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This study aimed to identify quantitative biomarkers of motor function for cerebellar ataxia by evaluating gait and postural control using an RGB-depth camera-based motion analysis system. In 28 patients with degenerative cerebellar ataxia and 33 age- and sex-matched healthy controls, motor tasks (short-distance walk, closed feet stance, and stepping in place) were selected from a previously reported protocol, and scanned using Kinect V2 and customized software. The Clinical Assessment Scale for the Assessment and Rating of Ataxia (SARA) was also evaluated. Compared with the normal control group, the cerebellar ataxia group had slower gait speed and shorter step lengths, increased step width, and mediolateral trunk sway in the walk test (all P < 0.001). Lateral sway increased in the stance test in the ataxia group (P < 0.001). When stepping in place, the ataxia group showed higher arrhythmicity of stepping and increased stance time (P < 0.001). In the correlation analyses, the ataxia group showed a positive correlation between the total SARA score and arrhythmicity of stepping in place (r = 0.587, P = 0.001). SARA total score (r = 0.561, P = 0.002) and gait subscore (ρ = 0.556, P = 0.002) correlated with mediolateral truncal sway during walking. These results suggest that the RGB-depth camera-based motion analyses on mediolateral truncal sway during walking and arrhythmicity of stepping in place are useful digital motor biomarkers for the assessment of cerebellar ataxia, and could be utilized in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Language dysfunction is a feature of cognitive impairment in amyotrophic lateral sclerosis (ALS) that may compromise communication. Objective: To elucidate language dysfunction in patients with ALS and its relationship with other neuropsychological tests and to identify the brain regions associated with this dysfunction using perfusion image. Methods: Overall, 37 patients with ALS were included in this study. Their neuropsychological function was investigated using the Western Aphasia Battery (WAB), Frontal Assessment Battery and Behavioral Assessment of the Dysexecutive Syndrome. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography was used to examine regional cerebral blood flow and its relationship with WAB scores was investigated using multiple regression analyses, controlled for age, sex and years of education. Results: Frequency of language abnormality in ALS was 8.5% for spontaneous speech, 25.7% for auditory verbal comprehension, 8.8% for repetition, 14.7% for naming, 17.6% for reading and 51.4% for writing. The writing error was mainly omission and substitution of kana letters. Executive tests were correlated with naming (r > 0.5, p < 0.001) and reading (r > 0.4, p < 0.01) scores. With respect to the writing sub-test, positive perfusional relationship was only detected in the left angular gyrus. Conclusions: The left angular gyrus is the region associated with the writing errors observed in ALS. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation of the bilateral subthalamic nucleus (STN-DBS) improves motor fluctuation and severe dyskinesia in advanced Parkinson's disease (PD). Effects on non-motor symptoms, such as neurocognitive side effects, can also influence the quality of life of both patients with PD and caregivers. Predictive quantitative factors associated with postoperative neurocognitive deterioration therefore warrant further attention. Here, we evaluated preoperative electroencephalogram (EEG) as a predictive marker for changes in neurocognitive functions after surgery. Methods: Scalp EEG was recorded preoperatively from 17 patients with PD who underwent bilateral STN-DBS. Global relative power in the theta, alpha, and beta bands was calculated. Cognitive function was assessed with neuropsychological batteries preoperatively and 1 year after STN-DBS. Results: Performance on the Symbol Search subtest of the WAIS III declined 1 year after DBS. The theta band was chosen for analysis with a 40% cutoff point for increased (≥ 40%) and decreased (< 40%) power. No significant differences between the two groups in baseline performance on most neuropsychological batteries were found, except for the Digit Symbol Coding subtest of the WAIS III. Changes in visual spatial functions were significantly different between groups. The increased theta band power group demonstrated a significant deterioration in performance on the WAIS III Matrix Reasoning subtest and the copy and immediate recall tasks of the Rey-Osterrieth complex figure test. Conclusions: These findings suggest that preoperative increases in theta power are related to postoperative deterioration of visuospatial function, which indicates the predictive potential of preoperative quantitative EEG for neurocognitive changes after STN-DBS. [ABSTRACT FROM AUTHOR]

Form birefringence originating from self-assembly of the bulk nanograting structures in silica glass with various anion dopants (OH, Cl and F) was induced by the femtosecond laser pulses. Despite the almost similar nanostructure, the photo-induced birefringence can be changed by the anion dopants in glass. Larger birefringence can be induced in silica glass doped with higher Cl ion concentration. Even if F-doped silica glass indicates lower thermal stability, its lifetime could be evaluated to be at least several billion years. [ABSTRACT FROM AUTHOR]

Ca2+distribution is spatially and temporally non-uniform inside cells due to cellular compartmentalization. However, Ca2+sensing with small organic dyes, such as fura-2 and fluo-4, has been practically applied at a single cell level where the averaged signal from freely diffusing dye molecules is acquired. In this study, we aimed to target azide-functionalized fura-2 (N3-fura-2) to a specific site of subcellular compartments to realize focal Ca2+sensing. Using scAVD (single-chain avidin)–biotin interaction and a copper-free click reaction system, we linked N3-fura-2 to specifically-targeted scAVD protein fused with a red fluorescent protein mCherry, so that Ca2+sensors conjugated with four N3-fura-2 dyes with dibenzocyclooctyne (DBCO)-PEG4-biotin as a linker were generated at subcellular compartments in living cells. In cytoplasm, N3-fura-2 showed a prolonged retention period after binding to scAVD. Furthermore, the reacted N3-fura-2 was retained inside cells even after free dyes were washed out by methanol fixation. When scAVD was overexpressed on endoplasmic reticulum (ER) membranes, N3-fura-2 was accumulated on ER membranes. Upon histamine stimulation, which increases cytosolic Ca2+concentration, ER-localized N3-fura-2 successfully sensed the Ca2+level changes at the cytosolic side of ER membrane. Our study demonstrated specific targeting of N3-fura-2 to subcellular compartments and the ability of sensing focal Ca2+level changes with the specifically targeted Ca2+sensors. [ABSTRACT FROM PUBLISHER]

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Objective: Biomechanical effects of laterally wedged insoles are assessed by reduction in the knee adduction moment. However, the degree of reduction may vary depending on the reference frame with which it is calculated. The purpose of this study was to clarify the effect of reference frame on the reduction in the knee adduction moment by laterally wedged insoles. Methods: Twenty-nine healthy participants performed gait trials with a laterally wedged insole and with a flat insole as a control. The knee adduction moment, including the first and second peaks and the angular impulse, were calculated using four different reference frames: the femoral frame, tibial frame, laboratory frame and the Joint Coordinate System. Results: There were significant effects of reference frame on the knee adduction moment first and second peaks (P < 0.001 for both variables), while the effect was not significant for the angular impulse (P = 0.84). No significant interaction between the gait condition and reference frame was found in either of the knee adduction moment variables (P = 0.99 for all variables), indicating that the effects of laterally wedged insole on the knee adduction moments were similar across the four reference frames. On the other hand, the average percent changes ranged from 9% to 16% for the first peak, from 16% to 18% for the second peak and from 17% to 21% for the angular impulse when using the different reference frames. Conclusion: The effects of laterally wedged insole on the reduction in the knee adduction moment were similar across the reference frames. On the other hand, Researchers need to recognize that when the percent change was used as the parameter of the efficacy of laterally wedged insole, the choice of reference frame may influence the interpretation of how laterally wedged insoles affect the knee adduction moment. [ABSTRACT FROM AUTHOR]

We synthesized a novel cyclooctyne-based clickable fluorescent probe with versatile properties such as high cell-membrane permeability and free diffusibility in the cell. Our probe “FC-DBCO” was conjugated to an azide-modified mannose via a Cu-free click reaction in living HeLa cells and displayed intracellular specific fluorescence imaging with low background signals. [ABSTRACT FROM AUTHOR]

We report the structural changes inside germania glass induced by femtosecond laser pulses. Inspection by polarization microscopy and secondary electron microscopy indicate that the periodic nanostructures consist of oxygen defects such as ODCs (oxygen deficient centers) and NBOHCs (nonbridging oxygen hole centers) for laser pulse energy less than 0.2 μJ. However, the glass network was dissociated and O2 molecules were generated for laser pulse energy greater than 0.4 μJ. Two different structural changes, form-birefringence and dissociation, were induced in GeO2 glass, depending on the laser pulse energy. The form-birefringence exhibited by the nanogratings in GeO2 glass is larger than that in SiO2 glass for pulse energy less than 0.2 μJ, as the density of nanovoids enclosed by ODCs in GeO2 glass is higher than that in SiO2 glass. Arrhenius plots of the phase retardation caused by the nanogratings in GeO2 and SiO2 indicate that the oxygen defects are relaxed at a temperature 100°C above the glass-transition temperature. [ABSTRACT FROM AUTHOR]

Mitochondrial thermodynamics is the key to understand cellular activities related to homeostasis and energy balance. Here, we report the first ratiometric fluorescent molecular probe (Mito-RTP) that is selectively localized in the mitochondria and visualize the temperature. We confirmed that Mito-RTP could work as a ratiometric thermometer in a cuvette and living cells. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this study was to investigate computed tomography (CT) and clinical features relating to calcifications within the parotid gland of patients with Sjögren''s syndrome (SS). Methods: Data from 30 patients with SS who had been examined by CT were extracted from our radiological information database accumulated from 2001 to 2011, and their CT images were reread carefully. Of these patients, 14 (all female; age range 20–95years; mean age 61.4years) with calcifications within the parotid gland were retrospectively investigated with CT findings. The relationship between calcification occurrence and clinical symptoms including parotid swelling and/or saliva colic was investigated. The degree of destruction of the parotid gland on CT images was also evaluated. Results: All calcifications of 14 patients were located within the parotid gland, not in the parotid duct. CT images of all calcifications showed small and regular round shapes. Multiple occurrences of calcifications were recognized in 10 patients, and a solitary occurrence was seen in 4 patients. Seven patients had bilateral calcifications. There was little relationship between the occurrence of calcifications and clinical symptoms, and the severity of destruction of the parotid gland. Conclusion: The presented CT and clinical features would be peculiar to SS because too many patients lacked the typical features of sialoliths within the parotid gland. [Copyright &y& Elsevier]

The purpose of this study was to use a cDNA microarray to identify new genes involved in healing of spinal cord injury. C57BL/6 mice (7-8 weeks, male) were subjected to spinal cord compression injury (SCI) at the T7/8 level (20 g, 5 min; SCI group). For the control group, mice underwent only laminectomy. Mice were killed at 1, 3 and 7 days. cDNA transcribed from mRNA was hybridized to NIA mice 15K microarrays at each time point. We found 84 genes showing significant expressional changes, including higher and lower expression levels in the SCI groups than in the control [more than 1.0 or less than -1.0 using log ratio (base 2)]. Five genes were selected for further quantitative gene expression analysis by real-time reverse transcription (RT)-PCR. For histological examination, we applied in situ hybridization and fluorescence immunohistochemistry. Cathepsin D, metallothionein-1 (MT-1), metallothionein-2 (MT-2), osteopontin (OPN), and tenascin-C were selected for quantitative and histological analysis. Microarray analysis revealed that SCI led to the up-regulation of OPN and cathepsin D expression at 7 days and also of MT-1, MT-2, and tenascin-C expression at 1 day. Tenascin-C was re-up-regulated at 7 days. These values agreed with those of real-time RT-PCR analysis. By double labeling with in situ hybridization and fluorescence immunohistochemistry, MT-1, MT-2 and tenascin-C expression was observed in neurons and glial cells at 1 day, whereas at 7 days the main MT-2 and tenascin-C expression was found in fibronectin-positive fibroblasts. The main cathepsin D and OPN expression was observed in activated macrophages/microglia at 3 and 7 days. The five genes picked up by microarray gene expression profiling were shown to exhibit temporal and spatial changes of expression after SCI. This system is potentially useful for identifying genes that are involved in the response to SCI. [ABSTRACT FROM AUTHOR]

Abstract Background : Cardiocirculatory effects of hemodynamically significant patent ductus arteriosus (hsPDA) have not been systematically studied in extremely low-birth-weight (ELBW) infants with respiratory distress syndrome (RDS). The objective of the present study was to evaluate the effects of hsPDA on the left ventricular output (LVO) and organ blood flows in ELBW infants with RDS. Methods : Extremely low-birth-weight infants (birth-weight <1000 g) treated with surfactant for RDS were studied by serial Doppler flow examinations. Doppler flow variables in 19 infants in whom hsPDA developed (hsPDA group) were compared with those in 19 infants without hsPDA matched for gestational age, birth-weight, and postnatal age (non-hsPDA group). All infants in the hsPDA group had pharmacologic closure of ductus arteriosus when hsPDA developed. Results : Before pharmacological closure of PDA, the hsPDA group had significantly higher LVO, lower blood flow volume of the abdominal aorta, and lower mean blood flow velocities in the celiac artery, superior mesenteric artery, and renal artery than the non-hsPDA group. These alterations in the hsPDA group reverted to the levels in the non-hsPDA group after the closure of PDA and had no deleterious effects on the cardiorespiratory status. No significant differences between the groups were found in mean blood flow velocities of the anterior cerebral artery throughout the study period. Conclusion : These results indicate that although LVO is increased, the splanchnic and renal blood flows are decreased when hsPDA develops in ELBW infants with RDS. The effects of these alterations of LVO and organ blood flows on the cardiorespiratory course seem to be minor when early pharmacologic closure of PDA is done. [ABSTRACT FROM AUTHOR]

The powerful strategy of “intracellular click reaction” was used to retain a chemical Ca2+ indicator in the cytosol. Specifically, a novel clickable Ca2+ indicator “N3-fura-2 AM” was coupled with dibenzylcyclooctyl-modified biomacromolecules via copper-free click reaction in living cells and Ca2+ oscillation was observed for an extended period of time. [ABSTRACT FROM AUTHOR]