The Immediate Economic Impact of Maternal Deaths on Rural Chinese Households

OBJECTIVE: To identify the immediate economic impact of maternal death on rural Chinese households. METHODS: Results are reported from a study that matched 195 households who had suffered a maternal death to 384 households that experienced a childbirth without maternal death in rural areas of three provinces in China, using quantitative questionnaire to compare differences of direct and indirect costs between two groups. FINDINGS: The direct costs of a maternal death were significantly higher than the costs of a childbirth without a maternal death (US$4,119 vs.$370, p<0.001). More than 40% of the direct costs were attributed to funeral expenses. Hospitalization and emergency care expenses were the largest proportion of non-funeral direct costs and were higher in households with maternal death than the comparison group (US$2,248 vs.$305, p<0.001). To cover most of the high direct costs, 44.1% of affected households utilized compensation from hospitals, and the rest affected households (55.9%) utilized borrowing money or taking loans as major source of money to offset direct costs. The median economic burden of the direct (and non-reimbursed) costs of a maternal death was quite high--37.0% of the household's annual income, which was approximately 4 times as high as the threshold for an expense being considered catastrophic. CONCLUSION: The immediate direct costs of maternal deaths are extremely catastrophic for the rural Chinese households in three provinces studied

The Effect of Vinpocetine on Human Cytochrome P450 Isoenzymes by Using a Cocktail Method

Vinpocetine is a derivative of the alkaloid vincamine, which had been prescribed for chronic cerebral vascular ischemia and acute ischemic stroke or used as a dietary supplement for its several different mechanisms of biological activities. However, information on the cytochrome P450 (CYP) enzyme-mediated drug metabolism has not been previously studied. The present study was performed to investigate the effects of vinpocetine on CYPs activity, and cocktail method was used, respectively. To evaluate the effects of vinpocetine on the activity of human CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, human liver microsomes were utilized to incubate with the mixed CYPs probe substrates and the target components. The results indicate that vinpocetine exhibited weak inhibitory effect on the CYP2C9, where the IC50 value is 68.96 μM, whereas the IC50 values for CYP3A4, CYP2C19, CYP2D6, and CYP2E1 were all over range of 100 μM, which showed that vinpocetine had no apparent inhibitory effects on these CYPs. In conclusion, the results indicated that drugs metabolized by CYP2C9 coadministrated with vinpocetine may require attention or dose adjustment

PO-252 Effect of acupuncture intervention on the changes of cytoplasmic and mitochondrial Ca2+ concentration following eccentric contractions in rat skeletal muscle

&nbsp; Objective The purpose of this study was to evaluate the effect of acupuncture intervention on the changes of cytoplasmic and mitochondrial Ca2+ concentration following eccentric contractions (ECC) in rat skeletal muscle. Methods 24 healthy male Wistar rats were randomly divided into 4 groups: control group (C, n=6)、electrical stimulation group (E, n=6)、electrical stimulation group with acupuncture intervention (EA, n=6)、electrical stimulation group with acupuncture +TRP channel inhibitor Gd3+ (EAI, n=6). The animal model of eccentric induced skeletal muscle injury was established by electrical stimulation on spinotrapezius muscle of anaesthetised rats in vivo, that is to say, the intact spinotrapezius muscle of adult Wistar rats was exteriorized, and tetanic eccentric contractions (100 Hz, 10 sets of 50 contractions) were elicited by electrical stimulation during synchronized muscle stretch of 10% resting muscle length. Cytoplasmic Ca2+ accumulation were determined by loading the muscle with fura 4-AM using fluorescent imaging in vivo, and mitochondrial Ca2+ concentration were determined by loading the muscle with fura 2-AM using fluorescent imaging in vitro, and recorded changes of muscle maximum tetanic force. Results (1) In vivo, compared with the C , cytoplasmic Ca2+ accumulation increased more rapidly during ECC in the E (P &lt; 0.001). Acupuncture intervention significantly reduced cytosolic Ca2+ accumulation in the EA compared with the E (P &lt; 0.01), and we discovered that muscle deformation generated by acupuncture intervention induced a robust Ca2+ spark response confined in close spatial proximity to the sarcolemmal membrane in intact muscle fibers. Although no significant differences between the EA and EAI, Gd3+ abolished the majority of cytoplasmic Ca2+ accumulation decrease during ECC in the EAI and a robust Ca2+ spark response disappeared compared with the EA. (2) In vitro, compared with the C, mitochondrial Ca2+ concentration did not elevations in MCC in the E. EA cytoplasmic Ca2+ increased rapidly above the C and E (P &lt; 0.01), respectively, but EAI significantly attenuated the increases in &nbsp;mitochondrial Ca2+ concentration compared with the EA (P &lt; 0.01). (3). Compared with the C , maximum tetanic force was significantly lower in the E after ECC (P &lt; 0.01). EA maximum tetanic force increased rapidly compared with the E after ECC (P &lt; 0.05), but EAL abolished the majority maximum tetanic force increase after ECC (P &lt; 0.05). Conclusions (1)Eccentric contraction caused cytoplasmic Ca2+ accumulation, but &nbsp;mitochondrial Ca2+ concentration decrease. (2)Acupuncture can effectively reduce cytosolic Ca2+ overload, following by mitochondrial Ca2+ concentration increase , which in turn abnormally high cytoplasmic Ca2+ levels are buffed by the mitochondria, and improved muscle function, and the effect was associated to the TRP channels. &nbsp

VMGuards:A Novel Virtual Machine Based Code Protection System with VM Security as the First Class Design Concern

Process-level virtual machine (PVM) based code obfuscation is a viable means for protecting software against runtime code tampering and unauthorized code reverse engineering. PVM-based approaches rely on a VM to determine how instructions of the protected code region are scheduled and executed. Therefore, it is crucial to protect the VM against runtime code tampering that alters the instructions and behavior of the VM. This paper presents VMGuards, a novel PVM-based code protection system that puts the security of VM as the first class design concern. Our approach advances prior work by promoting security of the VM as the first class design constraint. We achieve this by introducing two new instruction sets to protect the internal implementations of critical code segments and the host runtime environment where the VM runs in. Our new instruction sets not only have an identical code structure as standard virtual instructions, but also provide additional information to allow the VM to check whether the critical internal implementation or the runtime environment is affected. We evaluate our approach by using a set of real-life applications. Experimental results show that our approach provides stronger and more fine-grained protection when compared to the state-of-the-art with little extra overhead

A pan-cancer analysis of the prognostic and immunological roles of matrix metalloprotease-1 (MMP1) in human tumors

ObjectiveCancer remains the leading killer of human health worldwide. It has been shown that matrix metalloproteinase-1(MMP1) is related to poor prognosis in cancers such as BRCA, CESC and COAD. However, systematic pan-cancer analysis about the prognostic and immunological roles of MMP1 has not been explored. Here, the purpose of this study was to investigate the prognostic and immunological roles of MMP1 in pan-cancer and confirm cancer-promoting effect in pancreatic cancer.MethodsIn our study, bioinformatics were first used to analyze data from multiple databases. Then, several bioinformatics tools were utilized to investigate the role of MMP1 in 33 tumor types. Finally, molecular biology experiments were carried out to prove the cancer-promoting effect of MMP1 in pancreatic cancer.ResultsMMP1 expression was higher in tumor tissues than in control tissues in most tumor types. High expression of MMP1 was associated with poor overall survival (OS) and disease-free survival (DFS) in some tumor types. Further analysis of MMP1 gene mutation data showed that MMP1 mutations significantly influenced the prognosis of STAD. In addition, MMP1 expression was closely related to cancer-associated fibroblast (CAFs) infiltration in a variety of cancers and played an important role on immune infiltration score, tumor mutational burden (TMB) and microsatellite instability (MSI). Gene Ontology enrichment analysis indicated that these 20 genes were mainly related to extracellular structure organization/extracellular matrix organization/extracellular matrix disassembly/collagen metabolic process in the enriched biological processes. Finally, molecular biology experiments confirmed the cancer-promoting effect of MMP1 in pancreatic cancer.ConclusionsOur pan-cancer analysis comprehensively proved that MMP1 expression is related with clinical prognosis and tumor immune infiltration, and MMP1 can become a prognostic and immunological biomarker

Construction and validation of a risk prediction model for aromatase inhibitor-associated bone loss

PurposeTo establish a high-risk prediction model for aromatase inhibitor-associated bone loss (AIBL) in patients with hormone receptor-positive breast cancer.MethodsThe study included breast cancer patients who received aromatase inhibitor (AI) treatment. Univariate analysis was performed to identify risk factors associated with AIBL. The dataset was randomly divided into a training set (70%) and a test set (30%). The identified risk factors were used to construct a prediction model using the eXtreme gradient boosting (XGBoost) machine learning method. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods were used for comparison. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model in the test dataset.ResultsA total of 113 subjects were included in the study. Duration of breast cancer, duration of aromatase inhibitor therapy, hip fracture index, major osteoporotic fracture index, prolactin (PRL), and osteocalcin (OC) were found to be independent risk factors for AIBL (p &lt; 0.05). The XGBoost model had a higher AUC compared to the logistic model and LASSO model (0.761 vs. 0.716, 0.691).ConclusionThe XGBoost model outperformed the logistic and LASSO models in predicting the occurrence of AIBL in patients with hormone receptor-positive breast cancer receiving aromatase inhibitors

Facile One-Pot Synthesis of Self-Assembled Folate-Biotin-Pullulan Nanoparticles for Targeted Intracellular Anticancer Drug Delivery

The self-assembled folate-biotin-pullulan (FBP) nanoparticles (NPs) were prepared by facile one-pot synthesis and their physicochemical properties were characterized. The self-assembled FBP NPs were used as an anticancer drug nanocarrier entrapping doxorubicin (DOX) for targeting folate-receptors-overexpressing cancer cells. The identification of prepared NPs to folate-receptor-expressing cancer cells (KB cells) was affirmed by cell viability measurement, folate competition test, and flow cytometric analysis. Compared with the naked DOX and DOX/BP NPs, the DOX/FBP NPs had lower IC50 value compared to KB cells as a result of the folate-receptor-mediated endocytosis process. The cytotoxicity of DOX/FBP NPs to KB cells could be inhibited competitively by free folate. The cellular intake pattern of naked DOX and drug-loaded NPs was identified by confocal laser scanning microscopy (CLSM) observation and the higher cellular uptake of drug for DOX/FBP NPs over naked DOX was observed. The prepared FBP NPs had the potential to be used as a powerful carrier to target anticancer drugs to folate-receptor-expressing tumor cells and reduce cytotoxicity to normal tissues

Global Epidemiology of Dengue Outbreaks in 1990–2015: A Systematic Review and Meta-Analysis

Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV) infection and transmitted by Aedes mosquitoes. Approximately 50–100 million people are infected with DENV each year, resulting in a high economic burden on both governments and individuals. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, clinical characteristics, and serotype distribution and risk factors for global dengue outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of Science databases through December 2016 using the term “dengue outbreak.” In total, 3,853 studies were identified, of which 243 studies describing 262 dengue outbreaks met our inclusion criteria. The majority of outbreak-associated dengue cases were reported in the Western Pacific Region, particularly after the year 2010; these cases were primarily identified in China, Singapore and Malaysia. The pooled mean age of dengue-infected individuals was 30.1 years; of the included patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and 1.3% died. The mean age of dengue patients reported after 2010 was older than that of patients reported before 2010 (34.0 vs. 27.2 years); however, the proportions of patients who had DHF, had secondary infections and died significantly decreased after 2010. Fever, malaise, headache, and asthenia were the most frequently reported clinical symptoms and signs among dengue patients. In addition, among the identified clinical symptoms and signs, positive tourniquet test (OR = 4.86), ascites (OR = 13.91) and shock (OR = 308.09) were identified as the best predictors of dengue infection, DHF and mortality, respectively (both P &lt; 0.05). The main risk factors for dengue infection, DHF and mortality were living with uncovered water container (OR = 1.65), suffering from hypotension (OR = 6.18) and suffering from diabetes mellitus (OR = 2.53), respectively (all P &lt; 0.05). The serotype distribution varied with time and across WHO regions. Overall, co-infections were reported in 47.7% of the evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing programs focused on targeted prevention, early identification, and effective treatment