‘Functional Connectivity’ Is a Sensitive Predictor of Epilepsy Diagnosis after the First Seizure

Background: Although epilepsy affects almost 1 % of the world population, diagnosis of this debilitating disease is still difficult. The EEG is an important tool for epilepsy diagnosis and classification, but the sensitivity of interictal epileptiform discharges (IEDs) on the first EEG is only 30–50%. Here we investigate whether using ‘functional connectivity ’ can improve the diagnostic sensitivity of the first interictal EEG in the diagnosis of epilepsy. Methodology/Principal Findings: Patients were selected from a database with 390 standard EEGs of patients after a first suspected seizure. Patients who were later diagnosed with epilepsy (i.e. $two seizures) were compared to matched nonepilepsy patients (with a minimum follow-up of one year). The synchronization likelihood (SL) was used as an index of functional connectivity of the EEG, and average SL per patient was calculated in seven frequency bands. In total, 114 patients were selected. Fifty-seven patients were diagnosed with epilepsy (20 had IEDs on their EEG) and 57 matched patients had other diagnoses. Epilepsy patients had significantly higher SL in the theta band than non-epilepsy patients. Furthermore, theta band SL proved to be a significant predictor of a diagnosis of epilepsy. When only those epilepsy patients without IEDs were considered (n = 74), theta band SL could predict diagnosis with specificity of 76 % and sensitivity of 62%. Conclusion/Significance: Theta band functional connectivity may be a useful diagnostic tool in diagnosing epilepsy

Life history, distribution and abundance of the giant earthworm Rhinodrilus alatus RIGHI 1971: conservation and management implications

Rhinodrilus alatus is an endemic giant earthworm of the Brazilian Cerrado hotspot used as live bait for about 80 years. The goal of this study was to gather ecological data about this species, which will support the establishment of management strategies. The life history, distribution and abundance of R. alatus were investigated in Cerrado, pastures and Eucalyptus plantation areas following the harvesting activities of the local extractors of this species. We found that this earthworm is abundant in all of the sampled areas, showing its resilience to land-use conversion. The Capture Per Unit Effort was 4.4 ± 5 individuals per 100 metres of transect and 5.6 ± 3 individuals per hour. The earthworm's annual cycle is markedly seasonal, with an aestivation period throughout the driest and coldest season of the year. Significant differences in the length and diameter of the body and in the diameter and depth of the aestivation chambers were found between the juveniles and adults. The distribution range of the species was expanded from two to 17 counties. The life history, abundance, distribution and resilience of R. alatus to certain perturbations are key elements to be considered in conservation and management strategies for this species

Prevention of methamphetamine-induced microglial cell death by TNF-α and IL-6 through activation of the JAK-STAT pathway

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>It is well known that methamphetamine (METH) is neurotoxic and recent studies have suggested the involvement of neuroinflammatory processes in brain dysfunction induced by misuse of this drug. Indeed, glial cells seem to be activated in response to METH, but its effects on microglial cells are not fully understood. Moreover, it has been shown that cytokines, which are normally released by activated microglia, may have a dual role in response to brain injury. This led us to study the toxic effect of METH on microglial cells by looking to cell death and alterations of tumor necrosis factor-alpha (TNF-α) and interleukine-6 (IL-6) systems, as well as the role played by these cytokines.</p> <p><b>Methods</b></p> <p>We used the N9 microglial cell line, and cell death and proliferation were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and incorporation of bromodeoxyuridine, respectively. The TNF-α and IL-6 content was quantified by enzyme-linked immunosorbent assay, and changes in TNF receptor 1, IL-6 receptor-alpha, Bax and Bcl-2 protein levels by western blotting. Immunocytochemistry analysis was also performed to evaluate alterations in microglial morphology and in the protein expression of phospho-signal transducer and activator of transcription 3 (pSTAT3).</p> <p><b>Results</b></p> <p>METH induced microglial cell death in a concentration-dependent manner (EC₅₀ = 1 mM), and also led to significant morphological changes and decreased cell proliferation. Additionally, this drug increased TNF-α extracellular and intracellular levels, as well as its receptor protein levels at 1 h, whereas IL-6 and its receptor levels were increased at 24 h post-exposure. However, the endogenous proinflammatory cytokines did not contribute to METH-induced microglial cell death. On the other hand, exogenous low concentrations of TNF-α or IL-6 had a protective effect. Interestingly, we also verified that the anti-apoptotic role of TNF-α was mediated by activation of IL-6 signaling, specifically the janus kinase (JAK)-STAT3 pathway, which in turn induced down-regulation of the Bax/Bcl-2 ratio.</p> <p><b>Conclusions</b></p> <p>These findings show that TNF-α and IL-6 have a protective role against METH-induced microglial cell death via the IL-6 receptor, specifically through activation of the JAK-STAT3 pathway, with consequent changes in pro- and anti-apoptotic proteins.</p

ICAR: endoscopic skull‐base surgery

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Combined ab initio and kinetic Monte Carlo simulations of C diffusion on the root(3)X root(3) beta-SiC(111) surface

We investigate the kinetic behavior of a single C adatom on the √3 X √3 β-SiC(111) surface by means of combined ab initio and kinetic Monte Carlo simulations. After identifying the metastable binding locations, we calculate the energy barriers the adatom must overcome when jumping among them. The presence of the √3 X √3 reconstruction creates considerable differences among the diffusion mechanisms that can be thermally activated. This has important implications for the C mobility on the surface, and therefore for SiC growth. The kinetic simulation at realistic temperatures and time scales revealed that C diffusion occurs mostly around the Si adatoms forming the √3 X √3 reconstruction. A reduced adatom mobility, as observed in many studies of surfactant-mediated growth, can favor the formation of a high density of nuclei, and thus promote a layer-by-layer growth. As a further result of the kinetic simulation we obtained the adatom diffusion coefficient, a macroscopic quantity accessible in experiments. ©2005 The American Physical Society

Kinetic Monte Carlo simulations of C diffusion on root 3x root 3 beta-SiC(111) based on ab initio calculations

We performed ab initio calculations to identify and characterize the stationary points of the potential energy surface experienced by a C adatom deposited on the root 3- x root 3 beta-SiC(111) surface. A kinetic Monte Carlo simulation relying on the ab initio calculated parameters allowed us to follow C diffusion at realistic temperature and time scales. We found that the C diffusion occurs mostly around the Si adatoms characteristic of the root 3- x root 3- reconstruction

Monitoring metals in toenail samples of a population living in the vicinity of the solid waste incinerator of Modena, Northern Italy

Introduction: As part of the authorization process for the expansion of the solid waste incinerator (SWI), a cross-sectional biomonitoring study was conducted to identify markers of chronic exposure. Metals were measured in toenails, as a single sample is assumed to represent long-term exposure. Methods: Around 500 subjects aged 18-69 yrs. and living within 4-km from the plant were enrolled between Oct. 2013-May 2014. Sampling method implied stratification by exposure, gender and age-group. Toenails were disintegrated by acid mineralization and analyzed through inductively coupled plasma mass spectrometry for concentrations of Cd, Cr, Mn and Ni. SWI exposure was estimated through fallout maps. Biannual PM10 level prior to sampling was assigned according to subjects’ residence and workplace. Confounders were assessed by questionnaire covering personal and health data, lifestyle, residential and occupational information, traffic exposure and diet. Multivariate regression models were performed. Results: Cd, not detectable in &gt;50% of samples, was not further analyzed. Cr, Mn and Ni were detectable in &gt;95% of samples. Significant positive relations were observed for diet, personal and lifestyle characteristics, as well as for SWI exposure. Conclusions: results appear consistent with literature-known associations, suggesting that toenails can be appropriate in assessing chronic exposures of Ni, Mn and Cr, while Cd is probably poorly accumulated in nails. Relations observed with SWI exposure should be accurately considered

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified.

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK-. Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK- and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK-, respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated