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Abstract HOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disease-specific human induced pluripotent stem cells (hiPSCs). Myotubes differentiated from HOIL-1L-KO C2C12 cells exhibited deteriorated differentiation and mitotic cell accumulation. CMs differentiated from patient-derived hiPSCs had an abnormal morphology with a larger size and were excessively multinucleated compared with CMs differentiated from control hiPSCs. Further analysis of hiPSC-derived CMs showed that HOIL-1L deficiency caused cell cycle alteration and mitotic cell accumulation. These results demonstrate that abnormal cell maturation possibly contribute to the development of myopathy and DCM. In conclusion, HOIL-1L is an important intrinsic regulator of cell cycle-related myotube and CM maturation and cell proliferation.

Abstract Background Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. Case report The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications—including intra-abdominal hemorrhaging and ischemic changes in the intestine—her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. Conclusions To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease, thrombosis, and all-cause death. However, few studies have examined the association between CKD and the prognosis of patients with essential thrombocythemia (ET). We collected ET patients who met the WHO classification 2017 and performed a retrospective clinical study to clarify the association between the presence and onset of CKD and prognosis. Of 73 patients who met the diagnostic criteria, 21 (28.8%) had CKD at the time of ET diagnosis. The age of patients with CKD was significantly higher, and a high proportion of these patients had the JAK2V617F gene mutation. The presence of CKD was a risk factor for the prognosis (hazard ratio (HR): 3.750, 95% confidence interval (CI): 1.196–11.760, P=0.023), and the survival curve was significantly poorer. Furthermore, we analyzed patients without CKD at the time of ET diagnosis using the onset of CKD as a time-dependent variable and identified the onset of CKD as a risk factor for the prognosis (HR: 9.155, 95% CI: 1.542–54.370, P=0.005). In patients with renal hypofunction at the time of ET diagnosis or those with a reduction in the kidney function during follow-up, strict renal function monitoring at regular intervals is necessary.

With advancements in medical technology, the structure of disease is shifting from acute illnesses to chronic conditions, such as Alzheimer’s disease (AD). Consequently, there is an escalating need for evaluations that discourse on the potential effects on healthy life years, as well as disease onset. We aimed to evaluate the associations with AD disability-adjusted life year (AD-DALY) rates and protein intake by sex and age group. For the analysis, we used representative values for males and females in their 60s and aged over 70, extracted from the public dataset of the Global Burden of Disease Study and the National Health and Nutrition Survey in Japan, covering the years 1990 to 2019. In order to evaluate the association between AD-DALY rates and protein intake, we analyzed correlations and stratified multiple regression models. Additionally, we simulated alterations in AD-DALY rates associated with changes in protein intake by utilizing stratified multiple regression models. AD-DALY rates and protein intake indicated significant negative correlations across all sex and age groups. In stratified multiple regression models, significant associations were found between higher protein intake and lower AD-DALY rates in females. In the simulation, when protein intake was increased to 1.5 g/kg/day, AD-DALY rates decreased by 5–9 percent compared with 2019. However, the association between intake of animal and plant protein and AD-DALY rates were found to vary based on sex and age group. The present study suggests the possibility to improve AD-DALY rates by increasing population average protein intake levels in a recommended range.

ABSTRACT Aims/Introduction In addition to absolute insulin deficiency, dysregulated glucagon in type 1 diabetes is considered pathophysiologically important. Previously, we confirmed the presence of dysregulated glucagon in Japanese patients with type 1 diabetes, and found a significant correlation between plasma glucagon and blood urea nitrogen levels, suggesting an association between glucagon and amino acid metabolism. In this study, we evaluated plasma amino acid levels in Japanese patients with type 1 diabetes in the context of their functional relationship with glucagon. Materials and Methods We assessed plasma free amino acid levels using liquid chromatography–mass spectrometry in 77 Japanese patients with type 1 diabetes, and statistically analyzed their characteristics and relationships with clinical parameters, including glucagon. Results Participants with type 1 diabetes showed a large decrease in glutamate levels together with a characteristic change in plasma free amino acid profiles. The network structural prediction analyses showed correlations between each amino acid and glucagon in type 1 diabetes. Conclusions Participants with type 1 diabetes showed characteristic changes in plasma glutamate levels and free amino acid profiles compared with controls and type 2 diabetes patients. Glucagon showed a closer correlation with amino acids than with parameters of glucose metabolism, suggesting that type 1 diabetes includes dysregulation in amino acids through dysregulated glucagon from remaining pancreatic α‐cells, together with that in glucose by insulin deficiency.

Abstract Background Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. Methods We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. Results HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p

Background Can Background be changed from bold to normal text?: Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. Methods: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks’ HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. Results: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. Conclusions: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.

Abstract Background and Aim Treatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living‐donor liver transplantation (LDLT) for small HCC in a single institute. Methods We compared the overall survival, recurrence‐free survival, and cancer‐specific survival rates in patients with three HCC nodules

Portal vein thrombosis following liver transplantation is generally managed by endovascular treatment. Although several techniques are available for portal venous access, trans-splenic access is of interest because it avoids damage to the liver graft. However, the spleen cannot be punctured to access the portal vein after splenectomy. We herein report a case of portal vein thrombosis following living donor liver transplantation with simultaneous splenectomy successfully treated by percutaneous intervention with direct puncture of the retropancreatic splenic vein. The splenic vein was punctured under computed tomography guidance in the prone position. Portal venography revealed a contrast defect due to a thrombus in the extrahepatic to intrahepatic portal vein. The portal vein was reopened after thrombectomy, and the portal vein thrombosis did not recur for 2 y. The technique and advantages of our approach are described.

PurposeUpregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature.MethodsThe type I IFN signature was measured in patients’ whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature.ResultsA total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling.ConclusionsHalf of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.

Abstract Patients with hematological disorders are treated with multiple cycles of chemotherapy. As a result, they often require multiple insertions of the peripherally inserted central catheter (PICC) for prolonged periods of time. Although PICCs have been widely used worldwide in various patients, the safety and feasibility of the multiple insertions of the PICC in this population have not been fully verified. We performed a retrospective analysis to clarify the relationship between complications and multiple PICC insertions in patients with hematological disorders who were treated with either chemotherapy or immunotherapy. A total of 651 PICCs were inserted in 261 patients with a median age of 66 years. Acute myeloid leukemia (AML) and non-Hodgkin's lymphoma were the most common diseases in our patient cohort. The total catheter days (CDs) was 29,485 days, with a median catheter duration of 30 days. The rate of catheter-related bloodstream infection (CRBSI) in our patient cohort at high rate of re-insertion was 2.0/1000 CDs. Although multiple PICC insertions were not a risk factor of CRBSI, our findings suggest that a prolonged catheter dwell time may be associated with CRBSI. AML was an important risk factor of CRBSI. While the PICC dwell time depends on the treatment cycle, our findings indicate that it should be limited to approximately 30 days and catheters may be removed and re-inserted as needed.

Familial Mediterranean fever (FMF) is a hereditary, autoinflammatory disease that causes recurrent fever, arthritis, and serositis. The diagnosis of FMF is based on the presentation of typical clinical symptoms and the Mediterranean fever gene (MEFV) test. However, the challenge lies in diagnosing atypical cases. In this report, we have described a pediatric patient with complex FMF whose diagnosis required trio-whole exome sequencing (WES) and functional validation of a rare MEFV variant. A 3-year-old boy presented with recurrent episodes of elevated liver enzymes and arthralgia. He was diagnosed with autoimmune hepatitis (AIH), and his liver enzymes improved rapidly with steroid treatment. However, he exhibited recurrent arthralgia and severe abdominal attacks. Trio-WES identified compound heterozygous mutations in MEFV (V726A and I692del). Ex vivo functional assays of the patient’s monocytes and macrophages, which had been pre-treated with Clostridium difficile toxin A (TcdA) and colchicine, were comparable to those of typical FMF patients, thereby confirming the diagnosis of FMF. Although he was intolerant to colchicine because of liver toxicity, subsequent administration of canakinumab successfully ameliorated his abdominal attacks. However, it was ineffective against liver injury, which recurred after steroid tapering. Therefore, in this case, the pathogenesis of AIH was probably interleukin-1β (IL-1β)-independent. In fact, AIH might have been a concurrent disease with FMF, rather than being one of its complications. Nevertheless, further studies are necessary to determine whether FMF-induced inflammasome activation contributes to AIH development. Moreover, we must consider the possibility of mixed phenotypes in such atypical patients who present distinct pathologies simultaneously.

Purpose: This study reports a case of the spontaneous avulsion of primary pterygium with anterior segment optical coherence tomography (AS-OCT) findings. Observation: A 72-year-old woman complained of acute pain of the left eye. Primary pterygia were noted in both eyes on the initial examination 4 months ago. Slit-lamp microscopy revealed a nasal corneal epithelial defect, and the rolled elevated lesion in the corneal limbus of the left eye. She was diagnosed with a spontaneous avulsion of the corneal pterygium head. Then the avulsed pterygium head slowly recurred. The pterygium head of the fellow eye had a yellow-whitish elevated lesion beneath the epithelium with poor vascularity. AS-OCT revealed hyper-reflective foci beneath the epithelium corresponding to the yellow-whitish elevated lesion. Conclusions/importance: The present case revealed the spontaneous avulsion of the pterygium head leading to the corneal epithelial defects and ocular pain, while the pterygium head of the fellow eye showed subepithelial hyper-reflective foci suspicious of spheroidal degeneration on AS-OCT. In this case, the cause of spontaneous avulsion of the pterygium head might be potentially weak adhesion to the cornea due to spheroidal degeneration. Precis: This case is a primary pterygium leading to spontaneous avulsion, in which hyper-reflective foci were noted in OCT.

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The reactivity of expanded porphyrins is highly influenced by their scaffold architecture. Here, the authors construct two nonaromatic dumbbell-shaped benzene- and pyridine-incorporating octaphyrins via Suzuki-Miyaura cross-coupling; depending on the framework, different coordination modes are obtained upon metallation with Pd(II).

The concept of autoinflammation, first proposed in 1999, refers to a seemingly unprovoked episode of sterile inflammation manifesting as unexplained fever, skin rashes, and arthralgia. Autoinflammatory diseases are caused mainly by hereditary abnormalities of innate immunity, without the production of autoantibodies or autoreactive T cells. The revolutionary discovery of induced pluripotent stem cells (iPSCs), whereby a patient’s somatic cells can be reprogrammed into an embryonic pluripotent state by forced expression of a defined set of transcription factors, has the transformative potential to enable in vitro disease modeling and drug candidate screening, as well as to provide a resource for cell replacement therapy. Recent reports demonstrate that recapitulating a disease phenotype in vitro is feasible for numerous monogenic diseases, including autoinflammatory diseases. In this review, we provide a comprehensive overview of current advances in research into autoinflammatory diseases involving iPSC-derived monocytes/macrophages. This review may aid in the planning of new studies of autoinflammatory diseases.

Abstract Background Congenital absence of portal vein (CAPV) is a rare structural anomaly in which the portal vein (PV) blood that normally flow into the liver directly drains into the systemic venous system through other collateral circulation. Congenital portal vein shunts (CPSs) is classified into types I and II according to the absence or presence of the intrahepatic portal vein, respectively. The CPS type I is also known as CAPV. The liver transplantation may be the only treatment option for CAPV. The key point of liver transplantation for CAPV is the reconstruction of the PV. Case presentation A 29-year-old man was diagnosed with CAPV with splenomegaly and gastroesophageal varix when being treated for pancytopenia and liver dysfunction. A living donor liver transplantation was performed for him using the right lobe which had been donated by his mother. The PV was reconstructed using his own great saphenous vein (GSV) as a graft vein. The end of the GSV graft was anastomosed to the inferior mesenteric vein while the other end was anastomosed to the vein graft of the right hepatic vein from the explanted liver. Conclusion Using the patient’s own GSV for PV reconstruction during living donor transplantation in the patient with CAPV seems to be an effective method.

In the fields of control engineering and robotics, either the Lagrange or Newton–Euler method is generally used to analyze and design systems using equations of motion. Although the Lagrange method can obtain analytical solutions, it is difficult to handle in multi-degree-of-freedom systems because the computational complexity increases explosively as the number of degrees of freedom increases. Conversely, the Newton–Euler method requires less computation even for multi-degree-of-freedom systems, but it cannot obtain an analytical solution. Therefore, we propose a partial Lagrange method that can handle the Lagrange equation efficiently even for multi-degree-of-freedom systems by using a divide-and-conquer approach. The proposed method can easily handle system extensions and system reconstructions, such as changes to intermediate links, for multi-degree-of-freedom serial link manipulators. In addition, the proposed method facilitates the derivation of the equations of motion-by-hand calculations, and when combined with an analysis algorithm using automatic differentiation, it can easily realize motion analysis and control the simulation of multi-degree-of-freedom models. Using multiple pendulums as examples, we confirm the effectiveness of system expansion and system reconstruction with the partial Lagrangians. The derivation of their equations of motion and the results of motion analysis by simulation and motion control experiments are presented. The system extensions and reconstructions proposed herein can be used simultaneously with conventional analytical methods, allowing manual derivations of equations of motion and numerical computer simulations to be performed more efficiently.

Instrumented wheelsets are widely utilized in the railway industry for the purpose of the measurement of the wheel-rail interaction force. In the conventional instrumented wheelset, the measurement accuracy of the lateral force is reduced due to the bending moment induced by the wheel load. The authors have proposed a new configuration of the instrumented wheelset to reduce the influence of the wheel load on the measurement of the lateral force. This proposed configuration utilizes the shear strains of the wheel web as a measure of the lateral force. This paper describes the accuracy verification of the proposed configuration under the wheel rotating condition. The single-wheelset roller-rig tests are carried out and the test results show that the proposed method can reduce the influence of the wheel load even under the rotating condition.

Advances in micro-electro-mechanical systems technology have led to the emergence of compact attitude measurement sensor products that integrate acceleration, magnetometer, and gyroscope sensors on a single chip, making them important devices in the field of three-dimensional (3D) attitude measurement for unmanned aerial vehicles, smartphones, and other devices. Sensor fusion algorithms for posture measurement have become an indispensable technology in cutting-edge research, such as human posture measurement using wearable sensors, and stabilization problems in robot position and posture measurement. We have also developed wearable sensors and powered suits in our previous research. We needed a technology for the real-time measurement of a 3D human body motion. It is known that quaternions can be used to algebraically handle 3D rotations; however, sensor fusion algorithms for three sensors are presently complex. This is because these algorithms deal with the post-rotation attitude (pure quaternions) rather than rotation information (the rotor) to avoid a double covering problem involving the rotor. If we are dealing with rotation, it may be possible to make the algorithm simpler and faster by dealing directly with the rotor. In this study, to solve the double covering problem involving the rotor, we propose a stateful rotor and develop a technique for uniquely determining the time-varying states of the rotor. The proposed stateful rotor guarantees the continuity of the rotor parameters with respect to angular changes, and this paper confirms its effectiveness by simulating two rotations around an arbitrary axis. In addition, we verify experimentally that a fast sensor fusion method using stateful rotor can be used for attitude calculation. Experiments also confirm that the calculated results converge to the desired rotation angle for two spatial rotations around an arbitrary axis. Since the proposed stateful rotor extends and stabilizes the definition of the rotor, it is applicable to any algorithm that deals with time-varying quaternionic rotors. In this research, an algorithm based on a multiply–add operation is designed to reduce computational complexity as a high-speed calculation for embedded systems. This method is theoretically equivalent to other methods, while contributing to power saving and the cost reduction of products.

Vps13 family proteins are proposed to function in bulk lipid transfer between membranes, but little is known about their regulation. During sporulation of Saccharomyces cerevisiae, Vps13 localizes to the prospore membrane (PSM) via the Spo71-Spo73 adaptor complex. We previously reported that loss of any of these proteins causes PSM extension and subsequent sporulation defects, yet their precise function remains unclear. Here, we performed a genetic screen and identified genes coding for a fragment of phosphatidylinositol (PI) 4-kinase catalytic subunit and PI 4-kinase noncatalytic subunit as multicopy suppressors of spo73Δ. Further genetic and cytological analyses revealed that lowering PI4P levels in the PSM rescues the spo73Δ defects. Furthermore, overexpression of VPS13 and lowering PI4P levels synergistically rescued the defect of a spo71Δ spo73Δ double mutant, suggesting that PI4P might regulate Vps13 function. In addition, we show that an N-terminal fragment of Vps13 has affinity for the endoplasmic reticulum (ER), and ER-plasma membrane (PM) tethers localize along the PSM in a manner dependent on Vps13 and the adaptor complex. These observations suggest that Vps13 and the adaptor complex recruit ER-PM tethers to ER-PSM contact sites. Our analysis revealed that involvement of a phosphoinositide, PI4P, in regulation of Vps13, and also suggest that distinct contact site proteins function cooperatively to promote de novo membrane formation.

We report the cases of patient with primary mucosa-associated lymphoid tissue (MALT) lymphoma of the bladder who successfully treated with local radiation therapy after transurethral resection of the bladder tumor. She maintains good activity of daily living without relapse. We recommend this strategy for localized MALT lymphoma of the bladder, because it provide better quality of life for elderly patients.

The contributions of the complement system have been elucidated in the process of solid organ transplantation, including kidney transplantation. However, the role of complement in liver transplantation is unknown. We sought to elucidate the time-dependent changes of peritransplantational serum complement levels and the relationships with posttransplant outcomes and other immunological biomarkers. We enrolled 82 patients who underwent living-related donor liver transplantation (LDLT). Nine patients (11%) died within 90 days after LDLT (non-survivors). The following immunomarkers were collected preoperatively and at 1, 2, and 4 week(s) after LDLT: serum C3, C4, immunoglobulin G (IgG), and peripheral blood leukocyte populations characterized by CD3, CD4, CD8, CD16, CD19, CD20, CD22, and CD56. Consequently, C3 and C4 increased time-dependently after LDLT. Preoperatively, C3 was negatively correlated with the MELD score, Child–Pugh score, CD16-positive leukocyte percentage, and the CD56-positive leukocyte percentage. Non-survivors had lower levels of C3 at 2 weeks in comparison to survivors (median [interquartile range]: 56 [49-70] mg/dL vs. 88 [71-116] mg/dL, p=0.0059). When the cutoff value of C3 at 2 weeks to distinguish non-survivors was set to 71 mg/dL, the sensitivity, specificity, and area under the ROC curve were 87.5%, 75.0%, and 0.80, respectively. A principal component analysis showed an inverse relationship between the C3 and C4 levels and the percentage of CD8-, CD16-, and CD56-positive leukocytes at 1 and 2 week(s). All non-survivors were included in the cluster that showed higher percentages of CD8-, CD16-, and CD56-positive leukocytes at 2 weeks. In conclusion, we demonstrated the relationship between complement, outcomes, and other immunomarkers in LDLT and suggested the usefulness of C3 at 2 weeks after LDLT in distinguishing the mortality.

Purpose: To describe a rare case of racemose hemangioma which developed spontaneous macular macroaneurysm (MA) rupture and vitreaous hemorrhage. Observations: A 29-year-old healthy asian female visited our hospital and a racemose hemangioma was found in the left eye. At presentation, the best corrected visual acuity (BCVA) was 30/20 in her left eye. At 9 years after the first visit, MA-like lesion was noted in the macular area. After that, vitreous and subretinal hemorrhage appeared in the left eye. The patient underwent simultaneous vitrectomy and cataract surgery, but vitreous re-hemorrhage occurred two days after the operation. To avoid re-hemorrhage, silicone oil (SO) tamponade was added in the second vitrectomy. Two years after the second operation, SO was removed and postoperative BCVA in the left eye was 20/200 without re-bleeding in the vitreous. Conclusions and Importance: Although retinal hemorrhages have been reported in the patients with a racemose hemangioma, in our case the macular MA rupture occurred at 9 years after the first visit. Congenital retinal arteriovenous anastomosis can show a change in vascular shape in some cases, thus it is important to observe carefully.

Cystic artery pseudoaneurysm (CAP) is a rare disease, with small number of previous reports related to CAP. Besides, it is frequently prone to critical condition due to arterial bleeding. Here, we presented a case of ruptured CAP with acute calculus cholecystitis and its subsequent successful management with temporary endoscopic biliary drainage for obstructive jaundice and embolization for the culprit artery without cholecystectomy. Since CAP is at high risk of bleeding, intravascular treatment, which is only one currently available therapeutic option, is urgently required in the clinical sites.

The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.

Essential thrombocythemia (ET) occurs predominantly in the elderly, but approximately 20% of patients are

The self-assembly of discrete cyanometallates has attracted significant interest due to the potential of these materials to undergo soft metallophilic interactions as well as their optical properties. Diblock copolypeptide amphiphiles have also been investigated concerning their capacity for self-assembly into morphologies such as nanostructures. The present work combined these two concepts by examining supramolecular hybrids comprising cyanometallates with diblock copolypeptide amphiphiles in aqueous solutions. Discrete cyanometallates such as [Au(CN)2]−, [Ag(CN)2]−, and [Pt(CN)4]2− dispersed at the molecular level in water cannot interact with each other at low concentrations. However, the results of this work demonstrate that the addition of diblock copolypeptide amphiphiles such as poly-(L-lysine)-block-(L-cysteine) (Lysm-b-Cysn) to solutions of these complexes induces the supramolecular assembly of the discrete cyanometallates, resulting in photoluminescence originating from multinuclear complexes with metal-metal interactions. Electron microscopy images confirmed the formation of nanostructures of several hundred nanometers in size that grew to form advanced nanoarchitectures, including those resembling the original nanostructures. This concept of combining diblock copolypeptide amphiphiles with discrete cyanometallates allows the design of flexible and functional supramolecular hybrid systems in water.

Astaxanthin (AST), a natural marine carotenoid, possess a wide variety of biological functions. In particular, as a strong antioxidant, AST effectively scavenges oxygen free radicals and reduces oxidative stress. In addition, recent in vitro studies have suggested that AST attenuates glutamate-induced apoptosis and cytotoxicity. The glutamate/aspartate transporter (GLAST) deficient (GLAST-/-) mouse is a mouse model of normal tension glaucoma (NTG) caused by both the glutamate neurotoxicity and oxidative stress in the retina. In the present study, we investigated the effects of AST on the ganglion cell complex, indicator of glaucomatous structural damage, using spectral domain-optical coherence tomography. As a result, AST significantly attenuated the thinning of ganglion cell complex in GLAST-/- mice in comparison to an AST-free control group. Our results suggest the possibility that AST has protective effects against glutamate neurotoxicity and oxidative stress in the retina. At present, the only treatment for NTG that is available in the clinical setting is to reduce the IOP as much as possible. Thus, our results suggest that AST supplementation may be effective for some types of NTG in which glutamate neurotoxicity and oxidative stress are involved.

Abstract Background Recently, surgical stress due to breast cancer has been reduced, more so for elderly patients. However, an expanded resection is still required in some situations. Case presentation We present a case of a 90-year-old woman with a 15 × 15 cm2 erythema and localized skin ulceration with hemorrhage in her right breast. A punch biopsy indicated mammary Paget’s disease. Computed tomography showed that the tumor was only located on the surface of the breast with no metastasis, including of the axillar lymph nodes. We decided to perform surgery with sufficient informed consent. We performed muscle-sparing mastectomy with sampling of an axillar lymph node, adding two stress-relaxation sutures to avoid diastasis. The patient’s postoperative course was good. A histological examination revealed mammary Paget’s disease without invasion and no evidence of a residual tumor of the entire stumps. Her quality of life was improved after surgery. Conclusion Mammary Paget’s disease has a relatively good prognosis. However, advanced mammary Paget’s disease leads to a decrease of quality of life with symptoms such as skin ulcer and bleeding. Surgery should be performed in such cases, considering the risks and benefits, even in older patients with comorbidities.

Abstract Double flowers in cultivated camellias are divergent in floral patterns which present a rich resource for demonstrating molecular modifications influenced by the human demands. Despite the key principle of ABCE model in whorl specification, the underlying mechanism of fine-tuning double flower formation remains largely unclear. Here a comprehensive comparative transcriptomics interrogation of gene expression among floral organs of wild type and “formal double” and “anemone double” is presented. Through a combination of transcriptome, small RNA and “degradome” sequencing, we studied the regulatory gene expression network underlying the double flower formation. We obtained the differentially expressed genes between whorls in wild and cultivated Camellia. We showed that the formation of double flowers tends to demolish gene expression canalization of key functions; the faded whorl specification mechanism was fundamental under the diverse patterns of double flowers. Furthermore, we identified conserved miRNA-targets regulations in the control of double flowers, and we found that miR172-AP2, miR156-SPLs were critical regulatory nodes contributing to the diversity of double flower forms. This work highlights the hierarchical patterning of global gene expression in floral development, and supports the roles of “faded ABC model” mechanism and miRNA-targets regulations underlying the double flower domestication.

Two types of new bis-Pd(II) hexaphyrin π-ruthenium complexes are reported. A double-decker bis-Pd(II) hexaphyrin π-ruthenium complex 4 was obtained by oxidation-induced detachment of a ruthenoarene unit from the triple-decker complex 3 and oxygen-inserted triple-decker bis-Pd(II) hexaphyrin π-ruthenium complex 6 was obtained upon treatment of bis-Pd(II) [26]hexaphyrin 5 with [RuCl2(p-cymene)]2 under aerobic conditions. Although π-metal complexation of porphyrinoids often results in decreased global aromaticity due to the enhancement of local 6π aromatic segments, distinct aromatic characters were indicated for 4 and 6 by 1H-NMR spectral and theoretical calculations. These results are accounted for in terms of possible resonance contributors of hexaphyrin di- and tetraanion ligands. Thus, π-metal coordination has been shown to be effective for modulation of the overall aromaticity.

The purpose of this study is to develop a walking assist device by controlling trunk and pelvis motion. Human gait motion consists of whole body exercise including lower body motion and upper one. As all exercises are performed normally, walking with less energy loss is performed. If any exercises are incomplete, compensatory motion is performed and it is considered that there is energy loss. Therefore, this study aims at developing the walking assist device to make normal exercises and reduces energy loss by applying external forces, focusing on the trunk rotation and the pelvic rotation that involved in stride length and walking speed.

While cases of multiple myeloma (MM) with metastatic calcification have been reported, the mechanisms for this calcification have yet to be explained. We observed a case of MM in a patient with end-stage renal failure who developed vascular and pulmonary calcification. A 51-year-old male was diagnosed with Bence-Jones type MM and required maintenance hemodialysis. He was treated with bortezomib-dexamethasone, vincristine-doxorubicin-dexamethasone, the M2 protocol, and lenalidomide-dexamethasone (Rd) therapy. During the sixth cycle of Rd therapy, he complained of pain in both lower legs. Well-demarcated ulcers with severe pain had developed on the right lower leg, both exterior thighs, and penis. We found that the patient’s serum intact parathyroid hormone level was elevated, while it had previously been permissively controlled. Computed tomography scan showed widespread centrilobular opacities of the bilateral lungs and high-density lesions along small blood vessels in the trunk and all four extremities. Histological calcifications were identified in small blood vessels and the alveolar walls. The risk of metastatic calcification in MM appears to be associated with renal failure, but not with MM itself.

It is pointed out that the yaw dampers, which are often installed in between carbody and bogie frame of a high-speed railway vehicle, have such unfavorable points that the damping force is generated not only in the yawing direction but also in other direction. As a result the damping force is generated also to the longitudinal or pitching vibration of a bogie, and the excitation force acts in the longitudinal direction of the carbody resulting in the increase of the carbody vibration of the longitudinal or vertical direction. In this research, to enable the reduction of the excitation of the carbody vibration while maintaining the original function of yaw dampers to prevent bogie hunting motion, a new mounting structure of yaw dampers on railway vehicles has been developed. The new mounting structure enables to reduce the excitation force transmitted from a bogie frame to a carbody through yaw dampers. In this paper, the effect of yaw dampers on the carbody vertical vibration is firstly shown based on the results of an excitation test of a full-scale vehicle, then the outline of the new mounting structure for yaw dampers and the design and manufacture of the prototype device are presented. The vehicle dynamics model based on multi body dynamics was constructed and the suppression effect of the yaw damper force generated to movement in the direction other than the yawing direction of a bogie was verified by the numerical simulation. Moreover, the prototype device was installed on a full-scale test vehicle and a bogie hunting motion test was carried out to verify the running stability.

A 50-year-old male was examined at another hospital for fever, general fatigue and slight abdominal pain. He was treated with antibiotics and observed. However, his symptoms did not lessen, and laboratory tests revealed liver dysfunction, jaundice and an increased inflammatory response. He was then admitted to our hospital and underwent an abdominal computed tomography scan and magnetic resonance cholangiopancreatography (MRCP), which revealed common bile duct (CBD) stones. He was diagnosed with mild acute cholangitis. As the same time, he was admitted to our hospital and an emergency endoscopic retrograde cholangiopancreatography was performed. Vater papilla opening in the third portion of the duodenum and presence of a peripapillary duodenal diverticulum made it difficult to perform cannulation of the CBD. In addition, MRCP revealed that the CBD was extremely narrow (diameter 5 mm). We therefore performed laparoscopic cholecystectomy and endoscopic sphincterotomy using the rendezvous technique for choledocholithiasis simultaneously rather than laparoscopic CBD exploration. After the operation, the patient was discharged with no complications. Although the rendezvous technique has not been very commonly used because several experts in the technique and a large operating room are required, this technique is a very attractive and effective approach for treating choledocholithiasis, for which endoscopic treatment is difficult.

A corrole is a tetrapyrrolic macrocycle known as a ring-contracted porphyrinoid. Despite the progress of the synthetic chemistry of meso-aryl-substituted corroles since the early 2000s, meso-heteroatom-substituted corroles have been scarcely reported. Herein we report that the SNAr-type substitution reaction of a meso-chlorocorrole silver complex with diphenylamine or carbazole in the presence of NaH as a base produced meso-aminocorroles. The structures, ultraviolet⁻visible spectroscopy (UV/Vis), and emission spectra of these meso-aminocorroles were discussed. Furthermore, the oxidation reaction of a meso-diphenylaminocorrole was examined, which resulted in the formation of 10,10-diethoxyisocorrole.

Anteflexion of the spine is essential for many physical activities of daily living. However, this motion places the lumbar disks because it generats heavy load due to changes in the shape of the lumbar spine and can lead to low back pain. In older to reduce low back pain, here we proposed a wearable sensor system configuration that can estimate lumbosacral alignment and lumbar load by measuring the shape of the lumbar skin when the lumbosacral alignment changes. The shape of the lumbar skin and posture angle are measured by using curvature sensors and accelerometers. In addition, the system must be constructed in consideration of the physique, in order to absorb in a variety of human. We proposed this system by measuring the body parameters of anteflexion and studied the change in dimensions of the lumbar spine from changes in posture. By extracting the dimensions of the lumbosacral spine in X-ray images, the attitude angle, body surface area and the dimensions of the lumbosacral spine have relevance. The lumbosacral dimensions calibration method was developed by using that relation. Lumbosacral alignment estimation considering the difference in physiques is developed, and lumbosacral spine alignment was to improve the estimation accuracy. The proposed method could improve accuracy lumbosacral alignment estimation.

When railway vehicles pass through a sharp curve, yaw moment is generated at the bogie. This condition affects the increase of the lateral force of the outside wheel of the front axle of the leading bogie, which is important factor for assessing the running safety of railway vehicles. A Lateral-force/Wheel-load estimation equation has been developed as a method to calculate the lateral force and the wheel load during the curve passage of railway vehicles taking into account the yaw moment of the bogie. This equation is useful to estimate the risk of flange-climb derailment. The authors have newly suggested a more versatile Lateral-force/Wheel-load estimation equation with a focus on the improvement of the estimation of yaw moment of the bogie. Running tests using test track which has sharp curves were carried out to measure the generated forces of several components of the bogie, which are the sources of the yaw moment of the bogie. New equations were produced based on the test results, and compared with the measured lateral forces and wheel loads.

In previous work, we engineered functional cell sheets using bone marrow-derived mesenchymal stem cells (BM-MSCs) to promote islet graft survival. In the present study, we hypothesized that a cell sheet using dermal fibroblasts could be an alternative to MSCs, and then we aimed to evaluate the effects of this cell sheet on the functional viability of human islets. Fibroblast sheets were fabricated using temperature-responsive culture dishes. Human islets were seeded onto fibroblast sheets. The efficacy of the fibroblast sheets was evaluated by dividing islets into three groups: the islets-alone group, the coculture with fibroblasts group, and the islet culture on fibroblast sheet group. The ultrastructure of the islets cultured on each fibroblast sheet was examined by electron microscopy. The fibroblast sheet expression of fibronectin (as a component of the extracellular matrix) was quantified by Western blotting. After 3 days of culture, islet viabilities were 70.2 ± 9.8%, 87.4 ± 5.8%, and 88.6 ± 4.5%, and survival rates were 60.3 ± 6.8%, 65.3 ± 3.0%, and 75.8 ± 5.6%, respectively. Insulin secretions in response to high-glucose stimulation were 5.1 ± 1.6, 9.4 ± 3.8, and 23.5 ± 12.4 μIU/islet, and interleukin-6 (IL-6) secretions were 3.0 ± 0.7, 5.1 ± 1.2, and 7.3 ± 1.0 ng/day, respectively. Islets were found to incorporate into the fibroblast sheets while maintaining a three-dimensional structure and well-preserved extracellular matrix. The fibroblast sheets exhibited a higher expression of fibronectin compared to fibroblasts alone. In conclusion, human dermal fibroblast sheets fabricated by tissue-engineering techniques could provide an optimal substrate for human islets, as a source of cytokines and extracellular matrix.

ABSTRACT Sporulation of Saccharomyces cerevisiae is a developmental process in which an ascus containing four haploid spores forms from a diploid cell. During this process, newly formed membrane structures called prospore membranes extend along the nuclear envelope and engulf and package daughter nuclei along with cytosol and organelles to form precursors of spores. Proteins involved in prospore membrane extension, Vps13 and Spo71, have recently been reported; however, the overall mechanism of membrane extension remains unclear. Here, we identified Spo73 as an additional factor involved in prospore membrane extension. Analysis of a spo73∆ mutant revealed that it shows defects similar to those of a spo71∆ mutant during prospore membrane formation. Spo73 localizes to the prospore membrane, and this localization is independent of Spo71 and Vps13. In contrast, a Spo73 protein carrying mutations in a surface basic patch mislocalizes to the cytoplasm and overexpression of Spo71 can partially rescue localization to the prospore membrane. Similar to spo71∆ mutants, spo73∆ mutants display genetic interactions with the mutations in the SMA2 and SPO1 genes involved in prospore membrane bending. Further, our bioinformatic analysis revealed that Spo73 is a dysferlin domain-only protein. Thus, these results suggest that a dysferlin domain-only protein, Spo73, functions with a dual pleckstrin homology domain protein, Spo71, in prospore membrane extension. Analysis of Spo73 will provide insights into the conserved function of dysferlin domains, which is related to dysferlinopathy. IMPORTANCE Prospore membrane formation consists of de novo double-membrane formation, which occurs during the developmental process of sporulation in Saccharomyces cerevisiae. Membranes are formed into their proper size and shape, and thus, prospore membrane formation has been studied as a general model of membrane formation. We identified SPO73, previously shown to be required for spore wall formation, as an additional gene involved in prospore membrane extension. Genetic and cell biological analyses suggested that Spo73 functions on the prospore membrane with other factors in prospore membrane extension, counteracting the bending force of the prospore membrane. Spo73 is the first dysferlin domain-only protein ever analyzed. The dysferlin domain is conserved from yeast to mammals and is found in dysferlin proteins, which are involved in dysferlinopathy, although the precise function of the domain is unknown. Continued analysis of Spo73 will contribute to our understanding of the function of dysferlin domains and dysferlinopathy.

An 85-year-old male with advanced squamous cell carcinoma of the lung, who was diagnosed about 10 years prior to his current presentation, suddenly complained of abdominal pain and underwent an abdominal computed tomography scan, which revealed free air and massive ascites. He was admitted to our hospital for acute peritonitis and emergency surgery was performed. During the surgical procedure, a perforation of the jejunum was diagnosed and repaired. He was diagnosed to have a metastatic tumor originating from a squamous cell carcinoma of the lung. He improved and was transferred to the former hospital on the 27th postoperative day. Jejunal metastasis from squamous cell carcinoma of the lung is rare, and the prognosis of peritonitis due to a perforated intestinal metastasis from lung cancer is poor. There have been 10 reports of jejunal metastasis of squamous cell carcinoma of the lung reported in Japan between 2000 and 2011. Therefore, when patients with advanced lung cancer present with acute abdomen, it is necessary to keep in mind the possibility of a gastrointestinal metastatic tumor.

A 21-year-old male patient was transferred to the emergency room of our hospital after suffering seat belt abdominal injury in a traffic accident. Abdominal computed tomography revealed a massive hematoma in the abdominal cavity associated with deep hepatic lacerations in the right lobe. The presence of a solid tissue possibly containing pneumobilia was observed above the greater omentum. These findings were consistent with a tentative diagnosis of hepatic laceration due to blunt trauma; therefore, this prompted us to perform emergency laparotomy. The operative findings revealed a massive hematoma and pulsatile bleeding from the lacerated liver and a retroperitoneal hepatoma, which was most likely due to subcapsular injury of the right kidney. In accordance with the preoperative imaging studies, a pale liver fragment on the greater omentum was observed, which was morphologically consistent with the defect in the posterior segment of the liver. Since the damaged area of the liver broadly followed the course of the middle hepatic vein, we carefully inspected and isolated the inflow vessels and eventually performed a right hepatic lobectomy. The patient’s postoperative course was uneventful, and he was doing well at 10 months after surgery.

Silica-bearing magnetite was recognized in the Copiapó Nordeste prospect as the first documented occurrence in Chilean iron oxide⁻copper⁻gold (IOCG) deposits. The SiO2-rich magnetite termed silician magnetite occurs in early calcic to potassic alteration zones as orderly oscillatory layers in polyhedral magnetite and as isolated discrete grains, displaying perceptible optical differences in color and reflectance compared to normal magnetite. Micro-X-ray fluorescence and electron microprobe analyses reveal that silician magnetite has a significant SiO2 content with small amounts of other “impure„ components, such as Al2O3, CaO, MgO, TiO2, and MnO. The oscillatory-zoned magnetite is generally enriched in SiO2 (up to 7.5 wt %) compared to the discrete grains. The formation of silician magnetite is explained by the exchange reactions between 2Fe (III) and Si (IV) + Fe (II), with the subordinate reactions between Fe (III) and Al (III) and between 2Fe (II) and Ca (II) + Mg (II). Silician magnetite with high concentrations of SiO2 (3.8⁻8.9 wt %) was similarly noted in intrusion-related magmatic⁻hydrothermal deposits including porphyry- and skarn-type deposits. This characteristic suggests that a hydrothermal system of relatively high-temperature and hypersaline fluids could be a substantial factor in the formation of silician magnetite with high SiO2 contents.

Multi-portal Human Interface (M-HI) as an innovative human interface for power assist systems has been researched and developed. The M-HI allows users to apply the operational force anywhere on the power assist system. When users control the PAS on its arbitrary point, The operational point motion is different from the end-effecter motion, even if the end-effecter move as ideal motion for users. The phenomenon affects user's maneuverability decrease. In this paper, impedance paremeters on the operational point are forcused. The relationsihp between the operational point motion and maneuverability are analyzed in terms of the impedance parameters. To evaluate the maneuverability of PAS applied M-HI, The impedance parameters of each operational point is calculated. Furthermore, modification of impedance parameters on the operational point is proposed. However, the method raise end-effecter motion error, the modification amount optimization is required. In this paper, the optimization method and results of fundamental maneuverability evaluations are shown.

HAX1 was identified as the gene responsible for the autosomal recessive type of severe congenital neutropenia. However, the connection between mutations in the HAX1 gene and defective granulopoiesis in this disease has remained unclear, mainly due to the lack of a useful experimental model for this disease. In this study, we generated induced pluripotent stem cell lines from a patient presenting for severe congenital neutropenia with HAX1 gene deficiency, and analyzed their in vitro neutrophil differentiation potential by using a novel serum- and feeder-free directed differentiation culture system. Cytostaining and flow cytometric analyses of myeloid cells differentiated from patient-derived induced pluripotent stem cells showed arrest at the myeloid progenitor stage and apoptotic predisposition, both of which replicated abnormal granulopoiesis. Moreover, lentiviral transduction of the HAX1 cDNA into patient-derived induced pluripotent stem cells reversed disease-related abnormal granulopoiesis. This in vitro neutrophil differentiation system, which uses patient-derived induced pluripotent stem cells for disease investigation, may serve as a novel experimental model and a platform for high-throughput screening of drugs for various congenital neutrophil disorders in the future.