Objectives: ：Hyperactive delirium is a state of acute mental confusion including aggressive and impulsive behavior and it is burdensome for the family and caregivers of terminal cancer patients. Therefore, predicting the symptoms of hyperactive delirium can provide benefits to care terminal cancer patients. In this study, several risk factors were evaluated during hospitalization for predicting delirious symptom in terminal cancer patients. Methods: ：Patients who died of cancer in a palliative care unit from January 2011 to September 2012 were investigated by retrospective chart review. Clinical and laboratory data were collected to identify the factors associated with hyperactive delirium. Univariate and multivariate analysis by logistic regression were applied. Additional survival analysis was conducted to measure the onset of delirium symptoms after pneumonia. Results: ：During hospitalization, 49 of 201 patients showed the symptoms of hyperactive delirium (24.4%). Developing a delirious symptom was associated with male (OR=3.36, p=0.002), bone metastasis (OR=3.70, p=0.002), pneumonia during hospitalization (OR=3.17, p=0.02) and depressive mood (OR=2.53, p80.011). In additional survival analysis, half of patients developed symptoms of delirium within 3 days after pneumonia. Conclusion ：Our results suggest that male, bone metastasis, depressive mood, and pneumonia are risk factors that can affect hyperactive delirium in terminally ill cancer patients. In addition, many patients with pneumonia abruptly developed the symptoms of hyperactive delirium within 3 days. Our finding may provide clues for predicting hyperactive delirium, and it can be helpful to manage delirium symptoms.

An autopsy case of disseminated HSV type 2 infection occurring in a neonate at 32 weeks' gestation, delivered by cesarean section after premature rupture of membrane of 7 days duration, is presented. Herpes simplex virus type 2 was isolated from the vesicular skin lesion. The mother and patient had specific antibody to type 2 herpes simplex virus. Patient's parents had denied any herpetic orolabial or genital lesion during or before this pregnancy. Cultures from the cervical and vaginal swabs of the mother were negative for HSV. Postmortem examination showed hepatic necrosis, skin vesicle, devastating necrotizing inflammation of the brain, chorioretinitis and interstitial pneumonitis.
Autopsy ; Brain/pathology ; Encephalitis/*etiology ; Herpes Simplex/*congenital/pathology ; Humans ; Infant, Newborn ; Infant, Premature, Diseases/*pathology ; Liver/pathology ; Male ; Necrosis ; Skin/pathology

Purpose: Colorectal cancer (CRC) is a common malignancy worldwide and the second leading cause of cancer-related deaths. In addition, lymph node metastasis in CRC is considered an important prognostic factor for predicting disease recurrence and patient survival. Recent studies demonstrated that the microbiome makes substantial contributions to tumor progression, however, there is still unknown about the microbiome associated with lymph node metastasis of CRC. Here, we first reported the microbial and tumor-infiltrating immune cell differences in CRC according to the lymph node metastasis status. Materials and Methods: Using Next Generation Sequencing data acquired from 368 individuals diagnosed with CRC (N0, 266; N1, 102), we applied the LEfSe to elucidate microbial differences. Subsequent utilization of the Kaplan-Meier survival analysis enabled the identification of particular genera exerting significant influence on patient survival outcomes. Results We found 18 genera in the N1 group and 3 genera in the N0 group according to CRC lymph node metastasis stages. In addition, we found that the genera Crenobacter (P=0.046), Maricaulis (P=0.093), and Arsenicicoccus (P=0.035) in the N0 group and Cecembia (P=0.08) and Asanoa (P=0.088) in the N1 group were significantly associated with patient survival according to CRC lymph node metastasis stages. Further, Cecembia is highly correlated to tumor-infiltrating immune cells in lymph node metastasized CRC.Concolusion: Our study highlights that tumor-infiltrating immune cells and intratumoral microbe diversity are associated with CRC. Also, this potential microbiome-based oncology diagnostic tool warrants further exploration.

OBJECTIVES: Arsenic (As) is ubiquitously distributed in the environment and is known as a human carcinogen. In this study, acute As toxicity at lethal dosage in rats and mice was evaluated, and As-induced hepatotoxicity was characterized. METHODS: Male Sprague-Dawley rats, male ICR mice and trivalent inorganic As, sodium arsenite, were used in this experiment. LD50 and LD100 were calculated from 24-hour lethality after the single subcutaneous administration of As into rats and mice. Serum and liver were collected from the surviving animals. The activities of ALT, AST and gamma-GT in serum were determined, and the concentrations of MDA, GSH and CYP450 in liver were analyzed. RESULTS: The LD50 and LD100 of sodium arsenite were calculated as 12 mg/kg and 13 mg/kg for rats, and 16.5 mg/kg and 19 mg/kg for mice, respectively. Thus, the rat was more susceptible than the mouse to the acute lethal toxicity of As. The histopathological changes induced by As were similar between rats and mice. AST was increased in high-dose As-treated rats and mice, whereas ALT was increased in high-dose As-treated mice but not in rats. gamma-GT was not significantly changed between the two animal groups. As increased lipid peroxidation, but decreased GSH and CYP450 in the liver of both rats and mice, in dose-dependent patterns. These results indicate that oxidative stress might be one of the mechanisms in As-induced hepatotoxicity. CONCLUSION: Rats were more susceptive than mice to acute As toxicity, and oxidative stress might play a part in liver injury induced by As.
Animals ; Arsenic* ; Humans ; Lethal Dose 50 ; Lipid Peroxidation ; Liver ; Male ; Mice* ; Mice, Inbred ICR ; Oxidative Stress ; Rats* ; Rats, Sprague-Dawley ; Sodium

Brain damage resulting from perinatal cerebral hypoxia and ischemia is a major cause of acute mortality and neurological disabilities, including cerebral palsy (CP) and cognitive dysfunction. In order to establish an experimental hypoxia-ischemia (HI) model of CP for the screening of therapeutics, we operated bilateral common carotid artery ligation (BCAO) and monolateral carotid artery occlusion (MCAO), followed by 15 min of hypoxia (8% oxygen) in 4-day-old rats, and evaluated neurobehavioral disorders. After surgery, the survival rates of male and female BCAO rats were 33.3 and 7.1%, respectively, whereas 100% and 82.4% MCAO rats survived. In neurobehavioral performances, both male and female BCAO rats showed delayed achievement of righting reflex, in contrast to a negligible effect in MACO animals. However, both BCAO and MCAO rats exhibited impairment of cliff avoidance performances, although the physical dysfunction was more severe in BCAO than in MCAO. In global locomotor activity, MCAO rats also displayed decreased fast-moving time comparable BCAO animals, and increased resting and slow-moving times. In addition, MCAO rats showed marked learning and memory deficit in passive avoidance performances, similar to BCAO animals. From immunostaining analyses, severe degradation and loss of myelin basic proteins were observed in the brain of BCAO rats, in contrast to a mild aggregation in MCAO animals. Therefore, it is suggested that MCAO should be a more suitable CP model than BCAO, based on the high survival rate, relatively-mild brain injury, and enough neurobehavioral disorders for the research on preventive and therapeutic compounds.
Achievement ; Animals ; Anoxia ; Brain ; Brain Injuries ; Carotid Arteries ; Carotid Artery, Common ; Cerebral Palsy ; Demyelinating Diseases ; Female ; Humans ; Hypoxia, Brain ; Infant ; Ischemia ; Learning ; Ligation ; Male ; Mass Screening ; Memory Disorders ; Models, Theoretical ; Motor Activity ; Myelin Basic Protein ; Rats ; Reflex, Righting ; Survival Rate

Purpose: One of the novel cell sources of cell-based liver regenerative medicine is human chemically-derived hepatic progenitors (hCdHs). We previously established this cell by direct hepatocyte reprogramming with a combination of small molecules (hepatocyte growth factor, A83-01, CHIR99021). However, there have been several issues concerning the cell’s stability and maintenance, namely the occurrences of epithelial-mesenchymal transition (EMT) that develop fibrotic phenotypes, resulting in the loss of hepatic progenitor characteristics. These hepatic progenitor attributes are thought to be regulated by SOX9, a transcription factor essential for hepatic progenitor cells and cholangiocytes. Methods: To suppress the fibrotic phenotype and improve our long-term hCdHs culture technology, we utilized the epigenetic modulating drugs DNA methyltransferase inhibitor (5-azacytidine) and histone deacetylase inhibitor (sodium butyrate) that have been reported to suppress and revert hepatic fibrosis. To confirm the essential role of SOX9 to our cell, we used clustered regularly interspaced short palindromic repeats-interference (CRISPRi) to repress the SOX9 expression. Results: The treatment of only 5-azacytidine significantly reduces the fibrosis/mesenchymal marker and EMT-related transcription factor expression level in the early passages. Interestingly, this treatment also increased the hepatic progenitor markers expression, even during the reprogramming phase. Then, we confirmed the essential role of SOX9 by repressing the SOX9 expression with CRISPRi which resulted in the downregulation of several essential hepatic progenitor cell markers. Conclusion These results highlight the capacity of 5-azacytidine to inhibit EMT-driven hepatic fibrosis and the significance of SOX9 on hepatic progenitor cell stemness properties.