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The International Consensus on ANA Patterns (ICAP) is an ongoing international initiative dedicated to harmonizing technical and interpretation aspects of the HEp-2 IFA test. Comprised of internationally recognized experts in autoimmunity and HEp-2 IFA testing, ICAP has operated for the last 10 years by promoting accurate reading, interpretation, and reporting of HEp-2 IFA images by professionals involved in various areas related to autoimmune diseases, such as clinical diagnostic laboratories, academic research, IVD industry, and patient care. ICAP operates through continuous information exchange with the international community and encourages the participation of younger experts from all over the world. The 7th ICAP workshop has addressed several aspects that originated from this interaction with the international community and has effectively established objective goals and tasks to be delivered over the next two years. Some of these are outlined in this article, including the planning of three audio-visual educational modules to be posted at the www.anapattern.org website, the classification of two novel HEp-2 IFA patterns, the implementation of a project dedicated to continuously updating the information on the clinical and immunologic relevance of the HEp-2 IFA patterns, and the launch of two additional branches of the HEp-2 Clinical and Immunological (HEp-2 CIC) project., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luis E. C. Andrade reports a relationship with Inova that includes: consulting or advisory. May Choi receives consulting fees from Werfen, MitogenDx, AstraZeneca, GlaxoSmithKline, Celltrion, Organon, and Mallinckrodt Pharmaceuticals. Jan Damoiseaux is consultant for ThermoFisher/Phadia and Werfen/Inova and receives speaker fees from Euroimmun, ThermoFisher/Phadia, Werfen/Inova, and Menarini. Carlos Alberto von Mühlen is consultant for Euroimmun and ARTIVA Biotherapeutics. Marvin J. Fritzler was and/or continues to be a consultant to Inova/Werfen, Alexion Pharmaceuticals, and Bio-Rad. Marvin J. Fritzler and May Choi are directors of Mitogen Diagnostics Corporation. ICAP is partially supported by grants from the American Proficiency Institute, Grifols, Immunoconcepts, Bio-Rad, Aesku Group, Biosystems, Trinity Biotech, Mitogen Diagnostics, A.Menarini Diagnostics, Euroimmun, ThremoFischer Scientific, and Inova Diagnostics. The funding organizations played no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the report for publication. The corresponding author, Luis E. C. Andrade, is a member of the editorial board of Autoimmunity Reviews. Luis Andrade and the other authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The P of achieving pregnancy is an important trait of bull fertility in beef cattle and is defined as the bull conception rate (BCR). This study aimed to clarify and better understand the genetic architecture of the BCR calculated using artificial insemination and pregnancy diagnosis records from a progeny testing program in Japanese Black bulls. In this study, we estimated the genetic parameters of the BCR and their correlation with semen production traits. In addition, we assessed the correlated responses in BCR by considering the selection of semen production traits. Nine hundred and sixteen Japanese Black bulls were selected based on fertility, with 28 869 pregnancy diagnostic records from the progeny testing program. Our results showed that the heritability estimate was 0.04 in the BCR at the first service and 0.14 in BCR for the three services, and an increase in the inbreeding coefficient led to a significant decrease in BCR. The phenotypic trend of BCR remained almost constant over the years, whereas the genetic trend increased. In addition, the changes in the progeny testing year effect showed a similar tendency to the phenotypic trends, suggesting that the phenotypic trends could be mainly due to non-genetic effects, including progeny testing year effects. The estimated genetic correlation of BCR with sperm motility traits was favorably moderate to high (ranging from 0.49 to 0.97), and those with sperm quantity traits such as semen volume were favorably low to moderate (ranging from 0.23 to 0.51). In addition, the correlated responses in BCR at the first service by selection for sperm motility traits resulted in a higher genetic gain than direct selection. This study provides new insights into the genetic factors affecting BCR and the possibility of implementing genetic selection to improve BCR by selecting sperm motility traits in Japanese Black bulls., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: With the development of novel therapies for advanced malignant melanoma (MM), biomarkers that can accurately reflect the progression of MM are needed. Serum levels of melanin-related indole metabolites such as 5-hydroxy-6-methoxyindole-2-carboxylic acid (5H6MI2C) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are potential biomarkers for MM. Here, we describe the development of a mass spectrometry (MS)-based assay to determine serum levels of 5H6MI2C and 6H5MI2C., Materials and Methods: We developed a stable isotope dilution-selective reaction monitoring-MS protocol using liquid chromatography tandem mass spectrometry (LC-MS/MS) to measure human serum 5H6MI2C and 6H5MI2C levels. Analytical evaluations of the method were performed and the method was applied to serum samples from MM patients (n = 81)., Results: The method established in this study showed high reproducibility and linearity. This novel method also found that serum 6H5MI2C levels were significantly elevated in patients with metastatic MM compared to those with non-metastatic MM. Unfortunately, 5H6MI2C did not show a comparable significant difference., Conclusion: We successfully established measurement methods for serum 5H6MI2C and 6H5MI2C levels using LC-MS/MS. Serum 6H5MI2C levels offer a potential marker for MM., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Tomohiro Nakayama belongs to an endowment division, supported with a grant from JEOL Ltd. since June 2020. There are no other conflicts of interest to declare.’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chandipura virus (CHPV) is a negative-sense single-stranded RNA virus known to cause fatal encephalitis outbreaks in the Indian subcontinent. The virus displays tropism towards the pediatric population and holds significant public health concerns. Currently, there is no specific, effective therapy for CHPV encephalitis. In this study, we evaluated a novel C.B-17 severe combined immunodeficiency (SCID) mouse model which can be used for pre-clinical antiviral evaluation. Inoculation of CHPV developed a lethal infection in our model. Plaque assay and immunohistochemistry detected increased viral loads and antigens in various organs, including the brain, spinal cord, adrenal glands, and whole blood. We further conducted a proof-of-concept evaluation of favipiravir in the SCID mouse model. Favipiravir treatment improved survival with pre-symptomatic (days 5-14) and post-symptomatic (days 9-18) treatment. Reduced viral loads were observed in whole blood, kidney/adrenal gland, and brain tissue with favipiravir treatment. The findings in this study demonstrate the utility of SCID mouse for in vivo drug efficacy evaluation and the potential efficacy of favipiravir against CHPV infection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors of this manuscript have the following competing interests: Nozomi Nakajima, Takashi Komeno, and Yousuke Furuta are employees of FUJIFILM Toyama Chemical Co., Ltd. Yousuke Furuta is the inventor of favipiravir. Favipiravir used in this study was kindly provided by FUJIFILM Toyama Chemical Co., Ltd., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Elevated levels of circulating high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular disease. This study aimed to examine whether hs-cTnT levels are associated with incident stroke in the elderly population. The Iwate Tohoku Medical Megabank Organization pooled participant data for a community-based cohort study (n = 15,063, 69.6 ± 3.4 years), with a mean follow-up period of 5.23 years for all-cause death and incident stroke. The follow-up revealed 316 incident strokes, including atherothrombotic (n = 98), cardioembolic (n = 54), lacunar (n = 63), hemorrhagic (n = 101), and 178 all-cause deaths. Participants were classified into quartiles according to hs-cTnT levels (Q1 ≦ 4 ng/L, Q2: 5-6 ng/L, Q3: 7-9 ng/L, and Q4 > 9 ng/L). After adjusting for sex, age, smoking, drinking, systolic blood pressure, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide, hemoglobin A1c, and lipid profile, a Cox proportional hazard model showed that higher hs-cTnT levels were associated with ischemic stroke (Q1 vs. Q4, hazard ratio [HR] = 2.24, 95 % confidence interval [CI] = 1.12-4.51, p = 0.023). The incident of total stroke was not associated with hs-cTnT levels (Q1 vs. Q4, HR 1.39, 95 % CI = 0.89-1.74, p = 0.145). Numerical differences were highest regarding incident lacunar stroke subtypes; however, this association was not statistically significant. Higher hs-cTnT concentrations were associated with ischemic stroke in the elderly Japanese population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: 5-aminolevulinic acid (5-ALA) is used for photodynamic diagnosis-assisted surgeries. Hypotension is among 5-ALA-related adverse effects. 5-ALA metabolism requires iron. The red cell life span is 120 days and heme iron is daily recycled. Higher hematocrit is likely to correlate with higher recycled iron. We previously reported 5-ALA-induced hemodynamics in urological surgery. This analysis aimed to determine the association between 5-ALA-induced perioperative systolic blood pressure (SBP) changes and the hematocrit., Methods: This retrospective study enrolled consecutive patients who underwent transurethral resection of bladder tumor from August 2018 to December 2020. The patients were classified into the 5-ALA-pretreated patients (5-ALA group; n = 26) and non-pretreated patients (control group; n = 97). We evaluated the correlation between SBP change rates and hematocrit levels. The primary analyses included the difference in correlations between the two groups. Subsequently, the correlations were analyzed in the 5-ALA group and control group, respectively., Results: The correlations significantly differed between the two groups preoperatively (P<0.001), during surgery (P = 0.014), postoperatively (P = 0.001), and on the following morning (P = 0.002). The correlations between SBP changes and the hematocrit in the 5-ALA group were significant before patients entered the operation room (Spearman's rank correlation coefficient [rS]=-0.449, P = 0.024), before anesthesia induction (rS=-0.584, P = 0.002), during surgery (rS=-0.401, P = 0.047), after operation (rS=-0.658, P<0.001), and on the following morning (rS=-0.547, P = 0.004). Those in the control group were not significant., Conclusions: The hematocrit levels were significantly correlated with perioperative 5-ALA-induced SBP changes. The association was again observed the next day. Higher hematocrit may be a factor for 5-ALA-induced hemodynamic changes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Semen production traits are important aspects of bull fertility, because semen quantity leads to direct profits for artificial insemination centres, and semen quality is associated with the probability of achieving a pregnancy. Most genome-wide association studies (GWASs) for semen production traits have assumed that each quantitative trait locus (QTL) has an additive effect. However, GWASs that account for non-additive effects are also important in fitness traits, such as bull fertility. Here, we performed a GWAS using models that accounted for additive and non-additive effects to evaluate the importance of non-additive effects on five semen production traits in beef and dairy bulls. A total of 65 463 records for 615 Japanese Black bulls (JB) and 50 734 records for 873 Holstein bulls (HOL), which were previously genotyped using the Illumina BovineSNP50 BeadChip, were used to estimate genetic parameters and perform GWAS. The heritability estimates were low (ranged from 0.11 to 0.23), and the repeatability estimates were low to moderate (ranged from 0.28 to 0.45) in both breeds. The estimated repeatability was approximately twice as high as the estimated heritability for all traits. In this study, only one significant region with an additive effect was detected in each breed, but multiple significant regions with non-additive effects were detected for each breed. In particular, the region at approximately 64 Mbp on Bos taurus autosome 17 had the highest significant non-additive effect on four semen production traits in HOL. The rs41843851 single nucleotide polymorphism (SNP) in the region had a much lower P-value for the non-additive effect (P-value = 1.1 × 10 -31 ) than for the additive effect (P-value = 1.1 × 10 -8 ) in sperm motility. The AA and AB genotypes on the SNP had a higher phenotype than the BB genotype in HOL, and there was no bull with the BB genotype in JB. Our results showed that non-additive QTLs affect semen production traits, and a novel QTL accounting for non-additive effects could be detected by GWAS. This study provides new insights into non-additive QTLs that affect fitness traits, such as semen production traits in beef and dairy bulls., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Recently, automatic feeders have become popular for collecting daily feed intake data in the pig industry, making it possible to evaluate genetic effects on feed efficiency and resilience traits, expressed as day-to-day fluctuations in feeding records. This study aimed to understand the influence of genetic factors on feed efficiency traits, including residual intake and BW gain (RIG), and resilience traits, as well as to compare the differences in genetic parameter estimates among three purebred pig breeds. A total of 6 103 pigs from three breeds (Large White: 1 193 pigs, Landrace: 3 010 pigs, and Duroc: 1 900 pigs) were raised in a specific pathogen-free environment. The growth and feed intake records during the testing period were obtained using automatic feeders, and the average daily gain (ADG) and average feed intake (AFI) were calculated. Feed conversion ratio (FCR), residual feed intake (RFI), residual gain, and RIG were calculated as feed efficiency traits, and the log-transformed variance of deviation for the daily feed intake (LnVar&#95;FI), daily occupation time (LnVar&#95;OC), and the daily number of visits to the feeder (LnVar&#95;VT) was calculated as resilience traits. After estimating the genetic parameters for each breed, a meta-analysis was performed to obtain the weighted mean of heritability estimates (h m 2 ) and genetic correlation estimates (GC m ) for the three breeds. The h m 2 were moderate and ranged from 0.31 to 0.39 for feed efficiency traits and 0.31 to 0.40 for resilience traits, and there were no significant differences in heritability estimates among the three breeds except for AFI, RFI, and RIG. For feed efficiency traits, the FCR and RIG showed favourably moderate GC m with AFI (0.29 and -0.33, respectively) and ADG (-0.39 and 0.31, respectively). For resilience traits, the LnVar&#95;FI and LnVar&#95;VT showed favourably low to moderate GC m with FCR (0.33 and 0.28, respectively) and RIG (-0.37 and 0.28, respectively), and there were no genetic relationships of LnVar&#95;OC with FCR and RIG (the absolute value of GC m was 0.01). There was no significant difference in the genetic correlation estimates among the three breeds for feed efficiency and resilience traits. Our results suggest that feed efficiency and resilience traits were heritable, and resilience traits showed favourable or no genetic correlation with feed efficiency traits. In addition, the influence of genetic factors on feed efficiency and resilience traits could be the same among breeds., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aims: Direct measurement of arginine vasopressin (AVP) via immunoassays is not widely conducted, mainly because of technical constraints. Liquid chromatography-tandem mass spectrometry (LC/MS/MS) has been widely used as the gold standard in clinical chemistry. Here, we aimed to develop an MS-based assay to determine human plasma AVP and compare the results with those obtained using a conventional immunoassay., Materials and Methods: We developed a protocol using triple quadrupole MS coupled with LC for the measurement of human plasma AVP. Analytical evaluations of the method were performed, and the results obtained using LC/MS/MS and radioimmunoassay (RIA) were compared., Results: The lower limit of quantification (LLOQ) for plasma AVP obtained using LC/MS/MS and RIA were 0.2 and 0.4 pg/mL, respectively. Although there was a weak overall correlation between the results obtained using the two different methods, the RIA results did not agree with the LC/MS/MS results, particularly at low concentrations., Conclusions: AVP detection through RIA is not satisfactory compared with that using LC/MS/MS. Diagnostic values of direct AVP measurements must be evaluated based on the results obtained via sensitive and accurate MS-based methods rather than those obtained through RIA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Chronic kidney disease (CKD) is a global health burden. Previous studies have shown a J- or U-shaped association between serum uric acid (SUA) and cardiovascular mortality. We assessed the risk of CKD incidence in a refined SUA category in middle-aged adults stratified by sex., Methods: We analyzed data from 138,511 participants <65 years old (29.6% women; mean age 44.1 years) without CKD at baseline acquired from the JMDC database. The Cox model was used to assess the adjusted hazard ratio (HR)., Results: During the mean follow-up period of 4.68 years, 12,589 participants developed CKD. The fully adjusted HRs (95% confidence interval [CI], p-value) for CKD incidence in men with SUA <4.0, 10.0-10.9 and ≥ 11.0 mg/dL compared to men with SUA 4.0-4.9 mg/dL were 1.13 (1.01-1.26, p = 0.030), 1.98 (1.32-2.97, p = 0.0010), and 3.74 (1.68-8.35, p = 0.0013), respectively. The fully adjusted HRs for CKD incidence in women with SUA <4.0, 8.0-8.9, and ≥9.0 mg/dL compared to women with SUA 4.0-4.9 mg/dL were 1.08 (1.01-1.16, p = 0.032), 2.39 (1.07-5.35, p = 0.034), and 3.20 (0.80-12.8, p = 0.10), respectively., Conclusions: Both high and low SUA levels were identified as risk factors for CKD incidence in middle-aged men and women. The association of SUA levels with the increase in the risk of CKD incidence differed by sex, and the range of SUA levels associated with an increase in the risk of CKD incidence varied by sex., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Scleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to review studies reporting muscle biopsies from SSc patients with myositis and to identify unique histopathological features of SM., Methods: A scoping review was conducted and included all studies reporting histopathological findings in SSc patients with myositis searching the following databases: PubMed, MEDLINE, EMBASE, CINAHL and EBM-Reviews. Clinical, serological, and histopathological data were extracted using a standardized protocol., Results: Out of 371 citations, 77 studies that included 559 muscle biopsies were extracted. Fifty-seven percent (n = 227/400) had inflammatory infiltrates, predominantly T cells, which were endomysial (49%), perimysial (42%) and perivascular (41%). Few studies (18%, n = 8/44) evaluated the presence of B-cells. Myofiber atrophy was present in 48% (n = 104/218) of biopsies, and was predominantly perifascicular in 19% (n = 6/31), with necrosis reported in 56% (n = 162/290) of cases. Sarcolemmal MHC-I upregulation was found in 72% (n = 64/89) of biopsies. Non-specified C5b-9 deposition was described in 39% of muscle biopsies (n = 28/72). Neurogenic features were present in 23% (n = 44/191); endomysial fibrosis was reported in 35% (n = 120/340); and rimmed vacuoles were observed in 32% (n = 11/34) of biopsies. Capillaropathy, such as capillary dropout and/or ultrastructural endothelial abnormalities, was reported in 33% (n = 43/129) of cases. Reported ENMC categories were mainly polymyositis (21%), non-specific myositis (19%), immune-mediated necrotizing myopathy (16%), and dermatomyositis (8%). Histopathological features were analyzed according to serological subtypes in 28 studies, including anti-PM-Scl (n = 48), -Ku (n = 23) and -U1RNP (n = 90). Most of these biopsies demonstrated inflammatory infiltrates (range 49-85%) as well as MHC-I expression (range 63-81%). Necrosis was associated with anti-Ku (85%) and anti-U1RNP (73%), while anti-Ku was also associated with neurogenic features and rimmed vacuoles in 57% and 25% of cases, respectively., Conclusion: Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a highly reliable and efficient technology for the identification of microbial pathogens. We previously found that 40% humidity was the optimal condition for the preparation of samples (co-crystallization of the sample and matrix) for serum peptidomic analysis via MALDI-TOF MS profiling. This optimum temperature was applied to obtain the highest reproducibility and throughput and greatest number of peaks. We therefore hypothesized that humidity control was also essential for MALDI-TOF MS bacterial identification. In this study, we constructed a simple sample preparation device that enables humidity control and used it for co-crystallization of the sample and matrix. Identification scores for five Gram-negative bacteria and six Gram-positive bacteria were determined using the MALDI BioTyper® system at three humidity ranges (10-20%, 30-40%, and 50-60%). As a result, higher identification scores were obtained at 30-40% humidity than at 10-20% or 50-60% humidity. At 30-40% humidity, 517/550 (94.0%) isolates scored greater than 2.0, indicating the success of species-level identification. Similarly, 537/550 (97.6%) isolates scored greater than 1.7, indicating the success of genus-level identification. Thus, 30-40% humidity generated optimal MALDI-TOF MS identification scores and the highest percentage of correct identifications. These results could lead to further improvements in the accuracy of MALDI-TOF MS bacterial identification., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor for CVD in the Japanese general population., Methods: This was a genome-wide association study (GWAS) based on a cohort from the 2013 Tohoku Medical Megabank Project community study. The GWAS was performed using a HumanOmniExpressExome BeadChip array with 914,035 autosomal single-nucleotide polymorphisms. The Framingham Risk Score and the Suita score were used to evaluate the future risk of CVD., Results: The GWAS identified 10 loci reaching suggestive significance in the discovery cohort. A replication analysis confirmed that one of the 10 loci, rs7798496, is associated with elevated hs-cTnT levels. The combined P value in the discovery and replication cohorts for the association between the rs7798496 and hs-cTnT levels was 3.4 × 10 -8 , which indicates that the novel variant reached genome-wide significance. The rs7798496 loci was located at an intergenic region between the retinoblastoma gene product (RB)-associated Krüppell-associated box (KRAB) zinc finger, zinc finger protein 890, and pseudogene (ZNF890P). Logistic regression analysis revealed that the presence of the rs7798496 T allele was strongly associated with a high risk for CVD., Conclusions: This study provides insights into a link between a novel genetic variant, T allele of rs7798269, and elevated hs-cTnT levels as a future risk for CVD in the general Japanese population., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Cadmium (Cd) is an environmental contaminant that triggers toxic effects in various tissues such as the kidney, liver, and lung. Cd can also cause abnormal iron metabolism, leading to anemia. Iron homeostasis is regulated by intestinal absorption. However, whether Cd affects the iron absorption pathway is unclear. We aimed to elucidate the relationship between the intestinal iron transporter system and Cd-induced iron deficiency anemia. C57BL/6J female and male mice, 129/Sv female mice, and DBA/2 female mice were given a single oral dose of CdCl 2 by gavage. After 3 or 24 h, Cd decreased serum iron concentrations and inhibited the expression of iron transport-related genes in the duodenum. In particular, Cd decreased the levels of divalent metal transporter 1 and ferroportin 1 in the duodenum. In addition, human colon carcinoma Caco-2 cells were treated with CdCl 2 . After 72 h, Cd decreased the expression of iron transport-related factors in Caco-2 cells with a pattern similar to that seen in the murine duodenum. These findings suggest that Cd inhibits iron absorption through direct suppression of iron transport in duodenal enterocytes and contributes to abnormal iron metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Uveitis is a sight-threatening intraocular inflammatory disease that accounts for almost 10% of blindness worldwide. NF-κB signaling plays pivotal roles in inflammatory diseases. We have reported that IMD-0354, which inhibits NF-κB signaling via selective blockade of IKK-β, suppresses inflammation in several ocular disease models. Here, we examined the therapeutic effect of IMD-0354 in an experimental autoimmune uveoretinitis (EAU) model, a well-established animal model for endogenous uveitis in humans. Systemic administration of IMD-0354 significantly suppressed the clinical and histological severity, inflammatory edema, and the translocation of NF-κB p65 into the nucleus of retinas in EAU mice. Furthermore, IMD-0354 treatment significantly inhibited the levels of several Th1/Th17-mediated pro-inflammatory cytokines in vitro. Our current data demonstrate that inhibition of IKKβ with IMD-0354 ameliorates inflammatory responses in the mouse EAU model, suggesting that IMD-0354 may be a promising therapeutic agent for human endogenous uveitis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is one of the most promising technologies for the identification of microbial pathogens directly from positive blood culture bottles. As blood culture bottle medium contains various nonbacterial proteins, including those derived from blood cells, pretreatment to effectively remove host cells is key for successful proteome-based identification of microorganisms. Although the Sepsityper® kit is the most widely used pretreatment protocol, its performance is not satisfactory, particularly for gram-positive isolates. We developed a new in-house protocol, the centrifugation and membrane filtration technique (CMFT), in which vacuum-filtration is coupled with differential centrifugation. We prospectively evaluated the performance of this novel method compared with that of the Sepsityper®. For gram-negative bacterial isolates, the species-level identification rates obtained with the CMFT and the Sepsityper® were comparable (98.8% vs 92.9%). By contrast, for gram-positive isolates, the performance of the CMFT was significantly better than that of the Sepsityper® (P < 0.05). Using our new protocol, 81 (95.3%) isolates were identified with a score >2.0, and 85 (100%) isolates were identified with a score >1.7, versus 46 (54.1%) and 69 (81.2%), respectively, for the Sepsityper®. These results are preliminary, but considering that this novel protocol provides notably high species-level identification rates for gram-positive isolates, it deserves assessment in a larger-scale study with a variety of platforms for MS-based identification of microorganisms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Myositis specific antibodies (MSA) represent not only important diagnostic tools for idiopathic inflammatory myopathies (IIM), but also help to stratify patients into subsets with particular clinical features, treatment responses, and disease outcome. Consequently, standardization of MSA is of high importance. Although many laboratories rely on protein immunoprecipitation (IP) for the detection of MSA, IP standardization is challenging and therefore reliable alternatives are mandatory. Recently, we identified significant variation between IP and line immunoassay (LIA) for the detection of MSA and myositis associated antibodies. In this study we aimed to compare the results from our previous study to the results obtained with a novel fully automated particle-based technology for the detection of MSA and MAA., Methods: A total of 54 sera from patients with idiopathic inflammatory myopathy (IIM) were tested using three methods: IP, LIA (Euroimmun, Germany) and a novel particle-based multi-analyte technology (PMAT, Inova Diagnostics, US, research use only). The analysis focused on antibodies to EJ, SRP, Jo-1, NXP-2, MDA5, TIF1-γ, and Mi-2., Results: Significant variations were observed among all methods. Overall, the novel PMAT assays showed slightly better correlation with IP, but the kappa agreement was strongly dependent on the antibody tested. When the results obtained from IP were used as reference for receiver operating characteristic (ROC) curve analysis, good discrimination and a high area under the curve (AUC) value were found for PMAT (AUC = 0.83, 95% confidence interval, CI 0.70-0.95) which was significantly higher (p = .0332) than the LIA method (AUC = 0.70, 95% CI 0.56-0.84)., Conclusion: The novel PMAT used to detect a spectrum of MSA in IIM represents a potential alternative to IP and other diagnostic assays. Additional studies based on larger cohorts are needed to fully assess the performance of the novel PMAT system for the detection of autoantibodies in myositis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The study was conducted to determine the minimum inhibitory concentrations (MICs) of several antibacterial agents against Rickettsia japonica, which causes Japanese spotted fever. A plaque reduction assay as an in vitro culture method was conducted to determine the MICs of antibacterial agents (4 types of tetracyclines: tetracycline, doxycycline, minocycline, and tigecycline; 3 types of quinolones: ciprofloxacin, ofloxacin, and levofloxacin; and 2 types of macrolides: azithromycin and clarythromycin) against R. japonica. R. japonica was sensitive to the antibacterial agents tested with MICs similar to those against other spotted fever rickettsia determined in previously described plaque reduction assays., (Copyright © 2019. Published by Elsevier Ltd.)

Anti-OJ autoantibodies are rare myositis-specific autoantibodies that have been described to target isoleucyl-tRNA synthetase. Routinely used multiplex assays perform poorly in detection of anti-OJ antibodies. In this manuscript, we review the existing literature on critical issues in detection of anti-OJ and the clinical features associated with anti-OJ. The challenging detection with line/blot immunoassays and ELISAs is most likely related to the characteristics of the autoantigen involved, which is part of a multi-enzyme synthetase complex. Anti-OJ autoantibodies might therefore be more aptly termed anti-OJ complex autoantibodies. Anti-OJ autoantibodies are associated with the anti-synthetase syndrome, with interstitial lung disease (ILD) frequently being the sole manifestation. Myositis, present in the majority of patients with anti-OJ antibodies, is more severe than in patients with other anti-aminoacyl-tRNA synthetases. Most patients respond to glucocorticoid therapy. As detection of anti-OJ is relevant for treatment, reliable and practical detection is needed. Meanwhile, clinicians need to be aware of the possibility of anti-OJ in patients with ILD, isolated or in combination with myositis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Skipping breakfast has become a common trend that may lead to obesity and type 2 diabetes. Previous studies, which imposed a single incidence of breakfast skipping, did not observe any decrease in 24-h energy expenditure. Furthermore, the effects of breakfast skipping on diurnal blood glucose profiles over 24 h are contradictory., Objective: The aim of this study was to clarify the influence of 6 consecutive days of breakfast skipping and sedentary behavior on energy metabolism and glycemic control., Methods: Ten young men participated in 2 trials (with or without breakfast) that lasted for 6 consecutive days, and the 2 trials were conducted 1 wk apart with a repeated-measures design. During the meal intervention, each subject's blood glucose was measured using the continuous glucose monitoring system. If breakfast was skipped, subjects ate large meals at lunch and dinner such that the 24-h energy intake was identical to that of the 3-meal condition. At 2200 on the fifth day, the subjects entered a room-sized respiratory chamber, where they remained for 33 h, and were instructed to carry out sedentary behavior., Results: The glucose levels were similar between the 2 meal conditions during the first 5 d of meal intervention, but the blood glucose at 2300 was higher in the breakfast-skipping condition than in the 3-meal condition. Breakfast skipping elevated postprandial glycemic response after lunch on the first day of meal intervention. On the sixth day, there were no significant differences in 24-h energy expenditure and substrate oxidation. When subjects remained in a metabolic chamber, the level of physical activity significantly decreased, glycemic stability slightly deteriorated, and mean blood glucose over 24 h was higher in the breakfast-skipping trial than in the 3-meal trial., Conclusions: Sedentary lifestyle and repeated breakfast skipping caused abnormal glucose fluctuations, whereas 24-h energy metabolism remained unaffected. Clinical Trial Registry: This trial was registered at http://www.umin.ac.jp/english/ as UMIN000032346., (Copyright © American Society for Nutrition 2019.)

Diacylglycerol kinase (DGK) δ, which is a key enzyme in the pathogenesis of type 2 diabetes (T2D), preferentially generates saturated fatty acid (SFA)- and/or monounsaturated fatty acid (MUFA)-containing phosphatidic acids (PAs) such as 16:0/16:0-PA and 16:0/18:1-PA, but not polyunsaturated fatty acid (PUFA)-containing PAs, in glucose-stimulated myoblast cells. Here, we searched for the target proteins of 16:0/16:0-PA in the mouse skeletal muscle and identified an energy metabolizing enzyme, creatine kinase muscle type (CKM), which is correlated with T2D. CKM bound to 16:0/16:0-PA with the highest affinity (dissociation constant: 2.0 μM) among all the PA-binding proteins reported thus far. Intriguingly, CKM preferentially interacted with SFA- and/or MUFA-containing PAs, but not with PUFA-containing PAs. Notably, CKM exclusively interacted with PA, whereas the protein did not bind to other lipids such as diacylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol (3,4,5)-trisphosphate and cardiolipin. Taken together, these results demonstrate that CKM is a very unique PA-binding protein that possesses exceedingly high affinity for PA, exceptional preference for SFA/MUFA-PA and extremely high specificity to PA and suggest that SFA/MUFA-PAs produced by DGKδ are novel regulators of CKM function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Assessment of the cricoarytenoideus dorsalis muscle (CAD) in horses using a transesophageal ultrasound, computed tomography, or magnetic resonance imaging is available in a limited number of hospitals. This study assessed the ease of ultrasonographic imaging of the CAD using an external transcutaneous technique in horses. After confirmation of the CAD in the cadavers, ultrasonography in twenty live horses was carried out using a transcutaneous approach. In live horses, ultrasonographic imaging of the CAD was possible by pushing the larynx from the opposite side with the other hand. It is believed that the results of this study may be beneficial in the examination of recurrent laryngeal neuropathy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Carbohydrate-deficient transferrin is a biological marker of excessive drinking. The aim of this study was to evaluate the diagnostic value of a direct nephelometric immunoassay for the differential diagnosis of alcoholic and non-alcoholic liver diseases in comparison with gamma glutamyl transferase., Methods: Serum samples were obtained from 305 subjects, including 122 patients with alcoholic and 102 cases with non-alcoholic liver diseases. Serum levels of carbohydrate-deficient transferrin were expressed as a percentage of total transferrin., Results: Serum % carbohydrate-deficient transferrin levels were significantly higher in patients with alcoholic than with non-alcoholic liver diseases. Carbohydrate-deficient transferrin had better specificity than gamma glutamyl transferase to differentiate between alcoholic and non-alcoholic liver diseases.There were 8 alcoholic liver disease patients with normal gamma glutamyl transferase levels, and carbohydrate-deficient transferrin was significantly elevated in 6 of them. On the other hand, there were 25 non-alcoholic liver disease patients with elevated gamma glutamyl transferase levels; their carbohydrate-deficient transferrin levels were within the reference intervals in all cases., Conclusion: This simple carbohydrate-deficient transferrin immunoassay is useful to detect so-called gamma glutamyl transferase non-responding drinkers and also to exclude the possible role of excessive drinking in apparently non-alcoholic liver diseases. A large-scale prospective study is needed to further confirm the diagnostic utility of carbohydrate-deficient transferrin., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Haemophilus influenzae is a major pathogenic bacteria causing invasive disease, which is classified into six capsular serotypes (a-f) and non-typeable (NT) strains. Capsular serotyping of H. influenzae is traditionally determined by serological methods and more recently by PCR methods. However, these methods are time-consuming and expensive. In the present study, matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was evaluated as an alternative method for capsular serotyping of H. influenzae clinical strains. We created an in-house database of all six serotypes and NT H. influenzae strains using the main spectrum creation standard method set to the default parameters in MADI-TOF MS. We evaluated the performance of the in-house database using 79 clinical strains already identified by PCR and 58 prospectively collected clinical strains. Measurements were performed using the Bruker MALDI BioTyper system. The peak list was matched against the reference library using the integrated pattern algorithm of the software. The best-matched spectrum was considered the serotyping result. All 137 test strains were correctly identified as H. influenzae using MALDI-TOF MS. The sensitivity and specificity for identification for type b, type e, and type f capsular serotypes and NT H. influenzae using MALDI-TOF MS were 100%/94.3%, 94.7%/97.9%, 97.4%/97.9%, and 85.5%/99.2%, respectively. Our findings indicate that MALDI-TOF MS is a useful alternative method for capsular serotyping of H. influenzae strains. This method is faster and more cost-effective than traditional methods and will therefore be useful for routine applications in clinical laboratories., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe a new immunoprecipitation pattern identified in Italian patients affected by systemic sclerosis (SSc), corresponding to the pyruvate dehydrogenase antigen complex recognized by anti-mitochondrial antibodies (AMA) in primary biliary cholangitis (PBC)., Methods: Autoantibodies in sera from 85 patients with SSc were tested by protein- and RNA-immunoprecipitation. Immunoprecipitation-Western blot was used to determine the identified proteins, and medical records re-evaluated for liver function tests and PBC., Results: In 13/85 (15%) SSc sera, a unique set of 75-50-40-34kD proteins that had not been previously reported, was noted. The four proteins were identified as the proteins X/E3BP, E1α, E1β, and E2/E3 of the pyruvate dehydrogenase antigen complex by immunoprecipitation-Western blot. From clinical record evaluation, 9/13 (69%) SSc patients with this new pattern were positive for AMA by routine indirect immunofluorescence, and 7/13 (54%) had a diagnosis of PBC, while 4/13 (31%) manifested no biochemical signs of cholestasis. Twelve of 13 patients with SSc and AMA by immunoprecipitation have a limited cutaneous form of SSc and anti-centromere antibodies., Conclusions: We describe a pattern of 4 proteins in 15% of SSc patients, identified for the first time by protein-immunoprecipitation. This pattern corresponds to serum AMA against the pyruvate dehydrogenase antigen complex and it must be considered in the interpretation of protein-immunoprecipitation results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Anti-aminoacyl-tRNA synthetase (ARS) antibodies have been detected in patients with polymyositis/dermatomyositis (PM/DM) and are especially correlated with interstitial lung disease (ILD). The aim of this study was to clarify the clinical features of patients with anti-ARS antibody positive idiopathic interstitial pneumonias (IIPs)., Methods: Patients were classified into three groups: 1) IIP with anti-ARS antibodies (ARS(+)IIP), 2) IIP without anti-ARS antibodies (ARS(-)IIP), and 3) PM/DM-associated ILD with anti-ARS antibodies (ARS(+)PM/DM-ILD). Clinical characteristics were compared retrospectively between the ARS(+)IIP group and the ARS(-)IIP group or ARS(+)PM/DM-ILD group., Results: Eighteen ARS(+)IIP, 284 ARS(-)IIP, and 20 ARS(+)PM/DM-ILD patients were enrolled. The ARS(+)IIP group was significantly older and the male sex was predominant, had a lower prevalence of signs of connective tissue disease, differences in HRCT findings and patterns, and higher KL-6 levels compared to the ARS(+)PM/DM-ILD group. The findings in the bronchoalveolar lavage fluid (BALF) showing lymphocytosis and a lower CD4/CD8 ratio were similar between the two groups. However, the ARS(+)IIP group had significantly lower percentage of sputum, higher prevalence of mechanic's hand, higher KL-6 levels, lower percentage of vital capacity in the pulmonary function test, and lower CD4/CD8 ratio in BALF, compared to the ARS(-)IIP group., Conclusions: The present study demonstrated that features of pulmonary involvement were similar to those in the ARS(+)PM/DM-ILD group; however, some differences including HRCT findings and higher KL-6 levels suggest that ARS(+)IIP has severe ILD compared with ARS(+)PM/DM-ILD. Further prospective studies with a larger number of patients will elucidate the exact role of anti-ARS antibodies in IIPs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Although immunoassays have several limitations such as the cross-reactivities of antibodies, such techniques are widely used for serum/plasma 1,25(OH) 2 D quantification. An accurate method is required for the determination of the 1,25(OH) 2 D status., Methods: We designed a serum/plasma 1,25(OH) 2 D quantification method using LC-MS/MS. Immunoaffinity extraction (IE) and the recently developed Cookson-type reagent 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione (DAPTAD) were used for sample preparation and derivatization, respectively. Analytical and pre-analytical validations were performed. Serum 1,25(OH) 2 D 3 concentrations were determined in 232 healthy Japanese individuals., Results: The intra- and inter-assay CVs for 1,25(OH) 2 D 3 were 5.2% and 7.0%, respectively. The limit of quantification for 1,25(OH) 2 D 3 was 7.1pg/ml. Rheumatoid factor (RF) at concentrations below 517IU/ml did not affect serum 1,25(OH) 2 D analysis. No significant differences were observed for various blood collection tubes, repeated freeze-thaw cycles, whole blood standing time, or serum storage time. A strong correlation between LC-MS/MS and radioimmunoassay (RIA) was observed (r=0.786), but serum 1,25(OH) 2 D concentrations obtained from RIA were 2-fold higher than those obtained from LC-MS/MS. Serum 1,25(OH) 2 D 3 concentrations by LC-MS/MS were 18.7-53.9pg/ml., Conclusion: A highly sensitive and selective LC-MS/MS-based serum/plasma 1,25(OH) 2 D quantification method was developed using IE and DAPTAD derivatization. This method will enable the accurate determination of serum/plasma 1,25(OH) 2 D concentrations in the clinical setting., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Anti-Su antibodies are found in 5-20% of cases of various systemic autoimmune rheumatic diseases and in 5-10% of dermatomyositis (DM)/polymyositis (PM) patients. In 2006, the 100kDa Su antigen was identified as argonaute2 (Ago2), and it was found to play a major role in RNA interference. However, immunoprecipitation (IP) remains the main method for detecting anti-Su and the clinical significance of the antibodies is uncertain., Methods: Sera from patients with DM/PM (n=224) were screened by an ELISA that uses recombinant biotinylated Ago2 protein. Some serum samples were tested by IP and by indirect immunofluorescence (IIF) analysis., Results: Seventeen (7.5%, 17/224) sera from DM/PM were positive in ELISA. Of the 33 IP-tested sera (17 ELISA-positive and 16 ELISA-negative with high background), 13 were found to be anti-Ago2/Su-positive in IP and ELISA. Only one IP-positive serum was judged to be ELISA-negative. Among the 13 patients with anti-Su/Ago2, 7 cases also had myositis-specific autoantibodies. Six sera that were positive by both IP and ELISA showed the GW body pattern in IIF. Interestingly, one ELISA-positive serum with an inconclusive result in IP also showed the GW body pattern., Conclusion: Our novel ELISA appears to be useful for screening anti-Su/Ago2 antibodies (sensitivity: 93%, specificity: 79%)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). The aim of this study was to clarify whether SFTS is potentially mis-diagnosed as rickettsioses, including spotted fever, typhus fever, and scrub typhus, which are also tick-borne disease. A total of 464 serum samples collected from 222 patients with clinically suspected rickettsiosis between 1999 and 2012 were tested for antibodies against the SFTSV. Of the 464 serum samples, one was positive for antibodies against the virus in an enzyme-linked immunosorbent assay and indirect immunofluorescence assay. The patient of SFTSV antibody-positive sample (15 days after disease onset) was positive for SFTSV genome in the acute phase sample (3 days after disease onset) as determined via reverse transcription-quantitative polymerase chain reaction. This patient, who was a resident of the Yamaguchi prefecture in Western Japan, was in his 40s when he showed symptoms in 2011. As the result, 1 of 222 patients, who was clinically suspected of rickettsiosis, was retrospectively diagnosed with SFTS. In this case, both the C-reactive protein and white blood cell count levels were lower than the ranges of these parameters for patients diagnosed with rickettsiosis. Therefore, SFTS should be considered in the differential diagnosis for rickettsiosis in Japan., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Until now, metal allergies have been regarded as a Th1-type immune response.　However, because the contribution of a Th2-type immune response has been suggested by clinical findings, we previously examined the Th2-type immune response during the development of metal allergies using a GATA-3 transgenic (GATA-3 Tg) mouse model. As a result, a Th2-type immunization reaction was suggested to be involved in the early phase of metal allergies. Recently, the involvement of NKT cells in metal allergies has been suggested. We examined this possibility using the activation of NKT cells and an NKT cell-deficient mouse model to determine the contribution of NKT cells to nickel allergy in the present study. In NKT cell-deficient mice, ear swelling was remarkably increased, compared with that in control mice. Also, in mice that had been treated with α-galactosylceramide (α-GalCer) to activate NKT cells, the ear swelling response was remarkably inhibited, compared with that in untreated mice. These facts show that NKT cells are involved in the inhibition of nickel allergy-induced ear swelling responses., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: To analyze the performance of a line blot assay for the identification of autoantibodies in sera of patients affected by myositis, compared with immunoprecipitation (IP) as gold standard., Methods: 66 sera of patients with myositis (23 polymyositis, 8 anti-synthetase syndromes, 29 dermatomyositis and 6 overlap syndromes) were tested by commercial LB (Euroimmun, Lubeck, Germany); 57 sera were analyzed also by IP of K562 cell extract radiolabeled with (35)S-methionine. Inter-rater agreement was calculated with Cohen's k coefficient., Results: Myositis-specific antibodies (MSA) were detected in 36/57 sera (63%) by IP and in 39/66 sera (59%) by LB. The most frequent MSA found by LB were anti-Jo1 and anti-Mi2 found in 15% (10/66) of sera, followed by anti-NXP2 and anti-SRP detected in 106% (7/66) of sera. Anti-TIF1gamma and anti-MDA5 were found in 6 (9%) and 5 sera (7.6%), respectively. A good agreement between methods was found only for anti-TIF1γ, anti-MDA5 and anti-NXP-2 antibodies, while a moderate agreement was estimated for anti-Mi2 and anti-EJ. By contrast, a high discordance rate for the detection of anti-Jo1 antibodies was evident (k: 0.3). Multiple positivity for MSA were found in 11/66 (17%) by LB and 0/57 by IP (p: 0001). Comparing the clinical features of these 11 sera, we found total discrepancies between assays in 3 sera (27.3%), a relative discrepancy due to the occurrence of one discordant autoantibody (not confirmed by IP) in 5 cases (45.5%) and a total discrepancy between LB and IP results, but with a relative concordance with clinical features were found in other 3 sera (27.3%). The semiquantitative results do not support the interpretation of the data., Conclusions: The use of LB assay allowed the detection of new MSA, such as anti-MDA5, anti-MJ and anti-TIF1gamma antibodies, previously not found with routine methods. However, the high prevalence of multiple positivities and the high discondant rate of anti-Jo1 antibodies could create some misinterpretation of the results from the clinical point of view. These data should be confirmed by enlarging the number of myositis cases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: The neuronavigator has become indispensable for brain surgery and works in the manner of point-to-point navigation. Because the positional information is indicated on a personal computer (PC) monitor, surgeons are required to rotate the dimension of the magnetic resonance imaging/computed tomography scans to match the surgical field. In addition, they must frequently alternate their gaze between the surgical field and the PC monitor., Objective: To overcome these difficulties, we developed an augmented reality-based navigation system with whole-operation-room tracking., Methods: A tablet PC is used for visualization. The patient's head is captured by the back-face camera of the tablet. Three-dimensional images of intracranial structures are extracted from magnetic resonance imaging/computed tomography and are superimposed on the video image of the head. When viewed from various directions around the head, intracranial structures are displayed with corresponding angles as viewed from the camera direction, thus giving the surgeon the sensation of seeing through the head. Whole-operation-room tracking is realized using a VICON tracking system with 6 cameras., Results: A phantom study showed a spatial resolution of about 1 mm. The present system was evaluated in 6 patients who underwent tumor resection surgery, and we showed that the system is useful for planning skin incisions as well as craniotomy and the localization of superficial tumors., Conclusions: The main advantage of the present system is that it achieves volumetric navigation in contrast to conventional point-to-point navigation. It extends augmented reality images directly onto real surgical images, thus helping the surgeon to integrate these 2 dimensions intuitively., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The percentage of carbohydrate-deficient transferrin (%CDT) in serum is a marker of habitual alcohol intake that can be determined by antibody detection of abnormal disialo sugar chains at D432 and D630. However, this approach lacks specificity for alcoholic liver disease. To decrease the false-positive rate in patients with non-alcoholic liver diseases, we developed a screening method using the disialo sugar chain at D630 alone., Methods: Serum was obtained from 12 patients with alcoholic liver disease, 12 with type C chronic liver disease, 6 with non-alcoholic steatohepatitis (NASH), and 12 healthy non-alcohol drinkers. Transferrin with two sialic acids (disialotransferrin) was fractionated from serum using HPLC, digested with trypsin, and evaluated using MALDI-TOF MS., Results: An abnormal sugar chain at D630 of transferrin was not detected in healthy subjects or in patients with chronic liver disease or NASH, but was detected in 9 patients (75%) with alcoholic liver disease. Positive results were found in 3 samples that were negative using an N-Latex CDT kit and in one sample negative for γ-glutamylaminotransferase and CDT., Conclusions: Detection of CDT by HPLC/MALDI-TOF MS based on an abnormal sugar chain at D630 may permit identification of habitual alcohol drinkers when used in combination with current markers., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Antinuclear antibodies (ANA) represent valuable biomarkers in the diagnosis of systemic sclerosis (SSc) being present in the vast majority of the patients. Besides anti-topoisomerase I, anti-centromere and anti-RNA polymerase III antibodies as the main specificities, several other autoantibodies can be present in SSc patients including autoantibodies targeting the PM/Scl complex (also known as the exosome), U3-RNP/fibrillarin and the Th/To autoantigens. Anti-Th/To antibodies are one of the specificities that reportedly show homogenous nucleolar staining in conventional indirect immunofluorescence (IIF) ANA tests. Almost all protein components of the mitochondrial RNA processing (MRP) and the evolutionarily related RNase P complex have been reported to be the target of anti-Th/To antibodies in systemic autoimmune rheumatic disease (SARD) patients. However, Rpp25, Rpp38 and hPop1 have been described as the main autoantigen., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Monoclonal antibodies have demonstrated enormous potential as new classes of drugs that confer great benefits to patients, and more than 40 therapeutic antibodies have already been approved for clinical use. In particular, the past 5 years might be recognized as the period guiding the new era for "engineered antibodies," with the successful approval of numerous antibody-drug conjugates, bispecific antibodies, and glyco-engineered antibodies for clinical applications. In this review, we summarize the development of antibody engineering technologies that are proving their concepts in the clinic, mainly focusing on the latest trends in defucosylated antibody technologies., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Mammalian cells store excess fatty acids in the form of triglycerides within lipid droplets. The intracellular bacterium Orientia tsutsugamush is the causative agent of severe human rickettiosis. We found that O. tsutsugamushi infection induces the formation of lipid droplets in mouse L-929 fibroblasts. In infected cells, a parallel increase in the number of lipid droplets and pathogens was observed. Interestingly, the pathogen-infection induced the accumulation of triglycerides even without external supply of fatty acids. These results suggest that O. tsutsugamushi alters lipid metabolism of host cells to induce lipid droplets., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

In this study, we investigated the prevalence of genital Chlamydia trachomatis isolated in Japan using a high-resolution genotyping method, the multilocus VNTR analysis (MLVA)-ompA typing method. Seventeen serotypes of C. trachomatis standard strain (A-L3) and 44 clinical isolates were obtained from clinical settings. Genotyping of the ompA gene allowed clinical isolates to be divided into nine serotypes: B (6.8%), D (15.9%), E (25%), F (20.5%), G (18.1%), H (6.8%), Ia (2.3%), J (2.3%), and K (2.3%). These isolates were further divided into 28 types after combining ompA genotyping data with MLVA data (Hunter-Gaston discriminatory index D, 0.949). Thus, our results demonstrated that MLVA could identify clinical isolates that could not be distinguished by ompA typing., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Curcumin, a dietary phytopolyphenol isolated from a perennial herb (Curcuma longa), is a well-known compound effective for bacterial infections and tumors, and also as an antioxidant. In this study, we report the inhibitory effects of curcumin and its analogs on the Escherichia coli ATP synthase F1 sector. A structure-activity relationship study indicated the importance of 4'-hydroxy groups and a β-diketone moiety for the inhibition. The 3'-demethoxy analog (DMC) inhibited F1 more strongly than curcumin did. Furthermore, these compounds inhibited E. coli growth through oxidative phosphorylation, consistent with their effects on ATPase activity. These results suggest that the two compounds affected bacterial growth through inhibition of ATP synthase. Derivatives including bis(arylmethylidene)acetones (C5 curcuminoids) exhibited only weak activity toward ATPase and bacterial growth., (Copyright © 2014 Elsevier B.V. All rights reserved.)