A realistic morpho-anatomical connection strategy for modelling full-scale point-neuron microcircuits

The modeling of extended microcircuits is emerging as an effective tool to simulate the neurophysiological correlates of brain activity and to investigate brain dysfunctions. However, for specific networks, a realistic modeling approach based on the combination of available physiological, morphological and anatomical data is still an open issue. One of the main problems in the generation of realistic networks lies in the strategy adopted to build network connectivity. Here we propose a method to implement a neuronal network at single cell resolution by using the geometrical probability volumes associated with pre- and postsynaptic neurites. This allows us to build a network with plausible connectivity properties without the explicit use of computationally intensive touch detection algorithms using full 3D neuron reconstructions. The method has been benchmarked for the mouse hippocampus CA1 area, and the results show that this approach is able to generate full-scale brain networks at single cell resolution that are in good agreement with experimental findings. This geometric reconstruction of axonal and dendritic occupancy, by effectively reflecting morphological and anatomical constraints, could be integrated into structured simulators generating entire circuits of different brain areas facilitating the simulation of different brain regions with realistic models

High (≥6.5) Spontaneous and Persistent Urinary pH Is Protective of Renal Function at Baseline and during Disease Course in Idiopathic Membranous Nephropathy

Metabolic acidosis correction in advanced renal failure slows renal function decline attributed to tubulointerstitial damage (TID) reduction. No study evaluated if spontaneous baseline high urinary pH (UpH) is renoprotective in patients with normal renal function and without metabolic acidosis. The study tested this hypothesis in idiopathic membranous nephropathy (IMN). Eighty-five patients (follow-up 81 ± 54 months) measured UpH, serum creatinine, eGFR, protein/creatinine ratio, fractional excretion of albumin, IgG, α1-microglobulin, and urinary N-acetyl-β-D-glucosaminidase (β-NAG)/creatinine ratio. Twenty-eight patients (33%) had UpH ≥ 6.5 and 57 (67%) pH < 6.5; high versus low UpH patients had significantly lower values of the tubulointerstitial damage (TID) markers FE α1m and β-NAG and significantly better baseline renal function. These differences persisted over time in a subset of 38 patients with 5 measurements along 53 ± 26 months. In 29 patients with nephrotic syndrome (NS) treated with supportive therapy (follow-up: 80 ± 52 months) renal function was stable in 10 high and significantly worse in 19 low UpH patients. Steroids + cyclophosphamide treatment in 35 NS patients masks the renoprotection of high UpH. Conclusions. In IMN high and persistent UpH is associated with reduction of the proteinuric markers of tubulointerstitial damage and baseline better renal function in all patients and in NS patients treated only with supportive therapy during disease course. The factors associated with high pH-dependent renoprotection were lower values of TID markers, eGFR ≥ 60 mL/min, BP < 140/90 mmHg, and age < 55 years

In Crescentic IgA Nephropathy, Fractional Excretion of IgG in Combination with Nephron Loss Is the Best Predictor of Progression and Responsiveness to Immunosuppression

Background and objectives: The aim of this study was to evaluate the relationship between proteinuric markers (urinary excretion of IgG, α2-macroglobulin, α1-microglobulin) and serum creatinine (sCr), histologic lesions, progression, and immunosuppression responsiveness in crescentic IgA nephropathy

Characteristics of EMG frequency bands in temporomandibullar disoders patients

The aim of the present study was to determine whether any specific frequency bands of surface electromyographic (sEMG) signals are more susceptible to alterations in patients with temporomandibular disorders (TMD), when compared with healthy subjects. Twenty-seven healthy adults (19 women and eight men; mean age: 23 ± 6.68 years) and 27 TMD patients (20 women and seven men; mean age: 24 ± 5.89 years) voluntarily participated in the experiment. sEMG data were recorded from the right and left masseter muscles (RM and LM) and the right and left anterior temporalis muscles (RT and LT) as the participants performed tests of chewing (CHW) and maximal clenching effort (MCE). Frequency domain analysis of the sEMG signal was used to analyze differences between TMD patients and healthy subjects in relation to the Power Spectral Density Function (PSDF). The analysis focused on the median frequency (MDF) of the sEMG signal and PSDF frequency bands after the EMG spectrum was divided into twenty-five frequency band of 20 Hz each. The Mann-Whitney test was used to compare MDF between TMD patients and healthy subjects and the frequency bands were analyzed using three-way ANOVA with three factors: frequency band, muscle and group. The results of the analysis confirmed that the median frequency values in TMD patients were significantly higher (p < 0.05) than those recorded for healthy subjects in the two experimental conditions (MCE and CHW), for all of the muscles assessed (RM, LM, RT and LT). In addition, frequency content between 20 and 100 Hz of the normalized PSDF range was significantly lower (p < 0.05) in TMD patients than in healthy. This study contributes to quantitatively identify TMD dysfunctions, by non-invasive sEMGs; this assessment is clinically important and still lacking nowadays

Characteristics of EMG frequency bands in temporomandibullar disoders patients

The aim of the present study was to determine whether any specific frequency bands of surface electromyographic (sEMG) signals are more susceptible to alterations in patients with temporomandibular disorders (TMD), when compared with healthy subjects. Twenty-seven healthy adults (19 women and eight men; mean age: 23 ± 6.68 years) and 27 TMD patients (20 women and seven men; mean age: 24 ± 5.89 years) voluntarily participated in the experiment. sEMG data were recorded from the right and left masseter muscles (RM and LM) and the right and left anterior temporalis muscles (RT and LT) as the participants performed tests of chewing (CHW) and maximal clenching effort (MCE). Frequency domain analysis of the sEMG signal was used to analyze differences between TMD patients and healthy subjects in relation to the Power Spectral Density Function (PSDF). The analysis focused on the median frequency (MDF) of the sEMG signal and PSDF frequency bands after the EMG spectrum was divided into twenty-five frequency band of 20 Hz each. The Mann-Whitney test was used to compare MDF between TMD patients and healthy subjects and the frequency bands were analyzed using three-way ANOVA with three factors: frequency band, muscle and group. The results of the analysis confirmed that the median frequency values in TMD patients were significantly higher (p < 0.05) than those recorded for healthy subjects in the two experimental conditions (MCE and CHW), for all of the muscles assessed (RM, LM, RT and LT). In addition, frequency content between 20 and 100 Hz of the normalized PSDF range was significantly lower (p < 0.05) in TMD patients than in healthy. This study contributes to quantitatively identify TMD dysfunctions, by non-invasive sEMGs; this assessment is clinically important and still lacking nowadays

Realistic modeling of neurons and networks: towards brain simulation

Realistic modeling is a new advanced methodology for investigating brain functions. Realistic modeling is based on a detailed biophysical description of neurons and synapses, which can be integrated into microcircuits. The latter can, in turn, be further integrated to form large-scale brain networks and eventually to reconstruct complex brain systems. Here we provide a review of the realistic simulation strategy and use the cerebellar network as an example. This network has been carefully investigated at molecular and cellular level and has been the object of intense theoretical investigation. The cerebellum is thought to lie at the core of the forward controller operations of the brain and to implement timing and sensory prediction functions. The cerebellum is well described and provides a challenging field in which one of the most advanced realistic microcircuit models has been generated. We illustrate how these models can be elaborated and embedded into robotic control systems to gain insight into how the cellular properties of cerebellar neurons emerge in integrated behaviors. Realistic network modeling opens up new perspectives for the investigation of brain pathologies and for the neurorobotic field

Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness.

BACKGROUND: Treatment of idiopathic membranous nephropathy with nephrotic syndrome is still controversial. There is currently little known about the clinical use of renal biomarkers which may explain contradictory results obtained from clinical trials. In order to assess whether IgG-uria can predict the outcome in membranous nephropathy, we examined the value of baseline EF-IgG in predicting remission and progression of nephrotic syndrome. METHODS: In a prospective cohort of 84 (34 female) idiopathic membranous nephropathy patients with nephrotic syndrome we validated the ability of the clinically available urine biomarker, IgG, to predict the risk of kidney disease progression and the beneficial effect of immunosuppression with steroids and cyclophosphamide. The fractional excretion of IgG (FE-IgG) and α1-microglobulin (FE-α1m), urine albumin/creatinine ratio, and eGFR were measured at the time of kidney biopsy. Primary outcome was progression to end stage kidney failure or kidney function (eGFR) decline ≥ 50% of baseline. Patients were followed up for 7.2 ± 4.1 years (range 1-16.8). RESULTS: High FE-IgG (≥ 0.02) predicted an increased risk of kidney failure (Hazard Ratio, (HR) 8.2, 95%CI 1.0-66.3, p=0.048) and lower chance of remission (HR 0.18, 95%CI 0.09-0.38, p<0.001). The ten-year cumulative risk of kidney failure was 51.7% for patients with high FE-IgG compared to only 6.2% for patients with low FE-IgG. During the study, only 24% of patients with high FE-IgG entered remission compared to 90% of patients with low FE-IgG. Combined treatment with steroids and cyclophosphamide decreased the progression rate (-40%) and increased the remission rate (+36%) only in patients with high FE-IgG. CONCLUSION: In idiopathic membranous nephropathy patients with nephrotic syndrome, FE-IgG could be useful for predicting kidney disease progression, remission, and response to treatment

An account of the bio- and magnetostratigraphy of the Upper Tithonian-Lower Berriasian interval at Le Chouet, Drôme (SE France).

24 pagesInternational audienceThis paper discusses the results of a study of the Le Chouet section, its lithologies, facies, magnetic properties and fossil record (ammonites, calcareous nannofossils, calpionellids and calcareous dinoflagellates). Data obtained have been applied to give a precise biostratigraphy for this carbonate sequence as well as a paleoenvironmental reconstruction. Its relationship to magnetostratigraphy, based on a modern study of a French site, is important. Investigation of the micro- and macrofossils shows that the site comprises a sedimentary sequence in the Microcanthum to Jacobi ammonite Zones, and the Chitinoidella, Crassicollaria and Calpionella Zones. Several calpionellid and nannofossil bioevents have been recorded on the basis of the distribution of stratigraphically important planktonic organisms. The site allows us to calibrate the levels of various biomarkers and biozonal boundaries, and correlate them with the magnetozones M20n, M19r and M19n

Genetic and forensic implications in epilepsy and cardiac arrhythmias. a case series

Epilepsy affects approximately 3 % of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17 % of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24 % of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy