Effectiveness of acupuncture therapy for the prevention of emergence agitation in children: A systematic review and meta-analysis with trial sequential analysis.

This study aimed to evaluate the effectiveness of acupuncture therapy in preventing emergence agitation (EA) in children. A systematic review and meta-analysis were conducted across multiple locations according to the articles searched. Seven databases, including trial registration sites, were searched. A total of six trials were included involving 489 patients; of them, 244 received acupuncture therapy. Randomized clinical trials (RCTs) evaluating the incidence of EA compared with placebo/sham or standard care in children were included. The primary outcome was the incidence of EA, as evaluated using a specific assessment tool. Data about the incidence rate of EA, heterogeneity, quality of trials and evidence, and adverse events were collected. Additionally, data about patient demographic characteristics, type of anesthesia, duration and onset of acupuncture therapy, EA and pain score, time taken for extubation, and post-anesthesia care unit length of stay were collected. The results indicated that the overall incidence of EA in the acupuncture therapy group and the control group was 23.4% and 39.5%, respectively, with no significant difference (risk ratio, 0.62; 95% confidence interval, 0.26-1.48; I2 = 63%). Subgroup analysis showed a significant difference in the overall incidence of EA in the acupuncture therapy and control groups according to surgery type (high-risk vs. low-risk surgery), suggesting that acupuncture therapy may be effective in reducing EA for patients undergoing high-risk surgery. The quality of evidence was downgraded to "very low" due to the study designs, inconsistency, and possible publication bias. In conclusion, this meta-analysis shows that the currently available RCTs are insufficient to determine the effectiveness of acupuncture therapy in preventing EA in children undergoing general anesthesia.

A prospective randomized controlled study to assess the effectiveness of super FIXSORB WAVE® for sternal stabilization after sternotomy.

BACKGROUND: We developed a new sternal fixation device, Super FIXSORB WAVE®, a corrugated plate made of u-HA/PLLA, to improve sternal stability after sternotomy. This present study aimed to evaluate the new device clinically. METHODS: This prospective, single-blinded, multicenter trial randomized 69 patients to either wire cerclage only (group C, n = 30) or wire cerclage plus Super FIXSORB WAVE® (group W, n = 39). The primary endpoint was a degree of sternal displacement at six months. Displacement of the sternal halves in the anteroposterior and lateral directions was measured using computed tomography horizontal section images at the third costal and fourth intercostal levels. The secondary endpoints were sternal pain and quality-of-life over 6 months. RESULTS: Group W showed significantly reduced sternal anteroposterior displacement at both the third costal (0 [0-1.9] mm vs. 1.1 [0-2.1] mm; P = 0.014) and fourth intercostal (0 [0-1.0] mm) vs. 1.0 [0-1.8] mm; P = 0.015) levels than group C. In group W, lateral displacement was suppressed without a significant increase from 2 weeks to 6 months, while it increased in group C. There was no significant difference in postoperative sternal pain and quality-of-life between the two groups. No adverse events, such as infection, inflammation, or foreign body reaction, were observed with this device. CONCLUSIONS: Using Super FIXSORB WAVE®, sternal displacement was significantly suppressed in both the anteroposterior and lateral directions. The use of this device results in safe and easy sternal reinforcement without any adverse events, and sternal healing can be accelerated. CLINICAL TRIAL REGISTRY NUMBER: This study was registered in the Japan Registry of Clinical Trials (February 21, 2019; jRCTs032180146).

Association between knee cartilage thickness determined by magnetic resonance imaging three-dimensional analysis and the International Cartilage Repair Society (ICRS) arthroscopic grade.

BACKGROUND: The purpose of this study was to retrospectively investigate whether the average cartilage thickness calculated by magnetic resonance imaging (MRI) three-dimensional (3D) analysis system was correlated with the International Cartilage Repair Society (ICRS) grade at each subregion, as a representative scoring for arthroscopic evaluation. METHODS: The subjects were 102 patients who underwent arthroscopy for meniscus repair or high tibial osteotomy for medial osteoarthritis of the knee. Cartilage lesions were arthroscopically quantified according to the ICRS grade at each subregion. Fluoroscopy was used to compare the subregions on arthroscopic evaluation with subregions on MRI. The average cartilage thickness at each subregion was also automatically calculated from MRI data using our 3D analysis system. The association between ICRS grade and the average cartilage thickness at 18 subregions in the medial femoral and medial tibial regions was evaluated using Spearman's rank correlation coefficient. RESULTS: Examination of the fluoroscopic images revealed that the posterior subregions in the medial femoral region did not match the position between arthroscopy and MRI; therefore, those three subregions were excluded. In the medial femoral region, the ICRS grade correlated moderately with cartilage thickness at five subregions and weakly at one subregion. In the medial tibial region, the ICRS grade correlated moderately with cartilage thickness at four subregions and weakly at one subregion, but it did not correlate at the other four subregions. CONCLUSION: The average cartilage thickness determined by MRI 3D analysis correlated with arthroscopic grade at 11 of 15 subregions in the medial femoral and tibial regions.

Effects of melatonin on postoperative sleep quality: a systematic review, meta-analysis, and trial sequential analysis.

PURPOSE: Postoperative sleep disturbances are common. Although several studies have examined the effect of melatonin on postoperative sleep disturbances, the results have not reached any definitive conclusion. We sought to conduct a systematic review to compare the effects of melatonin and melatonin agonists on postoperative sleep quality with those of placebo or no treatment in adult patients who underwent surgery under general or regional anesthesia. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Web of Science, ClinicalTrials.gov, and the UMIN Clinical Trials Registry up to 18 April 2022. Randomized clinical trials examining the effects of melatonin or melatonin agonists in patients undergoing general or regional anesthesia with sedation for any surgery were eligible for inclusion. The primary outcome was sleep quality measured using a visual analog scale (VAS). The secondary outcomes were postoperative sleep duration, sleepiness, pain, opioid consumption, quality of recovery, and adverse events. A random-effects model was used to combine the results. We assessed study quality with the Cochrane Risk of Bias Tool version 2. We applied a trial sequential analysis to assess the precision of the combined results. RESULTS: Eight studies (516 participants) were analyzed for sleep quality. Of those, four studies used only a short duration of melatonin, either on the night before and the day of surgery or only on the day of surgery. A random-effects meta-analysis showed that melatonin did not improve sleep quality measured by VAS compared with placebo (mean difference, -0.75 mm; 95% confidence interval, -4.86 to 3.35), with low heterogeneity (I2, 5%). Trial sequential analysis revealed that the accrued information size (n = 516) reached the estimated required information size (n = 295). We downgraded the certainty of the evidence because of the high risk of bias. The effect on postoperative adverse events was comparable between the melatonin and control groups. CONCLUSION: Our results indicate that melatonin supplementation does not improve postoperative sleep quality measured with the VAS compared with placebo in adult patients (GRADE: moderate). STUDY REGISTRATION: PROSPERO (CRD42020180167); registered 27 October 2022.

RéSUMé: OBJECTIF: Les troubles du sommeil postopératoires sont fréquents. Bien que plusieurs études aient examiné l'effet de la mélatonine sur les troubles du sommeil postopératoires, les résultats n'ont abouti à aucune conclusion définitive. Nous avons tenté de réaliser une revue systématique afin de comparer les effets de la mélatonine et des agonistes de la mélatonine sur la qualité du sommeil postopératoire à ceux d'un placebo ou de l'absence de traitement chez des patients adultes ayant bénéficié d'une intervention chirurgicale sous anesthésie générale ou régionale. MéTHODE: Nous avons effectué des recherches dans les bases de données MEDLINE, le registre Cochrane des essais contrôlés, Embase, Web of Science, ClinicalTrials.gov et le registre des essais cliniques UMIN pour en tirer les manuscrits publiés jusqu'au 18 avril 2022. Les études cliniques randomisées examinant les effets de la mélatonine ou des agonistes de la mélatonine chez des patients bénéficiant d'une anesthésie générale ou régionale avec sédation pour toute intervention chirurgicale étaient éligibles pour l'inclusion. Le critère d'évaluation principal était la qualité du sommeil mesurée à l'aide d'une échelle visuelle analogique (EVA). Les critères d'évaluation secondaires étaient la durée du sommeil postopératoire, la somnolence, la douleur, la consommation d'opioïdes, la qualité de la récupération et les événements indésirables. Un modèle à effets aléatoires a été utilisé pour combiner les résultats. Nous avons évalué la qualité des études en utilisant l'outil de risque de biais de Cochrane version 2.0. Nous avons appliqué une analyse séquentielle des études pour évaluer la précision des résultats combinés. RéSULTATS: Huit études (516 participants) ont été analysées pour déterminer la qualité du sommeil. Parmi celles-ci, quatre études n'ont utilisé la mélatonine que pour une courte durée, c'est-à-dire soit la nuit précédant et le jour de la chirurgie, soit le jour de la chirurgie seulement. Une méta-analyse à effets aléatoires a montré que la mélatonine n'améliorait pas la qualité du sommeil mesurée par une EVA comparativement au placebo (différence moyenne, -0,75 mm; intervalle de confiance à 95 %, -4,86 à 3,35), avec une faible hétérogénéité (I2, 5 %). L'analyse séquentielle des études a révélé que la taille de l'information accumulée (n = 516) avait atteint la taille estimative de l'information requise (n = 295). Nous avons abaissé le niveau de confiance des données probantes en raison du risque élevé de biais. L'effet sur les événements indésirables postopératoires était comparable entre le groupe mélatonine et les groupes témoin. CONCLUSION: Nos résultats indiquent que la supplémentation en mélatonine n'améliore pas la qualité du sommeil postopératoire mesurée avec une EVA par rapport au placebo chez les patients adultes (GRADE : modérée). ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020180167); enregistrée le 27 octobre 2020.

Mechanism of transient photothermal inactivation of bacteria using a wavelength-tunable nanosecond pulsed laser.

There is a great demand for novel disinfection technologies to inactivate various pathogenic viruses and bacteria. In this situation, ultraviolet (UVC) disinfection technologies seem to be promising because biocontaminated air and surfaces are the major media for disease transmission. However, UVC is strongly absorbed by human cells and protein components; therefore, there are concerns about damaging plasma components and causing dermatitis and skin cancer. To avoid these concerns, in this study, we demonstrate that the efficient inactivation of bacteria is achieved by visible pulsed light irradiation. The principle of inactivation is based on transient photothermal heating. First, we provide experimental confirmation that extremely high temperatures above 1000 K can be achieved by pulsed laser irradiation. Evidence of this high temperature is directly confirmed by melting gold nanoparticles (GNPs). Inorganic GNPs are used because of their well-established thermophysical properties. Second, we show inactivation behaviour by pulsed laser irradiation. This inactivation behaviour cannot be explained by a simple optical absorption effect. We experimentally and theoretically clarify this inactivation mechanism based on both optical absorption and scattering effects. We find that scattering and absorption play an important role in inactivation because the input irradiation is inherently scattered by the bacteria; therefore, the dose that bacteria feel is reduced. This scattering effect can be clearly shown by a technique that combines stained Escherichia coli and site selective irradiation obtained by a wavelength tunable pulsed laser. By measuring Live/Dead fluorescence microscopy images, we show that the inactivation attained by the transient photothermal heating is possible to instantaneously and selectively kill microorganisms such as Escherichia coli bacteria. Thus, this method is promising for the site selective inactivation of various pathogenic viruses and bacteria in a safe and simple manner.

Alterations in cartilage quantification before and after injections of mesenchymal stem cells into osteoarthritic knees.

Several studies have reported improvement in knee pain following mesenchymal stem cell (MSC) injections for knee osteoarthritis (OA). We developed a novel 3D magnetic resonance imaging (MRI) analysis software program that provides "projected cartilage area ratios" for automatic detection of changes in cartilage amounts. The primary objective of this prospective interventional study was to compare alterations in the projected cartilage area ratio (thickness ≥ 1.5 mm) at the femoral posteromedial region between 30 weeks before and 30 weeks after synovial MSC injections. Secondary objectives were to assess the clinical scores and safety of MSC injections. Patients with OA who complained of knee pain underwent autologous synovial MSC injections into the knee at time 0 and again 15 weeks later. MRI examinations were performed at - 30, - 15, - 1, and 30 weeks. Patients showing < 3% decreases in the projected cartilage area ratio (thickness ≥ 1.5 mm) at the femoral the posteromedial region from - 30 weeks to - 15 weeks were excluded from the study. The Lysholm Knee Score, Knee Injury and Osteoarthritis Outcome Scale (KOOS), and Numerical Rating Scale (NRS) scores were evaluated at - 30, - 15, - 5, - 2, 0, 5, 10, 15, 20, 25, and 30 weeks. Five patients were excluded because 3D MRI analysis showed no cartilage loss at - 15 weeks. Ultimately, eight OA patients underwent MSC injections. The projected cartilage area ratio significantly decreased by 0.07 in the 30 weeks before MSC injections (p = 0.01), but no further decreases occurred in the 30 weeks after MSC injections. The projected cartilage area ratio at the femoral posteromedial region showed a significant difference between 30 weeks before and 30 weeks after MSC injections. The Lysholm Knee Score, KOOS, and NRS values improved significantly after the injections. MSC injection could not be ruled out as the cause of two adverse events: transient knee pain and itching in both hands. Fully automatic 3D MRI analysis showed that synovial MSC injections suppressed cartilage loss in patients with progressive OA.Trial registration: Intraarticular injections of synovial stem cells for osteoarthritis of the knee (Number UMIN 000026732). Date of registration; June 1, 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029967 .

Changes in serum KL-6 levels during short-term strict antigen avoidance are associated with the prognosis of patients with fibrotic hypersensitivity pneumonitis caused by avian antigens.

BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is the most common type of fibrotic hypersensitivity pneumonitis (HP). Antigen avoidance (AA) is a key step in the diagnosis and management of HP, but not all fibrotic HP patients improve through AA. Because of the poor prognosis of fibrotic HP, predictive biomarkers to identify patients showing rapid progression during AA are urgently needed. METHODS: From a retrospective review of the medical records of 1941 patients with interstitial lung disease, 75 cases of fibrotic BRHP confirmed by a provocation test or surgical lung biopsy were identified. To identify potential prognostic markers obtained at or around diagnosis, physiological and serological variables at diagnosis and the relative changes in those variables during strict AA were evaluated. Cox proportional hazards models with log-rank testing were used to compare the associations between these variables and survival. RESULTS: Univariate analyses showed that gender, smoking status, and the relative change in the serum levels of Krebs von den Lungen-6 (KL-6) were associated with prognosis (P = 0.02, 0.04, and 0.02, respectively), but the presence of honeycombing and the forced vital capacity were not associated with survival. The relative change in KL-6 levels (greater than vs. less than a 10% decrease) was significantly associated with survival in a stratified analysis (73.9 vs. 34.9 months; P = 0.04). CONCLUSIONS: The relative change in KL-6 levels is associated with the prognosis of patients with fibrotic BRHP independent of previously identified prognostic biomarkers. This finding could help pulmonologists identify fibrotic BRHP patients that are likely to show rapid progression.

A cognitive bias in diagnostic reasoning and its remediation by the "2-Dimensional Approach".

This article was migrated. The article was marked as recommended. Background Misdiagnoses are associated with various cognitive biases, which are difficult to reduce even if physicians think about clinical cases deliberately. We propose a new "2-Dimensional Approach" that combines two perspectives in diagnostic reasoning: organs (brain, heart, lung, intestine/liver, kidney) and systems (metabolic, endocrine, blood/tumor, infection, immune, circulatory, nervous systems). Systems involve throughout the whole body and can be pathogenesis of diseases. As a result of diseases, organs show abnormal vital signs and symptoms. We investigated: (1) whether each individual resident has a bias for either organs or systems when they diagnose clinical cases, and (2) whether the 2D Approach can reduce such a bias. Methods We randomly assigned PGY1 residents (n=105) to either the 2D Approach group (n=45) or a control group (n=60). After attending either a lecture on the 2D Approach or a non-related lecture, residents were asked to diagnose two clinical cases. We divided each diagnosis into one of the two categories, either "organs" or "systems". We investigated whether each resident would diagnose the two cases into the same category, either organs or systems (i.e., a bias for either organs or systems). Results The participants in the control group tended to diagnose the two cases into the same category, either organs or systems (OR: 5.63, 95% CI: 1.62-21.7, p=0.0030, Fisher's exact test). In the 2D Approach group, the category of diagnoses for the two cases were not related to each other (OR: 2.14, 95% CI: 0.50-9.81, p=0.33). Conclusion There is a bias for either organs or systems when residents diagnose clinical cases, suggesting that organs and systems are different perspectives in diagnostic reasoning. By combining these 2 different perspectives in a 2-dimensional matrix, the 2D Approach reduces this bias.

Corrugated Sheet of Unsintered Hydroxyapatite Poly-L-Lactide for Sternal Fixation: A Preclinical Study.

PURPOSE: To stabilize the sternum after median sternotomy, unsintered hydroxyapatite poly-L-lactide (u-HA/PLLA) sternal pins are frequently used in Japan. However, sternal pins are ineffective in the fragile bone marrow. Thus, a corrugated sheet made of u-HA/PLLA was developed as a new sternal fixation device. METHODS: To examine the effects of the device, we measured the shear force using a sternal model and cadaver. The shear force of the corrugated sheet, sternal pin, and simple wire was compared. The device size was determined after reviewing the sternal computed tomography (CT) of 128 patients. RESULTS: The shear force of the model with the corrugated sheet (286 [256-295] N) was higher than that with sternal pins (135 [134-139] N, p = 0.03) and simple wire (94 [90-104] N, p = 0.03) at 2-mm displacement. In the cadaver test, the shear force of the sternal halves with the device was about two times higher than that without the device. Retrospective CT showed that 18-mm wide device applies to 99% male and 87% female patients at the fourth intercostal level. CONCLUSION: The corrugated sheet might provide a stronger fixation effect in the fragile bone marrow. The device width was modified to 18 mm to be applicable for most Japanese patients.

Diabetic Retinopathy as a Risk Factor Associated with the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

BACKGROUND: The risk factors associated with the development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD) are still unclear. The aim of the present study was to identify such risk factors in NAFLD patients who developed HCC. METHODS: Between April 2000 and -December 2016, a total of 182 patients with NAFLD were enrolled in this study; of these, only 22 patients had HCC. To identify risk factors, univariate and multivariate analyses were performed. To identify risk factors other than the degree of fibrosis, propensity matched analysis adjusted by the NAFLD fibrosis score (NFS) was carried out on 44 patients. Multivariate and survival analyses were also performed in HCC patients. RESULTS: In 182 patients, multivariate analysis highlighted the NFS (OR 2.275; p < 0.001) and hypertension (OR 5.868; p = 0.037) as independent factors that were significantly associated with the development of HCC. After adjustment for the NFS, multivariate analysis identified diabetic retinopathy (OR 8.654; p = 0.017) as an independent factor that was significantly associated with the development of HCC. For predicting the development of HCC, the area under the receiver operating characteristic curve of diabetic retinopathy was significantly higher than that of diabetes (0.731 vs. 0.615; p < 0.001). In patients with HCC, multivariate analysis indicated that the NFS were significantly associated with diabetic retinopathy. CONCLUSIONS: Diabetic retinopathy as well as liver fibrosis is a risk factor that associates with the development of HCC in NAFLD patients. Therefore, NAFLD patients with diabetic retinopathy should undergo careful screening for HCC.

Global Distribution of Used and Unused Extracted Materials Induced by Consumption of Iron, Copper, and Nickel.

In today's global economy, sustainable resource management requires a consumption perspective of resource use and insight into actual resource use through the global supply chain. The estimated global amount of used and unused extraction caused by mineral extraction of iron, copper, and nickel more than doubled from 1990 to 2013 (iron, 2.8-6.7 Pg; copper, 2.7-5.5 Pg; nickel, 0.19-0.60 Pg). By incorporating global material flow into a global link input-output model (GLIO, a hybrid multiregional IO model), we estimated the total used and unused extraction caused by iron, copper, and nickel mining induced by Japanese final demand to be 0.44, 0.52, and 0.043 Pg in 2011, respectively, equivalent to 7.1% of the total global extraction amount caused by iron mining, 11% of the amount caused by copper mining, and 10% of the amount caused by nickel mining. Whereas the world extraction total caused by iron, copper, and nickel mining rapidly increased from 2005 to 2011, the extraction amount induced by Japanese final demand for the same period either stayed about the same (iron) or decreased slightly (copper, 99% of the 2005 amount; nickel, 92%).

Trends in isolated meniscus repair and meniscectomy in Japan, 2011-2016.

BACKGROUND: Meniscus surgery is the most commonly performed orthopedic surgery, and despite recent emphasis on saving the meniscus, the current status of meniscus surgeries is little known in many countries, including Japan. The National Database of Health Insurance Claims and Specific Health Checkups of Japan and the Statistics of Medical Care Activities in Public Health Insurance track meniscus surgeries through health insurance claims. The National Database provides the numbers for 2014 and 2015, and the Statistics of Medical Care Activities provides the numbers from June 2011 to June 2016. Our aim was to analyze isolated meniscus surgery numbers and meniscus repair ratios by age group based on the National Database and evaluate trends of meniscus repair ratios for the latest six years from the Statistics of Medical Care Activities. METHODS: Meniscus surgeries by age group were counted from the National Database for 2014-2015, and meniscus repair ratios (meniscus repairs/meniscus surgeries) were calculated. The numbers were also counted from the Statistics of Medical Care Activities in 2011-2016. For statistical analysis of annual trends of meniscus repair ratios, the Cochran-Armitage trend test was used. Meniscus surgeries with concomitant knee ligament surgeries were excluded. RESULTS: According to the National Database, isolated meniscus surgeries totaled 34,966 in 2015, with peak ages of patients in their late teens and 60s. The meniscus repair ratio was 19% in 2014 and 24% in 2015. According to the Statistics of Medical Care Activities, the meniscus repair ratio was 9% in 2011 and significantly increased to 25% in 2016 (p = 0.0008). The ratio also increased significantly in each age group between the early 20s and late 70s. CONCLUSIONS: Approximately 35,000 meniscus surgeries are performed in Japan annually, with peak ages in the late teens and 60s. The number of meniscus repairs has increased over the past six years.

Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration.

Exchange protein directly activated by cAMP (EPAC) is a mediator of a cAMP signaling pathway that is independent of protein kinase A. EPAC has two isoforms (EPAC1 and EPAC2) and is a cAMP-dependent guanine nucleotide exchange factor for the small GTPases, Rap1 and Rap2. Recent studies suggest that EPAC1 has both positive and negative influences on cancer and is involved in cell proliferation, apoptosis, migration and metastasis. We report that EPAC1 and EPAC2 expression levels were significantly lower in bladder cancer tissue than in normal bladder tissue. In addition, bladder cancer cell lines showed reduced EPAC1 mRNA expression. Furthermore, EPAC1 overexpression in bladder cancer cell lines induced morphologic changes and markedly suppressed cell migration without affecting cell viability. The overexpressed EPAC1 preferentially localized at cell-cell interfaces. In conclusion, reduced EPAC1 expression in bladder tumors and poor migration of EPAC1-overexpressing cells implicate EPAC1 as an inhibitor of bladder cancer cell migration.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

BACKGROUND: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. RESULTS: D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. CONCLUSION: It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. TRIAL REGISTRATION: UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C.

BACKGROUND AND AIMS: Although treatment for hepatitis C virus has been dramatically improved by the development of direct-acting antiviral agents (DAAs), whether interferon (IFN)-free therapy reduces hepatocarcinogenesis in an equivalent manner to IFN-based therapy remains controversial. The aims of this study were to evaluate the occurrence and recurrence of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients treated with DAAs and to identify biomarkers of HCC development after antiviral treatment. METHODS: A restrospective review of a prospective database of 1,897 CHC patients who were treated with IFN-based (1,145) or IFN-free therapies (752) was carried out. Cumulative HCC occurrence and recurrence rates were compared using propensity score-matched analysis. Predictors of HCC development after viral eradication were identified by multivariate analysis. RESULTS: Propensity score-matched analysis showed no significant difference in HCC occurrence (p=0.49) and recurrence rates (p=0.54) between groups treated with IFN-based or IFN-free therapies. In multivariate analysis, higher levels of post-treatment α-fetoprotein (AFP) or Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+M2BP) were independently associated with HCC occurrence and recurrence after viral eradication. Only post-treatment WFA+M2BP level was significantly associated with HCC occurrence and recurrence among patients without severe fibrosis. The area under the receiver operating characteristic (ROC) curve for WFA+M2BP levels was greater than that for AFP levels in ROC analysis. CONCLUSION: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy. Patients with high WFA+M2BP levels after antiviral treatment, even without severe fibrosis, must be followed up carefully for HCC development. Lay summary: The risks of early HCC occurrence and recurrence after viral eradication were similar between IFN-based and IFN-free therapies. Post-treatment levels of WFA+M2BP may be helpful screening biomarkers for assessing the risk of HCC after IFN-free therapy.

Global land-use change hidden behind nickel consumption.

Economic growth is associated with a rapid rise in the use of natural resources within the economy, and has potential environmental impacts at local and/or global scales. In today's globalized economy, each country has indirect flows supporting its economic activities, and natural resource consumption through supply chains influences environmental impacts far removed from the place of consumption. One way to control environmental impacts associated with consumption of natural resources is to identify the consumption of natural resources and the associated environmental impacts through the global supply chain. In this study, we used a global link input-output model (GLIO, a hybrid multiregional input-output model) to detect the linkages between national nickel consumption and mining-associated global land-use changes. We focused on nickel, whose global demand has risen rapidly in recent years, as a case study. The estimated area of land-use change around the world caused by nickel mining in 2005 was 1.9km2, and that induced by Japanese final demand for nickel was 0.38km2. Our modeling also revealed that the areas of greatest land-use change associated with nickel mining were concentrated in only a few countries and regions far removed from the place of consumption. For example, 57.7% of the world's land-use changes caused by nickel mining were concentrated in five countries in 2005: Australia, 13.7%; Russia, 12.9%; Indonesia, 12.5%; New Caledonia, 10.4%; and Colombia, 8.2%. The mining-associated land-use change induced by Japanese final demand accounted for 19.5% of the total area affected by land-use change caused by nickel mining. The top three countries accounted for 70.6% (Indonesia: 47.0%, New Caledonia: 16.0%, and Australia: 7.7%), and the top five accounted for 82.4% (the Philippines: 7.5%, and Canada: 4.3%, in addition to the top three countries and regions).

Effect of two desensitizing agents on dentin permeability in vitro

Abstract Objective The aim of this in vitro study was to investigate the effect of two desensitizing agents and water on hydraulic conductance in human dentin. Material and Methods GLUMA Desensitizer PowerGel (GLU) contains glutaraldehyde (GA) and 2-hydroxyethyl methacrylate (HEMA), and Teethmate Desensitizer (TD) is a powder comprising tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) that is mixed with water. Deionized water was used as a negative control (CTR). Thirty discs with a thickness of 1.2 mm were cut from the coronal dentin of the third molars and cleaned with 0.5 M EDTA (pH 7.4). After being mounted in a split-chamber device, the discs were pressurized with water at 1 kPa and 3 kPa in order to measure flow rates with a highly sensitive micro-flow sensor and to calculate hydraulic conductance as a baseline value (BL). Following the application of GLU, TD, and CTR (n=10), hydraulic conductance was remeasured with intermittent storage in water after 15 min, 1 d, 1 w, and 1 m. Reduction in permeability (PR%) was calculated from hydraulic conductance. Data were statistically analyzed using nonparametric methods (α<0.05). Representative discs were inspected by SEM. Results PR% for GLU and TD were 30-50% 15 min and 1 m after their application. Post hoc tests indicated that PR% of CTR was significantly greater than those of GLU and TD at all time points tested. The PR% of GLU and TD were not significantly different. SEM examinations showed noncollapsed collagen meshes at the tubular entrances after GLU, and crystalline precipitates occluding the tubular orifices after TD, whereas CTR specimens showed typical patterns of etched dentin. Conclusions The present study on hydraulic conductance in dentin discs treated with two chemically different desensitizing agents and water as a control demonstrated that both products may be characterized as effective.

Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury: A multicenter randomized controlled trial.

PURPOSE: To evaluate the effects of atrial natriuretic peptide (ANP) on renal function and medical costs in patients with acute kidney injury (AKI) associated with cardiac surgery. MATERIALS AND METHODS: The Japanese trial for AKI in Post-cardiovascular surgery patients by ANP (JAPAN) was a prospective, multicenter, randomized, double-blind, placebo-controlled study conducted in 11 hospitals in Japan. Acute kidney injury was defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours. The patients were randomly assigned to receive ANP (0.02 µg kg-1 min-1) or placebo. The primary end point was a change in renal function. The secondary end points were a need for renal replacement therapy, the lengths of intensive care unit and hospital stays, and medical costs incurred over the 90-day follow-up. RESULTS: Of the 77 randomized patients, 37 were in the ANP group and 40 were in the placebo group. Although ANP significantly (P = .018) increased urine output, it did not significantly improve renal function compared with placebo. There were no significant differences between the groups in the renal replacement therapy rate, the lengths of the intensive care unit and hospital stays, or medical costs. CONCLUSION: Atrial natriuretic peptide infusion did not show a renoprotective effect or cost-saving effect in the treatment of cardiac surgery-associated AKI.

Perioperative Elevation in Cell-Free DNA Levels in Patients Undergoing Cardiac Surgery: Possible Contribution of Neutrophil Extracellular Traps to Perioperative Renal Dysfunction.

Background. This study aimed to determine the perioperative change in serum double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil extracellular trap concentration in samples from patients undergoing cardiac surgery and to analyze a relationship between serum dsDNA concentrations and perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples that were collected during a previously conducted, prospective, multicenter, observational study were measured. Eighty patients undergoing elective cardiac surgery were studied. Serum samples were collected at baseline, immediately after surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration was significantly increased from baseline (median, 398 ng/mL [interquartile range, 372-475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437-682 ng/mL], p < 0.001), and they were reduced by POD-1 (median, 323 ng/mL [256-436 ng/mL]). The difference in serum creatinine concentration between baseline and POD-1 was correlated with dsDNA concentration on POD-1 (rs = 0.61, p < 0.001). Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is elevated postoperatively. Prolonged elevation in dsDNA concentration is correlated with perioperative renal dysfunction. Further large-scale studies are needed to determine the relationship between serum concentration of circulating dsDNA and perioperative renal dysfunction.

High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).