Background Breast cancer treatment with trastuzumab, a monoclonal antibody that targets human epidermal growth factor receptor type 2 (HER2), has largely been successful in improving the prognosis of HER2-positive disease. However, a critical issue associated with trastuzumab treatment is its cardiotoxic adverse effects, including cardiac insufficiency. Methods We measured levels of cardiac troponin I, a marker of myocardial damage, with a highly sensitive method (hs-cTnI) using a fully automated chemiluminescent immunoassay system (ADVIA Centaur Ò XP) in breast cancer patients and examined the relationship between administration of trastuzumab and epirubicin and concentrations of hs-cTnI. Results The coefficient of variation for within-run repeatability was 1.34-5.93 %, using plasma pools and controls of 3 concentrations, and that for between-run reproducibility was 3.99-8.79 %, indicating high precision of the assay. In a dilutional linearity test with highly concentrated specimens, hs-cTnI values could be measured up to 50 ng/mL with linearity. No influence from coexisting substances was observed. The concentration of hs-cTnI was at or above the reference range (0.04 ng/mL) in 9 of 214 total breast cancer cases (4.2 %). The hs-cTnI concentration was at or above the reference range in 4 of 49 cases (8.2 %) that were administered trastuzumab, and in 5 of 165 cases (3.0 %) that were not. Trastuzumab did not cause elevation of hs-cTnI when not administered in combination with epirubicin. Conclusions These results suggest that epirubicin and trastuzumab cause cardiotoxicity through different mechanisms. Epirubicin can cause myocardial necrosis, while trastuzumab can cause cardiomyopathy without myocardial necrosis.

Background Toe grip-related training requires individuals to actively exercise muscles that are not frequently used; therefore, it may improve not only toe grip strength but also cognitive function. The purpose of this study was to examine the effects of toe grip-related training on predictors of physical performance and cognitive function in nursing home residents. Methods A total of 35 nursing home residents (35 left and 35 right feet; mean age, 82.1 ± 7.9 years) were included in this study. The participants were divided into two groups: a training group and a control group. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function of the participants, and the Fall Risk Index (FRI) was used to evaluate the risk of falls. Toe grip-related physical function was also assessed. Baseline endpoints were evaluated and the effects of toe grip-related training were examined following a 12-week training intervention. Results The training group showed significant improvements in MMSE score, FRI score, toe grip strength, and the toe skill (TS) test; however, the control group did not show these changes. The training group showed significant increases in Δ MMSE, Δ toe grip strength, and Δ TS (right foot) than the control group. Stepwise regression analysis revealed that Δ toe grip strength is an independent factor of Δ MMSE. Conclusions Toe grip training improves not only toe grip strength itself, but also cognitive function. Furthermore, change in toe grip strength was an independent factor of change in MMSE in those populations. Trial registration UMIN, UMIN000027437 . Registered on 26 May 2017.

The bonanza-grade, low-sulfidation epithermal Hishikari gold deposit is located in the Plio-Pleistocene volcanic area of southern Kyushu, Japan. The concealed veins were discovered in 1981 and the mine has since produced 5.462 million metric tons (Mt) of ore averaging 44.3 g/t Au (242 t Au) from 1985 to the end of 2018, at which time reserves were 7.98 Mt at 20.9 g/t Au. The Hishikari deposit consists of the Honko, Sanjin, and Yamada ore zones, which occur in a NE-trending area 2.8 km long and 1.0 km wide. The veins are hosted by basement sedimentary rocks of the Cretaceous Shimanto Supergroup and by overlying Hishikari Lower Andesites of Pleistocene age. Sinter occurs about 100 m above the Yamada ore zone. Temperature-controlled hydrothermal alteration zones occupy an area of >5 km long and 2 km wide. The Honko and Sanjin veins occur within a chlorite-illite alteration zone (paleotemperature >230°C), whereas the Yamada veins occur within an interstratified clay mineral zone (150°–230°C). The marginal alteration comprises quartz-smectite (100°–150°C) and cristobalite-smectite (<100°C) zones. Ore-grade veins are located between –60- and 120-m elev, with the paleowater table over the Honko-Sanjim veins at ~300-m elev. Overall, the Ag/Au wt ratio is about 0.6. Vein-forming minerals consist of quartz, adularia, and clay minerals plus truscottite, with electrum and minor pyrite, chalcopyrite, naumannite, galena, and sphalerite. The major veins formed from repeated episodes of boiling and strong fluid flow inferred from bands of quartz, adularia, and smectite with bladed quartz, columnar adularia, and truscottite.

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Background The spinal nerve ligation (SNL) rat is well known as the most common rodent model of neuropathic pain without motor deficit. Researchers have performed analyses using only the von Frey and thermal withdrawal tests to evaluate pain intensity in the rat experimental model. However, these test are completely different from the neurological examinations performed clinically. We think that several behavioral reactions must be observed following SNL because the patients with neuropathic pain usually have impaired coordination of the motions of the right–left limbs and right–left joint motion differences. In this study, we attempted to clarify the pain behavioral reactions in SNL rat model as in patients. We used the Kinema-Tracer system for 3D kinematics gait analysis to identify new characteristic parameters of each joint movement and gait pattern. Results The effect of SNL on mechanical allodynia was a 47 ± 6.1% decrease in the withdrawal threshold during 1–8 weeks post-operation. Sagittal trajectories of the hip, knee and ankle markers in SNL rats showed a large sagittal fluctuation of each joint while walking. Top minus bottom height of the left hip and knee that represents instability during walking was significantly larger in the SNL than sham rats. Both-foot contact time, which is one of the gait characteristics, was significantly longer in the SNL versus sham rats: 1.9 ± 0.15 s vs. 1.03 ± 0.15 s at 4 weeks post-operation (p = 0.003). We also examined the circular phase time to evaluate coordination of the right and left hind-limbs. The ratio of the right/left circular time was 1.0 ± 0.08 in the sham rats and 0.62 ± 0.15 in the SNL rats at 4 weeks post-operation. Conclusions We revealed new quantitative parameters in an SNL rat model that are directly relevant to the neurological symptoms in patients with neuropathic pain, in whom the von Frey and thermal withdrawal tests are not used at all clinically. This new 3D analysis system can contribute to the analysis of pain intensity of SNL rats in detail similar to human patients’ reactions following neuropathic pain.