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Luedi, M. M., Singh, S. K., Mosley, J. C., Hatami, M., Gumin, J., Sulman, E. P., et al. (2017). A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients. J Neurosurg Anesthesiol, 29(1), 46–58.
Abstract: BACKGROUND: Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. METHODS: We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. RESULTS: Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included “role of breast cancer 1 in DNA damage response” (P=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and -3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing “stem-like” cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. CONCLUSIONS: Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects.
Keywords: Animals; Antineoplastic Agents, Hormonal/*pharmacology; Apoptosis; Blotting, Western; Brain Neoplasms/*mortality; Cell Line, Tumor; Cell Survival; Dexamethasone/*pharmacology; Flow Cytometry; Gene Expression Regulation, Neoplastic/*drug effects; Glioblastoma/*mortality; Humans; Mice; Prognosis; Stem Cells/drug effects; Survival Analysis
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Gragnani, A., de Oliveira, A. F., Boro, D., Pham, T. N., & Ferreira, L. M. (2017). Response and legislative changes after the Kiss nightclub tragedy in Santa Maria/RS/Brazil: Learning from a large-scale burn disaster. Burns, 43(2), 343–349.
Abstract: PURPOSE: A major fire occurred on January 27, 2013, at 02:30 at Kiss nightclub in the city of Santa Maria, State of Rio Grande do Sul, in Southern Brazil. In this retrospective report, we aimed to describe the nightclub fire event, its immediate consequences, and evaluated its impact on legislation. Our objective was to disseminate the lessons we learned from this large-scale nightclub fire disaster. METHODS: We conducted a literature review in PubMed and Lilacs database from 2013 to 2015 related to the nightclub Kiss, Santa Maria, fire, burns, and similar events worldwide over the past 15 years. We searched in the general press and online media information sites, and seeking legislation about this topic at the federal level in Brazil. We reported on the legislation changes that resulted from this nightclub fire. RESULTS: Current federal legislation on fire prevention and the scope of public safety, including night clubs and discos, states is the duty of the state and everyone's responsibility, pursuant to Article 144 of the Federal Constitution of Brazil. Thus, the federal union, individual states and municipalities have the power to legislate on fire prevention, and especially to ensure the security of the population. A state law called “Law Kiss”, was passed in 2014, establishing standards on safety, prevention and protection against fire in buildings and areas of fire risk in the state of Rio Grande do Sul. On a national level, a law of prevention and fire fighting in Brazil was also drafted after the Santa Maria disaster (Law project no. 4923, 2013). Currently, this bill is still awaiting sanction before it can take effect. CONCLUSION: As we push for enactment of the national law of prevention and fire fighting in Brazil, we will continue emphasizing fire prevention, fire protection, fire fighting, means of escape and proper management. All similar events in this and other countries remind us that similar tragedies may occur anywhere, and that the analysis of facts, previous mistakes, during and after the incident are crucial to our understanding, and will help us lessen the chance of future occurrences.
Keywords: Brazil/epidemiology; Burns/epidemiology/*prevention & control; Carbon Monoxide Poisoning/epidemiology; Crowding; Disasters/*prevention & control; Fires/legislation & jurisprudence/*prevention & control; Humans; Hydrolases/poisoning; Mass Casualty Incidents/*prevention & control/statistics & numerical data; *Public Policy; Retrospective Studies; Safety/*legislation & jurisprudence; Smoke Inhalation Injury/epidemiology; Burn disaster; Fire prevention and protection; Kiss nightclub; Legislation; Mass casualty incident; Santa Maria
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Nourallah, B., Digpal, R., Jena, R., & Watts, C. (2017). Irradiating the Subventricular Zone in Glioblastoma Patients: Is there a Case for a Clinical Trial? Clin Oncol (R Coll Radiol), 29(1), 26–33.
Abstract: Glioblastoma is the most common and aggressive adult brain tumour. Over the last 10 years it has emerged that the subventricular zone (SVZ), the largest adult neural stem cell niche, has an important role in the disease. Converging evidence has implicated transformation of adult neural stems in gliomagenesis and the permissive stem cell niche in disease recurrence. Concurrently, clinical studies have suggested that SVZ involvement is a negative prognostic marker. It would follow that irradiating the SVZ may improve outcomes in glioblastoma by directly targeting this putative sanctuary site. To investigate this potential strategy, 11 retrospective studies and 1 prospective study examined the relationship between dose to the SVZ and survival outcomes in glioblastoma patients. This review summarises the theoretical underpinning of this strategy, provides a critical evaluation of the existing evidence and discusses the rationale for a clinical trial.
Keywords: Adult; Brain Neoplasms/*radiotherapy; Glioblastoma/*radiotherapy; Humans; Lateral Ventricles/*radiation effects; Male; Neoplastic Stem Cells/radiation effects; Stem Cell Niche/radiation effects; Cancer stem cells; glioblastoma; neural stem cells; radiotherapy; subventricular zone
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Monge-Rojas, R., Fuster-Baraona, T., Garita-Arce, C., Sanchez-Lopez, M., Colon-Ramos, U., & Smith-Castro, V. (2017). How Self-Objectification Impacts Physical Activity Among Adolescent Girls in Costa Rica. J Phys Act Health, 14(2), 123–129.
Abstract: BACKGROUND: In Latin America, more than 80% of adolescent girls are physically inactive. Inactivity may be reinforced by female stereotypes and objectification in the Latin American sociocultural context. METHODS: We examined the influence of objectification on the adoption of an active lifestyle among 192 adolescents (14 and 17 years old) from urban and rural areas in Costa Rica. Analyses of 48 focus-groups sessions were grounded in Objectification Theory. RESULTS: Vigorous exercises were gender-typed as masculine while girls had to maintain an aesthetic appearance at all times. Adolescents described how girls were anxious around the prospect of being shamed and sexually objectified during exercises. This contributed to a decrease in girls' desire to engage in physical activities. Among males, there is also a budding tolerance of female participation in vigorous sports, as long as girls maintained a feminine stereotype outside their participation. CONCLUSION: Self-objectification influenced Costa Rican adolescent girls' decisions to participate in physical activities. Interventions may include: procuring safe environments for physical activity where girls are protected from fear of ridicule and objectification; sensitizing boys about girl objectification and fostering the adoption of a modern positive masculine and female identities to encourage girls' participation in sports.
Keywords: Adolescent; *Adolescent Behavior; Body Image/*psychology; Costa Rica; Cultural Characteristics; *Exercise; Female; Focus Groups; Humans; Male; Women's Health; Latin America; female identity; machismo; sexual harassment
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Monge-Rojas, R., Fuster-Baraona, T., Garita-Arce, C., Sanchez-Lopez, M., Colon-Ramos, U., & Smith-Castro, V. (2017). How Self-Objectification Impacts Physical Activity Among Adolescent Girls in Costa Rica. J Phys Act Health, 14(2), 123–129.
Abstract: BACKGROUND: In Latin America, more than 80% of adolescent girls are physically inactive. Inactivity may be reinforced by female stereotypes and objectification in the Latin American sociocultural context. METHODS: We examined the influence of objectification on the adoption of an active lifestyle among 192 adolescents (14 and 17 years old) from urban and rural areas in Costa Rica. Analyses of 48 focus-groups sessions were grounded in Objectification Theory. RESULTS: Vigorous exercises were gender-typed as masculine while girls had to maintain an aesthetic appearance at all times. Adolescents described how girls were anxious around the prospect of being shamed and sexually objectified during exercises. This contributed to a decrease in girls' desire to engage in physical activities. Among males, there is also a budding tolerance of female participation in vigorous sports, as long as girls maintained a feminine stereotype outside their participation. CONCLUSION: Self-objectification influenced Costa Rican adolescent girls' decisions to participate in physical activities. Interventions may include: procuring safe environments for physical activity where girls are protected from fear of ridicule and objectification; sensitizing boys about girl objectification and fostering the adoption of a modern positive masculine and female identities to encourage girls' participation in sports.
Keywords: Adolescent; *Adolescent Behavior; Body Image/*psychology; Costa Rica; Cultural Characteristics; *Exercise; Female; Focus Groups; Humans; Male; Women's Health; Latin America; female identity; machismo; sexual harassment
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