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Background: Dynamic chest radiography (DCR) produces sequential radiographs within a short examination time. It is also inexpensive and only uses a low dose of radiation. Because of the lack of reports of evaluating cardiac function using DCR in humans, we investigated its discriminative ability for left ventricular (LV) dysfunction in a study cohort., Methods and results: We analyzed the DCR pixel values of 4 circular regions of interest (ROIs) in the hearts of 61 patients with cardiovascular disease and 10 healthy volunteers. We evaluated the relationship between changes in pixel value in the heart and the LV ejection fraction (LVEF) by echocardiography. We constructed receiver operating characteristic (ROC) curves to evaluate whether the percent change in pixel value (%∆pixel value) could be used to identify patients with reduced LVEF. A total of 21 patients had reduced LVEF (LVEF <50%), and 40 had preserved LVEF (LVEF ≥50%). The correlation between LVEF and %∆pixel value in each ROI was significant, and the area under the ROC curve of the %∆pixel values for identifying patients with reduced LVEF was satisfactory (0.808-0.827) in 3 ROIs where the entire circular area was within the cardiac shadow., Conclusions: LV dysfunction can be detected by changes in the pixel value on DCR.

Orchidaceae has diversified in tree canopies and accounts for 68% of vascular epiphytes. Differences in mycorrhizal communities among epiphytic orchids can reduce species competition for mycorrhizal fungi and contribute to niche partitioning, which may be a crucial driver of the unusual species diversification among orchids. Mycorrhizal specificity-the range of fungi allowing mycorrhizal partnerships-was evaluated by assessment of mycorrhizal communities in the field (ecological specificity) and symbiotic cultures in the laboratory (physiological specificity) for three epiphytic orchids inhabiting Japan. Mycorrhizal communities were assessed with co-existing individuals growing within 10 cm of each other, revealing that ecological specificity varied widely among the three species, ranging from dominance by a single Ceratobasidiaceae fungus to diverse mycobionts across the Ceratobasidiaceae and Tulasnellaceae. In vitro seed germination tests revealed clear differences in physiological specificity among the three orchids, and that the primary mycorrhizal partners contributed to seed germination. In vitro compatibility ranges of three orchids strongly reflect the mycorrhizal community composition of wild populations. This suggests that differences in in situ mycorrhizal communities are not strongly driven by environmental factors, but are primarily due to physiological differences among orchid species. This study shows that the symbiotic strategy among the epiphytic orchid species varies from specialized to generalized association, which may contribute to biotic niche partitioning., (© 2023. The Author(s) under exclusive licence to The Botanical Society of Japan.)

Sulfite reduction by dissimilatory sulfite reductases is a key process in the global sulfur cycle. Sulfite reductases catalyze the 6e - reduction of SO 3 2- to H 2 S using eight protons (SO 3 2- + 8H + + 6e - → H 2 S + 3H 2 O). However, detailed research into the reductive conversion of sulfite on transition-metal-based complexes remains unexplored. As part of our ongoing research into reproducing the function of reductases using dinuclear ruthenium complex {(TpRu) 2 (μ-Cl)(μ-pz)} (Tp = HB(pyrazolyl) 3 ), we have targeted the function of sulfite reductase. The isolation of a key SO-bridged complex, followed by a sulfite-bridged complex, eventually resulted in a stepwise sulfite reduction. The reduction of a sulfite to a sulfur monoxide using 4H + and 4e - , which was followed by conversion of the sulfur monoxide to a disulfide with concomitant consumption of 2H + and 2e - , proceeded on the same platform. Finally, the production of H 2 S from the disulfide-bridged complex was achieved.

Viral hepatitis was previously the most common cause of chronic liver disease. However, in recent years, nonalcoholic fatty liver disease (NAFLD) cases have been increasing, especially in developed countries. NAFLD is histologically characterized by fat, fibrosis, and inflammation in the liver, eventually leading to cirrhosis and hepatocellular carcinoma. Although biopsy is the gold standard for the assessment of the liver parenchyma, quantitative evaluation methods, such as ultrasound, CT, and MRI, have been reported to have good diagnostic performances. The quantification of liver fat, fibrosis, and inflammation is expected to be clinically useful in terms of the prognosis, early intervention, and treatment response for the management of NAFLD. The aim of this review was to discuss the basics and prospects of MRI-based tissue quantifications of the liver, mainly focusing on proton density fat fraction for the quantification of fat deposition, MR elastography for the quantification of fibrosis, and multifrequency MR elastography for the evaluation of inflammation.

The incidence of hepatocellular carcinoma (HCC) is still on the rise in North America and Europe and is the second leading cause of cancer-related mortality. The treatment of HCC varies, with surgery and locoregional therapy (LRT) such as radiofrequency ablation and transcatheter arterial chemoembolization, and radiation therapy being the primary treatment. Currently, systemic therapy with molecular-targeted agents and immune checkpoint inhibitors (ICIs) is becoming a major treatment option for the unresectable HCC. As the HCC after LRT or systemic therapy often remains unchanged in size and shows loss of contrast effect in contrast-enhanced CT or MRI, the response evaluation criteria in solid tumors (RECIST) and World Health Organization criteria, which are usually used to evaluate the treatment response of solid tumors, are not appropriate for HCC. The modified RECIST (mRECIST) and the European Association for the Study of the Liver (EASL) criteria were developed for HCC, with a focus on viable lesions. The latest 2018 edition of the Liver Imaging Reporting and Data System (LI-RADS) also includes a section on the evaluation of treatment response. The cancer microenvironment influences the therapeutic efficacy of ICIs. Several studies have examined the utility of gadoxetic acid-enhanced MRI for predicting the pathological and molecular genetic patterns of HCC. In the future, it may be possible to stratify prognosis and predict treatment response prior to systemic therapy by using pre-treatment imaging findings.

Purpose: To investigate the added value of contrast enhancement boost (CE-boost) images in multiphasic contrast-enhanced CT (CE-CT) for diagnosing small (<20 mm) hypervascular hepatocellular carcinoma (HCC)., Materials and Methods: This retrospective study included 69 patients (age, 74 ± 8 years; 52 men) with 70 hypervascular HCCs (<20 mm) who underwent multiphasic CE-CT (pre-contrast, late arterial phase [LAP], portal venous phase [PVP], and equilibrium phase). Two types of CE-boost images were generated by subtracting PVP from LAP (LA-PV) images and LAP from PVP (PV-LA) images to enhance the contrast effect of hepatic arterial and portal venous perfusion more selectively. Tumor-to-liver contrast-to-noise ratios (CNRs) in CE-boost images were compared with those in CE-CT images using the Wilcoxon signed-rank test. Two independent readers reviewed the imaging datasets: CE-CT alone and CE-CT with CE-boost images. The diagnostic performance of each dataset was compared using jackknife alternative free-response receiver operating characteristics (JAFROC-1)., Results: The tumor-to-liver CNRs in the LA-PV (6.4 ± 3.0) and PV-LA (-3.3 ± 2.1) images were greater than those in the LAP (3.2 ± 1.7) and PVP images (-1.1 ± 1.4) (p <.001 for both). The reader-averaged figures of merit were 0.751 for CE-CT alone and 0.807 for CE-CT with CE-boost images (p <.001). Sensitivities increased by adding CE-boost images for both readers (p <.001 and = 0.03), while positive predictive values were equivalent (p >.99)., Conclusion: Adding CE-boost images to multiphasic CE-CT can improve the diagnostic accuracy and sensitivity for small hypervascular HCC by increasing the tumor-to-liver CNR., Competing Interests: Declaration of Competing Interest M.H. is supported by grants from Canon Medical Systems Corporation. M.N. is an employee of Canon Medical Systems Corporation., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the effect of deep learning image reconstruction (DLIR) on the accuracy of iodine quantification and image quality of dual-energy CT (DECT) compared to that of other reconstruction algorithms in a phantom experiment and an abdominal clinical study., Methods: An elliptical phantom with five different iodine concentrations (1-12 mgI/mL) was imaged five times with fast-kilovoltage-switching DECT for three target volume CT dose indexes. All images were reconstructed using filtered back-projection, iterative reconstruction (two levels), and DLIR algorithms. Measured and nominal iodine concentrations were compared among the algorithms. Contrast-enhanced CT of the abdomen with the same scanner was acquired in clinical patients. In arterial and portal venous phase images, iodine concentration, image noise, and coefficients of variation for four locations were retrospectively compared among the algorithms. One-way repeated-measures analyses of variance were used to evaluate differences in the iodine concentrations, standard deviations, coefficients of variation, and percentages of error among the algorithms., Results: In the phantom study, the measured iodine concentrations were equivalent among the algorithms: within ± 8% of the nominal values, with root-mean-square deviations of 0.08-0.36 mgI/mL, regardless of radiation dose. In the clinical study (50 patients; 35 men; mean age, 68 ± 11 years), iodine concentrations were equivalent among the algorithms for each location (all p > .99). Image noise and coefficients of variation were lower with DLIR than with the other algorithms (all p < .01)., Conclusions: The DLIR algorithm reduced image noise and variability of iodine concentration values compared with other reconstruction algorithms in the fast-kilovoltage-switching dual-energy CT., Key Points: • In the phantom study, standard deviations and coefficients of variation in iodine quantification were lower on images with the deep learning image reconstruction algorithm than on those with other algorithms. • In the clinical study, iodine concentrations of measurement location in the upper abdomen were consistent across four reconstruction algorithms, while image noise and variability of iodine concentrations were lower on images with the deep learning image reconstruction algorithm., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

A 63-year-old man visited our hospital with a complaint of penile swelling caused by metallic ring entrapment in the penis. He had put the ring around his penis 4 hours prior and was subsequently unable to remove it. We attempted to remove the ring using a ring cutter but that was unsuccessful. We then inserted two 18 G needles into the corpus cavernosum through the glans penis and removed blood by manual compression according to a technique called the "string method." The swelling gradually decreased, and we successfully removed the ring without destroying it. The total duration of strangulation was about 5 hours. The patient was subsequently discharged after ensuring he had no urinary difficulties. No complications were observed during the follow-up period.In almost all penile strangulation cases caused by hard objects, such as metallic rings, reported in Japan, the objects were typically destroyed and penile puncture and blood removal, as was performed in our case, was rare. Although penile puncture and blood removal is not commonly performed in Japan, this technique can be performed quickly and inexpensively in the emergency room and should be considered an initial treatment for penile strangulation caused by hard objects.

Aim This study aimed to investigate early rehabilitation in the intensive care unit (ICU) for patients with severe coronavirus disease 2019 (COVID-19) who require mechanical ventilation Methods Twenty patients with severe COVID-19 (COVID-19 group) who were admitted to the ICU between April 2020 and March 2022 were included. For the control (non-COVID-19) group, 20 individuals were selected among ICU patients admitted between April 2018 and March 2020. The controls were propensity score-matched by age, sex, and Sequential Organ Failure Assessment (SOFA) score. Results In the COVID-19 group, the percentage of extubated patients was significantly higher. Furthermore, mechanical ventilation and lengths of ICU stay were also significantly longer. There were no significant differences in discharge outcomes or mortality, but there was a significant difference in the number of muscle relaxants and steroid treatments utilized with the COVID-19 group, requiring more of these medications. The percentage of patients who achieved sitting on the edge of a bed was also significantly higher in the COVID-19 group, but the days between the first rehabilitation and first sitting were significantly greater in this group. Conclusion Early rehabilitation of patients with COVID-19 may be an effective measure to promote recovery. However, continued investigation is warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Iwai et al.)

Background: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) is useful in detecting liver metastases from pancreatic ductal adenocarcinoma (PDAC). However, the long examination time limits its utility in the initial workup of patients with PDAC., Purpose: To evaluate the incremental value of an abbreviated gadoxetic acid-enhanced MRI for the detection of liver metastases in patients with PDAC., Study Type: Retrospective., Population: Patients (N = 130) with potentially resectable PDAC (women, 58 [44.6%])., Field Strength/sequence: 1.5 T and 3 T; gradient dual-echo T1-weighted (in-phase and opposed-phase), fat-suppressed fast spin-echo T2-weighted, single-shot echo-planar diffusion-weighted, and three-dimensional fat-suppressed T1-weighted gradient-echo dynamic contrast-enhanced and hepatobiliary phase sequences, as well as contrast-enhanced computed tomography (CECT)., Assessment: Three radiologists independently reviewed three different image sets to detect liver metastases: set 1, CECT alone; set 2, CECT and abbreviated MRI comprising fat-suppressed T2-weighted, diffusion-weighted, and hepatobiliary phase images; and set 3, CECT and standard gadoxetic acid-enhanced MRI., Statistical Tests: Figure of merit (FOM) was compared using the jackknife alternative free-response receiver operating characteristics, and other per-lesion and per-patient diagnostic parameters for each image set were compared using McNemar's and Fisher's test. P < 0.05 was considered statistically significant., Results: A total of 43 liver metastases were identified in 13 patients. Reader-averaged FOM to detect liver metastases were significantly higher for sets 2 (0.884) and 3 (0.886) than for set 1 (0.609), while they were comparable between sets 2 and 3 (P = 0.96). The mean per-patient sensitivities, negative predictive values, and accuracies were significantly higher for sets 2 and 3 than for set 1, while those between sets 2 and 3 were not significantly different (not applicable, P > 0.99, and P > 0.99, respectively)., Data Conclusion: Gadoxetic acid-enhanced MRI combined with CECT had higher diagnostic performance than CECT alone for the detection of liver metastases in patients with PDAC. The incremental values were comparable for the abbreviated MRI and standard MRI., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2022 International Society for Magnetic Resonance in Medicine.)

We performed in-vitro germination tests on seeds from five Gastrodia orchids ( G. confusa , G. elata var. elata , G. elata var. pallens , G. nipponica , and G. pubilabiata ) using one Marasmiaceae and two Mycena isolates. Mycena sp. 1 promoted germination of all five Gastrodia orchids, with root and/or tuber formation observed in G. confusa , G. nipponica , and G. pubilabiata . No additional growth was observed in the other two orchids. Mycena sp. 2 induced G. confusa , G. elata var. elata , and G. nipponica germination, whereas Marasmiaceae sp. 1 induced G. nipponica and G. pubilabiata germination. Phylogenetic analyses indicated that the two Mycena isolates represent distinct lineages within the Mycenaceae . Mycena sp. 1 and Marasmiaceae sp. 1 are closely related to Mycena abramsii and Marasmiellus rhizomorphogenus , respectively. Our results imply that Mycena and marasmioid fungi play important roles in early development in Gastrodia species, and that Mycena fungi in particular may be common mycobionts of Gastrodia species. Root and/or tuber development was observed with four plant-fungus combinations, implying that these associations persist throughout the life cycle, whereas G. elata var. elata may require different associates over time. Our findings will contribute to elucidating the mycorrhizal associations of mycoheterotrophic orchids throughout their life cycle., (2022, by The Mycological Society of Japan.)

Objective: To investigate the diagnostic performance of the extracellular volume (ECV) fraction in multiphasic contrast-enhanced computed tomography (CE-CT) for estimating histologic pancreatic fibrosis and predicting postoperative pancreatic fistula (POPF)., Methods: Eighty-five patients (49 men; mean age, 69 years) who underwent multiphasic CE-CT followed by pancreaticoduodenectomy with pancreaticojejunal anastomosis between January 2012 and December 2018 were retrospectively included. The ECV fraction was calculated from absolute enhancements of the pancreas and aorta between the precontrast and equilibrium-phase images, followed by comparisons among histologic pancreatic fibrosis grades (F0‒F3). The diagnostic performance of the ECV fraction in advanced fibrosis (F2‒F3) was evaluated using receiver operating characteristic curve analysis. Multivariate logistic regression analysis was used to evaluate the associations of the risk of POPF development with patient characteristics, histologic findings, and CT imaging parameters., Results: The mean ECV fraction of the pancreas was 34.4% ± 9.5, with an excellent intrareader agreement of 0.811 and a moderate positive correlation with pancreatic fibrosis (r = 0.476; p < 0.001). The mean ECV fraction in advanced fibrosis was significantly higher than that in no/mild fibrosis (44.4% ± 10.8 vs. 31.7% ± 6.7; p < 0.001), and the area under the receiver operating characteristic curve for the diagnosis of advanced fibrosis was 0.837. Twenty-two patients (25.9%) developed clinically relevant POPF. Multivariate logistic regression analysis demonstrated that the ECV fraction was a significant predictor of POPF., Conclusions: The ECV fraction can offer quantitative information for assessing pancreatic fibrosis and POPF after pancreaticojejunal anastomosis., Key Points: • There was a moderate positive correlation of the extracellular volume (ECV) fraction of the pancreas in contrast-enhanced CT with the histologic grade of pancreatic fibrosis (r = 0.476; p < 0.001). • The ECV fraction was higher in advanced fibrosis (F2‒F3) than in no/mild fibrosis (F0‒F1) (p < 0.001), with an AUC of 0.837 for detecting advanced fibrosis. • The ECV fraction was an independent risk factor for predicting subclinical (odds ratio, 0.81) and clinical (odds ratio, 0.80) postoperative pancreatic fistula., (© 2021. European Society of Radiology.)

Aim: High mobility group box-1 (HMGB1) is a lethal mediator of sepsis that binds to haptoglobin (Hp) and is associated with its prognosis. We investigated the effect of the combination of HMGB1 and Hp on sepsis prognosis., Methods: This single-center, retrospective study registered 78 patients with sepsis according to Sepsis-3 criteria on day 1 of diagnosis from July 2016 to November 2018. We divided the patients into four groups according to the serum concentration of 6.2 ng/mL HMGB1 and the median value of Hp. The 180-day mortality rates and cytokine concentrations of the low and high HMGB1 groups were compared., Results: There was no difference in the 180-day mortality rate between the low Hp group and the high Hp group in the low HMGB1 group ( P  = 0.691). In the high HMGB1 group, a statistically significant difference was found between the low Hp group and the high Hp group ( P  = 0.002). In the high HMGB1 group, high Hp was associated with a better prognosis in univariate analysis (odds ratio, 0.131; 95% confidence interval [CI], 0.027-0.629; P  = 0.011), and multivariate analysis (adjusted odds ratio, 0.086; 95% CI, 0.013-0.582; P  = 0.009). In addition, in the high HMGB1 group, interleukin-8 levels were significantly higher in the low Hp group than in the high Hp group ( P  = 0.004)., Conclusion: Patients with sepsis-induced high serum HMGB1 levels and low serum Hp levels could have a poor long-term prognosis., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Plasma fibrinogen levels increase in response to infection, but they could also decrease due to degradation as in severe coagulopathy. We evaluated 60 septic patients with their CRP levels over 5.00 mg/dL. The patients were classified into three groups based on the ratio of the maximum or minimum fibrinogen concentration within day 3 to the initial concentration on day 0: down-, flat, and uptrend groups (n = 15, 30, and 15, respectively). Both down- and flat trend groups showed reduced inflammatory markers on day 3, and the degree of platelet loss (10 3 /μL) and the mortality rate (%) were more remarkable in the downtrend group ( - 108 vs  - 42 [ p  = 0.026] and 46.7 vs 10.0 [ p  = 0.027]). On day 0, in total 12 and 9 patients were diagnosed with non-overt DIC in the down- and uptrend groups, of which 5 (41.7%) and 1 (11.1%) died within 28 days after admission. In conclusion, decreasing fibrinogen levels in the ICU are associated with high mortality in patients with sepsis followed by decreasing platelet counts, even when they are diagnosed with non-overt DIC.

Primer bias toward Tulasnellaceae fungi during PCR is a known issue with metabarcoding analyses for the assessment of orchid mycorrhizal communities. However, this bias had not been evaluated for the fungal communities of epiphytic orchids, which account for 69% of all orchid species diversity. We compared the mycorrhizal communities detected using two primer pairs, a fungal universal primer pair (ITS86F/ITS4) and Tulasnella -specific primer pair (5.8STulngs/ITS4-Tul2), using a mock community of fungal isolates from epiphytic orchids and also environmental samples, including orchid roots and a tree bark tip from the host tree of an epiphytic orchid collected. The detected mycorrhizal communities differed widely depending on the primer pairs used. The fungal universal primer pair successfully identified Ceratobasidiaceae and Serendipitaceae fungi but did not reflect Tulasnellaceae diversity. Tulasnellaceae fungi were mainly detected using the Tulasnella -specific primer pair. These tendencies were observed in both the mock community and environmental samples. These results strongly suggest that the use of a Tulasnella -specific primer in combination with a fungal universal primer is essential for assessing the mycorrhizal communities of orchids through metabarcoding analysis, especially in epiphytic orchids. Our study contributes to further understanding of the diversity of mycorrhizal fungi in orchids., (2021, by The Mycological Society of Japan.)

Background: The transition process of migration to work abroad can be challenging and, depending on how it is handled, can impact the job satisfaction level of these foreign-educated nurses. A clear understanding of migrant nurses' job satisfaction is critical for effective translation of nursing practice across the health systems and cultures., Objective: This study examined the job satisfaction of the foreign-educated nurses in Malaysia, which includes the job satisfaction dimensions and the significant difference between sociodemographic status and job satisfaction., Methods: A cross-sectional survey of 102 foreign-educated nurses working in private hospitals, clinics, hemodialysis centers, nursing homes, and private homes in Malaysia was conducted from September 2017 to March 2018. Data were collected using a structured questionnaire. Descriptive statistics, Mann-Whitney U, and Kruskal Wallis tests were used to analyze the data., Results: The study revealed that the participants had a median satisfaction score of 22 ( IQR = 19 to 24). Serving the sick and needy and participants' self-respect were the highest satisfaction dimensions among the participants ( Median = 3, IQR = 3 to 3). Moreover, the job satisfaction was significantly higher for registered foreign-educated nurses (mean rank = 62.5) than for unregistered foreign-educated nurses (mean rank = 48.65) when working in other countries ( p = 0.02). Indian nurses (mean rank = 60.36) also expressed higher satisfaction in terms of working in other countries than Filipino nurses (mean rank = 46.88; p = 0.02). In addition, positive relationships with colleagues and superiors led to higher satisfaction among Indian nurses (mean rank = 61.02) than among Filipino nurses (mean rank = 47.24; p = 0.04). The job satisfaction of male foreign-educated nurses was significantly higher than their female counterparts in terms of self-respect, relationship with fellow nurses and superiors, working in other countries, career development, and ease of finding employment ( p < 0.05)., Conclusion: The overall job satisfaction among the foreign-educated nurses in Malaysia is high, mainly when serving the sick and needy, and their degree of self-respect. Understanding job satisfaction among foreign-educated nurses in Malaysia enables the management team to develop effective strategies for addressing nursing shortages and improving the quality of patient care., Competing Interests: The authors have no conflict of interest to disclose., (© The Author(s) 2021.)

Background: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients.Methods and Results:In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%., Conclusions: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

Objectives: This study investigated retrospectively the effect of early rehabilitation in the intensive care unit (ICU) by a dedicated therapist using a rehabilitation protocol., Methods: The subjects comprised patients admitted to our emergency ICU. A dedicated therapist and a rehabilitation protocol were instigated in April 2018. We enrolled 330 patients in phase I (April 2016-March 2018) and 383 patients in phase II (April 2018-March 2020). Patients in the ICU for only one night and pediatric patients were excluded. The following data were accessed from medical records: sex, height, age, Sequential Organ Failure Assessment, rehabilitation intervention, ventilation at admission, duration of mechanical ventilation, extubation, reintubation, tracheotomy, length of ICU stay, length of hospital stay, and outcome. The effectiveness of rehabilitation was assessed using the time from ICU admission to the first rehabilitation session, first sitting exercise, and first standing exercise. Clinical outcomes were analyzed separately for subjects discharged to home or transferred to another hospital., Results: The percentage of subjects undergoing rehabilitation intervention increased significantly from 23.4% to 56.7% (P<0.001) in phase II. Moreover, reintubation (P=0.045); the length of ICU stay (P=0.022); and the time from ICU admission to the first rehabilitation session (P<0.001), the first sitting exercise (P=0.001), and the first standing exercise (P=0.047) significantly decreased in phase II. Furthermore, the duration of mechanical ventilation (P=0.007) and the length of ICU stay (P=0.036) were significantly reduced in the transfer group., Conclusions: Although the effectiveness of early intervention was suggested, prospective multicenter studies are required to confirm this finding., Competing Interests: CONFLICTS OF INTEREST: None of the authors have any conflicts of interest to disclose., (©2021 The Japanese Association of Rehabilitation Medicine.)

Background: Recently, dynamic chest radiography (DCR) was developed to evaluate pulmonary function using a flat-panel detector (FPD), which can evaluate blood flow in the pulmonary artery without injection of contrast agents. This study investigated the ability of a FPD to measure physiological changes in blood flow and to detect pulmonary embolism (PE) in monkeys.Methods and Results:DCR was performed in 5 monkeys using a FPD. Regions of interest (ROI) were placed in both lung fields of the image, and maximum changes in pixel value (∆pixel value) in the ROI were measured during 1 electrocardiogram cardiac cycle. Next, a PE model was induced using a Swan-Ganz catheter and additional images were taken. The ∆pixel value of the lungs in normal and PE models were compared in both supine and standing positions. The lung ∆pixel value followed the same cycle as the monkey electrocardiogram. ∆pixel values in the upper lung field decreased in the standing as compared to the supine position. In the PE model, the ∆pixel value decreased in the area of pulmonary blood flow occlusion and increased in the contralateral lung as compared to the normal model (normal model 1.287±0.385, PE model occluded side 0.428±0.128, PE model non-occluded side 1.900±0.431)., Conclusions: A FPD could detect postural changes in pulmonary blood flow and its reduction caused by pulmonary artery occlusion in a monkey model.

Aim: We aimed to investigate the association between aortic calcification and 90-day mortality in sepsis patients admitted to the intensive care unit., Methods: We evaluated adult patients (≥18 years) diagnosed with sepsis based on the Sepsis-3 criteria and admitted to our intensive care unit between April 2011 and March 2015. They were classified according to the degree of abdominal aortic calcification (severe and non-severe), grouped per age (<65, 65-75, and >75 years), and matched. Survival curves were generated, and between-group differences were evaluated., Results: Overall, 164 patients were included. The Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were not significantly different between the severity groups, whereas there were significant differences in age ( P  < 0.001), sex ( P  = 0.017), and presence of diabetes mellitus ( P  < 0.001), hypertension ( P  < 0.001), dyslipidemia ( P  = 0.048), and maintenance dialysis ( P  = 0.001). The severe abdominal aortic calcification group showed significantly poorer prognosis than the non-severe group (log-rank P  = 0.009). The adjusted odds ratio of severe calcification was the highest in patients aged <65 years (7.167; 95% confidence interval, 1.042-49.28, P  = 0.045). Twenty-eight patients from each group were matched. The 90-day survival rate of the severe calcification group remained significantly lower than that of the non-severe calcification group (53.6% [15/28] versus 82.1% [23/28], P  = 0.022)., Conclusions: Severe abdominal aortic calcification is associated with the 90-day mortality of sepsis patients, particularly among those aged <65 years. Thus, caution is necessary in patients younger than 65 years; they may need to be treated with as much care as the elderly., Competing Interests: Approval of the research protocol: The protocol for this research project was approved by a suitably constituted Committee of Shiga Medical University Hospital (approval No. R2019‐197) and it conforms to the provisions of the Declaration of Helsinki. Informed consent: Informed consent was obtained from all the subjects. Registry and registration no. of the study/trial: N/A. Animal studies: N/A. Conflict of interest: None., (© 2021 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Aim: The complement system is important for defending against pathogens, however, excessive complement activation is associated with a poor prognosis and organ dysfunction in sepsis. Complement factor H (CFH) acts to prevent excessive complement activation and damage to the self through the regulation of the complement alternative pathway. We investigated the association between plasma CFH levels on admission to the intensive care unit (ICU) and 90-day mortality, severity scores, and organ dysfunction in patients with sepsis., Methods: We assessed the relationship between the plasma CFH on admission to the ICU and 90-day mortality, severity scores such as the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and Simplified Acute Physiology Score 2, and organ dysfunction., Results: This analysis included 62 patients. The plasma CFH levels were significantly lower in 90-day non-survivors than in survivors (70.0 μg/mL [interquartile range, 51.2-97.6] versus 104.8 μg/mL [interquartile range, 66.8-124.2]; P  = 0.006) . The plasma CFH levels were associated with 90-day mortality (odds ratio 0.977; 95% confidence interval, 0.957-0.994; P  = 0.01). The plasma CFH levels were negatively correlated with severity scores. The Sequential Organ Failure Assessment scores for the coagulation and neurological components were negatively correlated with the CFH concentration., Conclusion: Lower plasma levels of CFH were associated with increased severity and mortality in patients with sepsis on admission to the ICU and were correlated with central nervous system dysfunction and coagulopathy., Competing Interests: Ethical approval: This study was approved by the Scientific‐Ethical Committees of Shiga University of Medical Science (protocol ID R2015‐220). Informed consent: Written informed consent to participate in this study was obtained from the patients or their relatives. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. Conflict of interest: None., (© 2021 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Mycoheterotrophic plants (MHPs) are leafless, achlorophyllous, and completely dependent on mycorrhizal fungi for their carbon supply. Mycorrhizal symbiosis is a mutualistic association with fungi that is undertaken by the majority of land plants, but mycoheterotrophy represents a breakdown of this mutualism in that plants parasitize fungi. Most MHPs are associated with fungi that are mycorrhizal with autotrophic plants, such as arbuscular mycorrhizal (AM) or ectomycorrhizal (ECM) fungi. Although these MHPs gain carbon via the common mycorrhizal network that links the surrounding autotrophic plants, some mycoheterotrophic lineages are associated with saprotrophic (SAP) fungi, which are free-living and decompose leaf litter and wood materials. Such MHPs are dependent on the forest carbon cycle, which involves the decomposition of wood debris and leaf litter, and have a unique biology and evolutionary history. MHPs associated with SAP fungi (SAP-MHPs) have to date been found only in the Orchidaceae and likely evolved independently at least nine times within that family. Phylogenetically divergent SAP Basidiomycota, mostly Agaricales but also Hymenochaetales, Polyporales, and others, are involved in mycoheterotrophy. The fungal specificity of SAP-MHPs varies from a highly specific association with a single fungal species to a broad range of interactions with multiple fungal orders. Establishment of symbiotic culture systems is indispensable for understanding the mechanisms underlying plant-fungus interactions and the conservation of MHPs. Symbiotic culture systems have been established for many SAP-MHP species as a pure culture of free-living SAP fungi is easier than that of biotrophic AM or ECM fungi. Culturable SAP-MHPs are useful research materials and will contribute to the advancement of plant science.

Premise: Orchids depend primarily on mycorrhizal fungi to obtain nutrients throughout their life cycle. Epiphytic orchids account for 69% of orchid diversity. The unstable availability of water and nutrients in their arboreal habitats often results in severe water and nutrient stresses. Consequently, mycorrhizal associations may be important for the survival of epiphytic orchids, but our understanding thereof remains limited. Here, we investigated the mycorrhizal community in a single epiphytic orchid species, using more samples than in any previous study., Methods: We assessed the mycorrhizal communities of Thrixspermum japonicum, one of the most common epiphytic orchids in the temperate region of Japan. In total, 144 individuals were collected from 28 host tree species at 20 sites across 1300 km. The mycorrhizal fungi were identified based on nuclear ribosomal DNA internal transcribed spacer sequences and assigned operational taxonomic units (OTUs) based on 97% sequence similarity., Results: We obtained 24 OTUs; 9 belonged to the Ceratobasidiaceae and 15 to the Tulasnellaceae. These OTUs are widely distributed throughout the phylogenetic trees of the two fungal families. However, a single Ceratobasidiaceae OTU accounted for 49.7% of all fungal sequences and was predominant in samples from 15 host tree species and 12 sites., Conclusions: Our results imply that despite having a broad range of mycorrhizal partners, T. japonicum was predominantly associated with a single fungal taxon at most of the sites among the host-tree species investigated. These findings contribute to elucidating mycorrhizal symbiosis in epiphytic habitats., (© 2020 Botanical Society of America.)

Purpose: Accurate prediction of post-hepatectomy liver failure (PHLF) is important in advanced hepatocellular carcinoma (HCC). We aimed to retrospectively evaluate the utility of gadoxetic acid-enhanced MRI for predicting PHLF in patients who underwent anatomic hepatectomy for HCC with portal vein invasion., Methods: Forty-one patients (32 men, 9 women) were included. Hepatobiliary-phase MR images were acquired 20 min after injection of gadoxetic acid using a 3D fat-suppressed T1-weighted spoiled gradient-echo sequence. Liver-spleen ratio (LSR), remnant hepatocellular uptake index (rHUI), and HUI were calculated. The severity of PHLF was defined according to the International Study Group of Liver Surgery. Differences in LSR between the resected liver and the remnant liver, and HUI and rHUI/HUI between no/mild and severe PHLF were compared using the Wilcoxon signed-rank test and Wilcoxon rank-sum test, respectively. Univariate and multivariate logistic regression analyses were performed to identify predictors of severe PHLF. Areas under the receiver operating characteristic curves (AUCs) of rHUI and rHUI/HUI were calculated for predicting severe PHLF., Results: Nine patients developed severe PHLF. LSR of the remnant liver was significantly higher than that of the resected liver (P < 0.001). Severe PHLF demonstrated significantly lower rHUI (P < 0.001) and rHUI/HUI (P < 0.001) compared with no/mild PHLF. Multivariate logistic regression analysis showed that decreased rHUI (P = 0.012, AUC=0.885) and rHUI/HUI (P = 0.002, AUC=0.852) were independent predictors of severe PHLF., Conclusion: Gadoxetic acid-enhanced MRI can be a promising noninvasive examination for assessing global and regional liver function, allowing estimation of the functional liver remnant and accurate prediction of severe PHLF before hepatic resection., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: We sought to investigate the efficacy of perioperative tight glycemic control (TGC) in reducing of postoperative infectious complications (POICs) and study its impact on early inflammatory mediators in patients who underwent pancreaticoduodenectomy., Methods: In this non-randomized trial, the artificial pancreas (AP) group received TGC (target glucose range of 80-110 mg/dL; n = 14), while the control group received conventional glycemic control (range of 80-180 mg/dL; n = 15). The primary endpoint was POICs., Results: The AP group had a markedly decreased POIC rate (28.6% vs. 73.3%; P = 0.027), mean glycemic variability (13.5 ± 3.5% vs. 16.4 ± 5.9%; P = 0.038), and plasma interleukin-6 level (26.3 ± 33.8 vs 98.3 ± 89.1 pg/ml; P = 0.036) compared to the control group, but insulin dosage (27.0 ± 13.4 vs. 10.2 ± 16.2 U; P = 0.002) and the adiponectin ratio (i.e., postoperative/preoperative adiponectin; 0.8 ± 0.2 vs. 0.6 ± 0.3; P = 0.021) were markedly higher in the AP group., Conclusions: Among patients undergoing PD with impaired glucose tolerance, AP facilitated strict glycemic control and resulted in a reduction of anti-inflammatory mediators and POICs., Summary: Perioperative hyperglycemia increases postoperative infectious complications; however, tight glycemic control using artificial pancreas can reduce them via a dual effect. Artificial pancreas facilitates strict and safe glycemic control while reducing anti-inflammatory mediators, including adiponectin, following pancreaticoduodenectomy., Competing Interests: Declaration of competing interest The authors declare no other conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Neutrophils contribute to the clearance of pathogens through the formation of neutrophil extracellular traps (NETs) in a process known as NETosis, but the excessive release of NETs has been reported to be involved in the pathogenesis of various diseases, including vasculitis, by inducing tissue injury. The aim of the present study was to investigate whether or not NETosis is enhanced in the acute phase of Kawasaki disease (KD)., Methods: After neutrophils isolated from the peripheral blood of patients with KD and healthy control (HC) were cultured in vitro, the degree of spontaneous NETosis was evaluated by measuring the number of NETs formed and the titers of cell-free DNA (cfDNA) and neutrophil elastase (NE)-DNA complex., Results: Spontaneous NET formation in vitro was observed in neutrophils isolated from KD patients, and the number of NET formations was significantly higher in acute KD than in convalescent KD and HC. The increased levels of cfDNA and NE-DNA complexes in the acute phase of KD tended to decrease in the convalescent phase., Conclusions: Spontaneous NET formation was enhanced in neutrophils from patients with acute KD, suggesting that circulating neutrophils may be primed to undergo NETosis in KD vasculitis.

A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis. In addition to providing a cell and protein-rich environment for cancer growth and progression, ascitic fluid also confers physical stress on tumors. An understudied area in ovarian cancer research is the impact of fluid shear stress on treatment failure. Here, we investigate the effect of fluid shear stress on response to platinum-based chemotherapy and the modulation of molecular pathways associated with aggressive disease in a perfusion model for adherent 3D ovarian cancer nodules. Resistance to carboplatin is observed under flow with a concomitant increase in the expression and activation of the epidermal growth factor receptor (EGFR) as well as downstream signaling members mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and extracellular signal-regulated kinase (ERK). The uptake of platinum by the 3D ovarian cancer nodules was significantly higher in flow cultures compared to static cultures. A downregulation of phospho-focal adhesion kinase (p-FAK), vinculin, and phospho-paxillin was observed following carboplatin treatment in both flow and static cultures. Interestingly, low-dose anti-EGFR photoimmunotherapy (PIT), a targeted photochemical modality, was found to be equally effective in ovarian tumors grown under flow and static conditions. These findings highlight the need to further develop PIT-based combinations that target the EGFR, and sensitize ovarian cancers to chemotherapy in the context of flow-induced shear stress., Competing Interests: The authors declare no conflict of interest.

We had previously reported a prostaglandin E synthase (bmPGES) in the silkworm Bombyx mori that catalyzes the isomerization of PGH 2 to PGE 2 . The present study aimed to provide a genome-editing characterization of bmPGES in B. mori. Results showed bmPGES gene disruption to result in a reduced content of PGE 2 . The change affected the expression of chorion genes and egg formation in silkworms. Collectively, the results indicated that bmPGES could be involved in reproduction of B. mori. Therefore, this study provides insights into the physiological role of bmPGES and PGE 2 in silkworms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mycorrhizal symbiosis between plants and fungi is ubiquitous, and has been played key roles in plant terrestrialization and diversification. Although arbuscular mycorrhizal (AM) symbioses with Glomeromycotina fungi have long been recognized as both ancient and widespread symbionts, recent studies showed that Mucoromycotina fungi were also ancestral symbionts and would thus be expected to co-exist with many land plants. To explore whether Mucoromycotina colonize fern gametophytes, we subjected fungal associations with gametophytes of two distantly related ferns, Angiopteris lygodiifolia (Marattiales) and Osmunda japonica (Osmundales), to molecular analysis. Direct PCR amplification from intracellular hyphal coils was also performed. We detected Mucoromycotina sequences in the gametophytes of A. lygodiifolia and O. japonica at rates of 41% (7/17) and 50% (49/98) of gametophytes, respectively, and assigned them to 10 operational taxonomic units of Endogonales lineages. In addition, we used AM fungal-specific primers and detected Glomeromycotina sequences in all individuals examined. The results suggest that Glomeromycotina and Mucoromycotina colonized fern gametophytes simultaneously. We found that Mucoromycotina were present in fern gametophytes of Marratiales and Osmundales, which implies that a variety of fern taxa have Mucoromycotina associations.

Cardiogenic shock frequently leads to death even with intensive treatment. Although the leading cause of cardiogenic shock is acute coronary syndrome (ACS), the clinical characteristics and the prognosis of ACS with cardiogenic shock in the present era still remain to be elucidated. We analyzed clinical characteristics and predictors of 30-day mortality in ACS with cardiogenic shock in Japan. The Japanese Circulation Society Cardiovascular Shock registry was a prospective, observational, multicenter, cohort study. Between May 2012 and June 2014, 495 ACS patients with cardiogenic shock were analyzed. The primary endpoint was 30-day all-cause mortality. The median [interquartile range; IQR] age was 71.0 [63.0, 80.0] years. The median [IQR] value of systolic blood pressure (SBP) and heart rate were 75.0 [50.0, 86.5] mm Hg and 65.0 [38.0, 98.0] bpm, respectively. Multivariable analysis showed an odds ratio (OR) of 4.76 (confidence intervals; CI 1.97-11.5, p < 0.001) in the lowest SBP category (< 50 mm Hg) for SBP ≥ 90 mm Hg. Moreover, age per 10 years increase (OR 1.38, CI 1.18-1.61, p = 0.002), deep coma (OR 3.49, CI 1.94-6.34, p < 0.001), congestive heart failure (OR 3.81, CI 2.04-7.59, p < 0.001) and left main trunk disease (LMTD) (OR 2.81, CI 1.55-5.10, p < 0.001) were independent predictors. Severe hypotension, older age, deep coma, congestive heart failure, and LMTD were independent unfavorable factors in ACS complicated by cardiogenic shock in Japan. A prompt assessment of high-risk patients referring to those predictors in emergency room could lead to appropriate treatment without delay.

Aim: The effect of polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is controversial. The present study investigates whether outcome in septic shock patients is affected by the time until PMX-DHP initiation and the location of the infection site (intra- or extra-abdominal infection (IAI/EAI)]., Methods: This retrospective observational study included patients receiving PMX-DHP for septic shock but excluded those treated after cardiac surgery or cardiac arrest. Based on the median and/or quartile time from catecholamine treatment to PMX-DHP initiation, the patient cohort was divided into four groups and the IAI and EAI groups into two subgroups., Results: Among the 49 eligible patients, overall 90-day mortality in group 1 (PMX-DHP within 6 h) at 8.3% was significantly lower than in groups 2 (6-9 h; 46.1%), 3 (9-29 h; 58.3%) and 4 (>29 h; 75.0%) ( P  =   0.021). Multivariate logistic regression analysis showed that the duration from catecholamine treatment to PMX-DHP initiation correlated with 90-day mortality (odds ratio 1.060; 95% confidence interval, 1.004-1.117; P  =   0.028). Among the 29 IAI patients, 90-day mortality was significantly lower in the early (within 9 h) than the late group (>9 h) (13.3% versus 64.2%; P  =   0.003), but no significant intergroup difference was noted among the 20 EAI patients., Conclusion: Our results suggest that early PMX-DHP initiation (within 9 h after catecholamine treatment) reduces mortality from septic shock, especially in IAI patients., (© 2019 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Leafless epiphytes in the Orchidaceae undergo a morphological metamorphosis in which the root has chloroplast-containing cortical cells and is the sole photosynthetic organ for carbon gain. All orchids are entirely dependent on mycorrhizal fungi for their carbon supply during seed germination, and this mycorrhizal association generally persists in adult plants. However, our knowledge of the mycorrhizal association of leafless epiphytic orchids remains limited, and the contribution of the mycorrhizal association to nutrient acquisition in these orchid species is largely unknown. In this study, the mycorrhizal fungi of a leafless epiphytic orchid, Taeniophyllum glandulosum, were identified molecularly using 68 mature plants and 17 seedlings. In total, 187 fungal internal transcribed spacer sequences were obtained, of which 99% were identified as Ceratobasidiaceae. These sequences were classified into five operational taxonomic units (OTUs) based on 97% sequence similarity. The most frequent sequence was OTU1, which accounted for 91% of all Ceratobasidiaceae sequences, although other phylogenetically distinct Ceratobasidiaceae fungi were detected. These results show that T. glandulosum is specifically associated with a particular group of Ceratobasidiaceae. All mycorrhizal fungi found in T. glandulosum seedlings belonged to OTU1, which was also found in adult plants on the same host tree. The mycorrhizal fungi from 13 host tree species were compared, and T. glandulosum was preferentially associated with OTU1 on 11 tree species. In conclusion, T. glandulosum is specifically associated with Ceratobasidiaceae fungi and this specific association remains throughout the orchid life cycle and is found on divergent host tree species.

Background: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined., Objective: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT., Methods: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities., Results: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT., Conclusion: Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aim: To examine lymphocyte counts as a predictive prognostic marker in patients with coma after cardiac arrest., Methods: We retrospectively evaluated patients with coma after cardiac arrest admitted to the intensive care unit of Shiga University of Medical Science (Otsu, Japan). Lymphocyte counts were measured for 6 days from admission. Neurological outcome was assessed as favorable or unfavorable using cerebral performance categories. Associations between lymphocyte count and prognosis were investigated using multivariate logistic regression analysis and receiver operating characteristic curves., Results: Forty-six patients were assessed from February 2012 to December 2016. Survivors had significantly higher lymphocyte counts than non-survivors on days 2 and 5. Multivariate analysis showed that lymphocyte count was not associated with 90-day mortality. Patients with favorable neurological outcome at discharge had significantly higher lymphocyte counts on days 2-6 than patients with unfavorable outcomes. Multivariate logistic regression analysis, including possible confounders, showed that lymphocyte counts on days 2-4 and 6 were associated with neurological outcome (day 2: odds ratio [OR] = 0.75, 95% confidence interval [CI] = 0.58-0.97, P  = 0.029; day 3: OR = 0.68, 95% CI = 0.47-0.98, P  = 0.04; day 4: OR = 0.4, 95% CI = 0.16-1.00, P  = 0.05; day 6: OR = 0.69, 95% CI = 0.48-0.99, P  = 0.046). Receiver operating characteristic curve analysis indicated high accuracy for predicting neurological outcome for each lymphocyte count on days 2-6 using the area under the curve, day 4 values being most accurate (day 2: 0.776, day 3: 0.787, day 4: 0.909, day 5: 0.774, day 6: 0.839)., Conclusion: Lymphocyte counts on days 2-4 and 6 after cardiac arrest are associated with neurological outcome; counts on day 4 most accurately predict neurological outcome.

Activated PI3Kδ syndrome (APDS) is a primary immunodeficiency characterized by recurrent respiratory tract infections, lymphoproliferation, and defective IgG production. Heterozygous mutations in PIK3CD, PIK3R1 , or PTEN , which are related to the hyperactive phosphoinositide 3-kinase (PI3K) signaling, were recently presented to cause APDS1 or APDS2 (APDSs), or APDS-like (APDS-L) disorder. In this study, we examined the AKT phosphorylation of peripheral blood lymphocytes and monocytes in patients with APDSs and APDS-L by using flow cytometry. CD19 + B cells of peripheral blood in APDS2 patients showed the enhanced phosphorylation of AKT at Ser473 (pAKT) without any specific stimulation. The enhanced pAKT in CD19 + B cells was normalized by the addition of a p110δ inhibitor. In contrast, CD3 + T cells and CD14 + monocytes did not show the enhanced pAKT in the absence of stimulation. These findings were similarly observed in patients with APDS1 and APDS-L. Among CD19 + B cells, enhanced pAKT was prominently detected in CD10 + immature B cells compared with CD10 - mature B cells. Enhanced pAKT was not observed in B cells of healthy controls, patients with common variable immunodeficiency, and hyper IgM syndrome due to CD40L deficiency. These results suggest that the enhanced pAKT in circulating B cells may be useful for the discrimination of APDS1, APDS2, and APDS-L from other antibody deficiencies.

Objective: In the current study, we aimed to accurately evaluate donor/recipient or male/female chimerism in samples from patients who underwent hematopoietic stem cell transplantation (HSCT)., Methods: We designed the droplet digital polymerase chain reaction (ddPCR) for SRY and RPP30 to detect the male/female chimerism. We also developed mutation-specific ddPCR for four primary immunodeficiency diseases., Results: The accuracy of the male/female chimerism analysis using ddPCR was confirmed by comparing the results with those of conventional methods (fluorescence in situ hybridization and short tandem repeat-PCR) and evaluating dilution assays. In particular, we found that this method was useful for analyzing small samples. Thus, this method could be used with patient samples, especially to sorted leukocyte subpopulations, during the early post-transplant period. Four mutation-specific ddPCR accurately detected post-transplant chimerism., Conclusion: ddPCR-based male/female chimerism analysis and mutation-specific ddPCR were useful for all HSCT, and these simple methods contribute to following the post-transplant chimerism, especially in disease-specific small leukocyte fractions.

The climbing orchid Erythrorchis altissima is the largest mycoheterotroph in the world. Although previous in vitro work suggests that E. altissima has a unique symbiosis with wood-decaying fungi, little is known about how this giant orchid meets its carbon and nutrient demands exclusively via mycorrhizal fungi. In this study, the mycorrhizal fungi of E. altissima were molecularly identified using root samples from 26 individuals. Furthermore, in vitro symbiotic germination with five fungi and stable isotope compositions in five E. altissima at one site were examined. In total, 37 fungal operational taxonomic units (OTUs) belonging to nine orders in Basidiomycota were identified from the orchid roots. Most of the fungal OTUs were wood-decaying fungi, but underground roots had ectomycorrhizal Russula. Two fungal isolates from mycorrhizal roots induced seed germination and subsequent seedling development in vitro. Measurement of carbon and nitrogen stable isotope abundances revealed that E. altissima is a full mycoheterotroph whose carbon originates mainly from wood-decaying fungi. All of the results show that E. altissima is associated with a wide range of wood- and soil-inhabiting fungi, the majority of which are wood-decaying taxa. This generalist association enables E. altissima to access a large carbon pool in woody debris and has been key to the evolution of such a large mycoheterotroph., (© 2018 John Wiley & Sons Ltd.)

Purpose: A 42-year-old man with hyper-IgM syndrome type 2 caused by activation-induced cytidine deaminase (AID) deficiency developed a severe anaphylactic reaction to intravenous immunoglobulin. The purpose of this study was to clarify the cause of the anaphylactic reaction of the patient., Methods: We measured IgM-class anti-human IgG and anti-human IgA antibodies in his serum by sandwich enzyme-linked immunosorbent assay (ELISA)., Results: The sandwich ELISA assay revealed that serum from the patient, but not the controls, reacted to three different IgG products and purified human IgA. This indicated that the patient had IgM-class anti-human IgG and IgA antibodies in his serum, which associated with the anaphylactic reactions after the administration of IgG products. The anti-IgG antibody was likely to be the main cause of the reactions because an IgA-depleted IgG product also induced a severe reaction in this case and showed high absorbance in the ELISA system, similar to other IgG products containing more IgA., Conclusions: This is the first report of IgM-class anti-human IgG associated with an anaphylactic reaction to an IgG infusion. The anaphylactic reactions were very severe in this case, probably because IgM-class antibodies are potent activators of the complement pathway.

Background: Mycoheterotrophic plants are one of the most difficult plant groups to conserve because they are entirely dependent on symbiotic fungi. Establishment of viable culture systems would greatly aid their conservation. We describe a simple culture system for the mycoheterotrophic orchid, Gastrodia pubilabiata, that does not require laboratory facilities. The orchid is symbiotic with leaf-litter-decomposing fungi., Results: Gastrodia pubilabiata seeds were incubated in plastic boxes or glass bottles filled with leaf litter collected from the natural habitat of the species. Seed germination was observed after 35 days and seedling development followed. Fungal isolates from seedlings were identified as Mycenaceae (Basidiomycota), a leaf-litter-decomposing mycorrhizal fungus of Gastrodia species., Conclusion: Our method can be used to conserve endangered mycoheterotrophic plants associated with leaf litter-decomposing fungi efficiently, and can also serve as a model system for physiological and molecular studies of such plants.

Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes mediating cell survival, proliferation and angiogenesis and is aberrantly activated in various types of malignancies, including bladder cancer. We examined whether it could be a novel therapeutic target for bladder cancer using the STAT3 inhibitor WP1066. In T24 and UMUC-3 bladder cancer cells, 5 µM WP1066 prevented the phosphorylation of STAT3 and 2.5 µM WP1066 decreased cell survival and proliferation significantly (P<0.01). WP1066 also induced apoptosis accompanied by the suppression of the expression of Bcl-2 and Bcl-xL in T24 cells. Moreover, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased significantly (P<0.01) when cells were treated with WP1066. The activities of MMP-2 and MMP-9 were also decreased by treatment with 10 µM WP1066. Our results revealed that using WP1066 to inhibit the STAT3 signaling pathway suppressed the viability and invasiveness of bladder cancer cells effectively and could be a novel therapeutic strategy against bladder cancer.

A 67-year-old woman complained of urinary frequency and gross hematuria. She was referred to our hospital with the diagnosis of bladder tumor. Transurethral resection of the bladder tumor (TURBT) was performed and pathological diagnosis was urothelial carcinoma (G2>G3) with muscular invasion. Because she hoped bladder preservation therapy, she received two courses of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy, one course of arterial infusion chemotherapy, and chemoradiotherapy with cisplatin. After those therapies she underwent 4 times of TURBT and two courses intravesical BCG therapy. However, solitary lung metastasis appeared 19 months after the initial TURBT. Multidisciplinary treatments including 25 courses of various multiagent chemotherapies, radiation therapy to the lung metastasis and surgical resection of a urethral recurrence were performed. Although a localized radiation pneumonitis was developed, the lung metastasis appeared to be controlled for 26 months after the radiation therapy to the lung. Bilateral ureteral and renal pelvic tumors appeared after the radiation therapy. Severe bleeding was occurred from renal pelvic tumors several times and she needed the hospital stay 2 times. Active bleeding stopped after the administration of chemotherapy each time. Although she died of occlusive jaundice due to the liver metastasis, she had been alive due to the multidisciplinary treatment for 67 months after lung metastasis appearance with relatively good performance status.

(Objective) We investigated the efficacy and safety of percutaneous renal mass biopsy retrospectively. (Methods) A retrospective review was performed of 44 patients (46 renal masses) who received ultrasound and/or computed tomography guided percutaneous biopsy of a solid renal mass between April 2004 and December 2012 in National Defense Medical College Hospital. (Results) The median renal mass size was 45 (range 15-140) mm with a median of 2 (1-5) cores taken. Thirteen masses were biopsied for differential diagnosis between RCC and other malignancies (or benign renal tumors), 11 were biopsied for differential diagnosis between RCC and renal pelvic urothelial carcinoma, 10 unresectable masses were biopsied to confirm the diagnosis pathologically before starting medication, and 12 small masses were biopsied before radio-frequency ablation. Of the initial 46 biopsies, 38 (82.6%) were diagnostic. The median lesion sizes in the diagnostic and nondiagnostic biopsy specimens were 45 (15-140) mm and 43 (17-128) mm. The median numbers of diagnostic and nondiagnostic cores were 2 (1-5) and 1.5 (1-4). These size and core number differences between the diagnostic and nondiagnostic biopsy specimens are not statistically significant. Of initial nondiagnostic 8 masses, 3 masses that were performed repeat biopsy resulted in determined diagnosis finally. There were mild postprocedural hematomas not requiring blood transfusion. There was no tumor dissemination after renal mass biopsy. (Conclusions) Percutaneous biopsy of renal masses is a safe procedure that provides diagnostic information.

Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD). We investigated the potential significance of urinary lactate dehydrogenase (U-LDH) activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5) levels were compared among 120 patients with KD, 18 patients with viral infection (VI), and 43 patients with upper urinary tract infection (UTI) and additionally compared between intravenous immunoglobulin (IVIG) responders ( n = 89) and nonresponders ( n = 31) with KD. Total U-LDH activity was higher in KD (35.4 ± 4.8 IU/L, P < 0.05) and UTI patients (66.0 ± 8.0 IU/L, P < 0.01) than in VI patients (17.0 ± 6.2 IU/L). In the isozyme pattern analysis, KD patients had high levels of U-LDH1 and U-LDH2, while UTI patients had high levels of U-LDH3, U-LDH4, and U-LDH5. Furthermore, IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1 ± 4.7 IU/L, P < 0.05), especially U-LDH1 and U-LDH2 ( P < 0.05), than IVIG responders (32.0 ± 2.8 IU/L). KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients., Competing Interests: The authors declare that they have no competing interests.

Background: Activated phosphatidylinositol 3-kinase δ syndrome (APDS) is a recently discovered primary immunodeficiency disease (PID). Excess phosphatidylinositol 3-kinase (PI3K) activity linked to mutations in 2 PI3K genes, PIK3CD and PIK3R1, causes APDS through hyperphosphorylation of AKT, mammalian target of rapamycin (mTOR), and S6., Objective: This study aimed to identify novel genes responsible for APDS., Methods: Whole-exome sequencing was performed in Japanese patients with PIDs. Immunophenotype was assessed through flow cytometry. Hyperphosphorylation of AKT, mTOR, and S6 in lymphocytes was examined through immunoblotting, flow cytometry, and multiplex assays., Results: We identified heterozygous mutations of phosphatase and tensin homolog (PTEN) in patients with PIDs. Immunoblotting and quantitative PCR analyses indicated that PTEN expression was decreased in these patients. Patients with PTEN mutations and those with PIK3CD mutations, including a novel E525A mutation, were further analyzed. The clinical symptoms and immunologic defects of patients with PTEN mutations, including lymphocytic AKT, mTOR, and S6 hyperphosphorylation, resemble those of patients with APDS. Because PTEN is known to suppress the PI3K pathway, it is likely that defective PTEN results in activation of the PI3K pathway., Conclusion: PTEN loss-of-function mutations can cause APDS-like immunodeficiency because of aberrant PI3K pathway activation in lymphocytes., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The evolution of mycoheterotrophy has been accompanied by extreme reductions in plant leaf size and photosynthetic capacity. Partially mycoheterotrophic plants, which obtain carbon from both photosynthesis and their mycorrhizal fungi, include species with leaves of normal size and others that are tiny-leaved. Thus, plant species may lose their leaves in a gradual process of size reduction rather than through a single step mutation. Little is known about how the degree of mycoheterotrophy changes during reductions in leaf size. We compared the degree of mycoheterotrophy among five Japanese Cephalanthera species, four with leaves of normal size (Cephalanthera falcata, Cephalanthera erecta, Cephalanthera longibracteata and Cephalanthera longifolia), one with tiny leaves (Cephalanthera subaphylla), and one albino form of C. falcata (as reference specimens for fully mycoheterotrophic plants). The levels of mycoheterotrophy were determined by stable isotope natural abundance analysis. All Cephalanthera species were relatively enriched in 13 C and 15 N in comparison with surrounding autotrophic plants. Cephalanthera subaphylla was strongly enriched in 13 C and 15 N to levels similar to the albinos. Species with leaves of normal size were significantly less enriched in 13 C than C. subaphylla and the albinos. Thus, C. subaphylla was strongly mycoheterotrophic, obtaining most of its carbon from mycorrhizal fungi even though it has tiny leaves; species with leaves of normal size were partially mycoheterotrophic. Hence, during the evolutionary pathway to full mycoheterotrophy, some plant species appear to have gained strong mycoheterotrophic abilities before completely losing foliage leaves.

Background: Landiolol effectively controls rapid heart rate in atrial fibrillation or flutter (AF/AFL) patients with left ventricular (LV) dysfunction. However, predicting landiolol Responders and Non-Responders and patients who will experience adverse effects remains a challenge. The aim of this study was to clarify the potential applicability of landiolol for rapid AF/AFL and refractory ventricular tachyarrhythmias (VTs) in patients with heart failure., Methods: A total of 39 patients with AF/AFL with ventricular response ≥120 bpm and 12 VTs were retrospectively enrolled. Landiolol Responders for rapid AF/AFL were defined as patients whose ventricular response was suppressed to less than 110 bpm or decreased by ≥20% from the initial heart rate after administration of landiolol. Responders for VTs were defined as patients with no recurrent VTs during the 24 h after the initiation of landiolol., Results: For AF/AFL, 29 patients (74%) were Responders. In nine patients (31%), AF was spontaneously terminated after starting landiolol. Eight Non-Responders (80%) needed to have AF terminated by cardioversion. Left ventricular ejection fraction (LVEF) at baseline was significantly associated with landiolol efficacy. For VTs, seven patients (58%) were Responders, and smaller LV diastolic and systolic diameters were associated with landiolol efficacy. Hypotension after landiolol treatment occurred in 5 of 51 patients, and lower LV systolic function was associated with the development of adverse events., Conclusions: Landiolol is effective in patients with heart failure not only due to rapid AF/AFL but also due to VTs. However, preserved LVEF is important for efficacy and safety in landiolol treatment.