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This study aimed to investigate the antioxidant and anti-inflammatory properties of quercetin on the cellular components of the Enteric Nervous System in the ileum of rats with arthritis. Rats were distributed into five groups: control (C), arthritic (AIA), arthritic treated with ibuprofen (AI), arthritic treated with quercetin (AQ) and arthritic treated with both ibuprofen and quercetin (AIQ). The ileum was processed for immunohistochemical techniques for HuC/D, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. Measurements in histological sections, chemiluminescence assays, and total antioxidant capacity were also performed. Rheumatoid arthritis resulted in a decrease in neuronal density, yet neuroplasticity mechanisms were evident through observed changes in varicosities size and neuronal area compared to the control group. Reduced paw edema and neuroprotective effects were predominantly noted in both plexuses, as evidenced by the increased density preservation of HuC/D-IR neurons in the AIQ group. The increase of lipoperoxidation levels and paw edema volume in the AQ group was observed compared to the arthritic, whereas the AIQ group mainly showed similar results to those observed in the control. The enteropathy associated with arthritis proved to be significant in the field of gastroenterology, and the combination of quercetin and ibuprofen demonstrated promising anti-inflammatory and neuroprotective effects.
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Anti-Inflamatórios , Antioxidantes , Ibuprofeno , Quercetina , Ratos Wistar , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Ratos , Masculino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Neurônios/efeitos dos fármacos , Neurônios/patologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Sistema Nervoso Entérico/efeitos dos fármacos , Sistema Nervoso Entérico/patologia , Imuno-Histoquímica , Íleo/efeitos dos fármacos , Íleo/patologiaRESUMO
BACKGROUND: Brazil is among the countries in South America where the COVID-19 pandemic has hit the general population hardest. Self-testing for SARS-CoV-2 infection is one of the community-based strategies that could help asymptomatic individuals at-risk of COVID-19, as well as those living in areas that are difficult for health personnel to reach, to know their infectious status and contribute to impeding further transmission of the virus. METHODS: A population-based survey was conducted in November 2021, to assess the acceptability of rapid SARS-CoV-2 antigen self-testing among the population of São Paulo. Survey respondents were approached at more than 400 different street-points that were randomly selected using a five-stage randomization process. A 35-item structured questionnaire was used. Dependent variables for our analyses were the likelihood to use and willingness to pay for self-testing, and the likelihood of taking preventive measures to prevent onward transmission of SARS-CoV-2 following a reactive self-test result. Bivariate and multivariate regression analyses were performed. RESULTS: Overall, 417 respondents (44.12% female) participated; 19.66% had previously had COVID-19 disease. A minority (9.59%) felt at high-risk of COVID-19. The majority of both females and males (73.91% and 60.09%, respectively) were in favor of the idea of SARS-CoV-2 self-testing. Overall, if self-tests were available, almost half of the sample would be very likely (n = 54, 12.95%) or likely (n = 151, 36.21%) to use one if they felt they needed to. Upon receiving a positive self-test result, the majority of respondents would communicate it (88.49%), request facility-based post-test counseling (98.32%), self-isolate (97.60%), and warn their close contacts (96.64%). CONCLUSION: Rapid SARS-CoV-2 antigen self-testing could be an acceptable screening tool in São Paulo. The population would be empowered by having access to a technology that would allow them to test, even if asymptomatic, when traveling, or going to work or school. If there is a surge in the incidence of cases, self-testing could be a good approach for mass case detection by Brazil's already overstretched Unified Health System.
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COVID-19 , SARS-CoV-2 , Atitude , Brasil/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pandemias/prevenção & controle , Autoteste , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Heart rate variability (HRV), an index of the autonomic cardiac activity, is decreased in patients with epilepsy, and a low HRV is associated with a higher risk of sudden death. Generalized tonic-clonic seizures are one of the most consistent risk factors for SUDEP, but the influence (and relative risk) of each type of seizure on cardiac function is still unknown. Our objective was to assess the impact of the type of seizure (focal to bilateral tonic-clonic seizure - FBTCS - versus non-FBTCS) on periictal HRV, in a group of patients with refractory epilepsy and both types of seizures. METHODS: We performed a 48-hour Holter recording on 121 patients consecutively admitted to our Epilepsy Monitoring Unit. We only included patients with both FBTCS and non-FBTCS on the Holter recording and selected the first seizure of each type to analyze. To evaluate HRV parameters (AVNN, SDNN, RMSSD, pNN20, LF, HF, and LF/HF), we chose 5-min epochs pre- and postictally. RESULTS: We included 14 patients, with a median age of 36 (min-max, 16-55) years and 64% were female. Thirty-six percent had cardiovascular risk factors, but no previously known cardiac disease. In the preictal period, there were no statistically significant differences in HRV parameters, between FBTCS and non-FBTCS. In the postictal period, AVNN, RMSSD, pNN20, LF, and HF were significantly lower, and LF/HF and HR were significantly higher in FBTCS. From preictal to postictal periods, FBTCS elicited a statistically significant rise in HR and LF/HF, and a statistically significant fall in AVNN, RMSSD, pNN20, and HF. Non-FBTCS only caused statistically significant changes in HR (decrease) and AVNN (increase). SIGNIFICANCE/CONCLUSION: This work emphasizes the greater effect of FBTCS in autonomic cardiac function in patients with refractory epilepsy, compared to other types of seizures, with a significant reduction in vagal tonus, which may be associated with an increased risk of SUDEP.
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Epilepsia , Frequência Cardíaca , Convulsões , Adolescente , Adulto , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Convulsões/classificação , Convulsões/fisiopatologia , Morte Súbita Inesperada na Epilepsia/epidemiologia , Adulto JovemRESUMO
Deep brain stimulation of the Anterior Nucleus of the Thalamus (ANT-DBS) is an effective therapy in epilepsy. Poorer surgical outcomes are related to deviations of the lead from the ANT-target. The target identification relies on the visualization of anatomical structures by medical imaging, which presents some disadvantages. This study aims to research whether ANT-LFPs recorded with the PerceptTM PC neurostimulator can be an asset in the identification of the DBS-target. For this purpose, 17 features were extracted from LFPs recorded from a single patient, who stayed at an Epilepsy Monitoring Unit for a 5-day period. Features were then integrated into two machine learning (ML)-based methodologies, according to different LFP bipolar montages: Pass1 (nonadjacent channels) and Pass2 (adjacent channels). We obtained an accuracy of 76.6% for the Pass1-classifier and 83.33% for the Pass2-classifier in distinguishing locations completely inserted in the target and completely outside. Then, both classifiers were used to predict the target percentage of all combinations, and we found that contacts 3 (left hemisphere) and 2 and 3 (right hemisphere) presented higher signatures of the ANT-target, which agreed with the medical images. This result opens a new window of opportunity for the use of LFPs in the guidance of DBS target identification.
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Núcleos Anteriores do Tálamo , Estimulação Encefálica Profunda , Epilepsia , Núcleos Anteriores do Tálamo/fisiologia , Estimulação Encefálica Profunda/métodos , Eletrodos , Epilepsia/terapia , HumanosRESUMO
BACKGROUND: Diabetes has been recognized as a risk factor contributing to the incidence and progression of Parkinson's disease (PD). Although several hypotheses suggest a number of different mechanisms underlying the aggravation of PD caused by diabetes, less attention has been paid to the fact that diabetes and PD share pathological microvascular alterations in the brain. The characteristics of the interaction of diabetes in combination with PD at the vascular interface are currently not known. METHODS: We combined a high-fat diet (HFD) model of diabetes mellitus type 2 (DMT2) with the 6-OHDA lesion model of PD in male mice. We analyzed the association between insulin resistance and the achieved degree of dopaminergic nigrostriatal pathology. We further assessed the impact of the interaction of the two pathologies on motor deficits using a battery of behavioral tests and on microglial activation using immunohistochemistry. Vascular pathology was investigated histologically by analyzing vessel density and branching points, pericyte density, blood-brain barrier leakage, and the interaction between microvessels and microglia in the striatum. RESULTS: Different degrees of PD lesion were obtained resulting in moderate and severe dopaminergic cell loss. Even though the HFD paradigm did not affect the degree of nigrostriatal lesion in the acute toxin-induced PD model used, we observed a partial aggravation of the motor performance of parkinsonian mice by the diet. Importantly, the combination of a moderate PD pathology and HFD resulted in a significant pericyte depletion, an absence of an angiogenic response, and a significant reduction in microglia/vascular interaction pointing to an aggravation of vascular pathology. CONCLUSION: This study provides the first evidence for an interaction of DMT2 and PD at the brain microvasculature involving changes in the interaction of microglia with microvessels. These pathological changes may contribute to the pathological mechanisms underlying the accelerated progression of PD when associated with diabetes.
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Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Neurônios Dopaminérgicos/metabolismo , Microglia/patologia , Doença de Parkinson Secundária/patologia , Pericitos/patologia , Anfetamina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Resistência à Insulina/fisiologia , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Oxidopamina , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/metabolismo , Pericitos/efeitos dos fármacos , Pericitos/metabolismoRESUMO
PURPOSE: The aim of this study was to compare all retinal layers' thickness in full-term and preterm children without retinopathy of prematurity (ROP). METHODS: Cross-sectional study including two groups of patients: group 1 children with history of preterm gestation without ROP (gestational age < 37 weeks) and group 2 healthy children with history of full-term gestation. All subjects underwent an ophthalmic examination including spectral domain-optical coherence tomography. After automatic retinal segmentation, each retinal layer thickness (eight separate layers and overall thickness) was calculated in all nine Early Treatment Diabetic Retinopathy Study areas. Demographic, systemic, gestational, and birth data were collected. Generalized additive regression models were used to analyze the data. RESULTS: Fifty-one children (51 eyes) were recruited, 19 full-term and 32 preterm children, mean age at ophthalmic examination of 10.58 (4.21) and 14.13 (3.16), respectively. In multivariable analysis, the preterm group's retinal thickness was significantly decreased in total retina nasal outer sector, ganglion cell layer (GCL), and inner plexiform layer (IPL), specifically GCL temporal outer (p = 0.010), GCL superior outer (p = 0.009), IPL temporal outer (p = 0.022), and IPL superior outer (p = 0.004), when compared with full-term group. From the variables compared only with birth head circumference that influenced the models, a non-linear association was identified and consequently modeled with splines through a generalized additive model. CONCLUSION: This study suggests that preterm children without ROP have structural retinal alterations, mostly in GCL and IPL in outer areas of the macula. Therefore, it is crucial to question gestational history since these retinal changes may be found later in life leading to useless investigation.
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Macula Lutea , Retinopatia da Prematuridade , Criança , Estudos Transversais , Humanos , Recém-Nascido , Retina/diagnóstico por imagem , Retinopatia da Prematuridade/diagnóstico , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
Paracentral acute middle maculopathy (PAMM) is a recently identified spectral-domain optical coherence tomography (SD-OCT) finding characterized by a hyper-reflective band spanning the inner nuclear layer (INL), which typically evolves to INL atrophy in later stages. Typical clinical features include the sudden onset of one or multiple paracentral scotomas, normal or mild reduction in visual acuity, and a normal fundus appearance or a fundus with a deep grayish lesion. Although its pathophysiology is not yet fully understood, ischemia at the level of the intermediate and deep capillary plexa has been demonstrated to play a major role. Since its first description, an increasing number of publications on PAMM have been published in ophthalmology scientific journals. The purpose of this study is to provide a review of the current literature on PAMM.
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Degeneração Macular , Doenças Retinianas , Angiofluoresceinografia , Humanos , Doenças Retinianas/diagnóstico , Vasos Retinianos , Tomografia de Coerência ÓpticaRESUMO
Several countries included the assessment of environmental drift contamination risk for the registration of pesticides. This practice is not yet totality effective in Brazil; however, due to the large number of pesticides in use, it is important to identify the real contamination risk during pesticide spraying. Therefore, this study determined the indices of environmental risks for exposure to drift from terrestrial applications of fungicides, herbicides, and insecticides that are used in soybean crops under Brazilian climate conditions and established buffer zones for the application of these products. Based on the three prediction drift models for soybeans in Brazil, risk indices were computed for aquatic organisms and terrestrial organisms according to the modelling procedures proposed by the POCER (Pesticide Occupation and Environmental Risk) and HAIR (Harmonized Environmental Indicators for Pesticide Risk) methodologies. In general, aquatic organisms are the most sensitive to drift contamination, being chlorothalonil, trifluralin and chlorpyrifos the ones that presented the higher risk indexes. No risk was found for earthworms; in contrast, the insecticides chlorpyrifos, spinosad and thiamethoxam presented risks to bees regardless of the nozzle (droplet size) used for the determination of the drift curve, resulting in the demand for different buffer zones.
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Organismos Aquáticos/efeitos dos fármacos , Produtos Agrícolas , Monitoramento Ambiental/métodos , Glycine max , Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Organismos Aquáticos/classificação , Praguicidas/classificação , Medição de RiscoRESUMO
Deep brain stimulation (DBS) surgery is the gold standard therapeutic intervention in Parkinson's disease (PD) with motor complications, notwithstanding drug therapy. In the intraoperative evaluation of DBS's efficacy, neurologists impose a passive wrist flexion movement and qualitatively describe the perceived decrease in rigidity under different stimulation parameters and electrode positions. To tackle this subjectivity, we designed a wearable device to quantitatively evaluate the wrist rigidity changes during the neurosurgery procedure, supporting physicians in decision-making when setting the stimulation parameters and reducing surgery time. This system comprises a gyroscope sensor embedded in a textile band for patient's hand, communicating to a smartphone via Bluetooth and has been evaluated on three datasets, showing an average accuracy of 80%. In this work, we present a system that has seen four iterations since 2015, improving on accuracy, usability and reliability. We aim to review the work done so far, outlining the iHandU system evolution, as well as the main challenges, lessons learned, and future steps to improve it. We also introduce the last version (iHandU 4.0), currently used in DBS surgeries at São João Hospital in Portugal.
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Estimulação Encefálica Profunda , Procedimentos Neurocirúrgicos , Software , Punho/fisiologia , Humanos , Movimento (Física) , Processamento de Sinais Assistido por Computador , Dispositivos Eletrônicos VestíveisRESUMO
The Rho kinase (ROCK) signaling pathway is involved in several cellular events that include cell proliferation and cytoskeleton modulation leading to cell adhesion. The ROCK pathway in the human eye has been hypothesized to play important roles in corneal endothelial cell physiology and pathologic states. In addition, ROCK signaling has been identified as an important regulator of trabecular meshwork (TM) outflow, which is altered in glaucomatous eyes. These roles in corneal and glaucomatous disease states have led to the growing interest in the development of drugs selectively targeting this pathway (ROCK inhibitors). The authors provide a review of the literature on the pathobiology of the ROCK signaling in corneal endothelial disease, glaucoma, and vitreoretinal disease, as well as the clinical usefulness of ROCK inhibitors in Ophthalmology.
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Doenças da Córnea/tratamento farmacológico , Glaucoma/tratamento farmacológico , Oftalmologia/métodos , Doenças Retinianas/tratamento farmacológico , Quinases Associadas a rho/antagonistas & inibidores , Animais , Humor Aquoso/metabolismo , Células Cultivadas , Doenças da Córnea/metabolismo , Doenças da Córnea/patologia , Glaucoma/metabolismo , Glaucoma/patologia , Humanos , Pressão Intraocular , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Transdução de Sinais , Malha Trabecular/metabolismo , Malha Trabecular/patologiaRESUMO
Motion analysis systems based on a single markerless RGB-D camera are more suitable for clinical practice than multi-camera marker-based reference systems. Nevertheless, the validity of RGB-D cameras for motor function assessment in some diseases affecting gait, such as Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP), is yet to be investigated. In this study, the agreement between the Kinect v2 and a reference system for obtaining spatiotemporal and kinematic gait parameters was evaluated in the context of TTR-FAP. 3-D body joint data provided by both systems were acquired from ten TTR-FAP symptomatic patients, while performing ten gait trials. For each gait cycle, we computed several spatiotemporal and kinematic gait parameters. We then determined, for each parameter, the Bland Altman's bias and 95% limits of agreement, as well as the Pearson's and concordance correlation coefficients, between systems. The obtained results show that an affordable, portable and non-invasive system based on an RGB-D camera can accurately obtain most of the studied gait parameters (excellent or good agreement for eleven spatiotemporal and one kinematic). This system can bring more objectivity to motor function assessment of polyneuropathy patients, potentially contributing to an improvement of TTR-FAP treatment and understanding, with great benefits to the patients' quality of life.
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Neuropatias Amiloides Familiares/diagnóstico , Marcha/fisiologia , Polineuropatias/diagnóstico , Fenômenos Biomecânicos , Humanos , Qualidade de VidaRESUMO
INTRODUCTION: Image processing of optical coherence tomography scans through binarization techniques represent a non-invasive way to separately asses and measure choroidal components, in vivo. In this review, we systematically search the scientific literature regarding binarization studies published so far. METHODS: A systematic research was conducted at PubMed database, including English literature articles for all of the following terms in various combinations: binarization, choroid/al, enhanced depth spectral domain/swept source optic coherence tomography, and latest publications up to November 2018 were reviewed. RESULTS: Thirty-seven articles were included and analyzed regarding studied disease, binarization method, studied variables, and outcomes. Most of the studies have focused on the more common retinal pathologies, such as age-related macular degeneration, central serous chorioretinopathy and diabetic retinopathy but binarization techniques have also been applied to the study of choroidal characteristics in ocular inflammatory diseases, corneal dystrophies and in postsurgical follow-up. Advantages and disadvantages of binarization techniques are also discussed. CONCLUSION: Binarization of choroidal images seems to represent a promising approach to study choroid subcomponents in an increasingly detailed manner.
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Doenças da Coroide/diagnóstico , Corioide/diagnóstico por imagem , Técnicas de Diagnóstico Oftalmológico , Processamento de Imagem Assistida por Computador , Tomografia de Coerência Óptica/métodos , HumanosRESUMO
BACKGROUND: Stress is a complex process with an impact on health and performance. The use of wearable sensor-based monitoring systems offers interesting opportunities for advanced health care solutions for stress analysis. Considering the stressful nature of firefighting and its importance for the community's safety, this study was conducted for firefighters. OBJECTIVES: A biomonitoring platform was designed, integrating different biomedical systems to enable the acquisition of real time Electrocardiogram (ECG), computation of linear Heart Rate Variability (HRV) features and collection of perceived stress levels. This platform was tested using an experimental protocol, designed to understand the effect of stress on firefighter's cognitive performance, and whether this effect is related to the autonomic response to stress. METHOD: The Trier Social Stress Test (TSST) was used as a testing platform along with a 2-Choice Reaction Time Task. Linear HRV features from the participants were acquired using an wearable ECG. Self-reports were used to assess perceived stress levels. RESULTS: The TSST produced significant changes in some HRV parameters (AVNN, SDNN and LF/HF) and subjective measures of stress, which recovered after the stress task. Although these short-term changes in HRV showed a tendency to normalize, an impairment on cognitive performance was found after performing the stress event. CONCLUSION: Current findings suggested that stress compromised cognitive performance and caused a measurable change in autonomic balance. Our wearable biomonitoring platform proved to be a useful tool for stress assessment and quantification. Future studies will implement this biomonitoring platform for the analysis of stress in ecological settings.
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AIMS/HYPOTHESIS: Hypoxia in the initial days after islet transplantation leads to considerable loss of islet mass and contributes to disappointing outcomes in the clinical setting. The aim of the present study was to investigate whether co-transplantation of human non-endothelial bone marrow-derived multipotent adult progenitor cells (MAPCs), which are non-immunogenic and can secrete angiogenic growth factors during the initial days after implantation, could improve islet engraftment and survival. METHODS: Islets (150) were co-transplanted, with or without human MAPCs (2.5 × 105) as separate or composite pellets, under the kidney capsule of syngeneic alloxan-induced diabetic C57BL/6 mice. Blood glucose levels were frequently monitored and IPGTTs were carried out. Grafts and serum were harvested at 2 and 5 weeks after transplantation to assess outcome. RESULTS: Human MAPCs produced high amounts of angiogenic growth factors, including vascular endothelial growth factor, in vitro and in vivo, as demonstrated by the induction of neo-angiogenesis in the chorioallantoic membrane assay. Islet-human MAPC co-transplantation as a composite pellet significantly improved the outcome of islet transplantation as measured by the initial glycaemic control, diabetes reversal rate, glucose tolerance and serum C-peptide concentration compared with the outcome following transplantation of islets alone. Histologically, a higher blood vessel area and density in addition to a higher vessel/islet ratio were detected in recipients of islet-human MAPC composites. CONCLUSIONS/INTERPRETATION: The present data suggest that co-transplantation of mouse pancreatic islets with human MAPCs, which secrete high amounts of angiogenic growth factors, enhance islet graft revascularisation and subsequently improve islet graft function.
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Diabetes Mellitus Tipo 1/terapia , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Adulto , Animais , Glicemia/fisiologia , Células Cultivadas , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Neovascularização Fisiológica/fisiologia , Células-Tronco/fisiologiaRESUMO
BACKGROUND: The GPi (globus pallidus internus) is an important target nucleus for Deep Brain Stimulation (DBS) in medically refractory movement disorders, in particular dystonia and Parkinson's disease. Beneficial clinical outcome critically depends on precise electrode localization. Recent evidence indicates that not only neurons, but also axonal fibre tracts contribute to promoting the clinical effect. Thus, stereotactic planning should, in the future, also take the individual course of fibre tracts into account. OBJECTIVE: The aim of this project is to explore the GPi connectivity profile and provide a connectivity-based parcellation of the GPi. METHODS: Diffusion MRI sequences were performed in sixteen healthy, right-handed subjects. Connectivity-based parcellation of the GPi was performed applying two independent methods: 1) a hypothesis-driven, seed-to-target approach based on anatomic priors set as connectivity targets and 2) a purely data-driven approach based on k-means clustering of the GPi. RESULTS: Applying the hypothesis-driven approach, we obtained five major parcellation clusters, displaying connectivity to the prefrontal cortex, the brainstem, the GPe (globus pallidus externus), the putamen and the thalamus. Parcellation clusters obtained by both methods were similar in their connectivity profile. With the data-driven approach, we obtained three major parcellation clusters. Inter-individual variability was comparable with results obtained in thalamic parcellation. CONCLUSION: The three parcellation clusters obtained by the purely data-driven method might reflect GPi subdivision into a sensorimotor, associative and limbic portion. Clinical and physiological studies indicate greatest clinical DBS benefit for electrodes placed in the postero-ventro-lateral GPi, the region displaying connectivity to the thalamus in our study and generally attributed to the sensorimotor system. Clinical studies relating DBS electrode positions to our GPi connectivity map would be needed to complement our findings.
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Estimulação Encefálica Profunda/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Globo Pálido/diagnóstico por imagem , Adulto , Voluntários Saudáveis , HumanosRESUMO
Epilepsy being one of the most prevalent neurological disorders, affecting approximately 50 million people worldwide, and with almost 30-40% of patients experiencing partial epilepsy being nonresponsive to medication, epilepsy surgery is widely accepted as an effective therapeutic option. Presurgical evaluation has advanced significantly using noninvasive techniques based on video monitoring, neuroimaging, and electrophysiological and neuropsychological tests; however, certain clinical settings call for invasive intracranial recordings such as stereoelectroencephalography (SEEG), aiming to accurately map the eloquent brain networks involved during a seizure. Most of the current presurgical evaluation procedures focus on semiautomatic techniques, where surgery diagnosis relies immensely on neurologists' experience and their time-consuming subjective interpretation of semiology or the manifestations of epilepsy and their correlation with the brain's electrical activity. Because surgery misdiagnosis reaches a rate of 30%, and more than one-third of all epilepsies are poorly understood, there is an evident keen interest in improving diagnostic precision using computer-based methodologies that in the past few years have shown near-human performance. Among them, deep learning has excelled in many biological and medical applications, but has advanced insufficiently in epilepsy evaluation and automated understanding of neural bases of semiology. In this paper, we systematically review the automatic applications in epilepsy for human motion analysis, brain electrical activity, and the anatomoelectroclinical correlation to attribute anatomical localization of the epileptogenic network to distinctive epilepsy patterns. Notably, recent advances in deep learning techniques will be investigated in the contexts of epilepsy to address the challenges exhibited by traditional machine learning techniques. Finally, we discuss and propose future research on epilepsy surgery assessment that can jointly learn across visually observed semiologic patterns and recorded brain electrical activity.
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Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Cuidados Pré-Operatórios/métodos , Convulsões/fisiopatologia , Eletrodos Implantados , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Humanos , Aprendizado de Máquina , Convulsões/diagnóstico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Peripapillary retinal nerve fiber layer (pRNFL) and internal macular layer thinning have been demonstrated in Alzheimer's disease (AD) with optical coherence tomography (OCT) studies. The purpose of this study is to compare the pRNFL thickness and overall retinal thickness (RT) in AD patients with non-AD patients, using spectral domain optical coherence tomography (SD-OCT) and determine the sectors most characteristically affected in AD. METHODS: A cross-sectional study was performed to determine the pRNFL and overall macular RT thicknesses in AD and non-AD patients, attending a tertiary hospital center. For pRNFL, the global and six peripapillary quadrants were calculated, and for overall RT values, the nine Early Treatment Diabetic Retinopathy Study (ETDRS) areas were used. A multiple regression analysis was applied to assess the effects of disease, age, gender, spherical equivalent, visual acuity, intraocular pressure, axial length and blood pressure on pRNFL and overall macular RT. RESULTS: A total of 202 subjects, including 50 eyes of 50 patients with mild AD (mean age 73.10; SD = 5.36 years) and 152 eyes of 152 patients without AD (mean age 71.03; SD = 4.62 years). After Bonferroni correction, the pRNFL was significantly thinner for the AD group globally and in the temporal superior quadrant (10.76 µm and 20.09 µm mean decrease, respectively). The RT thickness was also decreased in superior sectors S3 and S6 (mean thinning of 9.92 µm and 11.65 µm, respectively). Spearman's correlation coefficient showed a direct association between pRNFL in the temporal superior quadrant and RT in superior S6 and S3 sectors (rS = 0.41; p < 0.001 and rS = 0.28; p < 0.001, respectively). CONCLUSIONS: Patients with AD showed a significant thickness reduction in global and temporal superior quadrants in pRNFL and in superior pericentral and peripheral sectors of RT. These findings may reflect a peripapillary and retinal changes characteristic of AD, suggesting the importance of SD-OCT as a potential adjuvant in early diagnosis of AD. Further studies are needed to understand which retinal layers and macular sectors are more useful as potential ocular biomarker over time in AD.
Assuntos
Doença de Alzheimer/diagnóstico , Macula Lutea/patologia , Fibras Nervosas/patologia , Doenças Retinianas/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Pressão Sanguínea/fisiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Disco Óptico , Doenças Retinianas/etiologia , Doenças Retinianas/fisiopatologia , Estudos RetrospectivosRESUMO
The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is able to promote the generation of tolerogenic mature dendritic cells (mDCs) with an impaired ability to activate autoreactive T cells. These cells could represent a reliable tool for the promotion or restoration of Ag-specific tolerance through vaccination strategies, for example in type 1 diabetes patients. However, successful transfer of 1,25(OH)2D3-treated mDCs (1,25D3-mDCs) depends on the capacity of 1,25(OH)2D3 to imprint a similar tolerogenic profile in cells derived from diabetes-prone donors as from diabetes-resistant donors. In this study, we examined the impact of 1,25(OH)2D3 on the function and phenotype of mDCs originating from healthy (C57BL/6) and diabetes-prone (NOD) mice. We show that 1,25(OH)2D3 is able to imprint a phenotypic tolerogenic profile on DCs derived from both mouse strains. Both NOD- and C57BL/6-derived 1,25D3-mDCs decreased the proliferation and activation of autoreactive T cells in vitro, despite strain differences in the regulation of cytokine/chemokine expression. In addition, 1,25D3-mDCs from diabetes-prone mice expanded CD25(+)Foxp3(+) regulatory T cells and induced intracellular IL-10 production by T cells in vitro. Furthermore, 1,25D3-mDCs exhibited an intact functional migratory capacity in vivo that favors homing to the liver and pancreas of adult NOD mice. More importantly, when cotransferred with activated CD4(+) T cells into NOD.SCID recipients, 1,25D3-mDCs potently dampened the proliferation of autoreactive donor T cells in the pancreatic draining lymph nodes. Altogether, these results argue for the potential of 1,25D3-mDCs to restore Ag-specific immune tolerance and arrest autoimmune disease progression in vivo.
Assuntos
Células Dendríticas/imunologia , Tolerância Imunológica/efeitos dos fármacos , Vitamina D/análogos & derivados , Animais , Quimiotaxia de Leucócito/efeitos dos fármacos , Quimiotaxia de Leucócito/imunologia , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Citometria de Fluxo , Imunofluorescência , Tolerância Imunológica/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Vitamina D/farmacologiaRESUMO
Diabetic retinopathy is an increasingly prevalent disease, and a leading contributor to the burden of all-cause blindness worldwide. In addition to retinal changes, choroidal abnormalities are common in patients with diabetes. The first studies concerning this vascular structure were based on histologic, indocyanine angiography and laser Doppler flowmetry techniques, but the development of new optical coherence tomography (OCT) technologies and imaging software for enhanced depth imaging (EDI)-OCT in recent years has made it possible to provide more detailed images of the choroidal anatomy and topography.In diabetic patients, several choroidal changes have been described in the literature throughout the years; the recent focus is choroidal thickness, which is significantly different from that in healthy patients. However, understanding choroidal manifestations of diabetic eye disease remains a real challenge, and this gap is hindering efforts towards better defining choroidal evaluation as a predictive factor for disease evolution and treatment response.This review aims to summarize the recent literature concerning changes in choroidal structure in diabetic patients, the relationship to diabetic retinal disease progression, and finally, the current and potential application of the measurement of variations in choroidal thickness for patient management.
Assuntos
Doenças da Coroide/etiologia , Corioide/diagnóstico por imagem , Retinopatia Diabética/complicações , Retina/diagnóstico por imagem , Doenças da Coroide/diagnóstico , Retinopatia Diabética/diagnóstico , Angiofluoresceinografia , Fundo de Olho , Humanos , Tomografia de Coerência ÓpticaRESUMO
The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal (p = 0.008) and inferior-temporal (p = 0.023) sectors of the ipsilateral eye and nasal sector (p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye (p = 0.004) and nasally in the contralateral eye (p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls (p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway.