Weighted risk score-based multifactor dimensionality reduction to detect gene-gene interactions in nasopharyngeal carcinoma.

Determining the complex relationships between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has been proven to be capable of effectively detecting the statistical patterns of epistasis, although classification accuracy is required for this approach. The imbalanced dataset can cause seriously negative effects on classification accuracy. Moreover, MDR methods cannot quantitatively assess the disease risk of genotype combinations. Hence, we introduce a novel weighted risk score-based multifactor dimensionality reduction (WRSMDR) method that uses the Bayesian posterior probability of polymorphism combinations as a new quantitative measure of disease risk. First, we compared the WRSMDR to the MDR method in simulated datasets. Our results showed that the WRSMDR method had reasonable power to identify high-order gene-gene interactions, and it was more effective than MDR at detecting four-locus models. Moreover, WRSMDR reveals more information regarding the effect of genotype combination on the disease risk, and the result was easier to determine and apply than with MDR. Finally, we applied WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a statistically significant high-order interaction among three polymorphisms: rs2860580, rs11865086 and rs2305806.

Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake.

OBJECTIVE: The aim of the study was to better understand blonanserin population pharmacokinetic (PK) characteristics in Chinese healthy subjects. METHODS: Data from two studies with 50 subjects were analyzed to investigate the population PK characteristics of blonanserin at single dose (4, 8, and 12 mg) under fasting, multidose (4 mg bid or 8 mg qd for 7 days) and under food intake condition (single dose, 8 mg). Blonanserin plasma concentrations were detected using the high performance liquid chromatography tandem mass spectrometry (LC/MS/MS). A nonlinear mixed-effects model was developed to describe the blonanserin concentration-time profiles. RESULTS: A two compartment model with first-order absorption was built to describe the time-course of blonanserin. The population-predicted system apparent clearance (CL/F), volume of apparent distribution in center (V(1)/F), and the first-order absorption rate constant (Ka) of blonanserin under fasting was 1230 L/h, 9500 L, and 3.02 h(-1), respectively. Food intake decreased Ka of blonanserin to 0.78 h(-1). The relative bioavailability between fasting and food intake estimated by the final model was 55%. No clinically significant safety issues were identified. CONCLUSION: This is the first study assessing the PK profile of blonanserin with population PKs method. The results can be used for simulation in further clinical trial and optimize individual dosage regimens using a Bayesian methodology in patients.

A prediction model of occupational manganese exposure based on artificial neural network.

Application of two statistical models to reconstruct occupational exposure to manganese (Mn) is discussed. Air monitoring of 635 samples were analyzed by a back-propagation artificial neural network (back-propagation ANN) in comparison with a multiple linear regression (MLR). The stepwise MLR yielded significant results with five selected variables for predicting airborne manganese dioxide (MnO(2)). However, a 6-12-1 back-propagation ANN was superior to the data from MLR. Statistical parameters and non-parametric paired tests indicated that back-propagation ANN represents the more useful and accurate tool. ANN was used to predict missing MnO(2) concentrations in the present study. The median of MnO(2) was 0.445 mg/m(3) (IQR 0.131-1.342). The MnO(2) characteristics of time, distance, and exposure site were defined. Airborne MnO(2) for three previous periods (1978-1988, 1989-1998, and 1998-2007) were 1.228 mg/m(3), 0.664 mg/m(3), and 0.501 mg/m(3), respectively. The medians were 0.350 mg/m(3), 0.281 mg/m(3), and 0.190 mg/m(3) at distances of 5, 10, and 25 m away from the site of exposure. Compared with levels encountered in other studies, mine concentrator sites were more seriously polluted, due to the practices of direct ore processing.

Developing genetic epidemiological models to predict risk for nasopharyngeal carcinoma in high-risk population of China.

To date, the only established model for assessing risk for nasopharyngeal carcinoma (NPC) relies on the sero-status of the Epstein-Barr virus (EBV). By contrast, the risk assessment models proposed here include environmental risk factors, family history of NPC, and information on genetic variants. The models were developed using epidemiological and genetic data from a large case-control study, which included 1,387 subjects with NPC and 1,459 controls of Cantonese origin. The predictive accuracy of the models were then assessed by calculating the area under the receiver-operating characteristic curves (AUC). To compare the discriminatory improvement of models with and without genetic information, we estimated the net reclassification improvement (NRI) and integrated discrimination index (IDI). Well-established environmental risk factors for NPC include consumption of salted fish and preserved vegetables and cigarette smoking (in pack years). The environmental model alone shows modest discriminatory ability (AUC = 0.68; 95% CI: 0.66, 0.70), which is only slightly increased by the addition of data on family history of NPC (AUC = 0.70; 95% CI: 0.68, 0.72). With the addition of data on genetic variants, however, our model's discriminatory ability rises to 0.74 (95% CI: 0.72, 0.76). The improvements in NRI and IDI also suggest the potential usefulness of considering genetic variants when screening for NPC in endemic areas. If these findings are confirmed in larger cohort and population-based case-control studies, use of the new models to analyse data from NPC-endemic areas could well lead to earlier detection of NPC.

Determination of allopurinol and oxypurinol in human plasma and urine by liquid chromatography-tandem mass spectrometry.

Allopurinol is used widely for the treatment of gout, but its pharmacokinetics is complex and some patients show hypersensitivity, necessitating careful monitoring and improved detection methods. In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed to determine the concentrations of allopurinol and its active metabolite oxypurinol in human plasma and urine using 2,6-dichloropurine as the internal standard (IS). Analytes and the IS were extracted from 0.5ml aliquots of plasma or urine using ethyl acetate and separated on an Agilent Eclipse Plus C18 column using methanol and ammonium formate-formic acid buffer containing 5mM ammonium formate and 0.1% formic acid (95:5, v/v) as the mobile phase (A) for allopurinol or methanol plus 5mM ammonium formate aqueous solution (95:5, v/v) as the mobile phase (B) for oxypurinol. Allopurinol was detected in positive ion mode and the analysis time was about 7min. The calibration curve was linear from 0.05 to 5µg/mL allopurinol in plasma and 0.5-30µg/mL in urine. The lower limit of quantification (LLOQ) was 0.05µg/mL in plasma and 0.5µg/mL in urine. The intra- and inter-day precision and relative errors of quality control (QC) samples were ≤11.1% for plasma and ≤ 8.7% for urine. Oxypurinol was detected in negative mode with an analysis time of about 4min. The calibration curve was linear from 0.05 to 5µg/mL in plasma (LLOQ, 0.05µg/mL) and from 1 to 50µg/mL in urine (LLOQ, 1µg/mL). The intra- and inter-day precision and relative errors were ≤7.0% for plasma and ≤9.6% for urine. This method was then successfully applied to investigate the pharmacokinetics of allopurinol and oxypurinol in humans.

Defective T wave combined with incomplete right bundle branch block: a new electrocardiographic index for diagnosing atrial septal defect.

BACKGROUND: Incomplete right bundle branch block (ICRBBB) is commonly associated with atrial septal defect (ASD), but lacks sufficient diagnostic test characteristics. An abnormal T wave is also often observed in ASD, with horizontal or inverted displacement of the proximal T wave limb in the right precordial leads, termed "defective T wave" (DTW). METHODS: We examined the diagnostic test characteristics of combining ICRBBB with DTW as a new index to diagnose ASD. A total of 132 consecutive patients with ASD and 132 cases of age/gender-matched controls without ASD were enrolled. RESULTS: Sensitivities of DTW, ICRBBB, and both were 87.1% - 87.9%. Specificities were 97.0%, 96.2%, and 100%, respectively. Positive predictive values were 1.3%, 1.1%, and 100.0% respectively, while negative predictive values were 99.9% for each. CONCLUSION: Combining ICRBBB with DTW in electrocardiogram (ECG) as a new index significantly increased the specificity and positive predictive values while maintaining a high sensitivity in diagnosing ASD.

[Literature review of the efficacy and safety of hyperthermic intraperitoneal perfusion chemotherapy after cytoreductive surgery in the treatment of pseudomyxoma peritonei].

OBJECTIVE: To evaluated the safety and efficacy of hyperthermic intraperitoneal perfusion chemotherapy(HIPC) in the prevention and treatment of pseudomyxoma peritonei (PMP) recurrence after cytoreductive surgery(CRS). METHODS: Studies published in English before 2010 on HIPC after CRS for PMP were searched in PubMed database. Each study was carefully evaluated based on pre-determined criteria. Study results were comprehensively displayed in a form. A descriptive systematic review was performed. RESULTS: A total of 11 studies were included. The median survival time of patients in these studies ranged from 25.6 months to 156 months. The ranges of 1-year, 2-year, 3-year, 5-year, and 10-year survival rates were 72%-100%, 55%-96%, 59%-96%, 52%-96%, and 55%-96%, respectively. The overall complication rate ranged from 2%-15%, and the total perioperative mortality were from 0 to 7%. CONCLUSION: HIPC after CRS is effective and safe for patients with PMP.

Anti-SARS-CoV immunoglobulin G in healthcare workers, Guangzhou, China.

To determine the prevalence of inapparent infection with severe acute respiratory syndrome (SARS) among healthcare workers, we performed a serosurvey to test for immunoglobulin (Ig) G antibodies to the SARS coronavirus (SARS-CoV) among 1,147 healthcare workers in 3 hospitals that admitted SARS patients in mid-May 2003. Among them were 90 healthcare workers with SARS. As a reference group, 709 healthcare workers who worked in 2 hospitals that never admitted any SARS patients were similarly tested. The seroprevalence rate was 88.9% (80/90) for healthcare workers with SARS and 1.4% (15/1,057) for healthcare workers who were apparently healthy. The seroprevalence in the reference group was 0.4% (3/709). These findings suggest that inapparent infection is uncommon. Low level of immunity among unaffected healthcare workers reinforces the need for adequate personal protection and other infection control measures in hospitals to prevent future epidemics.

[Investigation and analysis of quality of life for patients after laryngectomy].

OBJECTIVE: To institute and test the quality of life for laryngectomy, and evaluate the feasibility of above questionnaire in patients after laryngectomy. METHODS: A questionnaire of quality of life for laryngectomy was instituted. An investigation was conducted in patients treated by partial (36, Group A) or total (45, Group B) laryngectomy for laryngeal cancer with above questionnaire. The feasibility, reliability and validity of the questionnaire was evaluated, the quality of life and the influencing factors in laryngectomy were also analyzed. RESULTS: The questionnaire of quality of life for laryngectomy consists of 22 items, covering six aspects. The questionnaire has a comparatively good reliability, and the criterion-related validity and content validity of the questionnaire is valid. The correlation coefficient of split-half method and Cronback's alpha of questionnaire were 0.842 and 0.889 respectively. The composite quality of life scores of group A were significant higher than those of group B ( P < 0.001). The differences in physical function, laryngeal function, psychological state, the ability of living independently were statistically significant (P < 0.001; P < 0.001; P < 0.01; P < 0.05) as well. Seven factors including operative modality, tumor stage, postoperative complication, coexisted disease, family incomes, voicing modality and wearing tracheo-cannula were related to postlaryngectomy quality of life. CONCLUSIONS: The questionnaire of quality of life for laryngectomy has speciality in laryngectomy and a comparatively good reliability and validity, and it is suitable for quality of life research in patients after laryngectomy.