Abstract Objectives To examine the extent social support mediates resilience and quality of life in Wenchuan earthquake survivors. Study design Originals. Methods Self-report psychological ...questionnaires, the standard Chinese 12-item Short Form (SF-12v2), the Resilience Scale for Adults (RSA), and the Social Support Rating Scale (SSRS) were used to interview a total of 2080 survivors from 19 counties in the 2008 Wenchuan Earthquake area. A regression analysis was conducted to evaluate the mediating effect of social support on quality of life. Results Males and individuals with a higher level of education were found to have a better quality of life. The association between resilience and quality of life improved after social support was included, suggesting that at least a part of this association was mediated by the level of social support provided. Conclusions This analysis highlighted that the level of resilience and quality of life after an earthquake was associated with the level of social support. This result has clear policy implications, and indicates that more focus needs to be placed on policies that aim for the provision of early mental health intervention and social support to improve the quality of life of earthquake survivors.
Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma (HCC). The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance, but such ...correlation is unclear in sorafenib resistance of HCC.
Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line (Huh-7R; derived from sorafenib-sensitive Huh-7) were used. The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, and siRNA of hexokinase 2 (HK2) were used to target relevant pathways of cancer metabolism. Cell viability, mitochondrial membrane potential, and sub-G1 fraction were measured for in vitro efficacy. Reactive oxygen species (ROS), adenosine triphosphate (ATP) and glucose uptake were also measured. A subcutaneous xenograft mouse model was used for in vivo efficacy.
The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity (R(2)=0.9067, among sorafenib-naive cell lines; P=0.003, compared between Huh-7 and Huh-7 R). DCA reduced lactate production and increased ROS and ATP, indicating activation of oxidative phosphorylation (OXPHOS). DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis (sub-G1 (combination vs sorafenib): Hep3B, 65.4±8.4% vs 13±2.9%; Huh-7 R, 25.3± 5.7% vs 4.3±1.5%; each P<0.0001), whereas siRNA of HK2 did not. Sorafenib (10 mg kg(-1) per day) plus DCA (100 mg kg(-1) per day) also resulted in superior tumour regression than sorafenib alone in mice (tumour size: -87% vs -36%, P<0.001).
The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity, and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC.
This study was undertaken to establish reference values of exhaled nitric oxide fraction (F(eNO)) and its determinants in healthy Asian children. 693 healthy Asian children aged 5-18 yrs were ...assessed using a single-breath online F(eNO) measurement (exhaled flow 50 mL·s(-1)), questionnaires, anthropometric measurements, spirometry and total and specific immunoglobulin (Ig) E. Geometric mean F(eNO) and the upper 95% CI were 13.7 ppb and 49.7 ppb, respectively, for healthy children, and 11.2 ppb and 30.2 ppb, respectively, for those without allergic sensitisation. F(eNO) was positively associated with age, allergic sensitisation, total IgE, ambient nitric oxide, measurement in the afternoon, and drinking water within 1 h before testing, and was negatively associated with weight. In healthy children without allergic sensitisation, age was the single best explanatory variable. The F(eNO) predicted values were 1-2 ppb higher in Asian than in Caucasian children in earlier studies, while the upper 95% CI were 9-10 ppb higher. In conclusion, the upper limits of normal F(eNO) in Asian children depend on age, from 21 ppb in young children to 39 ppb in adolescents. Ethnicity, age, allergic sensitisation, total IgE, ambient nitric oxide, time of testing, drinking water and weight are important determinants.
Background
Lenalidomide has immunomodulatory and anti‐angiogenic effects and showed moderate anti‐tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC)
Aim
To explore potential ...biomarkers of lenalidomide efficacy as second‐line therapy for HCC.
Methods
Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child‐Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1‐21 every 4 weeks. The primary endpoint was 6 month progression‐free survival rate. Early α‐fetoprotein response was defined as a > 20% decline of α‐fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast‐enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed.
Results
Fifty‐five patients were enrolled. The response rate was 13%, and the disease‐control rate was 53%. The 6 month progression‐free survival rate was 9.1%. The median progression‐free and overall survival was 1.8 months and 8.9 months respectively. Early α‐fetoprotein response was significantly associated with higher disease‐control rate (76% vs 22%, P = .001) and longer progression‐free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre‐treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression‐free survival (P < .001) and overall survival (P = .042).
Conclusions
Lenalidomide exhibited moderate activity as second‐line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).
Traditional methods of disease diagnosis are both time-consuming and labor-intensive, and many tests require expensive instrumentation and trained professionals, which restricts their use to ...biomedical laboratories. Because patients can wait several days (even weeks) for the results, the consequences of delayed treatment could be disastrous. Therefore, affordable and simple point-of-care (POC) biosensor devices could fill a diagnostic niche in the clinic or even at home, as personal glucose meters do for diabetics. These devices would allow patients to check their own health conditions and enable physicians to make prompt treatment decisions, which could improve the chances for rapid recovery and cure. Compact discs (CDs) provide inexpensive substrate materials for the preparation of microarray biochips, and conventional computer drives/disc players can be adapted as precise optical reading devices for signal processing. Researchers can employ the polycarbonate (PC) base of a CD as an alternative substrate to glass slides or silicon wafers for the preparation of microanalytical devices. Using the characteristic optical phenomena occurring on the metal layer of a CD, researchers can develop biosensors based on advanced spectroscopic readout (interferometry or surface plasmon resonance). If researchers integrate microfluidic functions with CD mechanics, they can control fluid transfer through the spinning motion of the disc, leading to “lab-on-a-CD” devices. Over the last decade, our laboratory has focused on the construction of POC biosensor devices from off-the-shelf CDs or DVDs and standard computer drives. Besides the initial studies of the suitability of CDs for surface and materials chemistry research (fabrication of self-assembled monolayers and oxide nanostructures), we have demonstrated that an ordinary optical drive, without modification of either the hardware or the software driver, can function as the signal transducing element for reading disc-based bioassays quantitatively. In this Account, we first provide a brief introduction to CD-related materials chemistry and microfluidics research. Then we describe the mild chemistry developed in our laboratory for the preparation of computer-readable biomolecular screening assays: photochemical activation of the polycarbonate (PC) disc surface and immobilization and delivery of probe and target biomolecules. We thoroughly discuss the analysis of the molecular recognition events: researchers can “read” these devices quantitatively with an unmodified optical drive of any personal computer. Finally, and critically, we illustrate our digitized molecular diagnosis approach with three trial systems: DNA hybridization, antibody–antigen binding, and ultrasensitive lead detection with a DNAzyme assay. These examples demonstrate the broad potential of this new analytical/diagnostic tool for medical screening, on-site food/water safety testing, and remote environmental monitoring.
Primary retroperitoneal tumours (PRTs) are rare soft tissue tumours originating from the retroperitoneum. Although there has been considerable progress recently in diagnosis and treatment, the ...overall survival rate has not improved qualitatively. This study aimed to explore the clinical features, therapeutic strategies and prognosis of PRTs.
Retrospective analysis of clinical data for 121 PRT patients admitted to Peking University Shenzhen Hospital from April 2003 to February 2017.
A total of 113 patients underwent surgery and 8 chose nonsurgical palliative treatment. There were 53 males and 68 females (ratio, 1:1.3; average age, 40.75 years), and the average tumour diameter was 9.69(2-40)cm. A total of 104 patients (92.04%) underwent complete resection, 5 (4.42%) underwent palliative resection and 21 (18.58%) underwent combined visceral resection. The pathological diagnosis was benign in 88 cases (72.73%) and malignant in 33 cases (27.27%). A total of 101 patients (83.47%) were followed for an average of 5.82 years. At the end of follow up, the recurrence and survival rates were 2.63% and 93.42% for benign tumours, respectively, and 24.00% and 60.00% for malignant tumours (
<0.01).
Imaging plays important roles in localising and characterising tumours, guiding treatment strategies. Complete tumour resection is key to reducing postoperative recurrence and improving survival. According to the postsurgical pathological results, combinations including radiotherapy, chemotherapy or targeted therapy are beneficial for improving prognosis.
Lysosomal storage diseases (LSDs) are a group of genetic disorders, resulting from deficiencies of lysosomal enzyme. Genotype‐phenotype correlation is essential for timely and proper treatment ...allocation. Recently, by integrating prediction outcomes of 7 bioinformatics tools, we developed a SAAMP algorithm to predict the impact of individual amino‐acid substitution. To optimize this approach, we evaluated the performance of these bioinformatics tools in a broad array of genes. PolyPhen and PROVEAN had the best performances, while SNP&GOs, PANTHER and I‐Mutant had the worst performances. Therefore, SAAMP 2.0 was developed by excluding 3 tools with worst performance, yielding a sensitivity of 94% and a specificity of 90%. To generalize the guideline to proteins without known structures, we built the three‐dimensional model of iduronate‐2‐sulfatase by homology modeling. Further, we investigated the phenotype severity of known disease‐causing mutations of the GLB1 gene, which lead to 2 LSDs (GM1 gangliosidosis and Morquio disease type B). Based on the previous literature and structural analysis, we associated these mutations with disease subtypes and proposed a theory to explain the complicated genotype‐phenotype correlation. Collectively, an updated guideline for phenotype prediction with SAAMP 2.0 was proposed, which will provide essential information for early diagnosis and proper treatment allocation, and they may be generalized to many monogenic diseases.
The adsorption of crystal violet dye from aqueous solutions onto an activated carbon prepared from peanut shells was analyzed in this study. The effects of particle size, initial concentration, time ...and temperature on crystal violet removal were studied in batch experiments. Experimental results showed that the adsorption equilibrium was achieved within 100 min for all studied concentrations. Analysis of adsorption results showed that the adsorption isotherms could be well fitted to the Langmuir model. Kinetic parameters, rate constants, equilibrium adsorption capacities and related correlation coefficients for pseudo first-order and second-order kinetic models were calculated and discussed. The results revealed that the adsorption kinetics was in good agreement with the pseudo second-order equation. Thermodynamic parameters such as the change of Gibbs free energy (ΔG°), change of enthalpy (ΔH°) and change of entropy (ΔS°) have also been determined and it has been found that the adsorption process should be spontaneous, endothermic and physisorption in nature.
In addition to the role in regulating leukocyte trafficking, chemokines recently have been shown to be involved in cancer growth and metastasis. Chemokine network in tumor neovascularity may be ...regulated by decoy receptors. Duffy antigen receptor for chemokines (DARC) is a specific decoy receptor binding with the angiogenic CC and CXC chemokines. To investigate the effects of DARC on the tumorigenesis and the metastasis potential of human breast cancer cells, human DARC cDNA was reintroduced into the MDA-MB-231 and MDA-MB-435HM cells which have a high capability of spontaneous pulmonary metastasis. We demonstrated that DARC overexpression induced inhibition of tumorigenesis and/or metastasis through interfering with the tumor angiogenesis in vivo. This inhibition is associated with decreasing CCL2 protein levels, and MVD and MMP-9 expression in xenograft tumors. In human breast cancer samples, we also demonstrated that low expression of the DARC protein is significantly associated with estrogen receptor (ER) status, MVD, lymph node metastasis, distant metastasis and poor survival. Our results suggest for the first time that DARC is a negative regulator of growth in breast cancer, mainly by sequestration of angiogenic chemokines and subsequent inhibition of tumor neovascularity.
Cite this as: T‐C Yao, L‐S Ou, W‐I Lee, K‐W Yeh, L‐C Chen and J‐L Huang , for the PATCH study group, Clinical & Experimental Allergy, 2011 (41) 556–564.
Summary
Background
Fraction of exhaled nitric ...oxide (FeNO) as a biomarker of airway inflammation in children warrants better clarification.
Objective
To identify the determinants of FeNO in children and assess the validity of FeNO as a discriminative tool for asthma, rhinitis or allergic sensitization in a population setting.
Methods
Children aged 5–18 years (N=1717) were evaluated using online FeNO measurements, questionnaires, anthropometric measurements, pulmonary function tests and total and specific serum IgE.
Results
FeNO levels were age‐dependent, with an average increase of 7.4% per year of age. It decreased with increasing body mass index (BMI), estimated at 1.5% decrease per kg/m2. Children with allergic sensitization had elevated FeNO independent of allergic symptoms. In the combined analyses of asthma, rhinitis and allergic sensitization, elevated FeNO levels were confined mainly to children having allergic sensitization. After adjusting for allergic sensitization, a significant association between rhinitis and FeNO remained, but no such association was seen with asthma. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of FeNO at the optimum cut‐off of 28 p.p.b. for diagnosing asthma were 64.3%, 69.9%, 8.8%, and 97.7%, respectively (area under the ROC curve AUC 0.67), and were slightly better for diagnosing allergic asthma: 70.0%, 70.4%, 9.0%, 98.3%, respectively (AUC 0.71). FeNO had modest accuracy in discriminating rhinitis with an AUC value of 0.70, and performed better in discriminating allergic rhinitis (AUC 0.78). FeNO was a robust discriminator of allergic sensitization independent of symptoms at a cut‐off of 15.4 p.p.b. (AUC 0.80; sensitivity 72.2%; specificity 71.2%; PPV 76.9%; NPV 65.8%).
Conclusion and Clinical Relevance
FeNO measurement discriminates children with and without allergic sensitization independent of allergic symptoms. On the other hand, low FeNO levels in children may help exclude allergic asthma but high levels may be caused by allergic sensitization, older age, rhinitis, and lower BMI, in addition to asthma.
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