Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors.

Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. The expression of signaling molecules in tumors was determined by measuring either mRNA or protein expression. Compared with doxorubicin alone, combination treatment resulted in lower tumor sizes and fewer overall metastasis, lower GPR-40 mRNA levels, and higher expression of all selenoproteins. Doxorubicin-FO/Se combination treatment decreased expression of membrane EGFR and FGFR, down-regulated downstream PI3K/AKT/mTOR, MAPK/ERK, and JAK2/c-Src/STAT3 signaling, increased tumor suppressor PTEN/TSC1/TSC2 expression and P53 activation, and suppressed oncogenic transcription factor expression. Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.

Novel Approaches for Inhibiting the Indoor Allergen Der f 2 Excreted from House Dust Mites by Todomatsu Oil Produced from Woodland Residues.

House dust mite (HDM) is a globally ubiquitous domestic cause of allergic diseases. There is a pressing demand to discover efficient, harmless, and eco-friendly natural extracts to inhibit HDM allergens that are more likely to trigger allergies and challenging to be prevented entirely. This study, therefore, is aimed at assessing the inhibition of the allergenicity of major HDM allergen Der f 2 by todomatsu oil extracted from residues of Abies Sachalinensis. The inhibition was investigated experimentally (using enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)) and in silico using molecular docking. The results showed that todomatsu oil inhibits the allergenicity of Der f 2 by reducing its amount instead of the IgG binding capacity of a single protein. Moreover, the compounds in todomatsu oil bind to Der f 2 via alkyl hydrophobic interactions. Notably, most compounds interact with the hydrophobic amino acids of Der f 2, and seven substances interact with CYS27. Contrarily, the principal compounds fail to attach to the amino acids forming the IgG epitope in Der f 2. Interestingly, chemical components with the lowest relative percentages in todomatsu oil show high-affinity values on Der f 2, especially ß-maaliene (-8.0 kcal/mol). In conclusion, todomatsu oil has been proven in vitro as a potential effective public health strategy to inhibit the allergenicity of Der f 2.

Nutritional supplements in combination with chemotherapy or targeted therapy reduces tumor progression in mice bearing triple-negative breast cancer.

The potential anti-cancer properties of selenium (Se) and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) have been documented. However, few studies have been conducted examining anti-tumor effects of nutritional supplements (NS) containing Se and EPA/DHA in combination with anti-cancer agents, such as taxol (Tax), adriamycin (Adr), and avastin (Ava). Compared with triple-negative breast cancer (TNBC)-bearing positive control (TB) mice, a low dose of Tax, Adr, and Ava decreased tumor size and the incidence of metastasis in TB-Tax, TB-Adr, and TB-Ava groups. Combination treatment with anti-cancer agent and NS (2.7 µg Se and 5.1 mg EPA/3.7 mg DHA/g) induced additional decreases in TB-Tax-NS, TB-Adr-NS, and TB-Ava-NS groups. Th1-associated cytokines were increased, and Th2-type cytokines were decreased significantly in TB mice with combination treatment than that of anti-cancer agent treatment alone. Combination treatment with anti-cancer agents and NS has also been shown to further increased tumor malondialdehyde (MDA) levels, lowered hypoxia-inducible factor (HIF)-1α, angiogenic markers (vascular endothelial growth factor [VEGF] and CD31) and metastatic potential, as well as reduced heat shock proteins, receptor tyrosine kinase AXL, and surface markers of cancer stem cells, and increased apoptotic proteins. For immune checkpoint molecules, combination treatment was associated with a greater decrease in programmed cell death ligand-1 (PD-L1) in both tumors and mammary glands, but PD-1 level in primary tumors was increased. Our results suggest that combination treatment with low-dose anti-cancer agents (Tax, Adr, and Ava) and oral supplementation of Se/ EPA/DHA significantly decreased tumor growth and metastatic progression in TNBC mice through multiple anti-tumor mechanisms.

Comparative analysis and functional identification of temperature-sensitive miRNA in Arabidopsis anthers.

The anther is one of the most vulnerable organs to temperature stress. Many previous works focused on the genes regulating anthers development, but few results of miRNA in anther development were reported. In order to investigate the transcriptional regulation of temperature-sensitive anther development, RNA-Sequencing was used to study micRNA in anthers of Arabidopsis thaliana under 16 °C and 27 °C. A total of 46.26 million clean reads were generated and mapped to 715,748 small RNA sequences containing 281 miRNAs. Then 13 differentially expressed (DE) miRNAs, containing 3 novel miRNAs were found. Comprehensive analysis of miRNA expression showed 7 miRNAs were down-regulated and 6 miRNAs were up-regulated. Furthermore, 13 DE miRNAs putatively regulated 614 DE mRNAs. Among them, 20 important anther genes were predicted as target genes of MIR319A, MIR447A, MIR447B and MIR398B, respectively. Over-expression MIR319A and MIR447A could effectively inhibit the transcription of target genes and lead to male sterile. It suggested that DE miRNAs might mediate temperature signals and regulate anther and pollen development. Our work will provide a broader idea and valuable data information for further understanding the mechanism of thermo-sensitive male fertility in plants.

Studies on relationships between air pollutants and allergenicity of Humulus Scandens pollen collected from different areas of Shanghai.

Pollen pollution and allergy are becoming prominent issues in China. However, few studies on pollinosis have been reported. As an allergen in the atmosphere, allergenic Humulus scandens pollen was collected from four districts of Shanghai, including Wusong (WS), Jiading (JD), Xujiahui (XJH) and Songjiang (SJ). The mass concentrations of SO2, NO2, O3, PM10, and PM2.5 (particulate matter with air dynamic diameter less than 10 and 2.5 µm, respectively) near the four sampling sites were also recorded during Humulus scandens pollen season. The allergenicity of the Humulus scandens pollen was assessed by using of a rat model and enzyme linked immunosorbent assay (ELISA). Relationships between the allergenicity and air pollutants were correlated. Our results demonstrated that the biological viability of the pollens collected from the four districts exhibited no significant differences. ELISA and dot blotting results further demonstrated that the serum of sensitized rats exhibited much higher immune-reactive response than that of control groups. Western blotting showed that the 15 KD (1KD = 1000 dalton) proteins of Humulus pollen led to the allergic response. The allergenic intensity of Humulus pollen protein from different samples followed the pattern: WS > JD > XJ > SJ. There was a negative relationship between the allergenicity of Humulus pollens and PM10 (R = -0.99) / PM2.5 (R = -0.73), and a positive relationship with O3 (R = 0.92). These data clearly showed that PM10 and PM2.5 could enhance Humulus pollen protein release, and O3 could aggravate the allergenicity of the Humulus pollen.

Different Effects of Iron Indices on Mortality in Patients With Autosomal Dominant Polycystic Kidney Disease After Long-Term Hemodialysis: A Nationwide Population-Based Study.

OBJECTIVE: Iron supplementation and erythropoietin stimulating agents (ESAs) are essential for maintaining hemoglobin levels in hemodialysis patients. However, patients with autosomal-dominant polycystic kidney disease (PKD) have higher endogenous erythropoietin levels, so their recommended iron indices for hemodialysis patients may differ. This study evaluated iron profiles, including ferritin levels and transferrin saturation (TSAT) to identify factors affecting mortality in patients on dialysis, and those associated with mortality in patients with and without PKD. DESIGN: This cohort study from the Taiwan Renal Registry Data System stratified mortality risk by the presence of PKD recorded as the underlying disease. SUBJECTS: We enrolled 1346 hemodialysis patients with PKD and 82,873 hemodialysis patients without PKD. MAIN OUTCOME MEASURE: The primary outcome was 3-year all-cause mortality. Predictors included time-averaged and baseline serum ferritin levels and TSAT. Multivariate Cox regression analysis adjusting for age, comorbidities, and relevant laboratory parameters was used to estimate the all-cause hazard ratios (HRs) for mortality. RESULTS: The mean ages of patients with and without PKD were 56.2±13.2 and 61.7±13.5 years and the median follow-up time was 37 (15-76) months. The adjusted mortality risks for time-averaged ferritin levels >800 ng/mL (HR=1.52; 95% confidence interval: 1.40-1.65) or TSAT levels >50% (HR=1.46; 95% confidence interval: 1.30-1.65) were significantly higher among patients without PKD than those for patients with normal iron indices. However, a U-shaped curve of mortality against ferritin/TSAT levels was not observed in patients with PKD. In the sensitivity test, there was no difference among PKD patients who underwent regular ESA therapy and those who did not. CONCLUSION: Iron indices have different effects on mortality among patients with and without PKD. Iron supplementation, recommended serum ferritin levels, or TSAT should be monitored in hemodialysis patients, especially those without PKD. Clinicians should consider treating anemia in hemodialysis patients individually, especially in PKD.

Use of High-Dose Hydroxocobalamin for Septic Shock: A Case Report.

In this case report, we describe 2 patients with septic shock requiring high-dose vasopressors for hemodynamic support despite aggressive fluid resuscitation. After the administration of high-dose hydroxocobalamin for presumed septic vasoplegic syndrome, both patients had an immediate response to hydroxocobalamin with a rapid and lasting improvement of blood pressure that significantly reduced the need for vasopressor support.

Antrodia salmonea suppresses invasion and metastasis in triple-negative breast cancer cells by reversing EMT through the NF-κB and Wnt/ß-catenin signaling pathway.

Antrodia salonea (AS), a fungus that is indigenous to Taiwan has been well known for its anti-cancer properties. We investigated the anti-metastatic and anti-epithelial-mesenchymal transition (EMT) properties of AS in TNBC cells. To determine their EMT and metastasis levels, in vitro wound healing, wound invasion, Western blotting, RT-PCR, luciferase activity and immunofluorescence assays were performed, while the in vivo anti-metastatic efficacy of AS was evaluated in BALB/c-nu mice through bioluminescence imaging, HE staining, and immunohistochemical staining. MDA-MB-231 cells, when treated with AS concentrations (25-100 µg/mL) resulted in significant reduction of invasion and migration as well as the downregulation of VEGF, uPAR, uPA and MMP-9 (inhibition of PI3K/AKT/NFκB pathways). AS treatment prevented morphological changes and reversed EMT through the upregulation of E-cadherin and the downregulation of N-cadherin, Slug, Twist, and Vimentin. Inhibition of Smad3 signaling pathway, downregulation of ß-catenin pathway and upregulation of GSK3ß expression were also observed while, suppression of metastasis and EMT in TGF-ß1-stimulated non-tumorigenic MCF-10A cells was observed when treated with AS. Histological analysis confirmed that AS reduced tumor metastasis and upregulated E-cadherin expression in biopsied lung tissues. Our results indicated that AS exhibits anti-EMT and anti-metastatic activity, that could contribute to develop anticancer drugs against TNBC.

Characteristics of traditional Chinese medicine usage in children with precocious puberty: A nationwide population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Precocious puberty (PP) occurs in children with the early onset of pubertal development leading to physical and psychological problems. Current medical treatment is expensive and has its side effects. However, little is known about the utilization of traditional Chinese medicine (TCM) among patients with PP. To characterize the application of TCM among these patients, we conducted a nationwide population-based study. MATERIALS AND METHODS: We used the Taiwanese National Health Insurance Research Database (NHIRD), to perform a nationwide population-based study. The NHIRD has a derived dataset with the information for a randomly selected half of all insured children from 1997 to 2008 in Taiwan. We identified children <18 years of age with newly diagnosed sexual precocity (ICD-9 CM code: 259.1). The subjects were categorized based on the inclusion of TCM in their treatment plan. RESULTS: Overall, 3495 newly diagnosed subjects with sexual precocity were included. Among these children, 1.86% (N=65) had used TCM. There were significantly more subjects with no treatment, 87.32% (N=3052), than those with treatment of TCM, western medicine, or both. Most of the TCM users received Chinese herbal remedies (98.25%), and only 1.75% received acupuncture or manipulative therapies. Zhi-Bai-Di-Huang-Wan was the most frequently prescribed TCM formulation (23.73%), while Mai-Ya (Fructus Hordei Germinatus) was the most commonly prescribed single herb (10.87%). CONCLUSION: Our study identified the characteristics and prescription patterns of TCM for children with PP in Taiwan. Further basic mechanistic studies and clinical trials are needed to confirm the efficacy and mechanism.

P-N Cooperative Borane Activation and Catalytic Hydroboration by a Distorted Phosphorous Triamide Platform.

Studies of the stoichiometric and catalytic reactivity of a geometrically constrained phosphorous triamide 1 with pinacolborane (HBpin) are reported. The addition of HBpin to phosphorous triamide 1 results in cleavage of the B-H bond of pinacolborane through addition across the electrophilic phosphorus and nucleophilic N-methylanilide sites in a cooperative fashion. The kinetics of this process of were investigated by NMR spectroscopy, with the determined overall second-order empirical rate law given by ν = -k[1][HBpin], where k = 4.76 × 10-5 M-1 s-1 at 25 °C. The B-H bond activation process produces P-hydrido-1,3,2-diazaphospholene intermediate 2, which exhibits hydridic reactivity capable of reacting with imines to give phosphorous triamide intermediates, as confirmed by independent synthesis. These phosphorous triamide intermediates are typically short lived, evolving with elimination of the N-borylamine product of imine hydroboration with regeneration of the deformed phosphorous triamide 1. The kinetics of this latter process are shown to be first-order, indicative of a unimolecular mechanism. Consequently, catalytic hydroboration of a variety of imine substrates can be realized with 1 as the catalyst and HBpin as the terminal reagent. A mechanistic proposal implicating a P-N cooperative mechanism for catalysis that incorporates the various independently verified stoichiometric steps is presented, and a comparison to related phosphorus-based systems is offered.

Roles of Serum Calcium, Phosphorus, PTH and ALP on Mortality in Peritoneal Dialysis Patients: A Nationwide, Population-based Longitudinal Study Using TWRDS 2005-2012.

Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) correlate with morbidity and mortality in dialysis patients. However, the comparative roles of each CKD-MBD biomarker remained undetermined on long-term peritoneal dialysis (PD) patients. This retrospective study, employing a population-based database, aimed to evaluate the performance and provide the best evidence of each biomarker of CKD-MBD as predictor of all-cause mortality. Throughout the 8-year study period, total 12,116 PD patients were included in this study. Cox proportional regression and Kaplan-Meier method were used for survival analysis. For Cox regression model, baseline measurements and time-varying covariates were used for analysis. In Cox regression model using time-dependent covariates, serum calcium level of ≧9.5 mg/dL was associated with increased mortality. For phosphorus, serum levels of either ≧6.5 mg/dL or <3.5 mg/dL were associated with increased mortality. For parathyroid hormone (PTH), higher serum levels were not associated increased mortality. For alkaline phosphatase (ALP), mortality increased at levels ≧100 IU/L. Our findings suggested that the detrimental effect of ALP on survival was more consistent, while serum calcium, phosphorus and PTH may have a less prominent effect on mortality. This study provided additional information for manipulating CKD-MBD biomarkers in PD patients.

Health policies on dialysis modality selection: a nationwide population cohort study.

OBJECTIVES: In Taiwan, peritoneal dialysis (PD) and haemodialysis are fully accessible to patients with end-stage renal disease. However, the usage of PD is considered low in Taiwan. Since 2005, 4 major policies have been implemented by Taiwan's Ministry of Health and Welfare, namely a multidisciplinary predialysis care programme and usage increasing the PD incidence as a key performance indicator (KPI) for hospital accreditation, both of which were implemented in 2006; reimbursement of the glucose-free dialysate, icodextrin that was implemented in 2007; and insurance reimbursement for renting automated PD machines that was implemented in 2008. The aim of this study was to analyse the associations between the PD promotional policies and the actual PD selection rates. SETTING: We analysed data within the Taiwan Renal Registry Data System from 2006 to 2013, focusing on the PD incidence in relation to the timings of the 4 PD promotional policies; then we stratified the results according to age, sex and the presence of diabetes mellitus. PARTICIPANTS: From 2006 to 2013, 115 565 patients were enrolled in this study. The mean (SD) age of patients on PD was 54.6 (15.7) years. RESULTS: During the time frame in which the 4 PD promotional policies were implemented, the PD incidence increased from 12.8% in 2006 to 15.1% in 2009. The PD incidence started to decline in 2010 (13.8%) when the hospital accreditation policy was repealed. The 3 remaining policies were weakly associated with the PD incidence. The observational analysis determined that the patients' ages, sexes and diabetes mellitus incidence rates were relatively stable from 2006 to 2013. CONCLUSIONS: Of the 4 health policies intended to promote PD usage, using increasing the PD incidence as a KPI for hospital accreditation had the strongest association with the PD incidence.

Treatment effects of lysozyme-shelled microbubbles and ultrasound in inflammatory skin disease.

Acne vulgaris is the most common skin disorder, and is caused by Propionibacterium acnes (P. acnes) and can induce inflammation. Antibiotic therapy often needs to be administered for long durations in acne therapy, which results in extensive antibiotic exposure. The present study investigated a new treatment model for evaluating the antibacterial effects of lysozyme (LY)-shelled microbubbles (MBs) and ultrasound (US)-mediated LY-shelled MBs cavitation against P. acnes both in vitro and in vivo, with the aims of reducing the dose and treatment duration and improving the prognosis of acne vulgaris. In terms of the in vitro treatment efficacy, the growth of P. acnes was inhibited by 86.08 ± 2.99% in the LY-shelled MBs group and by 57.74 ± 3.09% in the LY solution group. For US power densities of 1, 2, and 3 W/cm2 in the LY-shelled MBs group, the growth of P. acnes was inhibited by 95.79 ± 3.30%, 97.99 ± 1.16%, and 98.69 ± 1.13%, respectively. The in vivo results showed that the recovery rate on day 13 was higher in the US group with LY-shelled MBs (97.8 ± 19.8%) than in the LY-shelled MBs group (90.3 ± 23.3%). Our results show that combined treatments of US and LY-shelled MBs can significantly reduce the treatment duration and inhibit P.-acnes-induced inflammatory skin diseases.

Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging.

Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm(-1)) and lipid (~2845 cm(-1)) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans.

Correlation between levofloxacin consumption and the incidence of nosocomial infections due to fluoroquinolone-resistant Escherichia coli.

BACKGROUND/PURPOSE: The relationship between fluoroquinolone resistance in Escherichia coli isolates causing nosocomial infection and hospital antibiotic consumption were investigated. Restriction of levofloxacin use was implemented to control the incidence of fluoroquinolone-resistant E coli in the hospital. METHODS: The study was conducted from January 2004 to December 2010. Antimicrobial agent consumption was obtained from the pharmacy computer system and presented as the defined daily doses per 1000 patient-days every 6 months. The incidence of fluoroquinolone-resistant E coli isolates causing nosocomial infections was obtained from the Department of Infection Control every 6 months. An antimicrobial stewardship program, restricting levofloxacain use, was implemented in July 2007. RESULTS: The incidence of fluoroquinolone-resistant E coli causing nosocomial infections was significantly correlated with fluoroquinolone usage (p = 0.005), but not with the use of third- or fourth-generation cephalosporins, piperacillin-tazobactam, or carbapenems. Parenteral (p = 0.002), oral (p = 0.018), and total levofloxacin (p = 0.001) use were significantly correlated with the extent of fluoroquinolone resistance. With a reduction of levofloxacin use, a decrease of the incidence of fluoroquinolone resistance in E coli isolates was observed. CONCLUSION: There is a significant correlation between levofloxacin use and the incidence of nosocomial fluoroquinolone-resistant E coli isolates. The incidence of fluoroquinolone-resistant E coli could be reduced by limiting levofloxacin consumption.

History of hyperthyroidism and long-term outcome of catheter ablation of drug-refractory atrial fibrillation.

BACKGROUND: Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status. OBJECTIVE: The purpose of this study was to compare the electrophysiologic characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism. METHODS: The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein (PV) isolation in paroxysmal AF and additional substrate modification in nonparoxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients. RESULTS: Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3 ± 0.4 vs 1.0 ± 0.2, P < .01), and higher prevalence of non-PV foci (42% vs 23%, P < .01). Ectopic foci from ligament of Marshall were demonstrated more often in hyperthyroid patients (7.1% vs 1.6%, P < .01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio 2.07, 95% confidence interval 1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and those without hyperthyroid history. CONCLUSION: Patients with hyperthyroid history had a significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci compared to euthyroid patients, which resulted in a higher AF recurrence rate after a single procedure.

Folic acid supplementation in end-stage renal disease patients reduces total mortality rate.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular disease and elevated serum homocysteine levels. Although folic acid supplementation has been documented to reduce serum homocysteine levels in ESRD patients, most trials of folic acid therapy for reducing cardiovascular diseases in ESRD patients have failed, mainly because of limited patient numbers. METHODS: We used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a matched-pair retrospective cohort study to clarify whether folic acid supplementation benefits ESRD patient survival. Patients were divided into a folic acid supplementation group and a control group. All-cause and cardiovascular-related mortality rates between groups were compared. RESULTS: In total, 55,636 stable incident hemodialysis patients were identified from the database. Using a propensity score-matched method and intention-to-treat analysis, the survival rate of 17,000 patients with folic acid supplementation was compared with a 1:1 matched control group. The baseline demographic data and comorbid disease incidence between the 2 groups were comparable. During the study period, the mortality rate in the matched pair cohort was 35.5% (n = 6,030) over a mean follow-up period of 3.0 years, corresponding to a mortality rate of 12.8/100 patient-years. The all-cause mortality rates were 12.3 and 13.4/100 patient-years in the folic acid group and control group, respectively (p = 0.005). CONCLUSIONS: In adult hemodialysis patients, folic acid supplementation improves cardiovascular and all-cause mortality rates.

Fluoroquinolone resistance of Pseudomonas aeruginosa isolates causing nosocomial infection is correlated with levofloxacin but not ciprofloxacin use.

This study investigated the correlation between fluoroquinolone (ciprofloxacin or levofloxacin) use and rates of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from patients with nosocomial infection at a medical centre in Taiwan. Antibiotic utilisation data were extracted on a monthly basis from the inpatient pharmacy computer system records from January 2003 to December 2008. Fluoroquinolone use was expressed as defined daily dose per 1000 patient-days and was correlated with rates of fluoroquinolone-resistant P. aeruginosa every 6 months. Regression analysis was performed to explore the relationship between ciprofloxacin and levofloxacin use (both parenteral and oral forms) and resistance of P. aeruginosa isolates. During the study period, the susceptibility of P. aeruginosa to fluoroquinolones decreased after increasing use of fluoroquinolones, and increased after decreasing use of levofloxacin. Parenteral levofloxacin use was significantly positively correlated with resistance of P. aeruginosa to ciprofloxacin (P=0.015) and fluoroquinolones (either ciprofloxacin or levofloxacin, P=0.014). Use of both parenteral and oral forms of levofloxacin was also significantly positively correlated with resistance of P. aeruginosa isolates to ciprofloxacin (P=0.029), levofloxacin (P=0.031) and fluoroquinolones (P=0.010). The total amount of ciprofloxacin (oral and parenteral) and parenteral ciprofloxacin use were negatively correlated with resistance of P. aeruginosa isolates to fluoroquinolones. However, the amounts of oral ciprofloxacin, parenteral levofloxacin, oral levofloxacin and total levofloxacin use were each positively correlated with resistance of P. aeruginosa to fluoroquinolones. Levofloxacin use was associated with increased resistance of P. aeruginosa to fluoroquinolones, whereas ciprofloxacin use did not have a significant impact on fluoroquinolone resistance rates.