YeeD is an essential partner for YeeE-mediated thiosulfate uptake in bacteria and regulates thiosulfate ion decomposition.

Uptake of thiosulfate ions as an inorganic sulfur source from the environment is important for bacterial sulfur assimilation. Recently, a selective thiosulfate uptake pathway involving a membrane protein YeeE (TsuA) in Escherichia coli was characterized. YeeE-like proteins are conserved in some bacteria, archaea, and eukaryotes. However, the precise function of YeeE, along with its potential partner protein in the thiosulfate ion uptake pathway, remained unclear. Here, we assessed selective thiosulfate transport via Spirochaeta thermophila YeeE in vitro and characterized E. coli YeeD (TsuB) as an adjacent and essential protein for YeeE-mediated thiosulfate uptake in vivo. We further showed that S. thermophila YeeD possesses thiosulfate decomposition activity and that a conserved cysteine in YeeD was modified to several forms in the presence of thiosulfate. Finally, the crystal structures of S. thermophila YeeE-YeeD fusion proteins at 3.34-Å and 2.60-Å resolutions revealed their interactions. The association was evaluated by a binding assay using purified S. thermophila YeeE and YeeD. Based on these results, a model of the sophisticated uptake of thiosulfate ions by YeeE and YeeD is proposed.

Comparison of remimazolam-based and propofol-based total intravenous anesthesia on hemodynamics during anesthesia induction in patients undergoing transcatheter aortic valve replacement: a randomized controlled trial.

PURPOSE: This study aimed to compare the hemodynamic effects of remimazolam- and propofol-based total intravenous anesthesia in patients who underwent transcatheter aortic valve replacement. METHODS: This was a single-center, single-blind, randomized controlled trial set at Nara Medical University, Kashihara, Japan. We included 36 patients aged ≥ 20 years scheduled to undergo elective transfemoral transcatheter aortic valve replacement (TAVR) under general anesthesia. The participants were randomly assigned to the remimazolam and propofol groups (n = 18 each). Remimazolam- or propofol-based total intravenous anesthesia was initiated at 12 mg/kg/min or 2.5 mcg/mL via target-controlled infusion, respectively, along with remifentanil. After confirming the loss of consciousness, the administration rate was adjusted using electroencephalographic monitoring. The primary outcome was the rate of arterial hypotension, defined as a mean arterial pressure < 60 mmHg, from anesthesia induction until the beginning of the surgical incision. The total doses of ephedrine and phenylephrine were also assessed. RESULTS: During anesthesia induction, the arterial hypotension rates were 11.9% and 21.6% in the remimazolam and propofol groups, respectively (P = 0.01). The total dose of ephedrine was higher in the propofol group (14.4 mg) than in the remimazolam group (1.6 mg) (P < 0.001); however, the total dose of phenylephrine was not significantly different between the two groups (propofol 0.31 mg vs. remimazolam: 0.17 mg, P = 0.10). CONCLUSION: Remimazolam-based total intravenous anesthesia resulted in a lower hypotension rate than propofol-based total intravenous anesthesia during induction in patients undergoing TAVR. Remimazolam-based total intravenous anesthesia can be used safely during anesthetic induction in patients with severe aortic stenosis.

Effect of nociception level-directed analgesic management on opioid usage in robot-assisted laparoscopic radical prostatectomy: a single-center, single-blinded, randomized controlled trial.

PURPOSE: To assess the importance of appropriate opioid administration methods according to nociceptive monitoring. METHODS: We conducted a randomized controlled trial involving 54 patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital. Patients were randomly allocated to either receive nociception level (NOL)-directed intraoperative opioid management with a minimum flow of remifentanil (NOL group) or conventional intraoperative analgesic management (control group). The primary outcome was the mean intraoperative remifentanil infusion flow rate (intraoperative remifentanil usage [µg]/ideal body weight [kg]/operation time [min]). The main secondary outcomes were plasma concentrations of three perioperative inflammatory biomarkers (interleukin-6, C-reactive protein [CRP], and cortisol levels) and postoperative pain (Numeric Rating Scale [NRS]) scores 2 h postoperatively and on postoperative days 1, 2, 3, and 7. RESULTS: Compared with standard analgesia management, NOL-directed analgesic management reduced remifentanil consumption by 20% ( - 0.038; 95% confidence interval, - 0.059 to - 0.017; p = 0.0007). NOL-directed management did not lead to an increase in IL-6, CRP, or cortisol levels compared with conventional analgesic management. Furthermore, this protocol led to improvements in the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3. CONCLUSION: NOL-directed analgesic management reduced remifentanil consumption by 20% and the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3 without an increase in inflammatory marker levels. REGISTRY NUMBER: Japan Registry of Clinical Trials, JRCTs052220034.

Persistent incisional pain at 1 year after craniotomy: a retrospective observational study.

BACKGROUND: There have been few reports on persistent incisional pain at 1 year after craniotomy. Hence, this study aimed to explore the distribution of pain at 1 year after elective craniotomy and its related factors. METHODS: This retrospective study included data prospectively collected to assess postoperative functional disability. We included patients aged > 55 years at the time of recruitment for our initial study and who had complete data regarding the pain numeric rating scale (NRS) score at 1 year post craniotomy. The primary outcome was the pain NRS score, which was assessed at the postanesthetic clinic as well as at 3 months and 1 year after craniotomy. Multivariable negative binomial regression analysis was performed to analyze the relationship between the pain NRS score at 1 postoperative year and 12 clinically meaningful covariates. These included the Short Form-8 scores for bodily pain and mental health, with higher scores indicating better health. RESULTS: We analyzed data from 102 patients. The mean (95% confidence interval) pain NRS scores at the three measurement points were 2.8 (2.3-3.3), 1.2 (0.8-1.6), and 0.6 (0.3-0.8), respectively. Multivariable analysis revealed that preoperative bodily pain (risk ratio, 0.93; 95% confidence interval, 0.88-0.98) and the pain NRS score at the postanesthetic clinic (risk ratio, 1.32; 95% confidence interval, 1.14-1.52) were associated with the risk of persistent pain at 1 postoperative year. CONCLUSIONS: The pain score at 1 year after elective craniotomy was minor; however, preoperative bodily pain and postoperative pain scores were significantly related factors.

Effects of preoperative nutritional status on disability-free survival after cardiac and thoracic aortic surgery: a prospective observational study.

PURPOSE: Preoperative malnutrition is associated with postoperative complications, prolonged intensive care unit stay, and mortality, leading to functional disability after non-cardiac surgery. However, its effects on cardiac and thoracic aortic surgery outcomes remain unknown. We examined the effects of preoperative malnutrition on disability-free survival after surgery and assessed the perioperative 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS2.0) score based on the preoperative nutritional status. METHODS: We included individuals aged ≥ 55 years who underwent elective cardiac and/or thoracic aortic surgery between April 1, 2016 and December 28, 2018 in a tertiary center. The nutritional status was assessed preoperatively using the Mini Nutritional Assessment Short Form, with scores < 12 points indicating a poor nutritional status. The JapanSCORE2 was calculated for surgical risk prediction. Our primary outcome was disability-free survival 1 year after surgery (WHODAS2.0 score: < 16%). The odds ratio of poor nutritional status for disability-free survival was calculated using multiple logistic regression analysis after adjusting for age, JapanSCORE2, and duration of surgery. RESULTS: One hundred patients were followed up for 1 year. Preoperatively, 41 of them had a poor nutritional status. The disability-free survival rates 1 year postoperatively were 46.3% (19/41) and 64.4% (38/59) in patients with and without poor preoperative nutritional status, respectively. The adjusted odds ratio of poor nutritional status for disability-free survival at 1 year after surgery was 0.42 (95% confidence interval, 0.17-0.99). CONCLUSION: Patients with a poor preoperative nutritional status had less likely to show disability-free survival 1 year after cardiac and thoracic aortic surgery.

Respiratory depression following cesarean section with single-shot spinal with 100 µg morphine.

PURPOSE: Little evidence is available regarding bradypnea measured using continuous monitoring following cesarean section. We aimed to evaluate the rate of cumulative bradypnea time (total bradypnea time/total monitoring time) and its related factors in these parturients. METHODS: This prospective observational study included women undergoing cesarean section under single-shot spinal anesthesia of 0.1 mg morphine. The Berlin Questionnaire was used to screen for sleep apnea syndrome preoperatively. Respiratory rate and oxygen saturation (SpO2) were monitored continuously using an adhesive acoustic respiration sensor and pulse oximeter, respectively, at least 6 h after cesarean section. Bradypnea was defined as a respiratory rate < 8 breaths/min lasting at least 25 s (sustained bradypnea) or at least 15 s (immediate bradypnea). Hypoxemia was defined as SpO2 < 92% lasting at least 25 s (sustained hypoxemia) or at least 15 s (immediate hypoxemia). Multiple regression analysis was applied to assess factors related to the rate of cumulative sustained bradypnea. RESULTS: Of 159 patients, the Berlin Questionnaire was positive in 16.3%, and 77 (48.4%) experienced sustained bradypnea. The median rate of cumulative sustained bradypnea time was 0.70% (interquartile range 0.35-1.45%) without any related factors. The incidence of immediate bradypnea and sustained and immediate hypoxemia were 58.5%, 24.5%, and 37.7%, respectively. However, none of the factors were significant. CONCLUSION: After cesarean section was performed with 0.1 mg intrathecal morphine, respiratory depression events were commonly observed. However, the rate of cumulative bradypnea time was very low and there were no related factors.

Persistent postoperative pain at 1 year after orthopedic surgery and its association with functional disability.

PURPOSE: Orthopedic hip, knee, and spinal surgeries have a relatively high incidence of persistent postoperative pain, with the highest risk observed in Asian ethnicity. This study aimed to investigate the distribution of persistent pain at 1 year after surgery and its associated factors and effects on functional disability. METHODS: This secondary analysis of a prospective observational study included 297 patients aged ≥ 55 years who underwent elective total hip arthroplasty, total knee arthroplasty, and spine and spinal cord surgeries under general anesthesia. Data were collected perioperatively and at 3 months and 1 year postoperatively to assess persistent postoperative pain on a numerical rating scale. RESULTS: At 1 year postoperatively, 34.6% (103/297) of patients reported pain, with a score of ≥ 1 and a mean score of 1.2. Multivariable negative binomial regression analysis revealed that less preoperative bodily pain (risk ratio [RR], 0.97; 95% confidence interval [CI] 0.94-0.99), preoperative C-reactive protein (CRP) level (RR, 1.19; 95% CI 1.01-1.39), and spine and spinal cord surgeries (RR, 2.48; 95% CI 1.30-4.75) increased the risk of persistent pain at 1 year after surgery, which was a significant factor for predicting the 12-item World Health Organization Disability Assessment Schedule 2.0 score (p < 0.001). CONCLUSION: The mean score for persistent pain at 1 year after surgery on the numerical rating scale was 1.2. Worse preoperative bodily pain, higher preoperative serum CRP level, and spine and spinal cord surgeries increased the persistent pain score at 1 year after surgery, which was associated with functional disability CLINICAL TRIAL REGISTRATION: This prospective observational study was registered on the University Hospital Medical Information Network (31 December 2015; UMIN000021671).

Factors associated with functional disability or mortality after elective noncardiac surgery: a prospective cohort study.

PURPOSE: Preoperative prediction of functional status after surgery is essential when practicing patient-centered medicine. We aimed to evaluate the incidence and factors associated with postoperative functional disability or all-cause mortality. Secondarily, we sought to describe the trajectory of disability in this population. METHODS: Adults aged ≥ 55 yr who underwent elective noncardiac surgery under general anesthesia in a tertiary care hospital were followed up one year after surgery. Pre- and intraoperative factors associated with a composite outcome of postoperative functional disability or all-cause mortality were assessed using a multiple logistic regression. The sequential changes in the 12-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 score were described and stratified by surgical invasiveness. RESULTS: Of the 2,921 patients included, 293 experienced postoperative functional disability (10.0%; 95% confidence interval [CI], 8.9 to 11.1) and 124 died (4.2%; 95% CI, 3.5 to 5.0). In a multiple regression model, the potentially modifiable risk factors, body mass index ≥ 30 kg·m-2 and poor preoperative nutritional status, were significantly associated with the primary composite outcome, as well as nonmodifiable factors such as age, preoperative comorbidities, and blood loss volume. Changes in the 12-item WHODAS 2.0 disability score varied between different levels of surgical invasiveness and types of surgery. CONCLUSION: Within one year after surgery, one in ten patients experienced postoperative functional disability and one in 20 died. We identified potentially modifiable factors (obesity, poor nutritional status) associated with these adverse outcomes. STUDY REGISTRATION: University Hospital Medical Information Network (UMIN000021671); registered 31 December 2015.

RéSUMé: OBJECTIF: La prédiction préopératoire du statut fonctionnel après chirurgie est essentielle dans la pratique d'une médecine centrée sur le patient. Nous avons cherché à évaluer l'incidence et les facteurs associés à l'incapacité fonctionnelle ou à la mortalité toutes causes confondues en postopératoire. En deuxième lieu, nous avons cherché à décrire la trajectoire de l'incapacité dans cette population. MéTHODE: Les adultes âgés de ≥ 55 ans qui ont subi une chirurgie non cardiaque non urgente sous anesthésie générale dans un hôpital de soins tertiaires ont été suivis jusqu'à un an après leur chirurgie. Les facteurs pré- et peropératoires associés à un devenir composite d'incapacité fonctionnelle postopératoire ou de mortalité toutes causes confondues ont été évalués à l'aide d'une régression logistique multiple. Les changements séquentiels dans le score de l'outil d'évaluation de l'invalidité de l'Organisation mondiale de la Santé (WHODAS - World Health Organization Disability Assessment Schedule) version 2.0 en 12 éléments ont été décrits et stratifiés en fonction du degré invasif de la chirurgie. RéSULTATS: Sur les 2921 patients inclus, 293 ont présenté une incapacité fonctionnelle postopératoire (10,0 %; intervalle de confiance [IC] à 95 %, 8,9 à 11,1) et 124 personnes sont décédées (4,2 %; IC 95 %, 3,5 à 5,0). Dans un modèle de régression multiple, les facteurs de risque potentiellement modifiables, un indice de masse corporelle ≥ 30 kg·m-2 et un mauvais état nutritionnel préopératoire étaient significativement associés au critère d'évaluation composite principal, ainsi qu'à des facteurs non modifiables tels que l'âge, les comorbidités préopératoires et le volume de perte de sang. Les changements dans le score d'incapacité WHODAS 2.0 à 12 éléments variaient entre les différents degrés invasifs de la chirurgie et les types de chirurgie. CONCLUSION: Dans l'année qui a suivi la chirurgie, un patient sur dix a présenté une incapacité fonctionnelle postopératoire et un sur 20 est décédé. Nous avons identifié des facteurs potentiellement modifiables (obésité, mauvais état nutritionnel) associés à ces effets indésirables. ENREGISTREMENT DE L'éTUDE: University Hospital Medical Information Network (UMIN000021671); enregistré le 31 décembre 2015.

Prevalence of undernutrition in surgical patients and the effect on length of hospital stay.

BACKGROUND: Low nutritional status is common among surgical patients. A low nutrition profile is related to muscle weakness and immune suppression, which may be associated with negative outcomes. In this study, we evaluated the prevalence of low nutrition and assessed the relationship between nutritional status and length of hospital stay in surgical patients. METHODS: The study participants were patients who underwent abdominal surgery between 2016 and 2018 at our hospital. The Mini Nutritional Status Short-Form score and patient demographics, including current medical status, were extracted from the medical records. Data on anesthesia time, blood loss, and use of epidural anesthesia were also recorded. The primary study outcome was the difference in length of hospitalization from the standard duration (hospitalization = actual length of hospitalization-standard length of hospitalization). RESULTS: Eight hundred and thirty five patients met the inclusion criteria. Their nutritional status was classified as normal (59.0%), at risk (29.6%), or malnutrition (11.4%). Linear regression analysis revealed that nutritional status, serum albumin level, and anesthesia time were associated with the length of hospital stay. CONCLUSION: Our results suggest that a low nutrition profile before surgery is associated with a prolonged hospital stay.

Translation and validation of the Japanese Version of the Quality of Recovery-15 Questionnaire.

PURPOSE: Patient-reported outcomes after surgery and anaesthesia have recently attracted attention. A recent systematic review and a consensus guideline recommend that patients' recovery can be adequately measured using the quality of recovery-15 (QoR-15) during the perioperative period; however, the Japanese version of the QoR-15 (QoR-15J) is not available. We aimed to translate the QoR-15 into Japanese and assess its validity. METHODS: After translating into Japanese, 205 patients who underwent various types of surgery under general anaesthesia were enrolled in the study. QoR-15J was evaluated before surgery and 24 h and 48 h after surgery. Additionally, 30 patients answered the QoR-15J at 25 h after surgery. We assessed the feasibility, reliability, validity, and responsiveness of the QoR-15J. RESULTS: One patient who did not undergo surgery and two patients who were discharged within 24 h were excluded. One hundred and eighty-seven patients answered the QoR-15J at 24 h after surgery (completion rate, 92.6%) and 183 patients with complete data were included in the final analysis. The Cronbach's alpha coefficient for internal reliability and Spearman rank correlation coefficient for test-retest reliability were 0.84 and 0.91, respectively. The Cohen effect size for all items was 1.42. CONCLUSIONS: QoR-15 was translated into Japanese and the Japanese version's validity was assessed in patients undergoing various types of surgery under general anaesthesia. Our results suggest that QoR-15J is feasible, reliable, valid, and responsive.

The incidence and reasons for canceled surgical cases in an academic medical center: a retrospective analysis before and after the development of a preoperative anesthesia clinic.

PURPOSE: The development of a preoperative anesthesia clinic (PAC) can reduce the number of surgical cases canceled on the day of surgery. However, there are only a few studies on the details of cancellations in the operating room. This study aimed to assess the incidence and reasons for surgical cases canceled from admission to the operating room to the start of surgery. METHODS: This retrospective study involved patients who underwent anesthesia performed by anesthesiologists between January 2008 and March 2019. We focused on case cancellations occurring from admission to the operating room to the start of surgery. We classified the reasons for cancellation into four categories: insufficient preoperative anesthetic assessment, anesthetic issues/complications, medical problems related to patients' comorbidity, and others. We evaluated and compared the incidence and reasons for cancellation before and after the establishment of a PAC. RESULTS: Among a total of 48,089 scheduled surgery, 18 (0.037%, 95% confidence interval 0.019-0.055) cases were canceled. The total cancellation rate before and after the development of a PAC was not statistically significant (0.051% vs 0.022%, P = 0.10). Before the development of a PAC, the most common reason was insufficient preoperative anesthetic assessment in 46.1%, followed by anesthetic issues/complications (23.0%), medical problems related to patients' comorbidity (15.3%), and others (15.3%). After the development of a PAC, surgeries were canceled for medical problems related to patients' comorbidity (80.0%) and anesthetic issues/complications (20.0%). CONCLUSIONS: The total incidence of surgical case cancellations was 0.037%. Before and after the development of a PAC, cancellation rate was comparable. After the development of a PAC, none case were canceled due to insufficient preoperative anesthetic assessment.

Prevalence and associated factors of preoperative functional disability in elective surgical patients over 55 years old: a prospective cohort study.

PURPOSE: In preoperative settings, patients may have functional disabilities due to the disease for which surgery is being performed or comorbidities, but the associated and predictive factors remain unknown. This study examined the prevalence of preoperative functional disability and clarified the associated factors. METHODS: Individuals aged ≥ 55 years who were scheduled to undergo surgery in a tertiary-care hospital in Japan between April 2016 and September 2016 were eligible for enrolment in the study. Patients with the diseases requiring psychiatric treatment and patients unable to complete the questionnaire without help were excluded. After obtaining informed consent, each patient was asked to complete the 12-item World Health Organization Disability Assessment Schedule-2.0, which is a standardized evaluation tool for assessing comprehensive living function. Data from these questionnaires and the patients' characteristics were evaluated. Multiple logistic regression analysis was conducted to determine independent factors associated with preoperative functional disability. RESULTS: Of 1201 recruited patients, 912 (75.9%) were included in our analysis. The prevalence of preoperative functional disability was 29.2%. Regression analysis identified six independent associated factors for preoperative functional disability: body mass index ≥ 30 kg m-2, mixed lung disease, serum albumin values, malnutrition, risk of malnutrition, and preoperative use of corticosteroids. CONCLUSIONS: In total, 29.2% of preoperative patients had functional disability. Obesity, nutritional deficiency, respiratory complications, and low serum albumin values were determined as potentially modifiable factors.

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study).

AIM: To evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100. MATERIALS AND METHODS: This multicentre, open-label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once-daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC0:00-4:00h ]) from baseline to day 29. RESULTS: Lixisenatide reduced PPG exposure to a statistically significantly greater extent than sitagliptin: least squares (LS) mean change from baseline in PPG AUC0:00-4:00h was -347.3 h·mg/dL (-19.3 h·mmol/L) in the lixisenatide group and -113.3 h·mg/dL (-6.3 h·mmol/L) in the sitagliptin group (LS mean between-group difference -234.0 h·mg/dL [-13.0 h·mmol/L], 95% confidence interval -285.02 to -183.00 h·mg/dL [-15.8 to -10.2 h·mmol/L]; P < .0001). Lixisenatide led to significantly greater LS mean reductions in maximum PPG excursion than sitagliptin (-122.4 vs -46.6 mg/dL [-6.8 vs -2.6 h·mmol/L]; P < .0001). Change-from-baseline reductions in exposure to C-peptide, fasting glycoalbumin levels, and the gastric emptying rate were greater in the lixisenatide than in the sitagliptin group. The incidence of treatment-emergent adverse events was higher with lixisenatide (60.9%) than with sitagliptin (16.4%), with no serious events or severe hypoglycaemia reported. CONCLUSION: Lixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

Hemoglobin Vesicles prolong the time to circulatory collapse in rats during apnea.

BACKGROUND: Hemoglobin vesicles (HbV) are hemoglobin-based oxygen carriers manufactured by liposome encapsulation of hemoglobin molecules. We hypothesised that the infusion of oxygenated HbV could prolong the time to circulatory collapse during apnea in rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into four groups (Air, Oxy, NS and HbV). The rats were anaesthetized with isoflurane and the trachea was intubated using 14-gauge intravenous catheters. Rats in the Air group were mechanically ventilated with 1.5% isoflurane in room air, and those in other groups received 1.5% isoflurane in 100% oxygen. Mechanical ventilation was withdrawn 1 min after the administration of rocuronium bromide to induce apnea. After 30 s, 6 mL saline and HbV boluses were infused at a rate of 0.1 mL/s in the NS and HbV groups, respectively. Circulatory collapse was defined as a pulse pressure < 20 mmHg and the time to reach this point (PP20) was compared between the groups. The results were analysed via a one-way analysis of variance and post-hoc Holm-Sidak test. RESULTS: PP20 times were 30.4 ± 4.2 s, 67.5 ± 9.7 s, 95 ± 17.3 s and 135 ± 38.2 s for the Air (ventilated in room air with no fluid bolus), Oxy (ventilated with 100% oxygen with no fluid bolus), NS (ventilated with 100% oxygen with a normal saline bolus), and HbV (ventilated in 100% oxygen with an HbV bolus) groups, respectively, and differed significantly between the four groups (P = 0.0001). The PP20 times in the HbV group were significantly greater than in the Air (P = 0.0001), Oxy (P = 0.007) and NS (P = 0.04) groups. CONCLUSION: Infusion of oxygenated HbV prolongs the time to circulatory collapse during apnea in rats.

Drebrin and Spine Formation.

Dendritic spines are the postsynaptic receptive regions of most excitatory synapses in the central nervous system. Thus, spines are supposed to act as a fundamental unit for information processing of the brains. Previous studies have demonstrated the roles of drebrin in the formation of dendritic spines and in the recruitment of synaptic proteins to postsynaptic sites. Further, a live imaging study has revealed the unique dynamics of drebrin in dendritic spines, which help to understand how drebrin is involved in dendritic spine formation. This review will provide a basic knowledge about dendritic spine and overview recent progresses in understanding of the roles of drebrin in dendritic spine morphogenesis and synaptogenesis.

Feasibility, reliability, and validity of the Japanese version of the 12-item World Health Organization Disability Assessment Schedule-2 in preoperative patients.

PURPOSE: The avoidance of postoperative functional disability is one of the most important concerns of patients facing surgery, but methods to evaluate disability have not been definitively established. The aim of our study was to evaluate the feasibility, reliability, and validity of the Japanese version of the 12-item World Health Organization Disability Assessment Schedule-2 (WHODAS 2.0-J) in preoperative patients. METHODS: Individuals aged ≥55 years who were scheduled to undergo surgery in a tertiary-care hospital in Japan between April 2016 and September 2016 were eligible for enrolment in the study. All patients were assessed preoperatively using the WHODAS 2.0-J, the 8-Item Short Form (SF-8) questionnaire, and the Tokyo Metropolitan Institute of Gerontology Index (TMIG Index). The feasibility, reliability, and validity of WHODAS2.0-J were evaluated using response rate, Cronbach's alpha (a measure of reliability), and the correlation between the WHODAS 2.0-J and the SF-8 questionnaire and TMIG Index, respectively. RESULTS: A total of 934 patients were enrolled in the study during the study period, of whom 930 completed the WHODAS 2.0-J (response rate 99.5%) preoperatively. Reliability and validity were assessed in the 898 patients who completed all three assessment tools (WHODAS 2.0-J, SF-8 questionnaire, and TMIG Index) and for whom all demographic data were available. Cronbach's alpha was 0.92. The total score of the WHODAS 2.0-J showed a mild or moderate correlation with the SF-8 questionnaire and TMIG Index (r = -0.63 to -0.34). CONCLUSION: The WHODAS 2.0-J is a feasible, reliable, and valid instrument for evaluating preoperative functional disability in surgical patients.

Neurotrophin-3 Enhances the Synaptic Organizing Function of TrkC-Protein Tyrosine Phosphatase σ in Rat Hippocampal Neurons.

Neurotrophin-3 (NT-3) and its high-affinity receptor TrkC play crucial trophic roles in neuronal differentiation, axon outgrowth, and synapse development and plasticity in the nervous system. We demonstrated previously that postsynaptic TrkC functions as a glutamatergic synapse-inducing (synaptogenic) cell adhesion molecule trans-interacting with presynaptic protein tyrosine phosphatase σ (PTPσ). Given that NT-3 and PTPσ bind distinct domains of the TrkC extracellular region, here we tested the hypothesis that NT-3 modulates TrkC/PTPσ binding and synaptogenic activity. NT-3 enhanced PTPσ binding to cell surface-expressed TrkC and facilitated the presynapse-inducing activity of TrkC in rat hippocampal neurons. Imaging of recycling presynaptic vesicles combined with TrkC knockdown and rescue approaches demonstrated that NT-3 rapidly potentiates presynaptic function via binding endogenous postsynaptic TrkC in a tyrosine kinase-independent manner. Thus, NT-3 positively modulates the TrkC-PTPσ complex for glutamatergic presynaptic assembly and function independently from TrkC kinase activation. Our findings provide new insight into synaptic roles of neurotrophin signaling and mechanisms controlling synaptic organizing complexes. Significance statement: Although many synaptogenic adhesion complexes have been identified in recent years, little is known about modulatory mechanisms. Here, we demonstrate a novel role of neurotrophin-3 in synaptic assembly and function as a positive modulator of the TrkC-protein tyrosine phosphatase σ complex. This study provides new insight into the involvement of neurotrophin signaling in synapse development and plasticity, presenting a molecular mechanism that may underlie previous observations of short- and long-term enhancement of presynaptic function by neurotrophin. Given the links of synaptogenic adhesion molecules to autism and schizophrenia, this study might also contribute to a better understanding of the pathogenesis of these disorders and provide a new direction for ameliorating imbalances in synaptic signaling networks.

Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis.

BACKGROUND: Various signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis. METHODS: Mice received a single dose of 3 mg/kg body weight of bleomycin (BLM) and were sacrificed at designated days post-instillation (dpi). Lung homogenates and sections from mice in the early inflammatory phase were subjected to phospho-protein array analysis and immunofluorescence studies, respectively. Bronchoalveolar lavage fluid (BALF) from mice was subjected to an enzyme-linked immunosorbent assay (EIA) for interleukin (IL)-6 and evaluation of infiltrated cell populations. The effects of endogenous and exogenous IL-6 on the BLM-induced apoptotic signal in A549 cells and type 2 pneumocytes were elucidated. In addition, the effect of IL-6-neutralizing antibody on BLM-induced lung injury was evaluated. RESULTS: Phospho-protein array revealed that BLM induced phosphorylation of molecules downstream of the IL-6 receptor such as Stat3 and Akt in the lung at 3 dpi. At 3 dpi, immunofluorescence studies showed that signals of phospho-Stat3 and -Akt were localized in type 2 pneumocytes, and that BLM-induced IL-6-like immunoreactivity was predominantly observed in type 2 pneumocytes. Activation of caspases in BLM-treated A549 cells and type 2 pneumocytes was augmented by application of IL-6-neutralizing antibody, a PI3K inhibitor or a Stat3 inhibitor. EIA revealed that BLM-induced IL-6 in BALF was biphasic, with the first increase from 0.5 to 3 dpi followed by the second increase from 8 to 10 dpi. Blockade of the first increase of IL-6 by IL-6-neutralizing antibody enhanced apoptosis of type 2 pneumocytes and neutrophilic infiltration and markedly accelerated fibrosis in the lung. In contrast, blockade of the second increase of IL-6 by IL-6-neutralizing antibody ameliorated lung fibrosis. CONCLUSIONS: The present study demonstrated that IL-6 could play a bidirectional role in the pathogenesis of lung fibrosis. In particular, upregulation of IL-6 at the early inflammatory stage of BLM-injured lung has antifibrotic activity through regulating the cell fate of type 2 pneumocytes in an autocrine/paracrine manner.