Association analysis of the ACTN3 R577X polymorphism with passive muscle stiffness and muscle strain injury.

Passive muscle stiffness is considered to be a major factor affecting joint flexibility and is thought to relate to the occurrence of muscle strain injury. In skinned muscle fiber experiments, the R577X polymorphism of the α-actinin-3 gene (ACTN3) has been associated with passive muscle stiffness. Our primary purpose was to clarify whether the ACTN3 R577X polymorphism influences passive stiffness of human muscle in vivo. We also examined whether the ACTN3 R577X polymorphism is associated with the occurrence of hamstring strain injury. Seventy-six healthy young male subjects were genotyped for the ACTN3 R577X (rs1815739) polymorphism. Shear modulus (an index of stiffness) of each hamstring muscle (biceps femoris, semitendinosus, and semimembranosus) was assessed using ultrasound shear wave elastography, and history of hamstring strain injury was collected via a questionnaire. The muscle shear moduli of the semitendinosus and semimembranosus were significantly higher in R-allele (RR + RX genotype) carriers than in XX genotype carriers, whereas the shear modulus of the biceps femoris did not differ among the ACTN3 R577X genotypes. Frequency of past hamstring strain injury also did not differ between the 3 genotypes nor between the R-allele and XX genotype carriers. This study indicates that RR and RX genotypes of the ACTN3 R577X polymorphism (corresponding to the presence of α-actinin-3 in type II muscle fibers) are associated with increased passive muscle stiffness of the human hamstring in vivo. However, this altered mechanical property might not affect the risk of hamstring muscle strain injury.

Effects of hamstring stretching on passive muscle stiffness vary between hip flexion and knee extension maneuvers.

The purpose of this study was to examine whether the effects of hamstring stretching on the passive stiffness of each of the long head of the biceps femoris (BFl), semitendinosus (ST), and semimembranosus (SM) vary between passive knee extension and hip flexion stretching maneuvers. In 12 male subjects, before and after five sets of 90 s static stretching, passive lengthening measurements where knee or hip joint was passively rotated to the maximal range of motion (ROM) were performed. During the passive lengthening, shear modulus of each muscle was measured by ultrasound shear wave elastography. Both stretching maneuvers significantly increased maximal ROM and decreased passive torque at a given joint angle. Passive knee extension stretching maneuver significantly reduced shear modulus at a given knee joint angle in all of BFl, ST, and SM. In contrast, the stretching effect by passive hip flexion maneuver was significant only in ST and SM. The present findings indicate that the effects of hamstring stretching on individual passive muscles' stiffness vary between passive knee extension and hip flexion stretching maneuvers. In terms of reducing the muscle stiffness of BFl, stretching of the hamstring should be performed by passive knee extension rather than hip flexion.

Development of a long-slot microwave plasma source.

A 20 cm long 10 cm wide microwave plasma source was realized by inserting two 20 cm long 1.5 mm diameter rod antennas into the plasma. Plasma luminous distributions around the antennas were changed by magnetic field arrangement created by permanent magnets attached to the source. The distributions appeared homogeneous in one direction along the antenna when the spacing between the antenna and the source wall was 7.5 mm for the input microwave frequency of 2.45 GHz. Plasma density and temperature at a plane 20 cm downstream from the microwave shield were measured by a Langmuir probe array at 150 W microwave power input. The measured electron density and temperature varied over space from 3.0 × 10(9) cm(-3) to 5.8 × 10(9) cm(-3), and from 1.1 eV to 2.1 eV, respectively.

Dust particle diffusion in ion beam transport region.

Dust particles of µm size produced by a monoplasmatron ion source are observed by a laser light scattering. The scattered light signal from an incident laser at 532 nm wavelength indicates when and where a particle passes through the ion beam transport region. As the result, dusts with the size more than 10 µm are found to be distributed in the center of the ion beam, while dusts with the size less than 10 µm size are distributed along the edge of the ion beam. Floating potential and electron temperature at beam transport region are measured by an electrostatic probe. This observation can be explained by a charge up model of the dust in the plasma boundary region.

Sandwich organization of non-ionic surfactant liquid crystalline phases as induced by large inorganic K4Nb6O17 nanosheets.

While retaining its lamellar liquid crystal phase, K4Nb6O17 nanosheets were used as a template to sandwich and stabilize an alkylpoly(ethylene oxide) nonionic surfactant-water system showing monodomain (lamella) formation within the inorganic niobate sheets that appears to be not dependent on the surfactant liquid crystalline state in solution but more its concentration.

Type 2 diabetes reduces the proliferation and survival of oligodendrocyte progenitor cells in ishchemic white matter lesions.

Diabetes mellitus (DM) is a major risk factor for stroke and it exacerbates tissue damage after ischemic insult. Diabetes is one of the important causes of the progression of white matter lesion, however, the pathological mechanisms remain unclear. The present study evaluated the influences of type 2 DM on ischemic subcortical white matter injury and the recruitment of oligodendrocyte progenitor cells (OPCs) under chronic cerebral hypoperfusion using type 2 diabetic (db/db) mice. After bilateral common carotid artery stenosis (BCAS), the rarefaction in the white matter was more severe in db/db mice than in db/+ mice, and the number of glutathione S-transferase-pi (GST-pi)-positive mature oligodendrocytes (OLG) was lower in db/db mice than in db/+ mice at 4 and 8 weeks after ischemia. There were no significant differences in the number of single-stranded DNA (ssDNA)-positive apoptotic cells in the deep white matter between the db/db and db/+ mice. We found a transient increase in the platelet-derived growth factor receptor-α (PDGFRα)-positive OPCs in white matter lesions after ischemia. However, significantly fewer PDGFRα-positive OPCs were detected in db/db than db/+ mice from 4weeks after BCAS. The number of Ki67-positive proliferating cells in the deep white matter was significantly lower in db/db mice than in db/+ mice from 4 to 8weeks after BCAS. Most of the Ki67-positive cells were PDGFRα-positive OPCs. Finally, we assessed the survival of 5-bromo-2'-deoxyuridine (BrdU)-positive proliferating cells in ischemic white matter, and found significantly poorer survival of BrdU/PDGFRα-positive OPCs or BrdU/GST-pi-positive OLGs in the db/db mice compared to the db/+ mice in the white matter after BCAS. Our findings suggest that the type 2 DM mice exhibited more severe white matter injury 8 weeks after chronic ischemia. Decreased proliferation and survival of OPCs may play an important role in the progression of white matter lesions after ischemia in diabetics.

No graduated pressure profile in compression stockings still reduces muscle fatigue.

Most sporting compression stockings possess a graduated pressure profile. However, it remains unclear whether the graduated pressure profile is an essential feature for reducing the development of muscle fatigue. This study sought to examine the effect of the pressure profile of compression stockings on the degree of muscle fatigue of lower leg muscles induced by submaximal running exercise. 15 male subjects performed 30-min treadmill running in 1 control and 4 compression stocking conditions with the following profiles; 1) graduated low pressure, 2) graduated high pressure, 3) uniform pressure distribution, and 4) localized pressure just over the gastrocnemius muscle belly. Before and immediately after the exercise, T2-weighted magnetic resonance images of the right lower leg were obtained without testing garments. T2 values of the triceps surae and tibialis anterior were calculated from the images. T2 was significantly increased after the running in all conditions. The magnitude of T2 increase was significantly greater in the control than in other 3 conditions except for the one with graduated low pressure, whereas there were no significant differences among the latter 3 conditions. The findings suggest that a graduated pressure profile is not an essential feature of compression stockings for reducing the development of muscle fatigue during submaximal running exercise.

Preliminary analysis for integration of spot-scanning proton beam therapy and real-time imaging and gating.

PURPOSE: Spot-scanning proton beam therapy (PBT) can create good dose distribution for static targets. However, there exists larger uncertainty for tumors that move due to respiration, bowel gas or other internal circumstances within the patients. We have developed a real-time tumor-tracking radiation therapy (RTRT) system that uses an X-ray linear accelerator gated to the motion of internal fiducial markers introduced in the late 1990s. Relying on more than 10 years of clinical experience and big log data, we established a real-time image gated proton beam therapy system dedicated to spot scanning. MATERIALS AND METHODS: Using log data and clinical outcomes derived from the clinical usage of the RTRT system since 1999, we have established a library to be used for in-house simulation for tumor targeting and evaluation. Factors considered to be the dominant causes of the interplay effects related to the spot scanning dedicated proton therapy system are listed and discussed. RESULTS/CONCLUSIONS: Total facility design, synchrotron operation cycle, and gating windows were listed as the important factors causing the interplay effects contributing to the irradiation time and motion-induced dose error. Fiducial markers that we have developed and used for the RTRT in X-ray therapy were suggested to have the capacity to improve dose distribution. Accumulated internal motion data in the RTRT system enable us to improve the operation and function of a Spot-scanning proton beam therapy (SSPT) system. A real-time-image gated SSPT system can increase accuracy for treating moving tumors. The system will start clinical service in early 2014.

Fluctuation of an ion beam extracted from an AC filament driven Bernas-type ion source.

Argon ion beam fluctuation from an AC filament driven Bernas-type ion source is observed. The ion beam was measured by an 8 measurement elements beam profile monitor. The amplitude of the beam current fluctuation stayed in the same level from 100 Hz to 1 kHz of the filament heating frequency. The beam current fluctuation frequency measured by the beam profile monitor was equal to the frequency of the AC filament operation. The fluctuation amplitudes of the beam current by AC operation were less than 7% and were in the same level of the DC operation.

Visceral fat accumulation is associated with cerebral small vessel disease.

BACKGROUND AND PURPOSE: Obesity is associated with the risk of coronary artery disease and stroke. Visceral fat plays a significant role in the atherogenic effects of obesity. Whether visceral fat accumulation, as measured by computed tomography (CT), is an independent risk factor for the presence of cerebral small vessel disease (SVD) was investigated. METHODS: This study comprised 506 Japanese subjects 35-74 years of age (mean 55.3 years) without a history of symptomatic cerebrovascular disease who underwent health screening tests, including brain magnetic resonance imaging, carotid echography and measurements of the visceral fat area (VFA) and subcutaneous fat area (SFA) on abdominal CT. Visceral fat accumulation was defined as VFA ≥ 100 cm(2) . Logistic regression analysis was performed to examine the associations between visceral fat accumulation and cerebral SVD such as white matter lesions (WMLs) and silent lacunar infarction (SLI). RESULTS: The prevalence of WMLs and SLI but not carotid plaque were significantly higher in subjects with VFA ≥ 100 cm(2) than those with VFA < 100 cm(2) . A VFA ≥ 100 cm(2) was associated with WMLs and SLI independent of age, cardiovascular risk factors and other measurements of obesity, such as waist circumference and body mass index. A large waist circumference was independently associated with SLI. SFA, the combination of VFA and SFA, and body mass index were not associated with WMLs or SLI. CONCLUSIONS: Visceral fat accumulation was independently associated with the presence of cerebral SVD in subjects without a history of symptomatic cerebrovascular disease.

Chronic brain ischemia induces the expression of glial glutamate transporter EAAT2 in subcortical white matter.

Glutamate plays a central role in brain physiology and pathology. The involvement of excitatory amino acid transporters (EAATs) in neurodegenerative disorders including acute stroke has been widely studied, but little is known about the role of glial glutamate transporters in white matter injury after chronic cerebral hypoperfusion. The present study evaluated the expression of glial (EAAT1 and EAAT2) and neuronal (EAAT3) glutamate transporters in subcortical white matter and cortex, before and 3-28 days after the ligation of bilateral common carotid arteries (LBCCA) in rat brain. K-B staining showed a gradual increase of demyelination in white matter after ischemia, while there was no cortical involvement. Between 3 and 7 days after LBCCA, a significant increase in EAAT2 protein levels was observed in the ischemic brain and the number of EAAT2-positive cells also significantly increased both in the cortical and white matter lesions. EAAT2 was detected in glial-fibrillary acidic protein (GFAP)-positive astrocytes in both the cortex and white matter, but not in neuronal and oligodendroglial cells. EAAT1 was slightly elevated after ischemia only in the white matter, but EAAT3 was at almost similar levels both in the cortex and white matter after ischemia. A significant increase in EAAT2 expression level was also noted in the deep white matter of chronic human ischemic brain tissue compared to the control group. Our findings suggest important roles for up-regulated EAAT2 in chronic brain ischemia especially in the regulation of high-affinity of extracellular glutamate and minimization of white matter damage.

High-density lipoprotein cholesterol subfractions and lecithin: cholesterol acyltransferase activity in collegiate soccer players.

Many of the published data on the lipid profile of athletes is based on studies of endurance athletes. The data on soccer players are rare. The purpose of this study was to examine serum high-density lipoprotein cholesterol subfractions and lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31 well-trained male collegiate soccer players were divided into 2 groups: 16 defenders and 15 offenders. They were compared with 16 sedentary controls. Dietary information was obtained with a food frequency questionnaire. The subjects were all non-smokers and were not taking any drug known to affect the lipid and lipoprotein metabolism. The offenders had significantly higher high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and apolipoprotein A-I than the defenders and controls, whereas the defenders had the significantly higher high-density lipoprotein2 cholesterol than the controls. Both groups of athletes had significantly higher lecithin:cholesterol acyltransferase activity than the controls. The results indicate that favorable lipid and lipoprotein profile could be obtained by vigorous soccer training.

High frequency operation of a hot filament cathode for a magnetized plasma ion source.

A tungsten filament cathode has been operated with an ac heating current to excite a plasma in a linear magnetic field. Both the discharge current and the ion saturation current in plasma near the extraction hole of the ion source exhibited fluctuations. The discharge current fluctuated with the amplitude less than 2% of the average, and the frequency two times the frequency of the heating current. Fluctuation amplitude of the ion saturation current was about 10% of the average, while the frequency was the same as that of the heating current. The ac operation has prolonged the lifetime of a hot filament cathode by about 50%.

SU-E-J-42: Motion Adaptive Image Filter for Low Dose X-Ray Fluoroscopy in the Real-Time Tumor-Tracking Radiotherapy System.

PURPOSE: In the real-time tumor-tracking radiotherapy system, fiducial markers are detected by X-ray fluoroscopy. The fluoroscopic parameters should be optimized as low as possible in order to reduce unnecessary imaging dose. However, the fiducial markers could not be recognized due to effect of statistical noise in low dose imaging. Image processing is envisioned to be a solution to improve image quality and to maintain tracking accuracy. In this study, a recursive image filter adapted to target motion is proposed. METHODS: A fluoroscopy system was used for the experiment. A spherical gold marker was used as a fiducial marker. About 450 fluoroscopic images of the marker were recorded. In order to mimic respiratory motion of the marker, the images were shifted sequentially. The tube voltage, current and exposure duration were fixed at 65 kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube current was 100 mA as high dose imaging. A pattern recognition score (PRS) ranging from 0 to 100 and image registration error were investigated by performing template pattern matching to each sequential image. The results with and without image processing were compared. RESULTS: In low dose imaging, theimage registration error and the PRS without the image processing were 2.15±1.21 pixel and 46.67±6.40, respectively. Those with the image processing were 1.48±0.82 pixel and 67.80±4.51, respectively. There was nosignificant difference in the image registration error and the PRS between the results of low dose imaging with the image processing and that of high dose imaging without the image processing. CONCLUSIONS: The results showed that the recursive filter was effective in order to maintain marker tracking stability and accuracy in low dose fluoroscopy.

MO-F-213AB-04: Biological Effect of Dose Shadowing by Fiducial Markers in Spot Scanning Proton Therapy with a Limited Number of Fields.

PURPOSE: In spot scanning proton therapy, accurate patient positioning before and during treatment is essential. A small gold ball marker is suitable as a fiducial for prostate treatment. However, it has been pointed out that the marker causes dose shadowing because the protons are scattered with their energy quickly diminished. In this research we explore the possibility that the biological effect of dose shadowing can be mitigated with a limited number of fields. METHODS: The proton dose distribution in prostate was simulated using Geant4. The simulations include the Hokkaido University spot scanning nozzle and a water phantom positioned isocentrically. The PTV was delineated at the center of the phantom and a gold ball of 2 mm in diameter was placed at the middle of the PTV. The plan was created by single-field optimization and each of the following beam arrangements was investigated; (1) single lateral field (2) two lateral fields (3) two lateral + one anterior fields (4) four-field box. The dose prescription was D95 = 74 GyE (37 fr). The minimum dose and tumor control probability (TCP) were compared for the four beam arrangements. RESULTS: For (1)-(4), the minimum dose values were 55%, 77%, 78%, and 84% of the prescribed dose, respectively. The reduction of the TCP values from those in the absence of the gold marker were 50%, 2%, 1.1%, and 0.7%, using the TCP model by Wang et al. (Int.J.Radiat.Oncol.Biol.Phys. 55, 2003) and 2%, 0.7%, 0.5%, and 0.4%, using the biological parameters in Levegrûn et al. (Int.J.RadiatOncol.Biol.Phys. 51, 2001), respectively. CONCLUSIONS: Although dose shadowing by the gold marker is locally non-negligible, the size of the affected domain is tiny. It was found that with a minimum number of fields, the TCP nearly recovers to the value without the gold marker.

SU-E-T-506: Dosimetric Study for Shallow-Seated Tumor Using Passive/active Scanning Proton Beam.

PURPOSE: To investigate the possibility of using a single spot scanning proton beam to treat superficial lesions. METHODS: A cylindrical phantom with a simulated superficial target (it seated 0.5-4cm depth from the surface, volume: 270cm3 ) was created in Eclipse treatment planning system. Three proton plans were generated: (a) a single AP uniform scanning beam with aperture and range compensator; (b) a single AP spot scanning beam with a pre-absorber. The location and thickness of the pre-absorber were calculated using Geant4 to Monte Carlo code to make use of the available spot scanning beams to get a conformal plan. (c) a five-beam spot scanning beam plan using multi-field optimization. The prescription is 54 cobalt grey equivalent (CGE) which covers 95% of the target. The target coverage, lateral penumbra at 2 and 4cm depth in water, the doses to normal tissue (phantom-target) and skin (2mm from the surface) were evaluated and compared for three plans. RESULTS: The mean doses to the target are comparable within 2.4% for all three plans. The conformity indices (at 95%) are 1.36, 1.04 and 0.98 for plan (a), (b) and (c) respectively. The lateral penumbra (80% to 20%) for plan (a), (b) are both 0.73 cm, while it is 3.75 cm for plan (c). The skin dose which received more than 40 (CGE) from plan (a) is 10% higher than that of other two plans. Plan (c) has 70% higher mean doses to normal tissue than that of plan (a) and (b). CONCLUSIONS: Each plan provides good coverage of target. And in this study, it showed that, with a properly designed pre-absorber, it is possible to use a single spot scanning beam to treat superficial lesion. The plan provides good target coverage and maintains normal tissue sparing in the mean time.

Computer-assisted system for diagnosis of Alzheimer disease using data base- independent estimation and fluorodeoxyglucose- positron-emission tomography and 3D-stereotactic surface projection.

BACKGROUND AND PURPOSE: Recently, voxel-based statistical parametric images have been developed as additional diagnostic tools for AD. However these methods require the generation of a data base of healthy brain images. The purpose of this study was to produce and evaluate an automatic method using a data base-independent estimation system for the diagnosis of mild AD. MATERIALS AND METHODS: We retrospectively selected 66 subjects, including 33 patients with early AD and 33 age-matched healthy volunteers. Individual brain metabolic images were obtained by using FDG-PET. These were transformed by using 3D-SSP. We then produced CADDIES, which compares the parietal and sensorimotor metabolic counts by using t tests. If parietal metabolism was significantly lower than the sensorimotor metabolism, the subject was automatically diagnosed as having AD. The FDG-PET images were also analyzed by using a previous automatic diagnosis system (CAAD) that is dependent on the construction of a "normal data base" of healthy brain images. Diagnostic performance was compared between the 2 methods. RESULTS: The CADDIES demonstrated a sensitivity of 88%, specificity of 79%, and accuracy of 85%, while the CAAD system demonstrated a sensitivity of 70%, specificity of 94%, and accuracy of 82%. The area under the ROC curve of CADDIES was 0.964. The areas under ROC curves of the CAAD method in the parietal and posterior cingulate gyri were 0.843 and 0.939, respectively. CONCLUSIONS: The CADDIES method demonstrated a diagnostic accuracy similar to that of the CAAD system. Our results indicate that this method can be applied to the detection of patients with early AD in routine clinical examinations, with the benefit of not requiring the generation of a normal data base.

Measurement of gray and white matter atrophy in dementia with Lewy bodies using diffeomorphic anatomic registration through exponentiated lie algebra: A comparison with conventional voxel-based morphometry.

BACKGROUND AND PURPOSE: DLB is recognized as the second major form of dementia in the elderly. The regional pattern of GM atrophy in DLB highly overlaps that in AD. The aim of this study was to identify the critical pattern of atrophy in DLB by using DARTEL, which provides improved registration accuracy compared with that of conventional VBM. MATERIALS AND METHODS: We evaluated 51 patients with probable AD, 43 patients with probable DLB, and 40 age-matched healthy controls. The pattern of GM atrophy in each group was compared by using conventional VBM and VBM-DARTEL. RESULTS: Regional patterns of atrophy identified by using conventional VBM differed significantly from those identified by using VBM-DARTEL. A decrease in GM volume in the MTLs in both AD and DLB was identified with VBM-DARTEL; the decrease was greater in patients with AD than in those with DLB. Comparisons with healthy controls revealed that the WM volume of the whole brain was preserved in patients with DLB. In contrast, a severe bilateral decrease in WM in the MTLs was detected in patients with AD. CONCLUSIONS: VBM-DARTEL provided more accurate results, and it enabled the identification of more localized morphologic alterations than did conventional VBM. Analysis of WM preservation in DLB could help to differentiate this condition from AD.

Study on transport of negative ion plasma using dc laser photodetachment method.

Transport of negative ion containing plasma was studied in a hydrogen plasma by injecting a semiconductor laser to make an electron density perturbation by photodetachment of negative ions. Change due to laser irradiation on electron saturation current to a Langmuir probe and that on electron current extracted through an orifice biased at the anode potential were measured phase sensitively by a lock-in-amplifier. The measured transport velocity of the negative ion containing plasma was about 1.4x10(5) cm/s for both cases. The photodetachment signal measured through the orifice had given a larger ratio of negative ion density to electron density. Change in transport of negative ion containing plasma around the Langmuir probe has been also investigated by detecting photodetachment signal onto electron current extracted through an orifice.

Ion beam oscillation due to fluctuation of a hot filament driven magnetized plasma.

Ion beam current extracted from a modified Bernas type ion source occasionally exhibits an oscillation at a frequency of several 100 kHz. Increase in the strength of a linear magnetic field induced to the ion source has either decreased or increased the frequency of this oscillation. The frequency showed an increase in proportion to the ion extraction voltage when the frequency decreased with increasing magnetic field. The change of extraction voltage did not affect the frequency when the frequency increased with the increasing magnetic field. Mechanisms causing these oscillations of an ion beam had been investigated.