Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research.

BackgroundThe long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman's life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention.Main textDespite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland's structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals-including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols-and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers.ConclusionsAn integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective

"The Bottle Is My Wife": Exploring Reasons Why Men Drink Alcohol in Ugandan Fishing Communities.

Fishing communities in Uganda have high rates of excessive alcohol consumption and negative health outcomes related to alcohol consumption, such as HIV acquisition and transmission and intimate partner violence victimization and perpetration. Research lacks understanding of alcohol use in Ugandan fishing communities, underlying reasons for excessive drinking among fishermen or how their community perceives negative health outcomes linked to excessive alcohol consumption. This qualitative study was conducted among Ugandan fisherfolk to determine why excessive alcohol consumption has overtaken their communities. Through analyzing in-depth interviews and focus group discussions, reasons for drinking and community perceptions of drinking were explored using the Socio Ecological Model and the Time Perspective Theory. Interviews were coded into two content themes: social influences on drinking and using alcohol to cope with stress. Participants acknowledged links between excessive alcohol consumption and negative health outcomes within their families and communities. These findings highlight the need for alcohol-related reduction interventions that are sensitive to contextual factors and self-identified contributors to problematic alcohol use within individuals and their communities. Such interventions must consider the social, ecological and economic conditions within fishing sites, focusing not only on individual-level behavioral change but also challenging the underlying structures that foster excessive alcohol consumption

Numerical Simulations of Gravity-Driven Fingering in Unsaturated Porous Media Using a Non-Equilibrium Model

This is a computational study of gravity-driven fingering instabilities in unsaturated porous media. The governing equations and corresponding numerical scheme are based on the work of Nieber et al. [Ch. 23 in Soil Water Repellency, eds. C. J. Ritsema and L. W. Dekker, Elsevier, 2003] in which non-monotonic saturation profiles are obtained by supplementing the Richards equation with a non-equilibrium capillary pressure-saturation relationship, as well as including hysteretic effects. The first part of the study takes an extensive look at the sensitivity of the finger solutions to certain key parameters in the model such as capillary shape parameter, initial saturation, and capillary relaxation coefficient. The second part is a comparison to published experimental results that demonstrates the ability of the model to capture realistic fingering behaviour

Estudio comparativo sobre las medidas implementadas por los países de Colombia y México frente a la crisis migratoria

Trabajo de investigaciónEn la actualidad la migración a nivel mundial se ha incrementado notablemente, por los problemas económicos y políticos que algunos países enfrentan, generando así que la mayoría de sus habitantes decidan salir a buscar mejores oportunidades, en otros países, como en este caso de estudio Colombia y México, por tal motivo se busca realizar un estudio comparativo sobre las diferentes medidas que han implementado estos países, y las medidas proteccionistas, con el fin de conocer el manejo que se ha brindado a esta misma problemática.RESUMEN INTRODUCCIÓN MARCO TEÓRICO CONCLUSIONES 1 ANEXOSEspecializaciónEspecialista en Formulación y Evaluación Social y Económica de Proyecto

SHP-1 negatively regulates neuronal survival by functioning as a TrkA phosphatase

Nerve growth factor (NGF) mediates the survival and differentiation of neurons by stimulating the tyrosine kinase activity of the TrkA/NGF receptor. Here, we identify SHP-1 as a phosphotyrosine phosphatase that negatively regulates TrkA. SHP-1 formed complexes with TrkA at Y490, and dephosphorylated it at Y674/675. Expression of SHP-1 in sympathetic neurons induced apoptosis and TrkA dephosphorylation. Conversely, inhibition of endogenous SHP-1 with a dominant-inhibitory mutant stimulated basal tyrosine phosphorylation of TrkA, thereby promoting NGF-independent survival and causing sustained and elevated TrkA activation in the presence of NGF. Mice lacking SHP-1 had increased numbers of sympathetic neurons during the period of naturally occurring neuronal cell death, and when cultured, these neurons survived better than wild-type neurons in the absence of NGF. These data indicate that SHP-1 can function as a TrkA phosphatase, controlling both the basal and NGF-regulated level of TrkA activity in neurons, and suggest that SHP-1 regulates neuron number during the developmental cell death period by directly regulating TrkA activity

Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies

Many challenges exist in the precise diagnosis and clinical management of secondary progressive multiple sclerosis (SPMS) because of the lack of definitive clinical, imaging, immunologic, or pathologic criteria that demarcate the transition from relapsing-remitting MS to SPMS. This review provides an overview of the diagnostic criteria/definition and the heterogeneity associated with different SPMS patient populations; it also emphasizes the importance of available prospective/retrospective tools to identify patients with SPMS earlier in the disease course so that approved disease-modifying therapies and nonpharmacological strategies will translate into better outcomes. Delivery of such interventions necessitates an evolving patient-clinician dialog within the context of a multidisciplinary team

Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer

epithelial reprogramming in breast cance