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Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant fraction of short-term hematopoietic stem cells (ST-HSCs) that contribute to the development of diabetic neuropathy in mice. The important role for these cells is supported by the fact that transplantation of either whole HSCs or CD106-positive ST-HSCs from diabetic mice to non-diabetic mice produces diabetic neuronal dysfunction in the recipient mice via cell fusion. Furthermore, we show that transient episodic hyperglycemia produced by glucose injections leads to abnormal fusion of pathological ST-HSCs with residential neurons, reproducing neuropathy in nondiabetic mice. In conclusion, we have identified hyperglycemia-induced aberrant CD106-positive ST-HSCs underlie the development of diabetic neuropathy. Aberrant CD106-positive ST-HSCs constitute a novel therapeutic target for the treatment of diabetic neuropathy., Katagi et al. show that abnormal bone marrow-derived cells originated from hematopoietic stem cells (CD106-positive short-term HSCs) aberrantly fuse with neurons to develop diabetic neuropathy. This study suggests that the pathological abnormality is memorized in the bone marrow and that it cannot be erased by conventional therapy.

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 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., Plasma complement factor H levels were significantly lower in non‐survivors than in survivors and healthy controls.

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 (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, We investigated the association between aortic calcification and the 90‐day prognosis of patients with intensive care unit admission for sepsis. Propensity score matching was used to minimize the effect of confounding factors (e.g., diabetes mellitus) that could lead to biased results. Severe aortic calcification (not calcification only) was associated with a 90‐day prognosis in patients with intensive care unit admission sepsis, especially those younger than 65 years of age.

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.

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., Survival study of patients with intra‐abdominal infection and extra‐abdominal infection. Kaplan‐Meier survival curves according to the infection site and the interval between catecholamine administration and PMX‐DHP initiation. (a) Intra‐abdominal infection group (n = 29): early group (within 9 h) and late group (>9 h). (b) Extra‐abdominal infection group (n = 20): early group (within 9 h) and late group (>9 h).

Introduction Dexmedetomidine is a sedative used during spinal anaesthesia. However, it frequently induces bradycardia. Although intravenous atropine is often used for treating bradycardia during regional anaesthesia, the response to atropine might be attenuated by concomitantly administering sedatives. Methods We examined the effects of atropine used for treating bradycardia during spinal anaesthesia among patients receiving dexmedetomidine (D group), propofol (P group), or neither (nonDnonP group) for sedation, retrospectively. Results A total of 108 patients were included. Heart rate was significantly slower at all time points in the D group (n = 69) than in the nonDnonP group (n = 14) (p

Unexpected reintubation may occur, even if the risk factors are considered and a spontaneous breathing trial is successful. Reintubation is thought to be caused by various factors. Several studies have investigated the risk factors of reintubation, but most did not classify reintubation by cause. We retrospectively classified patients undergoing reintubation at intensive care unit by cause (respiratory insufficiency vs. nonrespiratory insufficiency) to examine the cause-specific risk factors of reintubation. A total of 262 patients were included; reintubation within 48 hours after extubation was performed in 12 patients (reintubation rate, 4.5%). After classification by cause of reintubation, the pressure of arterial oxygen to fractional inspired oxygen concentration (P/F) ratio exhibited a significant association with reintubation only in the respiratory insufficiency group (odds ratio (OR) 0.989, 95% confidence interval (CI) 0.980 to 0.999, p=0.036, and OR 0.989, 95% CI 0.979 to 0.999, p=0.026, in the univariate and multivariate analyses, respectively). In the propensity score analysis, a P/F ratio ≤ 200 may be a risk factor for reintubation in the respiratory insufficiency group (OR 7.811, 95% CI 1.345 to 45.367, p=0.022). In the nonrespiratory insufficiency group, intubation duration was significantly related to reintubation (OR 1.165, 95% CI 1.012 to 1.342, p=0.033, and OR 1.163, 95% CI 1.004 to 1.348, p=0.044, in the univariate and multivariate analyses, respectively). In conclusion, a low P/F ratio at extubation may be a risk factor for reintubation due to respiratory insufficiency. In the nonrespiratory insufficiency group, intubation duration may be significantly related to reintubation. The risk factors for reintubation may differ by the cause of reintubation. Further large-scale randomized controlled trials are required.

Aim Emergency department overcrowding is problematic. Some emergency departments have established a triage system to prevent overcrowding; however, effective management of a triage system requires knowledge of factors that influence emergency department attendance. Therefore, we investigated the effect of ambient temperature on emergency department attendance, as well as the types of patients that may have been affected. Methods Data on emergency department attendance at Shiga University of Medical Science Hospital (Otsu, Japan) were retrospectively collected from 1 April, 2007 to 31 March, 2010. Attendance was classified into eight categories based on a combination of symptoms (trauma or non-trauma), transport (by ambulance or walk-in), and severity (serious or non-serious). Results A total of 7,755 patients (4,120 [53.1%] men and 3,635 [46.9%] women) attended the emergency department during the study period. Statistically significant seasonal differences were observed in emergency department attendance in walk-in and non-serious groups of both trauma and non-trauma patients (P

Background:Severe sepsis is commonly associated with mortality among critically ill patients and is known to cause coagulopathy. While antithrombin is an anticoagulant used in this setting, serum albumin levels are known to influence serum antithrombin levels. Therefore, this study aimed to evaluate the outcomes of antithrombin supplementation in patients with sepsis-associated coagulopathy, as well as the relationship between serum albumin levels and the effects of antithrombin supplementation.Methods:This retrospective study evaluated patients who were >18 years of age and had been admitted to either of two intensive care units for sepsis-associated coagulopathy. The groups that did and did not receive antithrombin supplementation were compared for outcomes up to 1 year after admission. Subgroup analyses were performed for patients with serum albumin levels of Results:Fifty-one patients received antithrombin supplementation and 163 patients did not. The Cox proportional hazards model revealed that antithrombin supplementation was independently associated with 28-day survival (hazard ratio [HR]: 0.374, P = 0.025) but not with 1 year survival (HR: 0.915, P = 0.752). In addition, among patients with serum albumin levels of Conclusion:Antithrombin supplementation may improve short-term survival, but not long-term survival, among patients with sepsis-associated coagulopathy.

Background Interstitial cells of Cajal (ICCs), which express c-Kit receptor tyrosine kinase (KIT), play an important role in gastrointestinal motility. Loss of ICCs likely contributes to diabetic gastrointestinal motility disorder, however, the mechanism of attrition remains unknown. Here, we test the hypothesis that the bone marrow-derived progenitors are an important source of intestinal ICCs and that decreased homing of these progenitors in diabetes contributes to ICC diminution.

Yatsushiro Sea is an enclosed water area, where the wave height is low and the tidal current is also quiet. Therefore, the seawater exchange with the open sea is not good. Furthermore, the driftage is running from Kumagawa River, and it drifts with the current of Yatushiro Sea. In this study, a drifting small buoy system equipped with a GPS receiver is used for the purpose of observing a tide of Yatsushiro Sea. The effect of current on the buoy was investigated experimentally and numerically, and it was developed the optimum shape of buoy.

Primary sensory neurons are important in regard to the initiation and propagation of intestinal inflammation. The vanilloid receptor subtype-1 (VR-1) is a cation channel located on the sensory nerves that, when stimulated, release proinflammatory peptides. Previous reports have indicated that inhibition of VR-1 with capsazepine (CPZ), a VR-1 antagonist, attenuates dextran sodium sulfate (DSS) colitis in rats. DSS-induced colitis resembles ulcerative colitis with regard to its pathologic features. In this study, we examined the effect of CPZ on trinitrobenzene sulfonic acid (TNBS)-induced colitis, an experimental model of intestinal inflammation that most closely resembles the histologic and microscopic features of Crohn's disease. Colitis was induced by administering a single enema of 100 mg/kg TNBS in 50% ethanol via catheter to lightly anesthetized rats. Subsets of rats were treated with either 1 micromol/kg/ml of CPZ or CPZ-vehicle via enema for 6 days. Seven days after TNBS administration, rats were sacrificed and inflammation was assessed using a validated macroscopic damage score (MDS) and by measuring myeloperoxidase (MPO) activity. In addition, histologic examination was performed. TNBS administration resulted in reproducible chronic erosive lesions extending into the muscularis propria and extensive recruitment of neutrophils in the distal colon. MDS and MPO scores were considerably elevated in the TNBS colons when compared with the TNBS vehicle animals. TNBS rats treated with CPZ enemas exhibited a substantial reduction in MDS and MPO scores and demonstrated dramatically improved pathologic findings. Topical CPZ resulted in considerable attenuation of TNBS-induced colitis. These results support the role of VR-1 and sensory neurons with regard to intestinal inflammation.

A 49-year-old female cardiomyopathic patient with heart, hepatic, and renal failure and lactic acidosis was transferred to the intensive care unit without a unifying diagnosis. She was of short stature (145 cm tall), had difficulty in hearing, a past history of complete atrioventricular block, and had received a permanent pacemaker. She had been diagnosed and treated as dilated cardiomyopathy by her primary doctor. Treatment in the intensive care unit for 21 days including plasma exchange, continuous hemodiafiltration, artificial ventilation, and administration of catecholamine, carperitide, and a large amount of coenzyme Q10 (210 mg/day) improved the symptoms. Genetic analysis using mitochondrial DNA from leukocytes and sternocleidomastoid muscle revealed a 3243A>G mutation in the mitochondrial tRNA(Leu (UUR)) gene, which is related to mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient recovered through intensive care and could be discharged from hospital without any sequelae. This case was mitochondrial cardiomyopathy diagnosed from the symptoms of multiple organ dysfunction syndrome. Cardiomyopathy due to the mutation of mitochondrial DNA is not a common disease. However, it should be considered as a possible cause of heart failure.

Cancer cachexia is reported to be a major cause of cancer-related death. Since the pathogenesis is not entirely understood, only few effective therapies have been established. Since myriad tumors produce parathyroid hormone-related protein (PTHrP), plasma concentrations of PTHrP are increased in cancer cachexia. We measured the food intake, gastric emptying, conditioned taste aversion (CTA), and gene expression of hypothalamic neuropeptides in mice after administering PTHrP intraperitoneally. We administered PTHrP intravenously in rats and examined the gastroduodenal motility and vagal nerve activities. We also examined whether chronic administration of PTHrP influenced the food intake and body weight. Peripherally administered PTHrP induced negative energy balance by decreasing the food intake and gastric emptying; however, it did not induce CTA. The mechanism involved the activation of hypothalamic urocortins 2 and 3 through vagal afferent pathways and the suppression of gastroduodenal motor activity. The continuous infusion of PTHrP reduced the food intake and body weight gain with a concomitant decrease in the fat and skeletal muscle. Our findings suggest that PTHrP influences the food intake and body weight; therefore, PTHrP can be considered as a therapeutic target for cancer cachexia.

Objective: To evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in a rat hemorrhagic shock (HS) model using the TRPV1 antagonist, capsazepine (CPZ). Summary Background Data: TRPV1, distributed within the sensory nerve, plays a role in the regulation of cardiovascular functions. TRPV1 may be involved in the cardiovascular responses to HS. Methods: Male rats were anesthetized and HS was induced with the mean arterial pressure (MAP) at 30 mm Hg for 90 minutes. CPZ (5.0 mol/kg) was administered at 30 minutes after the shock induction, and the 24-hour survival rates were assessed. The MAP, heart rate, and shed blood volume (SBV) were recorded throughout the experiment. Arterial blood gas analysis and the plasma catecholamines levels were measured before and after HS. Double-immunohistochemistry for Fos and tyrosine hydroxylase (TH) was performed in the rostral ventrolateral medulla (RVLM) of the brain. Results: CPZ significantly improved the 24-hour survival rates, which was accompanied by the increase in the MAP and the SBV, a decrease of the plasma catecholamines levels, and attenuation of the severe metabolic acidosis. Furthermore, CPZ reduced the percentage of double-labeled neurons for Fos and TH in the RVLM of the rat brain. Conclusions: TRPV1 may be involved in the regulation of the cardiovascular responses to HS, at least in part, by recruiting catecholaminergic neurons in the RVLM. CPZ appears to induce metabolic compensations, which may be potentially useful in HS.

Severe acute pancreatitis is a clinical entity that can develop into multiple organ failure (MOF), and still has a poor prognosis. It is generally agreed that excessive humoral mediators such as pro-inflammatory cytokines play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP). Furthermore, it has been reported that continuous hemodiafiltration (CHDF) can remove the excess humoral mediators during the hypercytokinemic state of systemic inflammatory response syndrome (SIRS). We experienced a case of severe acute pancreatitis induced by alcohol abuse, on whom we performed cytokine apheresis. The patient was a 46 year-old male. He received 14 cytokine apheresis procedures, for about 4 hours in each session, using a CTR-001 direct hemoperfusion (DHP) cartridge. His serum levels of pro-inflammatory cytokines such as interleukin-6 (IL-6; 1649.1+/-667.1-1257.1+/-489.4 pg/mL, P=0.013) decreased significantly after the CTR-001 procedures. However tumor necrosis factor-alpha (TNF-alpha) (26.2+/-1.7-24.3+/-1.9 pg/mL, P=0.087), IL-1beta (6.1+/-2.9-3.49+/-1.1 pg/mL, P=0.477), IL-8 (192.5+/-33.4-229.5+/-51.8 pg/mL, P=0.754) and IL-10 (14.4+/-2.7-14.0+/-1.9 pg/mL, P=0.726) did not decrease statistically. Therefore, we conclude that in this case, cytokine apheresis using a CTR-001 cartridge was effective for reducing the pro-inflammatory cytokines during severe acute pancreatitis.

Background and aims: The role of sensory neurones in colitis was studied by chemical denervation of primary sensory neurones as well as antagonism of the vanilloid receptor-1 (VR-1) in rats prior to administration of dextran sulphate sodium (DSS) to induce colitis. Methods: Neonatal rats were chemically denervated by subcutaneous administration of capsaicin; controls received capsaicin vehicle only. When animals reached maturity, colitis was induced by administration of 5% DSS in drinking water for seven days. Additionally, normal adult rats were treated with a VR-1 antagonist capsazepine (CPZ) or vehicle twice daily via an enema from day 0 to day 6 of the DSS regimen. Control rats were treated with an enema infusion of vehicle and 5% DSS, or without either an enema infusion or DSS in drinking water. For both groups of rats, severity of inflammation was quantitated by disease activity index (DAI), myeloperoxidase (MPO) activity, and histological examination. Results: DSS induced active colitis in all control rats with resultant epithelial ulceration, crypt shortening, and neutrophil infiltration. Both neonatal capsaicinised rats and normal adult rats treated with CPZ enemas exhibited significantly lower levels of DAI, MPO, and histological damage compared with vehicle treated rats (p Conclusions: Neonatal capsaicinisation and local administration of CPZ prevents intestinal inflammation in a well established model of colitis indicating that primary sensory neurones possessing VR-1 receptors are required in the propagation of colonic inflammation.

While the crosstalk between coagulopathy and inflammation plays a key role in the development of multiple organ dysfunction in critically ill patients, the mechanisms governing this crosstalk have yet to be established. Microparticles (MPs) are submicron vesicles shed from a variety of cells that are considered to have proinflammatory and prothrombotic properties. Although platelet- derived MPs (PDMPs) are the main form of MPs, the role of PDMPs in critically ill patients remains unclear [1]. The aims of this study were to investigate serum PDMP levels in critically ill patients and to assess their prognostic value.

In 2012, National Institute of Technology, Kumamoto, and Yatsushiro River and National Highway Office concluded a collaboration agreement for the joint research and education on the disaster prevention and mitigation in the Kumagawa River basin. The Watari region has often suffered inundation damages in the flood season, and we have examined countermeasures against disasters in the region. While a hydraulic model experiment was carried out to examine countermeasure construction, a lot of inhabitants and students, participating in the experiment, received education and information about how to cope with disasters. Through this public-academic collaboration, a training levee was constructed based on the experimental results, and the participants in the experiment became more conscious about their natural disaster prevention and mitigation. Language: ja