Protective Role of the Toll-Like Receptor 5 Agonist KMRC011 against Murine Colitis Induced by Citrobacter rodentium and Dextran Sulfate Sodium.

This study aimed to identify the therapeutic ability of a novel toll-like receptor (TLR) 5 agonist, KMRC011, on ulcerative colitis induced by Citrobacter rodentium and dextran sulfate sodium in a C57BL/6N mouse model. Ulcerative colitis was induced in the mice by the oral administration of 1% dextran sulfate sodium in sterile drinking water for seven days ad libitum, followed by C. rodentium infection on the seventh day by intra-gastric administration (DSS-CT group). KMRC011 was administered intramuscularly at both 24 h and 15 min before (Treatment 1 group), and at both 15 min and 24 h after (Treatment 2 group) the C. rodentium infection. The length of the large intestine and histopathological counts were significantly greater and mucosal thickness was significantly thinner in the Treatment 1 group compared to the DSS-CT and Treatment 2 groups. Il-6 and Il-10 mRNA expression levels were upregulated, while Ifn-γ and Tnf-α mRNA expression levels were significantly downregulated in the Treatment 1 group, compared to the DSS-CT group. NF-κB p65 expression level was elevated due to ulcerative colitis in the DSS-CT group, but was significantly downregulated in the Treatment 1 group. Overall, KMRC011 showed protective effects against murine colitis by inhibiting NF-κB signaling.

Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection.

INTRODUCTION: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation. METHOD: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. RESULTS: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1α, induced protein 10, interferon (IFN)-α, IFN-γ, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. CONCLUSION: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.

C1qa deficiency in mice increases susceptibility to mouse hepatitis virus A59 infection.

BACKGROUND: Mouse hepatitis virus (MHV) A59 is a highly infectious pathogen and starts in the respiratory tract and progresses to systemic infection in laboratory mice. The complement system is an important part of the host immune response to viral infection. It is not clear the role of the classical complement pathway in MHV infection. OBJECTIVES: The purpose of this study was to determine the importance of the classical pathway in coronavirus pathogenesis by comparing C1qa KO mice and wild-type mice. METHODS: We generated a C1qa KO mouse using CRISPR/Cas9 technology and compared the susceptibility to MHV A59 infection between C1qa KO and wild-type mice. Histopathological and immunohistochemical changes, viral loads, and chemokine expressions in both mice were measured. RESULTS: MHV A59-infected C1qa KO mice showed severe histopathological changes, such as hepatocellular necrosis and interstitial pneumonia, compared to MHV A59-infected wild-type mice. Virus copy numbers in the olfactory bulb, liver, and lungs of C1qa KO mice were significantly higher than those of wild-type mice. The increase in viral copy numbers in C1qa KO mice was consistent with the histopathologic changes in organs. These results indicate that C1qa deficiency enhances susceptibility to MHV A59 systemic infection in mice. In addition, this enhanced susceptibility effect is associated with dramatic elevations in spleen IFN-γ, MIP-1 α, and MCP-1 in C1qa KO mice. CONCLUSIONS: These data suggest that C1qa deficiency enhances susceptibility to MHV A59 systemic infection, and activation of the classical complement pathway may be important for protecting the host against MHV A59 infection.

Multi-slice representational learning of convolutional neural network for Alzheimer's disease classification using positron emission tomography.

BACKGROUND: Alzheimer's Disease (AD) is a degenerative brain disorder that often occurs in people over 65 years old. As advanced AD is difficult to manage, accurate diagnosis of the disorder is critical. Previous studies have revealed effective deep learning methods of classification. However, deep learning methods require a large number of image datasets. Moreover, medical images are affected by various environmental factors. In the current study, we propose a deep learning-based method for diagnosis of Alzheimer's disease (AD) that is less sensitive to different datasets for external validation, based upon F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). RESULTS: The accuracy, sensitivity, and specificity of our proposed network were 86.09%, 80.00%, and 92.96% (respectively) using our dataset, and 91.02%, 87.93%, and 93.57% (respectively) using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We observed that our model classified AD and normal cognitive (NC) cases based on the posterior cingulate cortex (PCC), where pathological changes occur in AD. The performance of the GAP layer was considered statistically significant compared to the fully connected layer in both datasets for accuracy, sensitivity, and specificity (p < 0.01). In addition, performance comparison between the ADNI dataset and our dataset showed no statistically significant differences in accuracy, sensitivity, and specificity (p > 0.05). CONCLUSIONS: The proposed model demonstrated the effectiveness of AD classification using the GAP layer. Our model learned the AD features from PCC in both the ADNI and Severance datasets, which can be seen in the heatmap. Furthermore, we showed that there were no significant differences in performance using statistical analysis.

Slice-selective learning for Alzheimer's disease classification using a generative adversarial network: a feasibility study of external validation.

PURPOSE: The aim of this feasibility study was to use slice selective learning using a Generative Adversarial Network for external validation. We aimed to build a model less sensitive to PET imaging acquisition environment, since differences in environments negatively influence network performance. To investigate the slice performance, each slice evaluation was performed. METHODS: We trained our model using a 18F-fluorodeoxyglucose ([18F]FDG) PET/CT dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and tested the model with a Severance Hospital dataset. We applied slice selective learning to reduce computational cost and to extract unbiased features. We extracted features of Alzheimer's disease (AD) and normal cognitive (NC) condition using a Boundary Equilibrium Generative Adversarial Network (BEGAN) for stable convergence. Then, we utilized these features to train a support vector machine (SVM) classifier to distinguish AD from NC. RESULTS: The slice range that covered the posterior cingulate cortex (PCC) using double slices showed the best performance. The accuracy, sensitivity, and specificity of our proposed network was 94.33%, 91.78%, and 97.06% using the Severance dataset and 94.82%, 92.11%, and 97.45% using the ADNI dataset. The performance on the two independent datasets showed no statistical difference (p > 0.05). Moreover, there was a statistical difference in the performance between using two slices and one slice as input (p < 0.05). CONCLUSIONS: Our model learned the generalized features of AD and NC for external validation when appropriate slices were selected. This study showed the feasibility of this model with consistent performance when tested using datasets acquired from a variety of image-acquisition environments.

Comparison of the virulence of Streptococcus pneumoniae in ICR mouse stocks of three different origins.

Streptococcus pneumoniae causes many people to suffer from pneumonia, septicemia, and other diseases worldwide. To identify the difference in susceptibility of and treatment efficacy against S. pneumoniae in three ICR mouse stocks (Korl:ICR, A:ICR, and B:ICR) with different origins, mice were infected with 2 × 106, 2 × 107, and 2 × 108 CFU of S. pneumoniae D39 intratracheally. The survival of mice was observed until three weeks after the infection. The three stocks of mice showed no significant survival rate difference at 2 × 106 and 2 × 107 CFU. However, the lung and spleen weight in the A:ICR stock was significantly different from that in the other two stocks, whereas the liver weight in B:ICR stock was significantly lower than that in the other two stocks. Interestingly, no significant CFU difference in the organs was observed between the ICR stocks. The level of interferon gamma inducible protein 10 in Korl:ICR was significantly lower than that in the other two stocks. The level of granulocyte colony stimulating factor in B:ICR was significantly lower than in the other two stocks. However, tumor-necrosis factor-alpha and interleukin-6 levels showed no significant difference between the ICR stocks. In the vancomycin efficacy test after the S. pneumoniae infection, both the single-dose and double-dose vancomycin-treated groups showed a significantly better survival rate than the control group. There was no significant survival difference between the three stocks. These data showed that Korl:ICR, A:ICR, and B:ICR have no susceptibility difference to the S. pneumoniae D39 serotype 2.

Percutaneous vertebroplasty for pregnancy-associated osteoporotic vertebral compression fractures.

Osteoporosis is a worldwide problem and it mainly affects postmenopausal women. Osteoporosis associated with pregnancy or lactation is a rare condition. The incidence and mechanism of this phenomenon has not been clarified, but it can cause one or more vertebral compression fractures with severe, prolonged back pain in the affected women. We experienced this uncommon case, treated it with percutaneous vertebroplasty. A 35-old-woman visited our hospital with complaints of severe back pain and flank pain 2 months after normal vaginal delivery. She was diagnosed with osteoporotic vertebral compression fractures on the T5, 8, 9 and 11 vertebral bodies and we performed percutaneous vertebroplasty on the T8, 9 and 11 vertebrae with a good result. We present here an unusual case of pregnancy-associated compression fractures treated by percutaneous vertebroplasty.

The retrial of percutaneous vertebroplasty for the treatment of vertebral compression fracture.

OBJECTIVE: For the treatment of osteoporotic vertebral compression fracture, percutaneous vertebroplasty (PVP) is currently widely used as an effective and relatively safe procedure. However, some patients do not experience pain relief after PVP. We performed several additional PVP procedures in those patients who did not have any improvement of pain after their initial PVP and we obtained good results. Our purpose is to demonstrate the effective results of an additional PVP procedure at the same previously treated level. METHODS: We reviewed the medical records and the radiologic data of the PVP procedures that were performed at our hospital from November 2005 to May 2008 to determine the patients who had undergone additional PVP. We identified ten patients and we measured the clinical outcomes according to the visual analogue scale (VAS) score and the radiologic parameters, including the anterior body height and the kyphotic angulation. RESULTS: The mean volume of polymethylmethacrylate injected into each vertebrae was 4.3 mL (range: 2-8 mL). The mean VAS score was reduced from 8 to 2.32. The anterior body height was increased from 1.7 cm to 2.32 cm. The kyphotic angulation was restored from 10.14 degrees to 2.32 degrees. There were no complications noted. CONCLUSION: The clinical and radiologic outcomes suggest that additional PVP is effective for relieving pain and restoring the vertebral body in patients who have unrelieved pain after their initial PVP. Our study demonstrates that additional PVP performed at the previously-treated vertebral levels could provide therapeutic benefit.

Extreme multi-level percutaneous vertebroplasty for newly developed multiple adjacent compression fractures.

Osteoporotic patients who undergo percutaneous vertebroplasty (PVP) have the risk of a repeated collapse of their adjacent vertebral body due to alteration of load transfer into the adjacent vertebral body. The authors have experienced a rare case of repeated osteoporotic vertebral compression fractures (VCF) resulting in extreme multi-level PVP. A 74-year-old female developed severe back pain after slipping down one month ago. Her X-ray and MR images indicated a T11 VCF. She underwent successful PVP with polymethylmethacrylate (PMMA). Two weeks later, she returned to our hospital due to a similar back pain. Repeated X-ray and MR images showed an adjacent VCF on T12. A retrial of PVP was performed on T12, which provided immediate pain relief. Since then, repeated collapses of the vertebral body occurred 12 times in 13 levels within a 24-month period. Each time the woman was admitted to our hospital, she was diagnosed of newly developed VCFs and underwent repeated PVPs with PMMA, which finally eased back pain. Based on our experience with this patient, repeated multiple PVP is not dangerous because its few and minor complications. Therefore, repeated PVP can serve as an effective treatment modality for extreme-multi level VCFs.

Analysis of results using percutaneous vertebroplasty for the treatment of avascular necrosis of the vertebral body.

OBJECTIVE: Avascular necrosis (AVN) of the vertebral body is known as a relatively uncommon phenomenon in a vertebral compression fracture (VCF). The outstanding radiologic findings of AVN are intravertebral vacuum phenomenon with or without fluid collection. Several reports revealed that PVP or balloon kyphoplasty might be the effective treatment modalities for AVN. We also experienced excellent results when using PVP for the treatment of AVN of the vertebral body, and intend to describe the treatment's efficacy in this report. METHODS: Thirty-two patients diagnosed with AVN of the vertebral body were treated with PVP. We measured the pre- and post-operative anterior body height and kyphotic angulation. The visual analogue scale (VAS) was used to determine the relief of back pain. RESULTS: The anterior body height (pre-operative : 1.49 cm, post-operative : 2.22 cm) and kyphotic angulation (pre-operative : 14.47 degrees, post-operative : 6.57 degrees) were significantly restored (p<0.001). VAS was improved from 8.9 to 3.7. Pseudoarthrosis was corrected in all cases, which was confirmed by dynamic radiographs. Fluid collection was found in sixteen cases and was aspirated with serous nature. No organism and tumor cell were noted. CONCLUSION: PVP proved to be an effective procedure for the treatment of AVN of the vertebral body, which corrected dynamic instability and significantly restored the anterior body height and kyphotic angulation.