Description: Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose–response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and “omic”-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug-disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations.

Description: Defects in distal oesophageal peristalsis was thought to be an indication of incomplete bolus transit (BT). However, the role of transition zone (TZ) defects in the BT in gastroesophageal reflux disease (GORD)...

Description: Background: Nonurgent use of hospital emergency departments (ED) is a controversial topic. It is thought to increase healthcare costs and reduce quality, but is also considered a symptom of unequal access to health care. In this article, we investigate whether convenience (as proxied by travel distances to the hospital ED and to the closest federally qualified health center) is associated with nonurgent ED use, and whether evidence of health disparities exist in the way vulnerable populations use the hospital ED for medical care in South Carolina. Methods: Our data includes 6,592,501 ED visits in South Carolina between 2005 and 2010 from the South Carolina Budget Control Board and Office of Research and Statistics. All ED visits by South Carolina residents with unmasked variables and nonmissing urgency measures, or approximately 76 % of all ED visits, are used in the analysis. We perform multivariable linear regressions to estimate correlations between (1) travel distances and observable sociodemographic characteristics and (2) measures of nonurgent ED use or frequent nonurgent ED use, as defined by the New York University ED Algorithm. Results: Patients with commercial private insurance, self-pay patients, and patients with other payment sources have lower measures of nonurgent ED use the further away the ED facility is from the patients’ home address. Vulnerable populations, particularly African American and Medicaid patients, have higher measures of nonurgent ED scores, and are more frequent users of the ED for both nonurgent and urgent reasons in South Carolina. At the same time, African Americans visit the hospital ED for medical conditions with higher primary care-preventable scores. Conclusions: Contrary to popular belief, convenient access (in terms of travel distances) to hospital ED is correlated with less-urgent ED use among privately insured patients and self-pay patients in South Carolina, but not publicly insured patients. Unequal access to primary care appears to exist, as suggested by African American patients’ use of the hospital ED for primary care-treatable conditions while experiencing more frequent and more severe primary care-preventable conditions.

Description: Background: Haemophilus parasuis (H. parasuis) can invade the body and cause systemic infection under stress conditions. Marbofloxacin has been recommended for the treatment of swine infections. However, few studies have investigated the PK/PD characteristics and PK/PD cutoff (CO PD ) of this drug against H. parasuis. Results: MICs of marbofloxacin against 198 H. parasuis isolates were determined. The MIC 50 and MIC 90 were 2 and 8 mg/L, respectively. An in vitro dynamic PK/PD model was established to study the PK/PD relationship of marbofloxacin against H. parasuis. The PK/PD surrogate markers C max /MIC, C max /MPC (the maximum concentration divided by MIC or mutant prevention concentration (MPC)) and AUC 24h /MIC, AUC 24h /MPC (the area under the curve during the first 24 h divided by MIC or MPC) simulated the antimicrobial effect of marbofloxacin successfully with the R 2 of 0.9928 and 0.9911, respectively. The target values of 3-log 10 -unit and 4-log 10 -unit reduction for AUC 24h /MPC were 33 and 42, while the same efficacy for AUC 24h /MIC were 88 and 110. The CO PD deduced from Monte Carlo simulation (MCS) for marbofloxacin against H. parasuis was 0.5 mg/L. The recommended dose of marbofloxacin against H. parasuis with MIC ≤ 2 mg/L was 16 mg/kg body weight (BW). Conclusions: The PK/PD surrogate markers AUC 24h /MIC, C max /MIC and AUC 24h /MPC, C max /MPC properly described the effects of marbofloxacin. Marbofloxacin can achieve the best efficacy at dosage of 16 mg/kg BW for strains with MIC values ≤ 2 mg/L, therefore, it is obligatory to know the sensitivity of the pathogen and to treat animals as early as possible. The very first CO PD provide fundamental data for marbofloxacin breakpoint determination.