Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

The transition between stochastic and deterministic behavior in an excitable gene circuit

We explore the connection between a stochastic simulation model and an ordinary differential equations (ODEs) model of the dynamics of an excitable gene circuit that exhibits noise-induced oscillations. Near a bifurcation point in the ODE model, the stochastic simulation model yields behavior dramatically different from that predicted by the ODE model. We analyze how that behavior depends on the gene copy number and find very slow convergence to the large number limit near the bifurcation point. The implications for understanding the dynamics of gene circuits and other birth-death dynamical systems with small numbers of constituents are discussed.Comment: PLoS ONE: Research Article, published 11 Apr 201

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

Detección molecular de infecciones múltiples en mujeres con y sin lesión de cuello uterino positivas para el virus del papiloma humano de alto riesgo, período 2007-2011

El cáncer de cuello uterino, causado por el virus del papiloma humano (HPV), constituye el tercer tipo de cáncer más común en mujeres en el mundo. El objetivo del presente trabajo fue determinar por reacción en cadena de la polimerasa seguida de hibridación reversa, la frecuencia de infecciones múltiples en mujeres positivas para HPV de alto riesgo oncogénico por captura híbrida II, según severidad de la lesión escamosa intraepitelial (SIL), carga viral relativa y edad, en el periodo 2007-2011. Este estudio de corte transverso incluyó 123 mujeres que acudieron al Instituto de Investigaciones en Ciencias de la Salud, 18 sin lesión (NSIL), 78 con SIL de bajo grado (LSIL) y 27 con SIL de alto grado (HSIL). Se detectaron infecciones múltiples en 37/123 mujeres (30,1%). Las mujeres con NSIL presentaron menor frecuencia de infecciones múltiples (5,6%) que las mujeres con SIL (34,3%) (p=0,03). No se observó aumento de frecuencia de infecciones múltiples con la severidad de la lesión, presentando las mujeres con LSIL un 34,6% y con HSIL, un 33,3%. No fue observada diferencia significativa entre la carga viral relativa de infecciones simples y múltiples, lo cual sugiere que en la infección múltiple podría ser solo uno de los tipos de HPV el que se esté replicando, causando una infección productiva. Además, se observó una alta frecuencia de infecciones múltiples (75%) en mujeres menores a 30 años. Finalmente los resultados sugieren que las infecciones múltiples podrían orientar la presencia de SIL, pero no el grado de severidad de la lesión cervical

Reorganisation of Wnt-response pathways in colorectal tumorigenesis

In most colorectal tumours, APC mutation stabilises β-catenin and mimics elements of Wnt growth factor signalling, but the high frequency of epigenetic loss of Wnt antagonists indicates an additional role for ligand-mediated Wnt signalling. Here, we have investigated the expression of key components of β-catenin-independent Wnt response pathways to determine whether their profiles change during the transition from normal mucosa to colorectal adenomas. Transcription of the Wnt/planar cell polarity pathway determinant NKD1 (naked cuticle homologue 1) was induced in adenomas by a median 135-fold and in cancers by 7.4-fold. While some Frizzleds (FZDs) were downregulated in adenomas, the Wnt/Ca2+ receptors FZD3 and FZD6 were induced by a median factor of 6.5 and 4.6, respectively. Naked cuticle homologue 1, FZD3 and FZD6 expression were coordinated in pre-malignant disease, but this relationship was lost in invasive cancers, where FZD induction was seen less frequently. Naked cuticle homologue 1 expression was associated with nuclear localisation of phospho-c-Jun in adenomas. In cultured cells, NKD1 transcription was induced by lithium chloride but FZD3 expression required Wnt growth factor treatment. These data show that Wnt responses are consistently directed towards both β-catenin-independent routes in early colorectal tumorigenesis and elements of this are retained in more advanced cancers. These β-catenin-independent Wnt signalling pathways may provide novel targets for chemoprevention of early colorectal tumours

Activation of the B cell receptor leads to increased membrane proximity of the Igα cytoplasmic domain.

Binding of antigen to the B cell receptor (BCR) induces conformational changes in BCR's cytoplasmic domains that are concomitant with phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs). Recently, reversible folding of the CD3ε and ξ chain ITAMs into the plasma membrane has been suggested to regulate T cell receptor signaling. Here we show that the Igα and Igβ cytoplasmic domains of the BCR do not associate with plasma membrane in resting B cells. However, antigen binding and ITAM phosphorylation specifically increased membrane proximity of Igα, but not Igβ. Thus, BCR activation is accompanied by asymmetric conformational changes, possibly promoting the binding of Igα and Igβ to differently localized signaling complexes

Reproductive medicine in northwest Argentina: traditional and institutional systems

<p>Abstract</p> <p>Background</p> <p>The state of conservation of the traditional cultures of Northwest Argentina is variable and somewhat problematic but to a lesser or a greater extent all the peoples are related to an hegemonic culture. We present a case study carried out in the rural communities of the Yungas biome (Salta) where the extent of isolation varies as does the type of access to public health services. The use of medicinal plants in the area is ordinary and widely spread.</p> <p>Methods</p> <p>The data can be organized in two categories, as medical systems public records (for the regional hospital at Los Toldos), and as ethnobotanical sets. A total of 59 surveys to 40 interviewees were undertaken using a semi structured questionnaire. We present an analysis of the relative importance of the medicinal herbs used in reproductive medicine considering the plants used in the traditional medical system and the factors that can affect the relationship between formal medicine and patients. We further analized how the degree of accessibility to the local hospital influences the diversity of use of plant species used to assist deliveries and to decrease infant mortality in children minor than one year of age.</p> <p>Results</p> <p>In reproductive medicine, 13 ailments and/or different physiological states are locally identified and treated. Local population uses 108 ethnospecies for this kind of illnesses. According to the local conception the hot/cold imbalance could be the principal cause for reproductive illnesses; pregnancy may have natural or supernatural origin, post partum and menstruation involve similar sanitary risks, and neonatal care has a strong magic connotation. In relation with the formal medicine, the more accessible is the health center the more women assist to it. We have not found a relation between accessibility and infant mortality.</p> <p>Conclusion</p> <p>In the local reproductive medicine, most of the practices are concerned with the hot/cold balance. According to their importance the factors involved are: the family medicine, the midwife, and the formal doctors. Plants have an important role; however there is a lack of total agreement among the families who use them. Reluctance to institutional deliveries may be due to the weak relationship between patients and doctors, and the lack of logistic assistance to delivering mothers coming from far away locations.</p