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Objective: We aimed to evaluate epidemiology, seizure type, EEG, and etiology of neonatal seizures (NS) in a tertiary neonatal intensive care unit., Methods: Data on infants with a neurophysiological confirmation of NS were collected between 2009 and 2022. Seizure types and epileptic syndromes were classified by the ILAE classification and EEG by the Italian Neonatal Seizure Collaborative Network (INNESCO) score., Results: Out of 91,253 neonates, 145 presented with NS; 69.7 % were born at term and 30.3 % were preterm infants. The incidence of NS in neonates born at our center was 1.2 per 1,000 live newborns (96/80697 neonates) while in the entire neonatal population admitted to our center it was 1.6 per 1,000 live births, increasing with lower preterm age. Compared to previous studies, we found a lower proportion of hypoxic-ischemic encephalopathy (HIE) (23.4 %) and a higher rate of genetic contribution (26.2 %). The infection rate was higher in preterm (31.8 %) than in full term (9.9 %) infants. Electrographic seizures were associated with acute provoked seizures (35.9 %), preterm age (52.3 %), and HIE (52.9 %). Vascular etiology was associated with focal clonic seizures (56.8 %). Non-structural neonatal genetic epilepsy was associated with sequential seizures (68.2 %), particularly KCNQ2 and SCN2A epilepsy. Background EEG was abnormal in all HIE, infections (85.7 %) and metabolic NS (83.3 %). In genetic epilepsy, background EEG depended on the epileptic syndrome: normal in 80 % of self-limited neonatal epilepsy and abnormal in 77.8 % of developmental and epileptic encephalopathy. Electroclinical seizures were associated with focal onset, while electrographic seizures correlated with a multifocal onset., Conclusions: A low incidence of HIE and a high incidence of genetic etiology were observed in our cohort of NS. Seizure type and EEG features are fundamental to address etiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Outdoor exposure to particulate matter (PM 2.5 and PM 10 ) in urban areas can vary considerably depending on the mode of transport. This study aims to quantify this difference in exposure during daily travel, by carrying out a micro-sensor measurement campaign. The pollutant exposure was assessed simultaneously over predefined routes in order to allow comparison between different transport modes having the same starting and ending points. During the six-week measurement campaign, the average reference values for PM background concentrations were 13.72 and 17.92μg/m 3 for the PM 2.5 and PM 10 , respectively. The results revealed that the mode with the highest exposure to PM 2.5 adjusted to background concentration (PM 2.5Norm ) was the bus (1.65) followed by metro (1.51), walking (1.33), tramway (1.31), car (1.09) and finally the bike (1.06). For PM 10Norm , the tramway had the highest exposure (1.86), followed by walking (1.68), metro (1.65), bus (1.61), bike (1.43) and finally the car (1.39). The level of urbanization around the route and the presence of preferential lanes for public transportation influenced the concentration to which commuters were exposed. For the active modes (bike and walking), we observed frequent variations in concentrations during the trip, characterized by punctual peaks in concentration, depending on the local characteristics of road traffic and urban morphology. Fluctuations in particulate matter inside public transport vehicles were partly explained by the opening and closing of doors during stops, as well as the passenger flows, influencing the re-suspension of particles. The car was one of the least exposed modes overall, with the lowest concentration variability, although these concentrations can vary greatly depending on the ventilation parameters used. These results encourage measures to move the most exposed users away from road traffic, by developing a network of lanes entirely dedicated to cycling and walking, particularly in densely populated areas, as well as encouraging the renewal of motorized vehicles to use less polluting fuels with efficient ventilation systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The current study aims to investigate the effect of Executive Functions (EFs) on Health Related Quality of Life (HRQoL) in a cohort of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to identify possible factors that impact HRQoL specifically related to epilepsy-related variables and EFs skills., Material and Method: The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) and The Behavior Rating Inventory of Executive Function (BRIEF-2 and BRIEF-P) were completed by the parents of 129 patients with SeLECTS. Demographic variables and epilepsy-related variables were collected., Results: Our sample performed in the average range across all the subscales and summary scores of the PedsQL and performed in the normal range of the BRIEF questionnaire. We observed that a lower functioning in EFs was associated with lower overall HRQoL scores. We explored the relationship between epilepsy characteristics and scores on the PedsQL. We found that the use of antiseizure medications (ASMs), longer duration of the treatment, and a higher seizure frequency were associated with a lower HRQoL. Moreover, we observed that executive dysfunction was a significant predictor of reduced HRQoL., Conclusion: Our results suggest the importance of the identification of patients with SeLECTS with a high level of risk for a poor HRQoL. We may now add executive dysfunction to the list of known risk factors for poor HRQoL in children with SeLECTS, along with such factors as seizure frequency, recent seizures, use of ASMs and longer duration of therapy. The early identification of children with SeLECTS at risk of a poor HRQoL could allow the activation of adequate interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This retrospective study assessed long-term effectiveness of add-on perampanel (PER) in patients with Lennox-Gastaut syndrome (LGS). Outcomes included time to PER failure and time to seizure relapse in responders. PER failure was defined as either discontinuation of PER or initiation of another treatment. Seizure relapse in responders was defined as occurrence of a seizure in seizure-free patients and increase of at least 50% in average monthly seizure frequency for those who were responders. Eighty-seven patients were included. Treatment failure occurred in 52 (59.8%) subjects at a median time of 12 months. Treatment failure was due to lack of efficacy in 27 (52.0%) patients, lack of tolerability in 14 (27.0%), and both reasons in 11 (21.0%). A slower titration was associated with a lower risk of PER failure compared to faster titration schedules, and the occurrence of adverse events increased the risk of treatment failure. Thirty-six patients (41.4%) were responders during a median follow-up of 11 months. Seizure relapse occurred in 13 of 36 (36.1%) patients after a median time of 21 months. The overall rate of seizure responders was 23 of 87 (26.4%) at the end of follow-up. This study provides real-world evidence on the effectiveness of PER as adjunctive treatment in LGS patients., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical similarity to humans. However, there is a considerable knowledge gap on the multiscale morphological and mechanical properties of the miniature pigs' jawbones, which is crucial for implant studies and a direct comparison to human tissue. In the present work, we demonstrate a multimodal framework to assess the jawbone quantity and quality for a minipig animal model that could be further extended to humans. Three minipig genotypes, commonly used in dental research, were examined: Yucatan, Göttingen, and Sinclair. Three animals per genotype were tested. Cortical bone samples were extracted from the premolar region of the mandible, opposite to the teeth growth. Global morphological, compositional, and mechanical properties were assessed using micro-computed tomography (micro-CT) together with Raman spectroscopy and nanoindentation measurements, averaged over the sample area. Local mineral-mechanical relationships were investigated with the site-matched Raman spectroscopy and micropillar compression tests. For this, a novel femtosecond laser ablation protocol was developed, allowing high-throughput micropillar fabrication and testing without exposure to high vacuum. At the global averaged sample level, bone relative mineralization demonstrated a significant difference between the genotypes, which was not observed from the complementary micro-CT measurements. Moreover, bone hardness measured by nanoindentation showed a positive trend with the relative mineralization. For all genotypes, significant differences between the relative mineralization and elastic properties were more pronounced within the osteonal regions of cortical bone. Site-matched micropillar compression and Raman spectroscopy highlighted the differences between the genotypes' yield stress and mineral to matrix ratios. The methods used at the global level (averaged over sample area) could be potentially correlated to the medical tools used to assess jawbone toughness and morphology in clinics. On the other hand, the local analysis methods can be applied to quantify compressive bone mechanical properties and their relationship to bone mineralization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Neurodevelopmental disorders comprise a clinically and genetically heterogeneous group of conditions that affect 2%-5% of children and represents a public health challenge due to complexity of the etiology. Only few patients with unexplained syndromic and non-syndromic NDDs receive a diagnosis through first-tier genetic tests as array-CGH and the search for FMR1 CGG expansion. The aim of this study was to evaluate the clinical performance of a targeted next-generation sequencing (NGS) gene panel as a second-tier test in a group of undiagnosed patients with NDDs. Method: A 221-gene next-generation sequencing custom panel was designed and used to analyze a cohort of 338 patients with a broad spectrum of NDDs (202 males and 136 females) including Intellectual Disability (ID), Autism Spectrum Disorders (ASD), Epilepsy, language and motor disorders. Results: A molecular diagnosis was established in 71 patients (21%) and a de novo origin was present in 38 (64.4%) of the available trios. The diagnostic yield was significantly higher in females than in males (29.4% vs. 15.3%; p = 0.0019) in particular in ASD (36.8% vs. 7.6%; p = 0.0026) and Epilepsy (38.9% vs. 14.4% p = 0.001). The most involved genes were SLC2A1 , SCN1A, ANKRD11 , ATP1A2 , CACNA1A , FOXP1 , and GNAS altered in more than two patients and accounting for the 19.7% of the diagnosis. Conclusion: Our findings showed that this NGS panel represents a powerful and affordable clinical tool, significantly increasing the diagnostic yield in patients with different form of NDDs in a cost- and time-effective manner without the need of large investments in data storage and bioinformatic analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mellone, Puricelli, Vurchio, Ronzani, Favini, Maruzzi, Peruzzi, Papa, Spano, Sirchia, Mandrile, Pelle, Rasmini, Vercellino, Zonta, Rabbone, Dianzani, Viri and Giordano.)

Rural children are exposed to several chemicals. This study evaluated the environmental co-exposure of rural children to cholinesterase inhibitor insecticides and metals/metalloids, and the resulting oxidative stress and DNA damage. Seventy-two children (5 to 16 years old) were studied at two different moments: period 1, when agrochemicals were less used, and period 2, when agrochemicals were extensively used in agriculture. Biomonitoring was performed by evaluating butyrylcholinesterase (BuChE) activity in serum; arsenic (As), chromium (Cr), lead (Pb), and nickel (Ni) levels in blood; malondialdehyde (MDA) in plasma; glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) activities in whole blood; non-protein thiol levels in erythrocytes; and micronuclei (MN) assay in exfoliated buccal cells. Cr and As levels were higher than the reference values in both periods, and Ni levels were higher than the reference values in period 2 alone. BuChE activity was inhibited in period 2 compared with period 1. In period 2, there was an increase in endogenous antioxidants and a decrease in MDA, probably demonstrating a compensatory mechanism as a response to increasing xenobiotics. Also in period 2, the MN frequency increased and BuChE and As were positively associated, suggesting co-exposure. On the other hand, in period 1, it was observed that Cr, Ni, and Pb blood levels were negatively associated with GSH-Px and GST, while MDA was positively associated with As levels. Our findings demonstrated an imbalance in endogenous antioxidants, contributing to genotoxicity and lipoperoxidation, probably in response to exposure to xenobiotics, especially carcinogenic elements (Cr, As, and Ni)., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The increased risk of fracture in the elderly associated with metabolic conditions like osteoporosis poses a significant strain on health care systems worldwide. Due to bone's hierarchical nature, it is necessary to study its mechanical properties and failure mechanisms at several length scales. We conducted micropillar compression experiments on ovine cortical bone to assess the anisotropic mechanical response at the lamellar scale over a wide range of strain rates (10 -4 to 8·10 2 s -1 ). At the microscale, lamellar bone exhibits a strain rate sensitivity similar to what is reported at the macroscale suggesting that it is an intrinsic property of the extracellular matrix. Significant shear band thickening was observed at high strain rates by HRSEM and STEM imaging. This is likely caused by the material's inability to accommodate the imposed deformation by propagation of thin kink bands and shear cracks at high strain rates, leading to shear band thickening and nucleation. The post-yield behavior is strain rate and direction dependent: hardening was observed for transverse oriented micropillars and hardening modulus increases with strain rate by a factor of almost 2, while axially oriented micropillars showed strain softening and an increase of the softening peak width and work to ultimate stress as a function of strain rate. This suggests that for compression at the micrometer scale, energy absorption in bone increases with strain rate. This study highlights the importance of investigating bone strength and post-yield behavior at lower length scales, under hydrated conditions and at clinically relevant strain rates. STATEMENT OF SIGNIFICANCE: We performed micropillar compression experiments of ovine cortical bone at two different orientations and over seven orders of magnitude of strain rate. Experiments were performed under humid condition to mimic the natural conditions of bone in a human body using a newly developed micro-indenter setup. The strain rate sensitivity was found to be of a similar magnitude to what has been reported for higher length scales, suggesting that the strain rate sensitivity is an intrinsic property of the bone extracellular matrix. In addition, localized shear deformation in thick bands was observed for the first time at high strain rates, highlighting the importance of investigating bone under conditions representative of an accident or fall at several length scales., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Osteogenesis imperfecta (OI) is an inheritable, genetic, and collagen-related disorder leading to an increase in bone fragility, but the origin of its "brittle behavior" is unclear. Because of its complex hierarchical structure, bone behaves differently at various length scales. This study aims to compare mechanical properties of human OI bone with healthy control bone at the extracellular matrix (ECM) level and to quantify the influence of the degree of mineralization. Degree of mineralization and mechanical properties were analyzed under dry conditions in 12 fixed and embedded transiliac crest biopsies (control n = 6, OI type I n = 3, OI type IV n = 2, and OI type III n = 1). Mean degree of mineralization was measured by microcomputed tomography at the biopsy level and the mineral-to-matrix ratio was assessed by Raman spectroscopy at the ECM level. Both methods revealed that the degree of mineralization is higher for OI bone compared with healthy control. Micropillar compression is a novel technique for quantifying post-yield properties of bone at the ECM level. Micropillars (d = 5 μm, h = 10 μm) were fabricated using focused ion beam milling and quasi-statically compressed to capture key post-yield properties such as ultimate strength. The qualitative inspection of the stress-strain curves showed that both OI and healthy control bone have a ductile response at the ECM level. The quantitative results showed that compressive strength is not reduced in OI bone and is increasing with OI severity. Nanoindentation measurements revealed that OI bone tends to have a higher Young's modulus, hardness, and dissipated energy compared with healthy bone. Micropillar strength and indentation modulus increased linearly and significantly (p < .0001) with mineral-to-matrix ratio. In conclusion, this study indicates that compressive mechanical properties of dry OI bone at the iliac crest are not inferior to healthy control at the ECM level and increase with mineralization. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

In several biomedical applications, the detection of biomarkers demands high sensitivity, selectivity and easy-to-use devices. Organic electrochemical transistors (OECTs) represent a promising class of devices combining a minimal invasiveness and good signal transduction. However, OECTs lack of intrinsic selectivity that should be implemented by specific approaches to make them well suitable for biomedical applications. Here, we report on a biosensor in which selectivity and a high sensitivity are achieved by interfacing, in an OECT architecture, a novel gate electrode based on aptamers, Au nanoparticles and graphene hierarchically organized to optimize the final response. The fabricated biosensor performs state of the art limit of detection monitoring biomolecules, such as thrombin-with a limit of detection in the picomolar range (≤ 5 pM) and a very good selectivity even in presence of supraphysiological concentrations of Bovine Serum Albumin (BSA-1mM). These accomplishments are the final result of the gate hierarchic structure that reduces sterich indrance that could contrast the recognition events and minimizes false positive, because of the low affinity of graphene towards the physiological environment. Since our approach can be easily applied to a large variety of different biomarkers, we envisage a relevant potential for a large series of different biomedical applications.

Bone is a natural composite possessing outstanding mechanical properties combined with a lightweight design. The key feature contributing to this unusual combination of properties is the bone hierarchical organization ranging from the nano- to the macro-scale. Bone anisotropic mechanical properties from two orthogonal planes (along and perpendicular to the main bone axis) have already been widely studied. In this work, we demonstrate the dependence of the microscale compressive mechanical properties on the angle between loading direction and the mineralized collagen fibril orientation in the range between 0° and 82°. For this, we calibrated polarized Raman spectroscopy for quantitative collagen fibril orientation determination and validated the method using widely used techniques (small angle X-ray scattering, micro-computed tomography). We then performed compression tests on bovine cortical bone micropillars with known mineralized collagen fibril angles. A strong dependence of the compressive micromechanical properties of bone on the fibril orientation was found with a high degree of anisotropy for both the elastic modulus (E a /E t =3.80) and the yield stress (σ a y /σ t y =2.54). Moreover, the post-yield behavior was found to depend on the MCF orientation with a transition between softening to hardening behavior at approximately 50°. The combination of methods described in this work allows to reliably determine structure-property relationships of bone at the microscale, which may be used as a measure of bone quality., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020. Published by Elsevier Ltd.)

The study aimed to evaluate the potential effects of the chronic exposure to chemical agents from air pollution on phenotypic and genotypic expressions of peripheral biomarkers and tumor-related proteins in mononuclear cells. This study evaluates 85 taxi drivers (outdoor workers) and 55 non-occupationally exposed persons (NOE) to air pollution (indoor workers). The biomarkers were urinary 1-hydroxypyrene (1-OHP), for organic agents, and blood As and Ni, for inorganic agents. Oxidative stress biomarkers; protein expression of ICAM-1 (CD54), β2-integrin, L-selectin (CD62-L), and MCP1; gene expression of ICAM-1, p53 and CD26 were performed. Urinary 1-OHP and blood As and Ni levels were increased in taxi drivers and were associated with inflammatory and oxidative stress biomarkers. These exposure biomarkers were also associated with each other, suggesting a common source of exposure. The gene expression of p53, CD26 and ICAM-1 were decreased in taxi drivers and were strongly associated between them, indicating a commom regulation point. The antioxidant non-protein thiols and lycopene were negatively associated with inflammatory biomarkers, maybe regulating the immune-response. We demonstrated, for the first time, that in occupational exposure to air pollution chemicals, oxidative and inflammatory processes are involved in the immune-regulatory process, and indirectly contribute to suppressing the p53 and CD26 expressions, increasing the risk of cancer development. On the other hand, antioxidants could contribute to improving the immune-regulation, but more studies are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate biomarkers of exposure to cholinesterase inhibitors insecticides (AChE and BuChE activities) and metals (As, Cd, Cr, Mn, Ni, and Pb blood levels) and their associations with biochemical, hematological, and immunological parameters in farmers from Southern Brazil. One hundred and sixteen individuals were divided into two groups: 62 farmers (exposed group) and 54 subjects non-occupationally exposed (NOE) to agrochemicals. Erythrocyte (AChE) and serum (BuChE) cholinesterases activities were significantly reduced as well as blood Cd and Pb levels were increased in farmers when compared to NOE group (p < 0.05). Farmers presented increased glucose and urea levels compared to NOE group, which were inversely associated with AChE and positively correlated with Cd (p < 0.05), respectively. In addition, Cd was inversely associated with the hematological cells counts, which were significantly reduced in farmers (p < 0.05). C3 complement was higher in farmers and was positively associated with blood Pb (p < 0.05). Surface protein expression analysis revealed a downregulation of LFA-1 and ICAM-1 in farmers. Inverse associations were found between LFA-1 and blood As, Cr, and Ni levels (p < 0.05). Taken together, our results pointed to a relationship between agrochemicals and metals exposure and biochemical, hematological, and immunological disorders that can lead to several chronic conditions.

Background: Red blood cells from smoking donors can have more lesions from oxidative stress, decreasing the benefits of blood transfusion. We aimed to explore the effect of cigarette smoking on the oxidative status of packed red blood cells (PRBCs) prior to storage., Materials and Methods: We compared serum vitamin C, plasmatic malondialdehyde (MDA), and non-protein thiol groups (GSH) levels in PRBCs, as well glutathione peroxidase (GPx) and glutathione s-transferase (GST) activity in PRBCs from smoking (n=36) and non-smoking (n=36) donors. We also correlated urinary cotinine levels with these parameters., Results: Cigarette smoking was associated with decreased serum levels of vitamin C and GPx, and increased GST activity in PRBCs. We found negative correlations between cotinine, GPx activity and vitamin C levels, and a positive correlation between cotinine and GST activity., Discussion: Cigarette smoking changed antioxidant defences of PRBCs prior to storage and these parameters are correlated with cotinine levels. Increased RBC antioxidants such as GST may reflect an exposure to oxidants during erythropoiesis. Because of the inability of mature RBCs to resynthesise antioxidants, PRBCs from smokers may have higher risk of storage lesions than those from non-smoker donors.

Workers chronically exposed to respirable crystalline silica (CS) are susceptible to adverse health effects like silicosis and lung cancer. This study aimed to investigate potential early peripheral biomarkers of inflammation and oxidative stress in miners. The subjects enrolled in this study were occupationally unexposed workers (OUW, n = 29) and workers exposed to crystalline silica (WECS), composed by miners, which were divided into two subgroups: workers without silicosis (WECS I, n = 39) and workers diagnosed with silicosis, retired from work (WECS II, n = 42). The following biomarkers were evaluated: gene expression of L-selectin, CXCL2, CXCL8 (IL-8), HO-1, and p53; malondialdehyde (MDA) plasma levels and non-protein thiol levels in erythrocytes. Additionally, protein expression of L-selectin was evaluated to confirm our previous findings. The results demonstrated that gene expression of L-selectin was decreased in the WECS I group when compared to the OUW group (p < 0.05). Regarding gene expression of CXCL2, CXCL8 (IL-8), HO-1, and p53, significant fold change decreases were observed in workers exposed to CS in relation to unexposed workers (p < 0.05). The results of L-selectin protein expression in lymphocyte surface corroborated with our previous findings; thus, significant downregulation in the WECS groups was observed compared to OUW group (p < 0.05). The MDA was negatively associated with the gene expression of CXCL-2, CXCL8 (IL-8), and p53 (p < 0.05). The participants with silicosis (WECS II) presented significant increased non-protein thiol levels in relation to other groups (p < 0.05). Taken together, our findings may contribute to help the knowledge about the complex mechanisms involved in the silicosis pathogenesis and in the risk of lung cancer development in workers chronically exposed to respirable CS.

Organic electrochemical transistors (OECTs) represent a powerful and versatile type of organic-based device, widely used in biosensing and bioelectronics due to potential advantages in terms of cost, sensitivity, and system integration. The benchmark organic semiconductor they are based on is poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), the electrical properties of which are reported to be strongly dependent on film morphology and structure. In particular, the literature demonstrates that film processing induces morphostructural changes in terms of conformational rearrangements in the PEDOT:PSS in-plane phase segregation and out-of-plane vertical separation between adjacent PEDOT-rich domains. Here, taking into account these indications, we show the thickness-dependent operation of OECTs, contextualizing it in terms of the role played by PEDOT:PSS film thickness in promoting film microstructure tuning upon controlled-atmosphere long-lasting thermal annealing (LTA). To do this, we compared the LTA-OECT response to that of OECTs with comparable channel thicknesses that were exposed to a rapid thermal annealing (RTA). We show that the LTA process on thicker films provided OECTs with an enhanced amplification capability. Conversely, on lower thicknesses, the LTA process induced a higher charge carrier modulation when the device was operated in sensing mode. The provided experimental characterization also shows how to optimize the OECT response by combining the control of the microstructure via solution processing and the effect of postdeposition processing.

Introduction: Shapiro syndrome (SS) is characterized by spontaneous recurrent episodes of hypothermia, hyperhidrosis and corpus callosum (CC) agenesis. Less than 60 cases have been reported to date and the pathogenic mechanism as well as the prognosis of this syndrome are still debated. We describe the clinical features and long-term follow-up of a pediatric cohort of SS patients., Methods: We collected 13 (10 novel) pediatric cases of SS and report their long-term follow-up and neurological outcome., Results: All patients experienced recurring hypothermia, with body temperature below 35 °C during the episodes, often accompanied by hyperidrosis. CC agenesis was an inconstant structural feature in the present series (2/13 patients). Seven patients received antiepileptic drugs (AEDs) or other drug therapy for a mean period of 12 months. At long-term follow-up (mean = 61 months, range: 60-96), all individuals were free from episodes of paroxysmal hypothermia independently from previous AED use or other drug therapy., Conclusion: Paroxysmal hypothermia, the core symptom of SS, behaved as a age-dependent feature in our cohort, supporting a good long-term prognosis for SS. A prompt diagnosis of SS is crucial to avoid unnecessary diagnostic investigations., (Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Endocrine disrupting chemicals (EDCs), including pesticides and metals, are present in rural areas, endangering the health of exposed populations. This work aimed to investigate the possible association between the exposure to these xenobiotics and thyroid dysfunction in children living in a rural community of Southern Brazil. Fifty-four children aged 5-16 years participated in this study. Peripheral biomarker evaluations were performed in periods of low and high exposure to pesticides. Thyroid ultrasonography was evaluated in the high exposure period. Blood levels of chromium (Cr), manganese (Mn), mercury (Hg), and lead (Pb), as well as hair Pb levels were positively correlated with thyroid stimulating hormone (TSH) concentrations and negatively associated with free thyroxine (fT4) levels in the low exposure period. Prolactin was positively associated with hair Mn in both periods. In the ultrasound tests, the majority of children presented a normal echogenicity of thyroid. Glucose was inversely associated with the biomarker of exposure to cholinesterase inhibitor insecticides, butyrylcholinesterase (BuChE). Lipid profile was above the recommended levels in both periods. In summary, our results show that children environmentally exposed to a mixture of xenobiotics in an agricultural community may have health impairments, especially on thyroid function, dyslipidemia, and glucose homeostasis disruption., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Workers involved in mining activities are exposed to crystalline silica, which leads to constant pulmonary inflammatory reactions and severe oxidative damage, resulting in silicosis. In this work, we aimed to evaluate inflammatory and oxidative stress parameters as potential early biomarkers of effect to assess crystalline silica toxicity in workers who had occupational exposure during mining. We enrolled 38 workers exposed to crystalline silica (WECS), 24 individuals with silicosis (IWS), and 30 occupationally unexposed workers (OUW), a total of 92 participants. The WECS were divided into 2 groups, according to the time of exposure: 19 workers with 1-15 years of occupational exposure (WECS I) and 19 workers with >16 years of occupational exposure (WECS II). The inflammatory parameters assessed were L-selectin, β-2 integrin, and intercellular adhesion molecule-1 (ICAM-1) surface protein expression in lymphocytes and monocytes, complement C3 and C4, high sensitivity C-reactive protein (hsCRP), and adenosine deaminase (ADA) in serum. Plasma levels of malondialdehyde (MDA) and serum levels of vitamin C were determined as biomarkers of oxidative stress. Biochemical and hematological parameters were also investigated. L-selectin surface protein expression was significantly decreased in the WECS II group (p < 0.05), indicating the importance of this immune system component as a potential marker of crystalline-silica-induced toxicity. The MDA levels were significantly increased in the WECS I, WECS II, and IWS groups compared to the OUW group (p < 0.05). Vitamin C levels were decreased, while C3, hsCRP, ADA, and aspartate aminotransferase (AST) levels were increased in the IWS group compared to the OUW group (p < 0.05). Glucose and urea levels were significantly higher in the WECS I, II, and IWS groups compared to the OUW group (p < 0.05). Negative partial association was found between L-selectin and time of exposure (p < 0.001), supporting the relevance of this biomarker evaluation in long-term exposure to crystalline silica. Significant associations were also observed among inflammatory and oxidative stress biomarkers. Therefore, our results demonstrated the relevance of L-selectin as a potential peripheral biomarker for monitoring crystalline silica-induced toxicity in miners after chronic exposure, before silicosis has developed. However, more studies are necessary for better understanding of the use L-selectin as an early biomarker in exposed workers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We evaluated the long-term prognosis of patients featuring the association of absences and myoclonic epilepsy of infancy. Our cohort consisted of 10 male subjects with mean age at seizure onset of 29 months. Follow-up data included seizure outcome and EEG findings. All individuals received antiepileptic drugs (AEDs) as monotherapy (6 patients) or polytherapy (4 patients) for a mean period of 24 months. Over a 30-60 month evaluation period (mean: 43 months), all patients were seizure-free. Follow-up data after withdrawal of antiepileptic therapy were obtained for a mean period of 22 months. None of the children did develop other age-related epileptic syndrome after AEDs discontinuation. Furthermore, follow-up EEG data after drugs withdrawal were normal and none of the patients showed cognitive impairment. In conclusion, we confirm that absence seizures may occur in association with myoclonic epilepsy of infancy. This condition shows excellent prognosis with either favourable neurologic development and seizure outcome in these children., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This is the second part of a retrospective and review MR imaging study aiming to define the frequency rate, timing, imaging features, and evolution of gray matter changes in Menkes disease, a rare multisystem X-linked disorder of copper metabolism characterized by early, severe, and progressive neurologic involvement. According to our analysis, neurodegenerative changes and focal basal ganglia lesions already appear in the early phases of the disease. Subdural collections are less common than generally thought; however, their presence remains important because they might challenge the differential diagnosis with child abuse and might precipitate the clinical deterioration. Anecdotal findings in our large sample seem to provide interesting clues about the protean mechanisms of brain injury in this rare disease and further highlight the broad spectrum of MR imaging findings that might be expected while imaging a child with the suspicion of or a known diagnosis of Menkes disease., (© 2017 by American Journal of Neuroradiology.)

Canaloplasty is a nonpenetrating blebless surgical technique for open-angle glaucoma, in which a flexible microcatheter is inserted within Schlemm's canal for the entire 360 degrees. When the microcatheter exits the opposite end, a 10-0 prolene suture is tied and it is then withdrawn, by pulling microcatheter back through the canal in the opposite direction. Ligation of prolene suture provides tension on the canal and facilitates aqueous outflow. The main advantage of canaloplasty is that this technique avoids the major complications of fistulating surgery related to blebs and hypotony. Currently, canaloplasty is performed in glaucoma patients with early to moderate disease and combination with cataract surgery is a suitable option in patients with clinically significant lens opacities.

Background: Neonatal seizures are a risk factor for later epilepsy and their etiology is known to be implicated in the outcome but, little is known about this issue in the subgroup of seizures symptomatic of perinatal arterial ischemic stroke. The aim of this study was to describe the long term risk of epilepsy after electroencephalographic confirmed neonatal seizures symptomatic of perinatal arterial ischemic stroke., Design/subject: Fifty-five patients with electroclinical ictal data, vascular territory confirmed by neuroimaging and a minimum follow up of 3.5 years were identified from a multi-centre prospective neonatal seizures registry. Primary outcome was occurrence of post-neonatal epilepsy. The association of outcome with family history of epilepsy, gender, location of the infarct, neonatal clinical and electroencephalogram data were also studied., Results: During a mean follow up of 8 years and 5 months, 16.4% of the patients developed post neonatal epilepsy. The mean age at first post neonatal seizure was 4 years and 2 months (range 1-10 years and 6 months). Location of the infarct was the only statistically significant risk factor (p=0.001); epilepsy was more represented in males but the difference was not statistically significant., Conclusions: Neonatal seizures symptomatic of perinatal arterial ischemic stroke had lower risk and later onset of post-neonatal epilepsy, compared to seizures described in the setting of other perinatal brain insults. Our data have implications for counseling to the family at discharge from neonatal intensive care unit., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess if absence seizures (ASs) occur in patients with myoclonic epilepsy of infancy (MEI)., Methods: A retrospective chart review was conducted in 37 patients with MEI followed at seven different paediatric epilepsy centres in Italy, between 2002 and 2014. To assess the possible occurrence of pure ASs or absences associated with myoclonias, ASs were defined according to the following criteria: (i) a sudden onset and interruption of ongoing activities; (ii) bilateral polyspikes or spike-and-wave (SW) complexes; spike SW complexes at 2-4Hz; (iii) duration of AS: 3-30seconds., Results: Thirty-seven MEI patients (25 boys and 12 girls) were identified. Nine patients (24.3%) had a history of simple FS during the first year of life. Ten patients (27%) had a family history of epilepsy, and six patients (16.2%) had a family history of FS. In 7/37 (18.9%) patients, during the occurrence of MSs, a total of nineteen brief ASs were captured by video-EEG recordings. ASs occurred both during a brief cluster of rhythmic MSs than after single myoclonic jerks. The ictal EEG abnormalities observed in patients with ASs were similar to the ictal EEG patterns associated with only myoclonias. No differences in relation to gender, family history, ictal EEG discharge were found between patients with myoclonic seizures with ASs and myoclonias without ASs., Conclusions: Absence seizures can occur in approximately 20% of MEI patients and the occurrence of ASs, though not essential to formulate the diagnosis, do not automatically exclude the diagnosis of MEI., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: The electrocardiogram (ECG) is an important, available, and inexpensive diagnostic tool to assess cardiac symptoms. Few studies address the prevalence of ECG abnormalities or changes of a normal tracing in ECG in outpatients. Our objective was to evaluate ECGs of adult outpatients to determine whether changes from a normal tracing could disclose the patients' cardiovascular health status., Methods: We evaluated all elective ECGs obtained in adult outpatients, from January 2009 to January 2010, at a municipal hospital in the city of São Paulo, Brazil. Electrocardiography was performed with a 3-channel, 12-lead machine (Dixtal Cardio-page EP-3, Dixtal Biomedica, São Paulo, Brazil), and results were interpreted by a cardiologist., Results: Electrocardiography was performed in 3567 adult outpatients, 62.5% of whom were women, with a mean age of 51 years (standard deviation [SD] = 16 years). Of the 1918 patients whose ECGs showed abnormalities (mean age = 56 years, SD = 15 years), 1137 were women. Electrocardiographic changes were found in 1184 of the patients. Minor changes were found in 38.3% of patients. A total of 3133 changes were found in 1918 abnormal ECG results. There was a statistical difference related to sex and age, and abnormal ECG results were more frequent in men. There was a high prevalence of abnormal ECG results in the population studied., Conclusions: There were more ECGs obtained from women; however, men and elderly patients more frequently had abnormal ECG results.

Non-epileptic attacks (NEAs) are a heterogeneous group of clinical entities which often complicate the differential diagnosis of epilepsy. NEAs usually have a benign course and are limited to a specific period of life. If motor manifestations are strongly suggestive of an epileptic phenomenon, the risk of misdiagnosis is greater. Here, we describe a novel NEA with infantile onset, characterised by repeated head drops, mimicking epileptic negative myoclonus of the neck. The frequency of the episodes was very high, at hundreds or thousands per day. The episodes appeared in the second semester of the first year of life and spontaneously disappeared within a few months. [Published with video sequences].

Purpose: To describe the EEG pattern of seizures in patients with benign childhood epilepsy with centro-temporal spikes (BCECTS)., Methods: The clinical and EEG data of 701 BCECTS patients with at least a 3 years follow-up were reviewed from 10 epilepsy centers., Results: Thirty-four seizures were recorded in 30 patients. Four different ictal EEG patterns (A-D) were identified. The most frequent (pattern A) was characterized by low voltage activity of fast rhythmic spikes, increasing in amplitude and decreasing in frequency, and occurred in 14 children. Pattern B (six patients) was constituted by a discharge of spikes intermixed with sharp waves increasing in frequency and amplitude. Pattern C (seven children) consisted of monomorphic theta which progressively formed a discharge increasing in amplitude and decreasing in frequency. Pattern D (5 children) was characterized by a initial focal depression of the electrical activity, followed by one of the three above described patterns. In 21 out of 28 children, the initial ictal pattern, altered from one pattern to another one. No clinical or EEG feature was predictive of a specific ictal pattern., Discussion: We failed to identify a unique ictal EEG pattern in our patients with BCECTS. The occurrence of per-ictal features, e.g., initial EEG depression or post-ictal slowing, is common and should not be interpreted with prejudice. Alteration of ictal EEG pattern from one to another is not in conflict with the diagnosis of BCECTS., (Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)