PURPOSE: The purpose of this study is to develop the optimal nursing fee for nurse-midwifery center (MC) in the national health insurance system. METHODS: The three methodologies used to calculate the conversion factors for the MCs in the national health insurance include cost accounting method, sustainable growth rate (SGR) model, and index model. In this study, the macro-economic indicators and the national statistics were used to estimate the conversion factors for the MCs. RESULTS: The optimal nursing fee for the MCs in 2011 was estimated to be an increase of 57.7% by cost accounting analysis, a decrease of 17.1% by SGR model, and a decrease of 16.1% by index model. The results from SGR model and index model could had been biased due to the upswing of medical spendings in the short-term period (2008~2009). A sensitivity analysis of pre-delivery subsidy program for OB & GYN hospitals and clinics showed that the program has substantially diminished the demand for the MC services. CONCLUSION: More reliable methodologies to estimate nursing fees precisely are required to prove the value of nurses' services and a government subsidy program for the MC services should be followed from a social perspective.
Accounting ; Bias (Epidemiology) ; Fees and Charges ; Financing, Government ; Insurance, Health ; Midwifery ; National Health Programs

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.

Alzheimer’s disease (AD) progressively inflicts impairment of synaptic functions with notable deposition of amyloid-β (Aβ) as senile plaques within the extracellular space of the brain. Accordingly, therapeutic directions for AD have focused on clearing Aβ plaques or preventing amyloidogenesis based on the amyloid cascade hypothesis. However, the emerging evidence suggests that Aβ serves biological roles, which include suppressing microbial infections, regulating synaptic plasticity, promoting recovery after brain injury, sealing leaks in the blood-brain barrier, and possibly inhibiting the proliferation of cancer cells. More importantly, these functions were found in in vitro and in vivo investigations in a hormetic manner, that is to be neuroprotective at low concentrations and pathological at high concentrations. We herein summarize the physiological roles of monomeric Aβ and current Aβ-directed therapies in clinical trials. Based on the evidence, we propose that novel therapeutics targeting Aβ should selectively target Aβ in neurotoxic forms such as oligomers while retaining monomeric Aβ in order to preserve the physiological functions of Aβ monomers.

Aucubin is a small compound naturally found in traditional medicinal herbs with primarily anti-inflammatory and protective effects. In the nervous system, aucubin is reported to be neuroprotective by enhancing neuronal survival and inhibiting apoptotic cell death in cultures and disease models. Our previous data, however, suggest that aucubin facilitates neurite elongation in cultured hippocampal neurons and axonal regrowth in regenerating sciatic nerves. Here, we investigated whether aucubin facilitates the differentiation of neural precursor cells (NPCs) into specific types of neurons. In NPCs cultured primarily from the rat embryonic hippocampus, aucubin significantly elevated the number of GAD65/67 immunoreactive cells and the expression of GAD65/67 proteins was upregulated dramatically by more than three-fold at relatively low concentrations of aucubin (0.01 µM to 10 µM). The expression of both NeuN and vGluT1 of NPCs, the markers for neurons and glutamatergic cells, respectively, and the number of vGluT1 immunoreactive cells also increased with higher concentrations of aucubin (1 µM and 10 µM), but the ratio of the increases was largely lower than GAD expression and GAD immunoreactive cells. The GABAergic differentiation of pax6-expressing late NPCs into GABA-producing cells was further supported in cortical NPCs primarily cultured from transgenic mouse brains, which express recombinant GFP under the control of pax6 promoter. The results suggest that aucubin can be developed as a therapeutic candidate for neurodegenerative disorders caused by the loss of inhibitory GABAergic neurons.
Animals ; Axons ; Brain ; Cell Death ; GABAergic Neurons* ; Hippocampus ; Mice ; Mice, Transgenic ; Nervous System ; Neurites ; Neurodegenerative Diseases ; Neurons ; Plants, Medicinal ; Rats ; Sciatic Nerve

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.

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

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.