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Background/purpose: Tooth extraction has been avoided in patients receiving antiresorptive agent (ARA) therapy. This study aimed to investigate dental findings associated with medication-related osteonecrosis of the jaw (MRONJ) development in patients. Materials and methods: First, in patients treated with high-dose ARAs, the relationship between dental findings and MRONJ development was examined. Next, in patients with MRONJ undergoing surgery, the relationship between dental findings and MRONJ occurring at a site distant from the initial site was examined. Results: MRONJ occurred in 13 of 172 patients (80 of 3725 teeth) during observation. Multiple tooth loss, periodontal ligament space enlargement, alveolar bone loss, periapical osteosclerosis, and local infection symptoms were associated with MRONJ development. Tooth extraction significantly reduced MRONJ development. Regarding other-site recurrence, new MRONJ developed at other sites in 54 of 357 patients with MRONJ (171 of 5038 teeth). Multiple tooth loss, apical lesions, periodontal ligament space enlargement, and periapical osteosclerosis were significantly associated with MRONJ development. In patients with malignant tumors, tooth extraction significantly reduced the subsequent incidence of MRONJ, while in patients with osteoporosis, there was no difference in the incidence of MRONJ between patients with and without tooth extraction. Conclusion: MRONJ was more likely to develop from teeth with local infections. Extraction of teeth with local infection in patients with malignancy may be more effective than tooth preservation in preventing MRONJ.

Background /purpose: The standard treatment for medication-related osteonecrosis of the jaw (MRONJ) is surgery. However, reports on the appropriate extent of bone resection are few. We aimed to examine the relationship between the extent of bone resection and postoperative outcomes in patients with mandibular MRONJ. Materials and methods: The clinical and imaging findings and treatment outcomes of 206 patients (258 surgeries) with mandibular MRONJ undergoing surgery were reviewed. Imaging findings were evaluated using computed tomography (CT) to sequestrum, osteolysis, periosteal reaction, and mixed-type osteosclerosis, and determine the extent of resection. In some cases, samples were taken from within the bone, and real-time polymerase chain reaction was used to confirm the presence of bacteria and fungi. Results: The three-year cumulative cure rate was 81.7%. Patients with malignant tumors showing no osteolysis and undergoing sequestrum removal or marginal mandibulectomy had significantly worse prognosis than those with osteoporosis showing osteolysis and undergoing segmental mandibulectomy. Furthermore, patients with residual osteolysis, periosteal reactions, and mixed-type osteosclerosis on CT were more likely to develop recurrence. Eleven patients showed no osteolysis on CT images. Patients with cancer administered with high-dose denosumab had significantly poorer prognosis. Bacteria and fungi were also detected in samples obtained from gap-type periosteal reaction and mixed-type osteosclerosis. Conclusion: Surgery for MRONJ requires resection of the infected bone. Aside from the osteolysis area, the gap-/irregular-type periosteal reaction and mixed-type osteosclerosis must also be included in the resection area. Methods for determining the extent of bone resection in MRONJ without osteolysis are a future challenge.

The Hybrid Ring with a superconducting-linac injector as a highly flexible synchrotron radiation source to enable new experimental techniques and enhance many existing ones is proposed. It is designed to be operated with the coexistence of the storage (SR) bunches characterized by the performance of the storage ring, and the single-pass (SP) bunches characterized by the performance of the superconducting linac. Unique experiments can be performed by simultaneous use of the SR and SP beams, in addition to research with various experimental techniques utilizing the versatile SR beam and research in the field of ultrafast dynamics utilizing the ultrashort pulse of the SP beam. The extendability of the Hybrid Ring will allow it to be developed into a synchrotron radiation complex.

Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent’s targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient’s nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.

The compact energy recovery linac (cERL) has been developed for industrial applications since 2017. Applications such as free electron laser require a compressed beam with a small energy spread and transverse emittance. The typical operation energy of cERL is an intermediate energy region close to 17.5 MeV; therefore, the electron bunch is easily affected by the longitudinal space-charge effects and the coherent synchrotron radiation wakefield effects. Bunch compression is demonstrated by optimizing a combination of a longitudinally chirped electron bunch and the arcs with nonzero R_{56} parameters. When the bunch compression procedure is applied for a bunch charge of 60 pC, an increase in energy spread is observed at the short bunch length. We systematically explored the chirp phase to determine the best condition. The measurement results of the energy spread, bunch length, and transverse emittance were compared with the tracking simulation results to understand the compressed beam dynamics.

Background/purpose: Although mandibular advancement oral appliances (OAs) are the most widely used and accepted therapeutic modality for obstructive sleep apnea (OSA), whether these maxillary and mandibular appliances should be semi-fixed or fixed remains uncertain. This randomized crossover pilot study compared the efficacy, side effects, and patient preference of semi-fixed and fixed OAs for the treatment of OSA. Materials and methods: Patients with mild to moderate OSA were recruited and randomly assigned to either the semi-fixed or fixed OA group, whereby they used their assigned OA for the first 4 weeks, followed by assessments for sleep parameters (including the Apnea-Hypopnea Index [AHI]) and temporomandibular joint pain as a side effect. After a two-week washout period, patients were switched to the alternative OA for 4 weeks, followed by repeated assessments. Patient preference was assessed at the end of the completed treatment period. Results: Fifteen patients were enrolled and completed the full study protocol. Both types of OAs were efficient in reducing the patient's AHI in comparison to baseline (i.e., without OA). However, there was no significant difference in AHI reduction between the semi-fixed and fixed OA devices. Regarding the side effect of temporomandibular joint pain and patient preference, the semi-fixed OA device was superior to the fixed OA device on both measures. Conclusion: While both semi-fixed and fixed OAs are effective in treating patients with OSA, semi-fixed OAs are superior in regards to both patient preference and reduced side effects. Thus, semi-fixed OAs may be the preferred therapeutic modality for OSA.

Pneumoperitoneum, the presence of free air within the peritoneal cavity, is often caused by the perforation of gas-containing viscus and commonly requires surgical treatment. However, in patients with peritoneal dialysis, free air is commonly seen on X-ray. We present the case of a patient with peritoneal dialysis with marked pneumoperitoneum. A 75-year-old Japanese male with end-stage renal disease due to antineutrophil cytoplasmic antigen-associated vasculitis had been receiving continuous ambulatory peritoneal dialysis for 9 years. He had a poor appetite and general malaise without abdominal pain or fever. These symptoms gradually worsened, and he was hospitalized. At the time of admission, chest X-ray revealed bilateral free air in the abdomen. Subsequent computed tomography of the abdomen revealed marked pneumoperitoneum. Peritonitis due to perforation of the digestive tract was considered; however, the absence of abdominal pain, fever, and turbidity of dialysis drainage indicated that peritonitis was unlikely. Insufficient air venting during continuous ambulatory peritoneal dialysis bag replacement was suspected. The bag was carefully changed, resulting in a gradual decrease in the free air. We encountered a patient with continuous ambulatory peritoneal dialysis who had significant free air in the abdominal cavity in the absence of peritonitis. The source of the air was determined to be the dialysis bag due to insufficient venting during replacement. This case underscores the importance of instructing patients with continuous ambulatory peritoneal dialysis on the thorough removal of air from the bag during replacement.

Abstract Background Direct-acting antivirals (DAAs) dramatically improve the treatment of hepatitis C virus (HCV) infections. However, the effects of DAAs on extra-hepatic manifestations such as HCV-associated glomerulonephritis, especially in cases with renal dysfunction, are not well elucidated. Case presentation A 69-year-old Japanese woman was diagnosed as having chronic hepatitis C, genotype 1b at the age of 55. She presented with hypertension, microscopic hematuria, proteinuria, renal dysfunction, purpura, and arthralgia at the age of 61. She also had hypocomplementemia and cryoglobulinemia. Renal biopsy revealed membranoproliferative glomerulonephritis (MPGN), and she was diagnosed as having HCV-associated cryoglobulinemic MPGN. She declined interferon therapy at the time and was treated with antihypertensive medications as well as oral corticosteroid that were effective in reducing proteinuria. However, when the corticosteroid dose was reduced, proteinuria worsened. She began antiviral treatment with daclatasvir/asunaprevir (DCV/ASV). Clearance of HCV-RNA was obtained by 2 weeks and sustained, and liver function was normalized. In addition, microhematuria turned negative, proteinuria decreased, hypocomplementemia and estimated glomerular filtration rate were improved, whereas cryoglobulinemia persisted. She completed 24 weeks of therapy without significant adverse effects. Conclusion In a case of HCV-associated cryoglobulinemic MPGN with renal dysfunction, DCV/ASV -based DAAs ameliorated microhematuria, proteinuria and renal function without significant side effects.

Background. Ethylene glycol intoxication causes severe metabolic acidosis and acute kidney injury. Fomepizole has become available as its antidote. Nevertheless, a prompt diagnosis is not easy because patients are often unconscious. Here we present a case of ethylene glycol intoxication who successfully recovered with prompt hemodialysis. Case Presentation. A 52-year-old Japanese male was admitted to a local hospital due to suspected food poisoning. The patient presented with nausea and vomiting, but his condition rapidly deteriorated, with worsening conscious level, respiratory distress requiring mechanical ventilation, hypotension, and severe acute kidney injury. He was transferred to the university hospital; hemodialysis was initiated because of hyperkalemia and severe metabolic acidosis. On recovering consciousness, he admitted having ingested antifreeze solution. Thirty-seven days after admission, the patient was discharged without requiring HD. Conclusions. We reported a case of ethylene glycol intoxication who presented with a life-threatening metabolic acidosis. In a state of severe circulatory shock requiring catecholamines, hemodialysis should be avoided, and continuous hemodiafiltration may be a preferred approach. However, one should be aware of the possibility of intoxication by unknown causes, and hemodialysis could be life-saving with its superior ability to remove toxic materials in such cases.

The beam halo mitigation is a very important challenge for reliable and safe operation of a high-energy machine. A systematic beam halo study was conducted at the KEK compact energy recovery linac (cERL) since non-negligible beam loss was observed in the recirculation loop during a common operation. We found that the beam loss can be avoided by making use of the collimation system. Beam halo measurements have demonstrated the presence of vertical beam halos at multiple locations in the beam line (except the region near the electron gun). Based on these observations, we made a conjecture that the transverse beam halo is attributed to the longitudinal bunch tail arising at the photocathode. The transfer of particles from the longitudinal space to a transverse halo may have been observed and studied in other machines, considering nonlinear effects as their causes. However, our study demonstrates a new unique halo formation mechanism, in which a transverse beam halo can be generated by a longitudinal bunch tail due to transverse rf kicks from the accelerating (monopole) fields of the radio-frequency cavities. This halo formation occurs when nonrelativistic particles enter the cavities with a transverse offset, even if neither nonlinear optics nor nonlinear beam effects are present. A careful realignment of the injector system will mitigate the present halo. Another possible cure is to reduce the bunch tails by changing the photocathode material from the present GaAs to a multi-alkali that is known to have a shorter longitudinal tail.

Aim. The goal of the study was to investigate quality of life (QOL) in adult patients with minimal change nephrotic syndrome (MCNS) and to test the relationship of QOL with the level of self-care. Materials and Methods. We distributed two questionnaires to 30 outpatients with MCNS. The MOS 36-item Short Form Health Survey (SF-36v2) was used to examine health-related QOL in comparison with normative data from the general Japanese population and a population with two chronic diseases. SF-36v2 consists of 36 questions classified into 8 subscales. We also used the Self-Care Behavior Scale for patients with chronic kidney disease (CKD), which consists of 31 questions with 4 subscales. Results. The SF-36v2 social functioning subscale was most impaired and bodily pain was least affected in patients with MCNS. The self-care subscales of information/communication and positive behavior had positive correlations with the QOL subscales of mental health () and vitality (). The correlation between social functioning and information/communication was close to significant (). Conclusion. In MCNS, social functioning was particularly impaired. Our results suggest that better self-care can have a positive impact on QOL in patients with MCNS.

We have developed a new beam injection system with a single pulsed sextupole magnet (PSM) at the photon factory storage ring (PF ring) in the High Energy Accelerator Research Organization. We demonstrated beam injection with this system and succeeded in storing a beam current of 450 mA, which is the normal operating beam current of the PF ring. Top-up injection was also achieved. Coherent dipole oscillation of the stored beam and fluctuation of photon intensity observed at synchrotron radiation beam lines during the PSM injection became very small compared with a pulsed bump injection system that is normally used in the beam injection at the PF ring. This experiment is the first demonstration of beam injection using the PSM in an electron storage ring.

We describe the improvements of a Fresnel zone plate (FZP) beam-profile monitor, which is being developed at the KEK-ATF damping ring to measure ultralow emittance electron-beam profiles. This monitor, which is designed to have a submicrometer spatial resolution, is based on x-ray imaging optics composed of two FZPs. Various improvements were performed to the old setup. First, a new crystal monochromator was introduced to suppress the beam image drift. Second, the two FZP folders were improved in order to realize a precise beam-based alignment during x-ray imaging. Third, a fast mechanical shutter was installed to achieve a shorter time resolution, and an x-ray mask system was also installed to obstruct direct synchrotron radiation through the FZPs. These improvements could make beam-profile measurements more precise and reliable. The beam profiles with less than 50 μm horizontal beam size and less than 6 μm vertical beam size could be measured within a 1 ms time duration. Furthermore, measurements of the damping time and the coupling dependence of the ATF damping ring were successfully carried out with this upgraded FZP monitor.

Background/Aim: The pathogenesis of cardiovascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX- 3) and the oxidative stress-related biomarker soluble lectinlike low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. Patients and Methods: This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. Results: We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX- 1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). Conclusion: In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.r [ABSTRACT FROM AUTHOR]

Background/Aim: Retinoic acid-inducible gene (RIG)-I like receptors (RLRs) are expressed on renal proximal tubular epithelial cells (RPTECs) in viral nephropathy, indicating the presence of RLR-mediated innate immune responses in RPTECs. Hypoxia is also known to affect innate immunity. This study investigated the effects of hypoxia, and hypoxia-inducible factor (HIF) on innate immunity in RPTECs. Materials and Methods: Primary human RPTECs were cultured under normoxic or hypoxic conditions and treated with a synthetic analog of doublestranded RNA (polyIC). The expression levels of RIG-I and MDA5, as RLRs, and IFNβ, IL6, and TNFα, as inflammatory mediators were evaluated using quantitative reverse transcription-polymerase chain reaction, western blotting, and lactate dehydrogenase activity (LDH) assays. To further investigate the role of hypoxia, a small interfering RNA was used to knockdown HIF1α. Results: Under normoxic conditions, polyIC increased RIG-I, MDA5, and IFNβ mRNA expression in RPTECs by, 9.4±0.4-, 10.8±0.5-, and 4.0±0.1- fold, respectively, compared to control, and by 5.4±0.1-, 7.4±0.1-, and 2.4±0.3-fold, respectively, under hypoxic conditions, the rate of increase was lower than that under normoxic conditions (p<0.01). Protein expression showed a similar trend. Under hypoxic conditions, polyIC treatment with HIF1α knockdown in RPTECs increased RIG-I, MDA5, and IFNβ mRNA expression by 3.1±0.5-, 2.9±0.4-, and 6.1±0.4-fold, respectively, and cytotoxicity, demonstrated by LDH assay, was increased compared to that without knockdown (all p<0.01). Conclusion: Hypoxia suppresses polyIC-induced RLRs mediated innate immune responses in RPTECs via HIF1α. [ABSTRACT FROM AUTHOR]

Background/Aim: Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and its incidence continues to increase. To decrease this, a countermeasure from an early stage is required. This is a DN stage 2 observation study that analyzed the results of a concurrent dietary survey in the Tsugaru study and discussed the relationship between dietary intake of n-3 fatty acid and DN. Patients and Methods: Patients with stage 2 DN and aged 20 years or older in the Tsugaru region of Aomori Prefecture were enrolled. We examined the association between urinary albumin excretion (UAE) at enrollment and 36 months later and n-3PUFA intake obtained from a dietary survey. Results: Of the 317 subjects at enrollment, 234 were followed for 36 months, of whom 123 were able to complete the dietary survey. After 36 months of follow-up of these 123 subjects, 28 were in remission and 18 had progressed. Correlations between UAE at 36 months and each of the parameters were examined and UAE at enrollment showed a positive correlation (r=0.4224, p<0.001); correlations between eicosapentaenoic acid (EPA)/arachidonic acid (AA), EPA+docosahexaenoic acid/AA, and n-6/n-3 and UAE at 36 months were weak. As shown by multiple regression analysis, the factor influencing UAE after 36 months was UAE at enrollment. Conclusion: Concerning the relationship between fatty acid intake balance and UAE, the previously reported renoprotective effect of n-3 fatty acids could not be demonstrated. [ABSTRACT FROM AUTHOR]

Background/Aim: Viral infection often exacerbates proteinuria, which has been suggested to be due to antiviral responses of podocytes. We examined the effect of polyinosinic-polycytidylic acid (polyIC) on the expression of retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in differentiated human podocytes in culture. Materials and Methods: The podocytes were treated with 2 ng/ml to 500 μg/ml of polyIC for 3 to 36 h, and also transfected with siRNA against RIGI and MDA5. F-actin staining was performed to assess actin reorganization. Results: PolyIC induced the expression of RIG-I and MDA5 in dose- and time-dependent manner, accompanied with interferon-β (IFN-β) and interleukin-6 (IL-6) up-regulation and actin reorganization. Temporal knockdown of RIG-I by siRNA decreased IFN-β expression, while MDA5 siRNA inhibited IFN-β and IL-6 expression. Actin reorganization was attenuated by RIG-I and MDA5 knockdown. Conclusion: RIG-I and MDA5 may play a role in the antiviral responses of podocytes. [ABSTRACT FROM AUTHOR]