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The way multipacting develops, depends strongly on the secondary emission property of the surface material. The knowledge of secondary electron yield is crucial for accurate prediction of the multipacting threshold. Variations in secondary electron yield parameters from experimental measurements create uncertainty, stemming from handling and surface preparation, and these uncertainties significantly affect multipacting threshold predictions. Despite their significance, the previous studies on the multipacting phenomenon did not adequately address the effect of an assumed random distribution of the secondary emission parameters on the multipacting threshold. Therefore, this paper aims to provide a comprehensive statistical study on how the different random distributions of the secondary emission parameters and, as a result, the uncertainty in the secondary electron yield affect multipacting thresholds. We focus on three commonly used distributions, namely uniform, normal, and truncated normal distributions, to define the uncertainty of random inputs. We use the chaos polynomial expansion method to determine how much each of the random parameters contributes to the multipacting threshold uncertainty. Additionally, we calculate Sobol sensitivity indices to evaluate the impact of the individual parameters or groups of parameters on the model outputs and study how different random distributions of these parameters affected the Sobol index results.
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OBJECTIVE: Hand and upper limb functional impairments following stroke lead to limitations in performing activities of daily living. We aimed to investigate feasibility and efficacy of an early sensory-motor rehabilitation program on hand and upper limb function in patients with acute stroke. DESIGN: A pilot, single-subject experimental, A-B-A study. SETTING: Stroke unit of an educational hospital and an outpatient occupational therapy clinic. PARTICIPANTS: A convenience sample including five people with acute stroke. PROCEDURES: Participants received 3 h of an intensive hand and upper limb sensory and motor rehabilitation program, 5 days per week for 3 months (15-min mental imagery, 15-min action observation, 30-min mirror therapy, 1.5-h constraint-induced movement therapy, and 30-min bilateral arm training). Activities were chosen based on the task-oriented occupational therapy approach. OUTCOME MEASURES: An assessor blinded to intervention program measured sensory and motor functions using action research arm test, box and block test, Semmes-Weinstein monofilaments, and upper extremity section of Fugl-Meyer assessment. RESULTS: Assessment data points in intervention and follow-up phases compared to baseline were in higher levels, sloped upwardly, and increased significantly for all participants in all outcome measures. CONCLUSIONS: The present pilot study showed that a package of nowadays evidence-based rehabilitation methods including mental imagery, action observation, mirror therapy, modified constraint-induced movement therapy, bilateral arm training, and task-oriented occupational therapy approach is able to improve sensory and motor functions of the hand and upper limb in patients with acute stroke.
Assuntos
Estudos de Viabilidade , Mãos , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Projetos Piloto , Masculino , Feminino , Pessoa de Meia-Idade , Mãos/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Idoso , Recuperação de Função Fisiológica/fisiologia , Terapia Ocupacional/métodos , Resultado do Tratamento , Extremidade Superior/fisiopatologiaRESUMO
BACKGROUND: Some degree of spontaneous recovery is usually observed after stroke. Experimental studies have provided information about molecular mechanisms underlying this recovery. However, the majority of pre-clinical stroke studies are performed in male rodents, and females are not well studied. This is a clear discrepancy when considering the clinical situation. Thus, it is important to include females in the evaluation of recovery mechanisms for future therapeutic strategies. This study aimed to evaluate spontaneous recovery and molecular mechanisms involved in the recovery phase two weeks after stroke in female rats. METHODS: Transient middle cerebral artery occlusion was induced in female Wistar rats using a filament model. Neurological functions were assessed up to day 14 after stroke. Protein expression of interleukin 10 (IL-10), transforming growth factor (TGF)-ß, neuronal specific nuclei protein (NeuN), nestin, tyrosine-protein kinase receptor Tie-2, extracellular signal-regulated kinase (ERK) 1/2, and Akt were evaluated in the peri-infarct and ischemic core compared to contralateral side of the brain at day 14 by western blot. Expression of TGF-ß in middle cerebral arteries was evaluated by immunohistochemistry. RESULTS: Spontaneous recovery after stroke was observed from day 2 to day 14 and was accompanied by a significantly higher expression of nestin, p-Akt, p-ERK1/2 and TGF-ß in ischemic regions compared to contralateral side at day 14. In addition, a significantly higher expression of TGF-ß was observed in occluded versus non-occluded middle cerebral arteries. The expression of Tie-2 and IL-10 did not differ between the ischemic and contralateral sides. CONCLUSION: Spontaneous recovery after ischemic stroke in female rats was coincided by a difference observed in the expression of molecular markers. The alteration of these markers might be of importance to address future therapeutic strategies.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Feminino , Infarto da Artéria Cerebral Média/tratamento farmacológico , Interleucina-10 , Masculino , Nestina , Gravidez , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/metabolismo , Fator de Crescimento Transformador betaRESUMO
Bacteria utilize complement regulators as a means of evading the host immune response. Here, we describe protocols for evaluating the role vitronectin acquisition at the bacterial cell surface plays in resistance to the host immune system. Flow cytometry experiments identified human plasma vitronectin as a ligand for the bacterial receptor outer membrane protein H of Haemophilus influenzae type f. An enzyme-linked immunosorbent assay was employed to characterize the protein-protein interactions between purified recombinant protein H and vitronectin, and binding affinity was assessed using bio-layer interferometry. The biological importance of the binding of vitronectin to protein H at the bacterial cell surface in evasion of the host immune response was confirmed using a serum resistance assay with normal and vitronectin-depleted human serum. The importance of vitronectin in bacterial adherence was analyzed using glass slides with and without vitronectin coating, followed by Gram staining. Finally, bacterial adhesion to human alveolar epithelial cell monolayers was investigated. The protocols described here can be easily adapted to the study of any bacterial species of interest.
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Aderência Bacteriana , Proteínas da Membrana Bacteriana Externa/metabolismo , Atividade Bactericida do Sangue , Vitronectina/metabolismo , Células Epiteliais/microbiologia , Infecções por Haemophilus , Haemophilus influenzae/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Ligação ProteicaRESUMO
Stroke is one of the leading causes of mortality and morbidity worldwide, and few therapeutic treatments have shown beneficial effect clinically. One reason for this could be the lack of risk factors incorporated into the preclinical stroke research. We have previously demonstrated phenotypic receptor changes to be one of the injurious mechanisms occurring after stroke but mostly in healthy rats. The aim of this study was to investigate if hypertension has an effect on vasoconstrictive receptor responses to endothelin 1, sarafotoxin 6c and angiotensin II after stroke by inducing transient middle cerebral artery occlusion in spontaneously hypertensive rats and Wistar-Kyoto rats using the wire-myograph. We demonstrated an increased contractile response to endothelin 1 and extracellular potassium as well as an increased carbachol-induced dilator response in the middle cerebral arteries from hypertensive rats after stroke. This study demonstrates the importance of including risk factors in experimental stroke research.
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Endotelina-1/farmacologia , Artéria Cerebral Média/efeitos dos fármacos , Potássio/farmacologia , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Carbacol/farmacologia , Hipertensão/fisiopatologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Artéria Cerebral Média/fisiologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Vasodilatação/efeitos dos fármacos , Venenos de Víboras/farmacologiaRESUMO
Hypertension is a major risk factor for stroke, which is one of the leading global causes of death. In the search for new and effective therapeutic targets in stroke research, we need to understand the influence of hypertension in the vasculature following stroke. We used Affymetrix whole-transcriptome expression profiling as a tool to address gene expression differences between the occluded and non-occluded middle cerebral arteries (MCAs) from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats after transient middle cerebral artery occlusion (tMCAO), to provide clues about the pathological mechanisms set in play after stroke. Verified by quantitative PCR, expression of Ccl2, Edn1, Tgfß2, Olr1 and Serpine1 was significantly increased in the occluded compared to non-occluded MCAs from both SHRs and WKY rats. Additionally, expression of Mmp9, Icam1, Hif1α and Timp1 was increased in the occluded compared to non-occluded MCAs isolated from WKY rats. In comparison between occluded MCAs from SHRs versus occluded MCAs from WKY rats, expression of Ccl2, Olr1 and Serpine1 was significantly increased in SHR MCAs. However, the opposite was observed regarding expression of Edn1. Thus these data suggest that Ccl2, Edn1, Tgfß2, Olr1 and Serpine1 may be possible mediators of the vascular changes in the occluded MCAs from both SHRs and WKY rats after tMCAO. The aforementioned genes possess biological functions that are consistent with early stroke injuries. In conclusion, these genes may be potential targets in future strategies for acute stroke treatments that can be used in patients with and without hypertension.
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Regulação da Expressão Gênica/genética , Infarto da Artéria Cerebral Média/metabolismo , Animais , Artérias Cerebrais/metabolismo , Artérias Cerebrais/patologia , Circulação Cerebrovascular/fisiologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Infarto da Artéria Cerebral Média/genética , Masculino , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Sex differences are well known in cerebral ischemia and may impact the effect of stroke treatments. In male rats, the MEK1/2 inhibitor U0126 reduces ischemia-induced endothelin type B (ETB) receptor upregulation, infarct size and improves acute neurologic function after experimental stroke. However, responses to this treatment in females and long-term effects on outcome are not known. Initial experiments used in vitro organ culture of cerebral arteries, confirming ERK1/2 activation and increased ETB receptor-mediated vasoconstriction in female cerebral arteries. Transient middle cerebral artery occlusion (tMCAO, 120 minutes) was induced in female Wistar rats, with U0126 (30 mg/kg intraperitoneally) or vehicle administered at 0 and 24 hours of reperfusion, or with no treatment. Infarct volumes were determined and neurologic function was assessed by 6-point and 28-point neuroscores. ETB receptor-mediated contraction was studied with myograph and protein expression with immunohistochemistry. In vitro organ culture and tMCAO resulted in vascular ETB receptor upregulation and activation of ERK1/2 that was prevented by U0126. Although no effect on infarct size, U0126 improved the long-term neurologic function after experimental stroke in female rats. In conclusion, early prevention of the ERK1/2 activation and ETB receptor-mediated vasoconstriction in the cerebral vasculature after ischemic stroke in female rats improves the long-term neurologic outcome.
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Butadienos/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Nitrilas/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/metabolismo , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Feminino , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Ratos , Ratos Wistar , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Vasoconstrição/efeitos dos fármacosRESUMO
Multiple sclerosis (MS) is a disease of young adults which is characterized by autoimmune demyelination of the central nervous system. Interaction of genetics and environmental factors are required to cause MS. Among the proposed environmental factors for MS, viral infections are thought to play a role in the pathogenesis of the disease. Torque teno mini virus (TTMV), which has recently been shown to infect humans, is a member of circoviridae, and has a circular DNA with 2860 nucleotides. Since there are a few data about the pathogenicity of this virus, this study sought to investigate the presence of TTMV in sera from MS patients and healthy individuals. We studied 149 serum samples from MS patients and 150 sera of healthy individuals. Serum DNA was extracted using phenol-chloroform and was subjected to nested polymerase chain reaction. TTMV-DNA was detected in 24 (16%) sera of the healthy blood donors and in 21 (14.1%) samples of the MS patients, where the difference did not reach significance (p > .05). The result of this study could not establish an association between TTMV infection and MS.