Reactive oxygen species accumulation is synchronised with growth inhibition of temperature-sensitive recAts polA Escherichia coli.

When combined with recombinase defects, chromosome breakage and double-strand break repair deficiencies render cells inviable. However, cells are viable when an SOS response occurs in recAts polA cells in Escherichia coli. Here, we aimed to elucidate the underlying mechanisms of this process. Transposon mutagenesis revealed that the hslO gene, a redox chaperone Hsp33 involved in reactive oxidative species (ROS) metabolism, was required for the suppression of recAts polA lethality at a restricted temperature. Recently, it has been reported that lethal treatments trigger ROS accumulation. We also found that recAts polA cells accumulated ROS at the restricted temperature. A catalase addition to the medium alleviates the temperature sensitivity of recAts polA cells and decreases ROS accumulation. These results suggest that the SOS response and hslO manage oxidative insult to an acceptable level in cells with oxidative damage and rescue cell growth. Overall, ROS might regulate several cellular processes.

Vitamin C Maintenance against Cell Growth Arrest and Reactive Oxygen Species Accumulation in the Presence of Redox Molecular Chaperone hslO Gene.

Chromosome damage combined with defective recombinase activity renders cells inviable, owing to deficient double-strand break repair. Despite this, recA polA cells grow well under either DNA damage response (SOS) conditions or catalase medium supplementation. Catalase treatments reduce intracellular reactive oxygen species (ROS) levels, suggesting that recA polA cells are susceptible to not only chronic chromosome damage but also ROS. In this study, we used a reducing agent, vitamin C, to confirm whether cell growth could be improved. Vitamin C reduced ROS levels and rescued colony formation in recAts polA cells under restrictive temperatures in the presence of hslO, the gene encoding a redox molecular chaperone. Subsequently, we investigated the role of hslO in the cell growth failure of recAts polA cells. The effects of vitamin C were observed in hslO+ cells; simultaneously, cells converged along several ploidies likely through a completion of replication, with the addition of vitamin C at restrictive temperatures. These results suggest that HslO could manage oxidative stress to an acceptable level, allowing for cell division as well as rescuing cell growth. Overall, ROS may regulate several processes, from damage response to cell division. Our results provide a basis for understanding the unsolved regulatory interplay of cellular processes.

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients.

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0×10-4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

Proposed model for the prediction of intrahepatic covalently closed circular DNA level in patients with chronic hepatitis B.

AIM: We sought to create a prediction model for intrahepatic covalently closed circular DNA (IH-cccDNA) level in chronic hepatitis B (CHB) patients and to validate the model's predictive accuracy. METHODS: Patients who did not receive previous nucleoside analogue (NA) therapy were assigned to the training cohort (n = 57), and those who received previous NA therapy were assigned to the validation cohort (n = 69). Factors linked to IH-cccDNA levels in the training cohort were analyzed and a formula to predict IH-cccDNA levels was constructed. Next, the reproducibility of that formula was assessed. RESULTS: In the multivariate analysis for the prediction of IH-cccDNA level in the training cohort, fasting blood sugar (FBS) (P = 0.0227), hepatitis B e antigen (HBeAg) (P = 0.0067) and log10 (HB surface antigen [HBsAg]) (P = 0.0497) were significant, whereas HB core-related antigen (HBcrAg) tended to be significant (P = 0.0562). The formula was constructed and named the FBS-cres score based on the variables used (FBS, HBcrAg, HBeAg, and HBsAg). The FBS-cres score was calculated as: 3.1686 - (0.0148 × FBS) + (0.1982 × HBcrAg) + (0.0008168 × HBeAg) + (0.1761 × log10 (HBsAg)). In the training cohort, a significant correlation was noted between HBcrAg and IH-cccDNA levels (P < 0.0001, r = 0.67), whereas the FBS-cres score was more closely correlated to IH-cccDNA level (P < 0.0001, r = 0.81). In the validation cohort, significant correlation was found between HBcrAg and IH-cccDNA levels (P = 0.0012, r = 0.38), whereas the FBS-cres score was more closely linked to IH-cccDNA levels (P < 0.0001, r = 0.51). Similar tendencies were observed in all subgroup analyses. CONCLUSION: Our proposed model for the prediction of IH-cccDNA level could be helpful in CHB patients.

Liver fibrosis markers as assessed by ultrasound elastography and serum samples: A large comparative study in hepatitis virus B and C liver diseases.

AIM: We aimed to compare the well-established liver fibrosis (LF) markers in Japanese patients with chronic hepatitis B (CHB, n = 331) and chronic hepatitis C (CHC, n = 886) and to discuss possible causes of differences in results between CHB patients and CHC patients. METHODS: Virtual touch quantification (VTQ) in acoustic radiation force impulse, Fibrosis-4 (Fib-4) index, aspartate aminotransferase to platelet ratio index (APRI), and hyaluronic acid (HA) were compared between the two cohorts. As an additional investigation, total collagen proportional area (TCPA, %) was tested using liver pathological samples (n = 83). RESULTS: Significant LF (F2 or greater) and advanced LF (F3 or greater) were identified in 153 (46.2%) and 76 (23.0%) patients in the CHB cohort and 579 (65.3%) and 396 (44.7%) patients in the CHC cohort. The median VTQ, Fib-4 index, APRI, and HA values in the CHB cohort were 1.20 m/s, 1.36, 0.44, and 25 ng/mL; those in the CHC cohort were 1.32 m/s, 2.60, 0.74, and 65.5 ng/mL (P-values, all <0.0001). Similar tendencies were noted by F stage-based stratification. The median TCPA in the CHB cohort and the CHC cohort were 8.5% and 12.7% (P < 0.0006). The TCPA values in the CHC cohort were higher than those in the CHB cohort regardless of LF stage. CONCLUSION: Values of LF markers in CHB patients can differ from those in CHC patients even in the same LF stage. Difference in total amount of collagen fiber in CHB and CHC appears to be linked to the difference.

Raftlin Controls Lipopolysaccharide-Induced TLR4 Internalization and TICAM-1 Signaling in a Cell Type-Specific Manner.

The clathrin-dependent endocytic pathway is crucial for endosomal TLR3- and TLR4-mediated Toll-IL-1R domain-containing adaptor molecule-1 (TICAM-1) signaling. TLR4 uses a different signaling platform, plasma membrane and endosomes, for activation of TIRAP-MyD88 and TICAM-2-TICAM-1, respectively. LPS-induced endocytosis of TLR4 is mandatory for TICAM-1-mediated signaling including IFN-ß production. Several molecules/mechanisms such as CD14, clathrin, and phosphatidylinositol metabolism have been reported to act as inducers of TLR4 translocation. However, the molecular mechanism of spatiotemporal regulation of TLR4 signaling remains unresolved. We have previously shown that Raftlin is essential for clathrin-dependent endocytosis of TLR3 ligand in human epithelial cells and myeloid dendritic cells (DCs). In this article, we demonstrate that Raftlin also mediated LPS-induced TLR4 internalization and TICAM-1 signaling in human monocyte-derived DCs and macrophages (Mo-Mϕs). When Raftlin was knocked down, LPS-induced TLR4-mediated IFN-ß promoter activation, but not NF-κB activation, was decreased in HEK293 cells overexpressing TLR4/MD-2 or TLR4/MD-2/CD14. LPS-induced IFN-ß production by monocyte-derived DCs and Mo-Mϕs was significantly decreased by knockdown of Raftlin. Upon LPS stimulation, Raftlin moved from the cytoplasm to the plasma membrane in Mo-Mϕs, where it colocalized with TLR4. Raftlin associated with clathrin-associated adaptor protein-2 in resting cells and transiently bound to TLR4 and clathrin at the cell surface in response to LPS. Thus, Raftlin appears to modulate cargo selection as an accessary protein of clathrin-associated adaptor protein-2 in clathrin-mediated endocytosis of TLR3/4 ligands.

Effects of night-time on-call work on heart rate variability before bed and sleep quality in visiting nurses.

PURPOSE: In Japan, many visiting nurses work carrying cell phones to respond to calls from users even at night (on-call work). The purpose of this study was to investigate whether on-call work affected heart rate variability (HRV) before bed and decreased sleep quality in visiting nurses even if their sleep was not interrupted due to actual calls. METHODS: Thirty-one visiting nurses (mean age, 49.8 years; standard deviation, 6.3 years) were asked to record their 2.5-min resting HRV before bed, and to undergo one-channel sleep electroencephalography (EEG) and subjective sleep evaluations upon waking (Oguri, Shirakawa, and Azumi Sleep Inventory) at home for 4-5 consecutive days, including both on-call and non-on-call days. Paired data sets of outcome measures, including HRV parameters, sleep macrostructure variables, and subjective sleep quality scores between on-call and non-on-call days were compared; the most recent measurements for each category were used for each subject. RESULTS: There were no differences in HRV measures and objective sleep EEG variables. A significant increase in "sleepiness on rising" and a decrease in "feeling refreshed" were observed on on-call days (P = 0.019 and 0.021, respectively), and younger subjects (≤ 51 years old) demonstrated a significant reduction in "sleepiness on rising" (significant interaction effect, P = 0.029). CONCLUSIONS: Adverse effects of on-call work on sleep quality in most visiting nurses are thought to be subjective, and relatively young nurses tend to notice a decrease in sleep quality. On-call work itself does not appear to be a substantial stressor that could affect HRV and sleep structure.

LRRC59 Regulates Trafficking of Nucleic Acid-Sensing TLRs from the Endoplasmic Reticulum via Association with UNC93B1.

Compartmentalization of nucleic acid (NA)-sensing TLR3, 7, 8, and 9 is strictly regulated to direct optimal response against microbial infection and evade recognition of host-derived NAs. Uncoordinated 93 homolog B1 (UNC93B1) is indispensable for trafficking of NA-sensing TLRs from the endoplasmic reticulum (ER) to endosomes/lysosomes. UNC93B1 controls loading of the TLRs into COPII vesicles to exit from the ER and traffics with the TLRs in the steady state. Ligand-induced translocation also happens on NA-sensing TLRs. However, the molecular mechanism for ligand-dependent trafficking of TLRs from the ER to endosomes/lysosomes remains unclear. In this study, we demonstrated that leucine-rich repeat containing protein (LRRC) 59, an ER membrane protein, participated in trafficking of NA-sensing TLRs from the ER. Knockdown of LRRC59 reduced TLR3-, 8-, and 9-mediated, but not TLR4-mediated, signaling. Upon ligand stimulation, LRRC59 associated with UNC93B1 in a TLR-independent manner, which required signals induced by ligand internalization. Endosomal localization of endogenous TLR3 was decreased by silencing of LRRC59, suggesting that LRRC59 promotes UNC93B1-mediated translocation of NA-sensing TLRs from the ER upon infection. These findings help us understand how NA-sensing TLRs control their proper distribution in the infection/inflammatory state.

Identification of a Regulatory Acidic Motif as the Determinant of Membrane Localization of TICAM-2.

TLR4 triggers LPS signaling through the adaptors Toll/IL-1R domain-containing adaptor molecule (TICAM)-2 (also called TRAM) and TICAM-1 (also called TRIF), together with Toll/IL-1R domain-containing adaptor protein (TIRAP) and MyD88. The MyD88 pathway mediates early phase responses to LPS on the plasma membrane, whereas the TICAM pathway mediates late-phase responses, which induce the production of type I IFN and activation of inflammasomes. TICAM-2 bridges TLR4 and TICAM-1 for LPS signaling in the endosome. Recently, we identified an acidic motif, E87/D88/D89 in TICAM-2, that provides the interaction surfaces between TICAM-2 and TICAM-1. In the present study, we found additional D91/E92 in TICAM-2, conserved across species, that is crucial for TICAM-1 activation. The D91A/E92A mutant protein was distributed largely to the cytosol, despite myristoylation, suggesting its importance for assistance of membrane localization of TICAM-2. An ectopically expressed D91A/E92A mutant per se failed to activate TICAM-1, unlike its wild-type counterpart that forms self-aggregation, but it still retained the ability to pass LPS-mediated IFN regulatory factor (IRF)3 activation. In a TICAM-2 knockout human cell line expressing TLR4/MD-2 with or without CD14, overexpression of the D91A/E92A mutant did not activate IRF3, but upon LPS stimulation, it induced sufficient TLR4-mediated IRF3 activation with high coefficient colocalization. Hence, the D91/E92 motif guides TICAM-2 membrane localization and self-activation for signaling. Our results suggest the presence of two distinct steps underlying endosomal LPS signaling on TICAM-2 for TICAM-1 activation: TICAM-2 assembling in TLR4 and/or TICAM-2 self-activation. D91A/E92A of TICAM-2 selectively associates the TLR4-dependent TICAM-2 assembling, but not cytosolic TICAM-2 self-aggregation, to activate TICAM-1.

Development of a simple predictive model for decreased skeletal muscle mass in patients with compensated chronic liver disease.

AIM: To develop and validate a simple predictive model using easily obtained clinical parameters to predict decreased skeletal muscle mass (DSMM) in chronic liver disease (CLD) patients (n = 652). METHODS: Study subjects were divided into a training set (n = 326) and a validation set (n = 326). Decreased skeletal muscle mass was diagnosed based on skeletal muscle mass index measured by bioimpedance analysis. Variables significantly associated with DSMM were identified using univariate and multivariate analyses in the training set and used to construct a predictive formula. Receiver operating characteristic (ROC) curve analysis was carried out and the predictive model was validated in the validation set. Subgroup analyses were undertaken based on gender, age, or cirrhosis status of patients. RESULTS: Body mass index (BMI), age, serum albumin, and branched-chain amino acid to tyrosine ratio (BTR) were determined to be significant predictive factors for DSMM. A composite formula "BALB score" was constructed [-7.740 + (0.539 × BMI) + (-0.112 × age) + (1.358 × albumin) + (-0.264 × BTR)]. The BALB score had the best predictive characteristics among all variables in both population sets (area under the ROC curve, 0.877-0.898). Patients with DSMM were stratified into three BALB score categories (>4, 0-4, and <0). Subgroup analyses also showed that BALB scoring was predictive of DSMM irrespective of gender, age, or cirrhosis status. The BALB score significantly correlated with psoas muscle index on computed tomography (rs = 0.6083 for men; rs = 0.6814 for women). CONCLUSION: The BALB scoring system based on routinely used clinical parameters offers a convenient and non-invasive method for predicting DSMM in compensated CLD patients with high accuracy.

Prognostic significance of low skeletal muscle mass compared with protein-energy malnutrition in liver cirrhosis.

AIMS: To investigate the impact of low skeletal muscle mass (LSMM) on survival as compared with protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC). METHODS: A total of 206 individuals with LC were analyzed. We retrospectively examined the impact of LSMM, as defined by psoas muscle mass at the third lumber on computed tomography, on survival as compared with PEM. In terms of comparison of the effects of LSMM and PEM on survival, we used time-dependent receiver operating characteristics (ROC) analysis. RESULTS: Our study cohort included 115 men and 91 women with a median age of 67 years. There were 140 patients with Child-Pugh A, 62 with Child-Pugh B, and 4 with Child-Pugh C. A total of 117 patients (56.8%) had LSMM and 52 patients (25.2%) had PEM. The proportion of PEM in patients with LSMM (31.62%, 37/117) was significantly higher than in patients without LSMM (16.85%, 15/89) (P = 0.0229). In the multivariate analysis for the entire cohort, the presence of hepatocellular carcinoma, lower body mass index, presence of LSMM, lower triglyceride value, poorer renal function, and higher des-γ-carboxy prothrombin value were found to be significant adverse predictors linked to overall survival, while presence of PEM tended to be significant. In the time-dependent ROC analysis, all area under the ROCs for survival in LSMM at each time point were higher than those in PEM except for Child-Pugh B patients. CONCLUSION: In this comparison of LSMM and PEM on clinical outcomes in LC patients, it was shown that LSMM may have stronger prognostic impact than PEM.

Relation between change in exercise capacity and change in blood amino acids in patients with chronic heart failure.

[Purpose] Although cardiac rehabilitation (CR) is recommended for patients with chronic heart failure (CHF), adequate exercise effect cannot be obtained in elderly patients. Administration of amino acids (AA) to CHF patients has been reported to improve exercise capacity, but the changes in AA composition in plasma before and after CR had not been reported. This study aimed to measure plasma levels of AA in CHF patients and compare with values of normal range. In addition the relationship between the change of exercise capacity and AA were examined. [Subjects and Methods] Twelve CHF patients (60% males, aged 68 ± 12 years) were studied. The correction between the rates of changes in exercise capacity parameters and in plasma AA levels was investigated. [Results] Anaerobic threshold (AT) and peak oxygen uptake (VO2) improved significantly after CR. The AA profile showed no specific pattern, and citrulline (Cit) was the amino acid showing a significant positive correlation with exercise capacity (∆Cit vs. ∆AT: r=0.602, ∆Cit vs. ∆AT-work rate (WR): r=0.681, ∆Cit vs. ∆VO2/WR: r=0.635). A tendency of positive correlation was observed between ∆Cit and ∆peak VO2 (r=0.456). [Conclusion] The AA profile showed no specific pattern, but a relationship between change in exercise capacity and Cit were found.

Endosomal localization of TLR8 confers distinctive proteolytic processing on human myeloid cells.

Nucleic acid-sensing TLRs are involved in both antimicrobial immune responses and autoimmune inflammation. TLR8 is phylogenetically and structurally related to TLR7 and TLR9, which undergo proteolytic processing in the endolysosomes to generate functional receptors. Recent structural analyses of human TLR8 ectodomain and its liganded form demonstrated that TLR8 is also cleaved, and both the N- and C-terminal halves contribute to ligand binding. However, the structures and ssRNA recognition mode of endogenous TLR8 in human primary cells are largely unknown. In this study, we show that proteolytic processing of TLR8 occurs in human monocytes and macrophages in a different manner compared with TLR7/9 cleavage. The insertion loop between leucine-rich repeats 14 and 15 in TLR8 is indispensable for the cleavage and stepwise processing that occurs in the N-terminal fragment. Both furin-like proprotein convertase and cathepsins contribute to TLR8 cleavage in the early/late endosomes. TLR8 recognizes viral ssRNA and endogenous RNA, such as microRNAs, resulting in the production of proinflammatory cytokines. Hence, localization sites of the receptors are crucial for the nucleic acid-sensing mode and downstream signaling.

Impact of Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein in Patients with Hepatitis C Virus-Related Compensated Liver Cirrhosis.

We aimed to examine the effect of Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA⁺-M2BP) level on survival comparing with other laboratory liver fibrosis markers in hepatitis C virus (HCV)-related compensated liver cirrhosis (LC) (n = 165). For assessing prognostic performance of continuous fibrosis markers, we adapted time-dependent receiver operating characteristics (ROC) curves for clinical outcome. In time-dependent ROC analysis, annual area under the ROCs (AUROCs) were plotted. We also calculated the total sum of AUROCs in all time-points (TAAT score) in each fibrosis marker. WFA⁺-M2BP value ranged from 0.66 cutoff index (COI) to 19.95 COI (median value, 5.29 COI). Using ROC analysis for survival, the optimal cutoff point for WFA⁺-M2BP was 6.15 COI (AUROC = 0.79348, sensitivity = 80.0%, specificity = 74.78%). The cumulative five-year survival rate in patients with WFA⁺-M2BP ≥ 6.15 COI (n = 69) was 43.99%, while that in patients with WFA⁺-M2BP < 6.15 COI (n = 96) was 88.40% (p < 0.0001). In the multivariate analysis, absence of hepatocellular carcinoma (p = 0.0008), WFA⁺-M2BP < 6.15 COI (p = 0.0132), achievement of sustained virological response (p < 0.0001) and des-γ-carboxy prothrombin < 41 mAU/mL (p = 0.0018) were significant favorable predictors linked to survival. In time-dependent ROC analysis in all cases, WFA⁺-M2BP had the highest TAAT score among liver fibrosis markers. In conclusion, WFA⁺-M2BP can be a useful predictor in HCV-related compensated LC.

[Preoperative screening of deep venous thrombosis: cutoff value of D-dimer, age and BMI for further examination of DVT by echo-color-Doppler].

BACKGROUND: Pulmonary embolism (PE) is morbid perioperative complication and deep vein thrombosis (DVT) is the most common cause of PE. Echo-color-Doppler examination for DVT is a specific test. But it would not be cost-effective to perform in all preoperative patients. The aim of this study was to determine the cut-off value of age body mass index (BMI) and D-dimer (DD) for further examination (echo) of DVT. METHODS: The age, BMI and DD of patients who had undergone echo-color-Doppler test were retrospectively examined. There were 94 patients scheduled for elective operation under general anesthesia from May 2004 to March 2005 in Himeji Red Cross Hospital. RESULTS: Forty five patients were with DVT and 49 patients were without DVT. There was no significant difference between the two groups in BMI. The cut-off value of age was 39 years and that of D-dimer was 0.8 µg x ml(-1). Discriminant function of DVT and D-dimer age were obtained in the formulae, Z = 0.0047 x (Age)(2) - 0.0565 x (D-D)(2) - 0.0046 (Age) x (DD) - 0.7085 x (Age) +0.546 x (DD) + 26.5674. CONCLUSIONS: We recommend that the patients above the discriminant function curve of DVT should undergo further examination for DVT.

[Increase in serum vecuronium concentration following sugammadex administration in a pediatric patient after prolonged sedation].

It is known that blood concentration of rocuronium increases after administration of sugammadex, but this is not clear in the case of vecuronium. We report a pediatric case in which serum vecuronium concentration increased following sugammadex administration after prolonged sedation using vecuronium. A 19-month-old girl weighing 7.8 kg had a history of aortic valvuloplasty at 4 months of age due to truncus arteriosus. She presented again to our hospital due to aortic regurgitation. She underwent aortic valvuloplasty and then aortic valve replacement. The postoperative course was complicated with severe heart failure and acute kidney injury requiring peritoneal dialysis. For that reason she required long-term sedation including administration of a large amount of muscle relaxant due to severe low cardiac output syndrome after aortic valvuloplasty. A total of 615 mg (79 mg x kg(-1)) of vecuronium was administered over a period of 24 days. On weaning from mechanical ventilation, 125 mg (16 mg x kg(-1)) of sugammadex was given. Vecuronium concentration measured by high-performance liquid chromatography (HPLC) was 5.03 ng x ml(-1) before sugammadex administration and increase to 13.98 ng x ml(-1) after that. However, blood concentration of metabolic products of vecuronium did not exceed the lower limits of measurement in each sample. She was successfully weaned from mechanical ventilation without recurarizarion. Serum concentration of vecuronium increased after administration of sugammadex because extravascular vecuronium was redistributed to intravascular space according to the concentration gradient induced by binding and clathration of vecuronium. The measured values of vecuronium after sugammadex administration on HPLC represented the total amount of free vecuronium and vecuronium combined with sugammadex. Recurarization might occur after sugammadex reversal in patients after long-term administration of vecuronium, especially if relatively smaller doses of sugammadex were given. We experienced a pediatric case in which serum vecuronium concentration increased following sugammadex administration after prolonged sedation using vecuronium. There is a risk of recurarization after sugammadex reversal in patients after long-term administration of vecuronium.

[Evaluation of the "Health management guideline on occupational allergy in nursing occupations and its primary prevention" by nursing managers].

OBJECTIVE: Individuals in nursing occupations are often exposed to various materials such as rubber products and drugs, and they comprise a population at high risk of developing occupational allergies. We therefore created a "Health management guideline on occupational allergy in nursing occupations and its primary prevention" (hereinafter referred to as "HMG") and conducted a questionnaire survey to elucidate its potential use and the challenges of implementing it in clinical practice. SUBJECTS AND METHODS: The HMG includes the following content: A. Basic knowledge of occupational allergies; B. Common occupational allergies in nursing occupations; C. Occupational allergies triggered by specific antigens in nursing occupations; D. Eczema and skincare for hands; and E. Health management for occupational allergies. A questionnaire survey was conducted on one nursing manager each from 80 hospitals, with at least 400 beds. The survey included questions to gauge the level of understanding the content described in the HMG and opinions on incorporating the management method. The ethics committee of the researcher's institution approved the study. RESULTS: Responses were obtained from 30 nursing managers. Over 70% responded that they understood the instructions for [occupational allergies], [common occupational allergies in nursing occupations], and [eczema and skincare for hands] presented in the HMG, and 100% said they either understood or mostly understood them. For [work management], 57% said they understood the content and 90% wanted to incorporate it. Furthermore, 10% responded that they wanted to incorporate the guidelines but did not believe it was feasible, given that "achieving general awareness and efforts involving other occupations are difficult." For [work environment management], 53% said they understood the content and 83% wanted to incorporate it. Additionally, 17% responded that they wanted to incorporate it but did not believe it was feasible, amid concerns that "allergen monitoring is difficult in reality" and "installation of local ventilation systems seems difficult." DISCUSSION AND CONCLUSIONS: The HMG was postulated to be useful in providing knowledge on occupational allergy and health management methods, and for employing in clinical practice. The study recommended that in order to specifically incorporate the management methods, it is imperative that the entire hospital, including staff from other occupations, understand the guidelines and make adjustments accordingly.

Remote Cardiac Rehabilitation With Wearable Devices.

Although cardiac rehabilitation (CR) has been shown to improve exercise tolerance and prognosis in patients with cardiovascular diseases, there remains low participation in outpatient CR. This may be attributed to the patients' busy schedules and difficulty in visiting the hospital due to distance, cost, avoidance of exercise, and severity of coronary disease. To overcome these challenges, many countries are exploring the possibility of remote CR. Specifically, there is increasing attention on the development of remote CR devices, which allow transmission of vital information to the hospital via a remote CR application linked to a wearable device for telemonitoring by dedicated hospital staff. In addition, remote CR programs can support return to work after hospitalization. Previous studies have demonstrated the effects of remote CR on exercise tolerance. However, the preventive effects of remote CR on cardiac events and mortality remain controversial. Thus, safe and effective remote CR requires exercise risk stratification for each patient, telenursing by skilled staff, and multidisciplinary interventions. Therefore, quality assurance of telenursing and multi-disciplinary interventions will be essential for remote CR. Remote CR may become an important part of cardiac management in the future. However, issues such as cost-effectiveness and insurance coverage still persist.

[Pacing lead extraction using an excimer laser sheath under general anesthesia].

An excimer laser sheath has recently been used for extraction of pacing and ICD leads. By using this technique, leads are removed more easily and it has to take a shorter time to extract leads. Although lead extraction with this method can cause fatal complications such as large vessel injury, little has been reported regarding anesthetic management during the lead extraction. We experienced two cases of pacing lead extraction using an excimer laser sheath under general anesthesia. The procedures were mainly performed by cardiologists in the operating theater. A wide area was prepared with sterile drapes as for cardiac surgery with cardiovascular surgeons standing by. Vascular access catheters were placed in the right femoral artery as well as vein, and in the right internal jugular vein so that immediate PCPS introduction could be performed in case of sudden hemodynamic collapse by massive bleeding. In the first case, lead extraction was completed without any complication, but in the second case sternotomy was performed by cardiac surgeons for safe separation of leads from vessels. There were also no bleeding episodes in the second case. Preparation for bleeding and cooperation among cardiologists, cardiovascular surgeons, medical engineers and anesthesiologists are necessary from the safety point of view of this procedure under general anesthesia.

RSOsPR10 expression in response to environmental stresses is regulated antagonistically by jasmonate/ethylene and salicylic acid signaling pathways in rice roots.

Plant roots play important roles not only in the absorption of water and nutrients, but also in stress tolerance. Previously, we identified RSOsPR10 as a root-specific pathogenesis-related (PR) protein induced by drought and salt treatments in rice. Transcripts and proteins of RSOsPR10 were strongly induced by jasmonate (JA) and the ethylene (ET) precursor 1-aminocyclopropane-1-carboxylic acid (ACC), while salicylic acid (SA) almost completely suppressed these inductions. Immunohistochemical analyses showed that RSOsPR10 strongly accumulated in cortex cells surrounding the vascular system of roots, and this accumulation was also suppressed when SA was applied simultaneously with stress or hormone treatments. In the JA-deficient mutant hebiba, RSOsPR10 expression was up-regulated by NaCl, wounding, drought and exogenous application of JA. This suggested the involvement of a signal transduction pathway that integrates JA and ET signals in plant defense responses. Expression of OsERF1, a transcription factor in the JA/ET pathway, was induced earlier than that of RSOsPR10 after salt, JA and ACC treatments. Simultaneous SA treatment strongly inhibited the induction of RSOsPR10 expression and, to a lesser extent, induction of OsERF1 expression. These results suggest that JA/ET and SA pathways function in the stress-responsive induction of RSOsPR10, and that OsERF1 may be one of the transcriptional factors in the JA/ET pathway.