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: Author(s): Minhao Liu, Jinsong Zhang, Cui-Zu Chang, Zuocheng Zhang, Xiao Feng, Kang Li, Ke He, Li-li Wang, Xi Chen, Xi Dai, Zhong Fang, Qi-Kun Xue, Xucun Ma, and Yayu Wang We report transport studies on magnetically doped Bi 2 Se 3 topological insulator ultrathin films grown by molecular beam epitaxy. The magnetotransport behavior exhibits a systematic crossover between weak antilocalization and weak localization with the change of magnetic impurity concentration, temper... [Phys. Rev. Lett. 108, 036805] Published Thu Jan 19, 2012

Description: Author(s): Hongwei Chen, Xi Kong, Bo Chong, Gan Qin, Xianyi Zhou, Xinhua Peng, and Jiangfeng Du The method of quantum annealing (QA) is a promising way for solving many optimization problems in both classical and quantum information theory. The main advantage of this approach, compared with the gate model, is the robustness of the operations against errors originated from both external control... [Phys. Rev. A 83, 032314] Published Wed Mar 23, 2011

Description: Background: Sensory consequences of our own actions are perceived differently from the sensory stimuli that are generated externally. The present event-related potential (ERP) study examined the neural responses to self-triggered stimulation relative to externally-triggered stimulation as a function of delays between the motor act and the stimulus onset. While sustaining a vowel phonation, subjects clicked a mouse and heard pitch-shift stimuli (PSS) in voice auditory feedback at delays of either 0 ms (predictable) or 500-1000 ms (unpredictable). The motor effect resulting from the mouse click was corrected in the data analyses. For the externally-triggered condition, PSS were delivered by a computer with a delay of 500-1000 ms after the vocal onset. Results: As compared to unpredictable externally-triggered PSS, P2 responses to predictable self-triggered PSS were significantly suppressed, whereas an enhancement effect for P2 responses was observed when the timing of self-triggered PSS was unpredictable. Conclusions: These findings demonstrate the effect of the temporal predictability of stimulus delivery with respect to the motor act on the neural responses to self-triggered stimulation. Responses to self-triggered stimulation were suppressed or enhanced compared with the externally-triggered stimulation when the timing of stimulus delivery was predictable or unpredictable. Enhancement effect of unpredictable self-triggered stimulation in the present study supports the idea that sensory suppression of self-produced action may be primarily caused by an accurate prediction of stimulus timing, rather than a movement-related non-specific suppression.

Description: Background: Maize is a major economic crop worldwide, with substantial crop loss attributed to flooding. During a stress response, programmed cell death (PCD) can be an effective way for plants better adapt. To identify flooding stress related PCD proteins in maize leaves, proteomic analysis was performed using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrometry. Results: Comparative proteomics was combined with physiological and biochemical analysis of maize leaves under flooding stress. Fv/Fm, qP, qN and relative water content (RWC) were found to be altered in response to flooding stress, with an increase in H2O2 content noted in vivo. Furthermore, DNA ladder detection indicated that PCD had occurred under flooding treatment. The maize leaf proteome was analyzed via 2D-DIGE gel, with a total of 32 differentially expressed spots isolated, 31 spots were successfully identified via MALDI-TOF/TOF MS which represent 28 proteins. The identified proteins were related to energy metabolism and photosynthesis, PCD, phytohormones and polyamines. To better characterize the role of translationally controlled tumor protein (TCTP) in PCD during a stress response, mRNA expression was examined in different plants by stress-induced PCD. These included heat stress induced rice protoplasts, Tobacco Mosaic Virus infected tobacco leaves and dark induced rice and Arabidopsis thaliana leaves, all of which showed active PCD, and TCTP expression was increased in different degrees. Moreover, S-adenosylmethionine synthase 2 (SAMS2) and S-adenosylmethionine decarboxylase (SAMDC) mRNA expression were also increased, but ACC synthase (ACS) and ACC oxidase (ACO) mRNA expression were not found in maize leaves following flooding. Lastly, ethylene and polyamine concentrations were increased in response to flooding treatment in maize leaves. Conclusions: Following flooding stress, the photosynthetic systems were damaged, resulting in a disruption in energy metabolism, with the noted photosynthetic decline also possibly attributed to ROS production. The observed PCD could be regulated by TCTP with a possible role for H2O2 in TCTP induction under flooding stress. Additionally, increased SAMS2 expression was closely associated with an increased polyamine synthesis during flooding treatment.

Description: Background: The role of postoperative adjuvant treatment for sinonasal malignant melanoma remains unclear. This study evaluates the impact of three different surgical and postoperative adjuvant treatment modalities: surgery alone(open and endoscopic approaches), surgery plus radiotherapy and surgery, radiotherapy plus chemotherapy on survival of patients with primary sinonasal malignant melanoma (SMM). Methods: The data of 69 patients who underwent primary surgical treatments at Eye & ENT hospital of Fudan University between January 1st, 2000 and December 31st, 2010 were retrospectively reviewed. Survival comparison of different surgical and postoperative adjuvant treatment modalities (surgery alone, surgery plus radiotherapy and surgery, radiotherapy plus chemotherapy), as well as survival comparison between open and endoscopic surgical approaches were performed. Curves depicting survival were performed using Kaplan-Meier method. Statistical analysis was performed using log-rank test software SPSS19 and p 〈 .05 is considered as statistically significant. Results: The median overall survival time was found to be 18 months for surgery alone (27 cases), 32 months for surgery plus radiotherapy (24 cases), 42 months for surgery, radiotherapy plus chemotherapy (18 cases). The 3 and 5 year survival rates for groups mentioned above were 14.8% and 5.6%, 45.1% and 31.6%, 55% and 32.1%, respectively. Statistical significances were found not only between surgery alone and surgery plus radiotherapy treatment group(P = 0.012), but also surgery alone and surgery, radiotherapy plus chemotherapy group (P = 0.002). There was no statistically significant survival difference found between the two different surgical approaches (41 cases for open approach and 28 cases for endoscopic approach) . Conclusions: Sinonasal malignant melanoma is a disease with a poor prognosis. Patients who underwent surgery plus radiotherapy or surgery, radiotherapy plus chemotherapy had better survival outcomes than those underwent surgery alone. Endoscopic approach provided similar survival outcome as an open approach.

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: Community health service center (CHSC) in China is always regarded as a good facility of primary care, which plays an important role in chronic non-communicable disease management. This study aimed to investigate the blood pressure (BP) control rate in a real life CHSC-based management program and its determinants. Methods: The study enrolled 3191 patients (mean age of 70 +/- 10 years, 43% males) in a hypertension management program provided by the Yulin CHSC (Chengdu, China), which had been running for 9 years. Uncontrolled BP was defined as the systolic BP of 〉=140 mmHg and/or the diastolic BP of 〉=90 mmHg, and its associated factors were analyzed by using logistic regression. Results: The duration of stay in the program was 33 +/- 25 months. When compared with the BP at entry, the recent BP was significantly lowered (147 +/- 17 vs. 133 +/- 8 mmHg; 83 +/- 11 vs. 75 +/- 6 mmHg) and the BP control rate was dramatically increased (32 vs. 85%) (all p 〈 0.001). The age of 〉70 years [1.40 (odds ratio), 1.15-1.71 (95% confidence interval)], female gender (0.76, 0.63-0.93), longer stay of 〉33 months (0.77, 0.63-0.94), doctor in charge (0.97, 0.95-0.99), and the use of calcium channel blocker (1.35, 1.09-1.67) were significantly related to uncontrolled BP at the recent follow up (all p 〈 0.05). Conclusions: This CHSC-run hypertension program provides an ideal platform of multi-intervention management, which is effective in achieving higher BP control rate in community patient population. However, the BP control status could be affected by age, gender and adherence of the patients, as well as practice behavior of the doctors.

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.