: Our objectives were to (1) determine the pharmacokinetic indices of vancomycin in pediatric patients; and (2) compare attainment of 2 target exposures: area under curve (AUC) / minimum inhibitory ...concentration (MIC) ≥400 and trough concentration ≥15 mcg/mL.
: The population-based pharmacokinetic modeling was performed using NONMEM 7.2 for children ≥3 months old who received vancomycin for ≥48 hours from 2003 to 2011. A 1-compartment model with first-order kinetics was used to estimate clearance, volume of distribution and AUC. Empiric Bayesian post hoc individual parameters and Monte Carlo simulations (N = 11,000) were performed.
: Analysis included 702 patients with 1660 vancomycin serum concentrations. Median age was 6.6 (interquartile range 2.2-13.4) years, weight 22.7 (12.6-46) kg and baseline serum creatinine 0.40 (0.30-0.60) mg/dL. Final model pharmacokinetic indices were clearance (L/h) = 0.248 * Wt * (0.48/serum creatinine) * (ln(age)/7.8) and volume of distribution (L) = 0.636 * Wt. Using these parameters and the observed MIC distribution, Monte Carlo simulation indicated that the initial median dose of 44 (39-52) mg/kg/day was inadequate in most subjects. Regimens of 60 mg/kg/day for subjects ≥12 years old and 70 mg/kg/day for those <12 years old achieved target AUC/MIC in ~75% and trough concentrations ≥15 in ~45% of virtual subjects. An AUC/MIC ~400 corresponded to trough concentration ~8 to 9 mcg/mL.
: Targeted exposure using vancomycin AUC/MIC, compared with trough concentrations, is a more realistic target in children. Depending on age, serum creatinine and MIC distribution, vancomycin in a dosage of 60 to 70 mg/kg/day was necessary to achieve AUC/MIC ≥ 400 in 75% of patients.
Project 254 signed in November 2011 which is relating to “Restructuring the system of credit institutions in the period of 2011–2015” has been considered as a milestone in marking the Vietnamese ...government to prevent the influence of the financial crisis of 2008. This paper identifies hypotheses evaluating the impact of restructuring measurements on the risk of the Vietnamese’s commercial banks in 10 years, starting from 2008. Using the OLS regression method for analysis by running Eviews and ANOVA test in SPSS with a unique database of 216 observations of 31 commercial banks in Vietnam, it was found that: (i) The bail-out activities of the State Bank of Vietnam in 2015 does not influence on bank risk, (ii) The mergers and acquisitions (M&A) do not support the bank to reduce risk, it increases the risk for acquiring banks, (iii) The global crisis 2008 exerts dire consequence on the bank system in Vietnam, (iv) There is the difference of risk among the groups of the bank experiencing a different number of years of operation. Basing on this result, the paper also makes recommendations to the Government, The State Bank of Vietnam and the commercial banks for effective risk management toward the development of the Vietnamese banking system.
The aim of this study was to characterize uterine, fecal, bedding, and airborne dust microbiota from postpartum dairy cows and their environment. The cows were managed by the free-stall housing ...system, and samples for microbiota and serum metabolite assessment were collected during summer and winter when the cows were at one and two months postpartum. Uterine microbiota varied between seasons; the five most prevalent taxa were
, and
during summer, and
, and
during winter. Although
and
were detected at high abundance in several uterine samples, the relationship between the uterine microbiota and serum metabolite concentrations was unclear. The fecal microbiota was stable regardless of the season, whereas bedding and airborne dust microbiota varied between summer and winter. With regards to uterine, bedding, and airborne dust microbiota,
, and
were more abundant during summer, and
and
were more abundant during winter. Canonical analysis of principal coordinates confirmed the relationship between uterine and cowshed microbiota. These results indicated that the uterine microbiota may vary when the microbiota in cowshed environments changes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Osteoporosis is a common bone health disorder in hemodialysis patients that is linked with a higher morbidity and mortality rate. While previous studies have explored the associated factors of ...osteoporosis, there is a lack of studies investigating the impacts of health literacy (HL) and digital healthy diet literacy (DDL) on osteoporosis. Therefore, we aimed to investigate the associations of HL, DDL, and other factors with osteoporosis among hemodialysis patients. From July 2020 to March 2021, a cross-sectional study was conducted on 675 hemodialysis patients in eight hospitals in Vietnam. The data were collected by using the osteoporosis self-assessment tool for Asians (OSTA) and the 12-item short form of the health literacy questionnaire (HLS-SF12) on digital healthy diet literacy (DDL) and hemodialysis dietary knowledge (HDK). In addition, we also collected information about the socio-demographics, the clinical parameters, the biochemical parameters, and physical activity. Unadjusted and adjusted multinomial logistic regression models were utilized in order to investigate the associations. The proportion of patients at low, medium, and high levels of osteoporosis risk was 39.6%, 40.6%, and 19.8%, respectively. In the adjusted models, women had a higher likelihood of osteoporosis risk than men (odds ratio, OR, 3.46; 95% confidence interval, 95% CI, 1.86, 6.44; p < 0.001; and OR, 6.86; 95% CI, 2.96, 15.88; p < 0.001). The patients with rheumatoid arthritis (OR, 4.37; 95% CI, 1.67, 11.52; p = 0.003) and stomach ulcers (OR, 1.95; 95% CI, 1.01, 3.77; p = 0.048) were more likely to have a higher likelihood of osteoporosis risk than those without. The patients who had a higher waist circumference (WC), HL, and DDL were less likely to have a medium level of osteoporosis risk (OR, 0.95; 95% CI, 0.92, 0.98; p = 0.004; OR, 0.92; 95% CI, 0.88, 0.96; p < 0.001; OR, 0.96; 95% CI, 0.93, 0.99; p = 0.017, respectively) and a high level of osteoporosis risk (OR, 0.93; 95% CI, 0.89, 0.97; p = 0.001; OR, 0.89; 95% CI, 0.84, 0.94; p < 0.001; OR, 0.95; 95% CI, 0.91, 0.99; p = 0.008, respectively) compared with a low level of osteoporosis risk and to those with a lower WC, HL, and DDL. In addition, higher levels of hemoglobin (Hb) (OR, 0.79; 95% CI, 0.66, 0.95; p = 0.014), hematocrit (Hct) (OR, 0.95; 95% CI, 0.92, 0.99; p = 0.041), albumin (OR, 0.91; 95% CI, 0.83, 0.99; p = 0.030), and education (OR, 0.37; 95% CI, 0.16, 0.88; p = 0.025) were associated with a lower likelihood of a high level of osteoporosis risk. In conclusion, osteoporosis risk is highly prevalent in hemodialysis patients. Improved HL, DDL, education, WC, albumin, Hb, and Hct levels should be considered in preventing hemodialysis patients from developing osteoporosis.
The polypharmacology of natural products Ho, Tu T; Tran, Quy TN; Chai, Christina LL
Future medicinal chemistry,
06/2018, Letnik:
10, Številka:
11
Journal Article
Recenzirano
The once-popular approach of using natural products as a prime source for medicinal chemistry and drug discovery has waned considerably in the past two decades due to the advent of high-throughput ...screening of small molecule mega libraries. However, the growing appreciation of network pharmacology as the next drug-discovery paradigm suggests that natural products and their unique polypharmacology offer significant advantages for finding novel therapeutics particularly for the treatment of complex and multifactorial diseases. Drug discovery process is awaiting the revitalization of interest in natural products and their derivatives. The current challenge is how to decipher this natural chemical diversity.
Global myocardial work (GMW) is an emerging method to characterize left ventricle (LV) function with potential advantages over both ejection fraction and global longitudinal strain (GLS). We aimed to ...determine the feasibility and reproducibility for echocardiographic-derived GMW in a healthy pediatric population; establish normal reference values; and investigate the influence of age, gender, and other clinical factor on normal reference ranges. We prospectively enrolled 212 individuals (median age of 9 years; interquartile range, 6 to 12 years, 112 female). Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were measured from LV pressure–strain loops. Quantification of GMW was performed using a GE Vivid E95 system and available software package (Echopac V.203, GE). The mean LV EF was 64 ± 3% with GLS of -21.3 ± 1.5%. GWI was 1688 ± 219 mmHg% with mean GWE of 96.5 ± 1.4%. The GCW was 1959 ± 207 mmHg%, and the mean GWW of 61.1 ± 30.9 mmHg%. No significant difference was found in MW indices across age group and gender (
p
> 0.05 for all). There were significant correlations between both GWI and GCW with GLS and systolic blood pressure (
p
< 0.001), but not with GWE and GWW. Linear regression model revealed that GWI and GCW were more closely correlated with systolic blood pressure than GLS. LV MW indices had good intra-observer and inter-observer reproducibility. This study establishes both the feasibility and reference ranges for non-invasive echocardiographic indices of GMW in healthy children. Myocardial work appears to be a complementary modality to assess LV performance in children.
Human breast milk (HBM) may have beneficial effects on
DSM 17938 (LR 17938) -mediated immunomodulation. We aimed to determine the effects of HBM on proliferation of LR 17938 in vitro and its ...associated proteins and metabolites in culture, in order to provide mechanistic insights into the health benefits of LR 17938. LR 17938 was cultured anaerobically in MRS bacterial culture media, HBM (from 6 mothers), and 2 types of cow-milk formula. The colony-forming unit (CFU) was calculated to evaluate LR 17938 growth. Sixteen-hour-fermented supernatants were used for metabolomics, and bacterial lysates were used for proteomics analysis. We found that growth of LR 17938 was 10 times better in HBM than in formula. We detected 261/452 metabolites upregulated when LR 17938 cultured in HBM compared to in formula, mainly participating in the glyoxylate cycle (succinate), urea cycle (citrulline), methionine methylation (N-acetylcysteine), and polyamine synthesis (spermidine). The significantly up-regulated enzymes were also involved in the formation of acetyl-CoA in the glyoxylate cycle and the antioxidant N-acetylcysteine. In conclusion, HBM enhances the growth of LR 17938 compared to formula and promotes LR 17938-associated metabolites that relate to energy and antioxidant status, which may be linked to the physiological effects of
.
This paper presents an analytical solution for the free vibration behavior of functionally graded carbon nanotube-reinforced composite (FG-CNTRC) doubly curved shallow shells with integrated ...piezoelectric layers. Here, the linear distribution of electric potential across the thickness of the piezoelectric layer and five different types of carbon nanotube (CNT) distributions through the thickness direction are considered. Based on the four-variable shear deformation refined shell theory, governing equations are obtained by applying Hamilton’s principle. Navier’s solution for the shell panels with the simply supported boundary condition at all four edges is derived. Several numerical examples validate the accuracy of the presented solution. New parametric studies regarding the effects of different material properties, shell geometric parameters, and electrical boundary conditions on the free vibration responses of the hybrid panels are investigated and discussed in detail.
Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity ...drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of Oil Red O staining and quantitative real-time polymerase chain reaction revealed that SW20.1 was more effective in reducing lipid accumulation in 3T3-L1 preadipocytes than the previously synthesized ST32db, and that it inhibited the expression of the genes involved in adipogenesis and lipogenesis. A chromatin immunoprecipitation assay indicated that SW20.1 inhibited adipogenesis and lipogenesis by binding to the upstream promoter region of resistin at two sites (-2861/-2854 and -241/-234). In mice, the intraperitoneal administration of SW20.1 reduced body weight, white adipocyte weight in different regions, serum cholesterol levels, adipogenesis-related gene expression, hepatic steatosis, and serum resistin levels. Overall, SW20.1 exerts antiobesity effects by inhibiting resistin through the ATF3 pathway. Our study results indicate that SW20.1 is a promising therapeutic drug for diet-induced obesity.
The research identifies hypotheses evaluating the impact of board characteristics on the risk of the commercial bank as well as examining the determinants of bank risk in Vietnam over a 10-year ...period, starting from 2008. Also, in this research, the differences between the roles of women and men in decision-making are tested. Based on this decision, risks of the banks may arise. Ordinary least squares (OLS) regression, Random effect method, and Fixed effect method are used to estimate the factors that have an impact on bank risk for dataset of all commercial banks in Vietnam. The results found that equity-to-asset ratio, bank performance and the economic growth have an inverse relationship with bank risk, while the size of bank has a positive relationship with the bank risk. One of the highlights of this paper is a demonstration of the relationship between CEO’s gender and bank risk. The test result shows that the bank led by a female faces a higher overall risk level and credit risk than a bank led by a male. Based on this result, the paper also makes recommendations to Government, the State Bank of Vietnam and the commercial banks for effective risk management.
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