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Chronic diabetic wounds are the most common complication for diabetic patients. Due to high oxidative stress levels affecting the entire healing process, treating diabetic wounds remains a challenge. Here, we present a strategy for continuously regulating oxidative stress microenvironment by the catalyst-like magnesium-gallate metal-organic framework (Mg-GA MOF) and developing sprayable hydrogel dressing with sodium alginate/chitosan quaternary ammonium salts to treat diabetic wounds. Chitosan quaternary ammonium salts with antibacterial properties can prevent bacterial infection. The continuous release of gallic acid (GA) effectively eliminates reactive oxygen species (ROS), reduces oxidative stress, and accelerates the polarization of M1-type macrophages to M2-type, shortening the transition between inflammation and proliferative phase and maintaining redox balance. Besides, magnesium ions adjuvant therapy promotes vascular regeneration and neuronal formation by activating the expression of vascular-associated genes. Sprayable hydrogel dressings with antibacterial, antioxidant, and inflammatory regulation rapidly repair diabetic wounds by promoting neurovascular network reconstruction and accelerating re-epithelialization and collagen deposition. This study confirms the feasibility of catalyst-like MOF-contained sprayable hydrogel to regulate the microenvironment continuously and provides guidance for developing the next generation of non-drug diabetes dressings.

Abstract Background Hyalinizing trabecular tumor (HTT) is an uncommon follicular cell-derived thyroid tumor classified as a low-risk neoplasm by the World Health Organization Classification of Tumors of Endocrine Organs, 5th edition. The PAX8-GLIS3 gene fusion is reportedly a pathognomonic genetic alteration of HTT. Case presentation A 43-year-old Japanese female was incidentally discovered to have an 8-mm, well-defined, hypoechoic mass in the left lobe of the thyroid gland by ultrasound examination. Contrast-enhanced computed tomography scan revealed a solid mass exhibiting slight homogeneous enhancement in the lower pole of the thyroid gland. The mass was diagnosed as atypia of undetermined significance by fine-needle aspiration cytology. The patient underwent left hemithyroidectomy with routine central compartment dissection. Histologic findings revealed tumor cells with elongated nuclei and intranuclear pseudoinclusions arranged with trabeculae architecture or small nests in hyalinized stroma. Weak membranous and cytoplasmic staining was found by MIB1 (Ki-67) immunostaining. The final diagnosis was HTT of the thyroid gland. Next-generation sequencing genetic analysis of a surgical specimen revealed no pathologic mutations, including BRAF, H/K/NRAS, or RET-PTC fusions. The PAX8-GLIS3 fusion was detected by RT-PCR. Conclusions A rare case of HTT was demonstrated through imaging, cytologic, histologic and molecular investigations. PAX8-GLIS3 fusion detected by RT-PCR and Sanger sequencing was confirmed to be a genetic hallmark of HTT.

Abstract Arthritis is a chronic disease whose etiology is difficult to pinpoint, and the difficulty of arthritis detection and subsequent treatment causes enormous distress to patients. In recent years, thanks to advances in medicine and detection, a variety of treatment modalities for arthritis have emerged. The combination of emerging detection technologies with different anti‐inflammatory medications and even advances in surgical techniques have all played a positive role in the treatment of arthritis. In the present work, we have collected relevant literature on fluorescence (FL) imaging and phototherapy of arthritis in recent years, intending to reveal the advantages and potential application value of FL imaging and phototherapy for researchers. Meanwhile, due to the shortcomings of FL imaging and phototherapy in the diagnosis and treatment of arthritis, we advocate overcoming these difficulties in future research.

Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectability, high strength, and biocompatibility simultaneously remains a significant challenge. Herein, we propose a strategy to develop high-performance bone cement and establish a trimagnesium phosphate cement (TMPC) system. The TMPC exhibits high early strength, low curing temperature, neutral pH, and excellent injectability, overcoming the critical limitations of recently studied magnesium phosphate cement. By monitoring the hydration pH value and electroconductivity, we demonstrate that the magnesium-to-phosphate ratio could manipulate the components of hydration products and their transformation by adjusting the pH of the system, which will influence the hydration speed. Further, the ratio could regulate the hydration network and the properties of TMPC. Moreover, in vitro studies show that TMPC has outstanding biocompatibility and bone-filling capacity. The facile preparation properties and these advantages of TMPC render it a potential clinical alternative to polymethylmethacrylate and calcium phosphate bone cement. This study will contribute to the rational design of high-performance bone cement.

There are very few reports of syndrome of inappropriate antidiuresis hormone secretion (SIADH) after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Herein, we present the case of an 84-year-old woman who developed severe hyponatremia following the second administration of the SARS-CoV-2 mRNA vaccine. The patient presented with nausea, vomiting, and headache. Laboratory tests showed a plasma sodium level of 119 mmol/L. After receiving 500 mL of intravenous saline over a 2-h period, her plasma sodium level raised to 121 mmol/L, but her symptoms persisted. Considering that rapid plasma sodium correction was necessary, we started 3% saline solution overnight. Her plasma sodium level raised to 132 mmol/L and her symptoms completely resolved. Clinical and laboratory findings were consistent with a diagnosis of SIADH. In the absence of any other triggering factors, we concluded that the condition was likely associated with the vaccination. Clinicians should be aware of the potential for hyponatremia, particularly SIADH, associated with SARS-CoV-2 mRNA vaccination.

Background: The development of temporal bone pneumatization is related to the postnatal middle ear environment, where the development of air cells is suppressed with otitis media in early childhood. However, whether air cell formation restarts when mastoidectomy is performed during temporal bone pneumatization remains unclear. Herein, we evaluated temporal bone pneumatization after canal wall up (CWU) tympanomastoidectomy for middle ear cholesteatoma in children. Methods: In total, 63 patients, including 29 patients with congenital cholesteatoma (CC) and 34 patients with acquired cholesteatoma (AC), were assessed using a set of pre- and postoperative computed tomography images. The air cells of the temporal bone were divided into five areas: periantral (anterior), periantral (posterior), periantral (medial), peritubal, and petrous apex. The number of areas with air cells before and after surgery was compared to evaluate temporal bone pneumatization after surgery. Results: A total of 63 patients, comprising 29 with CC and 34 with AC (pars flaccida; 23, pars tensa; 7, unclassified; 4), were evaluated. The median age of patients (18 males and 11 females) with CC was 5.0 (range, 2–15 years), while that of the AC group (23 males and 11 females) was 8 (range, 2–15 years). A significant difference in air cell presence was identified in the CC and AC groups after surgery (Mann–Whitney U, p < 0.001 and p = 0.003, respectively). Between the two groups, considerably better postoperative pneumatization was observed in the CC group. A correlation between age at surgery and gain of postoperative air cell area development was identified in the CC group (Spearman’s rank-order correlation coefficient, r = −0.584, p < 0.001). In comparison with the postoperative pneumatization rate of each classified area, the petrous apex area was the lowest in the CC and AC groups. Conclusions: Newly developed air cells were identified in the temporal bones after CWU mastoidectomy for pediatric cholesteatoma. These findings may justify CWU tympanomastoidectomy, at least for younger children and CC patients, who may subsequently develop air cell systems after surgery.

ABSTRACTFully dense Al2TiO5–Al2O3–TiN (ATN) composites were fabricated by reactive sintering using spark plasma sintering at 1400°C for 5 min under 100 MPa in vacuum. An equimolar ratio of Al2O3:TiO2 was used as the starting powder, while the addition of 0–36 mol% AlN was investigated. The thermodynamic calculation indicates that the initial reaction was that of TiO2 and AlN, forming TiN and Al2O3, and then the remaining TiO2 reacted with Al2O3 to produce Al2TiO5. With the increase in AlN precursor, Al2TiO5 gradually decreased, while Al2O3 and TiN increased. The lattice parameters of Al2TiO5 were enlarged with AlN addition, implying the incorporation of N atoms in the Al2TiO5 unit cell. The addition of AlN effectively produced fully densified bodies with small grain size, and microcrack-free, which therefore enhanced the mechanical properties of ATN composites. At 36 mol% AlN addition, the composite shows Vickers hardness and fracture toughness of 16.26 ± 1.61 GPa and 5.20 ± 0.46 MPa.m1/2, respectively.

The development of high-performance electrode materials with a far-from-enough energy density has still been crucial for the real applications of supercapacitor technology. In this paper, the N-doped and derivatized-carbon-intercalated Ti3C2Tx, abbreviated as N–Ti3C2Tx/C, was firstly fabricated using ZIF-67 as an intermediate precursor. Then N–Ti3C2Tx/C/CuS was prepared by further intercalation with CuS nanoparticles through a room-temperature-in-situ-reaction route. The doped pyridine N and pyrrolic N, together with derivatized carbon, optimized the surface charge distribution of Ti3C2Tx with increased active sites. In addition, CuS nanoparticles were observed distributed on the surface and between layers of single/multi-layered two-dimensional N–Ti3C2Tx/C nanosheets, forming a heterogeneous three-dimensional structure. Therefore, the specific capacitance of the N–Ti3C2Tx/C/CuS composite at a current density of 1 A g−1 reached 1205.8 F g−1, about 5 times that of N–Ti3C2Tx/C and 2 times of CuS, also much higher than other composite reported in the literature. The energy density and power density of N–Ti3C2Tx/C/CuS, as a symmetric supercapacitor electrode, are 77.22 Wh·kg−1 and 649.54 W kg−1, respectively. More importantly, N–Ti3C2Tx/C/CuS has an excellent stability after 3000 cycles, surpassing that of similar electrode materials reported in literature. This study opens a new direction for enhancing the energy density of supercapacitors with modified electrode materials through a MOF-mediated strategy.

To conquer the trade-off dilemma of the nanofiltration membranes for both high permeability for water and high rejection for pollutants has long been highly concerned. In this work, TiO2 and Bi2S3 nanoparticles were evenly dispersed successively into the interlayers of Ti3C2Tx nanosheets, and then filtered onto cellulose acetate support membranes. The as-obtained composite membranes exhibited a maximum water flux of 374.4 L m−2 h−1 bar−1, and a high rejection ratio for RhB, GR, MB and BSA at 97.8–100%, apparently higher than those of the Ti3C2Tx and the related membranes in literature. Such a high separation capacity was found quite stable for various dye-containing aqueous solutions, even in a high salinity environment of 5 wt% NaCl. Interestingly, 25% NaCl salt was also rejected accompanying the almost complete rejection of dye pollutants. After the filtering process, the membrane fouling of fouled Ti3C2Tx/TiO2/Bi2S3 membranes was verified quite lower than that of fouled Ti3C2Tx/TiO2 and Ti3C2Tx membranes. Furthermore, the flux recovery rate of the fouled composite membrane could reach 92.1% after washing under visible light, which could be ascribed to the composition of heterojunction causing the red shift of diffuse reflectance UV–vis spectra and the narrowing of the band gap. This study provides a new idea for the preparation of highly permeable and rejective nanofiltration membranes, and lays a foundation for its high-capacity dye removal applications.

Legumes develop root nodules in association with compatible rhizobia to overcome nitrogen deficiency. Rhizobia enter the host legume, mainly through infection threads, and induce nodule primordium formation in the root cortex. Multiple transcription factors have been identified to be involved in the regulation of the establishment of root nodule symbiosis, including ERF Required for Nodulation1 (ERN1). ERN1 is involved in a transcription network with CYCLOPS and NODULE INCEPTION (NIN). Mutation of ERN1 often results in misshapen root hair tips, deficient infection thread formation, and immature root nodules. ERN1 directly activates the expression of ENOD11 in Medicago truncatula to assist cell wall remodeling and Epr3 in Lotus japonicus to distinguish rhizobial exopolysaccharide signals. However, aside from these two genes, it remains unclear which genes are regulated by LjERN1 or what role LjERN1 plays during root nodule symbiosis. Thus, we conducted RNA sequencing to compare the gene expression profiles of wild-type L. japonicus and Ljern1-6 mutants. In total, 234 differentially expressed genes were identified as candidate LjERN1 target genes. These genes were found to be associated with cell wall remodeling, signal transduction, phytohormone metabolism, and transcription regulation, suggesting that LjERN1 is involved in multiple processes during the early stages of the establishment of root nodule symbiosis. Many of these candidate genes including RINRK1 showed decreased expression levels in Ljnin-2 mutants based on a search of a public database, suggesting that LjERN1 and LjNIN coordinately regulate gene expression. Our data extend the current understanding of the pleiotropic role of LjERN1 in root nodule symbiosis.

Abstract Delirium is a critical challenge in the intensive care unit (ICU) or high care unit (HCU) setting and is associated with poor outcomes. There is not much literature on how many patients in this setting are assessed for delirium and what tools are used. This study investigated the status of delirium assessment tools of patients in the ICU/HCU. We conducted a multicenter prospective observational study among 20 institutions. Data for patients who were admitted to and discharged from the ICU/HCU during a 1-month study period were collected from each institution using a survey sheet. The primary outcome was the usage rate of delirium assessment tools on an institution- and patient-basis. Secondary outcomes were the delirium prevalence assessed by each institution’s assessment tool, comparison of delirium prevalence between delirium assessment tools, delirium prevalence at the end of ICH/HCU stay, and the relationship between potential factors related to delirium and the development of delirium. Result showed that 95% of institutions used the Intensive Care Delirium Screening Checklist (ICDSC) or the Confusion Assessment Method for the ICU (CAM-ICU) to assess delirium in their ICU/HCU, and the remaining one used another assessment scale. The usage rate (at least once during the ICU/HCU stay) of the ICDSC and the CAM-ICU among individual patients were 64.5% and 25.1%, and only 8.2% of enrolled patients were not assessed by any delirium assessment tool. The prevalence of delirium during ICU/HCU stay was 17.9%, and the prevalence of delirium at the end of the ICU/HCU stay was 5.9%. In conclusion, all institutions used delirium assessment tools in the ICU/HCU, and most patients received delirium assessment. The prevalence of delirium was 17.9%, and two-thirds of patients had recovered at discharge from ICU/HCU. Trial registration number: UMIN000037834.

Abstract We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996–2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients

SiO2-diamond composites with 65–85 mass% diamond were fabricated by spark plasma sintering at 1873 K under 130 MPa for 300 s using bimodal diamond particle size of 2 and 25 µm in diameter. The diamond particles were coated with a SiC layer by chemical vapor deposition. The effects of diamond content on relative density, microstructure, and Vickers hardness of the SiO2-diamond composites were investigated. The SiO2-diamond composites exhibited relative density of 96%, and Vickers hardness of 36.2 ± 3.6 GPa at 75 mass% diamond content.

Lu2(Ti1-xHfx)2O7 (x = 0–0.5) transparent ceramics were fabricated by reactive spark plasma sintering using commercially available Lu2O3, TiO2 and HfO2 powders. Effect of Hf content x on the phase evolution, microstructure, density, transmittance and electrical conductivity of the resulting ceramics were investigated. Lu2(Ti1-xHfx)2O7 transparent ceramic had a pyrochlore structure in the range of x = 0–0.3, while preserved a defect-fluorite structure at x = 0.4–0.5. The lattice parameter and theoretical density increased linearly with increasing Hf content x. The average grain size decreased at x = 0–0.3 and kept almost constant at x = 0.4–0.5. All the samples exhibited a dense microstructure and the highest in-line transmittance was 57% at 550 nm at x = 0. The highest bulk conductivity was 1.7 × 10−2 S m−1 at 1073 K for Lu2(Ti0.8Hf0.2)2O7, with an activation energy of 1.16 eV.

Bone conduction implants (BCIs) and middle ear implants (MEIs) are promising options for individuals with persistent chronic inflammation of the middle or outer ear. However, the structure of the middle ear is often altered in patients who undergo mastoidectomy or posterior wall removal for refractory otitis media, leaving uncertainty regarding the efficacy of hearing devices. Only a few studies have examined auditory outcomes based on the etiology of hearing impairment. We investigated hearing outcomes, including speech audiometry, in patients who underwent implantation after surgery for refractory otitis media. Our findings indicated that patients who received BCIs or MEIs achieved favorable hearing outcomes. Furthermore, a correlation was observed between the preoperative bone-conduction threshold at 1 kHz in the better ear and the sound-field threshold at 1 kHz with BCIs, whereas no correlation was observed between the preoperative bone-conduction threshold and the sound-field threshold with MEIs. This study highlights the positive impact of BCIs and MEIs in patients who undergo implantation after surgery for refractory otitis media. Additionally, our study identified parameters that predict postoperative efficacy.

Laser chemical vapor deposition (LCVD) was applied to prepare SmBa2Cu3O7-δ (SmBCO) superconductive films on single-crystalline LaAlO3 (100) substrates. The effect of oxygen partial pressure (PO2) on the crystal orientation, microstructure, and superconducting property of SmBCO film were investigated thoroughly. The results of X-ray diffraction (XRD) and Raman showed that the crystal orientation of SmBCO film was pure c-axis orientation at the PO2 of 200 Pa, and the a-axis orientation grains gradually emerged in SmBCO film with the increase of PO2. The deposition rate, critical temperature (Tc), critical current density (Jc) firstly increased and then decreased with the increase of PO2. At the PO2 of 200 Pa, the SmBCO film had smooth and dense surface, the lowest FWHM of φ-scan (1.1°), the highest Tc (89.2 K) and Jc (2.04 MA/cm2), which indicated that SmBCO superconductive films possessed excellent crystal structure and superconducting performance.

Single-walled carbon nanotubes (SWCNTs) modified by introducing non-six-membered ring defects, such as five- and seven-membered rings, have attracted considerable attention because their conductivity is enhanced by increasing the electronic density of states at the Fermi energy level. However, no preparation method exists to efficiently introduce non-six-membered ring defects into SWCNTs. Herein, we attempt to introduce non-six-membered ring defects into SWCNTs by defect rearrangement of the nanotube framework using a fluorination–defluorination process. Defect-introduced SWCNTs were fabricated from SWCNTs fluorinated at 25 °C for different reaction times. Their structures were evaluated, and their conductivities were measured by operating a temperature program. Structural analysis of the defect-induced SWCNTs using X-ray photoelectron spectroscopy, Raman spectroscopy, high-resolution transmission electron microscopy, and visible–near-infrared spectroscopy did not reveal the presence of non-six-membered ring defects in the SWCNTs but indicated the introduction of vacancy defects. Meanwhile, conductivity measurements performed by operating a temperature program showed that the defluorinated SWCNTs prepared from SWCNTs fluorinated for 3 min (deF-RT-3m) exhibited decreased conductivity owing to the adsorption of water molecules to non-six-membered ring defects, thereby implying the possibility of non-six-membered ring defects being introduced into deF-RT-3m.

Abstract Introduction The combination of methotrexate (MTX) with biological disease-modifying antirheumatic drugs (bDMARDs) is a recommended treatment option for rheumatoid arthritis (RA) patients showing an inadequate response to MTX monotherapy. However, the adequate dose of MTX, especially in long-term treatment with bDMARDs/MTX combination therapy, remains under-addressed. Since RA patients require long-term treatment, we examined the effects of using golimumab (GLM) in the long run as well as its persistency and associated factors. Methods We used the Japan Medical Data Center Inc. (JMDC) administrative claims data of 489 patients receiving GLM therapy for calculating the persistency in patients with constant, reduced, or escalated MTX dosing. The factors associated with GLM persistency were assessed using Cox proportional hazard modeling, controlling for the dose adjustment of concomitant MTX, age, sex, RA disease period, and the initial dose of GLM or concomitant MTX during GLM/MTX combination therapy. Results During GLM/MTX combination therapy, up to 52% of patients were reported to experience dose adjustments of concomitant MTX treatment (i.e., dose reduction and escalation in 34% and 18% of patients, respectively). Persistency was similar in the MTX dose-reduction patients and the MTX dose-constant patients. In the Cox proportional hazard model, no significant differences were observed in association with GLM persistency, including with respect to MTX dose adjustment. Conclusions GLM prescription was continued in 80% or more (1 year) and 50% or more (3 years) of RA patients receiving reduced concomitant MTX dosing, suggesting that MTX dose adjustment (including MTX reduction) could be considered in GLM/MTX combination therapy.

Amorphous-nanocrystalline (a-nc) boron carbide thin films were prepared by chemical vapor deposition (CVD) by using ortho-carborane as a single-source precursor for inertial confinement fusion (ICF) application. The effects of deposition temperature (Tdep) and total pressure (Ptot) on chemical composition, microstructure, stoichiometry and morphology of the boron carbide films were investigated. The TEM results show that the structure of the film is mainly composed of amorphous boron carbide with dispersive nano-grains, which will be able to improve the mechanical properties of the film with relatively low roughness. The hardness of the (a-nc) boron carbide film obtained in this study reached 20.6 GPa, and roughness of 3.21 nm. The deposited films sized 0.2–1.9 μm in thickness with B/C atomic ratio ranged from 0.14 to 3.29. The deposition rate decreased with increasing deposition temperature and Ptot, while B/C ratio increased.

A polycrystalline diamond (PCD) ball-end mill is effective for processing molds made of hard and brittle materials, such as cemented carbide and ceramics and having fine and complex shapes with a high aspect ratio. The PCD ball-end mill has a distinctive feature of its cutting edge, which it has a simple spherical shape without sharp cutting edge found on conventional cemented carbide and cubic boron nitride (cBN) ball-end mills. The rake angle varies depending on the depth of cut. In cutting using the PCD ball-end mills, flow type chips are observed and mirror finish surface without micro fracture can be realized by adopting the ductile-cutting mode. However, the mechanism of chip generation in this cutting with the PCD ball-end mills has not been fully clarified. In this study, to simulate the cutting mechanism of the PCD ball-end mill, an orthogonal cutting experiment was conducted using an ultrafine PCD cutting insert having nose radius similar to that of the PCD ball-end mill, for basically understanding the chip formation mechanism of the PCD ball-end mill. Consequently, we designed an experimental setup with a spring constant force for applying simulation of thrust force of the PCD ball-end mill. As a result, the chips could be generated at down to −75° of rake angles and the relationship between the negative rake angles and the chip generation mechanisms were clarified.

Background and Objectives: The aim of this study was to determine whether a non-contact sensor that detects complexion changes can be used to assess the psychological state of patients with chronic lower back pain (LBP). Materials and Methods: Twenty-six patients with LBP (LBP group; mean age = 68.0 ± 13.9 years) and 18 control subjects without LBP (control group; mean age = 60.8 ± 16.1 years) were included in the study. All the subjects in the two groups wore headphones when asked LBP-related and LBP-unrelated questions. During questioning, the facial image of the subjects was captured using a video camera, and the complexion of the subjects was converted into red, green, and blue (RGB) values. RGB correlation coefficients (RGBCCs; range: 0–1) represent the difference in complexion between LBP-related and LBP-unrelated questions. A high RGBCC indicates that the brain is more activated by LBP-related questions than by LBP-unrelated questions. We also noted the scores of subjects on the Numerical Rating Scale (NRS), Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Pain Catastrophizing Scale (PCS), and Hospital Anxiety and Depression Scale (HADS). Results: There were no significant differences in RGBCC between the control and LBP groups (0.64 versus 0.56, p = 0.08). In the LBP group, no correlation was observed between RGBCC and each examination item of NRS, JOABPEQ, and HADS. In contrast, a correlation was observed between RGBCC and the rumination subscale of PCS in the LBP group (Spearman’s rank correlation coefficient = 0.40, p = 0.04). Conclusions: The complexion of patients with catastrophic thinking changes when the patients are asked LBP-related questions.

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

(Ti,W)C-based cermets are an ideal material for the preparation of high-performance cutting tools due to their excellent mechanical properties, high temperature oxidation resistance, and corrosion resistance. However, their lower toughness limits the application of cutting tools. In order to solve the problem of low toughness faced by the current materials used in tools, in this study, a (Ti,W)C solid solution was used as the hard phase to prepare cermets with high toughness via vacuum sintering. The effects of Ta content on the composition, morphology, and microstructure of the cermets were analyzed through XRD analysis and SEM and EDS characterization methods. The mechanical properties such as hardness, transverse fracture strength, and the fracture toughness of the cermets and corrosion resistance in an HNO3 solution were also investigated. The results show that the microstructure of (Ti,W)C solid solution-based cermets exhibit simpler core-rim (single-rim) and acyclic structures, which weaken the formation and propagation of cracks at the interface. The relative density and grain size of cermets increases and decreases, respectively, with the greater amount of Ta addition, while excessive Ta addition leads to a decrease in the relative density and agglomeration between grains. The cermet with 3 wt.% Ta addition possessed excellent mechanical properties with a Vickers hardness, transverse rupture strength, and fracture toughness of 13 GPa, 1907.4 MPa, and 15.5 MPa m1/2, respectively. The addition of Ta leads to the formation of a Ta-rich protective layer on the surface of the cermet under the corrosion of the acidic solution, and with the increase in the Ta content, the corrosion resistance of the cermet gradually improves.

Metastasis from lung carcinoma to the sphenoid bone is rare. Patients with symptoms related to sphenoid bone metastasis as the initial presentation of carcinoma are thus also rare. Herein, we report the case of a patient presenting with only cheek dysesthesia as the first sign of lung adenocarcinoma. The 74-year-old woman presented with a 2-month history of left cheek dysesthesia. CT showed a tumor around 2.5 cm in diameter with heterogeneous enhancement of the central focus at the left foramen rotundum in the sphenoid bone. We endoscopically biopsied the tumor through the left sphenoid sinus. Results of histologic examination were consistent with lung adenocarcinoma. FDG-PET/CT analysis demonstrated lung carcinoma that had already metastasized to mediastinal lymph nodes and multiple bones, such as the ribs and lumbar vertebras, in addition to the sphenoid bone. As EGFR gene mutation (p.L858R) was identified, the patient was treated with oral gefinitib. This treatment proved quite effective, and the patient remains alive without tumor growth as of 18 months.

A qualitative and quantitative study was performed on the carbonization temperature (TC) and carbonization time (tC) with respect to the microstructure and growth rate (Rg) of a 3C-SiC epitaxial layer on Si (111) substrates by carbonization via laser chemical vapor deposition (LCVD). The results showed that the density and size of the voids depended strongly on TC. The voids were sealed, and thin films were formed continuously and uniformly after a carbonization time of 6 min at TC = 1200 °C. Rg was also dependent on TC, and increased from 0.43 to 1.35μm·h−1 with increases in TC from 1000 to 1200 °C. These deposition rates are 10 to 100 times greater than those of observed for conventional CVD methods.

Abstract Background Infliximab, an anti-tumor necrosis factor-alpha antibody, has been reported to have excellent efficacy for refractory uveoretinitis in Behçet’s disease (RUBD), and was approved for this indication in Japan. However, the long-term safety profile and efficacy in real-world clinical settings in patients with RUBD have not been fully clarified. The BRIGHT study, a prospective, large-scale, long-term postmarketing surveillance (PMS) study, was conducted to investigate the long-term safety and efficacy of infliximab in Japanese patients with RUBD. Methods All patients with RUBD who started infliximab treatment between January 2007 and January 2010 were enrolled. Safety was evaluated every 6 months for up to 24 months after initiation of therapy in 656 patients, and efficacy was evaluated in 650 patients. Patient characteristics were compared using the chi-square or Fisher’s exact test. The frequency of ocular attacks before and after infliximab treatment was compared using the Wilcoxon signed-rank test. Independent associated factors for safety or efficacy were identified using multiple logistic regression analysis. A two-sided p value

Abstract Background IgG4-related disease (IgG4-RD) is a pathological condition that is characterized by an infiltrate composed of IgG4-positive plasma cells and recently recognized as an immune-mediated condition. It causes tissue throughout the body to become stiff and thickened due to autoimmune reactions that cause fibrosis and scarring. Disease-related changes commonly occur in the salivary glands, bile duct, pancreas, and lungs, but are seldom seen in the small bowel. A diagnosis of IgG4-RD is suspected if a high level of IgG4 is found on a blood test. The ideal diagnostic method is pathological examination, but because the clinical manifestations of IgG4-RD are very diverse and nonspecific, the disease may often go undiagnosed until an unrelated biopsy or resection specimen is obtained. The most common treatment for IgG4-RD is steroid use. However, tapering or stopping steroid administration is seen to result in recurrence in approximately 50% of cases. A complete cure is therefore considered extremely difficult. Case presentation A 69-year-old man with gastrointestinal obstruction underwent small bowel resection for two lesions. On histopathological examination, the specimen showed features of IgG4-RD. We performed several tests to detect other characteristics of IgG4-RD, but were unable to find any. The patient is being followed up regularly for a year and is being observed for any symptoms of recurrence. Conclusions We present a case of IgG4-RD wherein the ileum wall was significantly sclerosed, leading to gastrointestinal tract obstruction; therefore, we resected two sections of the ileum. We believe that resection of IgG4-RD lesions can help avoid long-term steroid use in patients, because the surgery completely eliminates the pathological origins of the condition.

Magnesium phosphate-based bone cements (MPBCs) have been widely applied in orthopedic and dental fields owing to their excellent self-setting ability and high strength. However, their lack of macroporosity and poor drug release properties restrict their use. In this study, we incorporated various degrees of cross-linking of gelatine microspheres (GM) into MPBC and improved the physicochemical and biocompatible properties, biodegradation and drug release behaviour of the composites. Diclofenac sodium (DS) was utilized as a model drug. Through experiments and observations, we found that the GM induced an adjustable setting time (12 min–16 min), high compression strength (23 MPa–58 MPa), abundant macropores (30.2%–37.8%) and sustained DS release with the double exponential biphasic kinetic model (more than 2 months) into the MPBC composites. Moreover, the sustained release of magnesium and calcium ions had a synergistic effect with GM on the proliferation, osteogenesis differentiation, mineralization ability and gene expression (COL I, OPN, and Runx2) of MC3T3-E1 cells. Subcutaneous implantation and histological analyses indicated that the MPBC-GM composites activated angiogenesis without inducing severe inflammatory reactions. In brief, we prepared biocompatible MPBC composites with adjustable physicochemical properties, formation of macropores, degradation and drug release behaviour.

Off-stoichiometric silicon carbide (SiC), C- and Si-added SiC (6H, α-type), with an excess amount of C or Si from 1 to 5 mol%, were fabricated by spark plasma sintering at 2373 K and 50 MPa in a vacuum. The microstructure, electrical, and thermal properties of off-stoichiometric SiC were investigated. The lattice parameters increased after the addition of C and Si, suggesting the formation of solid solutions of C and Si in SiC. The addition of C and Si increased the densification, while the addition of a small amount of Si (1 mol%) significantly improved the densification. The electrical conductivity (σ) of C-added SiC was 0.7–1.4 × 102 S m−1 at 298–1150 K. The Seebeck coefficient of C-added SiC changed from n- to p-type with increasing addition of C, whereas that of Si-added SiC was almost independent of the amount of Si added. The thermal conductivity of C- and Si-added SiC was in the range of 180–250 W m−1 K−1, which was greater than that of pristine SiC (100 W m−1 K−1) at room temperature.

A ZrB2–ZrN eutectic composite was prepared by arc-melting a mixture of ZrB2 and ZrN powders under a N2 atmosphere. The eutectic composition was 48ZrB2–52ZrN (mol%), resulting in a rod-like microstructure comprising hexagonally faceted ZrN single-crystal rods dispersed in a ZrB2 single-crystal matrix. The crystal orientation relationship between the ZrB2 matrix and the ZrN rod was ZrB2 $$\left\{ {11\bar 20} \right\}$$//ZrN{101} and ZrB2 //ZrN . The rod-like eutectic composite had a Vickers hardness of 16.2 GPa.

Abstract Although aberrations of intracellular vesicle transport systems towards lysosomes including autophagy and endocytosis are involved in the onset and progression of acute pancreatitis, the molecular mechanisms underlying such aberrations remain unclear. The pathways of autophagy and endocytosis are closely related, and Rab7 plays crucial roles in both. In this study, we analyzed the function of Rab7 in acute pancreatitis using pancreas-specific Rab7 knockout (Rab7Δpan) mice. In Rab7Δpan pancreatic acinar cells, the maturation steps of both endosomes and autophagosomes were deteriorated, and the lysosomal functions were affected. In experimental models of acute pancreatitis, the histopathological severity, serum amylase concentration and intra-pancreatic trypsin activity were significantly higher in Rab7Δpan mice than in wild-type mice. Furthermore, the autophagy process was blocked in Rab7Δpan pancreas compared with wild-type mice. In addition, larger autophagic vacuoles that colocalize with early endosome antigen 1 (EEA1) but not with lysosomal-associated membrane protein (LAMP)-1 were much more frequently formed in Rab7Δpan pancreatic acinar cells. Accordingly, Rab7 deficiency exacerbates the severity of acute pancreatitis by impairing the autophagic and endocytic pathways toward lysosomes.

Work characteristics and loss generation mechanism of a single-stage axial flow compressor at windmill operation were investigated by experiment and CFD analyses. When the inlet flow coefficient is gradually increased from the design point, the rotor blade gradually enters the windmilling operation from the tip toward hub. The research attentions were focused on two windmilling operations, those were free-windmilling and highly loaded windmilling conditions. Total pressure loss under windmilling operations was mainly caused by three flow structures, those were (1) tip leakage flow from suction to pressure surface near the leading edge and that from pressure to suction surface near the trailing edge, (2) the interaction of separation vortices due to the highly negative incidence and the rotor leading-edge vortex, and (3) the boundary layer separation near the hub wall. The distribution of the rotor operating mode was found to exist not only in the span-wise direction but also in the chord-wise direction under the windmilling operations. The turbine mode region was observed near the leading edge, while the compressor mode region was observed near the trailing edge even in the highly loaded windmilling condition. Therefore, driving force of the windmilling was dominated not by the area of the turbine mode on the rotor blade but by the static pressure difference of suction and pressure surfaces on the rotor.

Doping of nitrogen is a promising approach to improve the electrical conductivity of 3C-SiC and allow its application in various fields. N-doped, -oriented 3C-SiC bulks with different doping concentrations were prepared via halide laser chemical vapour deposition (HLCVD) using tetrachlorosilane (SiCl4) and methane (CH4) as precursors, along with nitrogen (N2) as a dopant. We investigated the effect of the volume fraction of nitrogen (ϕN2) on the preferred orientation, microstructure, electrical conductivity (σ), deposition rate (Rdep), and optical transmittance. The preference of 3C-SiC for the orientation increased with increasing ϕN2. The σ value of the N-doped 3C-SiC bulk substrates first increased and then decreased with increasing ϕN2, reaching a maximum value of 7.4 × 102 S/m at ϕN2 = 20%. Rdep showed its highest value (3000 μm/h) for the undoped sample and decreased with increasing ϕN2, reaching 1437 μm/h at ϕN2 = 30%. The transmittance of the N-doped 3C-SiC bulks decreased with ϕN2 and showed a declining trend at wavelengths longer than 1000 nm. Compared with the previously prepared -oriented N-doped 3C-SiC, the high-speed preparation of -oriented N-doped 3C-SiC bulks further broadens its application field.

BackgroundBone and soft tissue sarcomas are commonly treated with consecutive-day chemotherapy regimens consisting of multiple anticancer agents. Chemotherapy-induced nausea and vomiting (CINV) is a serious adverse effect of these regimens and may result in decreased energy intake during chemotherapy. Decreased energy intake may lead to undernutrition and may cause adverse effects on patient quality of life and survival.MethodsPatients with bone and soft tissue sarcomas who received consecutive-day chemotherapy were retrospectively evaluated. CINV and dietary energy intake were assessed, as well as the occurrences of hiccups and constipation during chemotherapy.ResultsA total of 13 patients, 10 males and 3 females, with a total 16 chemotherapy courses were included in the study. All patients received antiemetic prophylaxis. The CINV control rate, defined as no emesis and no rescue therapy, gradually decreased from chemotherapy day 1 (94%) to day 5 (75%). Four patients experienced emesis, two of whom had been treated with a cisplatin-containing regimen. Decreased dietary energy intake was possibly associated with CINV during chemotherapy. Anorexia was grade 2 except for one case of grade 3. The incidences of hiccups and constipation were high on days 3–5.ConclusionAntiemetic prophylaxis treatment did not prevent emesis due to consecutive-day chemotherapy, especially with cisplatin-containing regimens, in patients with bone and soft-tissue tumors. Dietary energy intake decreased during chemotherapy, and this appeared to be associated with CINV. In addition, the incidence of hiccups and constipation increased during the course of consecutive-day chemotherapy regimens. Although these results are based on a small number of patients, it may be important to observe nutritional status during chemotherapy, as this may reflect a patient’s general condition. Nutritional counseling might be useful in supporting nutritional status in patients undergoing chemotherapy.

We report a rare case of granulomatosis with polyangiitis (GPA) presenting with hypertrophic cranial pachymeningitis (HCP), abducens nerve palsy, and stenosis of the internal carotid artery (ICA). A 59-year-old Japanese man presented with a year history of nasal obstruction and a 2-month history of slight headache. Histopathological examination of the granulomatous mucosa in the ethmoid sinuses resected by endoscopic sinus surgery revealed necrotizing vasculitis with multinucleated giant cells. The patient was diagnosed with the limited form of GPA as a result of the systemic examination. He declined immunosuppressive treatment. Eighteen months after the diagnosis of GPA, he presented with diplopia and severe headache. Though nasal findings indicating GPA were not observed in the nasal cavity, CT scan revealed a lesion of the right sphenoid sinus eroding the bone of the clivus. Gadolinium-enhanced MRI of the brain showed thickening of the dura mater around the right cavernous sinus and clivus. Magnetic resonance angiography and cerebral angiography revealed narrowing at the C5 portion of the ICA. Intravenous methylprednisolone pulse therapy followed by oral prednisolone and cyclophosphamide resolved headache and dramatically improved HCP and stenosis of the ICA.

SiO2 nanolayer coated cubic boron nitride (cBN), cBN(core)/SiO2(shell) powder, was prepared by rotary chemical vapor deposition. The cBN/SiO2 powder was densified by spark plasma sintering at 1873 K for 0.3 ks. The hexagonal boron nitride (hBN) phase was not observed in the cBN–SiO2 composites, indicating that the SiO2 nanolayer depressed the phase transformation from cBN to hBN. The relative density of cBN–SiO2 increased with increasing SiO2 content (CSiO2). The highest hardness of the cBN–SiO2 composite was 17.5 GPa at CSiO2=38 wt% and a load of 0.98 N.

Transparent Nd-doped Lu2O3 bodies were fabricated by spark plasma sintering, and the effect of LiF addition on sintering, microstructure and transparency of Nd-doped Lu2O3 bodies were investigated. LiF promoted the densification at an early stage of sintering, resulted in high transparency of the Nd-doped Lu2O3 body. The optimal content of LiF was 0.2 wt% and that Nd-doped Lu2O3 body showed a transmittance of 81.8% (99.5% of theoretical) at 1080 nm after annealing in air for 21.6 ks.

Background & Aims: Proliferation, differentiation, and morphogenesis of the intestinal epithelium are tightly regulated by a number of molecular pathways. Coordinated action of intestine is achieved by gastrointestinal hormones, most of which exert these actions through G-proteinâcoupled receptors. We herein investigated the role of Gαq/11-mediated signaling in intestinal homeostasis. Methods: Intestinal tissues from control (Gnaqflox/floxGna11+/+), Int-Gq knock-out (KO) (VilCre+/-Gnaqflox/floxGna11+/+), G11 KO (Gnaqflox/floxGna11-/-), and Int-Gq/G11 double knock-out (DKO) (VilCre+/-Gnaqflox/floxGna11-/-) mice were examined by microscopy, transmission electron microscopy, and immunohistochemistry. The effect of Gαq/11-mediated signaling was studied in the cell lineage, proliferation, and apoptosis. Dextran sodium sulfate (DSS) colitis was induced to study the role of Gαq/11 in colon. Results: Paneth cells were enlarged, increased in number, and mislocalized in Int-Gq/G11 DKO small intestine. Paneth cells also reacted with PAS and Muc2 antibody, indicating an intermediate character of Paneth and goblet cells. The nuclear β-catenin, T-cell factor 1, and Sox9 expression were reduced severely in the crypt base of Int-Gq/G11 DKO intestine. Proliferation was activated in the crypt base and apoptosis was enhanced along the crypt. Int-Gq/G11 DKO mice were susceptible to DSS colitis. Proliferation was inhibited in the crypt of unaffected and regenerative areas. Cystic crypts, periodic acidâSchiffâpositive cells, and Muc2-positive cells were unusually observed in the ulcerative region. Conclusions: The Gαq/11-mediated pathway plays a pivotal role in the preservation of intestinal homeostasis, especially in Paneth cell maturation and positioning. Wnt/β-catenin signaling was reduced significantly in the crypt base in Gαq/G11-deficient mice, resulting in the defective maturation of Paneth cells, induction of differentiation toward goblet cells, and susceptibility to DSS colitis. Keywords: Paneth Cell, Intermediate Cell, Wnt, Gnaq, Gna11

Calcium Titanate (CaTiO3) has been introduced as an attractive biomaterial for the enhancement of calcium phosphate deposition in vivo and in vitro. We hypothesized that CaTiO3 directly coated on titanium (Ti) by metal-organic chemical vapor deposition (MOCVD) could be a suitable candidate for biocompatible coatings for medical devices, particularly dental implants. To prove this hypothesis, surface characterization, cell culture, and animal study were completed in this study. The result of this study showed that CTO 800, a CaTiO3 film prepared by heating at 800 °C, had a high hydrophilic surface. Mouse bone marrow stromal ST-2 cells cultured on substrates and CTO 800 exhibited cell differentiation, represented by alkaline phosphatase activity, compared with cells cultured on non-coated Ti and CTO 700 (a CaTiO3 film prepared by heating at 700 °C). The push-in test value of CTO 800, a parameter that indicates the degree of osseointegration, was significantly higher than that of Ti. Calcium titanate coated on Ti by MOCVD has the potential to accelerate the process of osseointegration; thus, our results support the use of CaTiO3 coating for biocompatible biomaterial for medical applications, particularly dental implants.

Highly-oriented polycrystal 3C-SiC bulks were ultra-fast fabricated via halide chemical vapor deposition (CVD) using tetrachlorosilane (SiCl4) and methane (CH4) as precursors. The effects of deposition temperature (Tdep) and total pressure (Ptot) on the orientation and surficial morphology were investigated. The results showed that the growth orientation of 3C-SiC columnar grains was strongly influenced by Tdep. With increasing Tdep, the columnar grains transformed from - to -oriented. The arrangement of -oriented columnar grains was controlled by Ptot. Lotus-, turtle-, thorn-, and strawberry-like surface morphologies were naturally contributed by different arrangements of -oriented grains, and the deposition mechanism was discussed. The wetting behaviors of CVD-SiC samples by molten aluminum were also examined at 1173 K in a high vacuum atmosphere.

In this study, we demonstrated the chemical vapor deposition (CVD) of vertically standing molybdenum disulfide (MoS2) nanosheets, with an unconventional combination of molybdenum hexacarbonyl (Mo(CO)6) and 1,2-ethanedithiol (C2H6S2) as the novel kind of Mo and S precursors respectively. The effect of the distance between the precursor’s outlet and substrates (denoted as d) on the growth characteristics of MoS2, including surface morphology and nanosheet structure, was investigated. Meanwhile, the relationship between the structure characteristics of MoS2 nanosheets and their catalytic performance for hydrogen evolution reaction (HER) was elucidated. The formation of vertically standing nanosheets was analyzed and verified by means of an extrusion growth model. The crystallinity, average length, and average depth between peak and valley (Rz) of MoS2 nanosheets differed depending on the spatial location of the substrate. Good crystalized MoS2 nanosheets grown at d = 5.5 cm with the largest average length of 440 nm, and the highest Rz of 162 nm contributed to a better HER performance, with a respective Tafel slope and exchange current density of 138.9 mV/decade, and 22.6 μA/cm2 for raw data (127.8 mV/decade and 19.3 μA/cm2 for iR-corrected data).

Newly approach using the formation process of polymer foam is introduced in this study to prepare porous hydroxyapatite (HAp) scaffolds for bone tissue engineering applications, which could provide a better control over the microstructures of scaffolds and enhance their mechanical properties. The scaffolds prepared have an open, relatively uniform and interconnected porous structure with a pore size ranging 50 to 300 µm. A compressive strength of 5 MPa for the scaffolds with HAp content 80 wt% and higher porosity of 77% was achieved. The pore morphology and size of the scaffolds were characterized using a scanning electron microscopy. X-ray diifraction was used to determine the crystal structure. Scaffolds with desired porosity, pore size, and geometry could be prepared by using the formation process of polymer foam with controlling process parameters.

Calcium phosphate coating films were fabricated on blast-treated titanium plates and screw-type titanium implants using RF magnetron sputtering. A uniform and dense coating film with a thickness of 0.5 µm could cover the blast-treated titanium plate efficiently, maintaining the surface roughness of the substrates. The as-sputtered coating films consisted of amorphous calcium phosphate (ACP) or oxyapatite (Ca10(PO4)6O, OAp). Heat treatments of the OAp coating films were conducted in a silica ampoule or in air, and it was observed that the crystallinity of the coating films increased after the heat treatment. The bonding strength between the as-sputtered coating films, subjected to heat treatment in air, and the blast-treated titanium plates exceeded 60 MPa. An immersion test was conducted and alkaline phosphatase (ALP) activity of osteoblasts was investigated in vitro. The dissolution rate of the coating films in the 0.9% NaCl solution decreased with an increase in their crystallinity. The ACP coating film exhibited high ALP activity. As the in vivo evaluation, the coated and non-coated titanium implants were implanted into the femur of Japanese white rabbits. The percentage of bone-implant contact and the removal torque value of the coated titanium implants were greater than those of the non-coated titanium implants.

Ammonia is a carbon-free fuel and its application to internal combustion engines is expected. However, few studies on ammonia flames, especially at high pressures, have been carried out because ammonia has not been considered to be a fuel owing to its lower combustion intensity. Most of NOx, which is formed by ammonia combustion, is considered to be the fuel NOx. The objectives of this study were to investigate the fundamental characteristics of NOx experimentally, such as NO emission and chemiluminescence of ammonia/air flames not only at the atmospheric pressure but also under high pressures and to explore NO formation/reduction mechanisms using numerical simulation. Experiments were carried out using a nozzle-type burner. NH2 ammonia α band spectra were observed, and it was clarified that the color of ammonia flame is mainly determined by the NH2 ammonia α band and H2O spectra. Burned gas was sampled from ammonia flame stabilized at the burner. The mole fraction of NO decreased with the increase in equivalence ratio at atmospheric pressure. Reaction flow analysis was performed, and it was clarified that the decrease in the mole fraction of NO for rich mixtures was caused by NHi (i = 2, 1, 0). High pressure experiments were performed using a high pressure combustion facility for stoichiometric ammonia flame. Consequently, the decrease in the mole fraction of NO was experimentally observed and its tendency was found to qualitatively agree with the results of the numerical simulation. It was clarified that the third body reaction of OH + H + M ⇔ H2O + M plays an important role in the reduction of the mole fraction of NO at the high pressure.

GB virus C (GBV-C) RNA positivity rates were examined in serum specimens from 231 patients with liver disease (23 patients with hepatitis B, 175 patients with hepatitis C, five patients with hepatitis B virus plus hepatitis C virus coinfection, and 28 patients with non-A, non-B, non-C hepatitis) to clarify the clinical significance of this virus. GBV-C RNA was detected in none of 12 patients with fulminant hepatitis, one of two patients with acute hepatitis positive for hepatitis B surface antigen and one of four patients with acute non-A, non-B, non-C hepatitis. Pathogenetic involvement of GBV-C was suspected in some patients in the latter group. Among patients with the non-B, non-C type of chronic disease, one of seven with cirrhosis (14%) and none with chronic hepatitis or hepatocellular carcinoma were GBV-C-positive. In chronic hepatitis C patients who had received interferon treatment, no difference was found in clinical findings, alanine aminotransferase (ALT) concentrations, histology or response to interferon between 11 patients who were GBV-C RNA-positive and 101 patients who were GBV-C RNA-negative. Moreover, changes in ALT after interferon therapy showed no relation to positivity for GBV-C RNA. On the basis of these findings, GBV-C appears to be an unlikely cause of initiation or progression of chronic hepatic diseases.

A controlled trial comparing combination therapy with ofloxacin (OFLX) and interferon (IFN) versus IFN monotherapy was conducted in patients with chronic hepatitis C who failed IFN therapy. Twenty patients were assigned randomly to two groups. Equal doses of recombinant IFNα-2b were administered to each group for 24 weeks. For the IFN plus OFLX group, OFLX was administered for 12 weeks at a daily dose of 600 mg. Levels of hepatitis C virus RNA declined significantly from the first month after the start of IFN treatment compared with those before administration in both groups. Serum alanine aminotransferase levels were significantly lower in the IFN plus OFLX group at two and six months after the start of treatment than levels in the IFN group. The fraction of subjects whose levels of serum ALT normalized was also higher in the IFN plus OFLX group. Larger clinical trials should be undertaken.

Introduction A viral breakthrough occurs when a patient achieves a response while on interferon (IFN) therapy and then loses the response despite continued IFN therapy. The cause of viral breakthroughs is not well understood. We encountered three cases with viral breakthrough during treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). Case presentation The three cases were all late virological responders. They did not express anti-IFN alpha-2b antibodies after PEG-IFN and RBV therapy. We analyzed amino acid substitutions of core 70, core 91, and interferon sensitivity-determining region (ISDR), which significantly influence sustained virological response (SVR). Their amino acid substitutions of core 91 were mutant in two cases. Amino acid substitutions of ISDR were wild pattern in two cases. PEG-IFN adherence was above 80% in three cases, and RBV adherence was below 80% in two cases. Conclusion During PEG-IFN and RBV therapy, we should watch for viral breakthrough in late virological responders with mutant type of amino acid substitutions of core 91, wild pattern of amino acid substitution of ISDR, and decrease of RBV adherence. Viral breakthrough is an important problem in PEG-IFN and RBV therapy for chronic hepatitis C. Therefore, it should be investigated more thoroughly in more cases.

The title compound, dicalcium nonaoxidodistannate(IV)dialuminate, is the second example which crystallizes in the isotypic structure of a pyroxene silicate, Na2Ti2Si2O9 (ramsayite). ∞1[Sn2O8] chains and pyroxene-type ∞1[Al2O6] chains are formed along the b axis by sharing O atoms. The Ca atoms are situated in the resulting channels and exhibit a coordination number of 7.