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Total phosphorus (TP) concentrations have increased in many remote mountain waterbodies across the western United States, and reports of algal blooms in these systems have increased in frequency. Explanations for observed TP increases are uncertain, and typical landscape drivers, such as agricultural/urban runoff, are implausible. We investigated multiple atmospheric and terrestrial-P loading mechanisms to explain the observed decadal increase in TP, including a novel hypothesis that warming soils may lead to elevated P fluxes to receiving water bodies. Using northern Utah mountains ranges as a case study, we measured prospective inputs of total and bioavailable P via dust deposition. Terrestrial loading was evaluated through soil leaching experiments designed to simulate soil acidification and recovery, as well as observed decadal increases in soil temperatures and extended growing season. In the Uinta Mountains, dust-P flux appears to be one of the most plausible mechanisms for P increases where we estimated bioavailable dust-P loading ranged from 1.6 to 23.1 mg P m-2 yr-1. However, our results revealed that an increase of soil pH by 0.5 units could lead to a rise in leached P, ranging from 4.7 to 65 mg P m-2. Rising temperatures also showed the potential to increase soil P leaching; Observed average historical (~ +3 °C) and future (+2 °C) increases in temperature led to a prospective increase in leached P from 2 to 264 mg SRP m-2. While we found that pH shifts can mobilize significant amounts of P in some locations, we found no evidence of pH changes through time in the Uinta Mountains. However, summer soil temperatures increased at most locations. The mechanisms evaluated in this study can help explain the widespread observed increases in P across Western US lakes, but the mechanisms that dominate in any given region are likely to vary based on local to regional factors.
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Lagos , Fósforo , Poeira , Monitoramento Ambiental , Eutrofização , Fósforo/análise , Estudos Prospectivos , SoloRESUMO
Tobacco use may initiate the process of oral carcinogenesis with clinically undetectable changes. Smoking cessation may prevent its progression. The objective of this study was to evaluate the association between DNA ploidy and micronucleus (MN) frequency in chronic smokers. Three groups were evaluated: Smoker Group, Former Smoker Group and Control Group. Exfoliative cytology was performed on the lateral border of the tongue and mouth floor. MN and DNA ploidy analyses were performed, as well as the correlation between the variables. The data showed a difference between the groups for the total MN (p = 0.0227), and the Smoker group had the highest mean (4.22 ± 4.12). The three groups did not differ statistically from each other on ploidy evaluation (p-value > 0.05). There was also an association between aneuploidy and increased MN frequency in the Former Smoker group (p = 0.0036). In conclusion, these results point out that there is a relationship between the frequency of MN and aneuploidy in former smokers. Moreover, smoking cessation, even for a short period of time, may promote the decrease of MN frequency caused by tobacco use.
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Aneuploidia , Micronúcleos com Defeito Cromossômico , Abandono do Hábito de Fumar , Fumar/genética , DNA , Feminino , Humanos , Masculino , Testes para Micronúcleos , FumantesRESUMO
The Seismic Experiment for Interior Structure (SEIS) of the InSight mission to Mars, has been providing direct information on Martian interior structure and dynamics of that planet since it landed. Compared to seismic recordings on Earth, ground motion measurements acquired by SEIS on Mars are made under dramatically different ambient noise conditions, but include idiosyncratic signals that arise from coupling between different InSight sensors and spacecraft components. This work is to synthesize what is known about these signal types, illustrate how they can manifest in waveforms and noise correlations, and present pitfalls in structural interpretations based on standard seismic analysis methods. We show that glitches, a type of prominent transient signal, can produce artifacts in ambient noise correlations. Sustained signals that vary in frequency, such as lander modes which are affected by variations in temperature and wind conditions over the course of the Martian Sol, can also contaminate ambient noise results. Therefore, both types of signals have the potential to bias interpretation in terms of subsurface layering. We illustrate that signal processing in the presence of identified nonseismic signals must be informed by an understanding of the underlying physical processes in order for high fidelity waveforms of ground motion to be extracted. While the origins of most idiosyncratic signals are well understood, the 2.4 Hz resonance remains debated and the literature does not contain an explanation of its fine spectral structure. Even though the selection of idiosyncratic signal types discussed in this paper may not be exhaustive, we provide guidance on best practices for enhancing the robustness of structural interpretations.
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AIM: The aim of this study was to develop a score to predict the outcome for patients brought to hospital following out-of-hospital cardiac arrest (OHCA). METHODS: All patients recorded in the German Resuscitation Registry (GRR) who suffered OHCA 2010-2017, who had ROSC or ongoing CPR at hospital admission were included. The study population was divided into development (2010-2016: 7985) and validation dataset (2017: 1806). Binary logistic regression analysis was used to derive the score. The probability of hospital discharge with good neurological outcome was defined as 1/(1â¯+â¯e-X), where X is the weighted sum of independent variables. RESULTS: The following variables were found to have a significant positive (+) or negative (-) impact: age 61-70 years (-0·5), 71-80 (-0·9), 81-90 (-1·3) and >â¯=â¯91 (-2·3); initial PEA (-0·9) and asystole (-1·4); presumable trauma (-1·1); mechanical CPR (-0·3); application of adrenalin >â¯0â¯-â¯<â¯2â¯mg (-1·1), 2â¯-â¯<4â¯mg (-1·6), 4â¯-â¯<â¯6â¯mg (-2·1), 6â¯-â¯<â¯8â¯mg (-2·5) and >â¯=â¯8â¯mg (-2·8); pre emergency status without previous disease (+0·5) or minor disease (+0·2); location at nursing home (-0·6), working place/school (+0·7), doctor's office (+0·7) and public place (+0·3); application of amiodarone (+0·4); hospital admission with ongoing CPR (-1·9) or normotension (+0·4); witnessed arrest (+0·6); time from collapse until start CPR 2â¯-â¯<â¯10â¯min (-0·3) and >â¯=â¯10â¯min (-0·5); duration of CPR <5â¯min (+0·6). The AUC in the development dataset was 0·88 (95% CI 0·87-0·89) and in the validation dataset 0·88 (95% CI 0·86-0·90). CONCLUSION: The CaRdiac Arrest Survival Score (CRASS) represents a tool for calculating the probability of survival with good neurological function for patients brought to hospital following OHCA.
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Reanimação Cardiopulmonar , Doenças do Sistema Nervoso , Parada Cardíaca Extra-Hospitalar , Análise de Sobrevida , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/prevenção & controle , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/terapia , Alta do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Fatores de RiscoRESUMO
In 2004, the FDA published a guideline to implement process analytical technologies (PAT) in biopharmaceutical processes for process monitoring to gain process understanding and for the control of important process parameters. Viable cell concentration (VCC) is one of the most important key performance indicator (KPI) during mammalian cell cultivation processes. Commonly, this is measured offline. In this work, we demonstrated the comparability and scalability of linear regression models derived from online capacitance measurements. The linear regressions were used to predict the VCC and other familiar offline biomass indicators, like the viable cell volume (VCV) and the wet cell weight (WCW), in two different industrially relevant CHO cell culture processes (Process A and Process B). Therefore, different single-use bioreactor scales (50-2000 L) were used to prove feasibility and scalability of the in-line sensor integration. Coefficient of determinations of 0.79 for Process A and 0.99 for Process B for the WCW were achieved. The VCV was described with high coefficients of determination of 0.96 (Process A) and 0.98 (Process B), respectively. In agreement with other work from the literature, the VCC was only described within the exponential growth phase, but resulting in excellent coefficients of determination of 0.99 (Process A) and 0.96 (Process B), respectively. Monitoring these KPIs online using linear regression models appeared to be scale-independent, enabled deeper process understanding (e.g. here demonstrated in monitoring, the feeding profile) and showed the potential of this method for process control.
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Técnicas de Cultura Celular por Lotes , Reatores Biológicos , Capacitância Elétrica , Modelos Biológicos , Animais , Biomassa , Células CHO , CricetulusRESUMO
Cheilostome Bryozoa Anoteropora latirostris, a colonial marine invertebrate, constructs its skeleton from calcite and aragonite. This study presents firstly correlated multi-scale electron microscopy, micro-computed tomography, electron backscatter diffraction and NanoSIMS mapping. We show that all primary, coarse-grained platy calcitic lateral walls are covered by fine-grained fibrous aragonite. Vertical lateral walls separating autozooid chambers have aragonite only on their distal side. This type of asymmetric mineralization of lateral walls results from the vertical arrangement of the zooids at the growth margins of the colony and represents a type of biomineralization previously unknown in cheilostome bryozoans. NanoSIMS mapping across the aragonite-calcite interface indicates an organic layer between both mineral phases, likely representing an organic template for biomineralization of aragonite on the calcite layer. Analysis of crystallographic orientations show a moderately strong crystallographic preferred orientation (CPO) for calcite (7.4 times random orientation) and an overall weaker CPO for aragonite (2.4 times random orientation) with a high degree of twinning (45%) of the aragonite grains. The calculated Young's modulus for the CPO map shows a weak mechanical direction perpendicular to the colony's upper surface facilitating this organism's strategy of clonal reproduction by fragmentation along the vertical zooid walls.
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Organismos Aquáticos/fisiologia , Biomineralização/fisiologia , Briozoários/fisiologia , Animais , Organismos Aquáticos/química , Organismos Aquáticos/ultraestrutura , Briozoários/química , Briozoários/ultraestrutura , Carbonato de Cálcio/química , Cristalografia , Microtomografia por Raio-XRESUMO
The large number of nanomaterial-based applications emerging in the materials and life sciences and the foreseeable increasing use of these materials require methods that evaluate and characterize the toxic potential of these nanomaterials to keep safety risks to people and environment as low as possible. As nanomaterial toxicity is influenced by a variety of parameters like size, shape, chemical composition, and surface chemistry, high throughput screening (HTS) platforms are recommended for assessing cytotoxicity. Such platforms are not yet available for genotoxicity testing. Here, we present first results obtained for application-relevant nanomaterials using an automatable genotoxicity platform that relies on the quantification of the phosphorylated histone H2AX (γ-H2AX) for detecting DNA double strand breaks (DSBs) and the automated microscope system AKLIDES® for measuring integral fluorescence intensities at different excitation wavelengths. This platform is used to test the genotoxic potential of 30 nm-sized citrate-stabilized gold nanoparticles (Au-NPs) as well as micellar encapsulated iron oxide nanoparticles (FeOx-NPs) and different cadmium (Cd)-based semiconductor quantum dots (QDs), thereby also searching for positive and negative controls as reference materials. In addition, the influence of the QD shell composition on the genotoxic potential of these Cd-based QDs was studied, using CdSe cores as well as CdSe/CdS core/shell and CdSe/CdS/ZnS core/shell/shell QDs. Our results clearly revealed the genotoxicity of the Au-NPs and its absence in the FeOx-NPs. The genotoxicity of the Cd-QDs correlates with the shielding of their Cd-containing core, with the core/shell/shell architecture preventing genotoxicity risks. The fact that none of these nanomaterials showed cytotoxicity at the chosen particle concentrations in a conventional cell viability assay underlines the importance of genotoxicity studies to assess the hazardous potential of nanomaterials.
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Cádmio/química , Histonas/metabolismo , Testes de Mutagenicidade/métodos , Nanoestruturas/toxicidade , Pontos Quânticos/química , Cádmio/toxicidade , Sobrevivência Celular , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Compostos Férricos/química , Compostos Férricos/toxicidade , Fluorometria , Ouro/química , Ouro/toxicidade , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Testes de Mutagenicidade/instrumentação , Nanoestruturas/química , Tamanho da Partícula , Fosforilação/efeitos dos fármacos , Pontos Quânticos/toxicidadeRESUMO
Wave-mixed bioreactors have increasingly replaced stainless steel stirred tank reactors in seed inoculum productions and mammalian cell-based process developments. Pre-sterilized, single-use plastic bags are used for cultivation, eliminating the risk of cross-contamination and cleaning procedures. However, these advantages come with high consumable costs which is the main barrier to more uptakes of the technology by academic institutions. As an academic Core Facility that faces high demand in protein production from insect cells, we have therefore developed a cost-effective alternative to disposable wave bags. In our study we identified: â¢A re-usable wave shaken polycarbonate bioreactor for protein production in insect cells achieves protein yields comparable to disposable bags.â¢The advantages of this re-usable bioreactor are low costs, long life cycle, flexible configuration of accessories and convenient handling due to its rigid shape.
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Murine models of Alzheimer's disease (AD) have been used to draw associations between atrophy of neural tissue and underlying pathology. In this study, the early-onset TgCRND8 mouse model of AD and littermate controls were scanned longitudinally with in vivo manganese-enhanced MRI (MEMRI) before and after the onset of amyloid plaque deposition at 12 weeks of age. Separate cohorts of mice were scanned at 1 week (ex vivo imaging) and 4 weeks (MEMRI) of age to investigate early life alterations in the brain. Contrary to our expectations, differences in neuroanatomy were found in early post-natal life, preceding plaque deposition by as much as 11 weeks. Many of these differences remained at all imaging time points, suggesting that they were programmed early in life and were unaffected by the onset of pathology. Furthermore, rather than showing atrophy, many regions of the TgCRND8 brain grew at a faster rate compared to controls. These regions contained the greatest density of amyloid plaques and reactive astrocytes. Our findings suggest that pathological processes as well as an alteration in brain development influence the TgCRND8 neuroanatomy throughout the lifespan.
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Doença de Alzheimer/patologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Atrofia , Encéfalo/metabolismo , Modelos Animais de Doenças , Imageamento por Ressonância Magnética/métodos , Camundongos Transgênicos , Placa Amiloide/metabolismo , Placa Amiloide/patologiaRESUMO
The success of locomotion training with robotic exoskeletons requires identifying control algorithms that effectively retrain gait patterns in neurologically impaired individuals. Here we report how the two training paradigms, performance-based error-augmentation versus error-reduction, modified walking patterns in four chronic post-stroke individuals as a proof-of-concept for future locomotion training following stroke. Stroke subjects were instructed to match a prescribed walking pattern template derived from neurologically intact individuals. Target templates based on the spatial paths of lateral ankle malleolus positions during walking were created for each subject. Robotic forces were applied that either decreased (error-reduction) or increased (error-augmentation) the deviation between subjects' instantaneous malleolus positions and their target template. Subjects' performance was quantified by the amount of deviation between their actual and target malleolus paths. After the error-reduction training, S1 showed a malleolus path with reduced deviation from the target template by 16%. In contrast, S4 had a malleolus path further away from the template with increased deviation by 12%. After the error-augmentation training, S2 had a malleolus path greatly approximating the template with reduced deviation by 58% whereas S3 walked with higher steps than his baseline with increased deviation by 37%. These findings suggest that an error-reduction force field has minimal effects on modifying subject's gait patterns whereas an error-augmentation force field may promote a malleolus path either approximating or exceeding the target walking template. Future investigation will need to evaluate the long-term training effects on over-ground walking and functional capacity.
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BACKGROUND AND PURPOSE: A recent study identified a preprocedural P2Y12 reaction units value of <60 or >240 as a strong independent predictor of perioperative thromboembolic and hemorrhagic complications after treatment of cerebral aneurysms with the Pipeline Embolization Device. This study aimed to determine whether a last-recorded P2Y12 reaction units value of <60 or >240 predicts thromboembolic and hemorrhagic complications up to 6 months after treatment of cerebral aneurysms with the Pipeline Embolization Device in the same patient cohort. MATERIALS AND METHODS: We recorded patient and aneurysm characteristics, P2Y12 receptor antagonist administered, P2Y12 reaction units value with VerifyNow, procedural variables, and thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures at our institution during an 8-month period. Complications causing a permanent disabling neurologic deficit or death were considered major. Multivariate regression analysis was performed to identify independent predictors of thromboembolic and hemorrhagic complications. RESULTS: Forty-four patients underwent 48 Pipeline Embolization Device procedures at our institution during the study period. There were 11 thromboembolic and hemorrhagic complications up to 6 months after treatment in our cohort (22.9%), 5 of which were major (10.4%). A last-recorded P2Y12 reaction units value of <60 or >240 was the only independent predictor of all (P = .002) and major (P = .03) thromboembolic and hemorrhagic complications in our cohort. Most patients (71%) required, on average, 2 adjustments to the dose or type of P2Y12 receptor antagonist to remain within the 60-240 target P2Y12 reaction units range. CONCLUSIONS: In our cohort, a last-recorded P2Y12 reaction units value of <60 or >240 was the only independent predictor of all and major thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures.
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Hemorragia Cerebral/sangue , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Aneurisma Intracraniano/terapia , Embolia Intracraniana/sangue , Trombose Intracraniana/sangue , Receptores Purinérgicos P2Y12/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Feminino , Humanos , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/complicações , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Trombose Intracraniana/diagnóstico , Trombose Intracraniana/etiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
B lymphocyte stimulator (BLyS; also known as B cell activating factor (BAFF)) plays a key role in peripheral B cell tolerance. Mounting evidence indicates that B cell tolerance can be either broken or modulated by deliberately manipulating BLyS levels, and belimumab, a BLyS-neutralizing antibody, was recently approved for the treatment of systemic lupus erythematosus (SLE). Thus, intense investigation has focused on understanding how therapeutics targeting BLyS may work, and accumulating evidence suggests multiple points of action. BLyS signaling, in conjunction with B cell receptor (BCR) signaling, determines the size and quality of the mature primary B cell compartment. Moreover, BLyS family members play roles in antigen-experienced B cell selection and differentiation. Together, these findings have implications for the continued development of novel therapeutics that target BLyS.
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Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Diferenciação Celular , Aprovação de Drogas , Humanos , Tolerância Imunológica/imunologia , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Transdução de Sinais/imunologiaRESUMO
BACKGROUND: Mortality in intensive care unit (ICU) patients is affected by multiple variables. The possible impact of the mode of ventilation has not yet been clarified; therefore, a secondary analysis of the "epidemiology of sepsis in Germany" study was performed. The aims were (1) to describe the ventilation strategies currently applied in clinical practice, (2) to analyze the association of the different modes of ventilation with mortality and (3) to investigate whether the ratio between arterial partial pressure of oxygen and inspired fraction of oxygen (PF ratio) and/or other respiratory variables are associated with mortality in septic patients needing ventilatory support. METHODS: A total of 454 ICUs in 310 randomly selected hospitals participated in this national prospective observational 1-day point prevalence of sepsis study including 415 patients with severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine criteria. RESULTS: Of the 415 patients, 331 required ventilatory support. Pressure controlled ventilation (PCV) was the most frequently used ventilatory mode (70.6 %) followed by assisted ventilation (AV 21.7 %) and volume controlled ventilation (VCV 7.7 %). Hospital mortality did not differ significantly among patients ventilated with PCV (57 %), VCV (71 %) or AV (51 %, p=0.23). A PF ratio equal or less than 300 mmHg was found in 83.2 % of invasively ventilated patients (n=316). In AV patients there was a clear trend to a higher PF ratio (204±70 mmHg) than in controlled ventilated patients (PCV 179±74 mmHg, VCV 175±75 mmHg, p=0.0551). Multiple regression analysis identified the tidal volume to pressure ratio (tidal volume divided by peak inspiratory airway pressure, odds ratio OR=0.94, 95 % confidence interval 95% CI=0.89-0.99), acute renal failure (OR=2.15, 95% CI=1.01-4.55) and acute physiology and chronic health evaluation (APACHE) II score (OR=1.09, 95% CI=1.03-1.15) but not the PF ratio (univariate analysis OR=0.998, 95 % CI=0.995-1.001) as independent risk factors for in-hospital mortality. CONCLUSIONS: This representative survey revealed that severe sepsis or septic shock was frequently associated with acute lung injury. Different ventilatory modes did not affect mortality. The tidal volume to inspiratory pressure ratio but not the PF ratio was independently associated with mortality.
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Respiração Artificial/métodos , Sepse/terapia , APACHE , Idoso , Intervalos de Confiança , Feminino , Alemanha/epidemiologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Oximetria , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Sepse/epidemiologia , Sepse/mortalidade , Choque Séptico/terapia , Volume de Ventilação PulmonarRESUMO
BACKGROUND AND PURPOSE: The yield of DSA in patients with SAH and negative initial noninvasive neurovascular examinations (CTA or MRA) is not well-understood. This study aimed to determine the yield of DSA for the detection of causative vascular lesions in this clinical scenario. MATERIALS AND METHODS: We examined the yield of DSA for the detection of causative vascular lesions in a cohort of patients presenting to our institution with SAH and negative initial noninvasive neurovascular examinations during a 5-year period. Two experienced neuroradiologists independently evaluated the NCCT to determine the SAH pattern (diffuse, perimesencephalic, or peripheral sulcal) and the catheter angiograms to assess the presence of a causative vascular lesion. RESULTS: Fifty-five patients were included in the study, with a mean age of 58.2 years (median, 58 years; range, 25-88 years). Twenty-eight patients were men (50.9%), and 27 were women (49.1%). The initial noninvasive examination was a CTA in 47 patients (85.5%) and an MRA in 8 patients (14.5%). Thirty-three patients had diffuse SAH (60%); 11, perimesencephalic SAH (20%); and 11, peripheral sulcal SAH (20%). DSA demonstrated a causative vascular lesion in 6 patients (10.9%), 5 of whom had diffuse SAH (yield of 15.2%) and 1 of whom had peripheral sulcal SAH (yield of 9.1%). No causative vascular lesions were found in patients with perimesencephalic SAH. CONCLUSIONS: DSA is a valuable tool in the evaluation of patients with diffuse and peripheral sulcal SAH who have negative initial noninvasive neurovascular examinations, demonstrating a causative vascular lesion in 15.2% and 9.1% of patients, respectively.
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Angiografia Digital/métodos , Angiografia Cerebral/métodos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital/normas , Angiografia Cerebral/normas , Reações Falso-Negativas , Feminino , Humanos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/normasRESUMO
Propofol may protect neuronal cells from hypoxia re-oxygenation injury, possibly via an antioxidant actions under hypoxic conditions. This study investigated the molecular effects of propofol on hypoxia-induced cell damage using a neuronal cell line. Cultured human IMR-32 cells were exposed to propofol (30 µm) and biochemical and molecular approaches were used to assess cellular effects. Propofol significantly reduced hypoxia-mediated increases in lactate dehydrogenase, a marker of cell damage (mean (SD) for normoxia: 0.39 (0.07) a.u.; hypoxia: 0.78 (0.21) a.u.; hypoxia+propofol: 0.44 (0.17) a.u.; normoxia vs hypoxia, p<0.05; hypoxia vs hypoxia+propofol, p<0.05), reactive oxygen species and hydrogen peroxide. Propofol also diminished the morphological signs of cell damage. Increased amounts of catalase, which degrades hydrogen peroxide, were detected under hypoxic conditions. Propofol decreased the amount of catalase produced, but increased its enzymatic activity. Propofol protects neuronal cells from hypoxia re-oxygenation injury, possibly via a combined direct antioxidant effect along with induced cellular antioxidant mechanisms.
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Anestésicos Intravenosos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Propofol/farmacologia , Western Blotting , Catalase/análise , Catalase/metabolismo , Linhagem Celular , Humanos , Peróxido de Hidrogênio/metabolismo , L-Lactato Desidrogenase/metabolismo , Oxigênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The link between visual information and postural control was investigated based on a multi-degree-of-freedom model using the framework of the uncontrolled manifold (UCM) hypothesis. The hypothesis was that because visual information specifies the position of the body in space, it would couple preferentially into those combinations of degrees of freedom (DOFs) that move the body in space and not into combinations of DOFs that do not move the body in space. Subjects stood quietly in a virtual reality cave for 4-min trials with or without a 0.2, 2.0 Hz, or combined 0.2 and 2.0 Hz visual field perturbation that was below perceptual threshold. Motion analysis was used to compute six sagittal plane joint angles. Variance across time of the angular motion was partitioned into (1) variance associated with motion of the body and (2) variance reflecting the use of flexible joint combinations that keep the anterior-posterior positions of the head (HD(POS)) and center of mass (CM(POS)) invariant. UCM analysis was performed in the frequency domain in order to link the sensory perturbation to each variance component at different frequencies. As predicted, variance related to motion of the body was selectively increased at the 0.2-Hz drive frequency but not at other frequencies of sway for both CM(POS) and HD(POS). The dominant effect with the 2.0-Hz visual drive also was limited largely to variance related to motion of the body.
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Movimento/fisiologia , Equilíbrio Postural/fisiologia , Postura/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Articulações/inervação , Masculino , Análise Multivariada , Estimulação Luminosa , Amplitude de Movimento Articular , Adulto JovemRESUMO
Motor equivalence expresses the idea that movement components reorganize in the face of perturbations to preserve the value of important performance variables, such as the hand's position in reaching. A formal method is introduced to evaluate this concept quantitatively: changes in joint configuration due to unpredictable elbow perturbation lead to a smaller change in performance variables than expected given the magnitude of joint configuration change. This study investigated whether motor equivalence was present during the entire movement trajectory and how magnitude of motor equivalence was affected by constraints imposed by two different target types. Subjects pointed to spherical and cylindrical targets both with and without an elbow joint perturbation produced by a low- or high-stiffness elastic band. Subjects' view of their arm was blocked in the initial position, and the perturbation condition was randomized to avoid prediction of the perturbation or its magnitude. A modification of the uncontrolled manifold method variance analysis was used to investigate how changes in joint configuration on perturbed vs. nonperturbed trials (joint deviation vector) affected the hand's position or orientation. Evidence for motor equivalence induced by the perturbation was present from the reach onset and increased with the strength of the perturbation after 40% of the reach, becoming more prominent as the reach progressed. Hand orientation was stabilized more strongly by motor equivalent changes in joint configuration than was three-dimensional position regardless of the target condition. Results are consistent with a recent model of neural control that allows for flexible patterns of joint coordination while resisting joint configuration deviations in directions that affect salient performance variables. The observations also fit a general scheme of synergic control with referent configurations defined across different levels of the motor hierarchy.
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Articulação do Cotovelo/fisiologia , Movimento/fisiologia , Orientação/fisiologia , Desempenho Psicomotor/fisiologia , Adolescente , Fenômenos Biomecânicos/fisiologia , Previsões , Humanos , Masculino , Adulto JovemRESUMO
This study investigated pointing movements in 3D asking two questions: (1) Is goal-directed reaching accompanied by self-motion, a component of the joint velocity vector that leaves the hand's movement unaffected? (2) Are differences in the terminal joint configurations among different speeds of reaching motor equivalent (i.e., terminal joint configurations differ more in directions of joint space that do not produce different pointer-tip positions than in directions that do) or non-motor equivalent (i.e., terminal joint configurations differ equally or more in directions of joint space that lead to different pointer-tip positions than in directions that do not affect the pointer-tip position). Subjects reached from an identical starting joint configuration and pointer-tip location to targets at slow, moderate, and fast speeds. Ten degrees of freedom of joint motion of the arm were recorded. The relationship between changes in the joint configuration and the three-dimensional pointer-tip position was expressed by a standard kinematic model, and the range- and null subspaces were computed from the associated Jacobian matrix. (1) The joint velocity vector and (2) the difference vector between terminal joint configurations from pairs of speed conditions were projected into the two subspaces. The relative length of the two components was used to quantify the amount of self-motion and the presence of motor equivalence, respectively. Results revealed that reaches were accompanied by a significant amount of self-motion at all reaching speeds. Self-motion scaled with movement speed. In addition, the difference in the terminal joint configuration between pairs of different reaching speeds revealed motor equivalence. The results are consistent with a control system that takes advantage of motor redundancy, allowing for flexibility in the face of perturbations, here induced by different movement speeds.