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The angular dependence of de Haas–van Alphen effect has been measured to reveal the electronic structure of filled skutterudite PrRu4Sb12. The angular dependence of de Haas–van Alphen frequency of PrRu4Sb12 is in good agreement with that of LaRu4Sb12. Compared with PrFe4P12, no anomalous enhancement of cyclotron effective mass has been observed in this system. This change of electronic structure is attributed to the difference in the c−f hybridization strength, which is expected from the large difference in the lattice parameters. [Copyright &y& Elsevier]

This paper describes the biological response of cultured HeLa S3 cells to non-thermal, intense burst sinusoidal electric fields (IBSEF). The proliferation activity of the cells subjected to 300 kV/m, 200 μs-long IBSEF with a frequency between 0.3 MHz and 100 MHz was evaluated by using an automatic cell event monitor, xCELLigence, for 48 hours. The experiment showed that the cell proliferation depended on the pulse number and the frequency band of the IBSEF. The application of the smaller number of the pulses enhances the proliferation, whereas the large number of pulses tends to kill the cells. The dependence on the pulse number indicates the effect of the pulse is accumulated. The cells seem to be more sensitive to the pulses at the lower frequencies less than 1 MHz. The frequency of 100 MHz, which is sufficiently large for the field to penetrate into the cell, did not appear to influence the proliferation and the immediate death process. When the cells were subjected to 30 pulses of 3 MHz IBSEF, the proliferation was promoted 1.6 times as fast as that of the sham exposure. The frequency dependence of the proliferation might be associated with the electrical stress at the plasma membrane where several proteins related to the cell cycling are located. [ABSTRACT FROM PUBLISHER]

This study elucidates the influence of the pulsing sequence of repetitive nanosecond pulsed electric fields on the viability of human cancer (HeLa S3) cells. A magnetic pulse compressor was used to repetitively deliver 70 ns-long high voltage pulses to cultured HeLa cells in a 4 mm-gap cuvette electrode. The repetition frequency was varied between 0.01 and 250 pulses per second (pps), corresponding to interval from 100 to 0.004 s, respectively. The electric field and the number of pulses were fixed at 25 kV/cm and 25, respectively, which is a sub-lethal condition for the cells. Propidium iodide was used to identify dead cells in the population. Statistical analysis of a cell death ratio in approximately 5000 cells was performed using a flow cytometer. This experiment shows repetition frequency affects cell viability even with identical intra-medium electrical energy expenditure. The dead cell ratio was increased with decreasing pulse repetition frequency down to 0.33 pps, whereas the ratio is decreased with decreasing frequency below 0.1 pps. Since the resealing mechanism of nano-pores caused by the application of ns pulse lasts for a minute, the dependence of the cell viability on the pulsing sequence might be associated with time constants of biological processes related to recovery from field-induced damage. [ABSTRACT FROM PUBLISHER]

Size-specific dose estimates (SSDEs) are dose indices that account for differences in body shape in computed tomography (CT) scans, allowing the evaluation of approximate absorbed doses in any cross section that could not be obtained with the volume CT dose index (CTDI vol ). When using automatic exposure control (AEC), CTDI vol is modulated in the body axis direction, but the value displayed after the examination is the mean CTDI vol for the entire scan, and it is expected that the SSDE value will change depending on which value is used in the calculation. In this study, using a human body phantom, we examined the influence of whether the mean CTDI vol or the modulation value for each slice is used to calculate the SSDE on local organ dose evaluation. A program to calculate water equivalent diameter according to the procedure in the American Association of Physicists in Medicine Report No. 220 was developed and compared. As a result, SSDE calculated using the mean CTDI vol (local-SSDE mean ) overestimated organ doses in the lung region by 18%-56% compared with those calculated by a web system for evaluating CT exposure doses (WAZA-ARIv2, Japan). In contrast, local-SSDE modulated , which was calculated using the modulated value of the CTDI vol , was able to estimate the organ dose with a relative error of 10%-13%. The average local-SSDE over the entire body axis direction was not significantly different between the two methods, regardless of which method was used for CTDI vol . If the mean CTDI vol is stored in the Digital Imaging and Communications in Medicine (DICOM) header tag (0018, 9345) of the CT image and the modulated CTDI vol value is not available for each slice, the calculated local SSDE will contain many errors and will not correctly reflect the organ doses at the scan region. In such cases, it is available to use the method of evaluating local organ doses by multiplying the SSDE, which is the average of the SSDE for the entire scan, by a factor for each organ.

We have reported that 25-hydroxyvitamin D 3 [25(OH)D 3 ] binds to vitamin D receptor and exhibits several biological functions directly in vitro. To evaluate the direct effect of 25(OH)D 3 in vivo, we used Cyp27b1 knockout (KO) mice, which had no detectable plasma 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] when fed a diet containing normal Ca and vitamin D. Daily treatment with 25(OH)D 3 at 250 μg kg -1  day -1 rescued rachitic phenotypes in the Cyp27b1 KO mice. Bone mineral density, female sexual cycles, and plasma levels of Ca, P, and PTH were all normalized following 25(OH)D 3 administration. An elevated Cyp24a1 mRNA expression was observed in the kidneys, and plasma concentrations of Cyp24a1-dependent metabolites of 25(OH)D 3 were increased. To our surprise, 1,25(OH) 2 D 3 was detected at a normal level in the plasma of Cyp27b1 KO mice. The F1 to F4 generations of Cyp27b1 KO mice fed 25(OH)D 3 showed normal growth, normal plasma levels of Ca, P, and parathyroid hormone, and normal bone mineral density. The curative effect of 25(OH)D 3 was considered to depend on the de novo synthesis of 1,25(OH) 2 D 3 in the Cyp27b1 KO mice. This suggests that another enzyme than Cyp27b1 is present for the 1,25(OH) 2 D 3 synthesis. Interestingly, the liver mitochondrial fraction prepared from Cyp27b1 KO mice converted 25(OH)D 3 to 1,25(OH) 2 D 3 . The most probable candidate is Cyp27a1. Our findings suggest that 25(OH)D 3 may be useful for the treatment and prevention of osteoporosis for patients with chronic kidney disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. A common characteristic of ALS pathology is cytoplasmic inclusions primarily composed of transactive response DNA-binding protein of 43 kDa (TDP-43). Production of TDP-43 in the central nervous system is strictly regulated, but it is not known whether this is also true in the skin of ALS patients. We found a gradual but significant reduction in epidermal TDP-43 mRNA expression with illness progression in ALS patients with upper-limb onset. However, the immunoblotting analysis revealed more TDP-43 protein in the skin of patients with upper-limb onset than of those with other onsets. There was no correlation between the TDP-43 mRNA expression and protein levels, indicating that the mechanism of TDP-43 autoregulation in the patients' skin gradually failed. ALS diagnosis depends on clinical signs and electrophysiological findings, making early diagnosis difficult. TDP-43, as quantified by immunoblot analysis of biopsied skin, is a potential new biomarker of ALS.

Aim: To identify the hepatic vascular architecture of patients with hepatitis C virus (HCV) using superb microvascular imaging (SMI) and investigate the use of SMI in the evaluation of liver fibrosis., Methods: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees (VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated., Results: There was a significant difference between SMI distribution pattern and fibrosis stage (P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic (AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index (r = 0.617, P < 0.0001)., Conclusion: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.

Pemetrexedis a key drug in the first and second -line therapy for non-small-cell lung cancer. It exhibits an increased area under the plasma drug concentration-time curve, and it has a prolonged half -life when administered to patients with reduced renal function, resulting in a high frequency of neutropenia. Accordingly, pemetrexed is administered to these patients with caution. Herein, we retrospectively investigated the background characteristics of patients with a creatinine clearance rate (Ccr) of<45 mL/min, who experienced severe adverse events due to pemetrexed. Thirty-eight patients with a Ccr of <45 mL/min were administered pemetrexed. Of these patients, 13 (34%) developed severe adverse events (≥Grade 3) such as neutropenia, thrombocytopenia, and nausea. Multiple logistic regression analysis revealed that a Ccr of <30 mL/min (p= 0.033) and the concomitant use of non-steroidal anti-inflammatory drugs (p=0.012) were significant risk factors for adverse events. Therefore, whenever possible, pemetrexed administration should be avoided in patients with a Ccr of <30 mL/ min and in those receiving concomitant non-steroidal anti-inflammatory drugs.

Objective: To investigate whether or not the lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation in the rostrocaudal direction along the spinal cord, as has been hypothesised (the 'single seed and simple propagation' hypothesis)., Methods: Subjects included 36 patients with sporadic ALS and initial symptoms in the bulbar, respiratory or upper limb regions. Abnormal spontaneous activities in needle electromyography (nEMG)-that is, fibrillation potentials, positive sharp waves (Fib/PSWs) or fasciculation potentials (FPs)-were compared among the unilateral muscles innervated by different spinal segments, especially between the T10 and L5 paraspinal muscles, and between the vastus medialis and biceps femoris. Axon length and the proportion of muscle fibre types, which are both related to motoneuronal vulnerability in ALS, are similar in the paired muscles., Results: Fourteen of 36 patients showed a non-contiguous distribution of nEMG abnormalities from the onset site, with skipping of intermediate segments. In eight of them, the non-contiguous pattern was evident between paired muscles with the same motoneuronal vulnerability. The non-contiguously affected lumbosacral lesions involved motoneuron columns horizontally or radially proximate to one another, appearing to form a cluster in four of the eight patients. FPs, known to precede Fib/PSWs, were shown more frequently than Fib/PSWs in all the lumbosacral segments but L5, suggesting that 2nd hits occur at L5 and then spread to other lumbosacral segments., Conclusions: In sporadic ALS, the distribution of lower motoneuron involvement cannot be explained by the 'single seed and simple propagation' hypothesis alone. We propose a 'multifocal hits and local propagation' hypothesis instead.

Aim:  Experimental materials incorporating fiberglass cloth were used to develop a thin and lightweight face guard (FG). This study aims to evaluate the effect of fiberglass reinforcement on the flexural and shock absorption properties compared with conventional thermoplastic materials., Material and Method:  Four commercial 3.2-mm and 1.6-mm medical splint materials (Aquaplast, Polyform, Co-polymer, and Erkodur) and two experimental materials were examined for use in FGs. The experimental materials were prepared by embedding two or four sheets of a plain woven fiberglass cloth on both surfaces of 1.5-mm Aquaplast. The flexural strength and flexural modulus were determined using a three-point bending test. The shock absorption properties were evaluated for a 5200-N impact load using the first peak intensity with a load cell system and the maximum stress with a film sensor system., Results and Conclusions:  The flexural strength (74.6 MPa) and flexural modulus (6.3 GPa) of the experimental material with four sheets were significantly greater than those of the 3.2-mm commercial specimens, except for the flexural strength of one product. The first peak intensity (515 N) and maximum stress (2.2 MPa) of the experimental material with four sheets were significantly lower than those of the commercial 3.2-mm specimens, except for one product for each property. These results suggest that the thickness and weight of the FG can be reduced using the experimental fiber-reinforced material., (© 2012 John Wiley & Sons A/S.)

An HPLC-peroxyoxalate chemiluminescence (PO-CL) method for simultaneous determination of methylphenidate (MPH) and ritalinic acid (RA) was developed. The method was used to monitor MPH and RA after administration of MPH to rats. Deproteinized plasma spiked with 1-(3-trifluoromethylphenyl)piperazine (IS) was dried and labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F). The labeled sample was cleaned with two kinds of solid-phase extraction cartridge, and the DBD-labels were separated on an ODS column with gradient elution using a mixture of CH(3)CN and imidazole-HNO(3) buffer. Separation of MPH and RA can be achieved within 33 min. The LODs of MPH and RA at a signal-to-noise ratio of 3 were 2.2 and 0.4 ng mL(-1), respectively. Moreover, monitoring of MPH and RA after MPH administration (10 mg kg(-1)) to rat could be performed. The concentration of RA 480 min after administration was eight times higher than that of MPH. The proposed HPLC-PO-CL method was useful for determination of MPH and RA in rat plasma and was successfully used to monitor these substances after MPH administration.

Background: The St. Jude Medical (SJM) Regent prosthetic valve (St. Paul, MN), a recently developed mechanical valve, is an improvement on the conventional SJM valve, having a wider valve area than the SJM HP valve. We evaluated this mechanical valve by Doppler echocardiography and dobutamine stress echocardiography (DSE)., Methods: The functions of the SJM Regent valve were evaluated by continuous-wave Doppler echocardiography and DES in 58 cases of aortic valve replacement during a stable postoperative period., Results: The peak pressure gradient of the replaced valves sized 17, 19, 21, and 23 mm was 27.5 +/- 11.1, 20.0 +/- 9.8, 15.6 +/- 5.7, and 14.3 +/- 9.1, mm Hg respectively, and the effective orifice area index was 0.97 +/- 0.32, 1.01 +/- 0.29, 1.09 +/- 0.30, and 1.41 +/- 0.54 cm(2)/m(2), respectively, with prosthesis-patient mismatch (PPM) found in 1, 3, 2, and 0 cases for the 17-, 19-, 21- and 23-mm valves, respectively, with a total incidence of 10.3%. In 20 cases, the peak pressure gradient and the effective orifice area index were significantly increased during DSE compared with those at rest., Conclusions: Although the PPM incidence was 6.6%, it was deemed from the data of DSE and clinical symptoms that there were no clinical issues for such cases of PPM in the early and intermediate phases after operation. Particularly, the effectiveness of the 17- and 19-mm valves in patients with a small aortic annulus was demonstrated, confirming the satisfactory functions of the SJM Regent prosthetic valve., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To elucidate the relation between a quantitative measure of the shape of the left ventricular cavity, cardiac function, and prognosis in patients with dilated cardiomyopathy (DCM)., Methods: The hearts of 20 healthy individuals and 18 patients with DCM were evaluated. Participants were aged 48.5 ± 5.0 years. On the basis of end-systolic four-chamber view echocardiograms, the endocardium of the left ventricle was traced and the resulting curve was segmented using 100 points. A line tangential to the curve was then drawn at each point, and the angle between two adjacent tangential lines was calculated. The deviation of these angles was designated as the circle index. The circle index and hemodynamic findings in patients with DCM were compared, and the rate of improvement in the circle index in these cases of DCM was determined. These patients were then placed into one of two groups: group R (11 patients), those with improvement rates of 10% or higher at time of discharge; and group NR (seven patients), those with rates less than 10%. Diuretic (furosemide) use, New York Heart Association (NYHA) classification, and readmission rate for the two groups were compared 2 years after discharge., Results: The circle index was 2.7 ± 0.9 in the DCM group and 17.5 ± 4.2 in the healthy group (P < 0.01). The circle index in the DCM group was correlated with pulmonary capillary wedge pressure (r(2) = 0.42). Use of furosemide was unchanged in group R 2 years after discharge, but had increased for all patients in group NR. All cases in group R were classified as NYHA I 2 years after discharge. In group NR, in contrast, although all cases were classified as NYHA I at discharge, five of seven cases had deteriorated to NYHA III-IV 2 years later and were readmitted to hospital., Conclusion: There appears to be a quantifiable correlation between the circularity of the left ventricular cavity and the circle index. This suggests that rate of improvement after treatment for heart failure could predict prognosis in patients with DCM.

In this study, we investigated the effects of delta-opioid receptor antagonists on the G protein-coupled inwardly rectifying potassium (GIRK) channel currents induced by serotonin (5-HT) and noradrenaline (NAd) in the dorsal raphe and the locus coeruleus neurons, respectively. Perforated patch and conventional whole-cell patch clamp recording techniques were used for the study. Neurons were acutely dissociated from neonatal rats. Both naltrindole (NTI) and naltriben (NTB), which are selective delta-antagonists possessing antitussive activity in in vivo animal studies, reversibly inhibited the 5-HT-induced GIRK channel currents (I(5-HT)) in dorsal raphe neurons. This inhibition was concentration-dependent and voltage-independent. The half-maximum inhibitory concentration (IC(50)) on I(5-HT) was 9.84x10(-5) M for NTI and 1.28x10(-5) M for NTB. The inhibition was not reversed by 10(-5) M DPDPE, a selective delta-opioid receptor agonist. NTI did not affect 50% effective concentration (EC(50)) on the concentration-response relationship for 5-HT but inhibited the maximum response. In neurons internally perfused with GTPgammaS, both NTI and NTB also inhibited the GIRK channel currents irreversibly activated by 5-HT. Furthermore, these antagonists concentration dependently inhibited 10(-6) M NAd-induced currents (I(NAd)) in locus coeruleus neurons. The IC(50) of NTI on I(NAd) was 8.44x10(-5) M, which was close to that on I(5-HT). The results suggest that NTI and NTB, which are delta-opioid receptor antagonists possessing antitussive activity, may inhibit GIRK channel currents through a non-opioid action, and give further support to our idea previously proposed that centrally acting non-narcotic antitussives have a common characteristic of the inhibitory action on GIRK channels.

In newt testis, spermatocytes never appear during winter, because secondary spermatogonia die by apoptosis just before meiosis. In the current study, we examined the effect of low temperatures on spermatogenesis. Incubation of newts at low temperatures (8, 12, 15 degrees C) induced defects in spermatogenesis in a temperature-dependent manner. At 8 degrees C, multinucleated giant cells (MGCs) were observed in spermatocytes and spermatogenesis never proceeded beyond meiosis. Although spermatocytes completed meiotic divisions at 12 degrees C, severe cell death was observed in the spermatids. At 15 degrees C both normal and abnormal spermiogenesis were observed. Under these conditions, impaired meiotic synapsis/recombination and down-regulation of the expression of the DMC1 protein, which play pivotal roles in meiotic pairing in eukaryotes, were also observed. Furthermore, to examine the quality of the sperm produced at low temperature for supporting development, artificial insemination was performed. The eggs inseminated with spermatozoa derived from newts kept at 15 degrees C demonstrated a restricted developmental capacity, even though these spermatozoa had an equal capacity for carrying out fertilization to those kept at 22 degrees C. These results suggest that meiosis at low temperatures cause the production of abnormal spermatozoa. Conservation and the significance of this phenomenon in poikilothermic vertebrates living in the temperate zones are also discussed., (Copyright 2003 Wiley-Liss, Inc.)