Effects of antisense oligonucleotide-mediated depletion of tumor necrosis factor (TNF) receptor 1-associated death domain protein on TNF-induced gene expression

Tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) is an adaptor protein known to be involved in the TNF signaling pathway as well as signaling of other members of the TNF receptor superfamily, including DR3, DR6, p75(NTR), and the Epstein-Barr virus latent membrane protein 1. Current knowledge of the function of the adaptor protein has been derived from studies examining its over-expression in either wild-type or mutated forms. In this study, we analyzed the consequences of antisense oligonucleotide (ASO)-mediated depletion of endogenous TRADD on TNF induction of inflammation-related gene products, such as intercellular adhesion molecule-1, and associated kinase signaling pathways in human umbilical vein endothelial cells. A broader perspective of TRADD's role in TNF signaling was indicated by microarray gene expression analysis, where 20 of 24 genes that showed a 5-fold or greater increase in TNF-induced mRNA expression levels displayed a reduction in TNF-induced expression as a consequence of ASO-mediated knockdown of TRADD. Reduced activation of the nuclear factor-kappaB and c-Jun NH(2)-terminal kinase pathways, as measured by IkappaB-alpha protein levels and the extent of c-Jun phosphorylation, was also observed. These results indicate usage of antisense inhibitors of TRADD expression for modulating diseases associated with TRADD-dependent signal transduction pathways.     

Circulating serum xenoestrogens and mammographic breast density

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; P_trend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; P_trend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.     

Risk factors for postpartum depression: a retrospective investigation

OBJECTIVE: To search for a possible correlation between incidence of postpartum depression (PPD) and any of the following factors recorded in patient charts at the routine, 4-week postnatal visit: age, breast-feeding status, smoker/nonsmoker, marital status, preexisting depression and type of delivery. STUDY DESIGN: Data were obtained from 588 obstetric charts for women who gave birth between June 1, 2003, and June 1, 2004, at 3 university clinics in Tulsa, Oklahoma. RESULTS: Prior history of depression and smoking cigarettes were significant risk factors for an Edinburgh Postnatal Depression Scale score of 13 or higher, indicating probable PPD. CONCLUSION: Our data and previous findings warrant continued investigation in a larger study to clearly delineate these and other possible risk factors for PPD and to facilitate prophylactic patient education and intervention strategies.     

Screening for domestic violence in public welfare offices: an analysis of case manager and client interactions

Despite a high prevalence of domestic violence among welfare clients, most studies of the implementation of the Family Violence Option (FVO) under welfare reform find that women rarely receive domestic violence services in welfare offices. This study reviews findings from current research on the factors that improve the likelihood that women will reveal their domestic violence experiences to service personnel, and uses the guidelines drawn from this review to evaluate domestic violence screening practices in welfare offices using 782 transcribed interviews between welfare workers and clients from 11 sites in four states. The analysis found that only 9.3% of case encounters involved screening for domestic violence. Screening rates differed by state, interview type, and length of worker employment. Qualitative analysis of the interviews showed that the majority of screening by workers was routine or consisted of informing clients of the domestic violence policy without asking about abuse. Only 1.2% of the interviews incorporated at least two of the procedures that increase the likelihood of disclosure among domestic violence survivors, suggesting deeply inadequate approaches to screening for abuse within the context of welfare offices, and a need for improved training, protocol, and monitoring of FVO implementation.     

Engineering the follicle microenvironment

In vitro ovarian follicle culture provides a tool to investigate folliculogenesis, and may one day provide women with fertility-preservation options. The application of tissue engineering principles to ovarian follicle maturation may enable the creation of controllable microenvironments that will coordinate the growth of the multiple cellular compartments within the follicle. Three-dimensional culture systems can preserve follicle architecture, thereby maintaining critical cell-cell and cell-matrix signaling lost in traditional two-dimensional attached follicle culture systems. Maintaining the follicular structure while manipulating the biochemical and mechanical environment will enable the development of controllable systems to investigate the fundamental biological principles underlying follicle maturation. This review describes recent advances in ovarian follicle culture, and highlights the tissue engineering principles that may be applied to follicle culture, with the ultimate objective of germline preservation for females facing premature infertility.     

美国、德国医疗保险服务协议相关法律问题及对中国的启示

重点对美国医疗保险经办机构和医疗机构的关系、医疗保险申请、医疗服务协议的协商谈判机制、工作程序、医疗保险的支付方式,经费报销结算计算及医保纠纷解决五步上诉机制等相关法律问题,以及德国的医疗保险模式和医疗服务协议相关情况进行了综述介绍,在此基础上论述了美、德医疗保险服务协议相关法律问题对我国的启示。     

Instituting a Curriculum for Cardio-Obstetrics Subspecialty Fellowship Training

Maternal mortality is rising in the United States, and cardiovascular disease is the leading cause. Adverse pregnancy outcomes such as preeclampsia and gestational diabetes heighten the risk of cardiovascular complications during pregnancy and the peripartum period and are associated with long-term cardiovascular risks. The field of cardio-obstetrics is a subspecialty within adult cardiology that focuses on the management of women with or at high risk for heart disease who are considering pregnancy or have become pregnant. There is growing recognition of the need for more specialists with dedicated expertise in cardio-obstetrics to improve the cardiovascular care of this high-risk patient population. Current recommendations for cardiovascular fellowship training programs accredited by the Accreditation Council for Graduate Medical Education involve establishing core competency in the knowledge of managing heart disease in pregnancy. However, little granular detail is available of what such training should entail, which can lead to knowledge gaps. Additionally, dedicated advanced subspecialty training in this area is not commonly offered. Multidisciplinary collaborative teams have been shown to improve outcomes in cardiac patients during pregnancy, and cardiovascular fellows-in-training interested in cardio-obstetrics should have the opportunity to participate in and contribute to a pregnancy heart team. In this document, we describe a proposed specialized cardio-obstetrics training pathway that could serve to adequately prepare trainees to competently and comprehensively care for women with cardiovascular disease before, during, and after pregnancy.