Globalization, Health Sector Reform, Gender and Reproductive Health

Explores the interrelationships between globalization and health sector reforms, and how changes in macro-economic and social policies affect women's reproductive health and rights

Firearms, Youth Homicide, and Public Health

Homicide is seven times as common among U.S. non-Hispanic Black as among non-Hispanic White youth ages 15 to 24 years. In 83% of these youth homicides, the murder weapon is a firearm. Yet, for more than a decade, the national public health position on youth violence has been largely silent about the role of firearms, and tools used by public health professionals to reduce harm from other potential hazards have been unusable where guns are concerned. This deprives already underserved populations from the full benefits public health agencies might be able to deliver. In part, political prohibitions against research about direct measures of firearm control and the absence of valid public health surveillance are responsible. More refined epidemiologic theories as well as traditional public health methods are needed if the U.S. aims to reduce disparate Black-White youth homicide rates

Lithium enhances cortical mRNA expression in ovariectomized C57BL/6J mice

The hippocampus and cortex of the mammalian brain are regions involved in learning and long-term memory. Estrogen and lithium affect similar learning and memory molecular processes. We hypothesized that in ovariectomized mice lithium treatment will enhance genetic factors in the brain that are involved in neuroprotection, learning and memory. Our study used bilaterally ovariectomized (bOVX) C57BL÷6J mice treated for one month with 14.2 mM LiCl in their drinking water. Results indicate that LiCl-treated bOVX mice show enhanced cortical increases in mRNA expression of ER-alpha, NR1, Bcl-2, BDNF, and CaMkII-alpha; hippocampal mRNA showed no changes. Our results indicate that in bOVX C57BL÷6J mice, lithium enhances the expression of specific cortical genes coded for proteins involved in learning, memory and neuroprotection

A Dyadic Approach to Managing Heart Failure with Confidence

Background: The majority of heart failure (HF) self-care research remains focused on patients, despite the important involvement of family caregivers. Although self-care confidence has been found to play an important role in the effectiveness of HF self-care management on patient outcomes, no known research has examined self-care confidence within a dyadic context. Objective: The purpose of this study was to identify individual and dyadic determinants of self-care confidence in HF care dyads. Methods: Multilevel modeling, which controls for the interdependent nature of dyadic data, was used to examine 329 Italian HF dyads (caregivers were either spouses or adult children). Results: Both patients and caregivers reported lower-than-adequate levels of confidence, with caregivers reporting slightly higher confidence than patients. Patient and caregiver levels of confidence were significantly associated with greater patient-reported relationship quality and better caregiver mental health. Patient confidence in self-care was significantly associated with patient female gender, nonspousal care dyads, poor caregiver physical health, and low care strain. Caregiver confidence to contribute to self-care was significantly associated with poor emotional quality of life in patients and greater perceived social support by caregivers. Conclusions: Findings are supportive of the need for a dyadic perspective of HF self-care in practice and research as well as the importance of addressing the needs of both members of the dyad to maximize optimal outcomes for both

The Public Health Exposome: A Population-Based, Exposure Science Approach to Health Disparities Research

The lack of progress in reducing health disparities suggests that new approaches are needed if we are to achieve meaningful, equitable, and lasting reductions. Current scientific paradigms do not adequately capture the complexity of the relationships between environment, personal health and population level disparities. The public health exposome is presented as a universal exposure tracking framework for integrating complex relationships between exogenous and endogenous exposures across the lifespan from conception to death. It uses a social-ecological framework that builds on the exposome paradigm for conceptualizing how exogenous exposures “get under the skin”. The public health exposome approach has led our team to develop a taxonomy and bioinformatics infrastructure to integrate health outcomes data with thousands of sources of exogenous exposure, organized in four broad domains: natural, built, social, and policy environments. With the input of a transdisciplinary team, we have borrowed and applied the methods, tools and terms from various disciplines to measure the effects of environmental exposures on personal and population health outcomes and disparities, many of which may not manifest until many years later. As is customary with a paradigm shift, this approach has far reaching implications for research methods and design, analytics, community engagement strategies, and research training

Erratum: Author Correction: Midbrain Circuit Regulation of Individual Alcohol Drinking Behaviors in Mice (Nature Communications (2017) 8 1 (2220))

The original version of this Article contained an error in the spelling of the author Scott Edwards, which was incorrectly given as Scott Edward. This has now been corrected in both the PDF and HTML versions of the Article

A Novel Function for Fragile X Mental Retardation Protein in Translational Activation

Fragile X syndrome, the most frequent form of inherited mental retardation, is due to the absence of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in several steps of RNA metabolism. To date, two RNA motifs have been found to mediate FMRP/RNA interaction, the G-quartet and the “kissing complex,” which both induce translational repression in the presence of FMRP. We show here a new role for FMRP as a positive modulator of translation. FMRP specifically binds Superoxide Dismutase 1 (Sod1) mRNA with high affinity through a novel RNA motif, SoSLIP (Sod1 mRNA Stem Loops Interacting with FMRP), which is folded as three independent stem-loop structures. FMRP induces a structural modification of the SoSLIP motif upon its interaction with it. SoSLIP also behaves as a translational activator whose action is potentiated by the interaction with FMRP. The absence of FMRP results in decreased expression of Sod1. Because it has been observed that brain metabolism of FMR1 null mice is more sensitive to oxidative stress, we propose that the deregulation of Sod1 expression may be at the basis of several traits of the physiopathology of the Fragile X syndrome, such as anxiety, sleep troubles, and autism

Ciudad-territorio sustentable. Procesos, actores y estructuras

En los últimos años, los estudios urbanos especializados insisten en que los procesos de urbanización por los que atraviesan los distintos países desarrollados, parecen dejar atrás las explicaciones de la urbanización industrial, han surgido otras construcciones y perspectivas unas más acabadas que otras (Indovina, 1998, la “ciudad difusa”; Dematteis 1998, ciudad sin centros; Nel-lo, 1998 ciudad sin confines, Soja, 2008, la exópolis). En suma se dice que se avanza hacia la urbanización generalizada, ello acaba con la larga trayectoria del funcionamiento y naturaleza de la ciudad moderna, el cambio urbano estructural actual, es nuevamente, consecuencia de la descentralización, difusión, redistribución del desarrollo, del crecimiento y las innovaciones ahora sobre una estructura en el territorio. Ha sido una mutación no sólo empírica sino que ha dado lugar a la confrontación teórica. El sistema urbano jerárquico ha reducido su valor interpretativo porque se han modificado los supuestos en los que se basaban las relaciones de dominio y dependencia de los centros principales, porque se han abaratado los costos de transporte y el efecto de la distancia ya no es una limitante absoluta, ahora los procesos productivos flexibles y descentralizados propician las relaciones técnicas horizontales con lo cual se consiguen economías de escala externas e internas a las empresas en un territorio ampliado y no sólo exclusivamente en la aglomeración económica (Precedo, 2003; Veltz, 1999; Boix, 2002; Camagni, 2005; De Santiago, 2008 y; Garmendia, 2010).El objetivo es examinar dentro de la descentralización del proceso urbano a la ciudad-territorio en América Latina, en particular en México. En contextos urbanos desarrollados se afirma la convergencia urbana con la apertura de las unidades funcionales de los sistemas urbanos donde operan redes e interrelaciones de desarrollo cualitativo en el territorio. América Latina registra evidencias empíricas poco claras, existe alta concentración de aquella economía que contribuye al crecimiento nacional, mientras la población se descentraliza rápidamente. México, es un caso de primacía urbana histórica aunque da paso a la formación de regiones urbanas, mismas que reproducen relaciones polarizadas y escasamente descentralizadas. De manera que, en tanto domine la concentración espacial económica, la ciudadterritorio se podrá presentar en el continente sólo con algunos rasgos en regiones urbanas con mayor desarrollo y crecimiento. Palabras claves: descentralización urbana, sistema urbano, ciudad-territorio

An Osteoblast-Derived Proteinase Controls Tumor Cell Survival via TGF-beta Activation in the Bone Microenvironment

Breast to bone metastases frequently induce a "vicious cycle" in which osteoclast mediated bone resorption and proteolysis results in the release of bone matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis of human breast to bone metastases unexpectedly revealed that bone forming osteoblasts were consistently positive for the proteinase, MMP-2. Given the role of MMP-2 in extracellular matrix degradation and growth factor/cytokine processing, we tested whether osteoblast derived MMP-2 contributed to the vicious cycle of tumor progression in the bone microenvironment.To test our hypothesis, we utilized murine models of the osteolytic tumor-bone microenvironment in immunocompetent wild type and MMP-2 null mice. In longitudinal studies, we found that host MMP-2 significantly contributed to tumor progression in bone by protecting against apoptosis and promoting cancer cell survival (caspase-3; immunohistochemistry). Our data also indicate that host MMP-2 contributes to tumor induced osteolysis (μCT, histomorphometry). Further ex vivo/in vitro experiments with wild type and MMP-2 null osteoclast and osteoblast cultures identified that 1) the absence of MMP-2 did not have a deleterious effect on osteoclast function (cd11B isolation, osteoclast differentiation, transwell migration and dentin resorption assay); and 2) that osteoblast derived MMP-2 promoted tumor survival by regulating the bioavailability of TGFβ, a factor critical for cell-cell communication in the bone (ELISA, immunoblot assay, clonal and soft agar assays).Collectively, these studies identify a novel "mini-vicious cycle" between the osteoblast and metastatic cancer cells that is key for initial tumor survival in the bone microenvironment. In conclusion, the findings of our study suggest that the targeted inhibition of MMP-2 and/or TGFβ would be beneficial for the treatment of bone metastases

Midbrain circuit regulation of individual alcohol drinking behaviors in mice

Alcohol-use disorder (AUD) is the most prevalent substance-use disorder worldwide. There is substantial individual variability in alcohol drinking behaviors in the population, the neural circuit mechanisms of which remain elusive. Utilizing in vivo electrophysiological techniques, we find that low alcohol drinking (LAD) mice have dramatically higher ventral tegmental area (VTA) dopamine neuron firing and burst activity. Unexpectedly, VTA dopamine neuron activity in high alcohol drinking (HAD) mice does not differ from alcohol naive mice. Optogenetically enhancing VTA dopamine neuron burst activity in HAD mice decreases alcohol drinking behaviors. Circuit-specific recordings reveal that spontaneous activity of nucleus accumbens-projecting VTA (VTA-NAc) neurons is selectively higher in LAD mice. Specifically activating this projection is sufficient to reduce alcohol consumption in HAD mice. Furthermore, we uncover ionic and cellular mechanisms that suggest unique neuroadaptations between the alcohol drinking groups. Together, these data identify a neural circuit responsible for individual alcohol drinking behaviors