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Past eccentric contraction (ECC)-induced muscle injury reduces the severity of symptoms of subsequent muscle injury; this phenomenon is known as a repeated bout effect (RBE). It has been reported that increases in the duration of the interval between the first and second bouts are linked to weakening of the RBE. However, the histology following the attenuation of the RBE remains unclear. We examined the sustained effects of the second bout with regard to myofiber permeability and muscle force. Sixty-four male rats were randomly assigned to eight groups that varied in the number of exercise sessions and the duration of the interval between the first and second bouts: the non-ECC (Control); the single-injury (Post 1st bout); groups that were allowed to recover for 1, 2, and 4 weeks after a single injury (Pre 2nd bout_1w, Pre 2nd bout_2w, and Pre 2nd bout_4w); and groups that were subjected to second injuries 1, 2, and 4 weeks after the first (Post 2nd bout_1w, Post 2nd bout_2w, and Post 2nd bout_4w). The tibialis anterior was electrically stimulated in each ECC group. Twenty-four hours before muscle sampling, Evans blue dye (EBD) (a marker of myofiber damage) was administered. The maximal isometric contraction tension was measured immediately before sampling. The number of EBD-positive (+) fibers was determined via histological analysis. An RBE was revealed by functional examination at the 1- and 2-week and histological examination at the 1-, 2-, and 4-week time points (P < 0.05). In terms of myofiber permeability, prolongation of the interval before the second bout weakened this effect (P < 0.05). Experiments with 1-, 2-, and 4-week intervals indicated that prolongation of the interval before the second bout weakened the RBE with regard to myofiber permeability.

BACKGROUND A low-volume polyethylene glycol (PEG) solution that combines ascorbic acid with PEG-based electrolyte solution (PEG-ASC) is gaining mainstream acceptance for bowel preparation due to reduced volume and improved taste. Although several reports showed that bowel preparation with PEG-ASC volume lower than 2.0 L with laxative agents could be an alternative to traditional preparation regimen, the cleansing protocols have not been fully investigated. AIM To evaluate the cleansing efficacy of 1.2 L PEG-ASC solution comparing with 2.0 L PEG electrolyte (PEG-ELS) for bowel preparations. METHODS A randomized, single-blinded, open-label, single-center, non-inferiority study was conducted. In total, 312 Japanese adult patients (aged > 18 years) who underwent colonoscopy were enrolled. Patients were randomly allocated to bowel lavage with either 1.2 L of PEG-ASC solution with at least 0.6 L of an additional clear fluid (1.2 L PEG-ASC group) or 2.0 L of PEG-ELS (PEG-ELS group). Then, 48 mg of sennoside was administered at bedtime on the day before colonoscopy, and the designated drug solution was administered at the hospital on the day of colonoscopy. Bowel cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS). The volume of fluid intake and required time for bowel preparation were evaluated. Furthermore, compliance, patient tolerance, and overall acceptability were evaluated using a patient questionnaire, which was assessed using a visual analog scale. RESULTS In total, 291 patients (1.2 L PEG-ASC group, 148; PEG-ELS group, 143) completed the study. There was no significant difference in successful cleansing, defined as a BBPS score ≥ 2 in each segment, between the two groups (1.2 L PEG-ASC group, 91.9%; PEG-ELS group, 90.2%; 95%CI: -0.03-0.09). The required time for bowel preparation was significantly shorter (164.95 min ± 68.95 min vs 202.16 min ± 68.69 min, P < 0.001) and the total fluid intake volume was significantly lower (2.23 L ± 0.55 L vs 2.47 L ± 0.56 L, P < 0.001) in the 1.2 L PEG-ASC group than in the PEG-ELS group. Palatability, acceptability of the volume of solution, and overall acceptability evaluated using a patient questionnaire, which was assessed by the visual analog scale, were significantly better in the 1.2 L PEG-ASC group than in the PEG-ELS group (7.70 cm ± 2.57 cm vs 5.80 cm ± 3.24 cm, P < 0.001). No severe adverse event was observed in each group. CONCLUSION The 1.2 L PEG-ASC solution was non-inferior to the 2.0 L PEG-ELS solution in terms of cleansing efficacy and had better acceptability among Japanese patients.

Electrical stimulation (ES)-induced muscle contraction has multiple effects; however, mechano-responsiveness of bone tissue declines with age. Here, we investigated whether daily low-frequency ES-induced muscle contraction treatment reduces muscle and bone loss and ameliorates bone fragility in early-stage disuse musculoskeletal atrophy in aged rats. Twenty-seven-month-old male rats were assigned to age-matched groups comprising the control (CON), sciatic nerve denervation (DN), or DN with direct low-frequency ES (DN+ES) groups. The structural and mechanical properties of the trabecular and cortical bone of the tibiae, and the morphological and functional properties of the tibialis anterior (TA) muscles were assessed one week after DN. ES-induced muscle contraction force mitigated denervation-induced muscle and trabecular bone loss and deterioration of the mechanical properties of the tibia mid-diaphysis, such as the stiffness, but not the maximal load, in aged rats. The TA muscle in the DN+ES group showed significant improvement in the myofiber cross-sectional area and muscle force relative to the DN group. These results suggest that low-frequency ES-induced muscle contraction treatment retards trabecular bone and muscle loss in aged rats in early-stage disuse musculoskeletal atrophy, and has beneficial effects on the functional properties of denervated skeletal muscle.

Objective The usefulness of contrast-enhanced ultrasonography (CEUS) for making decisions in the treatment of liver abscess is unknown. Methods We evaluated the internal blood flow in the arterial-predominant phase by CEUS using Sonazoid® in 21 patients. The stain area rate was evaluated in maximum parting plane of abscess in CEUS. Patients were divided into two groups: the vascular phase enhancement (VE) group, in which ≥50% of the abscess cavity was enhanced (12 patients), and the vascular phase non-enhancement (VNE) group, in which

Paired-pulse depression (PPD) has been widely used to investigate the functional profiles of somatosensory cortical inhibition. However, PPD induced by somatosensory stimulation is variable, and the reasons for between- and within-subject PPD variability remains unclear. Therefore, the purpose of this study was to clarify the factors influencing PPD variability induced by somatosensory stimulation. The study participants were 19 healthy volunteers. First, we investigated the relationship between the PPD ratio of each component (N20m, P35m, and P60m) of the somatosensory magnetic field, and the alpha, beta, and gamma band changes in power [event-related desynchronization (ERD) and event-related synchronization (ERS)] induced by median nerve stimulation. Second, because brain-derived neurotrophic factor (BDNF) gene polymorphisms reportedly influence the PPD ratio, we assessed whether BDNF genotype influences PPD ratio variability. Finally, we evaluated the test–retest reliability of PPD and the alpha, beta, and gamma ERD/ERS induced by somatosensory stimulation. Significant positive correlations were observed between the P60m_PPD ratio and beta power change, and the P60m_PPD ratio was significantly smaller for the beta ERD group than for the beta ERS group. P35m_PPD was found to be robust and highly reproducible; however, P60m_PPD reproducibility was poor. In addition, the ICC values for alpha, beta, and gamma ERD/ERS were 0.680, 0.760, and 0.552 respectively. These results suggest that the variability of PPD for the P60m deflection may be influenced by the ERD/ERS magnitude, which is induced by median nerve stimulation. Electronic supplementary material The online version of this article (10.1007/s10548-018-0648-5) contains supplementary material, which is available to authorized users.

The present study aimed to investigate the effects of changes in motor-evoked potential (MEP) amplitude on short-latency afferent inhibition (SAI) and short-interval intracortical inhibition (SICI). MEPs in response to transcranial magnetic stimulation (TMS) of the left primary motor cortex were measured from the right first dorsal interosseous muscle of 10 healthy participants. SAI was evaluated by measuring MEPs in response to variable-intensity test TMS pulses delivered 22 ms following electrical stimulation of the right ulnar nerve (intensity fixed at the motor threshold). SICI was evaluated by pairing a constant conditioning TMS pulse [80% of resting motor threshold (RMT)] with a second variable-intensity TMS test pulse (interstimulus interval of 2 ms). The intensity of the test stimulus was set at 110, 115, 120, 125, or 130%RMT on a given trial. SAI was significantly reduced when evoked by a 125%RMT test TMS pulse compared with 110%RMT, and absent at 130%RMT. There was no significant difference in SICI at 110-130%RMT. Significant positive correlations were detected between the unconditioned and conditioned MEP amplitudes at both SAI and SICI. This study demonstrated that SAI and SICI are highly sensitive to the MEP amplitude and SAI decreases with increasing MEP amplitude, whereas SICI does not change. The different responses for SAI and SICI to the increasing MEP amplitude is interpreted as evidence that different inhibitory neural circuits may be involved in SAI and SICI.

The enthesis transmits a physiological load from soft to hard tissue via fibrocartilage. The histological alterations induced by this physiological loading remain unclear. This study was performed to examine the histomorphological alterations in the collagen fiber bundle alignment and depth of collagen interdigitation between the calcified fibrocartilage and the bone. We examined the Achilles enthesis of rats with sciatic denervation to explore the mechanical effects of structural changes in the enthesis. The parallelism of the collagen fiber bundles was significantly reduced 8 weeks after denervation. However, the depth of collagen interdigitation significantly increased at 2 and 4 weeks after denervation and then significantly decreased 8 weeks after denervation. In conclusion, a lack of muscle loading induced structural alterations in the distal calcified fibrocartilage. These findings suggest that while structural changes in the enthesis are necessary for the development of physiological loading, structural deformities are required in the long term. Anat Rec, 300:2166-2174, 2017. © 2017 Wiley Periodicals, Inc.

[Purpose] Chondrocytes in articular cartilage are aligned as columns from the joint surface. Notably, loss of chondrocyte and abnormalities of differentiation factors give rise to osteoarthritis (OA). However, the relationship between chondrocyte alignment and OA progression remains unclear. This study was performed to investigate temporal alterations in surgically-induced OA rats. [Subjects and Methods] Thirteen-week-old Wistar rats (n=30) underwent destabilized medial meniscus surgery in their right knee and sham surgery in their left knee. Specimens (n=5) were collected at 0, 1, 2, 4 and 8 weeks after surgery. Histological analysis with Osteoarthritis Research Society International (OARSI) scores, cell density ratios, cell alignments and correlation between OARSI scores and cell density/alignment was performed. [Results] OARSI scores were significantly higher at 1, 2, 4 and 8 weeks in the DMM group than in the control. Cell density ratios were decreased significantly in the DMM group at 2, 4 and 8 weeks compared with the control. Chondrocyte alignment was decreased significantly in the DMM group at 4 and 8 weeks. There were negative correlations between OA severity and cell density / cell alignment. [Conclusion] The results suggest a relationship between chondrocyte alignment and cartilage homeostasis, which plays an important role in OA progression.

Objective: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. Methods: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. Results: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). Conclusion: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Magnetoencephalography is primarily sensitive to current sources tangential to the skull. Therefore, currents generated in area 3b of the primary somatosensory cortex (S1) and area 4 of primary motor cortex (M1) located on the posterior and anterior banks of the central sulcus, respectively, are easily detected. The movement-related cortical magnetic fields (MRCFs) following voluntary movement and the somatosensory magnetic fields (SEFs) generated by peripheral mixed nerve stimulation (e.g., median nerve) have been widely used to investigate the physiology of normal somatosensory cortical processing. Here, we describe the MRCFs produced by two types of movement (experiment 1) and the SEFs elicited by motor point stimulation (experiment 2), passive movement (experiments 3 and 4), and mechanical stimulation (experiments 5, 6, and 7). In addition, we examined the modulation of these fields.

Afferent somatosensory information is modulated before the afferent input arrives at the primary somatosensory cortex during voluntary movement. The aim of the present study was to clarify the effect of muscular contraction strength on somatosensory evoked fields (SEFs) during voluntary movement. In addition, we examined the differences in gating between innervated and non-innervated muscle during contraction. We investigated the changes in gating effect by muscular contraction strength and innervated and non-innervated muscles in human using 306-channel magnetoencephalography. SEFs were recorded following the right median nerve stimulation in a resting condition and during isometric muscular contractions from 10 % electromyographic activity (EMG), 20 and 30 % EMG of the right extensor indicis muscle and abductor pollicis brevis muscle. Our results showed that the equivalent current dipole (ECD) strength for P35m decreased with increasing strength of muscular contraction of the right abductor pollicis brevis muscle. However, changes were observed only at 30 % EMG contraction level of the right extensor indicis muscle, which was not innervated by the median nerve. There were no significant changes in the peak latencies and ECD locations of each component in all conditions. The ECD strength did not differ significantly for N20m and P60m regardless of the strength of muscular contraction and innervation. Therefore, we suggest that the gating of SEF waveforms following peripheral nerve stimulation was affected by the strength of muscular contraction and innervation of the contracting muscle.

Recent research has shown that the human motor cortex can be modulated by the application of static magnetic fields through the scalp. Transcranial static magnetic field stimulation (tSMS) has since received significant attention as a new non-invasive brain stimulation (NIBS) technique alongside conventional methods, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation. The advantages of the strong neodymium, iron and boron (NdFeB) magnet used in tSMS over other NIBS methods include the ease of use, absence of uncomfortable sensations for subjects, a lack of necessity for high operational skills and expensive devices, and conclusive sham stimulation allowing for controlled experiments and randomized controlled clinical trials. Hence, tSMS may be a new potential NIBS tool to modulate cerebral excitability.

Background In this study, we investigated the effects of short- and long-term exercise on motor functional recovery following intracerebral hemorrhage (ICH) in rats. Methods Male Wistar rats were randomly divided into 5 experimental groups: ICH without training (ICH group), ICH with long-term exercise for 14days from the second day after surgery (ICH + LT group), ICH with short-term exercise for 7days from the second day after surgery (ICH + EST group), ICH with short-term exercise for 7days from the ninth day after surgery (ICH + LST group), and sham operation without training (SHAM group). ICH was induced by collagenase injection into the left striatum. Forelimb sensorimotor function was evaluated using forelimb placing and horizontal ladder tests. Results In the behavioral test, the ICH + LT and ICH + EST groups improved significantly compared with the ICH and ICH + LT groups. The ICH + LT and ICH + EST groups recovered motor function in an almost analogous pattern. Conclusions Our results indicated that, when exercise was started from an early phase after ICH, both short- and long-term exercises had similar benefits on motor functional recovery. However, continuous training using simple treadmill running may have limitations to motor functional recovery.

We investigated the effects of different patterns of mechanical tactile stimulation (MS) on corticospinal excitability by measuring the motor-evoked potential (MEP). This was a single-blind study that included nineteen healthy subjects. MS was applied for 20 min to the right index finger. MS intervention was defined as simple, lateral, rubbing, vertical, or random. Simple intervention stimulated the entire finger pad at the same time. Lateral intervention stimulated with moving between left and right on the finger pad. Rubbing intervention stimulated with moving the stimulus probe, fixed by protrusion pins. Vertical intervention stimulated with moving in the forward and backward directions on the finger pad. Random intervention stimulated to finger pad with either row protrudes. MEPs were measured in the first dorsal interosseous muscle to transcranial magnetic stimulation of the left motor cortex before, immediately after, and 5–20 min after intervention. Following simple intervention, MEP amplitudes were significantly smaller than preintervention, indicating depression of corticospinal excitability. Following lateral, rubbing, and vertical intervention, MEP amplitudes were significantly larger than preintervention, indicating facilitation of corticospinal excitability. The modulation of corticospinal excitability depends on MS patterns. These results contribute to knowledge regarding the use of MS as a neurorehabilitation tool to neurological disorder.

Aerobic exercise produces changes in cerebral oxyhaemoglobin (O2Hb) concentration; however, the effects of exercise on O2Hb during the post-exercise period remain to be established. The aim of the present study was to evaluate O2Hb levels during and after a 20-min bout of moderate-intensity cycling exercise. After a 3-min rest period, 12 healthy volunteers (9 women, 3 men) cycled for 20 min at an intensity corresponding to 50% of their VO2max, after which they were monitored during a 15-min post-exercise rest period. O2Hb levels in the right (R-PFC) and left prefrontal cortices (L-PFC), right (R-PMA) and left premotor areas (L-PMA), supplementary motor area (SMA), and primary motor cortex (M1) were measured using near-infrared spectroscopy. A one-way repeated-measures analysis of variance (ANOVA) was performed to compare mean pre-exercise O2Hb levels with O2Hb levels during the last 5 min of exercise and the last 5 min of the post-exercise rest period. O2Hb levels increased significantly (p < 0.01) between the pre-exercise rest period and the last 5 min of the exercise session for each region of interest (range: 0.040–0.085 mM·cm). O2Hb levels did not return to pre-exercise values during the 15-min post-exercise rest period. O2Hb levels during the last 5 min of the post-exercise rest period were significantly higher than pre-exercise values in the L-PFC, L-PMA, SMA, and M1 (p < 0.01). Our results indicate that cortical oxygenation persists for at least 15 min following a 20-min bout of moderate-intensity cycling, and that aerobic exercise may facilitate neuroplasticity.

Improvement of forage nutritive value through breeding should lead to enhanced livestock productivity but often results in reduced agronomic performance. This study investigated the potential for simultaneous improvement of nutritive and agronomic traits in timothy (Phleum pratense L.). Two unrelated groups were used as the base populations: group A focused on agronomic traits and group N focused on three nutritive traits (low-digestible fiber, water-soluble carbohydrate content, and the ratio of low-digestible fiber to organic cell wall content). Although the two base populations contained few genotypes with both high nutritive and agronomic performance compared with the standard cultivar ‘Kiritappu’, the Cycle 1 populations selected for the traits simultaneously included promising genotypes. The two strains improved via two cycles of selection were superior to the Cycle 1 populations and ‘Kiritappu’ based on a comprehensive analysis of the targeted traits in a yield trial test. However, the nutritive traits of the strain derived from group A were more similar to the Cycle 1 population and ‘Kiritappu’ unlike in the successful case of group N. This may be attributable to the more similar phenotypic distribution of the strain A parental clones to ‘Kiritappu’ compared with that of group N for the nutritive traits. The strain derived from both groups showed high nutritive value with the best yield of all tested genotypes, suggesting the possibility of heterosis for yield. These results indicate that application of recurrent selection simultaneously for nutritive and agronomic traits is likely to provide effective improvement without detriment to important traits.

The aim of this study was to investigate the effects of cathodal transcranial direct current stimulation (tDCS) applied over the primary somatosensory cortex (S1) on short-interval afferent inhibition (SAI). Thirteen healthy individuals participated in this study. Cathodal tDCS was applied for 15 min at 1 mA over the left S1. Motor-evoked potentials (MEPs) were measured from the right first dorsal interosseous muscle in response to transcranial magnetic stimulation (TMS) of the left motor cortex before tDCS (pre), immediately after tDCS (immediately), and 15 min after tDCS (post-15 min). SAI was evaluated by measuring MEPs in response to TMS pulses applied 40 ms after peripheral electrical stimulation of the index finger. For each measurement period (pre, immediately, and post-15 min), MEP amplitude was significantly smaller when TMS followed index finger stimulation (SAI condition) than when TMS was delivered alone (single TMS) (P

Summary Purpose This study aimed to examine the effects of exercise training under mild hypoxic conditions on body composition and circulating adiponectin levels in postmenopausal women. Methods Fourteen postmenopausal women (56 ± 1 years) were assigned to a normoxic (N group) or hypoxic (H group) exercise group. Aquatic exercise training was performed at an intensity of 50% peak oxygen uptake level for 30 min per training session, 4 days per week, for 8 weeks. The H group performed the exercise under hypobaric hypoxic conditions, which corresponds to 2000 m above sea level, and each participant was exposed to these conditions for 2 h per session. Results After the training, no significant changes were observed in any of the measured values for the N group. Conversely, body mass (57·3 ± 2·5 to 54·5 ± 2·3 kg), body mass index (24·6 ± 0·8 to 23·4 ± 0·7 kg m−2), body fat (30·7 ± 1·9 to 28·1 ± 1·6%) and preperitoneal fat thickness as an index of visceral fat accumulation (10·3 ± 1·7 to 6·4 ± 1·0 mm) significantly reduced only in the H group. Circulating adiponectin levels significantly increased (9·5 ± 1·8 to 11·4 ± 2·0 μg ml−1), and the changes in adiponectin were significantly correlated with those in body mass (r = −0·81) and body mass index (r = −0·85). Conclusions These results suggest that exercise training under mild hypoxic conditions could more effectively reduce body fat and increase adiponectin levels in postmenopausal women in a shorter period, than exercise training in normoxia.

Purpose: We report the efficacy of percutaneous ultrasound (US) examination using a novel real-time virtual sonography (RVS) method that collates multiple Digital Imaging and Communications in Medicine (DICOM) data sources and displays reference images in color. Materials and Methods: A total of 7 patients with 9 hepatocellular carcinomas were evaluated. Using the SYNAPSE VINCENT volume analyzer, DICOM data of the portal vein, hepatic vein, tumor, and hepatic segment were isolated from contrast-enhanced computed tomography DICOM data. Each portion of DICOM data was uploaded into an US scanner (HI VISION Ascendus, Hitachi Aloka Medical Ltd., Tokyo, Japan) and unified on a US platform to create a single reference image. Each uploaded portion of DICOM data was assigned a different color. Further, conventional RVS was performed using this information. Results: The maximal tumoral diameter ranged from 6.4 to 15 mm (mean ± SD, 11.0 ± 2.8). DICOM data could be isolated, enabling the display of color RVS in all patients. Color RVS facilitated superior visibility compared with conventional grayscale RVS and facilitated the comprehension of spatial positioning. Conclusion: RVS with color display demonstrates utility in increasing operator comprehension of spatial and positional relationships during percutaneous US examination.

The authors have considered introducing a molecular breeding technique called ‘genomewide selection (GwS)’ to effectively improve the yield of maize for whole-crop silage use. The GwS for this purpose requires training populations (TPs) where individual plants having been developed from three-way crosses are examined in their phenotypes as well as in molecular-marker genotypes. The purpose of this study was to evaluate the (broad-sense) heritability of maturityand yield-related traits in such TPs, because a former simulation study by the authors showed that the heritability should exceed 25% for the success of the GwS. Five preliminary TPs were grown to estimate the heritability of silking date, ear dry weight and culm length from 2011 to 2013 on two planting density levels, the higher of which was for productivity testing and the lower for accurate individual phenotyping. The results indicated that heritability exceeded 25% in all cases, and that the higher planting density did not result in lower heritability. Accordingly, it was concluded that the maize GwS to improve yield is sufficiently feasible in terms of maintaining high heritability in the TPs, and that planting density for TPs should be that for productivity testing because it is known to have remarkable interaction on yield with genotypes. Discipline: Plant breeding Additional key words: best linear unbiased prediction (BLUP), culm length, inbred line, planting density, silking date * Corresponding author: e-mail htamaki@affrc.go.jp Received 10 March 2014; accepted 12 September 2014. Introduction There are concerns in Japan over the difficulties in ensuring long-term food supply, which has prompted the Japanese government to promote a policy to boost food self-sufficiency. A primary measure for this goal is to raise the feed self-sufficiency rate from 26 (in 2011) to 38% (MAFF 2011). The Japanese public sectors, to which the authors belong, are now expected to support this policy by breeding high-yield maize (Zea mays L.) varieties for whole-crop silage use highly adapted to Japanese climates. As the cost of molecular genotyping has rapidly declined in recent years (e.g. Yan et al. 2010), it has become feasible for maize breeding teams in the Japanese public sectors to adopt certain molecular breeding techniques, where markers should be arranged over the whole genome (Tamaki et al. 2012). ‘Genomewide selection (GwS)’ is one such technique, the details and concept of which are explained in Meuwissen et al. (2001) and Bernardo & Yu (2007). The focus of GwS is on accumulating favorable genes in many minor quantitative trait loci (QTLs) whereby the yield is deemed controlled (Yu & Buckler 2006), and can be started from a biparental population, i.e. with molecular-marker information on a small number of inbred lines (hereinafter referred to as inbreds). Accordingly, the authors considered introducing GwS to effectively improve yield because maize breeding teams of the Japanese public sectors have accumulated less molecular-marker information on their materials. The purpose of this study was to evaluate heritability (in the broad sense, hereafter the same) of maturityand yield-related traits (on a whole-crop basis) in training populations (TPs) for GwS. For decades, the maize breeding teams of the Japanese public sectors have adopted programs

Transcranial static magnetic field stimulation (tSMS) is a novel and inexpensive, non-invasive brain stimulation (NIBS) technique. Here, we performed non-invasive modulation of intra-epidermal electrical stimulation-evoked potentials (IES-EPs) by applying tSMS or sham stimulation over the primary motor (M1) and somatosensory (S1) cortices in 18 healthy volunteers for 15 min. We recorded EPs after IES before, right after, and 10 min after tSMS. The IES-EP amplitude was significantly reduced immediately after tSMS over M1, whereas tSMS over S1 and sham stimulation did not affect the IES-EP amplitude. Thus, tSMS may affect cortical nociceptive processing. Although the results of intervention for experimental acute pain in healthy subjects cannot be directly translated into the clinical situation, tSMS may be a potentially useful NIBS method for managing chronic pain, in addition to standard of care treatments.

Background & Aims We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 ( P Conclusions In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

Background We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). Methods Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. Results Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. Conclusions These changes may play a critical role in motor skills training-induced recovery after ICH.

Near-infrared spectroscopy (NIRS) can measure cortical activity during gross motor tasks based on the cerebral hemodynamic response. Although some reports suggest that cycling exercise improves cortical oxygenation, its after-effects are unknown. We examined the after-effects of low- and moderate-intensity cycling exercise on cortical oxygenation. Ten healthy volunteers (mean age 21.3 ± 0.7 years; 4 women) underwent cycle ergometer exercise at 30% or 50% of VO2peak for 20 min, followed by an 8-min post-exercise rest (PER). O2Hb levels of the supplementary motor area (SMA) and sensorimotor cortex (SMC) were recorded using a near-infrared spectroscopy system. Skin blood flow (SBF) and mean arterial pressure (MAP) were continuously measured. The peak values of O2Hb between exercise and PER were compared. The O2Hb, SBF, and MAP increased in the exercise phase. SBF degraded over time, and MAP decreased immediately after exercise. The O2Hb decreased immediately and increased again in the PER. There were no significant differences between exercise and PER in the SMC in the 30% VO2peak experiment or in the SMA and SMC in the 50% VO2peak experiment. The O2Hb in the motor-related area was elevated during both exercise and PER especially in the 50% VO2peak experiment.

The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES) on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP) immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON), denervation (DN), and denervation with direct ES (DN + ES). Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA), and capillary-to-fiber (C/F) ratio of the tibialis anterior (TA) muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs.

The present study examined the effects of intermittent hypobaric hypoxic exercise over a period of four weeks on cardiovascular adaptations. Twenty-four healthy male adults (age, 24 ± 3 yrs) who were matched for physical fitness levels were randomized into two groups, and was adjusted to be either normobaric normoxic (N; n = 12) or hypobaric hypoxic (H; n = 12). Both groups performed aquatic activities at an intensity of about 50% VO_2max for 30min/session, four days per week for four weeks in a pool within a chamber where the atmospheric pressure can be regulated. The H group exercised under hypobaric conditions corresponding to 2,000m above sea level, and were exposed for a total of 2.5h/session. Before and after experimental period, VO_2max and cardiovascular responses such as heart rate (HR), stroke volume (SV), cardiac output (CO), as well as systolic (SBP), diastolic (DBP), and mean blood pressure (MBP) were measured during cycling on an ergometer at an intensity of 50% VO_2max. Flowmediated vasodilation (FMD) was also evaluated by measuring changes in the diameter of the popliteal artery between rest and during reactive hyperemia. The VO_2max was not significantly changed after the four-week exercise period in both groups and changes in cardiovascular responses during moderate exercise were not evident in the N group. On the other hand, SV and CO were significantly increased (P＜0.05) in the H group, whereas DBP and MBP as well as the calculated TPR (MBP/CO) were significantly decreased (P＜0.05 for all). The FMD was significantly increased only in the H group (P＜0.05). These findings indicated that exercise under hypobaric hypoxic conditions could induce more beneficial cardiovascular adaptations in healthy male adults such as reductions in TPR and BP with an increase in FMD compared with exercise under normal conditions.

We tested whether daily muscle electrical stimulation (ES) can ameliorate the decrease in cortical bone strength as well as muscle and bone geometric and material properties in the early stages of disuse musculoskeletal atrophy. 7-week-old male F344 rats were randomly divided into three groups: age-matched control group (Cont); a sciatic denervation group (DN); and a DN + direct electrical stimulation group (DN + ES). Denervated tibialis anterior (TA) muscle in the DN + ES group received ES with 16 mA at 10 Hz for 30 min/day, 6 days/week. Micro CT, the three-point bending test, and immunohistochemistry were used to characterize cortical bone mechanical, structural, and material properties of tibiae. TA muscle in the DN + ES group showed significant improvement in muscle mass and myofiber cross-sectional area relative to the DN group. Maximal load and stiffness of tibiae, bone mineral density estimated by micro CT, and immunoreactivity of DMP1 in the cortical bone tissue were also significantly greater in the DN + ES group than in the DN group. These results suggest that daily ES-induced muscle contraction treatment reduced the decrease in muscle mass and cortical bone strength in early-stage disuse musculoskeletal atrophy and is associated with a beneficial effect on material properties such as mineralization of cortical bone tissue.

Purpose: Transcatheter arterial chemoembolization (TACE) is one of the most effective therapeutic options for hepatocellular carcinoma (HCC) and it is important to protect residual liver function after treatment as well as the effect. To reduce the liver function deterioration, we evaluated the automatic software to predict the embolization area of TACE in 3 dimensions. Materials and Methods: Automatic prediction software of embolization area was used in chemoembolization of 7 HCCs. Embolization area of chemoembolization was evaluated within 1 week CT findings after TACE and compared simulated area using automatic prediction software. Results: The maximal diameter of these tumors is in the range 12-42 mm (24.6 ± 9.5 mm). The average time for detecting tumor-feeding branches was 242 s. The total time to detect tumor-feeding branches and simulate the embolization area was 384 s. All cases could detect all tumor-feeding branches of HCC, and the expected embolization area of simulation with automatic prediction software was almost the same as the actual areas, as shown by CT after TACE. Conclusion: This new technology has possibilities to reduce the amount of contrast medium used, protect kidney function, decrease radiation exposure, and improve the therapeutic effect of TACE.

The efficacy of ERCP for histologic diagnosis of malignant biliary strictures is disappointingly low. The aim of this study was to investigate the diagnostic performance of a newly developed endoscopic device with scraping loops in combination with conventional biopsy forceps.We performed a multicenter single-arm prospective study. Between February 2013 and December 2014, 123 patients with suspected malignant biliary strictures were enrolled in the study. The new device and conventional biopsy forceps were applied for histologic diagnosis by ERCP. The primary outcome was to evaluate cancer detectability by biopsy forceps, the new device, and their combined use.Of the 123 patients, 119 were diagnosed with a malignant stricture. Sufficient samples were collected in 83.7% (103/123), 93.5% (115/123), and 95.9% (118/123) of patients using biopsy forceps, the new device, and their combination, respectively. Cancer detectability of forceps biopsy, the new device, and their combination were 51.3% (61/119), 64.7% (77/119), and 74.8% (89/119), respectively. The new device had a significantly higher sample yield and cancer detectability than biopsy forceps (P .01 and P = .018, respectively, McNemar test). Complementary use of the new device with biopsy forceps demonstrated a significantly additive effect in both sample yield and cancer detection (P .01 each, McNemar test). The new device detected 48.3% (28/58) of cancers that were not diagnosed as malignant by biopsy forceps.The new endoscopic scraper demonstrated a large sample yield and high cancer detectability. It could be a first-line tissue-sampling device for biliary strictures. (University Hospital Medical Information Network Clinical Trial Registry [UMIN-CTR] (http://www.umin.ac.jp/ctr/index.htm) registration number: UMIN000009895.).

We conducted two experiments to determine how differences in muscle contraction levels, muscle contraction types, and movement duration affect degree of post-exercise depression (PED) after non-exhaustive, repetitive finger movement. Twelve healthy participants performed repetitive abduction movements of the right index finger at 2.0 Hz. In experiment 1, we examined the effects of muscle contraction levels at 10%, 20%, and 30% maximum voluntary contraction and the effects of muscle contraction types at isotonic and isometric contraction. In experiment 2, we examined the effects of movement duration at 2.0 and 6.0 min. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle before movement tasks and 1–10 min after movement tasks. MEP amplitudes after isotonic contraction tasks were significantly smaller than those after isometric contraction tasks and decreased with increasing contraction levels, but were independent of movement duration. This study demonstrated that the degree of PED after non-exhaustive repetitive finger movement depended on muscle contraction levels and types. Thus, the degree of PED may depend on the levels of activity in the motor cortex during a movement task. This knowledge will aid in the design of rehabilitation protocols.

Near-infrared spectroscopy (NIRS) is a widely used noninvasive method for measuring human brain activation based on the cerebral haemodynamic response. However, systemic changes can influence the signal’s parameters. Our study aimed to investigate the relationships between NIRS signals and skin blood flow (SBF) or blood pressure during dynamic movement. Nine healthy volunteers (mean age, 21.3 ± 0.7 years; 6 women) participated in this study. The oxyhaemoglobin (O2Hb) signal, SBF, and mean arterial pressure (MAP) were measured while the volunteers performed multi-step incremental exercise on a bicycle ergometer, at workloads corresponding to 30, 50, and 70 % of peak oxygen consumption (VO2peak) for 5 min. The Pearson’s correlation coefficients for the O2Hb signal and SBF at 50 and 70 % VO2peak were 0.877 (P < 0.01) and −0.707 (P < 0.01), respectively. The correlation coefficients for O2Hb and MAP during warm-up, 30 % VO2peak, and 50 % VO2peak were 0.725 (P < 0.01), 0.472 (P < 0.01), and 0.939 (P < 0.01), respectively. Changes in the state of the cardiovascular system influenced O2Hb signals positively during low and moderate-intensity exercise, whereas a negative relationship was observed during high-intensity exercise. These results suggest that the relationship between the O2Hb signal and systemic changes is affected by exercise intensity.

Near-infrared spectroscopy (NIRS) is a widely used non-invasive method for measuring human brain activation based on the cerebral hemodynamic response during gross motor tasks. However, systemic changes can influence measured NIRS signals. We aimed to determine and compare time-dependent changes in NIRS signal, skin blood flow (SBF), and mean arterial pressure (MAP) during low-intensity, constant, dynamic exercise. Nine healthy volunteers (22.1 ± 1.7 years, 3 women) participated in this study. After a 4-min pre-exercise rest and a 4-min warm-up, they exercised on a bicycle ergometer at workloads corresponding to 30 % VO2 peak for 20 min. An 8-min rest period followed the exercise. Cortical oxyhaemoglobin signals (O2Hb) were recorded while subjects performed the exercise, using an NIRS system. Changes in SBF and MAP were also measured during exercise. O2Hb increased to 0.019 mM cm over 6 min of exercise, decreased slightly from 13 min towards the end of the exercise. SBF continued to increase over 16 min of the exercise period and thereafter decreased till the end of measurement. MAP fluctuated from −1.0 to 7.1 mmHg during the exercise. Pearson’s correlation coefficients between SBF and O2Hb, and MAP and O2Hb differed in each time phase, from −0.365 to 0.713. During low-intensity, constant, dynamic exercise, the profile of changes in measurements of O2Hb, SBF, and MAP differed. These results suggested that it is necessary to confirm the relationship between O2Hb and systemic factors during motor tasks in order to detect cortical activation during gross motor tasks.

Reciprocal inhibition of antagonist muscles is crucial for motor skill learning in humans. However, the changes in reciprocal inhibition function during the motor learning process are unknown. The aim of this study was to systematically observe the changes in reciprocal inhibition function. We investigated the optimal coil position for simultaneously eliciting motor evoked potentials (MEPs) of reciprocal muscles, and the reciprocal changes in input-output (IO) curves during motor skill training. From ten healthy volunteers, the IO curves of MEPs were measured for the midpoint between the center of gravity (CoG) of the extensor carpi radialis (ECR) and the flexor carpi radialis (FCR) muscles, for the CoG of ECR, and for the FCR muscles using transcranial magnetic stimulation (TMS). In addition, the IO curves of the ECR and the FCR muscles were measured before and after the motor skill training of rapid wrist extension. The IO curves measured at the midpoint between the CoGs of the ECR and the FCR muscles and the CoG of each muscle were homogenous. However, after training to perform rapid wrist extension, the IO curve of the agonist (ECR) muscle was increased, while the antagonist (FCR) muscle was decreased. The present findings validate the IO curves simultaneously measured for reciprocal muscles, and suggest that motor skill training could induce reciprocal change in corticospinal excitability.

Japanese public sectors are now expected to breed high-yielding silage maize varieties highly adapted to the Japanese climates in order to support the governmental policy to raise the feed self-sufficiency ratio from 26% (in 2008) to 38% by 2020. ‘Genomewide selection (GwS)’ is a technique to substitute a part of phenotyping with molecular marker genotyping, and is thought to be suitable to accumulate favorable genes in many minor quantitative trait loci (QTLs) whereby yield is thought to be controlled. The purpose of this study was to use computer simulations to evaluate the potential of GwS from the viewpoint of maize breeding sections of Japanese public sectors interested in rapider yield improvement through selection at early breeding stages. It was assumed in each repeat of the simulation experiments that eight S1 (first selfing generation) candidates were selected from 1000 solely on their molecular marker information obtained from testcross investigation with GwS. The experiments indicated that (i) shorter intervals of molecular marker loci led to moderately larger selection response (SR) when the intervals were more than 20 cM, but not when they were less than 20 cM, (ii) higher heritability unexceptionally led to larger SR, and (iii) larger training population size led to slightly larger SR in most cases. The results suggest that it is important for the success of GwS to obtain high heritability in the field for testcross investigation, and that GwS will be a powerful tool for maize breeding sections of Japanese public sectors targeting rapider yield improvement.

In the present study, we aimed to determine whether response training shortens visuo-motor related time in athletes performing a simple reaction task. 14 healthy male athletes were included in the study. Subjects were randomly divided into 2 groups: a training group, which underwent response training consisting of a mastication task in response to a visual signal, and a non-training (control) group, which did not undergo response training. Pre-motor time and transcranial magnetic stimulation over the primary motor cortex for recording motor evoked potentials were measured in the control group, and before and after the response training session in the training group. Both pre-motor time and visuo-motor related time, but not motor evoked potential latency, were significantly reduced after response training in the training group. Subjects who had a longer visuo-motor related time before training showed a greater reduction in visuo-motor related time after training. These results suggest that visuo-motor related time before training could be useful as a predictor of the reduction in reaction time following response training.

Improvement of the nutritive value of timothy (Phleum pratense L.) through breeding should result in enhanced livestock productivity. This study investigated the extent of genotype × crop interaction (G × C) between the first and second crops, and the extent of genotype × year interaction (G × Y) and narrow-sense heritability (hN2) of the second crop of the nutritive value of timothy. Twenty-six clones were used to evaluate these interactions in 2007 and 2008, and 17 clones and their half-sib progeny were used to evaluate the hN2 in 2010 in Kunneppu, Japan by analyzing their nutritive value. The content of water-soluble carbohydrate (WSC) was significantly correlated between the two crops in 12 clones with many internode elongation stems (IES) in the second crop and the 2 years, with non-significant effects of G × C in these clones and G × Y. However, the low-digestible fiber (Ob) content and the ratio of Ob to organic cell wall showed weak to medium correlations between the two crops, regardless of IES ratio or the elapsed time of 2 years, with significant effects shown for the two interactions. The hN2 of the three traits was medium to high. These results suggest that, in the second crop, selections for WSC content through the first crop in genotypes with many IES in the second crop, and under multiple environments in other traits are potentially useful; and that recurrent selection which utilizes an additive genetic variance is likely to be effective for the three traits.

The objective of this study was to examine the effects of exercise training in hypoxia on arterial stiffness and flow-mediated vasodilation (FMD) in postmenopausal women. Sixteen postmenopausal women (56 ± 1 years) were assigned to a normoxic exercise group (Normoxic group, n = 8) or a hypoxic exercise group (Hypoxic group, n = 8). The Hypoxic group performed exercise under hypobaric hypoxic conditions corresponding to 2000 m above sea level, and was exposed to these conditions for 2 h per session. Aquatic exercise was performed at an intensity of around 50% peak oxygen uptake for 30 min, 4 days per week, for 8 weeks. Arterial stiffness was assessed by brachial–ankle pulse wave velocity (baPWV), and FMD was evaluated by peak diameter of the popliteal artery during reactive hyperemia. After the 8 weeks of training, the Normoxic group showed no significant changes. In contrast, baPWV (P < 0.05) was significantly reduced and peak diameter (P < 0.05) and %FMD (P < 0.01) were significantly increased in the Hypoxic group after training. These results suggest that exercise training under mild intermittent hypoxic conditions could more effectively reduce arterial stiffness in postmenopausal women, compared with exercise training performed at the same relative intensity under normoxic conditions. Our data also indicate that hypoxic exercise training may induce vascular functional adaptation, for example an increase in FMD response. These findings therefore could have important implications for the development of a new effective exercise prescription program.

Timothy (Phleum pratense L.) is the most important perennial forage grass grown in parts of Canada, USA, the Nordic countries of Europe and Hokkaido, Japan. Improvement of its nutritive value through breeding should result in enhanced livestock productivity. The objective of the present study was to investigate the magnitude of genotype × maturity stage interaction (G × M), genotype × harvest time on sunny day interaction (G × TS) and genotype × harvest time on cloudy day interaction (G × TC) for the nutritive value of the first crop of timothy. Fifteen early-maturing clones of timothy were used to evaluate G × M and 13 clones were used to evaluate G × TS and TC in Kunneppu, Hokkaido in 2005 by analyzing the nutritive value of the first crops using near-infrared reflectance spectroscopy. Contents of low-digestible fiber (Ob) and water-soluble carbohydrate and the ratio of Ob to organic cell wall measured at early heading significantly correlated with their measurements at full heading stage, with non-significant effects of G × M. These traits also showed a significant correlation between morning and evening in both sunny and cloudy weather conditions, with non-significant effects of G × TS and TC. We conclude that the relative ranking of genotypes at different maturity stages from early to full heading stage and at different times within a day should be consistent for the required traits, and that selection for these traits at any stage of heading and any time of day should permit effective improvement of the nutritive value of timothy only if the plants are harvested at about the same time (within 1 h).

Recent evidence indicates that intravenous or oral therapy with tacrolimus (FK-506) is effective in treating patients with Crohn's disease. We evaluated the usefulness of tacrolimus therapy for Japanese patients with refractory Crohn's disease.Fourteen adult Japanese patients with Crohn's disease that was refractory to conventional therapies, including prednisolone (n = 5), azathioprine (n = 6), and infliximab (n = 5), were enrolled. Treatment with tacrolimus was started orally or intravenously and aimed for serum trough levels of 10-15 ng/ml. After the patients achieved clinical improvement, tacrolimus maintenance therapy was administered to maintain the trough level at 5-10 ng/ml.All patients achieved remission or significant improvement 40 days after starting tacrolimus treatment. By 120 days after the start of therapy, 9 (64%) patients achieved remission, 2 patients (14%) achieved significant improvement, and only 3 patients (21%) relapsed. The relapsed patients were treated with infliximab therapy and achieved remission. Steroids were discontinued by the 5 patients who had taken steroids before the study began. Adverse effects of tacrolimus included a temporary increase in serum creatinine concentration (n = 1, 7%), hyperkalemia (n = 1, 7%), and tremor (n = 1, 7%).Tacrolimus therapy is effective and well tolerated in patients with Crohn's disease that is refractory to conventional therapies.

Background Fistulas are a major complication of Crohn's disease (CD), but the treatment strategy for fistulizing Crohn's disease is controversial. The aim of this study is to analyze the efficacy of medical therapy for fistulizing Crohn's disease. Methods Therapeutic regimens and clinical outcome of medical therapy were evaluated in 10 patients with fistulizing Crohn's disease (6 with external fistulas, 4 with internal fistulas). Complete response was defined as fistula closure with complete arrest of drainage in cases of external fistula, and disappearance of the fistula demonstrated by imaging studies in cases of internal fistula. Clinical remission was defined as a Crohn's disease activity index of less than 150 points. Results Complete responses were observed in all 6 patients with external fistulas (4 patients treated with a combination of antibiotics and immunomodulators, and 2 also treated with infliximab). In contrast, fistula closure was observed in only 1 of 4 patients with internal fistulas. Clinical remission of CD was achieved in all patients with external fistulas, whereas there was no significant difference in the CD activity index before and after medical therapy in patients with internal fistulas. Conclusions External fistulas were more responsive to medical therapy than internal fistulas in patients with CD. Combined treatment with antibiotics and immunomodulators might be a suitable initial therapy for CD patients with external fistulas, and infliximab can be used as an additional therapy in cases refractory to this combination therapy. However, randomized controlled studies will be required to investigate what kinds of therapies are optimal for CD patients with fistulas.

A newly developed titanium alloy, Ti-15%Zr-4%Nb-4%Ta (Ti15Zr4Nb4Ta), has been shown to have excellent mechanical characteristics, corrosion fatigue strength, anticorrosion, cytocompatibility, and biocompatibility. The purpose of this study was to compare the bone mineral density (BMD) and area of newly formed bone around Ti15Zr4Nb4Ta implants to that around Ti-6%Al-4%V alloy (Ti6Al4V) implants. We inserted 2 types of implants (surface treat of the machine and the blast implant) in New Zealand white rabbit femurs under general anesthesia. The rabbit was done perfusion fixation of 4, 8, 16, 24, and 48 weeks later, and the femurs with the implants were collected and we observed the surrounding bone by an implant drawing test. We measured the BMD and the area of the newly formed bone surrounding the implant inserted part using image analysis software Image-Pro PLUS Ver. 4.0 ® which it developed newly in micro focus computed tomography (micro CT). The results showed the machine and the blast implant together, which the BMD and area around the Ti15Zr4Nb4Ta implants were comparable to or greater than those around the Ti6Al4V implants. These results suggested that the new alloy, Ti15Zr4Nb4Ta, might be useful for orthopedic or dental implants with the added advantage of superior biologic safety and mechanical properties than the current alloy, Ti6Al4V.

The aim of this study is to investigate the influence of passive movement repetition frequency at 1.5-Hz and 1-Hz on changes in cerebral oxygenation and assess the temporal properties of these changes using functional near-infrared spectroscopy (fNIRS). No significant differences in systemic hemodynamics were observed between resting and passive movement phases for either 1.5-Hz or 1-Hz trial. Changes in cortical oxygenation as measured by fNIRS in bilateral supplementary motor cortex (SMC), left primary motor cortex (M1), left primary somatosensory cortex (S1), and left posterior association area (PAA) during passive movement of the right index finger revealed greater cortical activity at only 1.5-Hz movement frequency. However, there were no significant differences in the time for peak oxyhemoglobin (oxyHb) among regions (bilateral SMC, 206.4 ± 14.4 s; left M1, 199.1 ± 14.8 s; left S1, 207.3 ± 9.4 s; left PAA, 219.1 ± 10.2 s). Therefore, our results that passive movement above a specific frequency may be required to elicit a changed in cerebral oxygenation, and the times of peak ΔoxyHb did not differ significantly among measured regions.

Background and Aim We conducted a randomized, double-blinded, placebo-controlled trial to investigate the efficacy of Bifidobacterium longum 536 (BB536) supplementation for induction of remission in Japanese patients with active ulcerative colitis (UC). Methods Fifty-six patients with mild to moderate UC were enrolled. Three patients had pancolitis, 36 had left-sided colitis, and 17 had proctitis. Patients were randomly treated with 2–3 × 1011 freeze-dried viable BB536 (28 patients) or placebo (28 patients) for 8 weeks. Results In total, 63% of patients receiving BB536 showed clinical remission (UC disease activity index [UCDAI] ≤2) at week 8 compared to 52% of those receiving placebo (P = 0.395). We observed a significant decrease of UCDAI scores (3.8 ± 0.4 at baseline to 2.6 ± 0.4 at week 8) in the BB536 group (P

Background & Aims: Thioredoxin-1 (TRX) is a small multifunctional protein with antioxidative and redox-regulating functions. In this study, we investigated the significance of TRX in patients with inflammatory bowel disease (IBD) and the ability and mechanism to ameliorate experimental colitis. Methods: Serum TRX and macrophage migration inhibitory factor (MIF) levels were measured in patients with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)-induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and control mice. We further evaluated the effect of recombinant human TRX (rhTRX) administration on DSS-induced colitis and colonic inflammation of interleukin (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically and histologically. Proinflammatory cytokine levels were examined in colonic tissues, and MIF levels were measured in colonic tissues and sera in mice. The effect of TRX on MIF production was also analyzed in vitro. Results: Serum TRX and MIF levels were significantly higher in patients with IBD than normal controls, and TRX levels correlated with disease activity. TRX significantly ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice. Increase of tumor necrosis factor-α and interferon-γ in colonic tissues was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF levels in colonic tissues and sera were significantly lower in TRX-TG mice than in wild-type mice, irrespective of DSS administration. Anti-TRX treatment exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX suppressed MIF production in human monocyte cells. Conclusions: TRX might have a potential as a novel therapeutic agent for the treatment of IBD.

Objectives: Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients. Methods: We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies. Results: We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies. Conclusions: These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of κB-α, thereby suppressing proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.