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A 43-year-old, previously healthy man experienced a decreased sensation in the left lower extremity without preceding spinal trauma. At presentation, the patient exhibited slight motor weakness in the left lower extremity, in addition to decreased pain sensation below the ipsilateral T7. Spinal magnetic resonance imaging (MRI) revealed abnormal findings consistent with idiopathic thoracic spinal cord herniation (ITSCH) at the T5/6 level. Computed tomography (CT) revealed a small vertebral erosion at the lower T5. The patient's symptoms gradually progressed over the next 3 years. MRI revealed marked lateral elongation of the cord at the T5/6 and apparent intravertebral cord herniation. The patient underwent ITSCH reduction through T5-6 laminectomies. The herniated cord was vertically long with a bulbous rostral part. Successful ITSCH reduction was achieved and the patient's postoperative course was uneventful. ITSCH is a progressive pathology that requires prompt surgical reduction. Certain ITSCHs may be complicated by intravertebral cord herniation.

Abstract Objective The objective of this study is to evaluate the need for sterile gloves during cystoscopy by comparing the incidence of UTI symptoms between patients in whom the procedure is performed with non‐sterile gloves with those performed with non‐sterile gloves. Patients and Methods This study had a randomized, prospective, single‐blind design and included patients aged >20 years who underwent cystoscopy in either of two outpatient clinics between September 2015 and November 2021. The patients were allocated to a sterile group or a non‐sterile group. Only the urologists were aware of whether or not the gloves were sterile. The patients were instructed to report any symptoms suggestive of UTI after cystoscopy. Results A total of 1258 patients were enrolled in the sterile group and 1376 in the non‐sterile group. Symptoms of UTI were reported by six patients (0.48%) in the sterile group and six (0.44%) in the non‐sterile group. The between‐group difference was not statistically significant (p = 0.88). Conclusion It is not necessary to use sterile gloves during routine cystoscopy.

Abstract Objectives Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long‐term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and

Abstract Background Japan's medical education system produces 9,000 graduates annually. Despite the government's implementation of several strategies, including increasing the number of doctors trained, the country still struggles with a shortage of physicians in rural areas. This study examined this issue, focusing on gender and considering years of physician experience, demographic and geographic factors. Methods We analyzed the Physician Census from 1994, 2004, and 2014, examining data on physicians’ gender and the number of years since licensure. To correct the impact of municipal mergers, the analysis was aligned with the number of municipalities in 2014 (1741). We examined data from each physician (gender and years of medical experience) and analyzed the demographic and geographic distribution trend using Spearman correlation coefficients. We then used the Gini coefficient to evaluate the distribution change of physicians based on gender and years of experience. Results The number of physicians increased 1.29-fold over the 20-year observation period (1.23-fold for male physicians and 2.17-fold for female physicians), and the percentage of female physicians increased from 13.4% to 20.4%. We found that 87.7% of physicians were concentrated in the top 1/3 municipalities in terms of population. The number of female physicians was higher at 91.8% compared to 86.8% for male physicians. The Gini coefficients were lower for veteran physicians of both sexes than for younger physicians. The Gini coefficient for all physicians was 0.315–0.298–0.298 (male physicians: 0.311–0.289–0.283, female physicians: 0.394–0.385–0.395) The Gini coefficients for female compared to male physicians were higher in all age groups, showing that The distribution of female physicians is skewed toward urban areas. Conclusion Female physicians are less distributed in rural areas than male physicians. In addition, despite the fact that the number of female physicians has increased more than male physicians over the past 20 years, the geographic ubiquity of female physicians has not improved. Since the trend of increasing the number of female physicians is expected to continue in the future, it is necessary to take some measures, such as providing a work-life balance suitable for female physicians.

Abstract Background Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry. Case presentation We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain. Conclusions This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.

Abstract Background The purpose of this meta-analysis was to comprehensively investigate the diagnostic ability of 1.5 T and 3.0 T whole heart coronary angiography (WHCA) to detect significant coronary artery disease (CAD) on X-ray coronary angiography. Methods A literature search of electronic databases, including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE, was performed to retrieve and integrate articles showing significant CAD detectability of 1.5 and 3.0 T WHCA. Results Data from 1899 patients from 34 studies were included in the meta-analysis. 1.5 T WHCA had a summary area under ROC of 0.88 in the patient-based analysis, 0.90 in the vessel-based analysis, and 0.92 in the segment-based analysis. These values for 3.0 T WHCA were 0.94, 0.95, 0.96, respectively. Contrast-enhanced 3.0 T WHCA had significantly higher specificity than non-contrast-enhanced 1.5 T WHCA on a patient-based analysis (0.87, 95% CI 0.80–0.92 vs. 0.74, 95% CI 0.64–0.82, P = 0.02). There were no differences in diagnostic performance on a patient-based analysis by use of vasodilators, beta-blockers or between Asian and Western countries. Conclusions The diagnostic performance of WHCA was deemed satisfactory, with contrast-enhanced 3.0 T WHCA exhibiting higher specificity compared to non-contrast-enhanced 1.5 T WHCA in a patient-based analysis. There were no significant differences in diagnostic performance on a patient-based analysis in terms of vasodilator or beta-blocker use, nor between Asian and Western countries. However, further large-scale multicentre studies are crucial for the widespread global adoption of WHCA.

Abstract Background The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate “patients without gastritis” (defined as true A patients) from those “with gastritis.” A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis. Methods Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the “pathologically-evaluated group” and “endoscopically-evaluated group,” according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group. Results The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12–126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80. Conclusion The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

Abstract Background Phase-contrast cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method for measuring coronary sinus blood flow and coronary flow reserve (CFR). However, its clinical utility has not yet been established. Here we performed a meta-analysis to clarify the clinical value of CMR-derived CFR in various cardiovascular diseases. Methods An electronic database search was performed of PubMed, Web of Science Core Collection, Cochrane Advanced Search, and EMBASE. We compared the CMR-derived CFR of various cardiovascular diseases (stable coronary artery disease [CAD], hypertrophic cardiomyopathy [HCM], dilated cardiomyopathy [DCM]) and control subjects. We assessed the prognostic value of CMR-derived CFR for predicting major adverse cardiac events (MACE) in patients with stable CAD. Results A total of 47 eligible studies were identified. The pooled CFR from our meta-analysis was 3.48 (95% confidence interval [CI], 2.98–3.98) in control subjects, 2.50 (95% CI, 2.38–2.61) in stable CAD, 2.01 (95% CI, 1.70–2.32) in cardiomyopathies (HCM and DCM). The meta-analysis showed that CFR was significantly reduced in stable CAD (mean difference [MD] = −1.48; 95% CI, −1.78 to −1.17; p

Abstract Background A new SARS‐CoV‐2 variant, Omicron, was reported on November 14, 2021, and it altered the COVID‐19 epidemic with a different peak timing by region in Japan. Residents in the Hiroshima prefecture, especially the vulnerable elderly, were threatened by this wave in advance of many other prefectures. We evaluated the effect of cognitive decline on discharge extension after the quarantine period. Methods Participants of this retrospective cohort study were patients who were admitted to the care unit for COVID‐19 treatment at Hiroshima University Hospital between January 1, 2022, and March 1, 2022 (60 days). Our primary outcome was the extended length of stay (LOS) in the hospital after the quarantine period (10 days after onset). A negative binomial regression analysis was performed to assess the extended LOS of patients with cognitive decline, adjusting for age classification, gender, and severity of COVID‐19. Results The total number of participants was 74. Per the level of cognitive function, there were 56 independent participants, 5 mild declines, and 13 severe declines. For the negative binomial regression analysis, the exponentiated coefficient of mild cognitive decline was 3.05 (95% confidential interval [CI]: 1.43–6.49) and that of severe cognitive decline was 1.95 (95% CI: 1.09–3.53). Conclusions Mild cognitive decline and severe cognitive decline elevated the risk of extended LOS after COVID‐19 patients finished the quarantine period.

Background: The global impact of the coronavirus disease 2019 (COVID-19) pandemic on public health has been significant. Upper gastrointestinal endoscopy for screening and diagnosis decreased along with new gastric cancer (GC) diagnoses. Methods: This study assesses how the pandemic affected GC mortality using data from Hiroshima Prefecture, comparing mortality rates between patients diagnosed during the pandemic (2020 and 2021) and pre-pandemic (2018 and 2019) periods. The crude hazard ratios (HRs) and HRs adjusted for age, sex, clinical stage, treatment status, and travel distance to the nearest GC screening facility were estimated using Cox regression models. Subgroup and sensitivity analyses were also performed. Results: A total of 9571 patients were diagnosed, with 4877 eligible for follow-up. The median age was 74 years, and 69% were male. The median follow-up period was 157 days, with events per 1000 person-years at 278 and 374 in the pre-pandemic and pandemic periods, respectively (crude HR, 1.37; adjusted HR, 1.17). The sensitivity and subgroup analyses yielded consistent results. Conclusions: The COVID-19 pandemic increased mortality risk in patients with GC. Further studies are required to observe long-term outcomes and identify the disparities contributing to the increased mortality risk.

Objectives: The clinical evidence for the effect of narrow-spectrum antimicrobial shortages on bacterial susceptibility is limited. Our purposes were to determine the affects of the disruption of most of the cefazolin (CEZ) supply in Japan on the susceptibility of pathogens and to analyze how long these changes persisted after the shortage of CEZ. Methods: We performed an interrupted time series analysis using the Japanese Infectious Disease Nationwide database. We analyzed each pathogen before and after CEZ shortage in 52 university hospitals from 2018 to 2020. May to November 2019 was designated as the implementation term for CEZ shortage. The primary outcome was the susceptibility to CEZ and other antimicrobial agents. Amongst all pathogens isolated from facilities, we identified pathogens that were tested for susceptibility to CEZ. Results: Of the 26 pathogens identified, analysis was performed on a total of 36,346 isolates of five pathogens (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, and Staphylococcus aureus). Amongst four Gram-negative pathogens with low susceptibility, there were no significant immediate changes after the CEZ shortage; however, the slope change significantly increased by 1.29 to 2.69% per month and continued to improve one year after the shortage. Regarding S. aureus, which was highly susceptible at the baseline, neither immediate change nor slope was significant. Conclusion: This quasi-experimental analysis using a nationwide-large database revealed that restriction of use because of narrow-spectrum antimicrobial shortages may lead to improved susceptibility over the subsequent year. The results suggest that temporary switching of antimicrobial agents on a national scale could be effective.

Abstract Background After the confirmation of coronavirus infection in Japan, a behavioral change caused people and physicians to refrain from visiting hospitals or undergoing examinations. This study aimed to assess how the trend of diagnosis in gastric cancers changed, and how it affected the therapeutic strategies and the interval from diagnosis to treatment during the COVID‐19 pandemic. Methods We use 15 cancer‐designated hospitals’ registries in Hiroshima, Japan. The target period was March to December 2020, and the same period in 2019 was set as the control period. The monthly mean of diagnoses and the interval from diagnosis to treatment were compared overall and separately by age, treatment procedure, diagnostic process, and clinical stage. Result In 2020, the monthly mean (standard deviation [SD]) of patients was 192.2 (29.9), a significant 20.1% decrease from 240.7 (20.7) in 2019 due to older age and curative treatment groups. By reason for performing endoscopy, the change rate in cancer screening, endoscopic follow‐up, and symptomatic status were ‐27.0%, ‐18.0%, and ‐17.3%, respectively. Meanwhile, the interval (days) from diagnosis to treatment (SD) was 37.8 (26.5) in 2020, significantly shorter than 46 (31.5) in 2019. Conclusion From 2019 to 2020, we observed a significant decrease in the diagnosis of curable early‐stage gastric cancer and treatments, although the interval from diagnosis to treatment decreased. This study suggests that cancer screening played a significant role in the decline in cancer diagnosis that occurred during the COVID‐19 pandemic. Even under COVID‐19 pandemic conditions, there should be an awareness of cancer screening and endoscopic follow‐up.

Abstract Background Gastric cancer remains a severe public health problem worldwide, particularly in Japan. Recent studies have demonstrated that serum markers are beneficial for risk stratification in gastric cancer development. We aimed to evaluate the usefulness of serum markers either alone or in combination (serum markers plus endoscopy) for effective risk stratification of gastric cancer development. Methods We enrolled 22,736 patients aged 20–95 years who underwent blood sampling and endoscopic examination at Hiroshima University Hospital in Japan between 1990 and 2014. The serum pepsinogen (PG) levels and anti-Helicobacter pylori antibody (Hp-Ab) titers were evaluated in each patient. The enrolled patients were matched with the database of the Hiroshima Prefecture Regional Cancer Registry. We processed the medical records and excluded patients with possible confounding factors for PG levels, such as proton pump inhibitor use, prior successful eradication therapy, post-gastrectomy, severe hepatorenal dysfunction, Zollinger–Ellison syndrome, and autoimmune gastritis. Among the remaining 5131 patients, we reviewed records of endoscopic examinations and selected 1507 patients (mean age, 62.5 years; 985 men and 522 women) who underwent endoscopic examination more than three months after blood sampling. First, based on the ABC method, patients were classified as follows: High PG levels and negative Hp-Ab, group A, high PG levels and positive Hp-Ab, group B, low PG levels and positive Hp-Ab, group C, and low PG levels and negative Hp-Ab, group D. Group A was further classified into two subgroups using endoscopic findings: true A without atrophic gastritis and pseudo A with atrophic gastritis. All patients underwent annual endoscopy follow-up. Results Among the 1,507 patients (mean age, 62.5 years; 985 men), 24 were diagnosed with newly developed gastric cancer. No significant difference in cancer development was found between group A (PG negative and Hp-Ab negative) and the other groups. Remarkably, no true A group subjects developed gastric cancer. Conclusions The combination of serum markers and endoscopic findings is essential for the risk evaluation of gastric cancer.

Abstract Background Solitary death is an emerging public health problem in developed countries. Alcohol abuse is associated with social isolation and excess mortality. However, data on the association between alcohol abuse and solitary death are limited. Our purposes were to assess whether alcohol abuse is associated with a long interval from death to discovery among people living alone. Methods This is a cross-sectional study using the data on subjects from the largest forensic database in Kyoto, Japan, from February 2012 to December 2015. Solitary death was defined as a phenomenon of dying alone at home and remaining undiscovered for more than 1 week. All the subjects who lived alone and aged over 18 at the time of death were included in the study. The presence of alcohol abuse was identified via an investigation during home visits. Proportional ratios were calculated using a fitted logit model to evaluate the association of alcohol abuse on solitary death after adjusting for possible confounders. Results A total of 235 subjects were included in the analysis. The mean age (standard deviation) of subjects at the time of death was 63.4 (15.1) years, and approximately 61.8% and 38.9% of subjects in the alcohol and non-alcohol abuse groups, respectively, experienced solitary death. Multivariable analyses revealed that alcohol abuse was associated with solitary death (adjusted proportion ratio: 1.50; 95% confidence interval: 1.12–2.00). Conclusions The findings of this study could help identify individuals at higher risk of solitary death. Moreover, calling the attention of people with alcohol abuse may be beneficial to prevent solitary death.

Background: Level of care-need (LOC) is an indicator of elderly person’s disability level and is officially used to determine the care services provided in Japan’s long-term care insurance (LTCI) system. The 2018 Japan Floods, which struck western Japan in July 2018, were the country’s second largest water disaster. This study determined the extent to which the disaster affected the LOC of victims and compared it with that of non-victims. Methods: This is a retrospective cohort study, based on the Japanese long-term care insurance claims from two months before (May 2018) to five months after the disaster (December 2018) in Hiroshima, Okayama, and Ehime prefectures, which were the most severely damaged areas in the country. A code indicating victim status, certified by a residential municipality, was used to distinguish between victims and non-victims. Those aged 64 years or younger, those who had the most severe LOC before the disaster, and those whose LOC increased even before the disaster were excluded. The primary endpoint was the augmentation of pre-disaster LOC after the disaster, which was evaluated using the survival time analysis. Age, gender, and type of care service were used as covariates. Results: Of the total 193,723 participants, 1,407 (0.7%) were certified disaster victims. Five months after the disaster, 135 (9.6%) of victims and 14,817 (7.7%) of non-victims experienced the rise of LOC. The victim group was significantly more likely to experience an augmentation of LOC than the non-victim group (adjusted hazard ratio 1.24; 95% confidence interval 1.06–1.45). Conclusions: Older people who were affected by the disaster needed more care than before and the degree of care-need increase was substantially more than non-victims. The result suggests that natural disasters generate more demand for care services among the older people, and incur more resources and cost for society than before.

The prevalence of gastric cancer after eradication (GCAE) is increasing dramatically in Japan. GCAE has characteristic features, and we must understand these features in endoscopic examinations. Differentiated cancer types were frequently found after eradication and included characteristic endoscopic features such as reddish depression (RD). However, benign RD can be difficult to distinguish from gastric cancer because of histological alterations in the surface structures (nonneoplastic epithelium or epithelium with low-grade atypia [ELA]) as well as multiple appearances of RD. Recently, we clarified similar alterations in genetic mutations between ELA and gastric cancer, suggesting that ELA is derived from gastric cancer. Clinically, submucosal invasive cancer was frequently found in patients after eradication therapy even if they received annual endoscopic surveillance. We can improve the diagnostic ability using image-enhanced endoscopy with magnified observation.

Abstract Non‐secretory multiple myeloma (NSMM) is a rare type of multiple myeloma characterized by the absence of the M protein, making its diagnosis challenging. Here, we report a 67‐year‐old female patient eventually diagnosed as NSMM with positron emission tomography‐computed tomography (PET/CT) imaging as a clue.

Abstract Direct sampling and analysis of fumarolic gas was conducted at Ebinokogen Ioyama volcano, Japan, between December 2015 and July 2020. Notable changes in the chemical composition of gases related to volcanic activity included a sharp increase in SO2 and H2 concentrations in May 2017 and March 2018. The analyses in March 2018 immediately preceded the April 2018 eruption at Ioyama volcano. The isotopic ratios of H2O in fumarolic gas revealed the process of formation. Up to 49% high-enthalpy magmatic vapor mixed with 51% of cold local meteoric water to generate coexisting vapor and liquid phases at 100–160 °C. Portions of the vapor and liquid phases were discharged as fumarolic gases and hot spring water, respectively. The CO2/SO2 ratio of the fumarolic gas was higher than that estimated for magmatic vapor due to SO2 hydrolysis during the formation of the vapor phase. When the flux of the magmatic vapor was high, effects of hydrolysis were small resulting in low CO2/SO2 ratios in fumarolic gases. The high apparent equilibrium temperature defined for reactions involving SO2, H2S, H2 and H2O, together with low CO2/SO2 and H2S /SO2 ratios were regarded to be precursor signals to the phreatic eruption at Ioyama volcano. The apparent equilibrium temperature increased rapidly in May 2017 and March 2018 suggesting an increased flux of magmatic vapor. Between September 2017 and January 2018, the apparent equilibrium temperature was low suggesting the suppression of magmatic vapor flux. During this period, magmatic eruptions took place at Shinmoedake volcano 5 km away from Ioyama volcano. We conclude that magma sealing and transport to Shinmoedake volcano occurred simultaneously in the magma chamber beneath Ioyama volcano.

Abstract Here, we report a case of traumatic pulmonary pseudocysts (TPPs) coinciding with vertebral fracture. Traumatic pulmonary pseudocysts (TPPs) are rare complications of blunt chest trauma. These clinical images of CT, presenting here, seemed to be valuable because they show the process of pseudocyst formation.

Several traditional Japanese Kampo formulas are known to have inhibitory effects on infections with viruses that cause respiratory symptoms. Although some herbs and their components have been reported to suppress SARS-CoV-2 replication in vitro, it is difficult to compare effective Kampo formulas because of the different methods used in studies. Thus, we carried out in vitro experiments on the suppression of SARS-CoV-2 infection by Kampo formulas and crude drugs used for the common cold to compare their suppressive effects on virus infection. After infecting VeroE6/TMPRSS2 cells with SARS-CoV-2, lysates of the Kampo formulas and crude drugs were added, and after 24 h, the infectious titer in the medium was measured by the TCID50 method. Maoto was the most effective among the Kampo formulas, and Ephedrae herba was the most effective among the constituent crude drugs. However, a comparison of the suppressive effects of Ephedrae herba and Kampo formulas containing Ephedrae herba showed that the suppressive effect on virus infection did not depend on the content of Ephedrae herba. Based on the results, we believe that the use of Maoto among Kampo formulas is suitable as a countermeasure against COVID-19.

Both chemical and isotopic compositions of concentrated volcanic plumes are highly useful in evaluating the present status of active volcanoes. Monitoring their temporal changes is useful for forecasting volcanic eruptions as well. Recently, we developed a drone-borne automatic volcanic plume sampler, called SelPS, wherein an output signal from a sulfur dioxide (SO2) sensor triggered a pump to collect plume samples when the SO2 concentration exceeded a predefined threshold. In this study, we added a radio transmission function to the sampler, which enabled our operator to monitor real-time SO2 concentration during flights and thus obtain more concentrated volcanic plume samples through precise adjustment of the hovering position. We attached the improved SelPS to a drone at Nakadake crater, Aso volcano (Japan), and successfully obtained volcanic plume samples ejected from the crater more concentrated than those obtained by using previous version of SelPS in 2019. Additionally, we found a significant linear correlation between the reciprocal of the concentration and isotopic ratios for the 2H/1H ratios of H2, 18O/16O ratios of CO2, and 13C/12C ratios of CO2 within the plume samples. Based on the isotopic ratios of fumarolic H2 (δ2H = −239 ± 6‰) and fumarolic CO2 (δ13C = −3.58 ± 0.85‰ and δ18O = +22.01 ± 0.68‰) determined from the linear correlations, we estimated the apparent equilibrium temperatures (AETs) with magmatic H2O simultaneously and precisely for the first time in erupting volcanoes, assuming hydrogen isotope exchange equilibrium between H2 and H2O (AETD = 629 ± 32°C) and oxygen isotope exchange equilibrium between CO2 and H2O (AET18O = 266 ± 65°C). We found that the AET18O was significantly lower than the AETD in the crater. While the temperature of the magmatic gases was originally 600°C or more, most of the gases cooled just beneath the crater to temperatures around the boiling point of water. The improved SelPS enable us to determine both AETD and AET18O in eruptive volcanoes, wherein fumaroles are inaccessible. Simultaneous and precise determination of both the AET18O and AETD can provide novel information on each volcano, such as the physicochemical conditions of magma degassing and the development of fluid circulation systems beneath each volcano.

Acid secretion inhibitors, such as proton pump inhibitors (PPIs) and potassium competitive acid blockers (PCABs), are used to treat ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer. These drugs can influence serum gastrin and pepsinogen (PG) levels; however, their definite effects remain unclear. This open-label, randomized study investigated the effect of acid secretion inhibitors on the serum gastrin and pepsinogen levels. In total, 76 patients were enrolled in the study. They underwent gastric ESD and received a PPI (n=21) or PCAB (n=55). Changes in the serum gastrin and PG levels before and 4 weeks after administration were examined. Patient factors associated with the alteration of serum PG or gastrin levels were identified. The median serum levels of gastrin, PGI, and PGII before the administration of the acid secretion inhibitors were 110.5 pg/mL, 36.4 ng/mL, and 8.9 ng/mL, respectively; after administration, the levels increased to 300 pg/mL, 64.7 ng/mL, and 15.8 ng/mL, respectively (P

Abstract Background Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in H. pylori-uninfected patients. Methods Seventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing. Results H. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H. pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one H. pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without H. pylori-infected. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples. Conclusions Some SRCCs in H. pylori-uninfected patients may have a malignant potential similar to that of SRCCs in H. pylori-infected patients. Smoking may not be the main carcinogenic factor for the development of SRCCs among the H. pylori-uninfected patients.

Abstract Background Many studies have revealed that mucosal healing improves the long-term prognosis of ulcerative colitis. Frequent colonoscopy is difficult because of its invasiveness and cost. Therefore, in diagnosing and treating ulcerative colitis, noninvasive, low-cost methods for predicting mucosal healing using useful biomarkers are required in the clinical setting. This study aimed to evaluate whether serum amyloid A is a better serum biomarker than C-reactive protein in predicting mucosal healing in ulcerative colitis patients in clinical remission. Methods Ulcerative colitis patients whose C-reactive protein and serum amyloid A were measured within 1 month before and after colonoscopy were included in this retrospective study, and the relationship between the C-reactive protein and serum amyloid A values and the mucosal condition was analyzed. Mucosal condition was assessed using the Mayo Endoscopic Score, with score 0 or 1 indicating mucosal healing. Results A total of 199 colonoscopic examinations were conducted in 108 ulcerative colitis patients who underwent C-reactive protein and serum amyloid A blood tests. In clinical remission patients, serum amyloid A showed a strong correlation with mucosal inflammation compared to C-reactive protein and had excellent sensitivity and specificity rates with significant statistical significance. Conclusions Serum amyloid A is a more useful marker compared to C-reactive protein in predicting mucosal inflammation in ulcerative colitis patients in clinical remission.

Background/Aims Dual red imaging (DRI) is a new, image-enhanced endoscopy technique. There are few reports about the usefulness of DRI during gastric endoscopic submucosal dissection (ESD). We aimed to examine the usefulness of DRI in endoscopic hemostasis during gastric ESD. Methods We enrolled a total of 20 consecutive patients who underwent gastric ESD. Five endoscopists compared DRI with white light imaging (WLI) for the visibility of blood vessels and bleeding points while performing endoscopic hemostasis. Results The visibility of blood vessels was increased in 56% (19/34) of the cases, and the visibility of bleeding points was improved in 55% (11/20) of the cases with the use of DRI compared with the use of WLI. Conclusions DRI improved the visibility of blood vessels and bleeding points in cases with oozing bleeding, blood pooling around the bleeding points, and multiple bleeding points.

Abstract Background Exercise‐induced bronchoconstriction (EIB), a strong positive predictor of asthma, becomes progressively less frequent with age. Although asthma tends to become less common only in boys during adolescence, sex differences in EIB, especially in preschoolers, remain unclear. To find EIB for early diagnosis and intervention asthma, mass‐screening tests considering sex differences in preschoolers are needed. In this study, we investigated whether sex differences influence the prevalence and severity of EIB in prepubertal children aged 5–6 years. Methods Fifty‐one children aged 5–6 years who were attending a kindergarten in Matsuyama City, Ehime, Japan, were enrolled in this cross‐sectional study. The children underwent a 6‐minute free‐running test in 2015. The peak expiratory flow rate (PEFR) was measured before exercise and 0, 3, 10, and 20 minutes after exercise. The severity of EIB was classified according to the reduction in PEFR, measured as the difference between the postexercise PEFR and the highest pre‐exercise PEFR. Results Of the 51 children (23 boys and 28 girls) enrolled, the prevalence of EIB defined as three criteria: a ≥15%, ≥20%, or ≥25% decrease was 54.9% (28/51), 41.2% (21/51), and 25.5% (13/51), respectively. The prevalence of EIB defined as ≥25% decrease was significantly higher in girls than in boys (39.3% vs 8.7%, P = .013). In girls, the mean percentage change in PEFR was significantly higher 20 minutes than 10 minutes postexercise (P = .043). Conclusions Sex difference in the prevalence and severity of EIB should be considered when evaluating EIB, even in young, prepubertal children.

Amid the global outbreak of coronavirus disease 2019 (COVID-19), it may be expected that low-toxicity natural compounds, such as Kampo formulas, will have a preventive effect on COVID-19. Although the biological properties and safety of the representative Kampo compounds, hochuekkito (HET) and kakkonto (KKT), have been confirmed in various animal model experiments, clinical studies, and a few human studies to induce biological effects on various infectious diseases without significant toxicity, it is unclear whether HET and KKT are safe and effective for COVID-19 prevention. The study population included healthcare workers (HCWs), as they are at a higher risk of infection than the other populations. We retrospectively investigated the immunological and preventive effects of HET and KTT against COVID-19. We included 27 HCWs (aged 21–72 years, F:M = 18:9) from hospitals and clinics of the Hokuriku-Tokai region. The HCWs received HET and KKT for general fatigue and myalgia during this period for 28 days. We obtained patient clinical data from electronic medical records. We analyzed the changes in immunomodulation before and after the administration of the formulas from residual specimens based on the expression of relevant surface markers. The specimens were also tested for the presence of antibodies against severe acute respiratory syndrome coronavirus 2. The following side effects were reported: abdominal discomfort in five patients, diarrhea in two, and loose or soft stool in three. All 27 HCWs tested negative for COVID-19 antibodies. HET and KKT administration significantly increased the absolute number of circulating lymphocytes expressing the activating receptors NKp46, NKp30, and suppressing receptor NKG2A. There was also a significant increase in the absolute number of circulating lymphocytes expressing the receptors TLR4, OX40, 4–1BB, GITR, PD-1, and ICOS. These data indicate that HET and KKT can enhance and modulate NK activity in circulating human immune cells. The immunomodulatory effects, such as activation and regulation of T cells, are consistent with a putative improvement in infectious immunosurveillance. An increase in the number of T cells and CD4/CD8-positive cells indicates an enhanced ability to protect against infection. HET and KKT may prevent the onset or worsening of COVID-19 through their immunomodulatory effects.

A previously healthy 43-year-old man presented with durable occipitalgia for 1 month. Neurological examination revealed severe pain in the right C2 area accompanied by neck stiffness. Magnetic resonance imaging revealed an enhancing, polycystic intradural mass at the C2 level, occupying the left dorsolateral part of the spinal canal. In addition, a rim-like enhancement was found along the surfaces of the spinal cord. Blood tests did not show signs of infection. A lumbar spinal tap revealed albuminocytologic dissociation without cultured organisms. Cranial computed tomography scans taken 20 days later revealed an overt ventriculomegaly. The patient underwent a total tumor resection through hemilaminectomy of the C2. Intraoperatively, the left dorsal C2 roots were found to be extremely redundant due to the tumor and surrounding thickened arachnoids. The roots restored normal morphologies after resection of the arachnoids and tumor. Postoperatively, the patient's symptoms resolved and histological diagnosis was endodermal cyst. Four weeks later, a ventriculoperitoneal shunt was placed to treat progressive ventriculomegaly. A polycystic intradural mass of the upper cervical spine should assume an endodermal cyst that may cause contralateral occipitalgia and aseptic meningitis. Keywords: Endodermal cyst, Contralateral occipitalgia, Aseptic meningitis

Background: Practical criteria for the use of serum pepsinogen (PG) values in diagnosing Helicobacter pylori infection have not yet been determined. Methods: The results of gastric endoscopies, H. pylori infection tests, and PG values were retrospectively reviewed. Subjects were assigned to groups, including never-infected (with neither infection nor gastric mucosal atrophy), infected (with atrophy or findings indicating infection in endoscopy and positive infection tests except for antibody tests), and ex-infected (with gastric mucosal atrophy and negative infection tests, except for antibody tests). The optimal criteria with combined use of the PG II concentrations and the PG I/PG II ratio were investigated separately for PG measurements obtained with the chemiluminescent magnetic particle immunoassay (CLIA) and latex agglutination (LA) methods, such that the specificity was greater than 70% and the sensitivity was no less than 95% among the never-infected and infected subjects. Similar analyses were performed by combining the data from ex-infected and infected subjects. Results: For the CLIA (LA) method, the optimal criterion among 349 (397) never-infected and 748 (863) infected subjects was a PG II value of at least 10 (12) ng/mL or a PG I/PG II ratio no more than 5.0 (4.0), which produced 96.3% (95.1%) sensitivity and 82.8% (72.8%) specificity. When 172 (236) ex-infected subjects were included, the optimal criterion was the same, and the sensitivity was 89.1% (86.9%). Conclusions: The above criteria may be practical for clinical use, and PG tests using these criteria might prevent unnecessary endoscopic examinations for never-infected subjects.

Abstract Definite increases in the components ratios of CO2/H2O, CO2/H2S, CO2/CH4 and He/CH4 were observed at the fumarolic gases from Owakudani geothermal area located at the center of Hakone volcanic caldera (Honshu Island, Japan), synchronized with the earthquake swarm in 2015. Such variations were due to the dominance of a magmatic component over a hydrothermal component, suggesting the earthquake swarm was produced by the injection of magmatic gases into the hydrothermal system. The CO2/H2O ratio of magmatic gas was estimated to be 0.0045 before the earthquake swarm, which increased up to 0.013 during the earthquake swarm, likely produced by the pressurization of magma as a result of magma sealing where the pressure increment in magma was estimated to be 3% to the lithostatic pressure. The H2O and CO2 concentration in magma were estimated to be 6.3 wt% and 20 wt ppm, respectively, assuming a temperature 900 °C and a rhyolitic composition. In May 2015, a few months prior to the earthquake swarm in May 2015, a sharp increase in the Ar/CO2 and N2/He ratios and a decrease in the isotopic ratio of H2O were observed at the fumarolic gas. The invasion of air into the hydrothermal system increased the Ar/CO2 and N2/He ratios. The decrease in the isotopic ratio of H2O was induced by partial condensation of H2O vapor.

To minimize motion-related distortion of reconstructed images, conventional positron emission tomography (PET) measurements of the brain inevitably require a firm and tight head restraint. While such a restraint is now a routine procedure in brain imaging, the physiological and psychological consequences resulting from the restraint have not been elucidated. To address this problem, we developed a restraint-free brain PET system and conducted PET scans under both restrained and non-restrained conditions. We examined whether head restraint during PET scans could alter brain activities such as regional cerebral blood flow (rCBF) and dopamine release along with psychological stress related to head restraint. Under both conditions, 20 healthy male participants underwent [15O]H2O and [11C]Raclopride PET scans during working memory tasks with the same PET system. Before, during, and after each PET scan, we measured physiological and psychological stress responses, including the State-Trait Anxiety Inventory (STAI) scores. Analysis of the [15O]H2O-PET data revealed higher rCBF in regions such as the parahippocampus in the restrained condition. We found the binding potential (BPND) of [11C]Raclopride in the putamen was significantly reduced in the restrained condition, which reflects an increase in dopamine release. Moreover, the restraint-induced change in BPND was correlated with a shift in the state anxiety score of the STAI, indicating that less anxiety accompanied smaller dopamine release. These results suggest that the stress from head restraint could cause unsolicited responses in brain physiology and emotional states. The restraint-free imaging system may thus be a key enabling technology for the natural depiction of the mind.

Minor seismicity may occur at volcanoes with hydrothermal system before a steam eruption. To forecast any steam eruption, it is indispensable to detect and understand the nature of this shallow seismicity. As the fumarolic gas resides in the hydrothermal system, it may provide insights for elucidating the nature of any seismicity and thus forecast steam eruptions. At Kusatsu-Shirane volcano Japan, intense seismic activity took place in 2014 and 2018. To investigate the relationship between the seismicity and gas chemistry, five fumarolic gas discharges have been repeatedly analyzed. Since July 2014 to November 2017 a monotonic decrease in CO2/H2O, He/H2O and N2/H2O ratios was recorded in the fumarolic gasses located north of the summit of volcano, suggesting the decline of the magmatic component. On the contrary the CH4/H2O ratio significantly increased during the seismically quiet period, indicating that reduced conditions developed in the hydrothermal system, favoring the formation of CH4. The high N2/He ratio in the quiet period indicates the addition of N2, likely deriving from the crustal rocks hosting hydrothermal reservoir. The N2/He ratio in 2018 was significantly lower than those recorded in 2014, indicating the evolution of magma with the progress of degassing. The δD(H2O) and δ18O(H2O) values and the CO2/H2O ratios of fumarolic gas discharges were modeled with the following processes: generation of vapor phase after the mixing between magmatic gas and a cold groundwater with meteoric origin, addition of vapor phase with meteoric origin, and partial condensation of water vapor near surface. Only a single magmatic gas is necessary for the above modeling. These data suggest that at Kusatsu-Shirane volcano the activation of seismicity was synchronized with the increase of the magmatic component in the fumarolic gas. It is postulated that the injection of magmatic gas increased the fluid pressure in the reservoir, which triggered seismicity. The injection would have been triggered by a break of the sealing zone surrounding the degassing magma. The injection of magmatic gas can be detected by monitoring the composition of the fumarolic gas, thus giving the possibility to forecast any future seismicity.

An epidermoid cyst is an infrequent entity among cysts found in the presacral region, frequently coexistent with a meningocele. Diffusion-weighted imaging is known to be a useful diagnostic measure for differentiating presacral epidermoid cysts. Here, we present a large but asymptomatic case found in the presacral region. Epidermoid cysts should be considered in patients with presacral cysts.

Background and aims: Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targets, and nearly all GC reports have been about advanced GC. The aim of this study is to identify recurrently mutated genes in non-invasive GC and, in particular, the driver mutations that are associated with the development of GC. Methods and results: We performed whole-exome sequencing of 19 fresh frozen specimens of differentiated-type non-invasive GC and targeted sequencing for 168 genes of 30 formalin-fixed paraffin-embedded archival specimens of differentiated-type non-invasive GC. We found that TP53 and LRP1 are significantly associated with non-invasive GC. It has been reported that LPR1 is associated with CagA autophagy in gastric mucosa. Therefore, we downloaded RNA sequence data for gastric cancer from the The Cancer Genome Atlas (TCGA) Genomic Data Commons Data Portal and examined the differences in LRP1 gene expression levels. The expression level was significantly lower in cases without LRP1 mutation than in cases with LRP1 mutation. Based on these results, fluorescent immunostaining for CagA was performed for 49 of the above samples to evaluate CagA accumulation within the cancerous tissue. Accumulation of CagA was significantly greater when an LRP1 mutation was present than without a mutation. Conclusion: These data suggest that LRP1 mutation is an important change promoting the transformation of gastric mucosa to GC early in the carcinogenesis of cancer.

OBJECTIVES:Follistatin-like 1 (Fstl1) is a circulating glycoprotein that plays a crucial role in cardiovascular diseases and inflammation-related disorders. We have shown that Fstl1 acts as an anti-inflammatory factor that protects against ischemic heart disease and chronic kidney disease. Here we examined whether plasma level of Fstl1 associates with markers of inflammation and oxidative stress in apparently healthy Japanese men. METHODS AND RESULTS:Plasma Fstl1 levels were measured by enzyme-linked immunosorbent assay. Circulating Fstl1 concentrations positively correlated with levels of fasting immune-reactive insulin (FIRI), high-sensitive CRP (hsCRP) and derivatives of reactive oxidative metabolites (dROMs), an indicator of oxidative stress. The levels of hsCRP positively associated with Fstl1, body mass index (BMI), triglyceride, FIRI and dROMs levels. dROMs levels positively associated with Fstl1, Hemoglobin A1c and hsCRP levels. Multiple regression analysis with confounding factors revealed that Fstl1 levels, together with BMI and FIRI, correlated with hsCRP and that Fstl1 levels correlated with dROMs. CONCLUSION:Our observations indicate that measurement of plasma Fstl1 levels can be valuable for assessment of pro-inflammatory and oxidative stress conditions.

We used photo irradiation to design core crosslinked polymeric micelles whose only significant physico-chemical change was in their physico-chemical stability, which helps elucidate poly(ethylene glycol) (PEG)-related immunogenicity. Synthetic routes and compositions of PEG-b-poly(aspartic acid) block copolymers were optimized with the control of n-alkyl chain length and photo-sensitive chalcone moieties. The conjugation ratio between n-alkyl chain and the chalcone moieties was controlled, and upon the mild photo irradiation of polymeric micelles, permanent crosslink proceeded in the micelle cores. In the optimized condition, the core crosslinked (CCL) micelles exhibited no dissociation while the non-CCL micelles exhibited dissociation. These results indicate that the photo-crosslinking reactions in the inner core were successful. A gel-permeation chromatography (GPC) measurement revealed a difference between the micellar-formation stability of CCL micelles and that of the non-CCL micelles. GPC experiments revealed that the CCL micelles were more stable than the non-CCL micelles. Our research also revealed that photo-crosslinking reactions did not change the core property for drug encapsulation. In conclusion, the prepared CCL micelles exhibited the same diameter, the same formula, and the same inner-core properties for drug encapsulation as did the non-CCL micelles. Moreover, the CCL micelles exhibited non-dissociable micelle formation, while the non-CCL micelles exhibited dissociation into single block copolymers.