Neonatal Androgenization Exacerbates Alcohol-Induced Liver Injury in Adult Rats, an Effect Abrogated by Estrogen

Alcoholic liver disease (ALD) affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2) and ethanol metabolizing enzymes (cytochrome P450, CYP450) are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl), androgenized females (Andro) and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood

Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain

The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in repair and reconstruction of the damaged brain. Two partially overlapping and complimentary functional macrophage states have been identified and are called alternative activation and acquired deactivation. The immunosuppressive and repair processes of each of these states and how alternative activation and acquired deactivation participate in chronic neuroinflammation in the brain are discussed

Design and evaluation of electron beam energy degraders for breast boost irradiation

BACKGROUND: For breast cancer patients who require electron boost energies between 6 and 9 MeV, an energy degraders (ED) in the 9 MeV beamline was specially designed and manufactured to increase the skin dose of 6 MeV and to reduce the penetration depth of 9 MeV beams. METHODS: We used Monte Carlo (MC) techniques as a guide in the design of ED for use with linear accelerators. In order to satisfy percent depth dose (PDD) characteristics and dose profile uniformity in water, the shape and thickness of Lucite® ED in the 9 MeV beamline was iteratively optimized and then manufactured. The ED geometry consists of a truncated cone attached on top of a plane plate, with total central thickness of 1.0 cm. The ED was placed on the lower most scraper of the electron applicator. The PDDs, profiles, and output factors were measured in water to validate the MC-based design. RESULTS: Skin doses with the EDs increased by 8–9 %, compared to those of the 9 MeV beam. The outputs with the EDs were 0.882 and 0.972 for 10 × 10 and 15 × 15 cm(2) cones, respectively, as compared to that of a conventional 9 MeV beam for a 10 × 10 cm(2) cone. The X-ray contamination remained less than 1.5 %. In-vivo measurements were also performed for three breast boost patients and showed close agreement with expected values. CONCLUSIONS: The optimally designed ED in the 9 MeV beamline provides breast conserving patients with a new energy option of 7 MeV for boost of the shallow tumor bed. It would be an alternative to bolus and thus eliminate inconvenience and concern about the daily variation of bolus setup

Child and family experiences with inborn errors of metabolism: a qualitative interview study with representatives of patient groups

© 2015, The Author(s). Background: Patient-centered health care for children with inborn errors of metabolism (IEM) and their families is important and requires an understanding of patient experiences, needs, and priorities. IEM-specific patient groups have emerged as important voices within these rare disease communities and are uniquely positioned to contribute to this understanding. We conducted qualitative interviews with IEM patient group representatives to increase understanding of patient and family experiences, needs, and priorities and inform patient-centered research and care. Methods: We developed a sampling frame of patient groups representing IEM disease communities from Canada, the United States, and United Kingdom. With consent, we interviewed participants to explore their views on experiences, needs, and outcomes that are most important to children with IEM and their families. We analyzed the data using a qualitative descriptive approach to identify key themes and sub-themes. Results: We interviewed 18 organizational representatives between February 28 and September 17, 2014, representing 16 IEMs and/or disease categories. Twelve participants voluntarily self-identified as parents and/or were themselves patients. Three key themes emerged from the coded data: managing the uncertainty associated with raising and caring for a child with a rare disease; challenges associated with the affected child’s life transitions, and; the collective struggle for improved outcomes and interventions that rare disease communities navigate. Conclusion: Health care providers can support children with IEM and their families by acknowledging and reducing uncertainty, supporting families through children’s life transitions, and contributing to rare disease communities’ progress toward improved interventions, experiences, and outcomes.The study was partially funded by the Rare Disease Foundation (RDF). In-kind support was provided by the Canadian Inherited Metabolic Diseases Research Network (CIMDRN) which is funded by the Canadian Institutes of Health Research (CIHR, grant TR3-119197) and administered by the University of Ottawa

Perceived Risk and Condom Use among Adolescents in Sub-Saharan Africa: A Latent Class Analysis

While studies have examined factors associated with condom use behaviors, few have assessed risk perception and condom use among SSA adolescents. This work sought to fill this gap. Data for this study are derived from the National Survey of Adolescents (2004-2005), a survey of 12-19 year olds in Burkina Faso, Ghana, Malawi, and Uganda. Latent class analysis was conducted. Two risk profiles emerged in the data. Percent of adolescents in the high perceived risk sub-groups ranged from 49.6% - 90.8% and moderate risk from 29.1-83.8%. Those in the high perceived risk class were 2.26 to 5.10 times more likely to report condom use. The findings provide additional information about the factors that influence condom use among adolescents in these four countries. Because an individual’s development is influenced by his/her settings and systems, expanded views of behavior must be included in prevention efforts.Keywords: Condom Use, Knowing Someone with HIV/AIDS, Perceived Risk, Health Belief, sub-Saharan AfricaAlors que des études ont étudié les facteurs associés aux comportements de l’utilisation du préservatif, il n’y en a que très peu qui ont évalué la perception du risque et l'utilisation du préservatif chez les adolescents d'Afrique subsaharienne. Ce travail a cherché à combler cette lacune. Les données pour cette étude sont tirées de l'Enquête nationale auprès des adolescents (2004-2005), une enquête auprès des adolescents âgés de 12 à 19 ans au Burkina Faso, au Ghana, au Malawi et en Ouganda. L’analyse de structure latente a été menée. Deux profils de risque sont apparus dans les données. Le pourcentage des adolescents dans les sous-groupes à risque élevé perçus variait de 49,6% - 90,8% et un risque modéré de 29,1 à 83,8%. Ceux de la classe de risque perçu élevé étaient 2.26 à 5.10 fois plus susceptibles de déclarer l'utilisation du préservatif. Les résultats fournissent des informations supplémentaires sur les facteurs qui influencent l'utilisation du préservatif chez les adolescents dans ces quatre pays. Parce que le développement d'un individu est influencé par ses paramètres et ses systèmes, il faut inclure des vues élargies de comportement dans les efforts de prévention. Mots-clés: utilisation du préservatif, connaissance d'une personne atteinte du VIH / sida, risque perçu, croyance à la santé, Afrique sub-saharienn

Network support, technology use, depression, and ART adherence among HIV-positive MSM of color.

Depression is associated with poor antiretroviral therapy (ART) adherence among people living with HIV/AIDS. This relationship may be moderated by an individual's social network characteristics. Our study sought to examine social network correlates of treatment adherence among HIV-positive men recruited from social service agencies throughout Los Angeles County (N = 150) to inform technology-driven social support interventions for this population. We administered egocentric social network and computer-assisted survey interviews focused on demographic characteristics, health history, depressive symptoms, and ART adherence, where adherence was assessed by the number of reasons participants missed taking their medication, if ever. Significant univariate correlates of adherence were included in a multivariable regression analysis, where the moderating effect of having a network member who reminds participants to take their HIV medication on the relationship between depression and adherence was tested. Over 60% of participants reported clinically significant depressive symptoms; this was significantly associated with lower adherence among those without someone in their social network to remind them about taking their HIV medication, even after adjusting for covariates in an ordinary least squares regression (adjusted mean difference b = -1.61, SE = 0.42, p = 0.0003). Having a network member who reminds participants to take their ART medication significantly ameliorated the negative association between depression and treatment adherence, especially for those reporting greater depressive symptoms (p = 0.0394). Additionally, participants demonstrated high rates of technology use to communicate with social network members. In order to achieve the aims of the National HIV/AIDS Strategy, innovative interventions addressing mental health to improve ART adherence are needed. Network strategies that leverage technology may be helpful for improving ART adherence among HIV-positive men with comorbid depressive symptoms