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A gold(III) complex of an N-heterocyclic carbene based hemilabile ligand with two pendant pyrazole arms (1,3-bis((1H-pyrazol-3-yl)methyl)-2,3-dihydro-1H-imidazole, LH) was synthesized. Complex [LAu(III)Cl3] is an excellent catalyst for promoting dihydroalkoxylation at room temperature, even catalyzing this reaction at 0 °C. [LAu(III)Cl3] is one of the most efficient catalysts reported to date for the spirocyclization of alkynyl diols. Furthermore, [LAu(III)Cl3] catalyzed intra- and intermolecular hydroamination reactions, achieving good to excellent conversions. [LAu(III)Cl3] is a more efficient catalyst than a gold(I) analogue, [LAu(I)Cl]. The dependence of the quantity of weakly coordinating anion [BArF4]- ((3,5-trifluoromethyl)phenyl borate) present on catalysis efficiency was probed for the dihydroalkoxylation reaction. X-ray diffraction analysis of single crystals demonstrated the solid-state structure of gold complexes [LAu(III)Cl3] and [LAu(I)Cl], which displayed the expected square-planar and linear coordination geometries, respectively.
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In computer-aided diagnosis (CAD) of mediolateral oblique (MLO) view of mammogram, the accuracy of tissue segmentation highly depends on the exclusion of pectoral muscle. Robust methods for such exclusions are essential as the normal presence of pectoral muscle can bias the decision of CAD. In this paper, a novel texture gradient-based approach for automatic segmentation of pectoral muscle is proposed. The pectoral edge is initially approximated to a straight line by applying Hough transform on Probable Texture Gradient (PTG) map of the mammogram followed by block averaging with the aid of approximated line. Furthermore, a smooth pectoral muscle curve is achieved with proposed Euclidean Distance Regression (EDR) technique and polynomial modeling. The algorithm is robust to texture and overlapping fibro glandular tissues. The method is validated with 340 MLO views from three databases-including 200 randomly selected scanned film images from miniMIAS, 100 computed radiography images and 40 full-field digital mammogram images. Qualitatively, 96.75 % of the pectoral muscles are segmented with an acceptable pectoral score index. The proposed method not only outperforms state-of-the-art approaches but also accurately quantifies the pectoral edge. Thus, its high accuracy and relatively quick processing time clearly justify its suitability for CAD.
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Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Reconhecimento Automatizado de Padrão/métodos , Músculos Peitorais/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Algoritmos , Bases de Dados Factuais , Feminino , Humanos , Reprodutibilidade dos TestesRESUMO
Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action-reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action-reward associations rather than stimulus-reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action-reward associations during reinforcement learning.
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Doença de Parkinson/terapia , Aprendizagem por Probabilidade , Reforço Psicológico , Substância Negra/fisiologia , Idoso , Estimulação Encefálica Profunda , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologiaRESUMO
Humans possess the remarkable ability to search their memory, allowing specific past episodes to be re-experienced spontaneously. Here, we administered a free recall test to 114 neurosurgical patients and used intracranial theta and high-frequency activity (HFA) to identify the spatiotemporal pattern of neural activity underlying spontaneous episodic retrieval. We found that retrieval evolved in three electrophysiological stages composed of: (1) early theta oscillations in the right temporal cortex, (2) increased HFA in the left hemisphere including the medial temporal lobe (MTL), left inferior frontal gyrus, as well as the ventrolateral temporal cortex, and (3) motor/language activation during vocalization of the retrieved item. Of these responses, increased HFA in the left MTL predicted recall performance. These results suggest that spontaneous recall of verbal episodic memories involves a spatiotemporal pattern of spectral changes across the brain; however, high-frequency activity in the left MTL represents a final common pathway of episodic retrieval.
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Córtex Cerebral/fisiopatologia , Ritmo Gama/fisiologia , Memória Episódica , Rememoração Mental/fisiologia , Ritmo Teta/fisiologia , Mapeamento Encefálico , Eletroencefalografia , Epilepsia/patologia , Epilepsia/cirurgia , Feminino , Lateralidade Funcional , Humanos , Idioma , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Análise Espectral , Fatores de Tempo , Aprendizagem VerbalRESUMO
The brain's sensitivity to unexpected gains or losses plays an important role in our ability to learn new behaviors (Rescorla and Wagner, 1972; Sutton and Barto, 1990). Recent work suggests that gains and losses are ubiquitously encoded throughout the human brain (Vickery et al., 2011), however, the extent to which reward expectation modulates these valence representations is not known. To address this question, we analyzed recordings from 4306 intracranially implanted electrodes in 39 neurosurgical patients as they performed a two-alternative probability learning task. Using high-frequency activity (HFA, 70-200 Hz) as an indicator of local firing rates, we found that expectation modulated reward-related neural activity in widespread brain regions, including regions that receive sparse inputs from midbrain dopaminergic neurons. The strength of unexpected gain signals predicted subjects' abilities to encode stimulus-reward associations. Thus, neural signals that are functionally related to learning are widely distributed throughout the human brain.
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Antecipação Psicológica/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Adulto , Algoritmos , Mapeamento Encefálico , Neurônios Dopaminérgicos/fisiologia , Epilepsia Resistente a Medicamentos/cirurgia , Eletrodos Implantados , Eletroencefalografia , Emoções/fisiologia , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Mesencéfalo/fisiologia , Reforço Psicológico , RecompensaRESUMO
It is hypothesized that disparate brain regions interact via synchronous activity to control behavior. The nature of these interconnected ensembles remains an area of active investigation, and particularly the role of high frequency synchronous activity in simplistic behavior is not well known. Using intracranial electroencephalography, we explored the spectral dynamics and network connectivity of sensorimotor cortical activity during a simple motor task in seven epilepsy patients. Confirming prior work, we see a "spectral tilt" (increased high-frequency (HF, 70-100 Hz) and decreased low-frequency (LF, 3-33 Hz) broadband oscillatory activity) in motor regions during movement compared to rest, as well as an increase in LF synchrony between these regions using time-resolved phase-locking. We then explored this phenomenon in high frequency and found a robust but opposite effect, where time-resolved HF broadband phase-locking significantly decreased during movement. This "connectivity tilt" (increased LF synchrony and decreased HF synchrony) displayed a graded anatomical dependency, with the most robust pattern occurring in primary sensorimotor cortical interactions and less robust pattern occurring in associative cortical interactions. Connectivity in theta (3-7 Hz) and high beta (23-27 Hz) range had the most prominent low frequency contribution during movement, with theta synchrony building gradually while high beta having the most prominent effect immediately following the cue. There was a relatively sharp, opposite transition point in both the spectral and connectivity tilt at approximately 35 Hz. These findings support the hypothesis that task-relevant high-frequency spectral activity is stochastic and that the decrease in high-frequency synchrony may facilitate enhanced low frequency phase coupling and interregional communication. Thus, the "connectivity tilt" may characterize behaviorally meaningful cortical interactions.
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Movimento , Córtex Sensório-Motor , Humanos , Masculino , Feminino , Adulto , Córtex Sensório-Motor/fisiologia , Córtex Sensório-Motor/fisiopatologia , Movimento/fisiologia , Adulto Jovem , Eletroencefalografia , Rede Nervosa/fisiologia , Epilepsia/fisiopatologiaRESUMO
BACKGROUND AND OBJECTIVES: Intracranial modulation paradigms, namely deep brain stimulation (DBS) and motor cortex stimulation (MCS), have been used to treat intractable pain disorders. However, treatment efficacy remains heterogeneous, and factors associated with pain reduction are not completely understood. METHODS: We performed an individual patient review of pain outcomes (visual analog scale, quality-of-life measures, complications, pulse generator implant rate, cessation of stimulation) after implantation of DBS or MCS devices. We evaluated 663 patients from 36 study groups and stratified outcomes by pain etiology and implantation targets. RESULTS: Included studies comprised primarily retrospective cohort studies. MCS patients had a similar externalized trial success rate compared with DBS patients (86% vs 81%; P = .16), whereas patients with peripheral pain had a higher trial success rate compared with patients with central pain (88% vs 79%; P = .004). Complication rates were similar for MCS and DBS patients (12% vs 15%; P = .79). Patients with peripheral pain had lower likelihood of device cessation compared with those with central pain (5.7% vs 10%; P = .03). Of all implanted patients, mean pain reduction at last follow-up was 45.8% (95% CI: 40.3-51.2) with a 31.2% (95% CI: 12.4-50.1) improvement in quality of life. No difference was seen between MCS patients (43.8%; 95% CI: 36.7-58.2) and DBS patients (48.6%; 95% CI: 39.2-58) or central (41.5%; 95% CI: 34.8-48.2) and peripheral (46.7%; 95% CI: 38.9-54.5) etiologies. Multivariate analysis identified the anterior cingulate cortex target to be associated with worse pain reduction, while postherpetic neuralgia was a positive prognostic factor. CONCLUSION: Both DBS and MCS have similar efficacy and complication rates in the treatment of intractable pain. Patients with central pain disorders tended to have lower trial success and higher rates of device cessation. Additional prognostic factors include anterior cingulate cortex targeting and postherpetic neuralgia diagnosis. These findings underscore intracranial neurostimulation as an important modality for treatment of intractable pain disorders.
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Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). Interactions between these regions have been studied indirectly using functional MRI, but the bases for interregional communication at a cellular level remain poorly understood. Here, we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus. We recorded extracellular spikes from 1854 single- and multi-units simultaneously with hippocampal local field potentials (LFPs) in 28 neurosurgical patients who completed virtual navigation experiments. A majority of hippocampal neurons phase-locked to oscillations in the slow (2-4 Hz) or fast (6-10 Hz) theta bands, with a significant subset exhibiting nested slow theta × beta frequency (13-20 Hz) phase-locking. Outside of the hippocampus, phase-locking to hippocampal oscillations occurred only at theta frequencies and primarily among neurons in the entorhinal cortex and amygdala. Moreover, extrahippocampal neurons phase-locked to hippocampal theta even when theta did not appear locally. These results indicate that spike-time synchronization with hippocampal theta is a defining feature of neuronal activity in the hippocampus and structurally connected MTL regions. Theta phase-locking could mediate flexible communication with the hippocampus to influence the content and quality of memories.
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Hipocampo , Ritmo Teta , Humanos , Ritmo Teta/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia , Lobo Temporal , Córtex EntorrinalRESUMO
Traumatic brain injury (TBI) remains a pervasive clinical problem associated with significant morbidity and mortality. However, TBI remains clinically and biophysically ill-defined, and prognosis remains difficult even with the standardization of clinical guidelines and advent of multimodality monitoring. Here we leverage a unique data set from TBI patients implanted with either intracranial strip electrodes during craniotomy or quad-lumen intracranial bolts with depth electrodes as part of routine clinical practice. By extracting spectral profiles of this data, we found that the presence of narrow-band oscillatory activity in the beta band (12-30 Hz) closely corresponds with the neurological exam as quantified with the standard Glasgow Coma Scale (GCS). Further, beta oscillations were distributed over the cortical surface as traveling waves, and the evolution of these waves corresponded to recovery from coma, consistent with the putative role of waves in perception and cognitive activity. We consequently propose that beta oscillations and traveling waves are potential biomarkers of recovery from TBI. In a broader sense, our findings suggest that emergence from coma results from recovery of thalamo-cortical interactions that coordinate cortical beta rhythms.
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A 72-year-old female with a history of hypertension and hyperlipidemia presented to the emergency department from an outside hospital with acute confusion and global amnesia immediately following cervical epidural steroid injection with fluoroscopic guidance for radiculopathy relief. On exam, she was oriented to self, but disoriented to place and situation. Otherwise, she was neurologically intact with no deficits. Head computed tomography (CT) revealed diffuse subarachnoid hyperdensities most prominent in the parafalcine region concerning for diffuse subarachnoid hemorrhage and tonsillar herniation concerning for intracranial hypertension. CT angiograms of head and neck were negative for vascular abnormalities. Dual-energy head CT was subsequently performed 4 hours later without IV contrast. The 80 kV sequence revealed prominent diffuse hyperdensity throughout the cerebrospinal fluid spaces in bilateral cerebral hemispheres, basal cisterns, and posterior fossa consistent with the initial CT, but these corresponding regions were relatively less dense on the 150 kV sequence. These findings were consistent with contrast material in the cerebrospinal fluid spaces without evidence of intracranial hemorrhage or transcortical infarct. Three hours later, the patient's transient confusion resolved, and she was discharged home the next morning without any neurological deficit.
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Hemorragia Subaracnóidea , Feminino , Humanos , Idoso , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Cabeça , Confusão , Hemorragias IntracranianasRESUMO
Healthy sleep signifies a good physical and mental state of the body. However, factors such as inappropriate work schedules, medical complications, and others can make it difficult to get enough sleep, leading to various sleep disorders. The identification of these disorders requires sleep stage classification. Visual evaluation of sleep stages is time intensive, placing a significant strain on sleep experts and prone to human errors. As a result, it is crucial to develop machine learning algorithms to score sleep stages to acquire an accurate diagnosis. Hence, a new methodology for automated sleep stage classification is suggested using machine learning and filtering electroencephalogram (EEG) signals. The national sleep research resource's (NSRR) study of osteoporotic fractures (SOF) dataset comprising 453 subjects' polysomnograph (PSG) data is used in this study. Only two unipolar EEG derivations C4-A1 and C3-A2 are employed individually and jointly in this work. The EEG signals are decomposed into sub-bands using a frequency-localized finite orthogonal quadrature Fejer Korovkin wavelet filter bank. The wavelet-based entropy features are extracted from sub-bands. Subsequently, extracted features are classified using machine learning techniques. Our developed model obtained the highest classification accuracy of 81.3%, using an ensembled bagged trees classifier with a 10-fold cross-validation method and Cohen's Kappa coefficient of 0.72. The proposed model is accurate, dependable, and easy to implement and can be employed as an alternative to a PSG-based system at home with minimal resources. It is also ready to be tested on other EEG data to evaluate the sleep stages of healthy and unhealthy subjects.
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Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Idoso , Sono , Fases do Sono , Polissonografia , Algoritmos , Eletroencefalografia/métodos , Osteoporose/complicaçõesRESUMO
BACKGROUND: There remains a number of factors thought to be associated with survival in spinal metastatic disease, but evidence of these associations is lacking. In this study, we examined factors associated with survival among patients undergoing surgery for spinal metastatic disease. METHODS: We retrospectively examined 104 patients who underwent surgery for spinal metastatic disease at an academic medical center. Of those patients, 33 received local preoperative radiation (PR) and 71 had no PR (NPR). Disease-related variables and surrogate markers of preoperative health were identified, including age, pathology, timing of radiation and chemotherapy, mechanical instability by spine instability neoplastic score, American Society of Anesthesiologists (ASA) classification, Karnofsky performance status (KPS), and body mass index (BMI). We performed survival analyses using a combination of univariate and multivariate Cox proportional hazards models to assess significant predictors of time to death. RESULTS: Local PR (Hazard Ratio [HR] = 1.84, P = 0.034), mechanical instability (HR = 1.11, P = 0.024), and melanoma (HR = 3.60, P = 0.010) were significant predictors of survival on multivariate analysis when controlling for confounders. PR vs NPR cohorts exhibited no statistically significant differences in preoperative age (P = 0.22), KPS (P = 0.29), BMI (P = 0.28), or ASA classification (P = 0.12). NPR patients had more reoperations for postoperative wound complications (11.3% vs 0%, P < 0.001). CONCLUSIONS: In this small sample, PR and mechanical instability were significant predictors of postoperative survival, independent of age, BMI, ASA classification, and KPS and in spite of fewer wound complications in the PR group. It is possible that PR was a surrogate of more advanced disease or poor response to systemic therapy, independently portending a worse prognosis. Future studies in larger, more diverse populations are crucial for understanding the relationship between PR and postoperative outcomes to determine the optimal timing for surgical intervention. CLINICAL RELEVANCE: These findings are clinically relevent as they provide insight into factors associated with survival in metastatic spinal disease.
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MYB transcription factor genes play important roles in developmental and various other processes in plants. In this study, functional characterization of AmMYB1, a single-repeat MYB transcription factor isolated from the salt-tolerant mangrove tree Avicennia marina is reported. AmMYB1 cDNA was 1046 bp in length with an open reading frame of 783 bp, encoding 260 amino acids. The corresponding gene had two introns and three exons and was present as a single copy in A. marina. The deduced amino acid sequence showed similarities to MYB proteins reported in other plants, including the conserved MYB binding domain. RNA gel blot analysis showed that the AmMYB1 transcript expression was more pronounced in green photosynthetic tissue and was strongly induced by stresses such as salt (500 mM), light (500 µE m(-2) s(-1)), and the exogenous application of ABA (100 µM). An analysis of the upstream sequence of AmMYB1 gene revealed the presence of regulatory elements identical to those present in the promoters of stress inducible genes. The promoter was responsive to NaCl and could enhance reporter gene expression in planta. An in vitro DNA binding assay using the promoter region (TGGTTAG) of the AtRD22 gene and a transactivation assay in yeast cells suggest the possibility of AmMYB1 protein regulating the expression of other genes during salt stress. Transgenic tobacco plants constitutively expressing the AmMYB1 transcription factor showed better tolerance to NaCl stress.
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Avicennia/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Nicotiana/fisiologia , Cloreto de Sódio/farmacologia , Fatores de Transcrição/metabolismo , Ácido Abscísico/farmacologia , Sequência de Aminoácidos , Avicennia/efeitos dos fármacos , Avicennia/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Luz , Dados de Sequência Molecular , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos da radiação , Caules de Planta/efeitos dos fármacos , Caules de Planta/genética , Caules de Planta/metabolismo , Caules de Planta/efeitos da radiação , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Tolerância ao Sal , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/metabolismo , Plântula/efeitos da radiação , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/metabolismo , Sementes/efeitos da radiação , Alinhamento de Sequência , Estresse Fisiológico , Nicotiana/efeitos dos fármacos , Nicotiana/genética , Nicotiana/efeitos da radiação , Fatores de Transcrição/genética , Ativação TranscricionalRESUMO
EM waves are extremely powerful when it comes to propagation of information during communication. There is no alternative to EM waves in such applications. However, the use of EM waves or antennas in general has not been explored fully as sensors for measuring the change in physical environment. This particular aspect has been exploited and the present work focuses on the application of antennas into the domain of classification. We propose accurate human activity classification (HAC) using on body miniaturized antennas. A simple patch antenna has been designed in order to be employed on human body for HAC. The antenna has been tested with respect to its Specific Absorption Ratio (SAR) values in order to make it body-mountable. The antenna has been fabricated and tested on human body while performing daily activities. The reflection co-efficient of antennas is a function of human motion activities and this principle is exploited to achieve the desired results. To explore different approaches, a miniaturized circularly polarized antenna is then designed and tested. The results of the two antennas are then compared. Dynamic Time Warping (DTW) algorithm has been used for the analysis of the Reflection co-efficient of the antenna. Excellent activity classification performance has been obtained using both the antennas, the miniaturized antenna giving better results.
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BACKGROUND: The ventral intermediate (VIM) thalamic nucleus is the main target for the surgical treatment of refractory tremor. Initial targeting traditionally relies on atlas-based stereotactic targeting formulas, which only minimally account for individual anatomy. Alternative approaches have been proposed, including direct targeting of the dentato-rubro-thalamic tract (DRTT), which, in clinical settings, is generally reconstructed with deterministic tracking. Whether more advanced probabilistic techniques are feasible on clinical-grade magnetic resonance acquisitions and lead to enhanced reconstructions is poorly understood. OBJECTIVE: To compare DRTT reconstructed with deterministic vs probabilistic tracking. METHODS: This is a retrospective study of 19 patients with essential tremor who underwent deep brain stimulation (DBS) with intraoperative neurophysiology and stimulation testing. We assessed the proximity of the DRTT to the DBS lead and to the active contact chosen based on clinical response. RESULTS: In the commissural plane, the deterministic DRTT was anterior (P < 10-4) and lateral (P < 10-4) to the DBS lead. By contrast, although the probabilistic DRTT was also anterior to the lead (P < 10-4), there was no difference in the mediolateral dimension (P = .5). Moreover, the 3-dimensional Euclidean distance from the active contact to the probabilistic DRTT was smaller vs the distance to the deterministic DRTT (3.32 ± 1.70 mm vs 5.01 ± 2.12 mm; P < 10-4). CONCLUSION: DRTT reconstructed with probabilistic fiber tracking was superior in spatial proximity to the physiology-guided DBS lead and to the empirically chosen active contact. These data inform strategies for surgical targeting of the VIM.
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Estimulação Encefálica Profunda , Tremor Essencial , Estimulação Encefálica Profunda/métodos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Humanos , Estudos Retrospectivos , Tálamo/diagnóstico por imagem , Tálamo/fisiologia , Tálamo/cirurgia , TremorRESUMO
BackgroundAn increasing number of studies utilize intracranial electrophysiology in human subjects to advance basic neuroscience knowledge. However, the use of neurosurgical patients as human research subjects raises important ethical considerations, particularly regarding informed consent and undue influence, as well as subjects' motivations for participation. Yet a thorough empirical examination of these issues in a participant population has been lacking. The present study therefore aimed to empirically investigate ethical concerns regarding informed consent and voluntariness in Parkinson's disease patients undergoing deep brain stimulator (DBS) placement who participated in an intraoperative neuroscience study.MethodsTwo semi-structured 30-minute interviews were conducted preoperatively and postoperatively via telephone. Interviews assessed participants' motivations for participation in the parent intraoperative study, recall of information presented during the informed consent process, and participants' postoperative reflections on the research study.ResultsTwenty-two participants (mean age = 60.9) completed preoperative interviews at a mean of 7.8 days following informed consent and a mean of 5.2 days prior to DBS surgery. Twenty participants completed postoperative interviews at a mean of 5 weeks following surgery. All participants cited altruism or advancing medical science as "very important" or "important" in their decision to participate in the study. Only 22.7% (n = 5) correctly recalled one of the two risks of the study. Correct recall of other aspects of the informed consent was poor (36.4% for study purpose; 50.0% for study protocol; 36.4% for study benefits). All correctly understood that the study would not confer a direct therapeutic benefit to them.ConclusionEven though research coordinators were properly trained and the informed consent was administered according to protocol, participants demonstrated poor retention of study information. While intraoperative studies that aim to advance neuroscience knowledge represent a unique opportunity to gain fundamental scientific knowledge, improved standards for the informed consent process can help facilitate their ethical implementation.
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Motivação , Doença de Parkinson , Humanos , Consentimento Livre e Esclarecido , Pessoa de Meia-Idade , Doença de Parkinson/cirurgia , Projetos de Pesquisa , PesquisadoresRESUMO
Environmental arsenic exposure, through drinking contaminated water, is a significant risk factor for developing vascular diseases and is associated with liver portal hypertension, vascular shunting, and portal fibrosis through unknown mechanisms. We found that the addition of low doses of arsenite to the drinking water of mice resulted in marked pathologic remodeling in liver sinusoidal endothelial cells (SECs), including SEC defenestration, capillarization, increased junctional PECAM-1 expression, protein nitration, and decreased liver clearance of modified albumin. Furthermore, the pathologic changes observed after in vivo exposure were recapitulated in isolated mouse SECs exposed to arsenic in culture. To investigate the role of NADPH oxidase-generated ROS in this remodeling, we examined the effect of arsenite in the drinking water of mice deficient for the p47 subunit of the NADPH oxidase and found that knockout mice were protected from arsenite-induced capillarization and protein nitration. Furthermore, ex vivo arsenic exposure increased SEC superoxide generation, and this effect was inhibited by addition of a Nox2 inhibitor and quenched by the cell-permeant superoxide scavenger. In addition, inhibiting either oxidant generation or Rac1-GTPase blocked ex vivo arsenic-stimulated SEC differentiation and dysfunction. Our data indicate that a Nox2-based oxidase is required for SEC capillarization and that it may play a central role in vessel remodeling following environmentally relevant arsenic exposures.
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Arsênio/toxicidade , Células Endoteliais/enzimologia , Fígado/enzimologia , Glicoproteínas de Membrana/metabolismo , NADPH Oxidases/metabolismo , Neovascularização Patológica/enzimologia , Superóxidos/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Células Endoteliais/patologia , Sequestradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hipertensão Portal/induzido quimicamente , Hipertensão Portal/enzimologia , Hipertensão Portal/genética , Hipertensão Portal/patologia , Fígado/irrigação sanguínea , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/enzimologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Knockout , NADPH Oxidase 2 , NADPH Oxidases/genética , Neovascularização Patológica/induzido quimicamente , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTPRESUMO
Recent functional neuroimaging and brain lesion studies have implicated a network of left hemisphere regions in human tool use: 1) posterior middle temporal cortex involved in conceptual knowledge of tools, 2) posterior inferior parietal cortex for representations of learned tool use gestures, and 3) anterior inferior parietal cortex, along with posterior inferior frontal and ventral premotor cortices, involved in grasping and manipulating objects. Here, we use diffusion tensor imaging (DTI) to investigate the anatomical connections that support this putative network. DTI scans were acquired from nineteen right-handed males and a deterministic tractography algorithm was used to identify connections between these regions implicated in tool use. Three of the resulting pathways were larger in the left than the right hemisphere. One connected posterior middle temporal cortex and the anterior inferior parietal cortex, a second connected posterior middle temporal cortex and the posterior inferior parietal cortex, and a third connected anterior inferior parietal cortex and the frontal lobe. In contrast, the connection between the posterior inferior parietal cortex and the frontal lobe was highly rightwardly asymmetric. Although further study is necessary to establish the functions of these pathways, we integrate our findings with previous evidence from functional neuroimaging and apraxia studies to suggest some possible functions.
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Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Imagem de Tensor de Difusão/métodos , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Vias Neurais , Adulto JovemRESUMO
The relationship between social determinants of health (SDOH) and neurosurgical outcomes has become increasingly relevant. To date, results of prior work evaluating the impact of social determinants in neurosurgery have been mixed, and the need for robust data on this subject remains. The present review evaluates how gender, race, and socioeconomic status (SES) influence outcomes following various brain tumor resection procedures. Results from a number of prior studies from the senior author's lab are summarized, with all data acquired using the EpiLog tool (Epilog Laser). Separate analyses were performed for each procedure, evaluating the unique, isolated impact of gender, race, and SES on outcomes. A comprehensive literature review identified any prior studies evaluating the influence of these SDOH on neurosurgical outcomes. The review presented herein suggests that the effect of gender and race on outcomes is largely mitigated when equal access to care is attained, and socioeconomic factors and comorbidities are controlled for. Furthermore, when patients are matched upon for a number of clinically relevant covariates, SES impacts postoperative mortality. Elucidation of this disparity empowers surgeons to initiate actionable change to equilibrate future outcomes.
Assuntos
Procedimentos Neurocirúrgicos , Determinantes Sociais da Saúde/estatística & dados numéricos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Humanos , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/mortalidade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Resultado do TratamentoRESUMO
OBJECTIVE: We studied the risk of associated spinal and nonspinal injuries (NSIs) in the setting of observed thoracolumbar transverse process fracture (TPF) and examined the clinical management of TPF. METHODS: Patients treated at a Level I trauma center over a 5-year period were screened for thoracolumbar TPF. Prevalence of associated spinal fractures and NSIs as well as relationship to level of TPF was explored. Clinical management and follow-up outcomes were reviewed. RESULTS: A total of 252 patients with thoracolumbar TPFs were identified. NSIs were commonly observed (70.6%, n = 178); however, associated spinal fractures were more rarely seen (24.6%, n = 62, P < 0.0001). No patients had neurological deficits attributable to TPFs, and only 3 patients with isolated TPFs were treated with orthosis. Among patients with outpatient follow-up (70.6%, n = 178), none developed delayed-onset neurological deficits or spinal instability. Thoracic TPFs (odds ratio = 3.56, 95% confidence interval = 1.20-10.56) and L1 TPFs (odds ratio = 2.48, 95% confidence interval = 1.41-4.36) were predictive of associated thoracic NSIs. L5 TPF was associated with pelvic fractures (odds ratio = 6.30, 95% confidence interval = 3.26-12.17). There was no difference in rate of NSIs between isolated TPF (70.0%) and TPF with associated clinically relevant spinal fracture (72.6%, P = 0.70). CONCLUSIONS: NSIs are nearly 3 times more common in patients with thoracolumbar TPFs than associated clinically relevant spinal fractures. Spine service consultation for TPF may be unnecessary unless fracture is associated with a clinically relevant spinal injury, which represents a minority of cases. However, detection of TPF should raise suspicion for high likelihood of associated NSIs.