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BACKGROUND Oxidative stress is thought to be closely related to epileptogenesis. We have previously reported that nitric oxide (NO) levels are higher in epilepsy-prone EL mice between the ages of 3 and 8 weeks than in control mice. However, NO is divided into two fractions, nitrite (NO2) and nitrate (NO3), which appear to play different roles in epileptogenesis. METHODS NO2 and NO3 levels were measured, in EL mice and the control mice, in the parietal cortex, which is thought to be the primary epileptogenetic center in EL mice, and measured in the hippocampus, which is thought to be the secondary center. RESULTS NO3 levels in the hippocampus and parietal cortex of the immature EL mice (3 to 8 weeks of age) were significantly higher than those in the control mice; NO2 levels were significantly higher in the EL mice throughout the study period. The NO3 levels were significantly higher than the NO2 levels in the immature EL mice, but after the onset of ictogenesis at 10 weeks of age, the relative levels of the two fractions reversed. CONCLUSION The reversal of the NO fraction distribution at the onset of seizures that we observed may be related to the developmental process of seizure susceptibility in the neural network of EL mice.

The present paper proposes a new treatment method for diamond-like carbon (DLC) coatings using electric discharge. DLC coatings exhibit excellent mechanical and tribological properties due to their unique carbonaceous structure. Several surface treatment methods were presented to achieve short running-in and low friction. However, in-situ surface treatment is needed to extend the life of machines and maintain their performance. Here, we propose an electric discharge treatment with a simple electrical circuit. As a result, the friction coefficient drastically drops from 0.3 to 0.11. Interestingly, the drop starts shortly after the discharge starts. Consequently, the running-in is shortened to about 6-m sliding compared to no discharge condition, which does not show any running-in more than 68-m sliding. Raman analysis reveals that a transfer layer on the ball surface is composed of carbonaceous material and the structure exhibits graphite-like characteristics. However, there is visible damage on the DLC surface. Another friction test shows a very low friction coefficient of 0.04 using a transfer layer-covered ball and a new DLC disk with a smooth surface. In conclusion, the combination of a transfer layer and smooth DLC surface is needed to exhibit excellent tribological performance, indicating the importance of less damage treatment. Next, pulse discharge treatment is demonstrated to achieve less damage to the DLC coating. As a result, the pulse discharge method reduces friction and surface damage. In conclusion, the proposed treatment methods using electric discharge not only show the potential for reducing friction, but also the feasibility of in-situ treatment during machine operation.

In general, Raman analysis is one of the useful candidates to obtain structure of carbonaceous coatings. To improve the depth resolution of Raman analysis, surface-enhanced Raman Scattering (SERS) using gold nanoparticles (Au nanoparticles: AuNPs) and Au sputtered particles were investigated. The analysis was conducted to approximately 1.7, 2.4, 4.7, and 10.0 nm thickness of carbon coatings on silicon substrate with a 532 nm incident wavelength laser. The results indicated that the underlying silicon substrate was detected in the results of the Au sputtering method. Contrastingly, the underlying silicon substrate was not detected by the AuNPs method. This result clarified that using the AuNPs method, the detection depth of the carbon film was approximately 1.7 nm or less. The a-C:H coating was processed using a calotester, and SERS measurements at different depths were performed for the 633 and 532 nm wavelengths using the AuNPs method. As a result, the IG peak position tended to increase from the vicinity of the inter face between the a-C:H coating and the substrate to the surface. In addition, the ID/IG ratio was as low as 0.28 near the substrate and 0.72 at 3800 nm.

We developed an ion-associate phase (IAP)-extraction/acid back-extraction system for the preconcentration and atomic spectrometric determination of lithium trace amounts in water. The chelating reagent for lithium also works as a constituent of the extraction phase. The lithium in a 10 mL sample solution was converted through a chelate complex reaction with 2,2,6,6-tetramethyl-3,5-heptanedione (HDPM). The addition of a benzyldimethyltetradecylammonium ion caused the formation of IAP suspension in the solution. Centrifugation of the solution led to the isolation of a liquid organic phase and the lithium complex was extracted as the upper phase from the centrifuge tube. After the aqueous phase was removed, lithium was back-extracted with a 400 μL nitric acid solution from the IAP. The acid phase was measured using liquid-electrode-plasma atomic-emission-spectrometry (LEP-AES) or graphite-furnace atomic-absorption spectroscopy (GF-AAS). The detection limits were 0.02 mg/L for LEP-AES and 0.02 μg/L for GF-AAS. This system was applied to the determination of environmental water. The HDPM in the organic phase was reusable.

Background The International Society for Peritoneal Dialysis guidelines recommends the topical application of antibiotics on the exit site for the prevention of peritoneal dialysis (PD)-related infections. However, the recommendation is based on meta-analyses on applying nasal mupirocin ointment or observational or retrospective studies. Here, we evaluated the efficacy of topical application of mupirocin on the exit site for the prevention of PD-related infections. Methods We searched the databases, MEDLINE and CENTRAL, documenting the topical application of antibiotics on the exit site in PD patients in April 2017. We included only randomized controlled trials (RCTs) with adult patients wherein the effects of mupirocin were examined. Exit site infection (ESI), peritonitis, and technical failure were assessed as the main outcomes. Results Overall, six RCTs were included in this study. It was uncertain whether the application of mupirocin ointment prevents ESI (rate ratio (RR), 0.36; 95% CI, 0.13–1.05), peritonitis (RR 0.78, 95% CI 0.50–1.21), and technical failure (RR, 1.35; 95% CI, 0.25–7.21). Moreover, a comparison between mupirocin and gentamicin showed no difference in the incidence of ESI (RR, 1.14; 95% CI, 0.27–4.81), peritonitis (RR, 0.85; 95% CI, 0.32–2.26), and technical failure (RR, 0.58; 95% CI, 0.28–1.20). Conclusions It remains unclear whether topical application of mupirocin on the exit site has any significant effects on PD-related infection or technical failure. Large-scale RCTs with high methodological quality are required to confirm the efficacy of topical application of antibiotics on the exit site. Trial registration UMINR000039267

Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcysteine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and immunofluorescence. Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.

Wear by fracture is among the factors associated with the DLC coating failures in the tribological application. The current study investigated the link between the wear and the fracture-toughness on the novel Pillar and Mesh structure ta-C coatings, in addition to conventional ta-C coatings. The tribological properties of these coatings were examined under base-oil lubrication via ball-on-disk tribo-tester and micro indentation technique was used to characterize the fracture toughness. The wear track and the indentation mark were analyzed using the optical microscope, 3D laser microscope and FE-SEM. The friction coefficient for ta-C, Pillar ta-C and Mesh ta-C are within the range of 0.071 to 0.106. Mesh ta-C indicated the highest wear resistance, followed by the Pillar ta-C and conventional ta-C. Also, Mesh ta-C demonstrated the highest fracture-toughness value with 16.6 MPa·m1/2, followed by Pillar ta-C with 13.4 MPa·m1/2 in contrast to ta-C. Greater resistance to wear for ta-C with Pillar and Mesh structure was detected with an increased fracture-toughness and improvement in crack propagation inhibition. Moreover, the Pillar and Mesh ta-C provides superior rate of crack-energy dissipation as compared to the ta-C.

Aims It was recently reported that lactate acts as a metabolic mediator and rises in the diabetic state, but the physiological effects are as yet poorly understood. The objective of the current study was to evaluate the significance of serum lactate elevation in type 2 diabetes mellitus (T2DM) patients. Methods Fasting serum lactate levels, hematological and inflammatory serum markers and anthropometric parameters, obtained employing bioelectric impedance analysis, were measured in 103 patients with T2DM. Results Statistically significant correlations of serum lactate levels with C-reactive peptide, insulin, aspartate aminotransferase, alanine aminotransferase (ALT), serum lipids, total bilirubin, adiponectin, homeostasis model assessment-insulin resistance, body weight, body mass index and body fat (weight or percentage of subcutaneous fat, visceral fat or total body fat), but neither fasting plasma glucose nor HbA1c, were detected. Stepwise regression analysis showed ALT to be independently positively associated with total bilirubin, while being negatively associated with serum lactate levels. Furthermore, serum lactate levels were significantly higher in patients with ALT-predominant liver dysfunction. Conclusion We found fasting serum lactate elevation in T2DM patients to be associated with the serum levels of ALT and total bilirubin independently of blood glucose control. Trial registration: UMIN clinical trials registry (UMIN000029178).

AIMS Rifaximin (RFX), a non-systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate the clinical profiles associated with gut bacterial loads using exploratory data analysis and the effects of RFX on the gut microbiota of patients with HE. METHODS We analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. Profiles associated with genera Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Changes in gut microbial consortia of seven patients with HE were then assessed 2 weeks after RFX treatment by principal component analysis. RESULTS In the CART, the first and second divergence variables for each higher bacterial load were as follows: (i) in Streptococcus, the number connection test-A ≥39.55 s and presence of portal-systemic shunt; (ii) in Veillonella, serum potassium levels

Introduction: Previous studies showed that the combination of peritoneal dialysis (PD) and once-weekly hemodialysis is associated with lower all-cause and cardiovascular mortality. This study aimed to compare the incidence of encapsulating peritoneal sclerosis (EPS) and infection-related mortality among those on combination therapy and those on PD alone. Methods: This prospective study on the Japanese Renal Data Registry included patients on PD from 2010 to 2014. Subjects were followed up until the end of 2015. Exposure of interest was combination therapy compared with PD alone. Patients who transitioned to combination therapy were matched with those on PD alone by propensity scores. Outcomes were EPS and infection-related mortality. Data were analyzed using Cox regression models. Results: Among the matched cohort, 608 and 869 patients were on combination therapy and on PD alone, respectively. Dialysate-to-plasma creatinine (D/P Cr) ratio decreased over time among those on combination therapy, while the ratio increased among those on PD alone ( p = 0.01 by the mixed-effects model). During a median follow-up of 2.5 years, 33 experienced EPS and 55 died of infection. Combination therapy was associated with lower infection-related mortality (HR [95% CI]: 0.52 [0.28–0.95]) but not with EPS (HR: 1.21 [0.61–2.40]). Lower mortality was not limited to intra-abdominal infection but also observed for pulmonary infection. Sensitivity analyses considering the effects of dialysis facilities yielded similar results. Conclusions: Combination therapy was associated with lower infection-related mortality. It was also associated with a decline in the D/P Cr ratio over time but not with lower incidence of EPS during the short observation period.

Gas-phase molecular adsorption was investigated as a model for molecular cloud formation. Molecular adsorption on cold gas-phase hydrogen-bonded clusters containing protonated tryptophan (Trp) enantiomers and monosaccharides such as methyl-α-D-glucoside, D-ribose, and D-arabinose was detected using a tandem mass spectrometer equipped with an electrospray ionization source and cold ion trap. The adsorption sites on the surface of cold gas-phase hydrogen-bonded cluster ions were quantified using gas-phase N2 adsorption-mass spectrometry. The gas-phase N2 adsorption experiments indicated that the number of adsorption sites on the surface of the hydrogen-bonded heterochiral clusters containing L-Trp and D-monosaccharides exceeded the number of adsorption sites on the homochiral clusters containing D-Trp and D-monosaccharides. H2O molecules were preferentially adsorbed on the heterochiral clusters, and larger water clusters were formed in the gas phase. Physical and chemical properties of cold gas-phase hydrogen-bonded clusters containing biological molecules were useful for investigating enantiomer selectivity and chemical evolution in interstellar molecular clouds.

Infrared neural stimulation has been studied for its potential to replace an electrical stimulation of a cochlear implant. No studies, however, revealed how the technic reliably evoke auditory cortical activities. This research investigated the effects of cochlear laser stimulation from the outer ear on auditory cortex using brain imaging of activity-dependent changes in mitochondrial flavoprotein fluorescence signal. An optic fiber was inserted into the gerbil's ear canal to stimulate the lateral side of the cochlea with an infrared laser. Laser stimulation was found to activate the identified primary auditory cortex. In addition, the temporal profile of the laser-evoked responses was comparable to that of the auditory responses. Our results indicate that infrared laser irradiation from the outer ear has the capacity to evoke, and possibly manipulate, the neural activities of the auditory cortex and may substitute for the present cochlear implants in future.

Hydrogenated amorphous carbon (a-C:H) coating exhibits different wear behaviors depending on its counterpart material in boundary lubricated sliding contact. In previous works, tribological behaviors of a-C:H coating were investigated against steel, chromium, and germanium counterpart materials. The specific wear rate of a-C:H coating was found to decrease with the ability of its counterpart material to react with or dissolve carbon. The present study investigated how graphitization of a-C:H coating's top layers and interactions of the counterpart material with carbon influence wear behaviors of a-C:H coating in boundary lubrication. Results show that a-C:H coating shows graphitization of its top layers regardless the counterpart material. Correlation with differences in wear behaviors of the a-C:H coating leads to the conclusion that graphitization will induce high wear of a-C:H coating only when there are also atomic interactions between the DLC coating and its counterpart material.

Investigations on tribological behaviors of Diamond-like Carbon (DLC) coating against other materials are strongly needed for scientific and industrial purposes. Recently, carbon diffusion has been found to play a key role in the wear of hydrogenated amorphous carbon (a-C:H) DLC coating when it is rubbed against steel counterpart material in boundary lubrication. Chromium has been reported to decrease carbon diffusion due to increase of the activation energy. In this research, we investigated on the effects of carbon diffusion on friction and wear properties of a-C:H coating when rubbed against Cr plating material. Results show that compared to steel counterpart, a-C:H coating exhibits lower friction coefficient, lower wear rate, and lower carbon diffusion rate when rubbed against Cr plating counterpart.

One of the solutions to reduce friction between two sliding surfaces in automobile engine is by applying DLC coating to engine components. However, it is critical that the effect of lubricant additives to DLC coating to be clarified before hands as to avoid components failure. In this study, tribological friction test between SUJ2 balls and as-deposited plus UV irradiated a-C:H coatings was conducted to clarify the effect of ultraviolet irradiation to DLC coating in four different additives added lubricant oils. AFM, nano-indentation hardness test, ellipsometery, Zygo, and EDS-SEM were used to investigate the effect of UV irradiation to a-C:H DLC before and after friction test. Prior the friction test, the results showed that UV irradiation presented no significant change in terms of hardness and roughness but the irradiation did penetrate into topmost surface of the a-C:H coating to several degree and created dangling bonds available to interact with lubricant additives elements. Friction test results showed that UV irradiated a-C:H coatings presented lower friction coefficient than as deposited a-C:H coatings. Worn surface analysis revealed that UV irradiated a-C:H coatings attracted more lubricant additives element to attach on its surface thus created thicker tribofilm on its own surface and its counter materials, resulted in lower friction coefficient than the as-deposited a-C:H coatings.

A silver-indium-cadmium (Ag-In-Cd, or AIC) alloy with a 1 eV high neutron cut-off energy was originaly developed as a decoupler to provide a narrow neutron pulse width with a short tail for the J-PARC 1-MW short-pulsed spallation neutron source. As a result of later studies, gold (Au) was chosen as a substitute for Ag for the production of spare decoupled moderators and reflector in order to reduce residual radioactivity thus easing handling and disposal of the spent moderator and reflector. The decoupler material Au-In-Cd (AuIC) was therefore investigated and developed. To implement it into an actual moderator-reflector assembly many critical engineering issues needed to be resolved with regard to large-sized bonding between AuIC and aluminum alloy A5083 by the hot isostatic pressing process (HIP). The HIP process for AuIC and aluminum was investigated in terms of surface condition, size, and heat capacity. Implementation of an AuIC decoupler into a spare reflector assembly was successfuly achieved and will result in a remarkable reduction of radioactivity compared to AIC without sacrificing neutronic performance.

Key Points Question Is the Simple Postoperative AKI Risk (SPARK) index, which was developed to predict postoperative acute kidney injury in noncardiac surgery, useful in a different population? Findings In a cohort study of 5135 adults in Japan, the incidence of postoperative acute kidney injury increased as scores on the SPARK index increased. However, the model’s discriminative and calibration powers were suboptimal owing to overestimated probability among those with especially high risk of developing acute kidney injury. Meaning These findings suggest that it is difficult to precisely predict the probability of acute kidney injury preoperatively in noncardiac surgery, which includes various surgical procedures and participants with various medical backgrounds., This cohort study externally validates the Simple Postoperative Acute Kidney Injury Risk (SPARK) index for prediction of acute kidney injury among patients undergoing noncardiac surgery., Importance The Simple Postoperative AKI Risk (SPARK) index is a prediction model for postoperative acute kidney injury (PO-AKI) in patients undergoing noncardiac surgery. External validation has not been performed. Objective To externally validate the SPARK index. Design, Setting, and Participants This single-center retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia from 2007 to 2011. Those with obstetric or urological surgery, estimated glomerular filtration rate (eGFR) of less than 15 mL/min/1.73 m2, preoperative dialysis, or an expected surgical duration of less than 1 hour were excluded. The study was conducted at Nara Medical University Hospital. Data analysis was conducted from January to July 2021. Exposures Risk factors for AKI included in SPARK index. Main Outcomes And Measures PO-AKI, defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours or 150% compared with preoperative baseline value or urine output of less than 0.5 mL/kg/h for at least 6 hours within 1 week after surgery, and critical AKI, defined as either AKI stage 2 or greater and/or any AKI connected to postoperative death or requiring kidney replacement therapy before discharge. The discrimination and calibration of the SPARK index were examined with area under the receiver operating characteristic curves (AUC) and calibration plots, respectively. Results Among 5135 participants (2410 [46.9%] men), 303 (5.9%) developed PO-AKI, and 137 (2.7%) developed critical AKI. Compared with the SPARK cohort, participants in our cohort were older (median [IQR] age, 56 [44-66] years vs 63 [50-73] years), had lower baseline eGFR (median [IQR], 82.1 [71.4-95.1] mL/min/1.73 m2 vs 78.2 [65.6-92.2] mL/min/1.73 m2), and had a higher prevalence of comorbidities (eg, diabetes: 3956 of 51 041 [7.8%] vs 802 [15.6%]). The incidence of PO-AKI and critical AKI increased as the scores on the SPARK index increased. For example, 10 of 593 participants (1.7%) in SPARK class A, indicating lowest risk, experienced PO-AKI, while 53 of 332 (16.0%) in SPARK class D, indicating highest risk, experienced PO-AKI. However, AUCs for PO-AKI and critical AKI were 0.67 (95% CI, 0.63-0.70) and 0.62 (95% CI, 0.57-0.67), respectively, and the calibration was poor (PO-AKI: y = 0.24x + 3.28; R2 = 0.86; critical AKI: y = 0.20x + 2.08; R2 = 0.51). Older age, diabetes, expected surgical duration, emergency surgery, renin-angiotensin-aldosterone system blockade use, and hyponatremia were not associated with PO-AKI in our cohort, resulting in overestimation of the predicted probability of AKI in our cohort. Conclusions and Relevance In this study, the incidence of PO-AKI increased as the scores on the SPARK index increased. However, the predicted probability might not be accurate in cohorts with older patients with more comorbidities.

MoDTC has also been reported to degrade into other Mo-derived compounds. It is essential to analyze the effects of each type of MoDTC-degraded material on DLC. Therefore, we chose powder-type MoDTC, MoS2, Mo, MoO3, and Mo2C additives to be dispersed individually into a base oil and tested on an a-C:H sliding against a steel ball under boundary lubrication conditions at 80 °C. We then obtained surface-enhanced Raman scattering (SERS), which proved that MoS2 has the possibility of extracting hydrogen from the topmost surface as chemical wear (hydrogen content decreased from 30 to 35 at.% to 20 at.% of as-deposited) and that MoO3, MoDTC, and Mo have the possibility of catalytic reactions with carbon atoms. Mo2C exhibited abrasive accelerate of the a-C:H wear.

Tetrahedral amorphous carbon nitride (ta-CNx), as an emerging and promising diamond-like carbon (DLC), has better mechanical properties than amorphous carbon nitride (a-CNx) to ensure the sufficient durability, and overcomes the limit of high internal stress of tetrahedral amorphous carbon (ta-C), which makes ta-CNx coatings of great worth of research for the tribological and mechanical applications. In this study, we present the effects of oil temperature and counterpart material on the wear behavior of ta-CNx coatings under base-oil lubrication, and further clarify the wear mechanism. ta-C and ta-CNx coatings with N/C atomic ratio of 2.2% and 11.0% were deposited by an ion beam assisted filtered arc deposition (IBA-FAD) system, and the tribological tests were performed using a ball-on-disk tribo-tester with ta-C and ta-CNx coated steel ball sliding against uncoated disk under base-oil lubrication. The results show that nitrogen doping tends to decrease the hardness and Young's modulus by reducing the sp3 structure. Sliding against steel disk, with increase of sliding distance ta-CNx shows obviously distinct wear behavior compared to ta-C, much more slowly increasing wear volume, exhibiting excellent wear resistance. Increasing oil temperature from room temperature to 120 °C results in rising wear rates of all the three coatings, with totally worn out ta-C and much lower wear rate of ta-CNx, which decreases by more than half than ta-C for high nitrogen content ta-CNx. However, as the counterpart material changed from steel to alumina, the wear rate presents oppositely increasing tendency with N/C ratio, probably caused by the change of deciding factor to hardness in this mechanical wear. It is found that the wear performance of ta-CNx coating has a clear dependence on the oil temperature and counterpart material. Based on the results, the better wear resistance of softer ta-CNx against steel could be attributed to the less tribo-chemical wear between carbon and iron, due to the nitrogen doping partial passivation effect.

Ras undergoes post-translational modifications including farnesylation, proteolysis, and carboxymethylation at the C terminus, which are necessary for membrane recruitment and effector recognition. Full activation of c-Raf-1 requires cooperative interaction of the farnesylated C terminus and the activator region of Ras with its cysteine-rich domain (CRD). However, the molecular basis for this interaction remains unclear because of difficulties in preparing modified Ras in amounts sufficient for structural studies. Here, we use Sortase A-catalyzed protein ligation to prepare modified Ras in sufficient amounts for NMR and X-ray crystallographic analyses. The results show that the farnesylated C terminus establishes an intramolecular interaction with the catalytic domain and brings the farnesyl moiety to the proximity of the activator region, which may be responsible for their cooperative recognition of c-Raf-1-CRD.

This work shows new method which controls adhesion strength between acrylic resin and metal mold with electric field. Usage of electric field is considered as a new solution to control adhesion of thermoplastic resin in Carbon-Fiber-Reinforced ThermoPlastic (thermoplastic CFRP) stamping process because this method can prevent CFRP from its degradation. In this work, we establish new adhesion tester which can apply Direct Current (DC) or Alternating Current (AC) field on metal specimens. In the results, when DC −12 V/mm is imposed on metal specimens, adhesion strength increases to 0.81 MPa which is 57% higher than that of no field condition. Negative component of surface energy after imposing DC −12 V/mm on metal specimens is 7.6 mJ/m2. This value is 56% smaller than that of no field condition. When AC electric fields is imposed, adhesion strength decreases from no electric field condition. The most effective AC field condition is AC 10 V/mm with 1 MHz, in which case adhesion strength is 0.29 MPa. This value is 44% lower than that of no field condition.

Background The pathophysiology of chronic rhinosinusitis (CRS) is still not well known due to the multifactorial etiologies involved. Bacteria play a role in the pathogenesis of CRS by various means, including biofilm adhesion, intracellular persistence, or inducing inflammation secondary to toxins. Endotoxins and exotoxins, especially Staphylococcus aureus superantigens, can produce significant immune responses in the host and are implicated in patients with CRS. The majority of animal models described for CRS revalidates the pathophysiology of acute sinusitis, ostium occlusion, or foreign body associated infection. Objectives To evaluate an experimental model of eosinophilic CRS using prolonged exposure to bacterial toxins. The histological changes in rabbits exposed to S. aureus enterotoxin B (SEB), lipopolysaccharide (LPS), or lipoteichoic acid (LTA) were compared. Methods After induction with ovalbumin (OVA) sensitization with subcutaneous injection for 2 weeks, rabbits underwent surgery to insert an indwelling catheter into the maxillary sinus. The sinus was irrigated with OVA 3 times weekly for 2 weeks, followed by sinus irrigation with bacterial toxin (SEB: 1 µg/mL, LPS: 100 ng/mL, or LTA: 100 ng/mL) 3 times weekly for 4 weeks. The histological changes in the treated sinus were compared with control rabbits. Results Sinuses exposed to bacterial toxins (SEB, LPS, and LTA) produced significant mucosal thickening with infiltration of inflammatory cells, notably eosinophils. SEB was the only toxin that promoted a mixed pattern of inflammation, including eosinophilic and neutrophilic infiltration. Conclusion Our experimental model of eosinophilic CRS in rabbits produced significant mucosal thickening and inflammation in the sinuses exposed to bacterial toxins, with histological changes analogous to what is observed in patients with CRS with nasal polyps. This model may serve as a basis for future investigation of the pathogenesis of eosinophilic CRS in relation to bacterial toxins or as a model for testing new therapeutic modalities for this disease.

The use of porous scaffolds created by additive manufacturing is considered a viable approach for the regeneration of critical-size bone defects. This paper investigates the xenotransplantation of polycaprolactone (PCL) tissue constructs seeded with differentiated and undifferentiated human adipose-derived mesenchymal stem cells (hADSCs) to treat calvarial critical-sized defect in Wistar rats. PCL scaffolds without cells were also considered. In vitro and in vivo biological evaluations were performed to assess the feasibility of these different approaches. In the case of cell seeded scaffolds, it was possible to observe the presence of hADSCs in the rat tissue contributing directly (osteoblasts) and indirectly (stimulation by paracrine factors) to tissue formation, organization and mineralization. The presence of bone morphogenetic protein-2 (BMP-2) in the rat tissue treated with cell-seeded PCL scaffolds suggests that the paracrine factors of undifferentiated hADSC cells could stimulate BMP-2 production by surrounding cells, leading to osteogenesis. Moreover, BMP-2 acts synergistically with growth factors to induce angiogenesis, leading to higher numbers of blood vessels in the groups containing undifferentiated and differentiated hADSCs.

Diamond-like carbon (DLC) coatings are designed to work under severe lubrication conditions. Depending on working environment, lubrication condition, and counterpart material, DLC coatings can exhibit crucial variations in their tribological behaviors. In the search of a counterpart material to improve tribological performances of DLC coatings in desired environment, we found out in previous work that carbon diffusion is an important parameter that influences the tribological behaviors of amorphous hydrogenated (a-C:H) coating in boundary lubrication. a-C:H coating exhibits high wear against steel counterpart material that has a high carbon affinity/solubility, while its exhibits lower wear against chromium counterpart material that has lower carbon affinity/solubility than steel. These recent findings imply that consideration of the carbon affinity/solubility when choosing a counterpart material for a-C:H coating in boundary lubrication might be of significant importance to improve tribological performances of a-C:H coating. This research investigates tribological behaviors of a-C:H coating against germanium counterpart material that has extremely low carbon affinity/solubility. Results show that there is no atomic interaction between a-C:H coating and germanium during friction and wear test, followed with a very low wear of a-C:H coating., ファイル公開：2020/06/01

AIMS Tocilizumab (TCZ), a humanized anti-interleukin-6 receptor monoclonal antibody, is used to treat rheumatic diseases. There is limited information about the administration of TCZ during lactation. The dried spot method, a simple technique for processing biological samples which involves placement of a drop of specimen onto filter paper, has been used in clinical pharmacology to determine various drug concentrations. This study examined the feasibility of sample collection using the dried milk spot (DMS) method for obtaining data about the transfer of TCZ into breast milk. METHODS Concentrations of TCZ determined using DMSs prepared by patients were compared with those using liquid breast milk. RESULTS In an enzyme-linked immunosorbent assay of TCZ in DMSs, the accuracy ranged from 93.0% to 113.8% and the precision ranged from 0.3% to 8.4%. All concentrations of TCZ were within 15% of the reference value when analyzed on separate days. TCZ in DMSs at room temperature, 4°C, and -20°C were stable for 28 days. Extracted TCZ concentrations from patient-prepared DMSs were strongly correlated with those of liquid samples (r = 0.996). In a pharmacokinetic study, the median (range) maximum and minimum concentrations were 113 ng/mL (68-205) and 8.5 ng/mL (4.8-13.4), respectively. The milk-to-serum ratio at the trough TCZ concentration of 3 lactating mothers were 0.0015, 0.00082 and 0.0014. CONCLUSIONS The DMS method for measuring TCZ transfer into breast milk may be reliable and feasible, and should contribute to evaluating the safety of breast-fed infants whose mothers receive TCZ during lactation.

Both adiponectin and secreted protein, acidic and rich in cysteine (SPARC) inhibit platelet-derived growth factor-BB (PDGF-BB)-induced and basic fibroblast growth factor (FGF2)-induced angiogenic activities through direct and indirect interactions. Although SPARC enhances nerve growth factor (NGF)-dependent neurogenesis, the physical interaction of NGF&beta, with adiponectin and SPARC remains obscure. Therefore, we first examined their intermolecular interaction by surface plasmon resonance method. NGF&beta, bound to immobilized SPARC with the binding constant of 59.4 nM, comparable with that of PDGF-BB (24.5 nM) but far less than that of FGF2 (14.4 &micro, M). NGF&beta, bound to immobilized full length adiponectin with the binding constant of 103 nM, slightly higher than those of PDGF-BB (24.3 nM) and FGF2 (80.2 nM), respectively. Treatment of PC12 cells with SPARC did not cause mitogen-activated protein kinase (MAPK) activation and neurite outgrowth. However, simultaneous addition of SPARC with NGF&beta, enhanced NGF&beta, induced MAPK phosphorylation and neurite outgrowth. Treatment of the cells with adiponectin increased AMP-activated protein kinase (AMPK) phosphorylation but failed to induce neurite outgrowth. Simultaneous treatment with NGF&beta, and adiponectin significantly reduced cell size and the number of cells with neurite, even after silencing the adiponectin receptors by their siRNA. These results indicate that NGF&beta, directly interacts with adiponectin and SPARC, whereas these interactions oppositely regulate NGF&beta, functions.

Diamond-like Carbon (DLC) film and Carbon Nitride (CNx) film are expected to be applied to automotive engine bearings because they show low friction and high wear resistance. Whereas many fundamental tribological re-searches of DLC and CNx have been conducted, practical researches of these coatings on engine bearings are still not enough. Therefore, clarifying friction and wear properties of the coatings on real engine bearings are strongly required. Especially, since lubrication conditions of engine bearings vary in automotive drive, clarifying the effect of lubrication conditions on tribological properties is important. For the reasons, we focus on the clarification of the effect of lubrication condition on friction and wear properties of the bearings coated with several DLC coatings. In this research, tribological properties of three different types of bearings, aluminium-alloy bearings without any coatings, a-C:H coated bearings and CNx coated bearings, are compared. The CNx coating was deposited by Ion Beam Assisted Deposition (IBAD) method on a-C:H coated bearings. As results, it is clarified that CNx coated bearings show the lowest friction coefficient, μ = 0.10, between three bearings under low sliding speed conditions. Under high sliding speed conditions, CNx after running-in also shows the lowest friction co-efficient. In the view point of wear, CNx coating reduces specific wear rate to 4.5 × 10−9 mm3/Nm from the value of a-C:H coating, 7.9 × 10−8 mm3/Nm. From these results, it is clarified that CNx coating on a-C:H coated bearing achieves low friction and high wear resistance coating on engine bearings.

The gas-phase adsorption of N2 on protonated serine (Ser, C3H7NO3), threonine (Thr, C4H9NO3), glycine (Gly, C2H5NO2), and 2-aminoethanol (C2H7NO) was investigated using a tandem mass spectrometer equipped with an electrospray ionization source and a cold ion trap. N2 molecules were adsorbed on the free X-H (X=O and N) groups of protonated molecules. Gas-phase N2 adsorption-mass spectrometry detected the presence of free X-H groups in the molecular structures, and was applied to the structural elucidation of small molecules. When the 93 structures with an elemental composition of C3H7NO3 were filtered using the gas-phase N2 adsorption-mass spectrometry results for Ser, the number of possible molecular structures was reduced to 8 via the quantification of the X-H groups. Restricting and minimizing the number of possible candidates were effective steps in the structural elucidation process. Gas-phase N2 adsorption-mass spectrometry combined with mass spectrometry-based techniques has the potential for being useful for elucidating the molecular structures of a variety of molecules.

Ring-linear blends composed of complexes bearing multiple rings are promising candidates for soft devices, and understanding the penetration of linear chains into rings is essential for enhancing their mechanical properties. Coarse-grained molecular dynamics simulations of ring-linear blends composed of bonded rings or polycatenanes bearing two or three rings were performed for revealing the conformations in blends. To investigate the relationship between the conformations of ring polymers and penetration of linear chains, we considered linear-rich systems with fring = 0.05 and 0.1, where fring is the fraction of ring complex. The number of linear chains penetrating rings ( n P ) was estimated from the Gauss linking number for all the pairs of ring polymers and linear chains. Dependence of penetration on the ring size was determined from the probability distributions of n P . Average n P ( " open=" n P ) of the systems with polycatenanes was slightly higher than those of the systems with bonded rings. For fring = 0.1, " open=" n P of the single ring was 3.41 when number of beads per a ring was Nring = 160. " open=" n P of the bonded two-ring system and poly-[2]-catenane with Nring = 80 was 2.60 and 2.87, respectively, while " open=" n P of the bonded three-ring system and poly-[3]-catenane with Nring = 80 was 3.63 and 3.87, respectively, which were slightly higher than that of the single ring with Nring = 160. Since the ring complexes had multiple chains penetrating even for low Nring, mechanical properties of the crosslinked ring-linear blend were expected to be controlled by the ring complexes instead of the single ring.

Chiral recognition between amino acids and monosaccharides in the gas phase was investigated as a model for chemical evolution in interstellar molecular clouds. Ultraviolet (UV) photodissociation spectra and product ion spectra of cold gas-phase hydrogen-bonded clusters of protonated tryptophan (Trp) and a pentose, including ribose and arabinose, were obtained using a tandem mass spectrometer equipped with an electrospray ionization source and a temperature-controlled ion trap. The relative intensity of the signal arising from the S1–S0 transition of protonated Trp observed at approximately 285 nm in the UV photodissociation spectrum of homochiral H+( d -Trp)( d -ribose) was significantly higher than that of heterochiral H+( l -Trp)( d -ribose), corresponding to the ππ* state of the Trp indole ring. Optical properties of Trp in the clusters induced by 285-nm photoexcitation were applied to the identification and quantification of pentose enantiomers in solution. Pentose enantiomeric excess in solution was determined from relative abundances observed in a single product ion spectrum of 285-nm photoexcited hydrogen-bonded clusters of H+( l -Trp) and pentose. A mixture of two pentoses could also be quantified by this method. The geometric and electronic structures of Trp enable recognition of biological molecules through hydrogen bonding.

Coarse-grained molecular dynamics simulations of Kremer–Grest-type bead-spring models were performed on mixtures of ring and linear polymers to investigate the effects of chain-penetration on polymer ring shape. We found that the number of linear chains penetrating through a ring increased with ring size, while penetration was inhibited for smaller rings composed of less than 80 beads. From the eigenvalue analyses of the gyration tensor of each ring, the ring shape was characterized by asphericity and prolateness. The number of chains penetrating through a ring (nP) was determined from the Gauss linking numbers of all ring and linear chain pairs. The radius of gyration of the rings were dependent on the nP value, suggesting that the linear chains expanded the ring upon penetration. The obtained results provide important insights in ring-linear blends for theoretical research as well as simulations and experiments especially for rheological measurements.