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Characterization of the elemental distribution of samples with rough surfaces has been strongly desired for the analysis of various natural and artificial materials. Particularly for pristine and rare analytes with micrometer sizes embedded on specimen surfaces, non-invasive and matrix effect-free analysis is required without surface polishing treatment. To satisfy these requirements, we proposed a new method employing the sequential combination of two imaging modalities, i.e., microenergy-dispersive X-ray fluorescence (micro-XRF) and Raman micro-spectroscopy. The applicability of the developed method is tested by the quantitative analysis of cation composition in micrometer-sized carbonate grains on the surfaces of intact particles sampled directly from the asteroid Ryugu. The first step of micro-XRF imaging enabled a quick search for the sparsely scattered and micrometer-sized carbonates by the codistributions of Ca2+and Mn2+on the Mg2+- and Fe2+-rich phyllosilicate matrix. The following step of Raman micro-spectroscopy probed the carbonate grains and analyzed their cation composition (Ca2+, Mg2+, and Fe2++ Mn2+) in a matrix effect-free manner via the systematic Raman shifts of the lattice modes. The carbonates were basically assigned to ferroan dolomite bearing a considerable amount of Fe2++ Mn2+at around 10 atom %. These results are in good accordance with the assignments reported by scanning electron microscopy–energy-dispersive X-ray spectroscopy, where the thin-sectioned and surface-polished Ryugu particles were applicable. The proposed method requires neither sectioning nor surface polishing; hence, it can be applied to the remote sensing apparatus on spacecrafts and planetary rovers. Furthermore, the non-invasive and matrix effect-free characterization will provide a reliable analytical tool for quantitative analysis of the elemental distribution on the samples with surface roughness and chemical heterogeneity at a micrometer scale, such as art paintings, traditional crafts with decorated shapes, as well as sands and rocks with complex morphologies in nature.

The Hayabusa2 spacecraft explored asteroid Ryugu and brought its surface materials to Earth. Ryugu samples resemble Ivuna-type (CI) chondrites—the most chemically primitive meteorites—and contain secondary phyllosilicates and carbonates, which are indicative of aqueous alteration. Understanding the conditions (such as temperature, redox state and fluid composition) during aqueous alteration is crucial to elucidating how Ryugu evolved to its present state, but little is known about the temporal changes in these conditions. Here we show that calcium carbonate (calcite) grains in Ryugu and Ivuna samples have variable 18O/16O and 13C/12C ratios that are, respectively, 24–46‰ and 65–108‰ greater than terrestrial standard values, whereas those of calcium–magnesium carbonate (dolomite) grains are much more homogeneous, ranging within 31–36‰ for oxygen and 67–75‰ for carbon. We infer that the calcite precipitated first over a wide range of temperatures and oxygen partial pressures, and that the proportion of gaseous CO2/CO/CH4molecules changed temporally. By contrast, the dolomite formed later in a more oxygen-rich and thus CO2-dominated environment when the system was approaching equilibrium. The characteristic isotopic compositions of secondary carbonates in Ryugu and Ivuna are not observed for other hydrous meteorites, suggesting a unique evolutionary pathway for their parent asteroid(s).

The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance1–3. Here, we show that antigen-specific avoidance behaviour in inbred mice4,5is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.

Study Design: Retrospective Study.Objectives: Sacroiliac buttress screws (SBS) and S2 alar iliac screws (SAI) are used as distal screws in cases with long fusion to the pelvis. Distal fixation ends, whether exceeding the sacroiliac joint (SIJ), may affect postoperative degenerative changes in the SIJ. The aim of this study was to investigate SIJ degeneration after lumbosacral and lumbopelvic fixation, using SBS and SAI in degenerative spine diseases, respectively.Methods: This study included 70 patients aged ≥50 years with lumbosacral fusion (>3 levels). They were divided into 2 groups (SBS 20 and SAI 50 cases) based on the type of distal screws. Radiographical and clinical data were reviewed with a minimum 2-year follow-up. Radiographical SIJ degeneration was analyzed using computed tomography; clinical outcomes were evaluated using visual analog scale (VAS) and Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ).Results: No significant differences were observed in patients’ preoperative characteristics between the 2 groups. The incidence of SIJ degeneration, including osteophyte formation (30.0% and 8.0%, p = 0.03), intraarticular air (75.0% and 16.0%, p < 0.001), and subchondral cyst (20.0% and 2.0%. p = 0.02) in SBS and SAI groups, respectively, at the follow-up, was significantly higher in the SBS group. Although SIJ degenerative changes were significantly different between the SBS and SAI groups, there was no significant difference in VAS and JOABPEQ scores between the groups at 2 years post-surgery.Conclusions: Lumbosacral fusion can cause SIJ degeneration, which is more frequent when SBS are used in fixation to the sacrum.

Carnitine is an amino acid derivative that plays an important role in the promotion and regulation of fatty acid metabolism, and carnitine deficiency is assumed in patients with anorexia nervosa associated with chronic starvation, but there are few reports on this issue. This study represents the inaugural documentation of hypocarnitinemia in severely malnourished patients with eating disorders, including anorexia nervosa. Hypocarnitinemia, particularly in cases of severe undernutrition (BMI < 13 kg/m2) was observed during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment was considered a potential indicator of hypocarnitinemia. Although no apparent association with adverse events other than anemia during refeeding was identified, clinical manifestations of hypocarnitinemia may occur when a sudden increase in energy demand is added to a change in the physical condition of the patient group. Further investigation is required to determine the clinical significance of hypocarnitinemia.

•A 3D-HPLC system was developed for the determination of chiral amino acids in Ryugu samples.•Enantiomers of 5 proteinogenic and 3 non-proteinogenic amino acids were determined.•Applicability of the system was evaluated by analyzing several types of carbonaceous meteorites.•In the Ryugu samples, all of the target amino acids were successfully determined quantitatively.•Non-proteinogenic amino acids were found as almost racemic mixtures with 47.1 to 55.2%L.

The crystal-orientation behavior of Sr2NaNb5O15(SNN) lead-free piezoelectric materials under a magnetic field was investigated by substituting rare-Earth elements (Ln = Nd, Eu, Ho, Yb), which were selected based on their ionic radii and magnetic or non-magnetic ions. The magnetic ions, Nd, Ho, and Yb, did not affect the magnetic anisotropy of the SNN. The nonmagnetic ions (Eu3+) changed from the a, b-axis orientation to the c-axis orientation in the direction of the magnetic field. The Eu-substituted SNN powders revealed that the degree of orientation of the c-axis increased as the Eu content increased. Consequently, c-axis-oriented Eu-substituted SNN ceramics were obtained with the degree of orientation of 0.9. The diamagnetism along the a, b-axis became larger than that along the c-axis owing to a decrease in the c-axis lattice constant. By substituting Eu with SNN, the piezoelectric properties decreased as the hardening of SNN progressed.

Purpose: This study aimed to compare the efficacy and safety of cutting balloon angioplasty (CBA) and conventional balloon angioplasty (control group) for recurrent vascular access stenosis in arteriovenous fistulas.Materials and methods: This prospective, randomized single-center clinical trial included patients with hemodynamically significant recurrent vascular access stenosis of an arteriovenous fistula. The Kaplan–Meier method was used to assess primary patency, whereas the log-rank test was used to evaluate differences in patency between groups. Functional evaluations were performed using Doppler ultrasonography.Results: Patients (n= 122) were randomly assigned to undergo CBA or conventional balloon angioplasty between December 2012 and November 2017. The clinical success rate was 100% in both groups. The anatomical success rates were 65% and 56% in the CBA and control groups, respectively. The primary patency of the target lesion was significantly better in the CBA group (33.3%) than in the control group (16.1%) at 6 months (hazard ratio, 0.50; 95% confidence interval, 0.33–0.77; p= 0.00171). The stenosis percentage decreased significantly after angioplasty in the CBA group (Δ-50.7%) compared with the control group (Δ-41.9%) (p= 0.0008). Access flow, measured using duplex Doppler ultrasonography, improved after angioplasty in both groups (300–526 ml/min in the control group and, 268–546 ml/min in the CBA group). Change in access flow (Δ + 278 ± 162) in the CBA group tended to be greater than that in the control group (Δ + 226 ± 151) (p= 0.07). However, the difference was not statistically significant.Conclusion: In patients with recurrent vascular access stenosis of the arteriovenous fistula CBA is effective and superior to conventional angioplasty.

Tyrosine kinase inhibitors (TKIs) that target the epidermal growth factor receptor (EGFR) have shown highly favourable outcomes in patients with advanced-stage non-small-cell lung cancer (NSCLC). The adverse effects of EGFR-TKIs are generally less severe than those of conventional cytotoxic therapies. We report a patient with NSCLC who presented with acute kidney injury associated with biopsy-proven acute tubular injury during osimertinib treatment and whose renal function recovered after reducing the osimertinib dose. A 61-year-old male smoker complained of dyspnoea on exertion for 1 month before his visit to the medical centre. He was diagnosed with lung adenocarcinoma of the left lower lobe (cT4N3M1a, stage IVA) and was positive for an EGFRmutation (exon 19 deletion). Osimertinib was initiated at 80 mg/day. At treatment initiation, the patient’s serum creatinine level was 0.64 mg/dL, with microscopic haematuria; by day 83, this level had increased to 1.33 mg/dL, with proteinuria. On day 83, we reduced the osimertinib dose to 40 mg/day and performed a kidney biopsy on day 98. The histological diagnosis was tubular injury with IgA deposition. Based on the clinical course and histological findings, we speculated that the kidney injury was associated with osimertinib. After dose reduction, the patient’s serum creatinine level decreased to 1.07 mg/dL, and proteinuria disappeared. He maintained a partial response for >6 months after osimertinib administration. We report the first case of biopsy-proven mild IgA deposition, crescent formation, and tubular injury probably caused by osimertinib and demonstrate how reducing the osimertinib dose could strike a balance between its anti-cancer efficacy and adverse effects.

The Japanese interplanetary probe Hayabusa2 was launched on December 3, 2014 and the probe arrived at the vicinity of asteroid 162173 Ryugu on June 27, 2018. During its 1.4 years of asteroid proximity phase, the probe successfully accomplished numbers of record-breaking achievements including two touchdowns and one artificial cratering experiment, which are highly expected to have secured surface and subsurface samples from the asteroid inside its sample container for the first time in history. The Hayabusa2 spacecraft was designed not to orbit but to hover above the asteroid along the sub-Earth line. This orbital and geometrical configuration allows the spacecraft to utilize its high-gain antennas for telecommunication with the ground station on Earth while pointing its scientific observation and navigation sensors at the asteroid. This paper focuses on the regular station-keeping operation of Hayabusa2, which is called “home position” (HP)-keeping operation. First, together with the spacecraft design, an operation scheme called HP navigation (HPNAV), which includes a daily trajectory control and scientific observations as regular activities, is introduced. Following the description on the guidance, navigation, and control design as well as the framework of optical and radiometric navigation, the results of the HP-keeping operation including trajectory estimation and delta-V planning during the entire asteroid proximity phase are summarized and evaluated as a first report. Consequently, this paper states that the HP-keeping operation in the framework of HPNAV had succeeded without critical incidents, and the number of trajectory control delta-Vwas planned efficiently throughout the period.

Subsurface exploration is one of the most ambitious scientific objectives of the Hayabusa2 mission. A small device called small carry-on impactor (SCI) was developed to create an artificial crater on the surface of asteroid Ryugu. This enables us to sample subsurface materials, which will provide a window to the past. The physical properties of the resulting crater are also useful for understanding the internal structure of Ryugu. Accurate understanding of the crater and ejecta properties, including the depth of excavation of subsurface materials, requires accurate information on impact conditions. In particular, the impact angle is a critical factor because it greatly influences the size and shape of the crater. On April 5, 2019, the Hayabusa2 spacecraft deployed the SCI at 500 m of altitude above the asteroid surface. The SCI gradually reduced its altitude, and it shot a 2 kg copper projectile into the asteroid 40 min after separation. Estimating the position of the released SCI is essential for determining the impact angle. This study describes the motion reconstruction of the SCI based on the actual operation data. The results indicate that the SCI was released with high accuracy.

Study Design: A retrospective review of clinical data and costs was performed for surgeries for adolescent idiopathic scoliosis (AIS) conducted from 2008 to 2017.Objective: Cost containment and healthcare value have become focal points in Japanese health care policy. The purpose of the study was to investigate trends over time in medical costs for surgery for AIS.Methods: A total of 83 patients underwent surgery for AIS from 2008 to 2017 at our hospital. Clinical data and length of stay were collected, and medical costs for surgery, local bone grafting, fees per day, and surgical instruments were evaluated.Results: There were slight year-by-year decreases in fees per day and decreases in costs of surgical instruments. The average length of stay was 16.4 days and gradually decreased over time. In contrast, scoliosis surgery costs increased about 1.6 times in 10 years from $9515 to $15 130.Conclusion: The trends for decreases in fees per day and prices for surgical instruments reflect recent government medical cost control policies. The cost for scoliosis surgery is also defined by the government, and the increase over 10 years may reflect the perspective of valuing effective and advanced surgeries. This study of cost trends of operative spinal intervention provides an assessment of surgical benefit and is likely to influence health care costs.

Idiopathic osteonecrosis of the femoral head (ONFH) is defined as necrosis of osteocytes due to a non-traumatic ischemia of the femoral head. Iatrogenic glucocorticoid administration and habitual alcohol intake are regarded as risk factors. It has been suggested that glucocorticoid-induced activation of platelets contributes to the local blood flow disturbance of the femoral head. Both activated platelets and alcohol can induce neutrophil extracellular traps (NETs). To determine the association of NETs with the development of idiopathic ONFH, surgically resected femoral heads of patients with idiopathic ONFH and osteoarthritis were assessed for existence of NET-forming neutrophils by immunofluorescence staining. NET-forming neutrophils were present in small vessels surrounding the femoral head of patients with idiopathic ONFH but not osteoarthritis. Moreover, Wistar-Kyoto rats were intravenously injected with NET-forming neutrophils or neutrophils without NET induction, and then the ischemic state of the tissue around the femoral head was evaluated by immunohistochemistry for hypoxia-inducible factor-1α. NET-forming neutrophils circulated into the tissue around the femoral head, and hypoxia-inducible factor-1α expression in the tissue was higher compared with that of rats intravenously administered with neutrophils without NET induction. Furthermore, ischemic change of osteocytes was observed in the femoral head of rats given an i.v. injection of NET-forming neutrophils. The collective findings suggest that NETs are possibly associated with the development of idiopathic ONFH.

In this paper we deal with positive radially symmetric solutions for a boundary value problem containing a strongly nonlinear operator.The proof of existence of positive solutions that we give uses the blow-up method as a main ingredient for the search of a-priori bounds of solutions.The blow-up argument is one by contradiction and uses a sort of scaling, reminiscent to the one used in the theory of minimal surfaces, see [B. Gidas and J. Spruck,A priori bounds for positive solutions of nonlinear elliptic equations,Comm. Partial Differential Equations 6 1981, 883–901], and therefore the homogeneity of the operators, Laplacian or p-Laplacian, and second members powers or power like functions play a fundamental role in the method.Thus, when the differential operators are no longer homogeneous, and similarly for the second members, applying the blow-up method to obtain a-priori bounds of solutions seems an almost impossible task.In spite of this fact, in [M. García-Huidobro, I. Guerra and R. Manásevich,Existence of positive radial solutions for a weakly coupled system via blow up,Abstr. Appl. Anal. 3 1998, 1–2, 105–131], we were able to overcome this difficulty and obtain a-priori bounds for a certain (simpler) type of problems.We show in this paper that the asymptotically homogeneousfunctions provide, in the same sense, a nonlinear rescaling, that allows us to generalize the blow-up method to our present situation.After the a-priori bounds are obtained, the existence of a solution follows from Leray–Schauder topological degree theory.

Carbonaceous (C-type) asteroids1are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites2,3and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth’s atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)4onboard the spacecraft Hayabusa25, indicating that the asteroid’s boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m−2s−0.5K−1(300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites6and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect7,8. We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites6. These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity9of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies10.

Study Design: Retrospective study.Objectives: To elucidate risk factors for early-onset (2 months after initial kyphoplasty) adjacent vertebral fracture (EO-AVF) after kyphoplasty.Methods: A total of 108 vertebral bodies (95 patients) were included in this study. We examined patient backgrounds, the spinal level of EO-AVFs, surgery-related factors, and imaging findings. We divided the cases into 2 groups: patients with EO-AVF and patients without EO-AVF. Univariate, correlation, and multivariate analyses were conducted to reveal the risks factors for EO-AVFs for these 2 groups.Results: EO-AVFs developed in 28 vertebral bodies; they did not develop in 80 vertebral bodies. The overall EO-AVF incidence rate was 26%. The spinal level was the thoracolumbar junction for 93% of patients and another level for 7%, thus demonstrating the concentration of EO-AVFs in the thoracolumbar junction. For patients without EO-AVF and those with EO-AVF, there were significant differences in age (76 and 80 years, respectively), preoperative vertebral angles (VAs) (17.8° and 23°, respectively), and corrected VAs (7.3° and 12.7°, respectively). Significant differences were not observed for other factors. Pearson’s correlation coefficient was 0.661 (P< .000), thereby showing a significantly positive correlation between preoperative VAs and corrected VAs. Logistic regression analysis indicated that age (odds ratio, 1.112; 95% CI, 1.025-1.206) and preoperative VAs (odds ratio, 1.08; 95% CI, 1.026-1.135) were covariates and that the presence of an EO-AVF was a dependent variable. Therefore, both were predictable risk factors for EO-AVFs.Conclusion: Age, preoperative VAs, and corrected VAs are risk factors for EO-AVFs after kyphoplasty.

ABSTRACTWe previously reported that MDA-MB-231 and MCF-7 cells, which are breast cancer cell lines and have cancer and cancer-initiating cells (CICs), were killed following normothermic microwave irradiation in which the cellular temperature was maintained at 37°C. In this study, we investigated the percentages of live or dead cells among CD44+/CD24−cells, which were defined as CICs among MDA-MB-231 and MCF-7 cells, and other types of cells in response to microwave irradiation. CD44+/CD24−cells among MDA-MB-231 cells were killed, thereby decreasing the number of cells, whereas the number of live CD44+/CD24−MCF-7 cells was increased following microwave irradiation. Moreover, adhesion, invasion, and migration were decreased in MDA-MB-231 cells, and the activation of matrix metalloproteinase-2 (MMP-2) in MDA-MB-231 cells was increased following microwave irradiation. These decreased cell activities might have been caused by MMP-2 activation and population changes in CD44+/CD24−in MDA-MB-231 cells.Abbreviations:APC: allophecocyanin; CBB: coomassie Brilliant Blue; CD: cluster of differentiation; CICs: cancer-initiating cells; FACS: fluorescence-activated cell sorting; FBS: fetal bovine serum; FITC: fluorescein isothiocyanate; FTDT: finite-difference time domain; HER2: human epidermal growth factor receptor type 2; PI: propidium iodide.

AbstractWhat determines the earnings of a worker relative to his peers in the same occupation? What makes a worker fail in one occupation but succeed in another? More broadly, what are the factors that determine the productivity of a worker-occupation match? To help answer questions like these, we propose an empirical measure of multidimensional skill mismatch that is based on the discrepancy between the portfolio of skills required by an occupation and the portfolio of abilities possessed by a worker for learning those skills. This measure arises naturally in a dynamic model of occupational choice and human capital accumulation with multidimensional skills and Bayesian learning about one’s ability to learn skills. Not only does mismatch depress wage growth in the current occupation, it also leaves a scarring effect—by stunting skill acquisition—that reduces wages in future occupations. Mismatch also predicts different aspects of occupational switching behavior. We construct the empirical analog of our skill mismatch measure from readily available US panel data on individuals and occupations and find empirical support for these implications. The magnitudes of these effects are large: moving from the worst- to best-matched decile can improve wages by 11 percent per year for the rest of one’s career. (JEL E24, J24, J31, J41)

We previously reported that MDA-MB-231 and MCF-7 cells, which are breast cancer cell lines and have cancer and cancer-initiating cells (CICs), were killed following normothermic microwave irradiation in which the cellular temperature was maintained at 37°C. In this study, we investigated the percentages of live or dead cells among CD44+/CD24-cells, which were defined as CICs among MDA-MB-231 and MCF-7 cells, and other types of cells in response to microwave irradiation. CD44+/CD24-cells among MDA-MB-231 cells were killed, thereby decreasing the number of cells, whereas the number of live CD44+/CD24-MCF-7 cells was increased following microwave irradiation. Moreover, adhesion, invasion, and migration were decreased in MDA-MB-231 cells, and the activation of matrix metalloproteinase-2 (MMP-2) in MDA-MB-231 cells was increased following microwave irradiation. These decreased cell activities might have been caused by MMP-2 activation and population changes in CD44+/CD24-in MDA-MB-231 cells.Abbreviations:APC: allophecocyanin; CBB: coomassie Brilliant Blue; CD: cluster of differentiation; CICs: cancer-initiating cells; FACS: fluorescence-activated cell sorting; FBS: fetal bovine serum; FITC: fluorescein isothiocyanate; FTDT: finite-difference time domain; HER2: human epidermal growth factor receptor type 2; PI: propidium iodide.

Lymphedema is a chronic condition caused by disruption of lymphatic vessels, which often occurs after invasive surgery. Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene (Calca). CGRP was initially identified as a neuropeptide released primarily from sensory nerves and involved in regulating pathophysiological nociceptive pain. However, recent studies have shown CGRP is also released from a variety of other cells and possesses multiple functions. In this study, CGRP knockout (−/−) mice were used to show the actions of endogenous CGRP in postoperative lymphedema. After generating a mouse postoperative tail lymphedema model, the edema was observed to be more severe in CGRP−/−mice than in wild-type mice. Numbers of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1)–positive lymphatic capillaries were decreased and lymphatic capillary formation–related factors were down-regulated in CGRP−/−mice. In addition, accumulation of M2 but not M1 macrophages was selectively reduced in the edematous tissue of CGRP−/−mice. Selective depletion of M2 macrophages decreased lymphatic capillary formation and worsened lymphedema in wild-type mice but not CGRP−/−mice, where numbers of M2 macrophages were already diminished. These findings suggest that endogenous CGRP acts to ameliorate postoperative lymphedema by enhancing lymphatic capillary formation and that M2 macrophages play critical roles. CGRP may be a useful therapeutic target for the treatment of postoperative lymphedema.

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Sufficient internal fixation for occipitocervical (OC) or C1–C2 instability in pediatric patients with Down syndrome is difficult owing to small osseous structures, congenital deformities, and immature ossification. The purpose of this study was to evaluate the clinical outcomes of patients aged 8 years or younger with Down syndrome who underwent OC or C1–C2 fusion using freeze-dried allograft as bone graft substitute. The participants included seven consecutive patients aged 8 years or younger with Down syndrome who were treated for upper cervical disorders with posterior OC or C1–C2 fusion using freeze-dried allografts at our hospital between 2007 and 2016 and had a minimum follow-up of 1 year. Postoperative flexion/extension cervical radiography and computed tomography were repeated at 3 months after surgery before removal of the collar. The modified McCormick scale was used to grade functional status. The seven patients had an age range of 5–8 years (mean: 5.9 years). The mean follow-up period was 36 months (12–120 months). Six patients had os odontoideum and one had basilar invagination. Three patients underwent C1–C2 fusion, and in all cases, bilateral C1 lateral mass screws and bilateral C2 pedicle screws were used. Four patients underwent OC fusion, and in three of these cases, occipital and bilateral pedicle screws were used. One patient underwent reoperation because of occipital screw back-out with autograft; therefore, C2 lamina screws were added to pedicle screws. Solid bony fusion was achieved, and stable constructs were maintained on radiography in all patients, without infection or implant failure. In this study, we used freeze-dried allograft as a bone graft substitute, and we were able to detect bony trabeculae at the graft–recipient interface on lateral cervical radiographs and on reconstructed sagittal computed tomographic images in all patients. These results suggest that use of allograft is effective for treatment of upper cervical spine abnormalities in pediatric patients with Down syndrome.

Purpose: The population of obese patients is increasing in general and also at hemodialysis initiation. For successful cannulation of arteriovenous fistula, the National Kidney Foundation-Dialysis Outcome Quality Initiative guidelines suggest that the required maturation parameters are at a depth of <6 mm. There are several reports describing two-stage superficialization of arteriovenous fistulas in obese cases. Therefore, we investigated the utility and complications of one-stage superficialization of radio-cephalic fistula.Methods: From January 2011 to March 2017, we simultaneously performed forearm radio-cephalic fistula creation and superficialization of the cephalic vein for 10 patients having obesity (body mass index > 30 kg/m2) and deep cephalic vein (>6 mm). Initially, an arteriovenous anastomosis was created at an appropriate site. Subsequently, an 8–10 cm longitudinal skin incision was made along the lateral aspect of the forearm cephalic vein. The cephalic vein was identified and exposed. The cephalic vein was repositioned superficially.Results: The mean age of the patients was 53 years (range: 40–72 years) and the mean body mass index was 40.2 kg/m2(33.1–59.7 kg/m2). The cause of renal failure in eight patients was diabetic nephropathy, and in two patients, it was unknown. After the procedure, vein depth became 3.4 mm (1.9–4.6 mm) from 8.2 mm (6.0–13.4 mm). All patients who initiated dialysis underwent successful two-needle cannulation. Primary patency rate was 71.4% at 12 months (two patients underwent percutaneous transluminal angioplasty) and secondary patency rate was 100%. There was one procedure-related complication and delayed wound healing, which was improved by observation without antibiotics.Conclusion: This small series of patients indicates that one-stage superficialization of radio-cephalic fistula is a safe and effective option to start hemodialysis in obese subjects.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the production of ANCAs and systemic necrotizing vasculitis in small vessels. Disordered regulation of neutrophil extracellular traps (NETs) is critically involved in the pathogenesis of AAV. NETs are web-like DNA decorated with antimicrobial proteins; they are extruded from activated neutrophils. The principal degradation factor of NETs in vivois DNase I; however, NETs resistant to DNase I can persist in tissues and can lead to the production of ANCAs. Deposition of NETs has been demonstrated in glomerular crescents and necrotizing vasculitis in AAV. Here, the amount of NETs in formalin-fixed, paraffin-embedded tissue sections was examined, and the results for AAV were compared with the results for diseases that should be distinguished from AAV. NETs were more abundant in necrotizing vasculitis of AAV than in non–ANCA-associated vasculitis, or in granulomatous angiitis. Pulmonary granulomas in AAV and non–ANCA-associated diseases were further studied. The amount of NETs was significantly greater in necrotizing granulomas of AAV than in granulomas of sarcoidosis without necrosis. Although NETs were formed in necrotizing granulomas of tuberculosis equivalently to those formed in AAV, they were more susceptible to degradation by DNase I than were NETs in AAV. The formation and disordered degradation of NETs in necrotizing lesions are characteristics of AAV and are possibly related to its pathogenesis.

Cell death, including apoptotic and non-apoptotic cell death, is frequently observed in liver disease. Upon activation of the mitochondrial apoptotic pathway, mitochondria release not only apoptogenic cytochrome cbut also mitochondrial DNA (mtDNA) into the cytosol. The impact of DNase II, a lysosomal acid DNase that degrades mtDNA, on hepatocyte death remains unclear. Administration of ABT-737, a Bcl-xL inhibitor, upregulated DNase II activity in murine hepatocyte cell line BNL CL.2 cells and induced apoptosis. In cells treated with DNase II siRNA, ABT-737 led to accumulation of mtDNA in the cytosol and increased expression of interferon (IFN)-β and induction of propidium iodide (PI)-positive cells, in addition to apoptosis. Induced PI-positive cells were suppressed by RIP1 inhibitor, Necrostatin-1, but not by pan-caspase inhibitor, ZVAD-FMK, suggesting non-apoptotic cell death. Both the increase in IFN-β and the induction of non-apoptotic cell death were abolished by administering a TLR9 antagonist, ODN2088, or by the removal of mtDNA from cells with ethidium bromide. Hepatocyte-specific Mcl-1 knockout mice developed hepatocyte apoptosis accompanied by upregulated DNase II activity in their livers. Further knockout of DNase II induced IFN-β expression and RIP1-dependent non-apoptotic hepatocyte death, both of which were suppressed by the administration of ODN2088. Mice fed a high-fat diet (HFD), an obesity-associated fatty liver model, showed increased expression of IFN-β with suppression of DNase II activity in their livers and developed not only hepatocyte apoptosis but also non-apoptotic hepatocyte death. Hepatocyte-specific knockout of DNase II exacerbated HFD-induced non-apoptotic hepatocyte death and liver fibrosis. In conclusion, without DNase II, apoptotic stimulation on hepatocytes induces TLR9-dependent IFN-β production and RIP1-dependent non-apoptotic cell death originating from mtDNA. In fatty livers, DNase II activity is suppressed in contrast to simple inactivation of Bcl-xL or Mcl-1, and both apoptotic and non-apoptotic hepatocyte death can develop, leading to the progression of liver fibrosis.