"Part and Parcel of Being a Woman": Female Urinary Incontinence and Constructions of Control

This article draws on extensive interviews with middle-aged Australian women experiencing urinary incontinence. Our discussion derives from the difficulties women face in seeking advice on the management of incontinence, as a consequence of their perception that the condition is an inevitability, a "normal" part of being female. Women do not, on the whole, support a single cause for incontinence but, rather, explain its incidence in terms of personal history, which may include childbearing and parturition, menopause and aging, and early socialization. In addition, women link their own continence problems with perceived personal failings (e.g., lack of exercise, being overweight) and, hence, see the condition as a symbol of their lack of moral worth. Following this, women's understandings of the relationship of incontinence to their social membership extend far beyond the difficulties of disguising their physical problems.     

Down syndrome: interaction between culture, demography, and biology in determining the prevalence of a genetic trait

The incidence of Down syndrome (DS) at conception is highly dependent upon the maternal age distribution and age-specific pregnancy rates. Live-birth prevalence of DS reflects these factors and fetal deaths. Since the introduction of prenatal diagnosis in the early 1970s, the role of fetal deaths in the equation has increased. Between 1920 and the early 1980s, DS live-birth prevalence decreased in many populations due to declining fertility rates, particularly among older women. In the late-1970s the trend reversed, as the median age of populations and birth rates among older women steadily increased. This paper illustrates these interactions using data we have analyzed for New York State (NYS) and comparative data obtained from the literature. Between 1983 and 1997 DS live-birth prevalence in NYS remained stable at about 9.9 per 10,000 live births. The number of prenatal tests performed increased by 158%, and the number of DS fetuses detected prenatally more than quadrupled. Fertility rates of women aged 35-49 continued to increase. The proportion of DS cases born to these older mothers increased from 23% in 1985 to 43% in 1997. We estimated that without prenatal diagnosis, DS live-birth prevalence would have been 17.0 per 10,000 live births by 1995. Cultural factors influence demographic trends, birthing technologies, physician practices, and women's decision-making regarding prenatal screening and diagnosis for DS.     

Human cytomegalovirus transmission from the uterus to the placenta correlates with the presence of pathogenic bacteria and maternal immunity

Prenatal cytomegalovirus infection may cause pregnancy complications such as intrauterine growth restriction and birth defects. How virus from the mother traverses the placenta is unknown. PCR analysis of biopsy specimens of the maternal-fetal interface revealed that DNA sequences from cytomegalovirus were commonly found with those of herpes simplex viruses and pathogenic bacteria. Cytomegalovirus DNA and infected cell proteins were found more often in the decidua than in the placenta, suggesting that the uterus functions as a reservoir for infection. In women with low neutralizing titers, cytomegalovirus replicated in diverse decidual cells and placental trophoblasts and capillaries. In women with intermediate to high neutralizing titers, decidual infection was suppressed and the placenta was spared. Overall, cytomegalovirus virions and maternal immunoglobulin G were detected in syncytiotrophoblasts, villus core macrophages, and dendritic cells. These results suggest that the outcome of cytomegalovirus infection depends on the presence of other pathogens and coordinated immune responses to viral replication at the maternal-fetal interface.     

Interaction of related Tn916-like transposons: analysis of excision events promoted by Tn916 and Tn5386 integrases

In recent work, we described the excision of a large genomic region from Enterococcus faecium D344R in which the sequence from "joint" regions suggested that excision resulted from the interaction of conjugative transposon Tn916 and the related mobile element Tn5386. In the present study, we examined the ability of integrases and integrase-excisase combinations from Tn916 and Tn5386 to promote the excision of constructs consisting of the termini of Tn916, Tn5386, and the VanB mobile element Tn5382. Integrases alone from either Tn916 or Tn5386 promoted the circularization of constructs from the three different transposons, even when the different termini used in the constructs were discordant in their transposon of origin. The termini of Tn916 and Tn5382 found in all joints were consistent with previously identified Tn916 and Tn5382 termini. Substantial variation was seen in the integrase terminus of Tn5386 used to form joints, regardless of the integrase that was responsible for circularization. Variability was observed in joints formed from Tn5386 constructs, in contrast to joints observed with the termini of Tn916 or Tn5382. The coexpression of excisase yielded some variability in the joint regions observed. These data confirm that integrases from some Tn916-like elements can promote circularization with termini derived from heterologous transposons and, as such, could promote excision of large genomic regions flanked by such elements. These findings also raise interesting questions about the sequence specificities of the C terminals of Tn916-like integrases, which bind to the ends and facilitate strand exchange.     

Community and school-based health education for dengue control in rural Cambodia: a process evaluation

Dengue fever continues to be a major public health problem in Cambodia, with significant impact on children. Health education is a major means for prevention and control of the National Dengue Control Program (NDCP), and is delivered to communities and in schools. Drawing on data collected in 2003-2004 as part of an ethnographic study conducted in eastern Cambodia, we explore the approaches used in health education and their effectiveness to control dengue. Community health education is provided through health centre outreach activities and campaigns of the NDCP, but is not systematically evaluated, is under-funded and delivered irregularly; school-based education is restricted in terms of time and lacks follow-up in terms of practical activities for prevention and control. As a result, adherence is partial. We suggest the need for sustained routine education for dengue prevention and control, and the need for approaches to ensure the translation of knowledge into practice.     

The unique N‐terminal insert in the ribosomal protein,phosphoprotein P0, of Tetrahymena thermophila: Bioinformatic evidence for an interaction with 26S rRNA

Phosphoprotein P0 (P0) is part of the stalk complex of the eukaryotic large ribosomal subunit necessary for recruiting elongation factors. While the P0 sequence is highly conserved, our group noted a 15–16 residue insert exclusive to the P0s of ciliated protists, including Tetrahymena thermophila. We hypothesized that this insert may have a function unique in ciliated protists, such as stalk regulation via phosphorylation of the insert. Almost no mention of this insert exists in the literature, and although the T. thermophila ribosome has been crystallized, there is limited structural data for Tetrahymena's P0 (TtP0) and its insert. To investigate the structure and function of the TtP0 insert, we performed in silico analyses. The TtP0 sequence was scanned with phosphorylation site prediction tools to detect the likelihood of phosphorylation in the insert. TtP0's sequence was also used to produce a homology model of the N‐terminal domain of TtP0, including the insert. When the insert was modeled in the context of the 26S rRNA, it associated with a region identified as expansion segment 7B (ES7B), suggesting a potential functional interaction between ES7B and the insert in T. thermophila. We were not able to obtain sufficient data to determine whether a similar relationship exists in other ciliated protists. This study lays the groundwork for future experimental studies to verify the presence of TtP0 insert/ES7 interactions in Tetrahymena, and to explore their functional significance during protein synthesis. Proteins 2015; 83:1078–1090. © 2015 Wiley Periodicals, Inc.     

Human cytomegalovirus interleukin-10 downregulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasiveness in vitro

At the uterine-placental interface, fetal cytotrophoblasts invade the decidua, breach maternal blood vessels, and form heterotypic contacts with uterine microvascular endothelial cells. In early gestation, differentiating- invading cytotrophoblasts produce high levels of matrix metalloproteinase 9 (MMP-9), which degrades the extracellular matrix and increases the invasion depth. By midgestation, when invasion is complete, MMP levels are reduced. Cytotrophoblasts also produce human interleukin-10 (hIL-10), a pleiotropic cytokine that modulates immune responses, helping to protect the fetal hemiallograft from rejection. Human cytomegalovirus (CMV) is often detected at the uterine-placental interface. CMV infection impairs cytotrophoblast differentiation and invasion, altering the expression of the cell adhesion and immune molecules. Here we report that infection with a clinical CMV strain, VR1814, but not a laboratory strain, AD169, downregulates MMP activity in uterine microvascular endothelial cells and differentiating-invading cytotrophoblasts. Infected cytotrophoblasts expressed CMV IL-10 (cmvIL-10) mRNA and secreted the viral cytokine, which upregulated hIL-10. Functional analyses showed that cmvIL-10 treatment impaired migration in endothelial cell wounding assays and cytotrophoblast invasion of Matrigel in vitro. Comparable changes occurred in cells that were exposed to recombinant hIL-10 or cmvIL-10. Our results show that cmvIL-10 decreases MMP activity and dysregulates the cell-cell and/or cell-matrix interactions of infected cytotrophoblasts and endothelial cells. Reduced MMP activity early in placental development could impair cytotrophoblast remodeling of the uterine vasculature and eventually restrict fetal growth in affected pregnancies.     

Insights into viral transmission at the uterine-placental interface

During human gestation, viruses can cause intrauterine infections associated with pregnancy complications and fetal abnormalities. The ability of viruses to spread from the infected mother to the fetus arises from the architecture of the placenta, which anchors the fetus to the uterus. Placental cytotrophoblasts differentiate, assume an endothelial phenotype, breach uterine blood vessels and form a hybrid vasculature that amplifies the maternal blood supply for fetal development. Human cytomegalovirus - the major cause of congenital disease - infects the uterine wall and the adjacent placenta, suggesting adaptation for pathogen survival in this microenvironment. Infection of villus explants and differentiating and/or invading cytotrophoblasts offers an in vitro model for studying viruses associated with prenatal infections.