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Purposes: To verify the relationship between muscle volume and muscular strength of different cross-sectional areas (CSAs) of the gluteus maximus and medius, and to clarify the effective evaluation index., Methods: Twenty healthy adults were enrolled in this cross-sectional study. Magnetic resonance images were evaluated, and CSAs of the gluteus maximus and medius were calculated. Calculation sites were the peak CSA, lowest end of the sacroiliac joint CSA, and just above the femoral head CSA. Muscle volume and muscular strength were measured. The correlation between muscular CSA, muscle volume, and muscular strength was verified using Pearson's correlation coefficient (p < 0.05). One-way analysis of variance and the Tukey-Kramer test were used to verify differences in each CSA (p < 0.05)., Results: A significantly positive correlation was found between muscular CSA, muscle volume, and muscular strength of both muscles (p < 0.05). For the gluteus maximus, the muscular CSA calculated just above the femoral head showed a significantly larger value than that calculated at the lowest end of the sacroiliac joint (p < 0.05). For the gluteus medius, the peak CSA and muscular CSA calculated at the lowest end of the sacroiliac joint were significantly larger than that calculated just above the femoral head (p < 0.05)., Conclusions: The maximum CSA of the gluteus maximus was found just above the femoral head and that of the gluteus medius was near the lowest end of the sacroiliac joint; hence, CSAs should be calculated at these sites. The CSA reflected muscle volume and strength.

Effective evaluation of costs and benefits is a core survival capacity that in humans is considered as optimal, "rational" decision-making. This capacity is vulnerable in neuropsychiatric disorders and in the aftermath of chronic stress, in which aberrant choices and high-risk behaviors occur. We report that chronic stress exposure in rodents produces abnormal evaluation of costs and benefits resembling non-optimal decision-making in which choices of high-cost/high-reward options are sharply increased. Concomitantly, alterations in the task-related spike activity of medial prefrontal neurons correspond with increased activity of their striosome-predominant striatal projection neuron targets and with decreased and delayed striatal fast-firing interneuron activity. These effects of chronic stress on prefronto-striatal circuit dynamics could be blocked or be mimicked by selective optogenetic manipulation of these circuits. We suggest that altered excitation-inhibition dynamics of striosome-based circuit function could be an underlying mechanism by which chronic stress contributes to disorders characterized by aberrant decision-making under conflict. VIDEO ABSTRACT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dysregulation of neurochemicals, in particular, dopamine, is epitomized in numerous debilitating disorders that impair normal movement and mood aspects of our everyday behavior. Neurochemical transmission is a neuron-specific process, and further exhibits region-specific signaling in the brain. Tools are needed to monitor the heterogeneous spatiotemporal dynamics of dopamine neurotransmission without compromising the physiological processes of the neuronal environment. We developed neurochemical probes that are ten times smaller than any existing dopamine sensor, based on the size of the entire implanted shaft and its sensing tip. The microfabricated probe occupies a spatial footprint (9 μm) coordinate with the average size of individual neuronal cells (∼10 μm). These cellular-scale probes were shown to reduce inflammatory response of the implanted brain tissue environment. The probes are further configured in the form of a microarray to permit electrochemical sampling of dopamine and other neurotransmitters at unprecedented spatial densities and distributions. Dopamine recording was performed concurrently from up to 16 sites in the striatum of rats, revealing a remarkable spatiotemporal contrast in dopamine transmission as well as site-specific pharmacological modulation. Collectively, the reported platform endeavors to enable high density mapping of the chemical messengers fundamentally involved in neuronal communication through the use of minimally invasive probes that help preserve the neuronal viability of the implant environment.

[Purpose] Increased compensatory pelvic movement is remarkable in limping patients with hip osteoarthritis (OA). However, a method of improving limping has not been established. The purpose of this study was to identify the effects of two types of Nordic walking by analyzing the pelvic movement and muscle activities of adults with hip OA. [Subjects and Methods] Ten patients with OA of the hip performed Japanese-style Nordic walking (JS NW), European-style Nordic walking (ES NW), and Ordinary walking (OW), and the muscle activities around the hip joint and pelvic movements were analyzed. [Results] The pelvic rotation angle was significantly larger in ES NW than in JS NW. In the stance phase, hip abductor muscle activity was significantly decreased in JS NW compared to both OW and ES NW. In the swing phase, rectus abdominis muscle activity was significantly increased in both JS NW and ES NW compared to OW and lumbar erector spinae activity was significantly lower in JS NW than in OW. [Conclusion] JS NW style may reduce the compensatory pelvic rotation in patients with hip OA. JS NW might be better for joint protection and prevention of secondary disorders of the hip in OA patients.

Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, alkylglycerol monooxygenase, and nitric oxide synthases (NOS). Inborn errors of BH4 metabolism lead to severe insufficiency of brain monoamine neurotransmitters while augmentation of BH4 by supplementation or stimulation of its biosynthesis is thought to ameliorate endothelial NOS (eNOS) dysfunction, to protect from (cardio-) vascular disease and/or prevent obesity and development of the metabolic syndrome. We have previously reported that homozygous knock-out mice for the 6-pyruvolytetrahydropterin synthase (PTPS; Pts-ko/ko) mice with no BH4 biosynthesis die after birth. Here we generated a Pts-knock-in (Pts-ki) allele expressing the murine PTPS-p.Arg15Cys with low residual activity (15% of wild-type in vitro) and investigated homozygous (Pts-ki/ki) and compound heterozygous (Pts-ki/ko) mutants. All mice showed normal viability and depending on the severity of the Pts alleles exhibited up to 90% reduction of PTPS activity concomitant with neopterin elevation and mild reduction of total biopterin while blood L-phenylalanine and brain monoamine neurotransmitters were unaffected. Yet, adult mutant mice with compromised PTPS activity (i.e., Pts-ki/ko, Pts-ki/ki or Pts-ko/wt) had increased body weight and elevated intra-abdominal fat. Comprehensive phenotyping of Pts-ki/ki mice revealed alterations in energy metabolism with proportionally higher fat content but lower lean mass, and increased blood glucose and cholesterol. Transcriptome analysis indicated changes in glucose and lipid metabolism. Furthermore, differentially expressed genes associated with obesity, weight loss, hepatic steatosis, and insulin sensitivity were consistent with the observed phenotypic alterations. We conclude that reduced PTPS activity concomitant with mildly compromised BH4-biosynthesis leads to abnormal body fat distribution and abdominal obesity at least in mice. This study associates a novel single gene mutation with monogenic forms of obesity.

A striking neurochemical form of compartmentalization has been found in the striatum of humans and other species, dividing it into striosomes and matrix. The function of this organization has been unclear, but the anatomical connections of striosomes indicate their relation to emotion-related brain regions, including the medial prefrontal cortex. We capitalized on this fact by combining pathway-specific optogenetics and electrophysiology in behaving rats to search for selective functions of striosomes. We demonstrate that a medial prefronto-striosomal circuit is selectively active in and causally necessary for cost-benefit decision-making under approach-avoidance conflict conditions known to evoke anxiety in humans. We show that this circuit has unique dynamic properties likely reflecting striatal interneuron function. These findings demonstrate that cognitive and emotion-related functions are, like sensory-motor processing, subject to encoding within compartmentally organized representations in the forebrain and suggest that striosome-targeting corticostriatal circuits can underlie neural processing of decisions fundamental for survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Various types of fiber reinforced cementitious composites (FRCCs) were experimentally studied to evaluate their self-healing capabilities regarding their watertightness and mechanical properties. Cracks were induced in the FRCC specimens during a tensile loading test, and the specimens were then immersed in static water for self-healing. By water permeability and reloading tests, it was determined that the FRCCs containing synthetic fiber and cracks of width within a certain range (<0.1 mm) exhibited good self-healing capabilities regarding their watertightness. Particularly, the high polarity of the synthetic fiber (polyvinyl alcohol (PVA)) series and hybrid fiber reinforcing (polyethylene (PE) and steel code (SC)) series showed high recovery ratio. Moreover, these series also showed high potential of self-healing of mechanical properties. It was confirmed that recovery of mechanical property could be obtained only in case when crack width was sufficiently narrow, both the visible surface cracks and the very fine cracks around the bridging of the SC fibers. Recovery of the bond strength by filling of the very fine cracks around the bridging fibers enhanced the recovery of the mechanical property.

Fontan procedure is one of the common surgical treatments of congenital heart diseases. Patients with Fontan circulation have single ventricle in the systemic circulation with the total cavopulmonary connection. We have been developing a pulmonary circulatory assist device using shape memory alloy fibers for Fontan circulation with total cavopulmonary connection. It consisted of the shape memory alloy fibers, the diameter of which are 100 µm. The fibers could wrap the ePTFE conduit for Fontan TCPC connection from the outside. We designed the sequential motion control system for sophisticated pulmonary hemodynamics by the pulsatile flow generation. In order to achieve pulsatile flow assistance in pulmonary arterial system, we fabricated a mechanical structure by sequential contraction of shape memory alloy fibers. Then, we developed a sequential contraction controller for the assist system, which could reproduce the wall contractile velocity at 6.0 to 20.0 cm/sec. We examined hemodynamic characteristic of its function using a mock circulatory system, which consisted of two overflow tanks representing venous and pulmonary arterial pressures in Fontan circulation. As a result, the pulmonary circulation assist device with sequential contraction could achieve effective promotion of the pulsatility in pulmonary arterial flow.

Diastolic counter-pulsation has been used to provide circulatory augmentation for short term cardiac support. The success of intra-aortic balloon pump (IABP) therapy has generated interest in long term counter-pulsation strategies to treat heart failure patients. The authors have been developing a totally implantable extra aortic pulsation device for the circulatory support of heart failure patients, using 150 µm Ni-Ti anisotropic shape memory alloy (SMA) fibers. These fibers contract by Joule heating with an electric current supply. The special features of our design are as follow: non blood contacting, extra aortic pulsation function synchronizing with the native heart, a wrapping mechanical structure for the aorta in order to achieve its assistance as the aortomyoplsty and the extra aortic balloon pump. The device consisted of rubber silicone wall plates, serially connected for radial contraction. We examined the contractile function of the device, as well as it controlling methods; the phase delay parameter and the pulse width modulation, in a systemic mock circulatory system, with a pneumatically driven silicone left ventricle model, arterial rubber tubing, a peripheral resistance unit, and a venous reservoir. The device was secured around the aortic tubing with a counter-pulsation mode of 1:4 against the heartbeat. Pressure and flow waveforms were measured at the aortic outflow, as well as its driving condition of the contraction phase width and the phase delay. The device achieved its variable phase control for co-pulsation or counter-pulsation modes by changing the phase delay of the SMA fibers. Peak diastolic pressure significantly augmented, mean flow increased (p<0.05) according to the pulse width modulation. Therefore the newly developed extra aortic counter-pulsation device using SMA fibers, through it controlling methods indicated its promising alternative extra aortic approach for non-blood contacting cardiovascular circulatory support.

Annuloplasty for functional mitral or tricuspid regurgitation has been made for surgical restoration of valvular diseases. However, these major techniques may sometimes be ineffective because of chamber dilation and valve tethering. We have been developing a sophisticated intelligent artificial papillary muscle (PM) by using an anisotropic shape memory alloy fiber for an alternative surgical reconstruction of the continuity of the mitral structural apparatus and the left ventricular myocardium. This study exhibited the mitral regurgitation with regard to the reduction in the PM tension quantitatively with an originally developed ventricular simulator using isolated goat hearts for the sophisticated artificial PM. Aortic and mitral valves with left ventricular free wall portions of isolated goat hearts (n=9) were secured on the elastic plastic membrane and statically pressurized, which led to valvular leaflet-papillary muscle positional change and central mitral regurgitation. PMs were connected to the load cell, and the relationship between the tension of regurgitation and PM tension were measured. Then we connected the left ventricular specimen model to our hydraulic ventricular simulator and achieved hemodynamic simulation with the controlled tension of PMs.

Postnatal development of dopaminergic system is closely related to the development of psychomotor function. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the biosynthesis of dopamine and requires tetrahydrobiopterin (BH4) as a cofactor. To clarify the effect of partial BH4 deficiency on postnatal development of the dopaminergic system, we examined two lines of mutant mice lacking a BH4-biosynthesizing enzyme, including sepiapterin reductase knock-out (Spr(-/-)) mice and genetically rescued 6-pyruvoyltetrahydropterin synthase knock-out (DPS-Pts(-/-)) mice. We found that biopterin contents in the brains of these knock-out mice were moderately decreased from postnatal day 0 (P0) and remained constant up to P21. In contrast, the effects of BH4 deficiency on dopamine and TH protein levels were more manifested during the postnatal development. Both of dopamine and TH protein levels were greatly increased from P0 to P21 in wild-type mice but not in those mutant mice. Serotonin levels in those mutant mice were also severely suppressed after P7. Moreover, striatal TH immunoreactivity in Spr(-/-) mice showed a drop in the late developmental stage, when those mice exhibited hind-limb clasping behavior, a type of motor dysfunction. Our results demonstrate a critical role of biopterin in the augmentation of TH protein in the postnatal period. The developmental manifestation of psychomotor symptoms in BH4 deficiency might be attributable at least partially to high dependence of dopaminergic development on BH4 availability.

Total cavopulmonary connection (TCPC) is commonly applied for the surgical treatment of congenital heart disease such as single ventricle in pediatric patients. Patients with no ventricle in pulmonary circulation are treated along with Fontan algorithm, in which the systemic venous return is diverted directly to the pulmonary artery without passing through subpulmonary ventricle. In order to promote the pulmonary circulation after Fontan procedure, we developed a newly designed pulmonary circulatory assist device by using shape memory alloy fibers. We developed a pulmonary circulatory assist device as a non-blood contacting mechanical support system in pediatric patients with TCPC. The device has been designed to be installed like a cuff around the ePTFE TCPC conduit, which can contract from outside. We employed a covalent type functional anisotropic shape memory alloy fiber (Biometal, Toki Corporation, Tokyo Japan) as a servo actuator of the pulmonary circulatory assist device. The diameter of this fiber was 100 microns, and its contractile frequency was 2-3 Hz. Heat generation with electric current contracts these fibers and the conduit. The maximum contraction ratio of this fiber is about 7% in length. In order to extend its contractile ratio, we fabricated and installed mechanical structural units to control the length of fibers. In this study, we examined basic contractile functions of the device in the mock system. As a result, the internal pressure of the conduit increased to 63 mmHg by the mechanical contraction under the condition of 400 msec-current supply in the mock examination with the overflow tank of 10 mmHg loading.

Thromboembolic and haemorrhagic complications are the primary causes of mortality and morbidity in patients with artificial hearts, which are known to be induced by the interactions between blood flow and artificial material surfaces. The authors have been developing a new mechanical artificial myocardial assist device by using a sophisticated shape memory alloy fibre in order to achieve the mechanical cardiac support from outside of the heart without a direct blood contacting surface. The original material employed as the actuator of artificial myocardial assist devices was 100um fibred-shaped, which was composed of covalent and metallic bonding structure and designed to generate 4-7 % shortening by Joule heating induced by the electric current input. In this study, we focused on the synchronization of the actuator with native cardiac function, and the phase delay parameter was examined in animal experiments using Saanen goats. Total weight of the device including the actuator was around 150g, and the electric power was supplied transcutaneously. The device could be successfully installed into thoracic cavity, which was able to be girdling the left ventricle. The contraction of the device could be controlled by the originally designed microcomputer. The mechanical contraction signal input had been transmitted with the phase delay of 50-200 msec after the R-wave of ECG, and hemodynamic changes were investigated. Cardiac output and systolic left ventricular pressure were elevated with 20% delay of cardiac cycle by 27% and 7%, respectively, although there was smaller difference under the condition of the delay of over 30%. Therefore, it was suggested that the synchronization measures should be examined in order to achieve sophisticated ventricular passive/active support on physiological demand.

The authors have been developing an artificial myocardium, which is capable of supporting natural contractile function from the outside of the ventricle. The system was originally designed by using sophisticated covalent shape memory alloy fibres, and the surface did not implicate blood compatibility. The purpose of our study on the development of artificial myocardium was to achieve the assistance of myocardial functional reproduction by the integrative small mechanical elements without sensors, so that the effective circulatory support could be accomplished. In this study, the authors fabricated the prototype artificial myocardial assist unit composed of the sophisticated shape memory alloy fibre (Biometal), the diameter of which was 100 microns, and examined the mechanical response by using pulse width modulation (PWM) control method in each unit. Prior to the evaluation of dynamic characteristics, the relationship between strain and electric resistance and also the initial response of each unit were obtained. The component for the PWM control was designed in order to regulate the myocardial contractile function, which consisted of an originally-designed RISC microcomputer with the input of displacement, and its output signal was controlled by pulse wave modulation method. As a result, the optimal PWM parameters were confirmed and the fibrous displacement was successfully regulated under the different heat transfer conditions simulating internal body temperature as well as bias tensile loading. Then it was indicated that this control theory might be applied for more sophisticated ventricular passive or active restraint by the artificial myocardium on physiological demand.

The authors have been developing a mechano-electric artificial myocardial assist system (artificial myocardium) which is capable of supporting natural contractile functions from the outside of the ventricle without blood contacting surface. In this study, a nano-tech covalent type shape memory alloy fibre (Biometal, Toki Corp, Japan) was employed and the parallel-link structured myocardial assist device was developed. And basic characteristics of the system were examined in a mechanical circulatory system as well as in animal experiments using goats. The contractile functions were evaluated with the mock circulatory system that simulated systemic circulation with a silicone left ventricular model and an aortic afterload. Hemodynamic performance was also examined in goats. Prior to the measurement, the artificial myocardial assist device was installed into the goat's thoracic cavity and attached onto the ventricular wall. As a result, the system could be installed successfully without severe complications related to the heating, and the aortic flow rate was increased by 15% and the systolic left ventricular pressure was elevated by 7% under the cardiac output condition of 3L/min in a goat. And those values were elevated by the improvement of the design which was capable of the natural morphological myocardial tissue streamlines. Therefore it was indicated that the effective assistance might be achieved by the contraction by the newly-designed artificial myocardial assist system using Biometal. Moreover it was suggested that the assistance gain might be obtained by the optimised configuration design along with the natural anatomical myocardial stream line.

Objective: To investigate the distribution of lower urinary tract symptoms (LUTS) in elderly Japanese men, to clarify which variables contributed to medical care-seeking behaviour, and to construct a structural-equation model (SEM) to explain overall quality of life (QoL)., Subjects and Methods: A dataset was obtained from 662 Japanese men aged 50-79 years who participated in the programme by accessing a website via the Internet between 10.30 hours on 19 February 2003 and 10.30 hours on 24 February 2003. The participants were queried about their International Prostate Symptom Score (IPSS), bother, QoL index and medical care-seeking behaviour., Results: Of the 662 participants, 314 reported intending to seek medical care for LUTS (intention group); the remaining 348 answered that they did not intend to see a doctor (no-intention group). The characteristic of weak stream had the strongest correlation with the QoL index, not only in the intention (r = 0.58) but also in the no-intention group (r = 0.48). Among several SEMs proposed, one that included a latent variable termed 'QoL sensitivity' was the most appropriate to explain overall QoL. In this model it was assumed that 'QoL sensitivity' was affected by other latent variables, termed the 'voiding symptom factors' and 'storage symptom factors', and affected the degree of bother related to each symptom., Conclusion: In Japanese men, voiding symptoms, especially weak stream, contributed to overall QoL for medical care-seeking behaviour. Differences in 'QoL sensitivity' among men may be one of the reasons why symptomatic severity is not always correlated with symptom-related bother.

The authors have been developing a newly-designed totally-implantable artificial myocardium using a covalent shape-memory alloy fibre (Biometal&#174;, Toki Corporation), which is attached onto the ventricular wall and is also capable of supporting the natural ventricular contraction. This mechanical system consists of a contraction assistive device, which is made of Ti-Ni alloy. And the phenomenon of the martensitic transformation of the alloy was employed to achieve the physiologic motion of the device. The diameter of the alloy wire could be selected from 45 to 250&#956;m. In this study, the basic characteristics of the fiber of 150&#956;m was examined to design the sophisticated mechano-electric myocardium. The stress generated by the fiber was 400gf under the pulsatile driving condition (0.4W, 1Hz). Therefore it was indicated that the effective assistance might be achieved by using the Biometal shape-memory alloy fiber.

We have used digital fluorescence microscopy to examine transport of LDL-containing endosomes in rat brain astroglial cells to show that individual middle endosomes undergo rapid transitions between forward/backward movements and immobile states over short distances. The population of rapidly moving endosomes (>0.04 microm/sec) was 35. 9%, and the remaining endosomes were slowly moving or temporarily immobile (<0.04 microm/sec). The averaged motion was, however, a very slow perinuclear motion with a velocity of 3.25 microm/h. This small velocity is mainly due to frequent changing of directions in movements, requiring 6 h for a significant concentration around the circumference of the cell nuclei. The application of both anti-dynein antibodies and vanadate in permeabilized cells resulted in peripherally concentrated distribution of endosomes, probably due to inhibition of perinuclear motion by dynein-like motor proteins. These results imply that both dynein-like and kinesin-like proteins bind to the same endosome resulting in both perinuclear and peripherally directed movements., (Copyright 2000 Academic Press.)

Following preliminary tests in which rats proved to be fairly insensitive to the depletory effect of paracetamol (CAS 103-90-2) on kidney glutathione levels, old male mice from a strain exhibiting particular susceptibility to paracetamol were investigated in respect of the comparative effects of paracetamol, acetylsalicylic acid (CAS 50-78-2, ASA) and caffeine (CAS 58-08-2), and a combination of these substances, on kidney glutathione levels. Additionally, the effects of paracetamol and ASA on hepatic glutathione in mice were also measured. When administered separately at oral doses of 150-600 mg/kg both paracetamol and ASA produced dose- and time-dependent depletion of kidney glutathione concentrations in the mice. The effect of ASA at a given dose was weaker than that of paracetamol. Caffeine showed only a very weak and transient depletory effect up to an oral dose of 60 mg/kg. The effects of the combined administration of paracetamol and ASA on kidney glutathione levels were only additive in nature. The administration of caffeine did not increase the reduction in kidney glutathione levels produced by the combination of paracetamol and ASA. The reduction in hepatic glutathione induced in the mice by paracetamol was considerably more pronounced than that observed in the kidneys. ASA, on the other hand, did not affect glutathione in the mouse liver at those doses which had led to a reduction in kidney glutathione levels.