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In this study, we investigated how the temporal properties of the preparation phase for upper limb movements are affected by the reaching direction and distance. Twelve right-handed participants performed three motor tasks: two types of reaching movements and one finger-lifting movement. The reaching movements were performed from the home position to 15 target locations (five directions and three distances) as quickly and precisely as possible under two conditions: pre-cueing the target to allocate the sufficient time for the motor-planning process before movement initiation, and no-cuing. The finger lifting movement was performed by lifting the index finger (from the home position) upward in the air as quickly as possible. The reaction time (RT), movement time (MT), and kinematics of the index finger were obtained for each condition. In addition, differential RTs (DRT) were calculated by subtracting the RT for no-cue lifting from that for no-cue reaching, thereby implicitly representing the time required for the motor-planning process for reaching movements. The results indicated the anisotropy of the DRTs being larger in the forward and left-forward directions than that in the right-forward direction, and larger in the forward direction than that in the right direction for the middle distance. It is suggested that the temporal costs of the motor-planning process depend on the movement direction and distance. In the kinematic analysis, the MTs showed the anisotropy being the largest in the left-forward among all directions. Meanwhile, the time from peak velocity to terminate the movement (TFPV) was significantly longer in the left-forward direction when no-cueing the target than when pre-cueing. These results suggest that reaching movement is refined during the online-control process to accomplish the intended performance if a reaching movement under the no-cue condition is initiated before building sufficient motor planning, especially in the direction requiring large temporal costs. It is likely that humans achieve their intended movements by allocating the temporal costs required before and after movement initiation according to the difficulty of motor control which varies with the direction and distance.
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Desempeño Psicomotor , Tiempo de Reacción , Humanos , Fenómenos Biomecánicos , Desempeño Psicomotor/fisiología , Masculino , Adulto Joven , Femenino , Adulto , Brazo/fisiología , Señales (Psicología) , Orientación , Movimiento/fisiología , Dedos/fisiologíaRESUMEN
BACKGROUND: Linguistic impairment following cerebellar lesions is characterized by a marked cerebellocerebral diaschisis with decreased perfusion in the left cerebral hemisphere. CASE: We report on a 60-year-old right-handed French chef who presented with linguistic deficits following a right cerebellar infarction. Neurolinguistic examinations in the acute phase showed impaired graphomotor planning, especially for kanji (Japanese morphograms). Despite the absence of any structural damage to the supratentorial brain regions, a quantitative 123I-IMP SPECT study revealed a relative hypoperfusion, mainly around the left posterior middle temporal gyrus, considered to be a crossed cerebellar-cerebral diaschisis. We performed functional near-infrared spectroscopy (fNIRS) and observed that a picture card task could increase blood perfusion in the affected area. This task was as follows: once he saw a picture card depicting a dish, the patient had to list the ingredients that make up the dish. For example, he had to name vegetables, meat, and spices upon seeing a "curry" picture card. We added this task to his daily speech-hearing therapy regimen. In the chronic phase, we confirmed symptom amelioration in linguistic performance-paralleled reduction in the level of hypoperfusion on SPECT study. Discussion. This case is the first report of an fNIRS approach used to evaluate evidence-based prospective speech-hearing tasks by observing blood flow to the hypoperfused area of the cerebral cortex surface.
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Radiometric calibration utilizing the Moon as a reference source is termed as lunar calibration. It is a useful method for evaluating the performance of optical sensors onboard satellites orbiting the Earth. Lunar calibration provides sufficient radiometric calibration opportunities without requiring any special equipment, and is suitable for nano/microsatellites. This study applies lunar calibration to a multispectral sensor, Ocean Observation Camera (OOC), on board a microsatellite named Rapid International Scientific Experiment Satellite. Simulating the brightness of the Moon based on the RObotic Lunar Observatory and SELENE/Spectrum Profiler models, sensitivity degradation was proven to be negligible in any of the four spectral bands of the OOC with the sensor temperature correction. A bluing trend in the OOC's sensor sensitivity was revealed, indicating a shorter observation wavelength shows larger irradiance. Comparing the top-of-atmosphere reflectance of Railroad Valley Playa with the Radiometric Calibration Network dataset revealed that the derived calibration parameter from the lunar calibration was valid for correcting the bluing trend in the visible range. Although the lunar and vicarious calibration parameters for the infrared band were unexpectedly inconsistent, lunar calibration could potentially contribute toward estimating the contaminated background radiance in the Earth observation images.
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Liposomal fasudil as a treatment for cerebral ischemia/reperfusion (I/R) injury has been demonstrated to be effective in animal models due to the high accumulation of liposomes in damaged brain tissue. However, it is still unclear what effect drug release rate has on the treatment of I/R injury, where pathology progresses dramatically in a short time. In the present study, we assessed four formulations of liposomal fasudil. The results of an in vitro drug release assay showed that the release properties of fasudil were changed by varying the lipid composition and internal phase of the liposomes. Based on these results, differences in the transition of fasudil plasma concentration were monitored after the administration of each type of liposomal fasudil in normal rats. A pharmacokinetic study showed that higher levels of drug retention in liposomal fasudil resulted in higher fasudil plasma concentration. Finally, treatment of I/R injury model rats with liposomal fasudil revealed that a mid-level release rate of fasudil from liposomes resulted in the greatest therapeutic effect among the formulations. In conclusion, these results demonstrate that an optimized drug release rate from liposomes enhances the therapeutic effect of fasudil for the treatment of cerebral I/R injury.
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Liposomas/química , Daño por Reperfusión/tratamiento farmacológico , 1,2-Dipalmitoilfosfatidilcolina/química , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/sangre , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacocinética , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Sulfato de Amonio/química , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Ácido Cítrico/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composición de Medicamentos , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Liposomas/farmacocinética , Masculino , Fosfatidilcolinas/química , Compuestos de Amonio Cuaternario/química , Ratas Wistar , Daño por Reperfusión/patología , Resultado del TratamientoRESUMEN
The authors wish to make the following corrections to this paper [...].
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Radiometric cross-calibration between the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and the Terra-Moderate Resolution Imaging Spectroradiometer (MODIS) has been partially used to derive the ASTER radiometric calibration coefficient (RCC) curve as a function of date on visible to near-infrared bands. However, cross-calibration is not sufficiently accurate, since the effects of the differences in the sensor's spectral and spatial responses are not fully mitigated. The present study attempts to evaluate radiometric consistency across two sensors using an improved cross-calibration algorithm to address the spectral and spatial effects and derive cross-calibration-based RCCs, which increases the ASTER calibration accuracy. Overall, radiances measured with ASTER bands 1 and 2 are on averages 3.9% and 3.6% greater than the ones measured on the same scene with their MODIS counterparts and ASTER band 3N (nadir) is 0.6% smaller than its MODIS counterpart in current radiance/reflectance products. The percentage root mean squared errors (%RMSEs) between the radiances of two sensors are 3.7, 4.2, and 2.3 for ASTER band 1, 2, and 3N, respectively, which are slightly greater or smaller than the required ASTER radiometric calibration accuracy (4%). The uncertainty of the cross-calibration is analyzed by elaborating the error budget table to evaluate the International System of Units (SI)-traceability of the results. The use of the derived RCCs will allow further reduction of errors in ASTER radiometric calibration and subsequently improve interoperability across sensors for synergistic applications.
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BACKGROUND: Genetic predisposition to life-threatening cardiac arrhythmias such as congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype-phenotype correlations associated with calmodulin mutations. METHODS AND RESULTS: We used conventional and next-generation sequencing approaches, including exome analysis, in genotype-negative LQTS probands. We identified 5 novel de novo missense mutations in CALM2 in 3 subjects with LQTS (p.N98S, p.N98I, p.D134H) and 2 subjects with clinical features of both LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or cardiac arrest) ranged from 1 to 9 years. Three of 5 probands had cardiac arrest and 1 of these subjects did not survive. The clinical severity among subjects in this series was generally less than that originally reported for CALM1 and CALM2 associated with recurrent cardiac arrest during infancy. Four of 5 probands responded to ß-blocker therapy, whereas 1 subject with mutation p.Q136P died suddenly during exertion despite this treatment. Mutations affect conserved residues located within Ca(2+)-binding loops III (p.N98S, p.N98I) or IV (p.D132E, p.D134H, p.Q136P) and caused reduced Ca(2+)-binding affinity. CONCLUSIONS: CALM2 mutations can be associated with LQTS and with overlapping features of LQTS and CPVT.
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Calmodulina/genética , Síndrome de QT Prolongado/genética , Taquicardia Ventricular/genética , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Edad de Inicio , Secuencia de Aminoácidos , Calcio/química , Calcio/metabolismo , Calmodulina/metabolismo , Niño , Preescolar , Electrocardiografía , Femenino , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Síndrome de QT Prolongado/tratamiento farmacológico , Síndrome de QT Prolongado/patología , Masculino , Datos de Secuencia Molecular , Mutación Missense , Linaje , Unión Proteica , Análisis de Secuencia de ADN , Taquicardia Ventricular/tratamiento farmacológico , Taquicardia Ventricular/patologíaRESUMEN
BACKGROUND: Sick sinus syndrome (SSS) is a common arrhythmia often associated with aging or organic heart diseases but may also occur in a familial form with a variable mode of inheritance. Despite the identification of causative genes, including cardiac Na channel (SCN5A), the pathogenesis and molecular epidemiology of familial SSS remain undetermined primarily because of its rarity. METHODS AND RESULTS: We genetically screened 48 members of 15 SSS families for mutations in several candidate genes and determined the functional properties of mutant Na channels using whole-cell patch clamping. We identified 6 SCN5A mutations including a compound heterozygous mutation. Heterologously expressed mutant Na channels showed loss-of-function properties of reduced or no Na current density in conjunction with gating modulations. Among 19 family members with SCN5A mutations, QT prolongation and Brugada syndrome were associated in 4 and 2 individuals, respectively. Age of onset in probands carrying SCN5A mutations was significantly less (mean±SE, 12.4±4.6 years; n=5) than in SCN5A-negative probands (47.0±4.6 years; n=10; P<0.001) or nonfamilial SSS (74.3±0.4 years; n=538; P<0.001). Meta-analysis of SSS probands carrying SCN5A mutations (n=29) indicated profound male predominance (79.3%) resembling Brugada syndrome but with a considerably earlier age of onset (20.9±3.4 years). CONCLUSIONS: The notable pathophysiological overlap between familial SSS and Na channelopathy indicates that familial SSS with SCN5A mutations may represent a subset of cardiac Na channelopathy with strong male predominance and early clinical manifestations.
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Canalopatías/genética , Predisposición Genética a la Enfermedad/epidemiología , Canal de Sodio Activado por Voltaje NAV1.5/genética , Síndrome del Seno Enfermo/genética , Adolescente , Distribución por Edad , Edad de Inicio , Canalopatías/diagnóstico , Canalopatías/epidemiología , Preescolar , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas/métodos , Humanos , Incidencia , Japón , Masculino , Linaje , Enfermedades Raras , Distribución por Sexo , Síndrome del Seno Enfermo/diagnóstico , Síndrome del Seno Enfermo/epidemiología , Adulto JovenRESUMEN
We investigated drug lifecycle management (LCM) activities in the Japanese market by examining new and updated approvals by the Pharmaceuticals and Medical Devices Agency (PMDA) between 2001 and 2010. PMDA gave a total of 726 approvals, of which 263 and 463 were new and updated approvals, respectively. Approvals for new indication comprised of more than 60% of updated approvals regardless of chemical or biological entities, therapeutic area and the company nationality. The case study on anti-rheumatoid arthritis biologics showed that the addition of new indications accelerated their sales exponentially. Thus, the development of new indications is an effective LCM approach for creation of new values of existing drugs.
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Aprobación de Drogas/estadística & datos numéricos , Diseño de Fármacos , Industria Farmacéutica/tendencias , Artritis Reumatoide/tratamiento farmacológico , Humanos , Factores Inmunológicos/uso terapéutico , JapónRESUMEN
BACKGROUND: The most common type of pollinosis in Japan is Japanese cedar pollinosis (JCP). While forest walking is a common form of recreation for Japanese people, it has been unclear whether forest walkers with JCP still choose to visit forested areas during the pollen season or whether they avoid those areas, and as such, the aim of this study was to investigate this question. METHODS: The study participants were all healthy men and women volunteers aged 20 years or over who visited the Tokyo University Forest in Chiba during 4 different days. The survey was conducted using self-administered questionnaires. RESULTS: The number of available responses was 498. Of these, 112 participants who experienced JCP were included in the analysis. Seventy-three participants (65.2%) responded that they visit forests even during the pollen season. The association between forest walking choices during the pollen season and self-rated levels of pollinosis symptoms was not statistically significant (Cramer's V = 0.13, p = 0.47). As many as 60% of the participants who reported serious symptom levels responded that they visit forested areas even during the pollen season. CONCLUSIONS: These results revealed that two thirds of forest walkers who had experienced JCP visited forests even during the pollen season. This indicates the further need for public service announcements informing people with JCP that the risk of pollen exposure and subsequent JCP reaction is increased by visiting forested areas during the pollen season.
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Cryptomeria/efectos adversos , Polen/efectos adversos , Rinitis Alérgica Estacional/epidemiología , Asunción de Riesgos , Alérgenos/efectos adversos , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Recreación , Rinitis Alérgica Estacional/etiología , Rinitis Alérgica Estacional/psicología , Estaciones del Año , Encuestas y Cuestionarios , ÁrbolesRESUMEN
Alzheimer's disease (AD) is a neurological disorder that has a considerable impact on the health of the elderly. Although oxidative stress has been implicated in the early stage of this disease, its detailed pathogenesis and therapeutic targets remain unknown. The diagnosis, particularly at the early stage, is important. In the present study, the levels of potential biomarkers such as total hydroxyoctadecadienoic acid (tHODE) and oxidatively modified peroxiredoxin (oxPrx)-2 and oxPrx-6 in plasma and/or erythrocytes were determined by a GC-MS apparatus and by two-dimensional electrophoresis, respectively. It was found that these levels in AD patients were significantly higher than those in the healthy controls. Furthermore, the tHODE levels increased with increasing clinical dementia ratings. Interestingly, vascular dementia patients could be distinguished by the correlation between plasma and erythrocyte tHODE levels or by that of tHODE with oxPrx in erythrocytes. These data further support that oxidative stress is indeed involved in AD and that the correlative measures of tHODE and oxPrx are potential biomarkers for its diagnosis.
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Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Demencia Vascular/sangre , Demencia Vascular/diagnóstico , Ácidos Grasos Insaturados/sangre , Peroxirredoxinas/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A 12-year-old girl who had undergone cardiac surgery for ventricular septal defect (VSD), atrial septal defect (ASD), and patent ductus arteriosus (PDA) in infancy was referred to our institution for fatigue and excessive sweating. Transthoracic and transesophageal echocardiographic studies revealed tunnel-type subaortic stenosis with aortic valvular stenosis, for which she underwent aortic valve replacement and myomectomy of left ventricular outflow tract. Progression of subaortic stenosis should be considered in patients with only mild aortic valve stenosis after previous cardiovascular surgery. Echocardiography contributed significantly to making the diagnosis and therapeutic decision in our patient.
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Synergistic applications of multi-resolution satellite data have been of a great interest among user communities for the development of an improved and more effective operational monitoring system of natural resources, including vegetation and soil. In this study, we conducted an inter-comparison of two remote sensing products, namely, visible/near-infrared surface reflectances and spectral vegetation indices (VIs), from the high resolution Advanced Thermal Emission and Reflection Radiometer (ASTER) (15 m) and lower resolution Moderate Resolution Imaging Spectroradiometer (MODIS) (250 m - 500 m) sensors onboard the Terra platform. Our analysis was aimed at understanding the degree of radiometric compatibility between the two sensors' products due to sensor spectral bandpasses and product generation algorithms. Multiple pairs of ASTER and MODIS standard surface reflectance products were obtained at randomly-selected, globally-distributed locations, from which two types of VIs were computed: the normalized difference vegetation index and the enhanced vegetation indices with and without a blue band. Our results showed that these surface reflectance products and the derived VIs compared well between the two sensors at a global scale, but subject to systematic differences, of which magnitudes varied among scene pairs. An independent assessment of the accuracy of ASTER and MODIS standard products, in which "in-house" surface reflectances were obtained using in situ Aeronet atmospheric data for comparison, suggested that the performance of the ASTER atmospheric correction algorithm may be variable, reducing overall quality of its standard reflectance product. Atmospheric aerosols, which were not corrected for in the ASTER algorithm, were found not to impact the quality of the derived reflectances. Further investigation is needed to identify the sources of inconsistent atmospheric correction results associated with the ASTER algorithm, including additional quality assessments of the ASTER and MODIS products with other atmospheric radiative transfer codes.
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We examined the suppressive effect of HIV-1 RNA gene cleavage on HIV-1 expression, using the catalytic RNA subunit RNase P and the 3'-half tRNA(Try) [external guide sequence (EGS)] in cultured cells. HIV-1 expression was inhibited by the tRNA(met)-EGS-U5 and U6-EGS-U5 from the tRNA(met) and U6 promoters, respectively. There was no difference in the inhibitory effects on HIV-1 expression between the tRNA(met) and U6 promoters.