Discrimination, Medical Distrust, Stigma, Depressive Symptoms, Antiretroviral Medication Adherence, Engagement in Care, and Quality of Life among Women Living with HIV in North Carolina: A Mediated Structural Equation Model

Background:Women represent 23% of all Americans living with HIV. By 2020, more than 70% of Americans living with HIV are expected to be 50 years and older.Setting:This study was conducted in the Southern United States - a geographic region with the highest number of new HIV infections and deaths.Objective:To explore the moderating effect of age on everyday discrimination (EVD); group-based medical (GBM) distrust; enacted, anticipated, internalized HIV stigma; depressive symptoms; HIV disclosure; engagement in care; antiretroviral medication adherence quality of life (QOL) among women living with HIV.Methods:We used multigroup structural equation modeling to analyze baseline data from 123 participants enrolled at the University of North Carolina at Chapel Hill site of the Women's Interagency HIV Study during October 2013-May 2015.Results:Although age did not moderate the pathways hypothesized, age had a direct effect on internalized stigma and QOL. EVD had a direct effect on anticipated stigma and depressive symptoms. GBM distrust had a direct effect on depressive symptoms and a mediated effect through internalized stigma. Internalized stigma was the only form of stigma directly related to disclosure. Depressive symptoms were a significant mediator between GBM, EVD, and internalized stigma reducing antiretroviral therapy medication adherence, engagement in care, and QOL.Conclusions:EVD, GBM, and internalized stigma adversely affect depressive symptoms, antiretroviral therapy medication adherence, and engagement in care, which collectively influence the QOL of women living with HIV

Targeting Signal Transduction Pathways in Metastatic Breast Cancer: A Comprehensive Review

This review summarizes some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for the treatment of metastatic breast cancer patients

Tyrosine kinase signalling in breast cancer: Fibroblast growth factors and their receptors

The fibroblast growth factors [Fgfs (murine), FGFs (human)] constitute a large family of ligands that signal through a class of cell-surface tyrosine kinase receptors. Fgf signalling has been associated in vitro with cellular differentiation as well as mitogenic and motogenic responses. In vivo, Fgfs are critical for animal development, and some have potent angiogenic properties. Several Fgfs have been identified as oncogenes in murine mammary cancer, where their deregulation is associated with proviral insertions of the mouse mammary tumour virus (MMTV). Thus, in some mammary tumours of MMTV-infected mouse strains, integration of viral genomic DNA into the somatic DNA of mammary epithelial cells was found to have caused the inappropriate expression of members of this family of growth factors. Although examination of human breast cancers has shown an altered expression of FGFs or of their receptors in some tumours, their role in the causation of breast disease is unclear and remains controversial

Transforming growth factor-β and breast cancer: Tumor promoting effects of transforming growth factor-β

The transforming growth factor (TGF)-βs are potent growth inhibitors of normal epithelial cells. In established tumor cell systems, however, the preponderant experimental evidence suggests that TGF-βs can foster tumor-host interactions that indirectly support the viability and/or progression of cancer cells. The timing of this 'TGF-β switch' during the progressive transformation of epithelial cells is not clear. More recent evidence also suggests that autocrine TGF-β signaling is operative in some tumor cells, and can also contribute to tumor invasiveness and metastases independent of an effect on nontumor cells. The dissociation of antiproliferative and matrix associated effects of autocrine TGF-β signaling at a transcriptional level provides for a mechanism(s) by which cancer cells can selectively use this signaling pathway for tumor progression. Data in support of the cellular and molecular mechanisms by which TGF-β signaling can accelerate the natural history of tumors will be reviewed in this section

Interactive visual music

How can Visual Music be composed and presented in such an engaging way that it will turn spectators into participants? How to connect a youthful, twenty-first century audience who are keen to update their Instagram story with Visual Music? Visual Music is an art form, which is “an equal and meaningful synthesis of the visible and audible” (Lund & Lund 2009 149) and “is typically non-narrative and non-representational” (Evans 2005 11). Visual Music is often presented as cinema. Cinema audiences are generally considered to be passive spectators, whose “reactions are pre-programmed by the director, crew, cast and writer” (Mackintosh 2003 2). This paper highlights the nexus between, to use McCall’s (2004) terms ‘the cinematic, the sculptural and the pictorial’, with a focus on creating interactive Visual Music installations

Role of novel targeted therapies in the clinic

The number and variety of novel, molecular-targeted agents offers realistic hope for significant advances in cancer treatment. The potential of these new treatment approaches is unquestionable, but the reality is something that only thorough clinical evaluation and experience can reveal. Clinical experience of targeted therapies is at an early stage but it is likely that we will have an increasing number of treatment options available to us in the near future. This manuscript explores our current understanding of molecular-targeted therapies and considers: What approach should be used? (single vs multitarget agents); When should they be administered? (identifying the optimal point for intervention); How should they be used? (monotherapy or combination therapy regimens); and Who should we be giving them to? (acknowledging the need for patient selection)

Breast tumour angiogenesis

The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI).S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the Delta simA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development.Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine