Background: Cigarette smoking has been shown to increase oxidative DNA damage in human sperm cells. Assessment of the role of cigarette smoking in the etiology of childhood cancer has focused ...primarily on the effect of maternal smoking. Similar studies in relation to paternal smoking, however, have been inconclusive. Few studies have evaluated the effect of paternal smoking in the preconception period, and most of these could not disentangle the effects of paternal from maternal smoking. Purpose: We investigated the relationship of paternal smoking, particularly in the preconception period, with childhood cancer among offspring of the nonsmoking mothers. Methods: We conducted a population-based, case-control study in Shanghai, People's Republic of China, where the prevalence of smoking is high among men but extremely low among women. The study included 642 childhood cancer case patients (<15 years of age) and their individually matched control subjects. Information concerning parental smoking, alcohol drinking, and other exposures of the index child was obtained by direct interview of both parents of the study subjects. Odds ratios (ORs), derived from conditional logistic regression models, were used to measure the association between paternal smoking and risk of childhood cancers. Results and Conclusions: Paternal preconception smoking was related to a significantly elevated risk of childhood cancers, particularly acute leukemia and lymphoma. The risks rose with increasing pack-years of paternal preconception smoking for acute lymphocytic leukemia (ALL) (P for trend = .01), lymphoma (P for trend = .07), and total cancer (P for trend = .006). Compared with children whose fathers had never smoked cigarettes, children whose fathers smoked more than five pack-years prior to their conception had adjusted ORs of 3.8 (95% confidence interval CI = 1.3-12.3) for ALL, 4.5 (95% CI = 1.2-16.8) for lymphoma, 2.7 (95% CI = 0.8-9.9) for brain tumors, and 1.7 (95% CI = 1.2-2.5) for all cancers combined. Statistically significant increased risks of cancer were restricted to children under the age of 5 years at diagnosis or those whose fathers had smoked during all of the 5 years prior to conception. Implications: Further studies are needed to confirm the association of paternal smoking with increased risk of cancer in offspring, to clarify the pattern of risks in relation to the timing of cigarette smoking, and to elucidate the biologic mechanism involved in predisposing the offspring to cancer. For example, it may be that paternal smoking induces prezygotic genetic damage that, in turn, acts as the predisposing factor.
Panax ginseng C.A. Meyer, one of the most popular and valued herbs, has been used extensively in traditional Chinese medicine for thousands of years. More than thirty ginsenosides, the ...pharmacologically active ingredients in ginseng, have been identified with various sugar moieties attached at the C-3, C-6 and C-20 positions of the steroidal skeleton. We herein review the current literature on the pharmacological effects of ginsenosides on the modulation of angiogenesis, dysregulations of which contribute towards many pathological conditions. Regarding the adaptogenic property of ginseng, the effects of ginsenosides on central nervous system are also discussed. Recent researches have pointed to the steroid hormone receptors as the target molecules to elicit the diverse cellular and physiological activities of ginseng. We believe that understanding the interaction between ginsenosides and various steroid hormone receptors may provide clues to unravel the secret of ginseng.
Quantitative classification and regression models for prediction of sensory irritants (log
RD
50) of volatile organic chemicals (VOCs) have been developed. Each compound was represented by the ...calculated structural descriptors to encode constitutional, topological, geometrical, electrostatic, and quantum–chemical features. The heuristic method (HM) was then used to search the descriptor space and select the descriptors responsible for activity. The best classification results were found using support vector machine (SVM): the accuracy for training, test and overall data set is 96.5%, 85.7% and 94.4%, respectively. The nonlinear regression models were built by radial basis function neural networks (RNFNN) and SVM, respectively. The root mean squared errors (RMS) in prediction for the training, test and overall data set are 0.4755, 0.6322 and 0.5009 for reactive group, 0.2430, 0.4798 and 0.3064 for nonreactive group by RBFNN. The comparative results obtained by SVM are 0.4415, 0.7430 and 0.5140 for reactive group, 0.3920, 0.4520 and 0.4050 for nonreactive group, respectively. This paper proposes an effective method for poisonous chemicals screening and considering.
Objective: This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine‐associated weight gain.
Method: This was a 12‐week double‐blind, placebo controlled, ...randomized trial of sibutramine for weight loss in obese clozapine‐treated schizophrenia or schizoaffective disorder subjects.
Results: Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels.
Conclusion: Sibutramine treatment did not show significant weight loss compared with placebo in clozapine‐treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow‐up duration is warranted.
Classification models of estrogen receptor-β ligands were proposed using linear and nonlinear models. The data set was divided into active and inactive classes on the basis of their binding ...affinities. The two-class problem (active, inactive) was firstly explored by linear classifier approach, linear discriminant analysis (LDA). In order to get a more accurate prediction model, the nonlinear novel machine learning technique, support vectors machine (SVM), was subsequently used to investigate. The heuristic method (HM) was used to pre-select the whole descriptor sets. The model containing eight descriptors founded by SVM, showed better predictive ability than LDA. The accuracy in prediction for the training, test and overall data sets are 92.9%, 85.8% and 91.4% for SVM, 83.1%, 76.1% and 81.9% for LDA, respectively. The results indicate that SVM can be used as a powerful modeling tool for QSAR studies.
Classification models of 105 estrogen receptor-β ligands were proposed using linear (linear discriminant analysis) and nonlinear models (support vectors machine). The results gave an insight into the descriptors that are likely to relate to the binding affinities of the newly reported diphenolic azoles.
Display omitted
The hydrophilic bile salt ursodeoxycholic acid (UDCA) is a potent inhibitor of apoptosis. In this paper, we further characterize the mechanism by which UDCA inhibits apoptosis induced by deoxycholic ...acid, okadaic acid and transforming growth factor beta1 in primary rat hepatocytes. Our data indicate that coincubation of cells with UDCA and each of the apoptosis-inducing agents was associated with an approximately 80% inhibition of nuclear fragmentation (P<0.001). Moreover, UDCA prevented mitochondrial release of cytochrome c into the cytoplasm by 70 - 75% (P<0.001), thereby, inhibiting subsequent activation of DEVD-specific caspases and cleavage of poly(ADP-ribose) polymerase. Each of the apoptosis-inducing agents decreased mitochondrial transmembrane potential and increased mitochondrial-associated Bax protein levels. Coincubation with UDCA was associated with significant inhibition of these mitochondrial membrane alterations. The results suggest that the mechanism by which UDCA inhibits apoptosis involves an interplay of events in which both depolarization and channel-forming activity of the mitochondrial membrane are inhibited.
The support vector machine (SVM), as a novel type of a learning machine, for the first time, was used to develop a QSPR model that relates the structures of 35 amino acids to their isoelectric point. ...Molecular descriptors calculated from the structure alone were used to represent molecular structures. The seven descriptors selected using GA-PLS, which is a sophisticated hybrid approach that combines GA as a powerful optimization method with PLS as a robust statistical method for variable selection, were used as inputs of RBFNNs and SVM to predict the isoelectric point of an amino acid. The optimal QSPR model developed was based on support vector machines, which showed the following results: the root-mean-square error of 0.2383 and the prediction correlation coefficient R = 0.9702 were obtained for the whole data set. Satisfactory results indicated that the GA-PLS approach is a very effective method for variable selection, and the support vector machine is a very promising tool for the nonlinear approximation.
Probabilistic neural networks (PNNs) were utilized for the classifications of 102 active compounds from diverse medicinal plants with anticancer activity against human rhinopharyngocele cell line KB. ...Molecular descriptors calculated from structure alone were used to represent molecular structures. A subset of the calculated descriptors selected using factor correlation analysis and forward stepwise regression was used to construct the prediction models. Linear discriminant analysis (LDA) was also utilized to construct the classification model to compare the results with those obtained by PNNs. The accuracy of the training set, the cross-validation set, and the test set given by PNNs and LDA were 100, 92.3, 90.9% and 71.8, 92.3, 54.5%, respectively, which indicated that the results obtained by PNNs agree well with the experimental values of these compounds and also revealed the superiority of PNNs over LDA approach for the classification of anticancer activities of compounds. The models built in this work would be of potential help in the design of novel and more potent anticancer agents.
Infection is a serious complication of external ventricular drain (EVD) and various strategies have been adopted to minimize its occurrence. The use of an extended subcutaneous tunnel (50 - 60 cm) ...was previously described, but has since received little attention in the literature. The authors reviewed their experience with this technique, with emphasis on the rate of infection and predisposing risk factors. This is a retrospective review of 114 patients who received EVD with extended subcutaneous tunnel ('long EVD'). Fourteen of the 114 patients underwent more than one insertion, and a total of 133 cases of 'long EVD' were included. The mean duration of drainage was 20 days. One-hundred-and-three cases started without pre-existent infection and seven became infected, yielding an overall infection rate of 6.8%. The majority of infections were found within the first 5 days and in the third week of drainage. There was, however, no statistically significant difference in daily infection risks between the first, second and third weeks. Only intraventricular instillation of urokinase was identified as a statistically significant risk factor. Non-infective complications occurred in 17 cases (12.8%). In the present study, the overall infection rate of the 'long EVD' was comparable with that of conventional EVD, as reported by other authorities in the literature. The extended subcutaneous tunnel technique did not affect the daily infection risk on a week-to-week basis. The 'long EVD' does not appear to offer any distinct advantage over the standard tunnelling technique in our unit. However, this is essentially an audit within a single centre, and the findings should be interpreted with caution and with the understanding that individual institutions may have their unique patterns and risks of EVD infection.
PDF
