Comparison of PCR ribotyping and multilocus variable-number tandem-repeat analysis (MLVA) for improved detection of Clostridium difficile

<p>Abstract</p> <p>Background</p> <p>Polymerase chain reaction (PCR) ribotyping is one of the globally accepted techniques for defining epidemic clones of <it>Clostridium difficile </it>and tracing virulence-related strains. However, the ambiguous data generated by this technique makes it difficult to compare data attained from different laboratories; therefore, a portable technique that could supersede or supplement PCR ribotyping should be developed. The current study attempted to use a new multilocus variable-number tandem-repeat analysis (MLVA) panel to detect PCR-ribotype groups. In addition, various MLVA panels using different numbers of variable-number tandem-repeat (VNTR) loci were evaluated for their power to discriminate <it>C. difficile </it>clinical isolates.</p> <p>Results</p> <p>At first, 40 VNTR loci from the <it>C. difficile </it>genome were used to screen for the most suitable MLVA panel. MLVA and PCR ribotyping were implemented to identify 142 <it>C. difficile </it>isolates. Groupings of serial MLVA panels with different allelic diversity were compared with 47 PCR-ribotype groups. A MLVA panel using ten VNTR loci with limited allelic diversity (0.54-0.83), designated MLVA10, generated groups highly congruent (98%) with the PCR-ribotype groups. For comparison of discriminatory power, a MLVA panel using only four highly variable VNTR loci (allelic diversity: 0.94-0.96), designated MLVA4, was found to be the simplest MLVA panel that retained high discriminatory power. The MLVA10 and MLVA4 were combined and used to detect genetically closely related <it>C. difficile </it>strains.</p> <p>Conclusions</p> <p>For the epidemiological investigations of <it>C. difficile</it>, we recommend that MLVA10 be used in coordination with the PCR-ribotype groups to detect epidemic clones, and that the MLVA4 could be used to detect outbreak strains. MLVA10 and MLVA4 could be combined in four multiplex PCR reactions to save time and obtain distinguishable data.</p

Carotid Artery Intima-Media Thickness, Carotid Plaque and Coronary Heart Disease and Stroke in Chinese

Background: Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited. Methods and Findings: We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements. Conclusions: This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese

Women's preference for cesarean delivery and differences between Taiwanese women undergoing different modes of delivery

<p>Abstract</p> <p>Background</p> <p>The rate of cesarean delivery was 35% in 2007 in Taiwan. It is unclear how many of the cesarean deliveries were without medical indications. Women's preference for cesarean delivery during their course of pregnancy has rarely been studied and therefore our objectives were to examine rate of cesarean deliveries without medical indications, to explore women's preference for cesarean delivery as their gestation advances, and to compare background and perinatal factors among women who underwent different modes of delivery in Taiwan.</p> <p>Methods</p> <p>This prospective study applied a longitudinal design. The study participants were 473 women who received prenatal care at four hospitals in Taipei and answered structured questionnaires at 20 to 24 weeks of pregnancy, 34 to 36 weeks of pregnancy, and 5 to 7 weeks after delivery.</p> <p>Results</p> <p>Of the 151 women (31.9%) who had cesarean deliveries, 19.9% were without medical indication. Three indications: malpresentation, prior cesarean section, and dysfunctional labor together accounted for 82.6% of cesarean section with medical indications. The prevalence of maternal preference for cesarean delivery was found to be 12.5% and 17.5% during the second and third trimester, respectively. Of the women who preferred cesarean delivery during the second trimester, 93.2% eventually had a cesarean delivery. Women who were older, with older spouses, and who had health problems before or during pregnancy were more likely to have cesarean deliveries.</p> <p>Conclusions</p> <p>About 20% of cesarean deliveries were without medical indications. Women's preference for cesarean delivery during the second trimester predicts subsequent cesarean delivery. Counseling regarding mode of delivery should be offered early in pregnancy, especially for women who are older or with older spouses, have health problems, or had a prior cesarean section.</p

Ascites Volumes and the Ovarian Cancer Microenvironment

Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy among women in developed countries. Epithelial ovarian cancer has a poor prognosis, due to the aggressive characteristics of the disease combined with the lack of effective therapies. Options for late-stage ovarian cancer are limited and invasive, especially once malignant ascites develops. Malignant ascites, a complication observed in terminal ovarian cancer, significantly contributes to poor quality of life and to mortality. Excess accumulation of fluid in the peritoneal cavity occurs due to a combination of impaired fluid drainage and increased net filtration, mostly due to increasing intraperitoneal vascular permeability. Here we applied non-invasive magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) of syngeneic mouse tumors in vivo, and high-resolution 1H MRS of mouse tumor extracts, to characterize the relationship between ascites volumes and the vasculature and metabolism of an experimental model of ovarian cancer. Differences were observed in the tumor vasculature and metabolism in tumors based on ascites volumes that provide new insights into the development of this condition

Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan

[[abstract]]ABSTRACT: BACKGROUND: The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. METHODS: A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. RESULTS: The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts. CONCLUSIONS: MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality

Probabilistic Daily ILI Syndromic Surveillance with a Spatio-Temporal Bayesian Hierarchical Model

BACKGROUND: For daily syndromic surveillance to be effective, an efficient and sensible algorithm would be expected to detect aberrations in influenza illness, and alert public health workers prior to any impending epidemic. This detection or alert surely contains uncertainty, and thus should be evaluated with a proper probabilistic measure. However, traditional monitoring mechanisms simply provide a binary alert, failing to adequately address this uncertainty. METHODS AND FINDINGS: Based on the Bayesian posterior probability of influenza-like illness (ILI) visits, the intensity of outbreak can be directly assessed. The numbers of daily emergency room ILI visits at five community hospitals in Taipei City during 2006-2007 were collected and fitted with a Bayesian hierarchical model containing meteorological factors such as temperature and vapor pressure, spatial interaction with conditional autoregressive structure, weekend and holiday effects, seasonality factors, and previous ILI visits. The proposed algorithm recommends an alert for action if the posterior probability is larger than 70%. External data from January to February of 2008 were retained for validation. The decision rule detects successfully the peak in the validation period. When comparing the posterior probability evaluation with the modified Cusum method, results show that the proposed method is able to detect the signals 1-2 days prior to the rise of ILI visits. CONCLUSIONS: This Bayesian hierarchical model not only constitutes a dynamic surveillance system but also constructs a stochastic evaluation of the need to call for alert. The monitoring mechanism provides earlier detection as well as a complementary tool for current surveillance programs

Systemic delivery of E6/7 siRNA using novel lipidic particles and its application with cisplatin in cervical cancer mouse models

Small interfering RNA (siRNA) shows great promise in cancer therapy, but its effectiveness in vivo still remains a crucial issue for its transition into the clinics. Although the successful use of polyethylene glycol (PEG)ylated lipidic delivery systems have already been reported, most of the formulation procedures used are labour intensive and also result in unstable end products. We have previously developed a simple yet efficient hydration-of-freeze-dried- matrix (HFDM) method to entrap siRNA within lipid particles, in which the products exhibited superior stability. Here, we show that these HFDM-formulated particles are stable in the presence of serum and can deliver siRNA efficiently to tumours after intravenous administration. Using these particles, around 50% knockdown of the target gene expression was observed in tumours. With the use of siRNA targeting the E6/7 oncogenes expressed in cervical cancer, we showed a 50% reduction in tumour size. This level of tumour growth suppression was comparable to that achieved from cisplatin at the clinically used dose. Overall, our results demonstrate the feasibility of using HFDM-formulated particles to systematically administer E6/7-targeted siRNA for cervical cancer treatment. The simplicity of preparation procedure along with superior product stability obtained from our method offers an innovative approach for the in vivo delivery of siRNA

Spatial autocorrelation analysis of health care hotspots in Taiwan in 2006

<p>Abstract</p> <p>Background</p> <p>Spatial analytical techniques and models are often used in epidemiology to identify spatial anomalies (hotspots) in disease regions. These analytical approaches can be used to not only identify the location of such hotspots, but also their spatial patterns.</p> <p>Methods</p> <p>In this study, we utilize spatial autocorrelation methodologies, including Global Moran's I and Local Getis-Ord statistics, to describe and map spatial clusters, and areas in which these are situated, for the 20 leading causes of death in Taiwan. In addition, we use the fit to a logistic regression model to test the characteristics of similarity and dissimilarity by gender.</p> <p>Results</p> <p>Gender is compared in efforts to formulate the common spatial risk. The mean found by local spatial autocorrelation analysis is utilized to identify spatial cluster patterns. There is naturally great interest in discovering the relationship between the leading causes of death and well-documented spatial risk factors. For example, in Taiwan, we found the geographical distribution of clusters where there is a prevalence of tuberculosis to closely correspond to the location of aboriginal townships.</p> <p>Conclusions</p> <p>Cluster mapping helps to clarify issues such as the spatial aspects of both internal and external correlations for leading health care events. This is of great aid in assessing spatial risk factors, which in turn facilitates the planning of the most advantageous types of health care policies and implementation of effective health care services.</p

Evaluation of cell-free DNA approaches for multi-cancer early detection

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test