperexcitable networks can generate either IESs or FRs and to reveal shared or distinct mechanisms that underlie both types of events. METHODS: This study is the first to comparatively analyze mechanisms that induce either IESs or FRs using an approach that combines computational modeling and experimental data (in vivo and in vitro). A detailed CA1 hippocampal network model is introduced. A parameter sensitivity analysis was conducted to determine which model parameters (cell related and network related) allow the most accurate simulation of FRs and IESs. RESULTS: Our model indicates that although FRs and IESs share certain common mechanisms (shifted gamma-aminobutyric acid [GABA]A reversal potential, altered synaptic transmission), there are also critical differences in terms of number of pyramidal cells involved (small vs large), spatial distribution of hyperexcitable pyramidal cells (clustered vs uniform), and firing patterns (weakly vs highly synchronized). In vitro experiments verified that subtle changes in GABAergic and glutamatergic transmission favor either FRs or IESs, as predicted by the model. INTERPRETATION: This study provides insights into the interpretation of 2 interictal markers observed in intracerebral electroencephalographic data. Depending on the degree and spatiotemporal features of hyperexcitability, not only IESs or FRs are generated but also transitions between both types of events.

Shape features of epileptic spikes are a marker of epileptogenesis in mice.

PURPOSE: To identify reliable biomarkers for quantitatively assessing the development of epilepsy in brain. METHODS: In a kainate mouse model of temporal lobe epilepsy, we performed long-term video-electroencephalography (EEG) monitoring (several weeks) of freely moving animals, from kainic acid injection to chronic epileptic stage. Using signal processing techniques, we automatically detected single epileptic spikes (ESs), and we quantified the evolution of shape features during the epileptogenesis process. Using a computational model of hippocampal activity (neuronal population level), we investigated excitatory-related and inhibitory-related parameters involved in morphologic changes of ESs. KEY FINDINGS: The frequency of ESs increases during epileptogenesis. Regarding shape features, we found that both the initial spike component and the wave component of opposite polarity of ESs gradually increase during epileptogenesis. These very specific alterations of the shape of ESs were reproduced in a computational physiologically relevant neuronal population model. Using this model, we disclosed some key parameters (related to glutamatergic and γ-aminobutyric acid [GABA]ergic synaptic transmission) that explain the shape features of simulated ESs. Of interest, the model predicted that the decrease of GABAergic inhibition is responsible for the increase of the wave component of ESs. This prediction (at first sight counterintuitive) was verified in both in vivo and in vitro experiments. Finally, from aforementioned electrophysiologic features, we devised a novel and easily computable index (wave area/spike amplitude ratio) indicative of the progression of the disease (early vs. late stage). SIGNIFICANCE: Results suggest that dendritic inhibition in hippocampal circuits undertake dramatic changes over the latent period. These changes are responsible for observed modifications in the shape of ESs recorded in local field potential (LFP) signals. The proposed index may constitute a biomarker of epileptogenesis.

Enzyme assisted juice extraction from Dacryodes macrophylla as a potential bio-resource for wine production.

Atom fruit (Dacryodes macrophylla) is a Non-timber Forest Product (NTFP) that comprises a large seed, thick pulp, and a thin hard outer covering. The structural component of its cell wall and thick pulp make it difficult in extracting the juice. Also, Dacryodes macrophylla fruit is greatly underutilized, therefore the need to process and transform it into other value-added products. This work aims to enzymatically extract juice from Dacryodes macrophylla fruit with the aid of pectinase, ferment and test the acceptability of wine produced from this extract. The enzyme and non-enzyme treatments were carried out under the same conditions and their physicochemical properties such as pH, juice yield, total soluble solids, and Vitamin C were compared. A central composite design was used for the optimization of the processing factors for the enzyme extraction process. Enzyme treatment had a great impact on the juice yield (%) and Total soluble solids (TSS) (0Brix) of samples as it was as high as 81 ± 0.7% and 10.6 ± 0.02 0Brix whereas, that of the non-enzyme treatments were 46 ± 0.7% and 9.5 ± 0.02 0Brix respectively. However, the Vitamin C content of enzyme-treated juice decreased to 11.32 ± 0.13 mg/ml as compared to that of the non-enzyme-treated juice sample (15.7 ± 0.04 mg/ml). The optimum processing condition in the extraction of juice from the atom fruit was 1.84% enzyme concentration, 49.02 Ö¯C Incubation temperature, and 43.58 min Incubation time. During wine processing within 14 days of primary fermentation, the pH of the must decreased from 3.42 ± 0.07 to 3.26 ± 0.07 whereas the Titratable acidity (TA) increased from 0.16 ± 0.05 to 0.51 ± 0.0. The wine produced from Dacryodes macrophylla fruit showed promising results as its sensorial scores for all attributes including color, clarity, flavor, mouthfeel, alcoholic burn after taste and overall acceptability were all above 5. Thus, enzymes can be used to improve the juice yield of Dacryodes macrophylla fruit and hence, can be a potential bioresource for wine production.

New analysis workflow for MALDI imaging mass spectrometry: application to the discovery and identification of potential markers of childhood absence epilepsy.

Childhood absence epilepsy is a prototypic form of generalized nonconvulsive epilepsy characterized by short impairments of consciousness concomitant with synchronous and bilateral spike-and-wave discharges in the electroencephalogram. For scientists in this field, the BS/Orl and BR/Orl mouse lines, derived from a genetic selection, constitute an original mouse model "in mirror" of absence epilepsy. The potential of MALDI imaging mass spectrometry (IMS) for the discovery of potential biomarkers is increasingly recognized. Interestingly, statistical analysis tools specifically adapted to IMS data sets and methods for the identification of detected proteins play an essential role. In this study, a new cross-classification comparative design using a combined discrete wavelet transformation-support vector machine classification was developed to discriminate spectra of brain sections of BS/Orl and BR/Orl mice. Nineteen m/z ratios were thus highlighted as potential markers with very high recognition rates (87-99%). Seven of these potential markers were identified using a top-down approach, in particular a fragment of Synapsin-I. This protein is yet suspected to be involved in epilepsy. Immunohistochemistry and Western Blot experiments confirmed the differential expression of Synapsin-I observed by IMS, thus tending to validate our approach. Functional assays are being performed to confirm the involvement of Synapsin-I in the mechanisms underlying childhood absence epilepsy.

Genetic association between helpless trait and depression-related phenotypes: evidence from crossbreeding studies with H/Rouen and NH/Rouen mice.

Genetic factors are believed to be involved in the aetiology of unipolar depressive disorders. We have previously described a model built up by selective breeding of mice with different responses in the tail suspension test, a screening test for potential antidepressants. In this model, helpless H/Rouen mice are essentially immobile in this test, as well as in the Porsolt forced-swim test, whereas non-helpless NH/Rouen mice show the opposite behaviour, i.e. very low immobility. However, it is unclear whether or not the other phenotypic differences (forced swim test, locomotor activity, sucrose test, sleep patterns, effect of fluoxetine) observed between H/Rouen and the NH/Rouen mice may be attributed to a genetic drift phenomenon during the selection step, rather than being related to the trait of selection. In this study we used reciprocal crossbreeding between H/Rouen and NH/Rouen mice and obtained a segregating F2 population in order to determine whether phenotypic differences between the two lines co-segregate with the trait of selection. In the segregating F2 population, we found significant and strong genetic correlations between helplessness in the tail suspension test and some phenotypical features associated with depressive disorders such as 'alterations of sleep patterns', behavioural response to fluoxetine, immobility duration in the forced swim test, and anhedonia. Our results converge with clinical observations in depressed humans. These results strengthen the validity of the H/Rouen mouse as a model of depression, notably for preclinical studies with antidepressants. In addition, this model should open the way to identifying genes related to depression-like behaviours.

Respiratory dysfunction in two rodent models of chronic epilepsy and acute seizures and its link with the brainstem serotonin system.

Patients with drug-resistant epilepsy can experience respiratory alterations, notably during seizures. The mechanisms underlying long-term alterations in respiratory function remain unclear. As the brainstem 5-HT system is a prominent modulator of respiratory function, this study aimed at determining whether epilepsy is associated with alterations in both the respiratory function and brainstem serotonin (5-HT) system in rats. Epilepsy was triggered by pilocarpine-induced status epilepticus in rats. Our results showed that 30-50% of epileptic (EPI) rats exhibited a sharp decrease in oxygen consumption (SDOC), low metabolic rate of oxygen, and slow regular ventilation (EPI/SDOC + rats). These alterations were detected only in rats with chronic epilepsy, independent of behavioral seizures, were persistent over time, and not associated with death. In these rats, 5-HT fiber density in the nucleus tractus solitarius was lower than that in the control and EPI/SDOC- rats. Both EPI/SDOC + rats and DBA/2 mice that present with audiogenic-induced seizure followed by fatal respiratory arrest-a model of sudden and expected death in epilepsy-had increased transcript levels of tryptophan hydroxylase 2 and 5-HT presynaptic transporter. Thus, our data support that 5-HT alterations are associated with chronic and acute epilepsy-related respiratory dysfunction.

Development and characterization of a PLGA-HA composite material to fabricate 3D-printed scaffolds for bone tissue engineering.

Additive manufacturing is a rising field in bone tissue engineering. Additive fabrication offers reproducibility, high precision and rapid manufacture of custom patient-specific scaffolds. The development of appropriate composite materials for biomedical applications is critical to reach clinical application of these novel biomaterials. In this work, medical grade poly(lactic-co-glycolic) acid (PLGA) was mixed with hydroxyapatite nanoparticles (nHA) to fabricate 3D porous scaffolds by Fused Deposition Modeling. We have first confirmed that the composite material could be printed in a reproductive manner. Physical characterization demonstrated a low degradation of the material during manufacturing steps and an expected loading and homogeneous distribution of nHA. In vitro biodegradation of the scaffolds showed modifications of morphological and physicochemical properties over time. The composite scaffolds were biocompatible and high cell viability was observed in vitro, as well as a maintain of cell proliferation. As expected, the addition of nHA displayed a positive impact on osteodifferentiation in vitro. Furthermore, a limited inflammatory reaction was observed after subcutaneous implantation of the materials in the rat. Overall, this study suggests that this composite material is suitable for bone tissue engineering applications.

Selection of two lines of mice based on latency to onset of methionine sulfoximine seizures.

PURPOSE: In various animals methionine sulfoximine (MSO) induces tonic-clonic seizures resembling the most striking form of human epilepsies. The aim of the present study was to select two lines of mice based upon differences in their latency to MSO-dependent seizures, in order to characterize them. METHODS: Random crosses involving eight inbred mice strains were used to generate the starting population in which the first MSO challenge (75 mg/kg, i.p.) was performed. Two groups of 16 breeding pairs were established by mating mice having the shortest (MSO-Fast) and the longest (MSO-Slow) convulsion latencies. Mating and selection by latency to MSO (75 mg/kg, i.p.) was carried out over six generations. RESULTS: MSO-Fast mice presented a significantly shorter MSO latency, and were more susceptible to MSO than MSO-Slow ones were. Electroencephalography (EEG) alterations were observed during the preconvulsive period when MSO-Fast mice were submitted to 75 mg/kg of MSO, and MSO-Slow ones to 200 mg/kg. Using another convulsant, kainic acid, the latency to convulse of MSO-Fast mice was significantly shorter than that of the MSO-Slow ones, whereas no difference was observed in response to pentylenetetrazole (PTZ). MSO-dependent convulsions were completely antagonized by MK-801, and partially by valproic acid, suggesting a preferential involvement of glutamatergic pathways. DISCUSSION: The model that we have developed for MSO "sensitive" and "resistant" mice could allow for a better understanding of MSO mechanisms of epileptogenesis, and it may also constitute a useful approach for therapeutic actions of drugs.

Synergistic interactions in dilute aqueous solutions between alginate and tropical vegetal hydrocolloids.

Encapsulation in alginate beads has always been limited by the leakage due to the too wide distribution of pore sizes. Mixing alginate with other polymers have sometimes reduced the problem. Hydrocolloids from seven tropical vegetal species (barks of Triumfetta cordifolia and Bridelia thermifolia, seeds of Irvingia gabonensis and Beilschmiedia obscura, and leaves of Ceratotheca sesamoides, Adansonia digitata and Corchorus olitorius) were screened for synergistic interactions with alginate in dilute aqueous solution. Mixtures with alginate were made at different volume proportions and deviations from the initial viscosity set at 1 were evaluated. In distilled water, the gums from T. cordifolia, B. obscura, C. sesamoides and C. olitorius presented synergies with alginate. In 2 mM calcium chloride, the seven gums showed positive synergy. Interactions are favored by gum flexibility and the presence of charges, although high charges reduced the interactions. Alginate fraction of maximum viscosity enhancement depends on the ability to conformational order of the gum. The measure by laser diffraction of alginate-gum particles sizes at different fractions showed that the cooperative interactions did not always involve the largest complexes formed in gums associations. The occurrence of these interactions predicts the formation of homogeneous mixed gels at higher polymer and calcium concentrations.

Ensemble Learning of Convolutional Neural Network, Support Vector Machine, and Best Linear Unbiased Predictor for Brain Age Prediction: ARAMIS Contribution to the Predictive Analytics Competition 2019 Challenge.

We ranked third in the Predictive Analytics Competition (PAC) 2019 challenge by achieving a mean absolute error (MAE) of 3.33 years in predicting age from T1-weighted MRI brain images. Our approach combined seven algorithms that allow generating predictions when the number of features exceeds the number of observations, in particular, two versions of best linear unbiased predictor (BLUP), support vector machine (SVM), two shallow convolutional neural networks (CNNs), and the famous ResNet and Inception V1. Ensemble learning was derived from estimating weights via linear regression in a hold-out subset of the training sample. We further evaluated and identified factors that could influence prediction accuracy: choice of algorithm, ensemble learning, and features used as input/MRI image processing. Our prediction error was correlated with age, and absolute error was greater for older participants, suggesting to increase the training sample for this subgroup. Our results may be used to guide researchers to build age predictors on healthy individuals, which can be used in research and in the clinics as non-specific predictors of disease status.

Practice style traits of student occupational therapists and physical therapists.

BACKGROUND: Intensive efforts are aimed at understanding student attributes in anticipation that this will lead to effective knowledge translation (KT) strategies. One attribute of interest is practice style trait: four have been identified ranging from the seeker, who is driven by scientific evidence, to the pragmatist, who is driven by practicality. PURPOSE: To identify the prevalence of the four traits among student clinicians and explore associations between these traits, clinician characteristics and practice behaviours. METHODS: Ninety-two occupational therapy and 86 physical therapy students completed a survey that elicited information on traits, clinician characteristics, and practice behaviours. FINDINGS: The most prevalent trait was pragmatic, the least, seeker at <1%. The most prevalent reason for choosing an intervention was "it was used by my clinical supervisor". IMPLICATIONS: Educators should carefully reconsider the implication of using KT strategies that cater primarily to seekers. Research is warranted to explore the impact of matching educational strategies to traits.

Publisher Correction: The effect of attention and working memory on the estimation of elapsed time.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.