The effect of parity on longitudinal maternal hemodynamics.

BACKGROUND: Parous women have a lower risk for pregnancy complications, such as preeclampsia or delivery of small-for-gestational-age neonates. However, parous women are a heterogeneous group of patients because they contain a low-risk cohort with previously uncomplicated pregnancies and a high-risk cohort with previous pregnancies complicated by preeclampsia and/or small for gestational age. Previous studies examining the effect of parity on maternal hemodynamics, including cardiac output and peripheral vascular resistance, did not distinguish between parous women with and without a history of preeclampsia or small for gestational age and reported contradictory results. OBJECTIVE: The objective of the study was to compare maternal hemodynamics in nulliparous women and in parous women with and without previous preeclampsia and/or small for gestational age. STUDY DESIGN: This was a prospective, longitudinal study of maternal hemodynamics, assessed by a bioreactance method, measured at 11+0 to 13+6, 19+0 to 24+0, 30+0 to 34+0, and 35+0 to 37+0 weeks' gestation in 3 groups of women. Group 1 was composed of parous women without a history of preeclampsia and/or small for gestational age (n = 632), group 2 was composed of nulliparous women (n = 829), and group 3 was composed of parous women with a history of preeclampsia and/or small for gestational age (n = 113). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables controlling for maternal characteristics, medical history, and development of preeclampsia or small for gestational age in the current pregnancy. RESULTS: In groups 1 and 2, cardiac output increased with gestational age to a peak at 32 weeks and peripheral vascular resistance showed a reversed pattern with its nadir at 32 weeks; in group 1, compared with group 2, there was better cardiac adaptation, reflected in higher cardiac output and lower peripheral vascular resistance. In group 3 there was a hyperdynamic profile of higher cardiac output and lower peripheral vascular resistance at the first trimester followed by an earlier sharp decline of cardiac output and increase of peripheral vascular resistance from midgestation. The incidence of preeclampsia and small for gestational age was highest in group 3 and lowest in group 1. CONCLUSION: There are parity-specific differences in maternal cardiac adaptation in pregnancy

Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer

Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

Survey of motivation for use of voluntary counseling and testing services for HIV in a high risk area of Shenyang, China

<p>Abstract</p> <p>Background</p> <p>HIV voluntary counseling and testing (VCT) is considered an effective prevention method of HIV infection. In order to understand the VCT environment and enhance the effective delivery of VCT services in a country, an accurate assessment of the current status of VCT services is very important.</p> <p>Methods</p> <p>From July 2006 to June 2007, we conducted a cross-sectional survey using a face to face interview among 2676 VCT clients from a high risk area in Shenyang city, China.</p> <p>Results</p> <p>The major demographic characteristics among 2,676 VCT clients were: 41.1% were in the age range 20 to 30 years; 73.1% were males; and 67.1% had attained the level of junior high school education. The primary information source for VCT services was mass media like television (TV) and newspaper in 88.9%. 34.3% were afraid of the result of infection which was the main barrier to accept VCT services among 540 participants answering the question. 75.2% were motivated by recently acquired knowledge about HIV. 47.9% had 3 or more male sex partners, 62.3% had used condoms sometimes, and 14.5% had been infected with a STD. 2.8% of the participants identified themselves as men who have sex with men (MSM). The main demographic characteristics of MSM did not differ from the total group of participants except with respect to age: 63.5% reported having one male sex partner in the preceding 12 months, 44.6% reported never using condoms in the preceding 12 months, and only 2.7% reported a history of sexually transmitted disease.</p> <p>Conclusion</p> <p>Public education offered by health workers in hospitals, private clinics and other medical institutions needs to be strengthened. Given the results from this study, we recommend: (1) making VCT a routine part of health services, especially in areas where many high-risk individuals live; (2) improving the information sources and increasing the understanding of HIV and HIV-infected individuals; (3) enhancing international collaboration in strategic planning, technical assistance, and protocols to translate policy into effective action; (4) supporting Chinese non-government organizations (NGOs) in playing a significant role in the battle against AIDS.</p

Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function

The mammary gland is unique in its requirement to develop in close association with a depot of adipose tissue that is commonly referred to as the mammary fat pad. As discussed throughout this issue, the mammary fat pad represents a complex stromal microenvironment that includes a variety of cell types. In this article we focus on adipocytes as local regulators of epithelial cell growth and their function during lactation. Several important considerations arise from such a discussion. There is a clear and close interrelationship between different stromal tissue types within the mammary fat pad and its adipocytes. Furthermore, these relationships are both stage- and species-dependent, although many questions remain unanswered regarding their roles in these different states. Several lines of evidence also suggest that adipocytes within the mammary fat pad may function differently from those in other fat depots. Finally, past and future technologies present a variety of opportunities to model these complexities in order to more precisely delineate the many potential functions of adipocytes within the mammary glands. A thorough understanding of the role for this cell type in the mammary glands could present numerous opportunities to modify both breast cancer risk and lactation performance

Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research.</p> <p>Methods</p> <p>A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction.</p> <p>Results</p> <p>Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% <it>vs </it>7.9%).</p> <p>Conclusions</p> <p>The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.</p

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy

Improved Measurement of Electron Antineutrino Disappearance at Daya Bay

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Cytoplasmic levels of cFLIP determine a broad susceptibility of breast cancer stem/progenitor-like cells to TRAIL

Background The clinical application of TRAIL receptor agonists as a novel cancer therapy has been tempered by heterogeneity in tumour responses. This is illustrated in breast cancer, where TRAIL is cytotoxic in cell lines of mesenchymal origin but refractory in lines with an epithelial-like phenotype. However, it is now evident that intra-tumour heterogeneity includes a minority subpopulation of tumour-initiating stem/progenitor-like cells (CSCs) that possess mesenchymal characteristics. We hypothesised therefore that TRAIL may target these phenotypically distinct CSC-like cells that are common to most - if not all - breast cancers, thus impacting on the source of malignancy in a much broader range of breast tumour subtypes than previously envisaged. Methods We used colony formation, tumoursphere, flow cytometry and xenograft tumour initiation assays to observe the TRAIL sensitivity of CSC-like cells in a panel of two mesenchymal-like (TRAIL-sensitive) and four epithelial-like (TRAIL-resistant) breast cancer cell lines. Subcellular levels of the endogenous TRAIL inhibitor, cFLIP, were determined by western blot and immunofluorescence microscopy. The effect of the subcellular redistribution of cFLIP on TRAIL sensitivity and Wnt signalling was determined using cFLIP localisation mutants and the TOPFlash reporter assay respectively. Results TRAIL universally suppressed the clonal expansion of stem/progenitors in all six of the breast cancer cell lines tested, irrespective of their phenotype or overall sensitivity to TRAIL. A concomitant reduction in tumour initiation was confirmed in the TRAIL-resistant epithelial cell line, MCF-7, following serial dilution xenotransplantation. Furthermore TRAIL sensitivity of breast CSCs was inversely proportional to the relative cytoplasmic levels of cFLIP while overexpression of cFLIP in the cytosol using subcellular localization mutants of cFLIP protected these cells from cytotoxicity. The accumulation of nuclear cFLIP on the other hand did not influence TRAIL cytotoxicity but instead promoted Wnt-dependent signalling. Conclusion These data propose a novel role for TRAIL as a selective CSC agent with a broad specificity for both epithelial and mesenchymal breast tumour subtypes. Furthermore we identify a dual role for cFLIP in the maintenance of breast CSC viability, dependent upon its subcellular distribution

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases