Role of DAXX as a Predictive Biomarker in Breast Cancer

Breast cancer is the most commonly diagnosed form of cancer in women, besides skin cancer, and second only to lung cancer for cause of mortality. It is divided into three subtypes, depending on different molecular or pathologic characteristics, including estrogen or progesterone receptor-positive (ER/PR+), human epidermal growth factor receptor-2-positive (HER2+) and triple negative breast cancer (TNBC). There are several therapies used to target these subtypes, but there is still a chance that the cancer will recur into a more aggressive, resistant form even if the therapies were successful before. This recurrence is believed to be due to the Cancer Stem Cell (CSC) hypothesis which states that within the heterogeneous breast cancer tumor, there is a population of CSCs that are responsible for resistance to therapy and tumor recurrence. Evidence shows that Notch signaling, a pathway regulating several cellular processes, could be the reason these CSCs survive, so new therapies are being developed to target Notch signaling. The problem is, that Notch gene targets are not enough to provide a predictive response in breast cancer, so new potential biomarkers have been identified to predict a response to therapy-- such as DAXX protein. This protein, which has been associated in pro-apoptotic pathways and gene expression repression, has been shown to be inhibiting bulk cell proliferation in cell lines representative of all three breast cancer subtypes. In a HER2+ and TNBC cell line this has been shown even in the presence of a Notch inhibitor. Because of this, it was believed that DAXX expression may be inhibiting Notch signaling.xResults show that DAXX expression is required to limit proliferation of TNBC and other subtypes such as the HER2+ (BT474) and not ER+ (MCF-7). Interestingly, DAXX depletion using a DAXX siRNA decreases sensitivity of breast cancer cells to standard of care therapy in the TNBC subtype, MDA-MB-231 cells, only. In other TNBC cell lines, this is not the case-- showing just how heterogenous this subtype is. Further, DAXX appears to be potentially regulating PARP activity in MDA-MB-231 cells, which is key to stabilize cells that have some type of DNA damage, since depletion of DAXX results in increased PARP-1 and PAR chains expression. These results indicate that DAXX expression plays a role in limiting proliferation. The mechanism by which this occurs is largely unknown. However, preliminary findings demonstrate that a DNA damaging agent such as Carboplatin may induce JNK phosphorylation and activation. This activation of JNK seems to be dependent on DAXX expression in MDA-MB-232 cells. We assessed whether targeting JNK would be a novel therapeutic strategy in combination with carboplatin. Results showed that the JNK inhibitor (SP600125) partially prevents the increase in cell proliferation upon DAXX depletion. Results together suggest: 1. DAXX expression limits proliferation of most subtypes of breast cancer; 2. DAXX expression is required for drug sensitivity to standard of care but this differs in TNBC subtypes; 3. DAXX activates JNK to limit proliferation in the mesenchymal stem-like subtype of TNBC; and 4. DAXX may regulate poly(ADP) ribosylation (PAR) of PARP1 to possibly regulate the DNA damage response

What Is the Relationship Between Conflict Management and Employee Empowerment? A Message Design Logic Perspective and its Importance for Managers and Supervisors

This study focused on how conflict management between employees affects employee empowerment. Conflict naturally occurs between individuals, and its management in organizations can result in positive or negative consequences. Employee empowerment influences greater job satisfaction and commitment to organizations. Based on the theory of message design logic, it was hypothesized that employees who employ rhetorical design while managing conflict will experience greater levels of empowerment. The sample consisted of 196 employees at an educational institution who completed a short, online survey. Results showed no relationship between levels of perception of empowerment and message design logic, thus not supporting the hypothesis

PERIFERIAS URBANAS. ESPACIOS CON DÉFICIT DE CIUDADANÍA

El concepto de ciudad no es algo nuevo en la historia de la humanidad. Desde hace siglos, las ciudades ocupan un lugar central en la organización humana en diversos rincones del mundo. Sin embargo, fue con la llegada de la modernidad y, sobre todo, con el desarrollo de los procesos que han empezado en la Revolución Industrial que las ciudades pasaron a alojar gran parte de la población mundial. Con el crecimiento de las ciudades han surgido, consecuentemente, los ambientes periféricos urbanos acompañados por una serie de problemas de carácter social. Este manuscrito trata de recrear la formación de las grandes ciudades y sus periferias a través del proceso de urbanización en el mundo contemporáneo. Además, presenta la problemática de estas periferias, es decir, desarrolla una discusión alrededor de la segregación espacial en el ambiente urbano. El artículo versa, también, sobre el tema de la pobreza y marginación, características de dichos espacios urbanos

Ewing sarcoma in a child with neurofibromatosis type 1.

We report here on a case of Ewing sarcoma (ES) occurring in a child with neurofibromatosis type 1. The sarcoma had an EWSR1-ERG translocation as well as loss of the remaining wild-type allele of NF1. Loss of the NF1 wild-type allele in the tumor suggests that activation of the Ras pathway contributed to its evolution. Review of available public data suggests that secondary mutations in the Ras pathway are found in ∼3% of ESs. This case suggests that Ras pathway activation may play a role in tumor progression in a subset of ESs

A gestão de políticas públicas sociais na periferia urbana. Uma tentativa para estabelecer um modelo explicativo

Esta análise trata do desempenho dos parceiros sociais em uma situação de gozo dos direitos econômicos e sociais em periferias urbanas das grandes cidades brasileiras no início do século XXI. Para analisar as mudanças no cenário de gozo desses direitos entre 2000 e 2010 em bairros urbanos foram realizados três estudos de caso nos subúrbios das cidades de Salvador e Recife. A pesquisa foi feita através da observação do desempenho de três atores sociais fundamentais, organizações da sociedade, o Estado e o mercado, em políticas e projetos em favor do gozo dos direitos econômicos e sociais por moradores destas áreas. Assim, a partir da proposta do modelo de parceria tri-setorial, este estudo propõe uma nova variação do desempenho desses três atores que favoreça o aumento do gozo dos direitos econômicos e sociais em bairros urbanos periféricos através de políticas públicas: a parceria comunitária tri-sector.El presente análisis investiga la actuación de los agentes sociales en el disfrute de los derechos económicos y sociales en las periferias urbanas de grandes ciudades brasileñas a principios del siglo XXI. Para hacer el análisis de los cambios en el escenario del disfrute de estos derechos entre los años 2000 y 2010 en las periferias urbanas se han llevado a cabo tres estudios de caso en barrios periféricos de las ciudades de Salvador y Recife. La investigación ha sido realizada por medio de la observación de la actuación de los tres actores sociales fundamentales, es decir, las organizaciones de la sociedad, el Estado y el mercado, en políticas y proyectos en favor del disfrute de los derechos económicos y sociales por la población local. Por lo tanto, a partir del modelo de la alianza trisectorial, este estudio propone una nueva variación de la actuación de estos tres actores que favorece el incremento del disfrute de los derechos económicos y sociales en periferias urbanas por medio de las políticas públicas locales: la alianza trisectorial comunitaria.This analysis investigates the performance of social partners in fulfilling the economic and social rights of individuals living in urban peripheries in large Brazilian cities in the early twenty-first century. To analyze the changes in the scenario of these rights between 2000 and 2010 in urban peripheral neighborhoods, three case studies were carried out in suburbs of Salvador and Recife. The research was conducted by observing the performance of the three key social stakeholders -societal organizations, the State and the market- in policies and projects for the enjoyment of economic and social rights by locals. Thus, based on the tri-sector partnership model, this study proposes a new variation in the performance of these three actors to favour increased enjoyment of economic and social rights in urban neighborhoods through public policies: the Community tri-sector partnership

Improving Nurse Handoff Communication with an End of Shift Summary SmartPhrase

https://digitalcommons.psjhealth.org/summit_all/1059/thumbnail.jp

Deconstructing the smoking-preeclampsia paradox through a counterfactual framework.

Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preeclampsia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preeclampsia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preeclampsia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery ( 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preeclampsia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preeclampsia paradox appears to be an example of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preeclampsia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the association between smoking and pregnancy outcomes