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Despite extensive temporal lobe epilepsy (TLE) research, understanding the specific limbic structures' roles in seizures remains limited. This weakness can be attributed to the complex nature of TLE and the existence of various TLE subsyndromes, including non-lesional TLE. Conventional TLE models like kainate and pilocarpine hinder precise assessment of the role of individual limbic structures in TLE ictogenesis due to widespread limbic damage induced by the initial status epilepticus. In this study, we used a non-lesional TLE model characterized by the absence of initial status and cell damage to determine the spatiotemporal profile of seizure initiation and limbic structure recruitment in TLE. Epilepsy was induced by injecting a minute dose of tetanus toxin into the right dorsal hippocampus in seven animals. Following injection, animals were implanted with bipolar recording electrodes in the amygdala, dorsal hippocampus, ventral hippocampus, piriform, perirhinal, and entorhinal cortices of both hemispheres. The animals were video-EEG monitored for four weeks. In total, 140 seizures (20 seizures per animal) were analyzed. The average duration of each seizure was 53.2+/-3.9 s. Seizure could initiate in any limbic structure. Most seizures initiated in the ipsilateral (41 %) and contralateral (18 %) ventral hippocampi. These two structures displayed a significantly higher probability of seizure initiation than by chance. The involvement of limbic structures in seizure initiation varied between individual animals. Surprisingly, only 7 % of seizures initiated in the injected dorsal hippocampus. The limbic structure recruitment into the seizure activity wasn't random and displayed consistent patterns of early recruitment of hippocampi and entorhinal cortices. Although ventral hippocampus represented the primary seizure onset zone, the study demonstrated the involvement of multiple limbic structures in seizure initiation in a non-lesional TLE model. The study also revealed the dichotomy between the primary epileptogenic lesion and main seizure onset zones and points to the central role of ventral hippocampi in temporal lobe ictogenesis.
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Modelos Animais de Doenças , Epilepsia do Lobo Temporal , Convulsões , Toxina Tetânica , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/patologia , Animais , Masculino , Toxina Tetânica/toxicidade , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Ratos , Ratos Sprague-Dawley , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , EletroencefalografiaRESUMO
Biocompatibility is one of the key issues for implants, especially in the case of stainless steel with medium to low biocompatibility, which may lead to a lack of osseointegration and consequently to implant failure or rejection. To precisely control preferential cell growth sites and, consequently, the biocompatibility of prosthetic devices, two types of surfaces were analyzed, containing periodic nanogrooves laser induced periodic surface structure (LIPSS) and square-shaped micropillars. For the fast and efficient production of these surfaces, the unique combination of high energy ultrashort pulsed laser system with multi-beam and beamshaping technology was applied, resulting in increased productivity by 526% for micropillars and 14 570% for LIPSS compared to single beam methods.In vitroanalysis revealed that micro and nanostructured surfaces provide a better environment for cell attachment and proliferation compared to untreated ones, showing an increase of up to 496% in the number of cells compared to the reference. Moreover, the combination of LIPSS and micropillars resulted in a precise cell orientation along the periodic microgroove pattern. The combination of these results demonstrates the possibility of mass production of functionalized implants with control over cell organization and growth. Thus, reducing the risk of implant failure due to low biocompatibility.
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Próteses e Implantes , Aço Inoxidável , Propriedades de Superfície , Aço Inoxidável/química , Osseointegração , Proliferação de CélulasRESUMO
This corrects the article DOI: 10.1103/PhysRevLett.116.071802.
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Additive manufacturing, also called 3D printing, is an effective method for preparing scaffolds with defined structure and porosity. The disadvantage of the technique is the excessive smoothness of the printed fibers, which does not support cell adhesion. In the present study, a 3D printed scaffold was combined with electrospun classic or structured nanofibers to promote cell adhesion. Structured nanofibers were used to improve the infiltration of cells into the scaffold. Electrospun layers were connected to 3D printed fibers by gluing, thus enabling the fabrication of scaffolds with unlimited thickness. The composite 3D printed/nanofibrous scaffolds were seeded with primary chondrocytes and tested in vitro for cell adhesion, proliferation and differentiation. The experiment showed excellent cell infiltration, viability, and good cell proliferation. On the other hand, partial chondrocyte dedifferentiation was shown. Other materials supporting chondrogenic differentiation will be investigated in future studies.
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Adesão Celular/fisiologia , Condrócitos/citologia , Nanofibras , Impressão Tridimensional , Alicerces Teciduais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas/fisiologia , Humanos , Nanofibras/química , Engenharia Tecidual/métodosRESUMO
Fibrous scaffolds are desired in tissue engineering applications for their ability to mimic extracellular matrix. In this study we compared fibrous scaffolds prepared from polycaprolactone using three different fabrication methods, electrospinning (ES), electro-blowing and melt-blown combined with ES. Scaffolds differed in morphology, fiber diameters and pore sizes. Mesenchymal stem cell adhesion, proliferation and osteogenic differentiation on scaffolds was evaluated. The most promising scaffold was shown to be melt-blown in combination with ES which combined properties of both technologies. Microfibers enabled good cell infiltration and nanofibers enhanced cell adhesion. This scaffold was used for further testing in critical sized defects in rabbits. New bone tissue formation occurred from the side of the treated defects, compared to a control group where only fat tissue was present. Polycaprolactone fibrous scaffold prepared using a combination of melt-blown and ES technology seems to be promising for bone regeneration. The practical application of results is connected with enormous production capacity and low cost of materials produced by melt-blown technology, compared to other bone scaffold fabrication methods.
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Osso e Ossos/patologia , Nanofibras/química , Osteogênese/efeitos dos fármacos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Regeneração Óssea , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Fêmur/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Microscopia Eletrônica de Varredura , Polímeros/química , CoelhosRESUMO
The MINERvA experiment observes an excess of events containing electromagnetic showers relative to the expectation from Monte Carlo simulations in neutral-current neutrino interactions with mean beam energy of 4.5 GeV on a hydrocarbon target. The excess is characterized and found to be consistent with neutral-current π^{0} production with a broad energy distribution peaking at 7 GeV and a total cross section of 0.26±0.02(stat.)±0.08(sys.)×10^{-39} cm^{2}. The angular distribution, electromagnetic shower energy, and spatial distribution of the energy depositions of the excess are consistent with expectations from neutrino neutral-current diffractive π^{0} production from hydrogen in the hydrocarbon target. These data comprise the first direct experimental observation and constraint for a reaction that poses an important background process in neutrino-oscillation experiments searching for ν_{µ} to ν_{e} oscillations.
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The first direct measurement of electron neutrino quasielastic and quasielasticlike scattering on hydrocarbon in the few-GeV region of incident neutrino energy has been carried out using the MINERvA detector in the NuMI beam at Fermilab. The flux-integrated differential cross sections in the electron production angle, electron energy, and Q^{2} are presented. The ratio of the quasielastic, flux-integrated differential cross section in Q^{2} for ν_{e} with that of similarly selected ν_{µ}-induced events from the same exposure is used to probe assumptions that underpin conventional treatments of charged-current ν_{e} interactions used by long-baseline neutrino oscillation experiments. The data are found to be consistent with lepton universality and are well described by the predictions of the neutrino event generator GENIE.
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Two different nuclear-medium effects are isolated using a low three-momentum transfer subsample of neutrino-carbon scattering data from the MINERvA neutrino experiment. The observed hadronic energy in charged-current ν_{µ} interactions is combined with muon kinematics to permit separation of the quasielastic and Δ(1232) resonance processes. First, we observe a small cross section at very low energy transfer that matches the expected screening effect of long-range nucleon correlations. Second, additions to the event rate in the kinematic region between the quasielastic and Δ resonance processes are needed to describe the data. The data in this kinematic region also have an enhanced population of multiproton final states. Contributions predicted for scattering from a nucleon pair have both properties; the model tested in this analysis is a significant improvement but does not fully describe the data. We present the results as a double-differential cross section to enable further investigation of nuclear models. Improved description of the effects of the nuclear environment are required by current and future neutrino oscillation experiments.
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Nanofibrous materials are essential components for a wide range of applications, particularly in the fields of medicine and material engineering. These include protective materials, sensors, cosmetics, hygiene, filtration and energy storage. The most widely used and researched technology in these fields is electrospinning. This method for producing fibers yields highly promising results thanks to its versatility and simplicity. Electrospinning is employed in multiple forms, among which needle and needleless direct current (DC) variants are the most distinctive. The former is based on the generation of just one single jet from a nozzle; hence this fabrication process is not very productive. The latter uses the destabilization of free liquid surfaces by means of an electric field, which enhances the throughput since it produces numerous jets, emitted from the surfaces of rollers, spheres, strings and spirals. However, although some progress in total producibility has been achieved, the efficiency of the DC method still remains relatively low. A further drawback of DC electrospinning is that both variants need a collector, which makes it difficult to combine DC electrospinning easily with other technologies due to the presence of the high field strength within the entire spinning zone. This paper describes our experiments with AC electrospinning. We show that alternating current (AC) electrospinning based on a needleless spinning-electrode provides a highly productive smoke-like aerogel composed of nanofibers. This aerogel rises rapidly from the electrode like a thin plume of smoke, without any need for a collector. Our work shows that AC needleless electrospinning gains its efficiency and collector-less feature thanks to the creation of a perpetually charge-changing virtual counter-electrode composed of the nanofibers emitted. High-speed camera recordings demonstrate the formation mechanism of the nanofibrous plume, which is wafted by an electric wind. This wind's velocity field is experimentally investigated. One potential use of AC needleless electrospinning is demonstrated here by spinning it into a yarn.
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We present measurements of ν(µ) charged-current cross section ratios on carbon, iron, and lead relative to a scintillator (CH) using the fine-grained MINERvA detector exposed to the NuMI neutrino beam at Fermilab. The measurements utilize events of energies 2
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Neutrino-induced coherent charged pion production on nuclei νµAâµ(±)π(∓)A is a rare, inelastic interaction in which a small squared four-momentum |t| is transferred to the recoil nucleus, leaving it intact in the reaction. In the scintillator tracker of MINERvA, we remove events with evidence of particles from nuclear breakup and reconstruct |t| from the final-state pion and muon. We select low |t| events to isolate a sample rich in coherent candidates. By selecting low |t| events, we produce a model-independent measurement of the differential cross section for coherent scattering of neutrinos and antineutrinos on carbon. We find poor agreement with the predicted kinematics in neutrino generators used by current oscillation experiments.
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We have isolated ν(µ) charged-current quasielastic (QE) interactions occurring in the segmented scintillator tracking region of the MINERvA detector running in the NuMI neutrino beam at Fermilab. We measure the flux-averaged differential cross section, dσ/dQ², and compare to several theoretical models of QE scattering. Good agreement is obtained with a model where the nucleon axial mass, M(A), is set to 0.99 GeV/c² but the nucleon vector form factors are modified to account for the observed enhancement, relative to the free nucleon case, of the cross section for the exchange of transversely polarized photons in electron-nucleus scattering. Our data at higher Q² favor this interpretation over an alternative in which the axial mass is increased.
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We report a study of ν(µ) charged-current quasielastic events in the segmented scintillator inner tracker of the MINERvA experiment running in the NuMI neutrino beam at Fermilab. The events were selected by requiring a µ- and low calorimetric recoil energy separated from the interaction vertex. We measure the flux-averaged differential cross section, dσ/dQ², and study the low energy particle content of the final state. Deviations are found between the measured dσ/dQ² and the expectations of a model of independent nucleons in a relativistic Fermi gas. We also observe an excess of energy near the vertex consistent with multiple protons in the final state.
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OBJECTIVES: We prepared 3D poly (ε-caprolactone) (PCL) nanofibre scaffolds and tested their use for seeding, proliferation, differentiation and migration of mesenchymal stem cell (MSCs). MATERIALS AND METHODS: 3D nanofibres were prepared using a special collector for common electrospinning; simultaneously, a 2D PCL nanofibre layer was prepared using a classic plain collector. Both scaffolds were seeded with MSCs and biologically tested. MSC adhesion, migration, proliferation and osteogenic differentiation were investigated. RESULTS: The 3D PCL scaffold was characterized by having better biomechanical properties, namely greater elasticity and resistance against stress and strain, thus this scaffold will be able to find broad applications in tissue engineering. Clearly, while nanofibre layers of the 2D scaffold prevented MSCs from migrating through the conformation, cells infiltrated freely through the 3D scaffold. MSC adhesion to the 3D nanofibre PCL layer was also statistically more common than to the 2D scaffold (P < 0.05), and proliferation and viability of MSCs 2 or 3 weeks post-seeding, were also greater on the 3D scaffold. In addition, the 3D PCL scaffold was also characterized by displaying enhanced MSC osteogenic differentiation. CONCLUSIONS: We draw the conclusion that all positive effects observed using the 3D PCL nanofibre scaffold are related to the larger fibre surface area available to the cells. Thus, the proposed 3D structure of the nanofibre layer will find a wide array of applications in tissue engineering and regenerative medicine.
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Técnicas de Cultura de Células/instrumentação , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Nanofibras/química , Poliésteres/química , Alicerces Teciduais , Técnicas de Cultura de Células/métodos , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Elasticidade , Humanos , Sialoproteína de Ligação à Integrina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Nanofibras/ultraestrutura , Osteocalcina/metabolismo , Osteogênese , Medicina Regenerativa , Propriedades de Superfície , Engenharia TecidualRESUMO
This study evaluated inflammatory, coagulation and microvascular responses to a continuous 24-h work day in 13 healthy intensive care physicians. Inflammatory markers (interleukin [IL]-2, IL-6, IL-10, tumour necrosis factor-α, matrix metalloproteinase [MMP]-9 and adiponectin), adhesion molecules (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1 [ICAM-1]), coagulation parameters (thrombin-anti thrombin, von Willebrand factor and tissue factor) and sublingual micro circulation were assessed before and after a 24-h work shift. The 24-h work shift had no effect on inflammatory markers and ICAM-1. Direct visualization of micro-circulation did not reveal stress-related perfusion abnormalities. A 24-h work shift in the intensive care unit was associated with significantly increased plasma levels of tissue factor - a potentially important mechanism linking acute job strain, haemostasis and atherosclerosis. The long-term consequences warrant further evaluation.
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Fenômenos Biológicos , Pessoal de Saúde , Saúde , Unidades de Terapia Intensiva , Estresse Fisiológico , Adulto , Biomarcadores/sangue , Endotélio Vascular/fisiopatologia , Feminino , Hemodinâmica , Hemostasia , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Microcirculação , Tromboplastina/metabolismo , Fatores de TempoRESUMO
Vasoactive intestinal peptide (VIP) is a neuropeptide released from the autonomic nerves exerting multiple antiinflammatory effects. The aim of the present study was to investigate the impact of severe sepsis and hemofiltration in two settings on plasma and tissue concentrations of VIP in a porcine model of sepsis. Thirty-two pigs were divided into 5 groups: 1) control group; 2) control group with conventional hemofiltration; 3) septic group; 4) septic group with conventional hemofiltration; 5) septic group with high-volume hemofiltration. Sepsis induced by faecal peritonitis continued for 22 hours. Hemofiltration was applied for the last 10 hours. Hemodynamic, inflammatory and oxidative stress parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-alpha, interleukin-6, thiobarbituric acid reactive species, nitrate + nitrite, asymmetric dimethylarginine) and the systemic VIP concentrations were measured before faeces inoculation and at 12 and 22 hours of peritonitis. VIP tissue levels were determined in the left ventricle, mesenteric and coronary arteries. Sepsis induced significant increases in VIP concentrations in the plasma and mesenteric artery, but it decreased peptide levels in the coronary artery. Hemofiltration in both settings reduced concentrations of VIP in the mesenteric artery. In severe sepsis, VIP seems to be rapidly depleted from the coronary artery and, on the other hand, upregulated in the mesenteric artery. Hemofiltration in both settings has a tendency to drain away these upregulated tissue stores which could result in the limited secretory capacity of the peptide.
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Hemofiltração , Peritonite/complicações , Sepse/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Vasos Coronários/metabolismo , Feminino , Masculino , Artérias Mesentéricas/metabolismo , Estresse Oxidativo , Sepse/etiologia , Sepse/fisiopatologia , Suínos , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/genéticaRESUMO
The kidney is a common "victim organ" of various insults in critically ill patients. Sepsis and septic shock are the dominant causes of acute kidney injury, accounting for nearly 50 % of episodes of acute renal failure. Despite our substantial progress in the understanding of mechanisms involved in septic acute kidney injury there is still a huge pool of questions preclusive of the development of effective therapeutic strategies. This review briefly summarizes our current knowledge of pathophysiological mechanisms of septic acute kidney injury focusing on hemodynamic alterations, peritubular dysfunction, role of inflammatory mediators and nitric oxide, mitochondrial dysfunction and structural changes. Role of proteomics, new promising laboratory method, is mentioned.
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Injúria Renal Aguda/etiologia , Choque Séptico/etiologia , Animais , Apoptose , Humanos , Inflamação/metabolismo , Óxido Nítrico/metabolismo , Proteômica/métodos , Circulação Renal/fisiologiaRESUMO
A 24-year-old man presented with cough, sore throat, fever, maculopapulous exanthema, pericardial and pleural effusion. Despite extensive evaluation neither infectious, autoimmune, hematological nor oncological disorders were revealed. Broad spectrum antibiotic and subsequently corticosteroid treatment failed to resolve the symptoms. Multiorgan failure with rapid progress of acute respiratory distress syndrome and circulatory failure developed and patient died. Adult onset Still's disease (AOSD), a diagnosis considered in this patient, is a rare disease with unknown prevalence, pathogenesis and etiology. Clinically it is characterized by spiking fever, arthritis, rash, and impairment of multiple organs. There is no single diagnostic test for AOSD. Rather, the diagnosis is based on the clinical criteria and requires the exclusion of infectious, neoplastic, and other autoimmune diseases. Rarely the course of the disease can be rapidly progressive to death. Treatment includes the use of non-steroid antirheumatic drugs and corticosteroids. Limited data suggest that biological agents (e.g. anti-TNF-alpha, anti-IL-1), rituximab or intravenous immunoglobulins might be promising for the treatment of severe cases.
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Febre/etiologia , Insuficiência de Múltiplos Órgãos/complicações , Síndrome do Desconforto Respiratório/complicações , Doença de Still de Início Tardio/diagnóstico , Adulto , Progressão da Doença , Evolução Fatal , Humanos , Masculino , Adulto JovemRESUMO
We present a case report of a 59-year-old man with a history of arterial hypertension and excision of malignant melanoma. He was admitted to the hospital because of two months history of diarrhoea, weight loss and circulatory collapse. In addition, the patient suffered from marked vegetative instability with symptomatic hypotension, polyneuropathy and progression of renal insufficiency, without proteinuria. Complex examination did not reveal neoplasms, endocrine, autoimmune, infectious or neurodegenerative disorders. A serial biopsy of colon failed to provide a clue to the diagnosis. However, AA amyloidosis was found on the kidney biopsy. Neither chronic inflammation nor malignancy was revealed and, hence, no causal treatment could have been established. The patient died from multiple organ failure. The autopsy confirmed systemic AA amyloidosis. The triad consisting ofdiarrhoea, polyneuropathy and hypotension should rise the suspicion on amyloidosis.
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Amiloidose/diagnóstico , Diarreia/complicações , Hipotensão/complicações , Polineuropatias/complicações , Amiloidose/complicações , Amiloidose/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Sepsis is the leading cause of mortality in non-coronary intensive care units. The uncontrolled and deregulated systemic inflammatory response to infection plays a central role in the pathophysiology of sepsis. This response is mediated by a broad spectrum of endogenous mediators leading to dysfunction in multiple organs remote from the primary infectious site. The failure of numerous clinical trials aimed at eliminating a single mediator stimulated the research to focus on non-selective removal of excessively produced mediators of sepsis. This "detoxification" forms the theoretical basis and biological rationale for the use of hemopurification therapies as an adjunctive treatment of sepsis. Our article reviews the current evidence of hemopurification methods in the supportive treatment of sepsis, briefly discusses new trends and summarizes the recommendations for clinical practice.