Pulse pressure modifies the association between diastolic blood pressure and decrease in kidney function: the Japan Specific Health Checkups Study.

Background: Unlike systolic blood pressure (SBP), the prognostic value of diastolic blood pressure (DBP) in kidney function has not been established. We hypothesized that pulse pressure (PP), which is associated with arteriosclerosis, would affect the prognostic value of DBP. Methods: This longitudinal study used data from the Japan Specific Health Checkups Study was conducted between 2008 and 2014. The participants were stratified into three PP subgroups (low PP ≤39, normal PP 40-59 and high PP ≥60 mmHg). The exposures of interest were SBP and DBP, and the association between SBP/DBP and kidney outcomes (30% decline in the estimated glomerular filtration rate from baseline) was examined in each PP subgroup using a Cox proportional hazards model. Results: Among 725 022 participants, 20 414 (2.8%) developed kidney outcomes during a median follow-up period of 34.6 months. Higher SBP was consistently associated with a higher incidence of kidney outcome in all PP subgroups. Although DBP had a positive linear association with the incidence of kidney outcome in low- and normal-PP subgroups, both lower (≤60 mmHg) and higher (≥101 mmHg) DBP were associated with a higher incidence of kidney outcome in the high-PP subgroup, with a U-shaped curve. Hazard ratios (95% confidence intervals) of ≤60 mmHg (reference: 61-80 mmHg in normal-PP subgroup) and ≥101 mmHg were 1.26 (1.15-1.38) and 1.86 (1.62-2.14), respectively. Conclusions: In this large population-based cohort, DBP was differently associated with kidney outcome by PP level; lower DBP was significantly associated with a higher incidence of kidney outcome in the high-PP subgroup but not in the low- and normal-PP subgroups.

Role of kicking action in front crawl: the inter-relationships between swimming velocity, hand propulsive force and trunk inclination.

This study aimed to investigate the essential role of the kicking action in front crawl. To achieve this objective, we examined the relationships of the hand propulsive force and trunk inclination with swimming velocity over a wide range of velocities from 0.75 m·s-1 to maximum effort, including the experimental conditions of arm stroke without a pull buoy. Seven male swimmers performed a 25 m front crawl at various speeds under three swimming conditions: arm stroke with a pull buoy, arm stroke without a pull buoy (AWOB) and arm stroke with a six-beat kick (SWIM). Swimming velocity, hand propulsive force and trunk inclination were calculated using an underwater motion-capture system and pressure sensors. Most notably, AWOB consistently exhibited greater values than SWIM for hand propulsive force across the range of observed velocities (p < 0.05) and for trunk inclination below the severe velocity (p < 0.05), and these differences increased with decreasing velocity. These results indicate that 1) the kicking action in front crawl has a positive effect on reducing the pressure drag acting on the trunk, thereby allowing swimmers to achieve a given velocity with less hand propulsive force, and 2) this phenomenon is significant in low-velocity ranges.

Utility of serum ß2-microglobulin for prediction of kidney outcome among patients with biopsy-proven diabetic nephropathy.

AIM: To examine whether serum ß2-microglobulin (ß2-MG) could improve the prediction performance for kidney failure with replacement therapy (KFRT) among patients with diabetic nephropathy (DN). METHODS: Patients with biopsy-proven DN at Nara Medical University Hospital were included. The exposure of interest was log-transformed serum ß2-MG levels measured at kidney biopsy. The outcome variable was KFRT. Multivariable Cox regression models and competing-risk regression models, with all-cause mortality as a competing event, were performed. Model fit by adding serum ß2-MG levels was calculated using the Akaike information criterion (AIC). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indexes were used to evaluate the improvement of predictive performance for 5-year cumulative incidence of KFRT by serum ß2-MG levels. RESULTS: Among 408 patients, 99 developed KFRT during a median follow-up period of 6.7 years. A higher serum ß2-MG level (1-unit increase in log-transformed serum ß2-MG level) was associated with a higher incidence of KFRT, even after adjustments for previously known clinical and histological risk factors (hazard ratio [95% confidence interval {CI}]: 3.30 [1.57-6.94] and subdistribution hazard ratio [95% CI]: 3.07 [1.55-6.06]). The addition of log-transformed serum ß2-MG level reduced AIC and improved the prediction of KFRT (NRI and IDI: 0.32 [0.09-0.54] and 0.03 [0.01-0.56], respectively). CONCLUSIONS: Among patients with biopsy-proven DN, serum ß2-MG was an independent predictor of KFRT and improved prediction performance. In addition to serum creatinine, serum ß2-MG should probably be measured for DN.

Differential impact of glomerular and tubule-interstitial histological changes on kidney outcome between non-proteinuric and proteinuric diabetic nephropathy.

BACKGROUND: Studies on kidney function and histological findings in diabetic nephropathy (DN) with low urinary protein (UP) are few. We examined the differential impact of histological changes on kidney outcomes between non-proteinuric and proteinuric DN. METHODS: Patients diagnosed with DN by renal biopsy during 1981-2014 were divided into non-proteinuric (UP ≤ 0.5 g/day) and proteinuric (UP > 0.5 g/day) DN. The Cox proportional hazard model was used to examine the association of glomerular lesions (GLs) and interstitial fibrosis and tubular atrophy (IFTA) with end-stage kidney disease (ESKD) development after adjusting for relevant confounders. RESULTS: The non-proteinuric and proteinuric DN groups included 197 and 199 patients, respectively. During the 10.7-year median follow-up period, 16 and 83 patients developed ESKD in the non-proteinuric and proteinuric DN groups, respectively. In the multivariable Cox hazard model, hazard ratios (HRs) [95% confidence intervals (CIs)] of GL and IFTA for ESKD in proteinuric DN were 2.94 [1.67-5.36] and 3.82 [2.06-7.53], respectively. Meanwhile, HRs [95% CIs] of GL and IFTA in non-proteinuric DN were < 0.01 [0-2.48] and 4.98 [1.33-18.0], respectively. IFTA was consistently associated with higher incidences of ESKD regardless of proteinuria levels (P for interaction = 0.49). The prognostic impact of GLs on ESKD was significantly decreased as proteinuria levels decreased (P for interaction < 0.01). CONCLUSIONS: IFTA is consistently a useful predictor of kidney prognosis in both non-proteinuric and proteinuric DN, while GLs are a significant predictor of kidney prognosis only in proteinuric DN.

Trace proteinuria detected via dipstick test is associated with kidney function decline and new-onset overt proteinuria: the Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: Microalbuminuria is associated with mortality, cardiovascular disease, and end-stage kidney disease. The association between trace proteinuria (detected via dipstick test) and kidney outcomes is unclear. METHODS: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted during 2008-2014. The frequency of trace proteinuria (detected via dipstick test) during first two visits was used as an exposure variable (TrUP 0/2, no trace proteinuria; TrUP 1/2, detected once; TrUP 2/2, detected twice), and kidney outcomes were evaluated. The association between the frequency of trace proteinuria and incidence of 1.5-fold increase in serum creatinine levels and overt proteinuria was analyzed using Cox regression analysis. Trajectories of estimated glomerular filtration rate (eGFR) were compared using a mixed-effect model. RESULTS: Among 306,317 participants, 3188 and 17,461 developed a 1.5-fold increase in serum creatinine levels and new-onset overt proteinuria, respectively, during the median follow-up period of 36.2 months. The adjusted hazard ratio (HR) and 95% confidence interval (CI) for 1.5-fold increase in serum creatinine level in the TrUP 1/2 and TrUP 2/2 groups, compared to TrUP 0/2 group, were 1.23 (1.07-1.42) and 1.39 (1.01-1.92), respectively, and the adjusted HR (95% CI) for overt proteinuria were 2.94 (2.83-3.06) and 5.14 (4.80-5.51), respectively. The eGFR decline rates in the TrUP 1/2 and TrUP 2/2 groups were higher than that in the TrUP 0/2 group (p for interaction < 0.001). CONCLUSIONS: Trace proteinuria (detected via dipstick test) was associated with subsequent kidney function decline and overt proteinuria in the general population.

Association of triglycerides to high-density lipoprotein cholesterol ratio with incident cardiovascular disease but not end-stage kidney disease among patients with biopsy-proven diabetic nephropathy.

Increased triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) are dyslipidemias characteristic of diabetes. Here, we aimed to examine associations of TG/HDL-C ratio with cardiovascular disease (CVD) and kidney dysfunction among patients with diabetic nephropathy. This retrospective observational study consists of patients with biopsy-proven diabetic nephropathy at Nara Medical University Hospital. Exposure of interest was TG/HDL-C ratio measured at kidney biopsy. Outcome variables were kidney histological findings, incident CVD and end-stage kidney disease (ESKD). Multivariable logistic regression models and Cox proportional hazard models were used to examined these associations. A total of 353 subjects were divided into quartiles based on TG/HDL-C ratio: Quartile 1 (reference), <1.96; Quartile 2, 1.96-3.10; Quartile 3, 3.11-4.55; and Quartile 4, ≥4.56. TG/HDL-C ratio was not a predictor of any histological findings in fully adjusted models. During median follow-up periods of 6.2 and 7.3 years, 152 and 90 subjects developed CVD and ESKD, respectively. Higher TG/HDL-C ratio was independently associated with higher incidences of CVD even after adjustments for potential confounders (hazard ratio [95% confidence interval] for Quartile 3 vs. reference; 1.73 [1.08-2.79] and Quartile 4 vs. reference; 1.86 [1.10-3.17]). Although there was a weak association between TG/HDL-C ratio and ESKD in the univariable model, the association was not significant in fully adjusted models. In conclusion, among patients with biopsy-proven diabetic nephropathy, higher TG/HDL-C ratio was independently associated with higher incidences of CVD but not with kidney outcomes, suggesting different impact of TG/HDL-C ratio on cardiorenal outcomes.

Novel Method for Estimating Propulsive Force Generated by Swimmers' Hands Using Inertial Measurement Units and Pressure Sensors.

Propulsive force is a determinant of swimming performance. Several methods have been proposed to estimate the propulsive force in human swimming; however, their practical use in coaching is limited. Herein, we propose a novel method for estimating the propulsive force generated by swimmers' hands using an inertial measurement unit (IMU) and pressure sensors. In Experiment 1, we use a hand model to examine the effect of a hand-mounted IMU on pressure around the hand model at several flow velocities and water flow directions. In Experiment 2, we compare the propulsive force estimated using the IMU and pressure sensors (FIMU) via an underwater motion-capture system and pressure sensors (FMocap). Five swimmers had markers, pressure sensors, and IMUs attached to their hands and performed front crawl swimming for 25 m twice at each of nine different swimming speeds. The results show that the hand-mounted IMU affects the resultant force; however, the effect of the hand-mounted IMU varies with the flow direction. The mean values of FMocap and FIMU are similar (19.59 ± 7.66 N and 19.36 ± 7.86 N, respectively; intraclass correlation coefficient(2,1) = 0.966), and their waveforms are similar (coefficient of multiple correlation = 0.99). These results indicate that the IMU can estimate the same level of propulsive force as an underwater motion-capture system.

Cardiac Dysfunction Due to Thiamine Deficiency after Hemodialysis for Biguanide-related Lactic Acidosis.

Biguanide is an ideal drug for the treatment of type 2 diabetes mellitus. When used appropriately, the incidence of lactic acidosis is reported to be very low. Risk factors associated with biguanide-related lactic acidosis include chronic kidney disease, congestive heart failure, alcohol use, severe dehydration, shock, hypoxic states, sepsis, and advanced age. We herein report a case of cardiac dysfunction due to thiamine deficiency after hemodialysis in a patient with suspected biguanide-related lactic acidosis. Patients who develop severe lactic acidosis while taking biguanides should be given a large dose of thiamine without delay, given the possibility of thiamine deficiency as a complication.

The Efficacy of Sonazoid-enhanced Ultrasonography in Decision-making for Liver Abscess Treatment.

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 <50% of the abscess cavity was enhanced (9 patients). The rate of patients who were cured by conservative treatment alone was examined in both groups. The defect rate of all liver abscesses in the post-vascular phase was also evaluated. Results In the VE group, improvement by conservative treatment alone was obtained in 11 out of 12 patients (91.7%), while in the VNE group, improvement by conservative treatment alone was obtained in only 1 out of 9 patients (11.1%), a significant difference (p<0.001). In the VE group, one patient did not improve with conservative treatment alone because the abscess ruptured near the liver surface. In the VE group, the abscess size was smaller than in the VNE group. By examining the defect rate in the post-vascular phase, it was found that 16 out of 21 patients (76.2%) showed 71% or more defects. Conclusion The enhancement rate in the arterial-predominant phase of CEUS was considered useful for determining the treatment approach for liver abscess.

Deletion of the Golgi Ca2+-ATPase PMR1 gene potentiates antifungal effects of dodecanol that depend on intracellular Ca2+ accumulation in budding yeast.

One strategy for overcoming infectious diseases caused by drug-resistant fungi involves combining drugs rendered inactive by resistance with agents targeting the drug resistance mechanism. The antifungal activity of n-dodecanol disappears as incubation time passes. In Saccharomyces cerevisiae, anethole, a principal component of anise oil, prolongs the transient antifungal effect of dodecanol by downregulating genes of multidrug efflux pumps, mainly PDR5. However, the detailed mechanisms of dodecanol's antifungal action and the anethole-induced prolonged antifungal action of dodecanol are unknown. Screening of S. cerevisiae strains lacking genes related to Ca2+ homeostasis and signaling identified a pmr1Δ strain lacking Golgi Ca2+-ATPase as more sensitive to dodecanol than the parental strain. Dodecanol and the dodecanol + anethole combination significantly increased intracellular Ca2+ levels in both strains, but the mutant failed to clear intracellular Ca2+ accumulation. Further, dodecanol and the drug combination reduced PMR1 expression and did not lead to specific localization of Pmr1p in the parental strain after 4-h treatment. By contrast with the parental strain, dodecanol did not stimulate PDR5 expression in pmr1Δ. Based on these observations, we propose that the antifungal activity of dodecanol is related to intracellular Ca2+ accumulation, possibly dependent on PMR1 function, with anethole enabling Ca2+ accumulation by restricting dodecanol efflux.

Low-Frequency Electrical Stimulation of Denervated Skeletal Muscle Retards Muscle and Trabecular Bone Loss in Aged Rats.

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.

Efficacy of 1.2 L polyethylene glycol plus ascorbic acid for bowel preparations.

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.

Behavioral Effect of Short- and Long-Term Exercise on Motor Functional Recovery after Intracerebral Hemorrhage in Rats.

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.

Changes in Cerebral Oxyhaemoglobin Levels During and After a Single 20-Minute Bout of Moderate-Intensity Cycling.

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.

Modulation of Corticospinal Excitability Depends on the Pattern of Mechanical Tactile Stimulation.

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.

Variability and Reliability of Paired-Pulse Depression and Cortical Oscillation Induced by Median Nerve Stimulation.

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.

Transcranial Static Magnetic Field Stimulation over the Primary Motor Cortex Induces Plastic Changes in Cortical Nociceptive Processing.

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.

Effects of Streptomycin Administration on Increases in Skeletal Muscle Fiber Permeability and Size Following Eccentric Muscle Contractions.

The purpose of this study was to investigate the preventive effect of streptomycin (Str) administration on changes in membrane permeability and the histomorphological characteristics of damaged muscle fibers following eccentric contraction (ECC ). Eighteen 7-week-old male Fischer 344 rats were randomly assigned to three groups: control (Cont), ECC, and ECC with Str (ECC + Str). The tibialis anterior (TA) muscles in both ECC groups were stimulated electrically and exhibited ECC. Evans blue dye (EBD), a marker of muscle fiber damage associated with increased membrane permeability, was injected 24 hr before TA muscle sampling. The number of EBD-positive fibers, muscle fiber cross-sectional area (CSA), and roundness were determined via histomorphological analysis. The ECC intervention resulted in an increased fraction of EBD-positive fibers, a larger CSA, and decreased roundness. The fraction of EBD-positive fibers was 79% lower in the ECC + Str group than in the ECC group. However, there was no difference in the CSA and roundness of the EBD-positive fibers between the two ECC groups. These results suggest that Str administration can reduce the number of myofibers that increase membrane permeability following ECC, but does not ameliorate the extent of fiber swelling in extant EBD-positive fibers. Anat Rec, 301:1096-1102, 2018. © 2018 Wiley Periodicals, Inc.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

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.

Modulation of short-latency afferent inhibition and short-interval intracortical inhibition by test stimulus intensity and motor-evoked potential amplitude.

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.