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Key Clinical Message We report an extremely rare occurrence of adult‐onset Still's disease (AOSD) in a patient with ulcerative colitis. The possibility of autoinflammatory conditions such as AOSD should be considered when evaluating or treating symptoms suspected as side effects of the severe acute respiratory syndrome coronavirus 2 vaccination, regardless of the associated comorbidities. Summary A woman in her 50s with a history of stable ulcerative colitis (UC) for 20 years, managed using salazosulfapyridine, presented with migratory rashes, spiking fever, edema, and joint pain that started 1 week after receiving the BNT162B2 mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Laboratory tests revealed extremely high serum ferritin levels. The patient was diagnosed with adult‐onset Still's disease (AOSD) based on the relevant classification criteria after ruling out other diseases. Detection of high levels of interleukin‐18, an inflammatory cytokine related to AOSD, supported the diagnosis. Nonsteroidal anti‐inflammatory drug monotherapy alone resulted in significant improvements in both the abovementioned symptoms and the elevated inflammatory marker levels. AOSD in a patient with UC is extremely rare. Only one case of AOSD with UC was reported before the coronavirus disease 2019 era. This case indicates that SARS‐CoV‐2 vaccination can trigger a hyperinflammatory response, classified as AOSD, in a patient with UC, which is extremely rare.

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B-cell lymphomas are neoplastic diseases occasionally associated with chronic inflammation. mRNA vaccines for coronavirus disease 2019 (COVID-19) induce inflammatory responses, which often lead to fever and lymphadenopathies indistinguishable from lymphomas. Although both lymphadenopathies and lymphomas can be influential, the correlation between them is unclear. Herein, we present the first case of marginal zone B-cell lymphoma following mRNA COVID-19 vaccination. An 80-year-old Japanese woman presented with a right temporal mass that appeared the morning after she was administered her first mRNA COVID-19 vaccination (BNT162b2). The mass gradually decreased in size but persisted over 6 weeks after her first vaccination (3 weeks after her second vaccination). At her first visit to our hospital, ultrasound revealed the size of the mass to be 28.5 × 5.7 mm, and computed tomography revealed multiple lymphadenopathies in the right parotid, submandibular, jugular, and supraclavicular regions. Initially, we suspected head-and-neck benign lymphadenopathy as a side effect of vaccination. Nine weeks later, the number of swollen submandibular and parotid glands increased, and the lymph nodes further enlarged. Finally, the right temporal mass was diagnosed as marginal zone B-cell lymphoma based on immunohistochemical and flow cytometry findings of biopsy specimens. Our findings suggest that although 4–6 weeks of observation for lymph node inflammation after the second vaccination is recommended, malignancy should also be considered in the differential diagnosis of lymphadenopathy following vaccination.

The effect of Rashba spin orbit coupling (SOC) on superconductivity remains elusive. Here, the authors report largely enhanced in-plane upper critical magnetic field due to Rashba SOC induced dynamic spin-momentum locking on the surfaces of an atomic-layer superconductor.

Abstract Background and aim Endoscopic transpapillary gallbladder drainage (ETGBD) is widely performed. However, there is no consensus on the appropriate diameter, length, and shape of the stent that should be used in this procedure. In addition, there are limited data on the outcomes of permanent ETGBD. In our facility, a stent with a novel spiral structure (IYO‐stent) is permanently placed in patients with acute cholecystitis who are not indicated for surgery. This study examined the efficacy and safety of the IYO‐stent in cases of permanent ETGBD. Methods We retrospectively examined patients who underwent permanent ETGBD using the IYO‐stent from April 2018 to December 2020. Results Eleven patients were included in this study. The technical success and the clinical success rate were 91%. One patient had a post‐procedure adverse event (post‐endoscopic sphincterotomy bleeding). Within the median observation period of 312 days (range: 109–742), late adverse events, including cholangitis (n = 1) and incomplete stent migration (n = 1), were observed. However, none of the patients experienced cholecystitis relapse. Conclusion Permanent ETGBD with IYO‐stent is an effective treatment for the patients with acute cholecystitis who are not indicated for surgery.

We report the case of a 70-year-old woman with hypertrophic obstructive cardiomyopathy, who was admitted because of severe heart failure and cardiogenic shock and mechanical support requiring extracorporeal membrane oxygenation. She recovered well by percutaneous transluminal septal myocardial ablation under the extracorporeal membrane oxygenation support and was discharged without complications. (Level of Difficulty: Advanced.)

Abstract Background Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles’ and fibres’ risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios. Conclusions Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.

Background and study aims The diagnosis of malignant lymphoma (ML) is sometimes difficult, especially in patients with primary splenic malignant lymphomas (psML) which have no lymph nodes capable of acting as the biopsy target. We carried out endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for “splenic parenchyma” in patients suspected of having a psML, even without any obvious neoplastic lesions in the spleen. Patients and methods A retrospective study using medical records was conducted of eight patients suspected of having a psML that received EUS-FNA for the splenic parenchyma between January 2016 and January 2019. Data analyzed included clinical background, EUS-FNA procedure (puncture needle/route), diagnostic ability (pathological/flow cytometry [FCM]), and complications. Results EUS-FNA was performed from the stomach in all eight cases, and no patients had complications. As a result of splenic parenchymal biopsy found on EUS-FNA, 75 % of patients (6/8) were histologically diagnosed with MLs, monoclonality of B-cells was identified in all cases (8/8) with FCM, and all patients (8/8) were definitively diagnosed with psMLs. Conclusion EUS-FNA for “splenic parenchyma” is useful for patients with spML, even if they have no obvious neoplastic lesions in the spleen.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the digestive tract. Recurrences may occur even after radical resection; however, recurrence later than 10 years after surgery is rare. We report a case of GIST with recurrence of liver metastasis 25 years after surgery. A 56-year-old man complained of sudden epigastric pain and was transferred to the emergency department. He had undergone partial resection of the small intestine for leiomyosarcoma 25 years previously. Abdominal computed tomography showed multiple liver tumors with massive hemorrhage. Ultrasound-guided percutaneous biopsy was performed for the 15-mm hepatic tumor in segment 2. Pathological findings revealed proliferation of spindle-shaped atypical cells, and immunostaining for c-kit and CD34 was both positive; the patient was therefore diagnosed with GIST. He then underwent chemotherapy for 7 years but died of multiple organ failure due to GIST. Autopsy revealed GIST occupying the entire liver with peritoneal dissemination, and minute lung metastases that could not be identified by CT were also detected. This case is interesting in considering the recurrence of GIST, and we will report it together with the literature review.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is one of the most challenging endoscopic procedures. Although single- or double-balloon endoscopes have been widely used, reaching the papilla of Vater (hepaticojejunostomy/pancreaticojejunostomy site) is often difficult. For patients in whom treatment cannot be completed in a single session, we placed endoscopic nasobiliary drainage (ENBD) at the end of the procedure; in the second session, the scope was inserted following ENBD placement. Patients and methods Three patients with surgically altered anatomy and who underwent ENBD-guided ERCP were retrospectively examined using the medical records. Results There were two men and one woman, with an average age of 75 years. The surgical procedure were distal gastrectomy and Roux-en-Y reconstruction in all patients. The diagnosis were choledocholithiasis in two and bile duct stricture in one. Average time to reach the papilla was 50 minutes (range, 21–102) for the first ERCP and was shortened to 11 minutes (range, 5–17) for the second session under an indwelling ENBD. Treatment was successful in all patients without complications. Conclusion ENBD-guided ERCP in patients with surgically altered anatomy was a useful method that facilitated scope insertion and shortened the procedure time.

Norovirus infection cause epidemic nonbacterial gastroenteritis in patients. The immune mechanisms responsible for the clearance of virus are not completely understood. We examined whether NKT cells are effective against norovirus infection using CD1d KO mice. The body weights of 4-weeks-old CD1d KO mice that were infected with murine norovirus-S7 (MNV-S7) were significantly lower than those of non-infected CD1d KO mice. On the other hand, the body weights of infected WT mice were comparable to those of non-infected WT mice. Correspondingly, CD1d KO mice had an almost 1000-fold higher MNV-S7 burden in the intestine after infection in comparison to WT mice. The mechanism responsible for the insufficient MNV-S7 clearance in CD1d KO mice was attributed to reduced IFN-γ production early during MNV-S7 infection. In addition, the markedly impaired IL-4 production in CD1d KO mice resulted in an impaired MNV-S7-specific secretory IgA production after MNV-S7 infection which is associated with mucosal immunity. Thus, the present results provide evidence that NKT cells play an essential role in MNV-S7 clearance. Keywords: Murine norovirus-S7, NKT cells, Secretory IgA, Delayed growth

Abstract Background Patients with anorexia nervosa (AN) often present with pancytopenia. In most cases described in the literature, AN with pancytopenia demonstrates gelatinous marrow transformation (GMT), which is a typical bone marrow feature of malnutrition. Differentiation of AN-associated pancytopenia from other types of pancytopenia, especially idiopathic aplastic anemia (IAA), has not been studied. We encountered a case of pancytopenia in a patient with AN and relatively poor nutritional status, whose hematological findings mimicked those of IAA, specifically fatty bone marrow and absence of GMT. Case presentation The patient was a 32-year-old woman with poorly controlled AN. At 31 years of age, her body mass index (BMI) had fallen from 17.0 kg/m2 to below 13.8 kg/m2. The patient presented with ongoing fatigue and thus was examined by a hematologist. Hematological findings were consistent with IAA: peripheral blood tests revealed pancytopenia, whereas the bone marrow displayed fatty replacement without GMT. Despite the absence of bone marrow features typically seen in malnutrition, the patient’s hematological abnormalities had manifested after a decrease in body weight. Thus, although the bone marrow findings indicated IAA, we considered that the nutritional etiology of pancytopenia could not be thoroughly ruled out. Using nutritional therapy alone, the hematological abnormalities improved as BMI increased to 16.5 kg/m2. The final diagnosis was pancytopenia secondary to malnutrition because pancytopenia and fatty bone marrow improved after implementation of nutritional therapy alone. Conclusions The present case is the first documented case of AN with pancytopenia for which bone marrow examination confirmed fatty marrow without any evidence of GMT. IAA and pancytopenia secondary to malnutrition can present the same clinical findings. This case is significant because it suggests a need to differentiate between malnutrition and IAA.

A 25-year-old woman had undergone removal of a cryptogenic tumor in the left maxillary sinus 1 year prior to presentation. The patient experienced abdominal pain for 4 days with repeated vomiting episodes; therefore, she was transferred to our hospital by an ambulance. Contrast-enhanced computed tomography revealed a 3-cm tumor in the ileocecal region, which caused small bowel obstruction. Contrast imaging of the ileus tube showed extrinsic compression of the ileocecal region. Forward-viewing linear echoendoscope revealed an irregular hypoechoic tumor measuring 3 cm outside the gastrointestinal tract. Using a 25G needle, endoscopic ultrasound-guided fine needle aspiration (EUS–FNA) was performed. Pathological finding was an inflammatory fibrous tissue with diffuse lymphoplasmacytic infiltration, with more than 10 IgG4-positive cells detected in a high-power field. Re-examination of a pathology specimen of the maxillary sinus tumor provided by the previous attending physician revealed that the inflammatory tissue had diffuse lymphoplasmacytic infiltration, which were accompanied by storiform fibrosis and obliterative phlebitis. Immunostaining revealed more than 50 IgG4-positive cells in a high-power field, a finding suggestive of IgG4-related disease. The serum IgG4 level was 21 mg/dl, which was within the normal range. Treatment was initiated with prednisolone at a dose of 50 mg/day, and the dose was later tapered off. CT and MRI performed 2 months later showed complete disappearance of the ileocecal tumor. The final diagnosis was asynchronously occurring IgG4-related maxillary sinusitis and sclerosing mesenteritis.

Soybeans and fermented soy-derived foodstuffs contain many functional components and demonstrate various beneficial effects. In this report, we demonstrate the anti-fatty liver effect of miso, a traditional fermented product made from soybeans and rice molded in Aspergillus oryzae and forming a common part of the Japanese diet. After acclimation for 2 weeks, male and female C57BL/6J mice were fed with a normal diet (ND), a high-fat diet (HFD), a HFD containing 5% miso (HFD+M), or a HFD containing 5% pre-fermented miso (HFD+PFM) for 20 weeks. Although mice in the HFD group developed typical fatty liver, the consumption of miso or PFM significantly ameliorated the progression of fatty liver in female mice. The liver weight and the average nonalcoholic fatty liver disease activity score (NAS) were significantly reduced in the HFD+M and HFD+PFM groups. In addition, leptin and resistin levels in the serum were decreased in the HFD+M and HFD+PFM groups. The progression of fatty liver was also prevented by the consumption of miso or PFM in male mice, although there were no decreases in NAS. Therefore, miso appears to be a potential food to prevent lifestyle-related diseases such as metabolic syndrome.

Background and study aims In endoscopic retrograde cholangiopancreatography (ERCP), precutting is widely used when achieving biliary cannulation is difficult. However, no consensus has been reached with regard to the best time to initiate precutting. Patients and methods We retrospectively examined 63 patients who underwent precutting for naïve papilla with difficulty in biliary cannulation between 2009 and 2016. The outcomes of the early precut group (≤ 20 min from cannulation until initiating precutting) and the late precut group (> 20 min) were compared. Results Of the 63 patients, 17 (27 %) were in the early precut group and 46 (73 %) were in the late precut group; median time until the initiating precutting was 28 minutes (7 – 50). No significant difference was observed between the two groups in terms of clinical features (age, sex, and indication for ERCP), precutting method, and rate of pancreatic duct stent placement. Significantly higher rates of successful biliary cannulation were observed in the early precut group (16/17; 94 %) than in the late precut group (32/46; 70 %) (P

Osteoclasts are important target cells for osteoporosis treatment. Recently, a real-time cell analysis (RTCA) system was developed to observe cell morphology and adhesion; however, the use of RTCA to study osteoclastogenesis has not been reported. Here, we investigated whether osteoclast formation could be monitored in real-time using RTCA. The cell index determined via electrical impedance using RTCA, and the number of osteoclasts exhibited a significant positive correlation. RTCA was useful for determining the effect of (−)-epigallocatechin-3-gallate on the inhibition of bone resorption. We established a new method of measuring osteoclast formation in real-time using RTCA.

Objectives. Primary mediastinal germ cell tumors (PMGCTs) are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. Methods. We examined 6 patients (median age: 25 years, range: 19–27 years) with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8–84 months). Results. Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP) or etoposide and cisplatin (EP)). One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. Conclusions. Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.

After the publication of this article [1] it was hihglighted that the number of deaths related to natural disasters was incorrectly reported in the second paragraph of section Hazards from Natural particulates and the evolution of the biosphere. This correction article shows the correct and incorrect statement. This correction does not change the idea presented in the article that from an evolutionary view point, natural disasters account only for a small fraction of deaths on the planet. The original article has been updated.

Peroxisome proliferator-activated receptors (PPARs) and related inflammatory and oxidative molecule expression were investigated in a hyperoxaluric rodent model to evaluate the in vivo efficacy of PPAR agonists in preventing renal crystal formation. PPAR expression was examined in a mouse hyperoxaluria kidney stone model induced by daily intra-abdominal glyoxylate injection. Therapeutic effects of the PPARα agonist fenofibrate and PPARγ agonist pioglitazone were also assessed in a 1% ethylene glycol-induced rat model of hyperoxaluria. Crystal formation, inflammation, cell injury, apoptosis, and oxidative stress were compared to those of vehicle-treated controls. Quantitative reverse transcription-polymerase chain reaction revealed that PPARα and PPARγ expression decrease and increase, respectively, during crystal formation in hyperoxaluric kidneys. In addition, PPARα localized to the cytoplasm of both proximal and distal tubular cells, whereas PPARγ accumulated in the nucleus of proximal tubular cells. Furthermore, renal crystal formation was significantly less prevalent in pioglitazone-treated rats but higher in the fenofibrate-treated and fenofibrate/pioglitazone-cotreated groups compared to controls, thus indicating that pioglitazone, but not fenofibrate, markedly decreased cell inflammation, oxidative stress, and apoptosis. Collectively, the results demonstrated that PPARγ suppressed renal crystal formation via its antioxidative and anti-inflammatory effects; however, the renotoxicity of PPARα may elicit the opposite effect.

Two different conformational isoforms or amyloid strains of insulin with different cytotoxic capacity have been described previously. Herein these filamentous and fibrillar amyloid states of insulin were investigated using biophysical and spectroscopic techniques in combination with luminescent conjugated oligothiophenes (LCO). This new class of fluorescent probes has a well defined molecular structure with a distinct number of thiophene units that can adopt different dihedral angles depending on its binding site to an amyloid structure. Based on data from surface charge, hydrophobicity, fluorescence spectroscopy and imaging, along with atomic force microscopy (AFM), we deduce the ultrastructure and fluorescent properties of LCO stained insulin fibrils and filaments. Combined total internal reflection fluorescence microscopy (TIRFM) and AFM revealed rigid linear fibrous assemblies of fibrils whereas filaments showed a short curvilinear morphology which assemble into cloudy deposits. All studied LCOs bound to the filaments afforded more blue-shifted excitation and emission spectra in contrast to those corresponding to the fibril indicating a different LCO binding site, which was also supported by less efficient hydrophobic probe binding. Taken together, the multi-tool approach used here indicates the power of ultrastructure identification applying AFM together with LCO fluorescence interrogation, including TIRFM, to resolve structural differences between amyloid states.

In order to clarify the effects of the Lactococcus lactis (L. lactis) 11/19-B1 strain, a double-blind controlled study of yogurt fermented with the strain was carried out. For the study, two kinds of yogurt, the control and test yogurt, were prepared; the control yogurt was fermented with Streptococcus thermophiles, Lactobacillus delbrueckii subspecies bulgaricus, and Lactobacillus acidophilus, and the test yogurt was enriched with L. lactis 11/19-B1 and Bifidobacterium lactis (B. lactis) BB-12 strains. Seventy-six volunteers who had not received treatment with pharmaceuticals were randomly divided into two groups with each group ingesting 80 g of either the test or control yogurt every day for 8 weeks. Before and after yogurt intake, fasting blood was taken and blood sugar, blood lipids, and anti-cytomegalovirus cellular immunity were estimated. In the test yogurt group, low-density lipoprotein (LDL) was significantly decreased (159.1 ± 25.7 to 149.3 ± 24.4; p = 0.02), but this effect was not observed in the control yogurt group. When the test yogurt group was divided into two groups based on LDL levels of over or under 120 mg/dL, this effect was only observed in the high LDL group. No LDL-lowering effect of B. lactis BB-12 strain was previously reported; therefore, the hypocholesterolemic effects observed in this study are thought to be caused by the L. lactis 11/19-B1 strain alone or its combination with the B. lactis BB-12 strain.

The design limits of a hot water fired absorption chiller in a cycle simulation were examined. The authors have already proposed how to determine the lowest limiting value of the smaller of the two temperature differences to get a logarithmic mean temperature difference when designing each element. This new algorithm was applied, based on the trend toward the hot water fired absorption chiller that employs a multi-stage absorption system. After performing a cycle simulation, the effects of stage number for the lowest hot water temperature that could be used in air conditioning were clarified. As a result, it was found that the limits of stage number were existed. It was also found that the lowest limiting temperature of hot water could be theoretically determined in the condition of the infinite-stage absorption system.