Serum Creatinine-Cystatin C Based Screening of Sarcopenia in Community Dwelling Older Adults: A Cross-Sectional Analysis.

OBJECTIVES: To compare the discriminative capabilities for the manifestation of sarcopenia or physical frailty between serum creatinine- and cystatin C-derived indices among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING: Primary Care and Community. PARTICIPANTS: We utilized a subset of data from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, which was initiated in 2015 to gather comprehensive information on various health-related parameters among community-dwelling older individuals (age ≥65 years). MEASUREMENTS: Five serum creatinine-cystatin C based indices including the Sarcopenia Index, the serum creatinine/cystatin C ratio, the disparity between serum cystatin-C-based and creatinine-based estimated GFR, the total body muscle mass index (TBMM), and the prediction equation for skeletal muscle mass index (pSMI) were employed. Sarcopenia and physical frailty were identified based on the Asian Working Group for Sarcopenia criteria and the revised Japanese version of the Cardiovascular Health Study criteria, respectively. The receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the discriminative abilities of these tools. RESULTS: In the analysis of 954 participants, 52 (5.5%) were identified with sarcopenia and 35 (3.7%) with physical frailty. Regarding sarcopenia discrimination, TBMM and pSMI both exhibited area under the curve (AUC) values exceeding 0.8 for both men and women. Concerning the identification of physical frailty, AUC values ranged from 0.61 to 0.77 for males and 0.50 to 0.69 for females. In the multivariate logistic regression analyses, only TBMM and pSMI consistently displayed associations with sarcopenia, irrespective of sex (P<0.001, respectively). On the other hand, no consistent associations were observed between the indices and physical frailty. CONCLUSIONS: This study provides a robust association of a serum creatinine- and cystatin C-derived indices, especially TBMM and pSMI, with sarcopenia among community-dwelling older adults. Conversely, the application of these indices for the screening of physical frailty has its constraints, necessitating further investigation.

Influence of concurrent and staggered dosing of semi-solid nutrients on the pharmacokinetics of orally administered carbamazepine in rats.

In the present study, we examined the effects of concurrent and staggered dosing of PG-soft ace-MP TM (PG), novel semi-solid enteral nutrients, on the pharmacokinetics of orally administered carbamazepine (CBZ) in rats due to the high possibility of drug interaction during the absorption process. The pharmacokinetic behavior of CBZ was considerably altered when administered concurrently with PG. The maximum serum CBZ concentration (Cmax) significantly decreased and the mean residence time (MRT) significantly increased. The elimination constant (ke) also significantly increased, but there were no significant changes in the area under the serum CBZ concentration versus time curve (AUC) and the time to reach Cmax (Tmax). However, these changes in the pharmacokinetic parameters were eliminated by waiting 20 min, the time interval equivalent to the Tmax described above, between CBZ administration and PG dosing. This study suggested that PG interferes with CBZ absorption from the digestive tract, although staggered administration of CBZ and PG prevented their interaction.

Detecting halfmetallic electronic structures of spintronic materials in a magnetic field.

Band-gap engineering is one of the fundamental techniques in semiconductor technology and also applicable in next generation spintronics using the spin degree of freedom. To fully utilize the spintronic materials, it is essential to optimize the spin-dependent electronic structures in the operando conditions by applying magnetic and/or electric fields. Here we present an advanced spectroscopic technique to probe the spin-polarized electronic structures by using magnetic circular dichroism (MCD) in resonant inelastic soft X-ray scattering (RIXS) under an external magnetic field. Thanks to the spin-selective dipole-allowed transitions in RIXS-MCD, we have successfully demonstrated the direct evidence of the perfectly spin-polarized electronic structures for the prototypical halfmetallic Heusller alloy [Formula: see text]. RIXS-MCD is a promising tool to probe the spin-dependent carriers and band-gap induced in the buried magnetic layers in an element specific way under the operando conditions.

The asymmetry of antimatter in the proton.

The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.

Reduced cytotoxicity in doxorubicin-exposed HepG2 cells pretreated with menthol due to upregulation of P-glycoprotein.

The aim of the present study was to examine changes in the expression and activity of P-glycoprotein (P-gp) in human hepatocellular carcinoma HepG2 cells after exposure to menthol, and their relationship to the cytotoxicity of and apoptotic responses to doxorubicin (DOX), a substrate of P-gp, in the cells. The expression of P-gp in HepG2 cells was significantly increased by menthol treatment. Intracellular accumulation of DOX in HepG2 cells was significantly lower in the menthol-treated group than in the control group, but this phenomenon was abolished in the presence of verapamil. Decreased cell viability by DOX was significantly attenuated by 24-h menthol treatment prior to DOX exposure, which coincided with the changes in mRNA expression of Bcl-xl and caspase-3. These results demonstrate that menthol causes hepatocellular carcinoma cells to acquire resistance to DOX by increasing its efflux through the upregulation of P-gp.

Urinary biomarkers of kidney tubule injury, risk of acute kidney injury, and mortality in patients with acute ischaemic stroke treated at a stroke care unit.

BACKGROUND AND PURPOSE: Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). The aim of this study was to investigate whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischaemic stroke. METHODS: Acute ischaemic stroke patients hospitalized in the stroke care unit (SCU) within 24 h after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured on admission. We evaluated the associations among urinary L-FABP, incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria and other potentially predictive variables, using multivariable analysis. RESULTS: In total, 527 acute ischaemic stroke patients (342 men, median age 74 years) were enrolled in the study. Twenty-seven patients (5.1%) experienced AKI within 7 days of admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI [53.8 µg/g creatinine (Cr) vs. 3.9 µg/g Cr; P < 0.001] and 90-day mortality (15.5 µg/g Cr vs. 4.0 µg/g Cr; P < 0.001). In the multivariate analysis, elevated urinary L-FABP level (per 10-µg/g Cr increase) was independently associated with AKI (odds ratio 1.225, 95% confidence interval (CI) 1.083-1.454; P = 0.003) and 90-day mortality (hazard ratio 1.091, 95% CI 1.045-1.138; P < 0.001). CONCLUSION: Urinary biomarkers of kidney tubule injury are independently associated with the development of AKI and 90-day mortality in patients with acute ischaemic stroke treated at the SCU.

Sesame lignans increase sympathetic nerve activity and blood flow in rat skeletal muscles.

Beneficial effects of sesame lignans, especially antioxidative effects, have been widely reported; however, its potential effects on autonomic nerves have not yet been investigated. Therefore, the current study aimed to investigate the effect of sesame lignans on the autonomic nervous system. The sympathetic nerve activity in rat skeletal muscle was measured using electrophysiological approaches, with blood flow determined using the laser Doppler method. Sesame lignans were administered intragastrically at 2 and 20 mg/kg, and after 60 min, the sympathetic nerve activity was observed to increase by 45.2% and 66.1%, respectively. A significant increase in blood flow (39.6%) was also observed for the 20-mg/kg dose when measured at 55 min after administration. These sympathomimetic effects were completely prevented by subdiaphragmatic vagotomy, and the increase in blood flow was eliminated in the presence of the beta2-adrenergic receptor inhibitor butoxamine. Thus, it is proposed that sesame lignans can increase the blood flow of skeletal muscle, possibly by exciting sympathetic nerve activity through the afferent vagal nerve.

Clinical and experimental studies of intraperitoneal lipolysis and the development of clinically relevant pancreatic fistula after pancreatic surgery.

BACKGROUND: Visceral obesity is one of the risk factors for clinically relevant pancreatic fistula after pancreatic resection. The objective of this study was to evaluate the impact of intraperitoneal lipolysis on postoperative pancreatic fistula. METHODS: The degree of intraperitoneal lipolysis was investigated by measuring the free fatty acid concentration in drain discharge in patients after pancreatic resection. An experimental pancreatic fistula model was prepared by pancreatic transection, and the impact of intraperitoneal lipolysis was evaluated by intraperitoneal administration of triolein (triglyceride) with, or without orlistat (lipase inhibitor). RESULTS: Thirty-three patients were included in the analysis. The free fatty acid concentration in drain discharge on postoperative day 1 was significantly associated with the development of a clinically relevant pancreatic fistula (P = 0·004). A higher free fatty acid concentration in drain discharge was associated with more visceral adipose tissue (P = 0·009). In the experimental model that included 98 rats, intraperitoneal lipolysis caused an increased amount of pancreatic juice leakage and multiple organ dysfunction. Intraperitoneal administration of a lipase inhibitor reduced lipolysis and prevented deterioration of the fistula. CONCLUSION: Intraperitoneal lipolysis significantly exacerbates pancreatic fistula after pancreatic resection. Inhibition of lipolysis by intraperitoneal administration of a lipase inhibitor could be a promising therapy to reduce clinically relevant postoperative pancreatic fistula. Surgical relevance Clinically, there are two types of pancreatic fistula after pancreatic resections: harmless biochemical leak and harmful clinically relevant pancreatic fistula. Visceral obesity is one of the known risk factors for clinically relevant pancreatic fistula; however, the underlying mechanisms remained to be elucidated. Patients with clinically relevant pancreatic fistula had a higher free fatty acid concentration in the drain discharge, suggesting a relationship between intraperitoneal lipolysis and pancreatic fistula. The experimental model of pancreatic fistula demonstrated that intraperitoneal lipolysis caused deterioration in pancreatic fistula, suggesting that intraperitoneal lipolysis is one of the mechanisms that drives biochemical leakage to clinically relevant pancreatic fistula. Intraperitoneal administration of a lipase inhibitor prevented lipolysis as well as pancreatic fistula deterioration in the experimental model, suggesting a future clinical application for lipase inhibitors in prevention of clinically relevant pancreatic fistula.

Effect of Lactobacillus delbrueckii LAB4 on hepatic and pancreatic sympathetic nerve activity and blood glucose levels in rats.

Various lactobacilli have been suggested to exert beneficial effects in humans. In this study, we examined the effects of intraduodenal (ID) administration of heat-killed Lactobacillus delbrueckii LAB4 (LAB4) on activities of efferent sympathetic nerves innervating the liver and pancreas. Consequently, it was observed that ID administration of LAB4 significantly reduced either the efferent hepatic sympathetic nerve activity (hepatic-SNA) or pancreatic sympathetic nerve activity (pancreatic-SNA) in urethane-anaesthetised rats. Moreover, the effect of acute and chronic administration of LAB4 (1×109 cells/ml) on hyperglycaemia induced by intracranial injection of 2-deoxy-D-glucose (2DG) were examined in conscious rats. We found that LAB4 significantly inhibited 2DG-induced hyperglycaemia. These findings suggest that ID administration of heat-killed LAB4 might lower plasma glucose level via changes in the autonomic nervous system in rats.

Downregulation of organic cation transporter 1 and breast cancer resistance protein with the induction of Pregnane X receptor in rat kidney impaired by doxorubicin.

Transporters expressed in the kidney play an important role in the excretion of endogenous substances and chemical drugs. The Pregnane X receptor (PXR) has been reported to be involved in regulating the expression of numerous transporters. In the present study, we examined the alteration in expression level of PXR, organic cation transporter 1 (OCT1) and breast cancer resistance protein (BCRP) in renal cell lines of rat origin and the kidney of rats when damaged by doxorubicin (DOX). The expression level of PXR in renal tubular epithelium NRK-52E cells was significantly increased by DOX at a concentration confirmed to cause cellular damage. The expression levels of OCT1 and BCRP were significantly lower in the DOX-treated cells than in the untreated cells. In model rats with DOX-induced nephrotoxicity, the alterations in renal expression of PXR, OCT1 and BCRP were similar to those in NRK-52E cells, although there was a difference in the degree of the changes.

Spermatic and oxidative profile of domestic cat (Felis catus) epididymal sperm subjected to different cooling times (24, 48 and 72 hours).

Cooling stored epididymal samples for several days allows facilities to transport and process genetic material post-mortem. Improvements to this practice allow the preservation of sperm from domestic cats, which are the ideal study model for wild felids. However, the modifications in spermatic features and the oxidative profile are not fully understood in cats. This information is necessary for the development of biotechniques, such as new extenders for cryopreservation. Therefore, the purpose of this study was to evaluate the spermatic and oxidative profile in samples from the epididymal cauda of domestic cats cooled at 5°C for 24, 48 and 72 hr. Spermatozoa were collected from the epididymis cauda. Evaluations consisted of computer-assisted sperm analysis (CASA), plasma membrane integrity (eosin/nigrosin), acrosome integrity (fast green/rose bengal), sperm morphology, sperm DNA integrity (toluidine blue), mitochondrial activity (3'3 diaminobenzidine), activity of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD), measurement of lipid peroxidation (TBARS) and protein oxidation. A decrease in sperm motility parameters was observed after 72 hr of cooling (i.e. total and progressive) with a higher percentage of minor (37.7 ± 6.3%) and total defects (53.4 ± 6.3%). Additionally, a decrease in high mitochondrial activity (Class I: 16.6 ± 2.2%) occurred after 72 hr. The decrease in motility rates after a long cooling time probably was caused by the increase in sperm abnormalities. A long cooling time causes cold shock and mitochondrial exhaustion, but there was no observed change with the oxidative stress condition. Therefore, cat epididymal sperm stored at 5°C appear to maintain a high quality for up to 48 hr of cooling time.

Relationship of Serum Carnitine Level with Falls and Gait Disturbance in the Elderly.

BACKGROUND: Gait disturbance and falls are serious events that can impair activities of daily living (ADL) in the elderly. On the other hand, carnitine plays essential roles in energy production, and carnitine deficiency leads to low activity levels. OBJECTIVES: We examined whether a lower serum carnitine concentration was correlated with falls and gait disturbances in the elderly. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study. One hundred and ninety-eight elderly patients (male, 83; female, 115; 81 ± 6 years old) were enrolled in this study. MEASUREMENTS: Physical performance (hand grip strength, leg strength, walking speed, one-leg standing time, and tandem gait steps) and frailty status (The Edmonton Frail Scale: EFS) were evaluated. The serum total, free, and acylated carnitine levels were measured using an enzyme cycling method. We then investigated the associations between the serum carnitine level, history of falls, and the results of these physical examinations. RESULTS: Of the 198 subjects, 56 (28%) had a history of falls within the past one year. The patients with a history of falls had lower serum total carnitine and free carnitine levels than those without a history of falls. Regarding the physical performance results, the patients with a history of falls had higher EFS scores, a weaker hand grip strength, a slower walking speed, a shorter one-leg standing time, and a smaller number of tandem gait steps than those without a history of falls. A logistic regression analysis showed that the low serum total carnitine concentration was identified as an independent factor associated with a history of falls, a slow walking speed after adjustments for age, sex and modified EFS. CONCLUSIONS: A low serum carnitine level is associated with a history of falls and gait disturbances in elderly people.

Composition of the microbiota in forestomach fluids and feces of Japanese Black calves with white scours.

The objective of this study was to characterize the composition of the forestomach and fecal microbiota in Japanese Black calves with white scours. Forestomach fluid, feces, and peripheral blood were collected from healthy calves ( = 5; age 10 ± 2 d) and scouring calves ( = 5; age 10 ± 1 d) on the day on which white scours occurred. The pH and concentrations of VFA, lactic acid, and ammonia nitrogen (NH-N) of the forestomach fluids were determined. Microbiota composition and gene copy numbers in the forestomach fluid and feces were analyzed by 454 pyrosequencing and quantitative real-time PCR (qPCR), respectively. The cytokine mRNA level in peripheral leukocytes was evaluated by qPCR. The pH of the forestomach fluid of the scouring calves tended to be higher than that of the healthy calves ( = 0.056). No significant difference was detected in the total VFA, lactic acid, or NH-N concentrations in the forestomach fluids of the 2 groups. Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla in the forestomach fluid and feces. At the genus level, the relative abundance of in the forestomach fluid was significantly higher in the scouring calves ( < 0.05) and the relative abundance of in the feces was significantly higher than that in the forestomach in the healthy calves ( < 0.05). Furthermore, the bacterial diversity indices of feces were lower in the scouring calves. Quantitative PCR amplification using some of the primer pairs failed in the forestomach fluid and feces in both groups. These results suggested that fermentation in the forestomach may affect the occurrence of white scours, resulting in changes in the composition and diversity of the forestomach fluid and fecal microbiota in Japanese Black calves.

Higher gene expression of CYP1A2, 2B1 and 2D2 in the brain of female compared with male rats.

Cytochrome P450 (CYP) in the brain plays an essential role in the local metabolism of various compounds, including clinically used drugs, toxins, and endogenous substances. In the present study, we compared the expression profiles of mRNAs for several CYP subtypes in the brain between male and female rats. The expression of CYP1A2, CYP2B1, and CYP2D2 in females was significantly higher than that in males. On the other hand, the expression level of the other CYP subtypes examined in the male brain was similar to that in the female brain. These results strongly suggest that marked gender differences exist in the expression profiles of some CYP subtypes in rat brain.