Central venous catheter use increases ischemic stroke risk: a nationwide population-based study.

BACKGROUND: Central venous catheter (CVC) placement is a common procedure used for the treatment of critically ill patients. However, ischemic stroke is a complication after CVC placement. AIM: This study investigated the association between CVC placement and ischemic stroke risk in an Asian population. DESIGN: Population-based retrospective study. METHODS: We enrolled 37 623 patients who ever-received CVC placement over 2000-10 and propensity score-matched individuals without CVC placement as the comparison cohort from the Taiwan National Health Insurance Research Database. We determined the cumulative incidence rates and adjusted hazard ratios (aHRs) for ischemic stroke. RESULTS: We finally identified and enrolled 34 164 propensity score-matched pairs of individuals. Compared with the comparison group, CVC placement increased the average annual ischemic stroke incidence [19.5 vs. 11.6 per 10 000 person-years; crude HR=1.28, 95%, confidence interval (CI)=1.21-1.35; adjusted subhazard ratio (aSHR)=1.4, 95% CI = 1.33-1.47; P<0.001). In addition, compared with those aged >35 years, stroke risk was significantly higher in <35-year-old patients with CVC placement (aSHR=14.3, 95% CI=6.11-33.4; P<0.001). After <1-year follow-up, the ischemic stroke incidence rate in the CVC placement group was ∼3.25-fold higher than that in the comparison group (aHR=3.25, 95% CI=2.9-3.63; P<0.0001). CONCLUSION: CVC placement increases ischemic stroke risk, particularly in those aged ≤35 years; this trend warrants further investigation.

[Analysis on epidemiological characteristics and related factors of dyslipidemia among adult residents of Xinjiang Uygur Autonomous Region during 2013-2014].

Objective: To study the epidemiological characteristics and related factors of dyslipidemia among adult residents in Xinjiang Uygur Autonomous Region (Xinjiang) in 2013-2014. Methods: A total of 4 120 adult residents consisting of Han and Uygur group aged over 18 years old were selected by using a stratified cluster random sampling method in 8 counties of Xinjiang from 2013 to 2014. The related factors of dyslipidemia were collected by questionnaire and physical measurement. The total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected by enzyme method. Factors associated with dyslipidemia were analyzed by chi-squared test and a multivariate unconditioned logistic regression model adjusted for gender, urban or rural area, age-group, body mass index (BMI), central obesity, smoking, drinking, education attainment, diabetes mellitus and hypertension. Results: The prevalence of dyslipidemia was 45.00% (1 854 cases). The prevalence of dyslipidemia was higher in Uygur group (47.80% (977/2 044)) than that in Han group (42.24% (877/2 076)) (χ(2)=12.84, P<0.001). The analysis showed that dyslipidemia was related with gender (OR=0.41, 95%CI: 0.33-0.51), urban area (OR=0.54, 95%CI: 0.39-0.76), BMI (overweight group (OR=1.52, 95%CI: 1.18-1.96); obesity group (OR=2.20, 95%CI: 1.64-2.96)), central obesity (OR=1.66, 95%CI: 1.29-2.14) and diabetes mellitus (OR=1.49, 95%CI: 1.06-2.11) in Uygur group. The analysis also showed that dyslipidemia was related with BMI (overweight group (OR=1.72, 95%CI: 1.32-2.25), obesity group (OR=2.60, 95%CI: 1.85-3.64)), central obesity (OR=1.45, 95%CI: 1.13-1.87), smoking (OR=1.46, 95%CI: 1.09-1.95), diabetes mellitus (OR=1.77, 95%CI: 1.38-2.25) and hypertension (OR=1.62, 95%CI: 1.31-2.00) in Han group. Conclusions: The prevalence of dyslipidemia in Xinjiang was higher than the national average prevalence. The prevalence of dyslipidemia in Uygur group was significantly higher than that in Han group. The gender, living area, BMI, central obesity and diabetes mellitus were risk factors of dyslipidemia in Uygur group, and BMI, central obesity, smoking, diabetes mellitus and hypertension were risk factors of dyslipidemia in Han group in Xinjiang.

C-terminus of Hsc70-interacting protein (CHIP) enhances stemness properties of human Wharton's jelly mesenchymal stem cell.

Mesenchymal stem cells are an attractive source of multipotent cells in part because they are easy to obtain. Several E3 ligases regulate the stability and functions of various factors in different adult stem cells through the ubiquitylation pathway. We investigated the C-terminus of Hsc70-interacting protein (CHIP) E3 ligase that regulates pluripotency of human Wharton's jelly mesenchymal stem cells (hWJMSC). We found that CHIP increases protein kinase B (Akt) phosphorylation by decreased expression of phosphatase and tensin homolog (PTEN), which suggests improvement of the survival pathway by CHIP over-expression. We also found that increased CHIP expression induced Sox2 and NANOG, which can promote stem cell self-renewal and prevent oxidative stress-induced senescence of hWJMSC by decreased p21. We found that CHIP could be used to enhance the multiple functions of hWJMSC.

Microwave enhanced advanced oxidation treatment of dairy manure.

The microwave enhanced advanced oxidation process (MW-AOP) was used to treat dairy manure in a continuous-flow 915 MHz microwave wastewater treatment system. The treatment efficiency increased with an increase in temperature, as well as hydrogen peroxide dosage. The settling property was also improved in all treated sets, regardless of temperature applied. The system operated at temperatures >100 °C had a much higher soluble chemical oxygen demand than at temperatures <100 °C. The highest soluble carbonaceous compounds, orthophosphate and ammonia were obtained at 110 °C and 0.6%H2O2 per % of total solids content. The process should be operated at higher temperatures and higher hydrogen peroxide dosages for maximizing solids disintegration, nutrient release and energy efficiency. An energy fingerprint correlating the cumulative energy consumption and temperature rise was developed. The results demonstrated that the custom designed MW-AOP system is suitable for the effective treatment of dairy manure. The system can readily be scaled up and integrated into a dairy farm manure treatment and resource recovery system.

Single-fabrication-step Ge nanosphere/SiO2/SiGe heterostructures: a key enabler for realizing Ge MOS devices.

We report channel and strain engineering of self-organized, gate-stacking heterostructures comprising Ge-nanosphere gate/SiO2/SiGe-channels. An exquisitely-controlled dynamic balance between the concentrations of oxygen, Si, and Ge interstitials was effectively exploited to simultaneously create these heterostructures in a single oxidation step. Process-controlled tunability of the channel length (5-95 nm diameters for the Ge-nanospheres), gate oxide thickness (2.5-4.8 nm), as well as crystal orientation, chemical composition and strain engineering of the SiGe-channel was achieved. Single-crystalline (100) Si1-x Ge x shells with Ge content as high as x = 0.85 and with a compressive strain of 3%, as well as (110) Si1-x Ge x shells with Ge content of x = 0.35 and corresponding compressive strain of 1.5% were achieved. For each crystal orientation, our high Ge-content, highly-stressed SiGe shells feature a high degree of crystallinity and thus, provide a core 'building block' required for the fabrication of Ge-based MOS devices.

Phosphorylation of cofilin-1 by ERK confers HDAC inhibitor resistance in hepatocellular carcinoma cells via decreased ROS-mediated mitochondria injury.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Despite the availability of several treatment strategies, resistance to chemotherapeutic agents, which limits the effectiveness of anticancer drugs, is a major problem in cancer therapy. In this study, we used a histone deacetylases inhibitor (HDACi) to establish drug-resistant HCC cells and further analyzed the molecular mechanisms underlying the development of resistance in HCC cells. Compared with the parental cells, HDACi-resistant cells showed high metastatic and pro-survival abilities. Two-dimensional electrophoresis data showed that the cofilin-1 (CFL-1) protein was altered in HDACi-resistant cells and was highly expressed in resistant cells compared with parental cells. The molecular function of CFL-1 is actin depolymerization, and it is involved in tumor metastasis. In this study, we showed that CFL-1 inhibition decreased cell migration and increased cell apoptosis in HDACi-resistant cells. We observed that HDACi induced ROS accumulation in cells and apoptosis via promotion of the CFL-1 interaction with Bax and CFL-1 translocation to the mitochondria, resulting in cytochrome C release. Importantly, phosphorylation of CFL-1 by activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) confers strong protection against HDAC inhibitor-induced cell injury. p-CFL-1 shows a loss of affinity with Bax and will not translocate to mitochondria, stably remaining in the cytoplasm. These results indicate that phosphorylation to inactivate CFL-1 decreased the chemosensitivity to HDAC inhibitors and resulting in drug resistance of HCC cells.

Effects of irradiation intensity and pH on nutrients release and solids destruction of waste activated sludge using the microwave-enhanced advanced oxidation process.

Using the microwave-enhanced advanced oxidation process (MW/H2O2-AOP), the pH and irradiation intensity on waste activated sludge samples were investigated to provide insight to the athermal effects on nutrients release, solids destruction, particle size distribution and dewaterability, and to demonstrate their interrelationships. Carbonaceous matters and nutrients released into solution depended on the irradiation intensity and time. Higher irradiation levels tended to be more effective in the solubilization of nutrients and had more pronounced effects in the dewaterability of sludge. In terms of particle size distribution, detectable particles increased in size for treatments in acidic conditions, while the dewaterability of treated sludge was improved. In treatments under neutral and alkaline conditions, the particle size range increased, with more small particles formed, thereby significantly deteriorating the dewaterability of sludge treated in alkaline conditions. The best results for the solubilization of nutrients were in alkaline conditions with high irradiation power, but dewaterability of the sludge was compromised. Sludge treatment with the MW/H2O2-AOP in acidic conditions with high irradiation power yielded the best dewaterable sludge and significant nutrient solubilization; therefore, it is the recommended treatment condition for activated sludge.

Extraction of nutrients from foam in a membrane activated sludge system.

This study investigated the feasibility of treating the foams generated in enhanced biological phosphorus removal processes with the microwave-enhanced advanced oxidation process to reduce solids and solubilize nutrients for recovery purposes. It was found that more than half of the total chemical oxygen demand was solubilized during the treatment with just a small dose of hydrogen peroxide, signifying effective destruction of foam solids. Significant solubilization of phosphates, volatile fatty acids and ammonia was also observed, along with the release of metals contained in the foam, including calcium, potassium, and magnesium, which thereby represents additional potential benefits for nutrient recovery via subsequent crystallization processes. Since the solids content of foam is typically high, pretreatment for thickening sludge solids is not necessary prior to the use of microwave-enhanced advanced oxidation processes. As a result, this also offers further potential for reduction of energy costs. The process could be an efficient method for the removal and control of foam and the recovery of all available phosphorus at the same time.

Disinfection and solubilization of sewage sludge using the microwave enhanced advanced oxidation process.

The microwave enhanced advanced oxidation process (MW/H(2)O(2)-AOP) was used to treat municipal sewage sludge for solids disintegration, nutrient solubilization, with an emphasis on pathogen destruction and regrowth. Pathogen reduction, in terms of fecal coliform concentrations were found below detection limit (1000 CFU/L) immediately after treatment when sludge was treated at 70 degrees C with more than 0.04% of H(2)O(2) (w/w). Significant regrowth of fecal coliforms was observed for the treated samples after 72 h. However, no regrowth was observed for samples treated at 70 degrees C with 0.08% H(2)O(2) or higher, suggesting a complete elimination of fecal coliforms. The range of hydrogen peroxide used did not have a significant effect on orthophosphate release regardless of temperature. Ammonia release at these low temperatures was found to be insignificant. The soluble chemical oxygen demand increased with an increase of hydrogen peroxide dosage at 70 degrees C. However, there was no clear trend of soluble chemical oxygen demand over varying hydrogen peroxide dosage at 55 degrees C. The MW/H(2)O(2)-AOP is a novel process for the pasteurization and stabilization of sewage sludge to meet and maintain Class A biosolids criteria.

Recent progress in the development of inhibitors of human immunodeficiency virus (HIV) integrase for the management of HIV infection.

Current therapy of acquired immune deficiency syndrome (AIDS) involves the use of a combination of at least three antiviral drugs to inhibit Human immunodeficiency virus 1 and 2 (HIV-1 and 2, in short HIV) replication via targeting of viral reverse transcriptase and protease. However, all anti-HIV drugs give rise to the new retroviral resistant strains. Therefore, new therapeutic agents against the emerging resistant HIV strains without secondary effects are very much needed. In HIV infection, the integration of viral DNA obtained from RNA genome into the chromosome of the host cell by viral integrase (IN) is essential for an effective viral replication. Moreover, no cellular IN has been found in the cells suggesting that viral IN appears to be one of the best candidates for the development of an antiviral drug. In recent years, promising results have proved that IN inhibitors are useful for treatment of retroviral infections. In this review, we briefly introduce IN and summarize potential inhibitors of IN, which are classified into several groups according to their origin and chemical structure. The resistance to the IN inhibitors is also discussed. Currently, several IN inhibitors are either being used in the clinical treatment or tested in clinical trials. Nevertheless, a great effort must be made to elicit wide knowledge with respect to the design of better viral inhibitors and the synthesis of new chemical derivatives with an anti-HIV activity.

Rapid determination of total Kjeldahl nitrogen using microwave digestion.

A closed-vessel microwave digestion process for the determination of total Kjeldahl nitrogen (TKN) has been developed for sewage and wastewater. TKN values obtained from the microwave digestion method were in excellent agreement with those of the thermal digestion method. The accuracy of both analytical methods is comparable. In comparison to the conventional thermal digestion, the microwave method shortened the time required for complete digestion from 4 h to 25 min, and also decreased the maximum digestion temperature from 380 degrees C to 200 degrees C. This developed method may contribute to a significant reduction in sample digestion time, resulting in an increase in analytical throughput. The microwave digestion method developed in this study could be a rapid and efficient means for TKN determination for sewage wastewater and sludge.

Activation of p53 signalling in acetylsalicylic acid-induced apoptosis in OC2 human oral cancer cells.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid (ASA, aspirin) are well known chemotherapeutic agents of cancers; however, the signalling molecules involved remain unclear. The aim of this study was to investigate the possible existence of a putative p53-dependent pathway underlying the ASA-induced apoptosis in OC2 cells, a human oral cancer cell line. MATERIALS AND METHODS: The methyl tetrazolium (MTT) assay was employed to quantify differences in cell viability. DNA ladder formation on agarose electrophoresis was used as apoptosis assay. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Flow cytometry was used to confirm the effect of ASA on cell cycle. Patterns of changes in expression were scanned and analyzed using the NIH image 1.56 software (NIH, Bethesda, MD, USA). All the data were analyzed by ANOVA. RESULTS: Acetylsalicylic acid reduced cell viability and presence of internucleosomal DNA fragmentation. In the meanwhile, phosphorylation of p53 at serine 15, accumulation of p53 and increased the expression of its downstream target genes, p21 and Bax induced by ASA. The expression of cyclooxygenase-2 was suppressed. Disruption of p53-murine double minute-2 (MDM2) complex formation resulted in increasing the expression of MDM2 60-kDa cleavage fragment. Inhibited the activation of p42/p44 mitogen-activated protein kinase (MAPK) by PD98059, a specific inhibitor of extracellular regulatory kinase (ERK), significantly decreased cell viability and enhanced the expression of p53 induced by ASA. The result of the cell-cycle analysis showed that ASA and PD98059 induced the cell cycle arrested at the G0/G1 phase and resulted in apoptosis. CONCLUSION: Nonsteroidal anti-inflammatory drug-inhibited cyclooxygenase is not the only or even the most important mechanism of inhibition. Our study presents evidences that activation of p53 signalling involved in apoptosis induced by ASA. Furthermore, the apoptotic effect was enhanced by blocking the activation of p42/p44 MAPK in response to treatment with ASA, thus indicating a negative role for p42/p44 MAPK.

Synergistic effect of cadmium chloride and acetaldehyde on cytotoxicity and its prevention by quercetin and glycyrrhizin.

Cadmium chloride at concentrations of 10-50mM and acetaldehyde (AA) at 1-5mM showed synergistic toxic effects on V79 cells in vitro. Furthermore, synergistic effects of these chemicals were also observed in mutagenicities of the Hprt gene within certain dose ranges (cadmium chloride 5-10mM, and AA 1-2.5mM). Moreover, lipid peroxide formation, malondialdehyde (MDA) formation, detected by 2-thiobarbituric acid (TBA) reaction and the mitochondrial membrane potentials detected by rhodamine 123 uptake were significantly increased with the combined effect of cadmium and AA in V79. Thus, the cytotoxicity and genotoxicity displayed by combination of these chemicals can be considered to be associated with oxidative stress. Further, these effects were efficiently reduced by quercetin and less efficiently with glycyrrhizin.

Adenomatous polyposis coli gene mutation and decreased wild-type p53 protein expression in oral submucous fibrosis: a preliminary investigation.

OBJECTIVE: The purpose of this study was to identify the adenomatous polyposis coli (APC) tumor suppressor gene mutation and level of wild-type p53 protein expression in patients with oral submucous fibrosis (OSF). STUDY DESIGN: Cells from OSF and control subjects were cultured in Dulbecco modified Eagle medium with 10% fetal bovine serum at 37 degrees C. Genomic DNA was extracted from cultured cells and used as a template for polymerase chain reaction amplification of the APC tumor suppressor gene. The presence of wild-type p53 protein in cell lysates of cultured cells was analyzed by Western blot. Data were analyzed by the sign test for nonparametric samples and by analysis of variance. RESULTS: The results showed that the APC gene of explant cultured cells from OSF patients (8/8) had a CGA-to-GGA transition mutation at codon 498 that resulted in an Arg-to-Gly missense mutation (P <.01). All (8/8) normal HGF cultures revealed expression of the wild-type APC protein. Cells cultured from 7 of 8 OSF patients were also found to have a single nucleotide deletion at nucleotide 1494 that resulted in creating a stop codon (TGA) at codon 504 (P <.01). This created a premature signal for the endpoint of translation and thus resulted in the generation of a truncated protein product that encodes a polypeptide of 503 amino acid residue. It was found that wild- type p53 protein in human gingival fibroblast cell cultures was significantly higher than in OSF cells (P <.01). CONCLUSION: Alterations of the APC and wild-type p53 tumor suppressor genes in OSF may imply a risk for progression to oral cancer.

Mutagenesis and expression of the E3-19k lumenal domain of adenovirus type 2.

CD8+ T cells recognize viral or tumor antigens of 8-10 residues derived from cytosolic proteins that are bound to the class I molecules of the major histocompatibility complex (MHC). To escape this immune surveillance, adenovirus expresses a protein, E3-19k, that specifically down-regulates the cell surface expression of class I MHC molecules on infected cells. To most effectively manipulate the T-cell response to virus-infected cells, it is essential to understand the mechanism by which viruses, such as adenoviruses, down-regulate the class I MHC function. We have subcloned the lumenal domain of adenovirus E3-19k protein in order to characterize its interactions with the class I MHC molecules. Several point mutations have also been generated on the E3-19k lumenal domain with either the first 96 or 108 amino acids. Attempts to crystallize the complexes between E3-19k and class I MHC molecule had been initiated.

Mutation of p53 gene codon 63 in saliva as a molecular marker for oral squamous cell carcinomas.

The inactivation of tumor suppressor gene (TSG) is important during multistage carcinogenesis. The p53 TSG is frequently mutated in oral squamous cell carcinomas. These mutations can serve as very specific markers for the presence of tumor cells in a background of normal cells. In this study, 10 oral squamous cell carcinoma patients and 27 normal dental students were collected from Chung Shan Medical and Dental College Hospital, Taichung, Taiwan. Extractions of DNA from saliva were obtained. Exon 4 and intron 6 within the p53 gene were amplified with polymerase chain reactions (PCRs) followed by DNA sequence analysis. DNA sequence analysis of PCR products revealed that five of eight (62.5%) tumor saliva samples and five of 27 (18. 52%) healthy saliva samples contained p53 exon 4 codon 63 mutations. These results were significantly different by using Chi-square test (P<0.05). The majority of the base substitutions were C deletions. Probable hot spots for the mutation were identified at exon 4 codon 63, which has not been observed before in head and neck cancers. Our study indicated that mutation of p53 codon 63 in saliva might be a molecular marker for oral squamous cell carcinomas. In addition, the amount of DNA recovered from saliva in most cases is sufficiently large and its quality suitable to enable PCR amplification which could be used in the search for mutations. The protocol described is rapid, cheap, and easy to perform, and may be useful for epidemiological studies for oral carcinogenesis.

Preferential cytotoxicity of caffeic acid phenethyl ester analogues on oral cancer cells.

As part of our previous search for new compounds with improved biological activities including antibiotic, antiviral, anti-inflammatory, and tumor growth inhibition activities, we synthesized some caffeic acid phenethyl ester (CAPE)-like compounds from commercially available caffeic acid. Nine chemicals were tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the growth of buccal mucosal fibroblast (BF), oral submucosus fibroblast (OSF), neck metastasis of Gingiva carcinoma (GNM), and tongue squamous cell carcinoma (TSCCa) cells. CAPE and its ethyl analogue show significant cytotoxicity on OSF, GNM, and TSCCa cells, but not on BF cells. The results suggest that CAPE-like compounds may be potential chemotherapy agents against oral cancer.

Purification and crystallization of precursors and autoprocessed enzymes of Flavobacterium glycosylasparaginase: an N-terminal nucleophile hydrolase.

Glycosylasparaginase (GA) represents a novel group of proteins that are activated by self-catalyzed peptide-bond cleavage from a single-chain precursor to yield the two subunits required for hydrolase activity. The wild-type GA precursor autoproteolyzes spontaneously into alpha and beta subunits. Strategies are reported here for purification to homogeneity of GA from Flavobacterium meningosepticum in both single-chain precursor and mature (autoprocessed) forms. The recombinant proteins crystallize in different space groups: P1 and P2(1) for the precursor and mature enzymes, respectively. The precursor crystals diffract to 1.9 A resolution with laboratory X-ray radiation.

Reduction of ornithine decarboxylase antizyme (ODC-Az) level in the 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model.

Ornithine decarboxylase (ODC) activity is elevated in and necessary for oral carcinogenesis, but the mechanism for its deregulation is unclear. Using subtractive hybridization, a 1029 bp full-length cDNA encoding a 222 amino acid open reading frame has been isolated from normal hamster oral keratinocytes. The hamster cDNA is homologous to the human, mouse and rat ornithine decarboxylase antizyme gene (ODC-Az). The hamster ODC-Az gene demonstrated a restriction fragment length polymorphism (RFLP) upon Southern blot analysis comparing normal and tumor hamster genomic DNA. Northern blot analysis revealed that normal hamster oral keratinocytes express readily detectable level of ODC-Az mRNA. Malignant oral keratinocytes demonstrate reduced expression of the ODC-Az mRNA. In contrast, malignant hamster oral keratinocytes have elevated ODC mRNA levels and lengthened ODC protein half-life when compared to the normal counterparts. This was corroborated by direct measurement of ODC enzymatic activity. These data support the hypothesis that the reduced and/or loss of expression and function of the ODC-Az gene is an important event for the early de-regulation of cellular proliferation during oral tumor development.

Methane production using whole and screened dairy manure in conventional and fixed-film reactors.

The technical feasibility of adopting the fixed-film reactor concept for biogas production from screened dairy manure was investigated. The methane production capability of laboratory-scale 4-L anaerobic reactors (conventional and fixed-film) receiving screened dairy manure and operated at 35 degrees C was compared. Dairy manure filtrate with 4.4% total solids (TS) and 3.4% volatile solids (VS) (average value) was prepared from 1:1 manure-water slurry. The feed material was added intermittently at loading rates ranging from 2.34 to 25 and 2.25 to 785 g VS/L d, respectively, for the conventional and fixed-film reactors. Maximum methane production rate (L CH(4)/L d) for the conventional reactor was 0.63 L CH(4)/L d achieved at a 6-day hydraulic retention time (HRT). For the fixed-film reactor the maximum production rate was 3.53 L CH(4)/L d when operated at a loading rate of 262 g VS/L d (3 h HRT). The fixed-film reactor was capable of sustaining a loading of 785 g VS/L d (1 h HRT). The fixed-film reactor performed much better than the conventional reactors. These results indicate that a large reduction of required reactor volume is possible through application of a fixed-film concept combined with a liquid-solid separation pretreatment of dairy manure.