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Visual errors induced by movement drive implicit corrections of that movement. When similar errors are experienced consecutively, does sensitivity to the error remain consistent each time? This study aimed to investigate the modulation of implicit error sensitivity through continuous exposure to the same errors. In the reaching task using visual error-clamp feedback, participants were presented with the same error in direction and magnitude for four consecutive trials. We found that implicit error sensitivity decreased after exposure to the second error. These results indicate that when visual errors occur consecutively, the sensorimotor system exhibits different responses, even for identical errors. The continuity of errors may be a factor that modulates error sensitivity.
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The emergence and dissemination of carbapenem-resistant species of Acinetobacter and Pseudomonas have become a serious health concern. Routine antimicrobial disk susceptibility tests in clinical laboratories cannot distinguish between isolates that are highly carbapenem-resistant and those that are moderately carbapenem-resistant. The present study describes antimicrobial susceptibility tests using disks containing high doses (1000 µg) of meropenem. The diameters of inhibition zones were significantly negatively correlated with the MICs of Pseudomonas and Acinetobacter species for meropenem (R2: 0.93 and 0.91, respectively) and imipenem (R2: 0.75 and 0.84, respectively). Double disk synergy tests using clavulanic acid or sodium mercaptoacetate can detect ESBL or MBL producers. Susceptibility tests using disks containing high doses of meropenem can easily detect highly carbapenem-resistant isolates in a quantitative manner. These disks may be useful in bacteriological laboratories because of their technical ease, stability, and relatively low cost.
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Acinetobacter , Antiinfecciosos , Meropenem/farmacología , Pseudomonas , Tienamicinas/farmacología , Carbapenémicos/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , beta-LactamasasRESUMEN
Simultaneous measurement of X-ray ptychography and fluorescence microscopy allows high-resolution and high-sensitivity observations of the microstructure and trace-element distribution of a sample. In this paper, we propose a method for improving scanning fluorescence X-ray microscopy (SFXM) images, in which the SFXM image is deconvolved via virtual single-pixel imaging using different probe images for each scanning point obtained by X-ray ptychographic reconstruction. Numerical simulations confirmed that this method can increase the spatial resolution while suppressing artifacts caused by probe imprecision, e.g., probe position errors and wavefront changes. The method also worked well in synchrotron radiation experiments to increase the spatial resolution and was applied to the observation of S element maps of ZnS particles.
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Introduction: Various stressors have been identified in patients in the intensive care unit (ICU), including postoperative pain, ventilatory management, and nursing care. However, sedated patients are less responsive, and nurses have difficulty capturing their stressors. Objective: To investigate patient stress caused by nursing care performed in the ICU on sedated patients based on changes in physiological indices. Methods: We observed nursing care performed on patients with postoperative esophageal cancer under sedation in the ICU. This included endotracheal suctioning and turning, the time required for the care, and the patients' behavioral responses. Information on arousal levels, autonomic nervous system indices, and vital signs were also obtained. The changes in indicators before and after care were then compared and analyzed. Results: There were 14 patients in the study. The mean age of the patients was 68 years. Ninety-nine scenes of nursing care were observed, and in six of these, additional bolus sedation was administered because of the patient's significant body movements. In endotracheal suctioning, no significant changes were observed in all indicators. In turning, vital signs changed significantly, and when both were continued, all indicators changed significantly. Conclusion: Our study found that different types and combinations of nursing care may cause different stresses to the patients. Moreover, the autonomic nervous system indices may be more likely to react to stresses in a variety of nursing care, while arousal levels may be more likely to react to burdensome stresses. If the characteristics of these physiological indicators can be understood and effectively utilized during care, it may be possible to better identify and reduce patient stress during sedation management.
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Ptychographic coherent diffraction imaging (PCDI) is a synchrotron X-ray microscopy technique that provides high spatial resolution and a wide field of view. To improve the performance of PCDI, the performance of the synchrotron radiation source and imaging detector should be improved. In this study, ptychographic diffraction pattern measurements using the CITIUS high-speed X-ray image detector and the corresponding image reconstruction are reported. X-rays with an energy of 6.5â keV were focused by total reflection focusing mirrors, and a flux of â¼2.6 × 1010â photonsâ s-1 was obtained at the sample plane. Diffraction intensity data were collected at up to â¼250â Mcounts s-1 pixel-1 without saturation of the detector. Measurements of tantalum test charts and silica particles and the reconstruction of phase images were performed. A resolution of â¼10â nm and a phase sensitivity of â¼0.01â rad were obtained. The CITIUS detector can be applied to the PCDI observation of various samples using low-emittance synchrotron radiation sources and to the stability evaluation of light sources.
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Our movements and movement outcomes are disturbed by environmental changes, leading to errors. During ongoing environmental changes, people should correct their movement using sensory feedback. However, when the changes are momentary, corrections based on sensory feedback are undesirable. Previous studies have suggested that implicit motor adaptation takes place despite the realization that the presented visual feedback should be ignored. Although these studies created experimental situations in which participants had to continuously ignore the presented visual feedback, in daily lives, people intermittently encounter opportunities to ignore sensory feedback. In this study, by intermittently presenting visual error clamp feedback, always offset from a target by 16° counterclockwise, regardless of the actual movement in a reaching experiment, we provided intermittent opportunities to ignore the visual feedback. We found that in the trials conducted immediately after presenting the visual error clamp feedback, reaching movements shifted in the direction opposite to the feedback, which is a hallmark of implicit motor adaptation. Moreover, the magnitude of the shift was significantly correlated with the rate of motor adaptation to gradual changes in the environment. Therefore, the results suggest that people unintentionally react to momentary environmental changes, which should be ignored. In addition, the sensitivity to momentary changes is greater in people who can quickly adapt to gradual environmental changes.
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Aprendizaje , Desempeño Psicomotor , Humanos , Movimiento , Adaptación Fisiológica , Retroalimentación , Retroalimentación Sensorial , Percepción VisualRESUMEN
Previous studies have demonstrated the effects of motor variability on motor adaptation. However, their findings have been inconsistent, suggesting that various factors affect the relationship between motor variability and adaptation. This study focused on the size of errors driving motor adaptation as one of the factors and examined the relationship between different error sizes. Thirty-one healthy young adults participated in a visuomotor task in which they made fast-reaching movements toward a target. Motor variability was measured in the baseline phase when a veridical feedback cursor was presented. In the adaptation phase, the feedback cursor was sometimes not reflected in the hand position and deviated from the target by 0°, 3°, 6°, or 12° counterclockwise or clockwise (i.e., error-clamp feedback). Movements during trials following trials with error-clamp feedback were measured to quantify implicit adaptation. Implicit adaptation was driven by errors presented through error-clamp feedback. Moreover, motor variability significantly correlated with implicit adaptation driven by a 12° error. The results suggested that motor variability accelerates implicit adaptation when a larger error occurs. As such a trend was not observed when smaller errors occurred, the relationship between motor variability and motor adaptation might have been affected by the error size driving implicit adaptation.
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Lithium-rich disordered rocksalt-type cathode materials are promising for high-capacity and high-power lithium-ion batteries. Many of them are synthesized by mechanical milling and may have heterogeneous structures and chemical states at the nanoscale. In this study, we performed X-ray spectroscopic ptychography measurements of Li-rich disordered rocksalt-type oxide particles synthesized by mechanical milling before and after delithiation reaction at the vanadium K absorption edge, and visualized their structures and chemical state with a spatial resolution of â¼100 nm. We classified multiple domains with different chemical states via clustering analysis. A comparison of the domain distribution trends of the particles before and after the delithiation reaction revealed the presence of domains, suggesting that the delithiation reaction was suppressed.
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Thymic stromal lymphopoietin (TSLP), positioned at the top of the inflammatory cascade, is a key regulator that enhances allergic inflammatory responses by activating T helper type 2 cells, Group 2 innate lymphoid cells (ILC2), and myeloid dendritic cells (mDCs) via the TSLP receptor (TSLPR). We evaluated the inhibitory effects of ASP7266, a novel recombinant fully human IgG1 monoclonal antibody against TSLPR, on TSLP signaling and inflammation. The inhibitory effects of ASP7266 and the control antibody tezepelumab on TSLP and TSLPR interactions were investigated using a proliferation assay with TSLP stimulation and a chemokine production assay. The pharmacological effects of ASP7266 were investigated by examining differentiation of naive CD4+ T cells, ILC2 cytokine production, and ascaris extract-induced skin allergic reaction in cynomolgus monkeys. ASP7266 potently inhibited TSLP-induced cell proliferation and C-C motif chemokine ligand 17 production. Furthermore, ASP7266 inhibited TSLP-stimulated mDC-mediated naive CD4+ T-cell differentiation and interleukin 5 production by lineage-negative peripheral blood mononuclear cells, which can be considered ILC2 in vitro. In sensitized monkeys, ASP7266 completely suppressed ascaris extract-induced allergic skin reactions. Based on these results, ASP7266, a novel human therapeutic antibody against TSLPR, is a potential therapy for patients with allergic diseases. SIGNIFICANCE STATEMENT: TSLP, positioned at the top of the inflammatory cascade, plays a key role in various allergic diseases, including asthma, chronic rhinosinusitis with nasal polyposis, and atopic dermatitis. Here we show that the anti-TSLPR antibody ASP7266 exhibited excellent pharmacological activity in preclinical studies. Therefore, ASP7266 has the potential to be a promising treatment option for patients with allergic disorders.
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Anticuerpos Monoclonales/inmunología , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Receptores de Citocinas/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Línea Celular , Proliferación Celular , Células Cultivadas , Citocinas/metabolismo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Humanos , Macaca fascicularis , Masculino , Ratones , Receptores de Citocinas/antagonistas & inhibidores , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
Ptychographic coherent diffraction imaging (CDI) allows the visualization of both the structure and chemical state of materials on the nanoscale, and has been developed for use in the soft and hard X-ray regions. In this study, a ptychographic CDI system with pinhole or Fresnel zone-plate optics for use in the tender X-ray region (2-5â keV) was developed on beamline BL27SU at SPring-8, in which high-precision pinholes optimized for the tender energy range were used to obtain diffraction intensity patterns with a low background, and a temperature stabilization system was developed to reduce the drift of the sample position. A ptychography measurement of a 200â nm thick tantalum test chart was performed at an incident X-ray energy of 2.500â keV, and the phase image of the test chart was successfully reconstructed with approximately 50â nm resolution. As an application to practical materials, a sulfur polymer material was measured in the range of 2.465 to 2.500â keV including the sulfur K absorption edge, and the phase and absorption images were successfully reconstructed and the nanoscale absorption/phase spectra were derived from images at multiple energies. In 3â GeV synchrotron radiation facilities with a low-emittance storage ring, the use of the present system will allow the visualization on the nanoscale of the chemical states of various light elements that play important roles in materials science, biology and environmental science.
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A heterogeneous phase/structure distribution in the bulk of spinel lithium nickel manganese oxides (LNMOs) is the key to maximizing the performance and stability of the cathode materials of lithium-ion batteries. Herein, we report the use of two-dimensional ptychographic X-ray absorption fine structure (XAFS) to visualize the density and valence maps of manganese and nickel in as-prepared LNMO particles and unsupervised learning to classify the three-phase group in terms of different elemental compositions and chemical states. The described approach may increase the supply of information for nanoscale characterization and promote the design of suitable structural domains to maximize the performance and stability of batteries.
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Coherent diffraction imaging (CDI) is a powerful method for visualizing the structure of an object with a high spatial resolution that exceeds the performance limits of the lens. Single-frame CDI in the X-ray region has potential use for probing dynamic phenomena with a high spatiotemporal resolution. Here, we experimentally demonstrate a general method for single-frame X-ray CDI using a triangular aperture and a Fresnel zone plate. Using 5 keV synchrotron radiation X-rays, we reconstructed the object image of the locally illuminated area with a spatial resolution of higher than 50 nm and an exposure time of more than 0.1 s without prior information about the sample. After a 10 s exposure, a resolution of 17 nm was achieved. The present method opens new frontiers in the study of dynamics at the nanoscale by using next-generation synchrotron radiation X-rays/free-electron lasers as light sources.
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Studies have shown that pneumococcal vaccination reduces the incidence of Streptococcus pneumoniae infections but does not change the prevalence of S. pneumoniae nasopharyngeal colonization. To comprehensively and longitudinally assess the epidemiology of S. pneumoniae after the introduction of pneumococcal vaccination, we monitored the prevalence and antimicrobial susceptibility of S. pneumoniae, irrespective of its serotypes or pathogenicity, by analyzing specimens collected from a large number of patients at Jikei University Hospitals from 2009 to 2017. A total of 5763 S. pneumoniae isolates were identified out of 375,435 specimens from various sources of patients in different age groups. The prevalence of S. pneumoniae isolated only from patients <5 years old was significantly reduced with the widespread use of pneumococcal vaccines, although this reduction differed by areas where patients resided. The incidence of pneumococcal infections, including bacteremia and otitis media, clearly decreased among patients <5 years old after the introduction of pneumococcal vaccination, while the prevalence of S. pneumoniae isolated from blood specimens of patients 15-64 years old increased, suggesting the involvement of non-vaccine serotypes in the incidence of invasive pneumococcal infections. The antimicrobial susceptibility of S. pneumoniae improved after the introduction of pneumococcal vaccination. Our results show that pneumococcal vaccination has a suppressive effect on the prevalence of S. pneumoniae and the incidence of pneumococcal infections, at least for children <5 years old, in association with an improvement in the antimicrobial susceptibility of S. pneumoniae. However, further measures will be needed to control invasive pneumococcal infections caused by non-vaccine serotypes.
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Antibacterianos/farmacología , Programas de Inmunización , Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/efectos de los fármacos , Adolescente , Adulto , Factores de Edad , Anciano , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Bacteriemia/microbiología , Niño , Preescolar , Femenino , Hospitales Universitarios/estadística & datos numéricos , Humanos , Incidencia , Japón/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Otitis Media/tratamiento farmacológico , Otitis Media/epidemiología , Otitis Media/microbiología , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/prevención & control , Prevalencia , Evaluación de Programas y Proyectos de Salud , Factores de Riesgo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Resultado del Tratamiento , Adulto JovenRESUMEN
During joint action, two or more persons depend on each other to accomplish a goal. This mutual recursion, or circular dependency, is one of the characteristics of cooperation. To evaluate the neural substrates of cooperation, we conducted a hyperscanning functional MRI study in which 19 dyads performed a joint force-production task. The goal of the task was to match their average grip forces to the target value (20% of their maximum grip forces) through visual feedback over a 30-s period; the task required taking into account other-produced force to regulate the self-generated one in real time, which represented cooperation. Time-series data of the dyad's exerted grip forces were recorded, and the noise contribution ratio (NCR), a measure of influence from the partner, was computed using a multivariate autoregressive model to identify the degree to which each participant's grip force was explained by that of their partner's, i.e., the degree of cooperation. Compared with the single force-production task, the joint task enhanced the NCR and activated the mentalizing system, including the medial prefrontal cortex, precuneus, and bilateral posterior subdivision of the temporoparietal junction (TPJ). In addition, specific activation of the anterior subdivision of the right TPJ significantly and positively correlated with the NCR across participants during the joint task. The effective connectivity of the anterior to posterior TPJ was upregulated when participants coordinated their grip forces. Finally, the joint task enhanced cross-brain functional connectivity of the right anterior TPJ, indicating shared attention toward the temporal patterns of the motor output of the partner. Since the posterior TPJ is part of the mentalizing system for tracking the intention of perceived agents, our findings indicate that cooperation, i.e., the degree of adjustment of individual motor output depending on that of the partner, is mediated by the interconnected subdivisions of the right TPJ.
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Encéfalo/fisiología , Conducta Cooperativa , Desempeño Psicomotor/fisiología , Adulto , Femenino , Fuerza de la Mano/fisiología , Humanos , Masculino , Vías Nerviosas/fisiología , Adulto JovenRESUMEN
It has been reported that the elderly use co-contraction of the tibialis anterior (TA) and plantarflexor muscles for longer duration during quiet standing than the young. However, the particular role of ankle muscle co-contractions in the elderly during quiet standing remains unclear. Therefore, the objective of this study was to investigate the association between ankle muscle co-contractions and postural steadiness during standing in the elderly. Twenty-seven young (27.2±4.5yrs) and twenty-three elderly (66.2±5.0yrs) subjects were asked to stand quietly on a force plate for five trials. The center of pressure (COP) trajectory and its velocity (COPv) as well as the center of mass (COM) trajectory and its velocity (COMv) and acceleration (ACC) were calculated using the force plate outputs. Electromyograms were obtained from the right TA, soleus (SOL), and medial gastrocnemius (MG) muscles. Periods of TA activity (TAon) and inactivity (TAoff) were determined using an EMG threshold based on TA resting level. Our results indicate that, in the elderly, the COPv, COMv, and ACC variability were significantly larger during TAon periods compared to TAoff periods. However, in the young, no significant association between respective variability and TA activity was found. We conclude that ankle muscle co-contractions in the elderly are not associated with an increase, but a decrease in postural steadiness. Future studies are needed to clarify the causal relationship between (1) ankle muscle co-contractions and (2) joint stiffness and multi-segmental actions during standing as well as their changes with aging.
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Tobillo/fisiología , Actividad Motora/fisiología , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Equilibrio Postural/fisiología , Postura/fisiología , Descanso/fisiología , Anciano , Electromiografía , Femenino , Voluntarios Sanos , Humanos , Masculino , Presión , Factores de TiempoRESUMEN
Variability in motor performance results from the interplay of error correction and neuromotor noise. This study examined whether visual amplification of error, previously shown to improve performance, affects not only error correction, but also neuromotor noise, typically regarded as inaccessible to intervention. Seven groups of healthy individuals, with six participants in each group, practiced a virtual throwing task for three days until reaching a performance plateau. Over three more days of practice, six of the groups received different magnitudes of visual error amplification; three of these groups also had noise added. An additional control group was not subjected to any manipulations for all six practice days. The results showed that the control group did not improve further after the first three practice days, but the error amplification groups continued to decrease their error under the manipulations. Analysis of the temporal structure of participants' corrective actions based on stochastic learning models revealed that these performance gains were attained by reducing neuromotor noise and, to a considerably lesser degree, by increasing the size of corrective actions. Based on these results, error amplification presents a promising intervention to improve motor function by decreasing neuromotor noise after performance has reached an asymptote. These results are relevant for patients with neurological disorders and the elderly. More fundamentally, these results suggest that neuromotor noise may be accessible to practice interventions.
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Modelos Neurológicos , Destreza Motora/fisiología , Análisis y Desempeño de Tareas , Adulto , Algoritmos , Biología Computacional , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies.
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Enfermedades Renales/fisiopatología , Proteínas de la Membrana/orina , Podocitos/fisiología , Animales , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/fisiopatología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/orina , Biomarcadores/orina , Creatinina/orina , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Doxorrubicina/farmacología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/orina , Masculino , Ratones , Ratones Endogámicos BALB C , Puromicina Aminonucleósido/farmacología , Ratas , Ratas WistarRESUMEN
Immunological tests based on antigen-antibody reactions are widely used to detect and quantify tumor markers, hormones, infections, and other targets. The detection sensitivity and specificity of these tests have recently improved markedly as a result of technical advances in antibody preparation and optical meas- urement. Despite these technical innovations however, it remains impossible to completely prevent non- specific reactions. In this paper, we describe the causes of such non-specific reactions as obstacles to im- munological testing, mainly in automated testing; special reference is given to some cases of interference by cross-reactions, heterophile antibodies, and autoantibodies that we encountered while measuring carcinoem- bryonic antigens (CEAs). Since not only non-specific reactions but also exogenous factors, such as sample processing, can cause abnormal data, noteworthy points in actual test settings are also described. To cope with the abnormal data, it is necessary to raise risk awareness among technicians who perform immunological tests, and establish an information-sharing system that allows queries from physicians to be quickly relayed to staff in the actual test setting. [Review].
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Pruebas Inmunológicas , Autoanticuerpos/sangre , Antígeno Carcinoembrionario/sangre , Servicios de Laboratorio Clínico/normas , Humanos , Inmunoglobulinas/aislamiento & purificación , Pruebas Inmunológicas/métodosRESUMEN
A common source of error when detecting heel-strike moments utilizing split force-plate treadmills is unwillingly stepping on contra-lateral force-plate. In this study, we quantified this error when heel-strike was detected based on such erroneous data and compared three methods to investigate how well the heel-strikes and stride-intervals were detected with erroneous data. Eleven subjects walked on a split force-plate treadmill for more than 20min. We used 20N and 50% body-weight thresholds to detect the heel-strike moments (HS20N and HS50%, respectively). Besides, we used linear approximation to estimate the unaffected force profile from affected force-plate data, and subsequently to detect the heel-strike moments (HSest). We used heel-strike moments detected by a foot-switch as a reference to compare accuracy of HS20N, HS50% and HSest. HS20N and HSest detected heel-strike moments accurately for unaffected force-plate data (median(max) errors for all subjects: 9(23) and 9(37) ms) but HS50% showed significantly larger errors (52(74) ms). Unlike HS50% and HSest, HS20N was considerably affected by the affected force-plate data (23(68) ms). The error in stride-interval measurement was relatively small using any methods for unaffected force-plate data (3(7), 6(8), and 6(12) ms), while stride-interval errors were large for some subjects when using HS20N for affected data (6(175) ms). We concluded that unwillingly stepping on contra-lateral force-plate occurred a few percent and up to 37.7% of all strides (median: 12.9%). Our proposed method (HSest) robustly showed small errors for heel-strike detection and stride-interval calculation consistently among subjects, while HS50% and HS20N showed large errors depending on subjects.
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Prueba de Esfuerzo/instrumentación , Marcha/fisiología , Talón/fisiología , Imagenología Tridimensional/métodos , Caminata/fisiología , Adulto , Voluntarios Sanos , Humanos , MasculinoRESUMEN
Renal inflammation is a final common pathway of chronic kidney disease (CKD), and its progression can be used to effectively gauge the degree of renal dysfunction. Interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK-4) has been reported to be a pivotal molecule for IL-1 receptor- and Toll-like receptor-induced signaling and activation of proinflammatory mediators. In this study, we hypothesized that if inflammation plays a key role in renal failure, then the anti-inflammatory effect of IRAK-4 inhibitor should be effective in improving CKD. To determine its pharmacological potency, we investigated the renoprotective properties of the novel IRAK-4 inhibitor AS2444697 (N-[3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-2-(2-methylpyridin-4-yl)-1,3-oxazole-4-carboxamide hydrochloride (1:1)) in 5/6 nephrectomized (Nx) rats, a model of CKD. Six weeks' repeated administration of AS2444697 (0.3-3 mg/kg, twice daily) dose-dependently and significantly reduced urinary protein excretion and prevented the development of glomerulosclerosis and interstitial fibrosis without affecting the blood pressure. In addition, AS2444697 showed beneficial effects on renal function as demonstrated by the decrease in levels of plasma creatinine and blood urea nitrogen and attenuation of decline in creatinine clearance. 5/6 Nx rats exhibited low-grade inflammation as evidenced by increased renal mRNA expression and plasma levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α, and MCP-1) and C-reactive protein as a marker of systemic inflammation. AS2444697 significantly reduced or showed a decreasing trend in expression and levels of these inflammatory parameters. These results suggest that AS2444697 suppresses the progression of chronic renal failure via anti-inflammatory action and may therefore be potentially useful in treating CKD patients.