Increased fucosyl glycoconjugate by Mycoplasma hyopneumoniae enhances adherences of Pasteurella multocida type A in the ciliated epithelial cells of the respiratory tract

BACKGROUND: The objective of this study was to elucidate the pathogenic mechanisms of how Mycoplasma hyopneumoniae enhances secondary Pasteurella multocida type A infection which leads to porcine enzootic pneumonia in infected pigs. Sixteen pigs were experimentally infected with M. hyopneumoniae and then euthanized at 7, 14, 21 and 28 days post inoculation. In situ hybridization for M. hyopneumoniae DNA and Ulex europaeus agglutinin-I (UEA-I) lectin histochemistry for fucosyl glycoconjugate, was performed in serial lung sections to determine alteration of fucosyl glycoconjugate in M. hyopneumoniae-infected bronchial and bronchiolar epithelium. Bacterial overlay assay was performed to determine the affinity of P. multocida type A with L-fucose. RESULTS: The luminal surface of bronchial and bronchiolar epithelial cells that were stained with UEA-I always showed hybridization signals for M. hyopneumoniae but it was negative in the unaffected parts of the lung from M. hyopneumoniae-infected pigs and in lung from negative control pigs. Colocalization of M. hyopneumoniae and UEA-I was especially prominent in the luminal surface of bronchial and bronchiolar epithelial cells in serial section of lung. The mean number of M. hyopneumoniae-positive cells correlated with the mean number of UEA-I-positive cells in lungs from infected pigs throughout the experiment. All eight P. multocida type A isolates from naturally occurring enzootic pneumonia, bound strongly at levels of 2 μg and 5 μg of L-fucose. CONCLUSIONS: The results of the present study demonstrate that M. hyopneumoniae increases the L-fucose composition to enhance adherence of P. multocida type A to the bronchial and bronchiolar epithelial cells

Abnormal synergistic gait mitigation in acute stroke using an innovative ankle–knee–hip interlimb humanoid robot: A preliminary randomized controlled trial

Abnormal spasticity and associated synergistic patterns are the most common neuromuscular impairments affecting ankle–knee–hip interlimb coordinated gait kinematics and kinetics in patients with hemiparetic stroke. Although patients with hemiparetic stroke undergo various treatments to improve gait and movement, it remains unknown how spasticity and associated synergistic patterns change after robot-assisted and conventional treatment. We developed an innovative ankle–knee–hip interlimb coordinated humanoid robot (ICT) to mitigate abnormal spasticity and synergistic patterns. The objective of the preliminary clinical trial was to compare the effects of ICT combined with conventional physical therapy (ICT-C) and conventional physical therapy and gait training (CPT-G) on abnormal spasticity and synergistic gait patterns in 20 patients with acute hemiparesis. We performed secondary analyses aimed at elucidating the biomechanical effects of Walkbot ICT on kinematic (spatiotemporal parameters and angles) and kinetic (active force, resistive force, and stiffness) gait parameters before and after ICT in the ICT-C group. The intervention for this group comprised 60-min conventional physical therapy plus 30-min robot-assisted training, 7 days/week, for 2 weeks. Significant biomechanical effects in knee joint kinematics; hip, knee, and ankle active forces; hip, knee, and ankle resistive forces; and hip, knee, and ankle stiffness were associated with ICT-C. Our novel findings provide promising evidence for conventional therapy supplemented by robot-assisted therapy for abnormal spasticity, synergistic, and altered biomechanical gait impairments in patients in the acute post-stroke recovery phase. Trial Registration: Clinical Trials.gov identifier NCT03554642 (14/01/2020)

Comparative pathogenesis of type 1 (European genotype) and type 2 (North American genotype) porcine reproductive and respiratory syndrome virus in infected boar

Background : Porcine reproductive and respiratory syndrome virus (PRRSV) now has two main genotypes, genotype 1 (European) and genotype 2 (North American). There is a lack of data on the comparison of pathogenicity of the two genotypes in boars. The objectives of the present study were to evaluate the amount of PRRSV present in semen over time and compare the viral distribution and microscopic lesions of type 1 and type 2 PRRSV-infected boars. Methods : Twenty-four 8-month-old PRRSV-naïve Duroc boars were randomly allocated to 3 treatment groups. The boars in groups 1 (n = 9) and 2 (n = 9) were intranasally inoculated with type 1 or type 2 PRRSV, respectively. The boars in groups 1 (n = 6) served as negative controls. Semen and blood samples were collected up to 35 days post-inoculation (dpi), and necropsies were performed on 14, 21, and 35 dpi. Results : There were no significant differences in the genomic copy number of PRRSV, microscopic testicular lesion score, number of PRRSV-positive germ cells, or number of apoptotic cells between the type 1 and type 2 PRRSV-infected boars throughout the experiment. Histopathological changes were manifested by the desquamation of spermatocytes and the presence of multinucleated giant cells in seminiferous tubules of both type 1 and type 2 PRRSV-infected boars. The distribution of PRRSV-positive cells was focal; the virus was found in single germ cells or small clusters of germ cells, localized to the spermatogonia, spermatocytes, spermatids, and non-sperm cells in type 1 and type 2 PRRSV-infected boars. Conclusions : The results of this study demonstrated that two genotypes of PRRSV do not have significantly different virulence toward the male reproductive system of pigs.This research was supported by contract research funds of the Research Institute for Veterinary Science (RIVS) from the College of Veterinary Medicine and by Brain Korea 21 Program for Veterinary Science in the Republic of Korea.Peer Reviewe

Translation and validation of the Korean version of PROMIS® pediatric and parent proxy measures for emotional distress

This study was funded by Seoul National University (Grant Number: 810–20160011)

Statistical modeling of health space based on metabolic stress and oxidative stress scores

Abstract Background Health space (HS) is a statistical way of visualizing individuals health status in multi-dimensional space. In this study, we propose a novel HS in two-dimensional space based on scores of metabolic stress and of oxidative stress. Methods These scores were derived from three statistical models: logistic regression model, logistic mixed effect model, and proportional odds model. HSs were developed using Korea National Health And Nutrition Examination Survey data with 32,140 samples. To evaluate and compare the performance of the HSs, we also developed the Health Space Index (HSI) which is a quantitative performance measure based on the approximate 95% confidence ellipses of HS. Results Through simulation studies, we confirmed that HS from the proportional odds model showed highest power in discriminating health status of individual (subject). Further validation studies were conducted using two independent cohort datasets: a health examination dataset from Ewha-Boramae cohort with 862 samples and a population-based cohort from the Korea association resource project with 3,199 samples. Conclusions These validation studies using two independent datasets successfully demonstrated the usefulness of the proposed HS

Subclinical vascular inflammation in subjects with normal weight obesity and its association with body Fat: an 18 F-FDG-PET/CT study

BACKGROUND: Although body mass index (BMI) is the most widely accepted parameter for defining obesity, recent studies have indicated a unique set of patients who exhibit normal BMI and excess body fat (BF), which is termed as normal weight obesity (NWO). Increased BF is an established risk factor for atherosclerosis. However, it is unclear whether NWO subjects already have a higher degree of vascular inflammation compared to normal weight lean (NWL) subjects; moreover, the association of BF with vascular inflammation in normal weight subjects is largely unknown. METHODS: NWO and NWL subjects (n = 82 in each group) without any history of significant vascular disease were identified from a 3-year database of consecutively recruited patients undergoing (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG-PET/CT) at a self-referred Healthcare Promotion Program. The degree of subclinical vascular inflammation was evaluated using the mean and maximum target-to-background ratios (TBRmean and TBRmax) of the carotid artery, which were measured by (18) F-FDG-PET/CT (a noninvasive tool for assessing vascular inflammation). RESULTS: We found that metabolically dysregulation was greater in NWO subjects than in NWL subjects, with a significantly higher blood pressure, higher fasting glucose level, and worse lipid profile. Moreover, NWO subjects exhibited higher TBR than NWL subjects (TBRmean: 1.33 ± 0.16 versus 1.45 ± 0.19, p < 0.001; TBRmax: 1.52 ± 0.23 versus 1.67 ± 0.25, p < 0.001). TBR was significantly associated with total BF (TBRmean: r = 0.267, p = 0.001; TBRmax: r = 0.289, p < 0.001), age (TBRmean: r = 0.170, p = 0.029; TBRmax: r = 0.165, p = 0.035), BMI (TBRmean: r = 0.184, p = 0.018; TBRmax: r = 0.206, p = 0.008), and fasting glucose level (TBRmean: r = 0.157, p = 0.044; TBRmax: r = 0.182, p = 0.020). In multiple linear regression analysis, BF was an independent determinant of TBRmean and TBRmax, after adjusting for age, BMI, and fasting glucose level (TBRmean: regression coefficient = 0.020, p = 0.008; TBRmax: regression coefficient = 0.028, p = 0.005). Compared to NWL, NWO was also independently associated with elevated TBRmax values, after adjusting for confounding factors (odds ratio = 2.887, 95% confidence interval 1.206–6.914, p = 0.017). CONCLUSIONS: NWO is associated with a higher degree of subclinical vascular inflammation, of which BF is a major contributing factor. These results warrant investigations for subclinical atherosclerosis in NWO patients

Double-stranded RNA induces inflammatory gene expression in schwann cells: Implication in the Wallerian degeneration

Schwann cells play an important role in peripheral nerve regeneration. Upon neuronal injury, activated Schwann cells clean up the myelin debris by phagocytosis, and promote neuronal survival and axon outgrowth by secreting various neurotrophic factors. However, it is unclear how the nerve injury induces Schwann cell activation. Recently, it was reported that certain cytoplasmic molecules, which are secreted by cells undergoing necrotic cell death, induce immune cell activation via the toll-like receptors (TLRs). This suggests that the TLRs expressed on Schwann cells may recognize nerve damage by binding to the endogenous ligands secreted by the damaged nerve, thereby inducing Schwann cell activation. Accordingly, this study was undertaken to examine the expression and the function of the TLRs on primary Schwann cells and iSC, a rat Schwann cell line. The transcripts of TLR2, 3, 4, and 9 were detected on the primary Schwann cells as well as on iSC. The stimulation of iSC with poly (I：C), a synthetic ligand for the TLR3, induced the expression of TNF-α and RANTES. In addition, poly (I：C) stimulation induced the iNOS expression and nitric oxide secretion in iSC. These results suggest that the TLRs may be involved in the inflammatory activation of Schwann cells, which is observed during Wallerian degeneration after a peripheral nerve injury.This work was supported by the Korea Research Foundation Grant (KRF-2003-003-E00178)

CWAS-Plus: estimating category-wide association of rare noncoding variation from whole-genome sequencing data with cell-type-specific functional data.

Variants in cis-regulatory elements link the noncoding genome to human pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS), enhances noncoding variant analysis by integrating both whole-genome sequencing (WGS) and user-provided functional data. With simplified parameter settings and an efficient multiple testing correction method, CWAS-Plus conducts the CWAS workflow 50 times faster than CWAS, making it more accessible and user-friendly for researchers. Here, we used a single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type-specific enhancers and promoters. Examining autism spectrum disorder WGS data (n = 7280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimers disease WGS data (n = 1087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Pluss utility in genomic disorders and scalability for processing large-scale WGS data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively