Search

Avian pathogenic Escherichia coli (APEC), which has potential zoonotic risk, can cause severe systemic infections such as septicemia and meningitis in poultry. Colibactin is a hybrid non-ribosomal peptide/polyketide secondary metabolite produced by bacteria, which induces double-strand DNA breaks and chromosome instability in eukaryotic cells. ClbA is a 4'-phosphopantetheinyl transferase (PPTase) that is essential for colibactin and plays a role in siderophore synthesis. However, whether ClbA is associated with meningitis development in APEC is unclear. In this study, we abolished the clbA gene in the APEC XM strain, investigated the effect of clbA on colibactin synthesis and evaluated the pathogenic capacity of colibactin on meningitis development. Deletion of clbA reduced DNA damage to cells and hindered the normal synthesis of colibactin. Compared with the mice infected by wild-type APEC XM, the clbA deletion mutant infected mice had significant reduction in a series of characteristics associated with meningitis including clinical symptoms, bacterial loads of blood and brain, disruption of the blood brain barrier and the expression of inflammatory factors in the brain tissue. Complementation of ClbA recovered some APEC XM virulence. We conclude that ClbA is obligatory for the synthesis of colibactin and is responsible for the development of meningitis in mice infected by APEC.

It is unclear in Chinese patients with acute stroke how the SOAR (stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestrike modified Rankin) and mSOAR (modified-SOAR) scores performed in predicting discharge mortality and 3-month mortality. We aimed to validate the predictability of these scores in this cohort.Data from the China National Stroke Registry (CNSR) study was used to perform the mSOAR and SOAR scores for predicting the discharge and 3-month mortality in acute stroke patients.A total of 11073 acute stroke patients were included in present study. The increased mSOAR and SOAR scores were closely related to higher death risk in acute stroke patients. For discharge mortality, the area under the receiver-operator curve (AUC) of the mSOAR and SOAR scores were 0.784 (95% CI 0.761-0.807) and 0.722 (95% CI: 0.698-0.746). For 3-month mortality, they were 0.787 (95% CI: 0.771-0.803) and 0.704 (95% CI: 0.687-0.721), respectively. The mSOAR and SOAR scores showed significant correlation between the predicted and observed probabilities of discharge mortality (mSOAR: r = 0.945, P = 0.001; SOAR: r = 0.994, P

Growing evidence indicates that the cross-linked N-telopeptide of type I collagen (NTx) is likely to be involved in the development of bone metastasis among lung cancer patients. We perform a meta-analysis to disclose the correlation between bone metastasis and NTx and also to evaluate its value in diagnosis of bone metastasis (BM) in lung cancer.Electronic databases were searched and calculated the weighted mean difference (WMD) with 95% confidence interval (CI) to assess the expression difference of NTx between BM+ and BM- lung cancer patients. Moreover, we conducted a sensitivity and specificity test and drew a summary receiver operating characteristic curve (SROC) to assess the diagnostic value of NTx in discerning bone metastasis.A total of eleven studies with 1108 individuals were included in this analysis. The results showed an increased NTx was correlated with the incidence of lung cancer (P < 0.001). The overall sensitivity and specificity of serum NTx (sNTx) for discerning bone metastasis was 0.74 (95% CI = 0.67 to 0.79) and 0.85 (95% CI = 0.80 to 0.89), respectively. As for urine NTx (uNTx) the pooled sensitivity and specificity was 0.77(95% CI = 0.67 to 0.86) and 0.81(95% CI = 0.76 to 0.86). The area under the SROC curve was 0.8889(SE = 0.0255) and 0.8655(SE = 0.0254) for sNTx and uNTx respectively.The elevation of NTx in lung cancer was positively related with the development and progression of bone metastasis. A higher specificity over sensitivity of NTx suggested that it is a more accurate biomarker to distinguish patients without bone metastasis. Regarding SROC curve, sNTx may be a better choice.

A case-mix adjustment model has been developed and externally validated, demonstrating promise. However, the model has not been thoroughly tested among populations in China. In our study, we evaluated the performance of the model in Chinese patients with acute stroke.The case-mix adjustment model A includes items on age, presence of atrial fibrillation on admission, National Institutes of Health Stroke Severity Scale (NIHSS) score on admission, and stroke type. Model B is similar to Model A but includes only the consciousness component of the NIHSS score. Both model A and B were evaluated to predict 30-day mortality rates in 13,948 patients with acute stroke from the China National Stroke Registry. The discrimination of the models was quantified by c-statistic. Calibration was assessed using Pearson's correlation coefficient.The c-statistic of model A in our external validation cohort was 0.80 (95% confidence interval, 0.79-0.82), and the c-statistic of model B was 0.82 (95% confidence interval, 0.81-0.84). Excellent calibration was reported in the two models with Pearson's correlation coefficient (0.892 for model A, p

Colorectal cancer is the leading cause of cancer-related deaths worldwide. The disease is curable when detected at an early stage. However, the compliance rate with current screening recommendations remains poor. An accurate, minimally invasive blood test that has the potential for greater patient compliance would be a welcome addition to the current methods. Recent data have shown that gene expression profile of peripheral blood cells can reflect disease states and thus have diagnostic value. In this study, genome-wide gene expression profiling of peripheral blood cells from 20 healthy controls and 20 colorectal cancer patients were performed using PAXgene™ technology and Affymetrix GeneChip® microarrays. We identified a list of 1,469 genes that were differentially expressed between the healthy controls and cancer patients. Gene annotation and functional enrichment analysis revealed that those genes are mainly related to immune functions. Particularly, a set of genes belonging to the Toll-Like Receptor pathways were up-regulated in the colorectal cancer patients. These findings provide a new understanding of blood gene expression profile in colorectal cancer. Our result may serve as the basis for further development of blood biomarkers for the diagnosis and treatment of colorectal cancer.

BACKGROUND: After cancer diagnosis, therapy for the patient is largely dependent on the tumor origin, especially when a metastatic tumor is being treated. However, cases such as untypical metastasis, poorly differentiated tumors or even a limited number of tumor cells may lead to challenges in identifying the origin. Moreover, approximately 3% to 5% of total solid tumor patients will not have to have their tumor origin identified in their lifetime. The THEROS CancerTYPE ID® is designed for identifying the tumor origin with an objective, rapid and standardized procedure. METHODOLOGY AND PRINCIPAL FINDINGS: This is a blinded retrospective study to evaluate performance of the THEROS CancerTYPE ID® in a Chinese population. In total, 184 formalin-fixed paraffin-embedded (FFPE) samples of 23 tumor origins were collected from the tissue bank of Fudan University Shanghai Cancer Center (FDUSCC). A standard tumor cell enrichment process was used, and the prediction results were compared with reference diagnosis, which was confirmed by two experienced pathologists at FDUSCC. All of the 184 samples were successfully analyzed, and no tumor specimens were excluded because of sample quality issues. In total, 151 samples were correctly predicted. The agreement rate was 82.1%. A Pearson Chi-square test shows that there is no difference between this study and the previous evaluation test performed by bioTheranostics Inc. No statistically significant decrease was observed in either the metastasis group or tumors with high grades. CONCLUSIONS: A comparable result with previous work was obtained. Specifically, specimens with a high probability score (>0.85) have a high chance (agreement rate = 95%) of being correctly predicted. No performance difference was observed between primary and metastatic specimens, and no difference was observed among three tumor grades. The use of laser capture micro-dissection (LCM) makes the THEROS CancerTYPE ID® accessible to almost all of the cancer patients with different tumor statuses.

BACKGROUND: Human peripheral blood is a promising material for biomedical research. However, various kinds of biological and technological factors result in a large degree of variation in blood gene expression profiles. METHODOLOGY/PRINCIPAL FINDINGS: Human peripheral blood samples were drawn from healthy volunteers and analysed using the Human Genome U133Plus2 Microarray. We applied a novel approach using the Principle Component Analysis and Eigen-R(2) methods to dissect the overall variation of blood gene expression profiles with respect to the interested biological and technological factors. The results indicated that the predominating sources of the variation could be traced to the individual heterogeneity of the relative proportions of different blood cell types (leukocyte subsets and erythrocytes). The physiological factors like age, gender and BMI were demonstrated to be associated with 5.3% to 9.2% of the total variation in the blood gene expression profiles. We investigated the gene expression profiles of samples from the same donors but with different levels of RNA quality. Although the proportion of variation associated to the RNA Integrity Number was mild (2.1%), the significant impact of RNA quality on the expression of individual genes was observed. CONCLUSIONS: By characterizing the major sources of variation in blood gene expression profiles, such variability can be minimized by modifications to study designs. Increasing sample size, balancing confounding factors between study groups, using rigorous selection criteria for sample quality, and well controlled experimental processes will significantly improve the accuracy and reproducibility of blood transcriptome study.

Background: Loneliness and mobile phone addiction are common phenomena in our daily life that can lead to physical and psychological maladaptation. Although loneliness has been considered to be correlated with adolescents' mobile phone addiction, the underlying mechanisms of the relation between loneliness and mobile phone addiction are still unclear. In order to address the problem of mobile phone addiction among adolescents, the association of loneliness with mobile phone addiction was explored from the perspective of Compensatory Internet Use Theory. The mediating role of anthropomorphism and the moderating role of family support were examined. Methods: Data were collected through convenience sampling from a comprehensive university in China. A total of 582 Chinese college students (279 men and 303 women), aged from 17 to 24 (Mage = 20.22 years, SD = 1.46), participated in this study. Their loneliness, anthropomorphism, family support and mobile phone addiction were measured using well-validated self-report questionnaires. Regression-based statistical mediation and moderation were conducted using the PROCESS macro for SPSS. Results: Loneliness was significantly and positively associated with mobile phone addiction, and this link could be mediated by anthropomorphism. Moreover, the direct effect of loneliness on mobile phone addiction and the indirect effect of anthropomorphism in this link were moderated by family support. Both these two effects were stronger for college students with lower family support. Conclusion: The present study broadened our knowledge of the underlying mechanisms between loneliness and mobile phone addiction. These findings may contribute to a better understanding of the impact loneliness can have on mobile phone addiction as well as its paths. Moreover, the results can also provide advice for parents and constructive suggestions for rationalizing college students' mobile phone use in the mobile Internet era. Educational professionals and parents should pay special attention to the problem of mobile phone addiction among lonely adolescents, especially for those with low family support. [ABSTRACT FROM AUTHOR]

There is evidence from longitudinal studies that being light at birth and weaning is associated with subsequent rapid weight gain in infants. This is referred to as "centile crossing", which can lead to increased risk of lifetime obesity, glucose dysregulation and type 2 diabetes. Here, pregnant CD-1 mice were hemi-ovariectomized so that the entire litter was contained in one uterine horn to increase variability in fetal growth rate. Pregnant females were implanted on gestation day (GD) 9 with a Silastic capsule containing 6, 60 or 600 μg bisphenol A (BPA). On GD 18 the mean fetal serum unconjugated BPA concentrations were 17, 177 and 1858 pg/ml, respectively. Capsules were not removed, to avoid maternal stress, and were predicted to release BPA for at least 3 weeks. Body weight at weaning was strongly negatively correlated with post-weaning weight gain in both control and BPA-treated male mice, consistent with human data; female offspring were excluded, avoiding complications associated with postpubertal estrogens. Within each treatment group, male offspring were sorted into tertiles based on relative weight gain during the two weeks after weaning, designated as having Rapid (R), Medium (M) or Slow (S) growth rate. BPA exposure was associated with altered growth rate between weaning and postnatal week 12 (young adulthood), when a low-dose (20 mg/kg, i.p.) glucose tolerance test (GTT) was performed. We found altered glucose regulation in response to all doses of BPA. However, glucose tolerance was only significantly impaired (blood glucose levels were elevated) compared to controls in males in the rapid post-weaning growth group exposed perinatally to BPA. We conclude that male mice that are light at weaning, but then experience rapid catch-up growth immediately after weaning, represent a sensitive sub-population that is vulnerable to the metabolic disrupting effects of very low pg/ml fetal serum concentrations of BPA.

OBJECTIVE:To evaluate the association between the risk of ectopic pregnancy (EP) and the use of common contraceptives during the previous and current conception/menstrual cycle. METHODS:A multi-center case-control study was conducted in Shanghai. Women diagnosed with EP were recruited as the case group (n = 2,411). Women with intrauterine pregnancy (IUP) (n = 2,416) and non-pregnant women (n = 2,419) were matched as controls at a ratio of 1∶1. Information regarding the previous and current use of contraceptives was collected. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and the corresponding 95% confidential intervals (CIs). RESULTS:Previous use of intrauterine devices (IUDs) was associated with a slight risk of ectopic pregnancy (AOR1 = 1.87 [95% CI: 1.48-2.37]; AOR2 = 1.84 [1.49-2.27]), and the risk increased with the duration of previous use (P1 for trend

Whereas prey are known to avoid habitats with their predators, it is less well established whether they are triggered to emigrate to new habitats when exposed to predators in their current habitat. We studied plant-to-plant dispersal of adult whiteflies in response to the presence of predatory mites on the plant on which the whiteflies were released. These predators attack whitefly eggs and crawlers, but not the adults, which can fly to other plants and can learn to avoid plants with predators. Being tiny and wingless, the predatory mites are slow dispersers compared to adult whiteflies. This offers the whiteflies the opportunity to escape from plants with predatory mites to plants without predators, thus avoiding predation of their offspring. To test for this escape response, a greenhouse experiment was carried out, where whiteflies were released on the first of a row of 5 cucumber plants, 0.6 m or 2 m apart, and predators either on the same plant, on the next plant, or nowhere (control). Adult whiteflies dispersed significantly faster from plants with predatory mites onto neighbouring plants when the plants were 0.6 m apart, but not when plants were 2 m apart. However, the final numbers of whiteflies that had successfully dispersed at the end of the experiments did not differ significantly for either of the two interplant distances. Overall, the proportion of whiteflies that did disperse was low, suggesting that adult whiteflies were apparently reluctant to disperse, even from plants with predators. Our results suggest that this reluctance increases with the distance between the plants, so most likely depends on the uncertainty to find a new plant. Thus, whiteflies do not always venture to fly even when they can easily bridge the distance to another plant.