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Objective While greater body mass index (BMI) is associated with increased risk of developing atrial fibrillation (AF), the impact of BMI on outcomes in newly diagnosed AF is unclear. We examine the influence of BMI on outcomes and whether this is modified by sex and evaluate the effect of non-vitamin K oral anticoagulants (NOACs) in patients with high BMI.Methods GARFIELD-AF is a prospective registry of 52 057 newly diagnosed AF patients. The study population comprised 40 482 participants: 703 underweight (BMI

Illusory directional sensations are generated through asymmetric vibrations applied to the fingertips and have been utilized to induce upper-limb motions in the rehabilitation and training of patients with visual impairment. However, its effects on motor control remain unclear. This study aimed to verify the effects of illusory directional sensations on wrist motion. We conducted objective and subjective evaluations of wrist motion during a motor task, while inducing an illusory directional sensation that was congruent or incongruent with wrist motion. We found that, when motion and illusory directional sensations were congruent, the sense of agency for motion decreased. This indicates an induction sensation of the hand being moved by the illusion. Interestingly, although no physical force was applied to the hand, the angular velocity of the wrist was higher in the congruent condition than that in the no-stimulation condition. The angular velocity of the wrist and electromyography signals of the agonist muscles were weakly positively correlated, suggesting that the participants may have increased their wrist velocity. In other words, the congruence between the direction of motion and illusory directional sensation induced the sensation of the hand being moved, even though the participants’ wrist-motion velocity increased. This phenomenon can be explained by the discrepancy between the sensation of active motion predicted by the efferent copy, and that of actual motion caused by the addition of the illusion. The findings of this study can guide the design of novel rehabilitation methods.

IntroductionThere is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens.Materials and methodsPatients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay.ResultsA total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups.ConclusionThe patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001–2020. During 2010–2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.

Abstract Pancreatic cancer primarily arises from microscopic precancerous lesions, such as pancreatic intraepithelial neoplasia (PanIN) and acinar-to-ductal metaplasia (ADM). However, no established method exists for predicting pancreatic precancerous conditions. Endoscopic ultrasonography (EUS) can detect changes in pancreatic parenchymal histology, including fibrosis. This study aimed to elucidate the relationship between pancreatic parenchymal EUS findings and microscopic precancerous lesions. We retrospectively analyzed 114 patients with pancreatobiliary tumors resected between 2010 and 2020 and evaluated the association between pancreatic parenchymal EUS findings and the number of PanIN, ADM, and pancreatic duct gland (PDG). Of the 114 patients, 33 (29.0%), 55 (48.2%), and 26 (22.8%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. Multivariate analyses revealed that abnormal EUS findings were significantly associated with the frequency of PanIN (hyperechoic foci/stranding without lobularity: OR [95% CI] = 2.7 [1.0–7.3], with lobularity: 6.5 [1.9–22.5], P trend = 0.01) and ADM (hyperechoic foci/stranding without lobularity: 3.1 [1.1–8.2], with lobularity: 9.7 [2.6–36.3], P trend = 0.003) but not with PDG (hyperechoic foci/stranding without lobularity: 2.2 [0.8–5.8], with lobularity: 3.2 [1.0–10.2], P trend = 0.12). We observed a trend toward a significantly higher number of precancerous lesions in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Pancreatic parenchymal EUS findings were associated with the increased frequency of PanIN and ADM. Lobularity may help predict the increased number of precancerous lesions.

Healthcare for truck drivers is an important issue. To prevent fatigue-related collisions among drivers, objective assessments of their physiological states are essential. A simple and quantitative evaluation method for fatigue involves the use of autonomic nerve function (ANF) indices obtained from heart rate variability analysis. However, predicting the occurrence of crashes using only physiological data is challenging. In most previous studies, the targets of driving situations have been often limited, or the prediction targets have been set as the driver’s internal state rather than the accident. In this paper, we propose a novel collision risk prediction model using ANF and several simple external information types, which can be extracted from standard in-vehicle sensors without limiting the driving scene. Our experiments using actual truck drivers’ data reveal that the proposed model can achieve collision risk prediction for the following 30 min with an accuracy of 74.9% recall and 0.79 AUC. Furthermore, we discover that simple external information obtained based on the vehicle speed significantly contributes to the prediction accuracy. As our prediction method only requires commonly equipped sensors as the sources of external information, this method is expected to be easily implemented not only for truck driving but also for general vehicle driving, where crashes are often likely.

For visually impaired people, a white cane is an important aid for obtaining information about the surrounding environment. Although the visually impaired should attend this training by orientation & mobility (O&M) specialists to learn proper cane technique, the number of specialists is limited. In our previous study, we developed a training system that enabled the visually impaired to learn white cane techniques using illusory pulling cues. In the previous prototype system, a cane grip-type device was developed with a built-in vibrator to generate asymmetric vibration stimuli, and illusory pulling cues were fed according to the position of the cane tip. Although the prototype system showed positive results, issues related to the lack of user-friendliness of the device associated with the wired drive and the impractical gripping method were observed. This study developed a more practical white-cane-type device for O&M training, envisioning independent training for the visually impaired, which improved the above-mentioned issues. Specifically, the device was wireless and had a vibration mechanism for the gripping method of the general cane technique, and its validity was demonstrated by evaluation experiments. In addition, the paper explains the usefulness of the device as per discussion with an active O&M specialist. The results of the evaluation experiments indicated that the devices were implemented to satisfy the requirements for cane training.

When the etiology of pancreatitis cannot be determined despite sufficient investigation, recurrence and progression to chronic pancreatitis often involve genetic mutations. Herein, we describe a case of recurrent pancreatitis with the IVS3+2T>C mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene that progressed to chronic pancreatitis in only 3 years. A 35-year-old man was referred to our hospital, where he was diagnosed with mild pancreatitis and was treated conservatively. However, the patient experienced recurrent episodes of pancreatitis, which progressed to become chronic pancreatitis with a pancreatic calcification 1 year later. After 3 years, the patient developed pancreatic duct stenosis and required a pancreatic duct stent placement. Regarding the cause of chronic pancreatitis, alcohol abuse was ruled out based on history taking. Considering the course of treatment, autoimmune pancreatitis and obstructive pancreatitis, such as pancreatic divisum, were also ruled out. Finally, a germline genetic test was performed to determine the etiology of pancreatitis, which revealed the IVS3+2T>C mutation in SPINK1. This case shows the importance of genetic testing in patients with idiopathic pancreatitis to determine their etiology and is a rare incident that can report the progression of the disease from acute to chronic pancreatitis.

IntroductionControlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC.MethodsA total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry.ResultsThe response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01–0.0001 and P < 0.05–0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01–0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells.ConclusionThere is a characteristic cytokine profile at each clinical stage of MAC.

Abstract Many genes responsible for Malignant mesothelioma (MM) have been identified as tumor suppressor genes and it is difficult to target these genes directly at a molecular level. We searched for the gene which showed synthetic lethal phenotype with LATS2, one of the MM causative genes and one of the kinases in the Hippo pathway. Here we showed that knockdown of SMG6 results in synthetic lethality in LATS2-inactivated cells. We found that this synthetic lethality required the nuclear translocation of YAP1 and TAZ. Both are downstream factors of the Hippo pathway. We also demonstrated that this synthetic lethality did not require SMG6 in nonsense-mediated mRNA decay (NMD) but in regulating telomerase reverse transcriptase (TERT) activity. In addition, the RNA-dependent DNA polymerase (RdDP) activity of TERT was required for this synthetic lethal phenotype. We confirmed the inhibitory effects of LATS2 and SMG6 on cell proliferation in vivo. The result suggests an interaction between the Hippo and TERT signaling pathways. We also propose that SMG6 and TERT are novel molecular target candidates for LATS2-inactivated cancers such as MM.

Abstract Background and Aim Regarding the gut–liver axis, fecal dysbiosis is implicated in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The significance of mucosa‐associated microbiota (MAM, which is present in the mucin layer covering the intestinal mucosa) has not been well explored. We aimed to clarify the characteristics of MAM in patients with NAFLD. Methods MAM were obtained from seven patients with early‐stage NAFLD and seven controls by colonoscopy in five locations (terminal ileum, cecum, ascending and sigmoid colon, and rectum) using mucosal brushes. The microbial 16S rDNA profiles of the MAM and fecal microbiota of patients in the NAFLD and control groups were analyzed. Results α‐diversities of fecal microbiota were decreased in patients with NAFLD (observed species, Shannon index, and Chao1: 174.57 vs 134.86, 5.51 vs 4.65, and 206.34 vs 167.91; P = 0.048, 0.067, and 0.087, respectively), and microbial composition analyses by principal coordinate analysis differed between the fecal microbiota of patients with NAFLD and those of controls (permutational analysis of variance [PERMANOVA] of weighted and unweighted: Pseud‐F: 1.4179/P‐value: 0.05 and Pseud‐F: 2.1497/P‐value: 0.049, respectively). However, α‐diversities or microbial composition of MAM in most parts of the intestine did not differ significantly between the NAFLD and control groups. Unclassified Rikenellaceae, Oscillospira, Odoribacter, unclassified clostridiales, and Holdemania were decreased in the feces of patients with NAFLD (determined by linear discriminant analysis effect size), but five (except Holdemania) of the six genera were not decreased in the MAM of these patients. Conclusion In early‐stage NAFLD, MAM was uniform and relatively stable throughout the intestine, even when fecal dysbiosis appeared.

Abstract Endoscopic papillectomy for early ampullary tumors is considered a minimally invasive and useful alternative to pancreatoduodenectomy; however, its indications remain unclear. This study aimed to clarify the advantages of endoscopic papillectomy by investigating the clinical outcomes of patients who underwent endoscopic papillectomy or pancreatoduodenectomy for early ampullary tumors. Patients diagnosed with early ampullary tumors (adenoma, Tis, T1a) who underwent endoscopic papillectomy or pancreatoduodenectomy between June 2008 and October 2019 were included, and their clinical outcomes were analyzed. Seventy-four patients (34 patients with adenomas and 40 patients with adenocarcinomas) were divided into two groups, namely endoscopic papillectomy (n = 43) and pancreatoduodenectomy (n = 31). The estimated 5-year overall survival rate of all early ampullary tumors was 92%. Complete resection rate was significantly lower for endoscopic papillectomy patients versus pancreatoduodenectomy patients (48.8% vs. 100%; p

Abstract Background It is challenging to diagnose infected aneurysm in the early phase. This study aimed to describe the clinical and microbiological characteristics of infected aneurysm, and to elucidate the difficulties in diagnosing the disease. Methods Forty-one cases of infected aneurysm were diagnosed in Nagasaki University Hospital from 2005 to 2019. Information on clinical and microbiological characteristics, radiological findings, duration of onset, and type of initial computed tomography (CT) imaging conditions were collected. Factors related to diagnostic delay were analyzed by Fisher’s exact test for categorical variables or by the Wilcoxon rank-sum test for continuous variables. Results Pathogens were identified in 34 of 41 cases; the pathogens were Gram-positive cocci in 16 cases, Gram-negative rods in 13 cases, and others in five cases. Clinical characteristics did not differ in accordance with the identified bacteria. At the time of admission, 16 patients were given different initial diagnoses, of which acute pyelonephritis (n = 5) was the most frequent. Compared with the 22 patients with an accurate initial diagnosis, the 19 initially misdiagnosed patients were more likely to have been examined by plain CT. The sensitivities of plain CT and contrast-enhanced CT were 38.1% and 80.0%, respectively. Conclusions In cases of infected aneurysm, diagnostic delay is attributed to non-specific symptoms and the low sensitivity of plain CT. Clinical characteristics of infected aneurysm mimic various diseases. Contrast-enhanced CT should be considered if infected aneurysm is suspected.

A white cane is conventionally used by visually impaired persons to assist their mobility. To learn its proper operation, training by an orientation & mobility specialist is necessary. However, because the number of specialists is limited, visually impaired persons often do not receive sufficient training. To rectify this issue, a training environment in which the visually impaired can train independently is required. This paper proposes a training system that enables the visually impaired to learn white cane techniques using illusory pulling cues. Specifically, in the white cane touch technique, which is a basic white cane technique, a system that targets the swing width of the white cane is presented by illusory pulling cues. To verify the efficacy of the system, a prototype was implemented and evaluated via user tests. The results confirmed that the error of the swing width of the white cane decreased following use of the proposed system. The proposed system will contribute to the development of the mobility of the visually impaired by enabling them to train with the white cane independently and spontaneously, thereby reducing the workload of specialists.

In April 2020, a coronavirus disease (COVID-19) outbreak occurred on the cruise ship Costa Atlantica in Nagasaki, Japan. Our outbreak investigation included 623 multinational crewmembers onboard on April 20. Median age was 31 years; 84% were men. Each crewmember was isolated or quarantined in a single room inside the ship, and monitoring of health status was supported by a remote health monitoring system. Crewmembers with more severe illness were hospitalized. The investigation found that the outbreak started in late March and peaked in late April, resulting in 149 laboratory-confirmed and 107 probable cases of infection with severe acute respiratory syndrome coronavirus 2. Six case-patients were hospitalized for COVID-19 pneumonia, including 1 in severe condition and 2 who required oxygen administration, but no deaths occurred. Although the virus can spread rapidly on a cruise ship, we describe how prompt isolation and quarantine combined with a sensitive syndromic surveillance system can control a COVID-19 outbreak.

Abstract Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p

Cardiovascular calcification is the lead predictor of cardiovascular events and the top cause of morbidity and mortality worldwide. To date, only invasive surgical options are available to treat cardiovascular calcification despite the growing understanding of underlying pathological mechanisms. Key players in vascular calcification are vascular smooth muscle cells (SMCs), which transform into calcifying SMCs and secrete mineralizing extracellular vesicles that form microcalcifications, subsequently increasing plaque instability and consequential plaque rupture. There is an increasing, practical need for a large scale and inexhaustible source of functional SMCs. Here we describe an induced pluripotent stem cell (iPSC)-derived model of SMCs by differentiating iPSCs toward SMCs to study the pathogenesis of vascular calcification. Specifically, we characterize the proteome during iPSC differentiation to better understand the cellular dynamics during this process. First, we differentiated human iPSCs toward an induced-SMC (iSMC) phenotype in a 10-day protocol. The success of iSMC differentiation was demonstrated through morphological analysis, immunofluorescent staining, flow cytometry, and proteomics characterization. Proteomics was performed throughout the entire differentiation time course to provide a robust, well-defined starting and ending cell population. Proteomics data verified iPSC differentiation to iSMCs, and functional enrichment of proteins on different days showed the key pathways changing during iSMC development. Proteomics comparison with primary human SMCs showed a high correlation with iSMCs. After iSMC differentiation, we initiated calcification in the iSMCs by culturing the cells in osteogenic media for 17 days. Calcification was verified using Alizarin Red S staining and proteomics data analysis. This study presents an inexhaustible source of functional vascular SMCs and calcifying vascular SMCs to create an in vitro model of vascular calcification in osteogenic conditions, with high potential for future applications in cardiovascular calcification research.

Abstract Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia.

The title crystalline compound, [Cu2(NCS)2(C9H16N2)2], was obtained from the reaction of copper(I) thiocyanate (CuSCN) with (N-prop-2-en-1-yl)piperidine-1-carbothioamide as a chelating and bridging thiourea ligand in chlorobenzene. The Cu2S2 core of the dimeric molecule is situated on a crystallographic inversion centre. The copper atom is coordinated by a thiocyanate nitrogen atom, each sulfur atom of the two thiourea ligands, and the C=C double bond of the ligand in a distorted tetrahedral geometry. The dimers are linked by N—H...S hydrogen bonds, forming a network extending in two dimensions parallel to (100).

Periodontal disease develops as a result of oral microbiota in dysbiosis, followed by the growth of periodontal pathogens such as Porphyromonas gingivalis and Prevotella intermedia. In case of acute symptoms, antibacterial agents and disinfectants are administered, however the appearance of drug-resistant bacteria and allergies cause problems. In recent years, studies on the effects of probiotics have been conducted as an alternative therapy for periodontitis. However, the basic mechanism of the inhibitory effect of probiotic bacteria on periodontal disease has not been clearly elucidated. To clarify the antibacterial mechanism of probiotics against periodontal pathogens, we used Limosilactobacillus (Lactobacillus) fermentum ALAL020, which showed the strongest antibacterial activity against P. gingivalis and P. intermedia among 50 screened lactic acid bacteria strains. The antibacterial substances produced were identified and structurally analyzed. After neutralizing the MRS liquid culture supernatant of ALAL020 strain, the molecular weight (m/z) of the main antibacterial substance separated by gel filtration column chromatography and reverse phase HPLC was 226.131. This low molecular weight compound was analyzed by LC-MS and disclosed the composition formula C11H18O3N2, however the molecular structure remained unknown. Then, structural analysis by NMR revealed C11H18O3N2 as the cyclic dipeptide, “hexahydro-7-hydroxy-3- (2-methylpropyl) pyrrolo [1,2-a] pyrazine-1,4-dion cyclo (Hyp-Leu) “. Based on the results of this analysis, cyclo (Hyp-Leu) was chemically synthesized and the antibacterial activity against P. gingivalis and P. intermedia was measured. The minimum inhibitory concentration (MIC) was 2.5 g/L and the minimum bactericidal concentration (MBC) was shown to be less than 5 g/L. In addition, an in vitro epithelial tissue irritation test at 10 g/L showed no tissue toxicity. So far there are no reports of this peptide being produced by probiotic bacteria. Furthermore, antibacterial activity of this cyclic dipeptide against periodontal disease bacteria has not been confirmed. The results of this study might lead to a comprehensive understanding of the antibacterial mechanism against periodontal disease bacteria in future, and are considered applicable for the prevention of periodontal disease.

Vascular calcification is a cardiovascular disorder with no therapeutic options. We recently reported that o-octanoyltransferase (CROT) suppression can inhibit vascular calcification in vivo and in vitro through amelioration of mitochondrial function and fatty acid metabolism. Inhibiting calcification with a small molecule compound targeting CROT-associated mechanisms will be a promising non-invasive treatment of vascular calcification. Here we used a computational approach to search for existing drugs that can inhibit vascular calcification through the CROT pathway. For screening of the compounds that reduce CROT expression, we utilized the Connectivity Map encompassing the L1000 computational platform that contains transcription profiles of various cell lines and perturbagens including small molecules. Small molecules (n = 13) were identified and tested in human primary smooth muscle cells cultured in osteogenic media to induce calcification. Niclosamide, an FDA-improved anthelmintic drug, markedly inhibited calcification along with reduced alkaline phosphatase activity and CROT mRNA expression. To validate this compound in vivo, LDL receptor (Ldlr)-deficient mice fed a high fat diet were given oral doses of niclosamide (0 or 750 ppm admixed with diet) for 10 weeks. Niclosamide treatment decreased aortic and carotid artery calcification as determined by optical near infrared molecular imaging (OsteoSense680) and histological analysis. In addition, niclosamide improved features of fatty liver, including decreased cholesterol levels along with decreased Crot expression, while plasma total cholesterol levels did not change. Proteomic analysis of aortic samples demonstrated that niclosamide affected wingless/integrated (Wnt) signaling pathway and decreased runt-related transcription factor 2 (Runx2) expression, an essential factor for calcification. Our target discovery strategy using a genetic perturbation database with existing drugs identified niclosamide, that in turn inhibited calcification in vivo and in vitro, indicating its potential for the treatment of vascular calcification.

Abstract Background and Aims Imaging tools for predicting pancreatic atrophy after steroid therapy in autoimmune pancreatitis (AIP) have not been established. As delayed equilibrium‐phase contrast enhancement in computed tomography (CE‐CT) may reflect interstitial fibrosis, we evaluated the ability of equilibrium‐phase CT imaging for predicting pancreatic atrophy. Methods Forty‐six steroid‐treated AIP patients who underwent contrast‐enhanced CT at our university hospital were included in this retrospective study. CT attenuation (Hounsfield units [HU]) values in noncontrast images (NC) and equilibrium‐phase images (EP) and the differences in HU values between NC and EP images (SUB) were measured. Pancreatic volume was measured in CE‐CT before (Volpre) and after (Volpost) steroid therapy. The volume reduction rate was calculated. The relationships of CT values with pancreatic atrophy, Volpost, volume reduction rate, and diabetes exacerbation were investigated. Results CT values in the EP and SUB images before steroid therapy were associated with pancreatic atrophy after steroid therapy (atrophy vs nonatrophy 114.5 ± 12.8 vs 99.5 ± 11.1, P = 0.0002; 70.9 ± 14.72 vs 57.2 ± 13.1, P = 0.003, respectively), but CT values in NC images were not (P = 0.42). CT values in EP and SUB images before steroid therapy were correlated with Volpost (EP images r = −0.70, P = 0.002; SUB images r = −0.68, P = 0.03) and volume reduction rate after steroid therapy (EP images: r = −0.55, P

Abstract Although Streptococcus suis has attracted public attention as a major swine and human pathogen, this bacterium has also been isolated from other animals, including ruminants. However, recent taxonomic studies revealed the existence of other species that were previously identified as S. suis, and some of these isolates were reclassified as the novel species Streptococcus ruminantium. In Japan, biochemically identified S. suis is frequently isolated from diseased ruminants; however, such isolates have not yet been identified accurately, and their aetiological importance in ruminants is unclear. Therefore, to understand the importance of S. suis and S. suis-like bacteria in ruminants, we reclassified S. suis isolates from ruminants according to the updated classification and investigated their genetic diversity. Although both S. suis and S. ruminantium were isolated from healthy and diseased ruminants, most of the isolates from diseased animals were S. ruminantium, implying that S. ruminantium is more likely to be associated with ruminant disease than S. suis. However, the ruminant S. suis and S. ruminantium isolates from diseased animals were classified into diverse genotypes rather than belonging to certain clonal groups. Genome sequence analysis of 20 S. ruminantium isolates provided information about the antibiotic resistance, potential virulence, and serological diversity of this species. We further developed an S. ruminantium-specific PCR assay to aid in the identification of this bacterium. The information obtained and the method established in this study will contribute to the accurate diagnosis of ruminant streptococcal infections.