Oxidative Stress Levels and DNA Repair Kinetics in Senescent Primary Human Fibroblasts Exposed to Chronic Low Dose Rate of Ionizing Radiation.

BACKGROUND: Exposure to low dose rate (LDR) radiation may accelerate aging processes. Previously, we identified numerous LDR-induced pathways involved in oxidative stress (OS) and antioxidant systems, suggesting that these pathways protect against premature senescence (PS). This study aimed to investigate if there are differences between young replicative senescent (RS) and PS cells considering DNA repair kinetics, OS, and DNA damage localized in the telomeres. METHODS: We established PS cells by culturing and passaging young primary fibroblasts exposed to LDR. Then, RS cells were established by culturing and passaging young fibroblasts until they stopped proliferating. Senescence was characterized by analyzing telomere length and senescence-associated ß-galactosidase (SA-ß-gal) staining. DNA damage and repair were evaluated with γH2AX foci formation; telomere identification was carried out using the fluorescence in situ hybridization (FISH) probe; and oxidative stress was assessed by measuring 8-oxo-dG in the medium. RESULTS: The data indicate the following: young cells have a better ability to cope with LDR-induced oxidative stress; RS and PS have higher steady-state levels of DNA damage; RS have slower DNA repair kinetics; and PS/RS have elevated levels of telomeric DNA damage. CONCLUSION: Our main conclusion is that PS and RS differ regarding DNA repair kinetics and SA-ß-gal levels.

Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.

The coordinating role of nuclear factor erythroid-2-related factor 2 (Nrf2) in cellular function is undeniable. Evidence indicates that this transcription factor exerts massive regulatory functions in multiple signaling pathways concerning redox homeostasis and xenobiotics, macromolecules, and iron metabolism. Being the master regulator of antioxidant system, Nrf2 controls cellular fate, influencing cell proliferation, differentiation, apoptosis, resistance to therapy, and senescence processes, as well as infection disease success. Because Nrf2 is the key coordinator of cell defence mechanisms, dysregulation of its signaling has been associated with carcinogenic phenomena and infectious and age-related diseases. Deregulation of this cytoprotective system may also interfere with immune response. Oxidative burst, one of the main microbicidal mechanisms, could be impaired during the initial phagocytosis of pathogens, which could lead to the successful establishment of infection and promote susceptibility to infectious diseases. There is still a knowledge gap to fill regarding the molecular mechanisms by which Nrf2 orchestrates such complex networks involving multiple pathways. This review describes the role of Nrf2 in non-pathogenic and pathogenic cells.

Obstructive sleep apnea screening in different age groups: performance of the Berlin, STOP-Bang questionnaires and Epworth Sleepiness Scale.

OBJECTIVE: To evaluate the performance of the Berlin Questionnaire, the STOP-Bang Questionnaire, and the Epworth Sleepiness Scale in screening for the disease in adults of different age groups by comparing them with polysomnography. METHODS: Cross-sectional study with prospective patient allocation, in which individuals underwent a medical interview, completion of the three screening instruments, and polysomnography. Individuals were categorized into three age groups: 18-39, 40-59, and ≥60 years. The results of the screening instruments were compared to the diagnostic criteria of the International Classification of Sleep Disorders-third edition. Performance was assessed using 2×2 contingency tables, estimating sensitivity, specificity, predictive value, likelihood ratio, and accuracy. Receiver Operating Characteristic curves were also constructed and the area under the curve was estimated for each instrument by age group. RESULTS: We obtained a sample with 321 individuals suitable for analysis. The mean age was 50 years, with a predominance of females (56%). The prevalence of the disease in the overall sample was 79%, more prevalent in males in any age group and more frequent in the middle age group. The analyzes revealed that STOP-Bang performed better, both for the overall sample and for all age groups, followed by Berlin Questionnaire and Epworth Sleepiness Scale. CONCLUSION: In an outpatient setting with individuals with characteristics similar to those in this study, it seems sensible to choose the STOP-Bang as a screening tool for the disease, regardless of age group. LEVEL OF EVIDENCE ACCORDING THE GUIDE FOR AUTHORS: level 2.

Obstructive sleep apnea screening in different age groups: performance of the Berlin, STOP-Bang questionnaires and Epworth Sleepiness Scale

Abstract Objective To evaluate the performance of the Berlin Questionnaire, the STOP-Bang Questionnaire, and the Epworth Sleepiness Scale in screening for the disease in adults of different age groups by comparing them with polysomnography. Methods Cross-sectional study with prospective patient allocation, in which individuals underwent a medical interview, completion of the three screening instruments, and polysomnography. Individuals were categorized into three age groups: 18-39, 40-59, and ≥60 years. The results of the screening instruments were compared to the diagnostic criteria of the International Classification of Sleep Disorders—third edition. Performance was assessed using 2 × 2 contingency tables, estimating sensitivity, specificity, predictive value, likelihood ratio, and accuracy. Receiver Operating Characteristic curves were also constructed and the area under the curve was estimated for each instrument by age group. Results We obtained a sample with 321 individuals suitable for analysis. The mean age was 50 years, with a predominance of females (56%). The prevalence of the disease in the overall sample was 79%, more prevalent in males in any age group and more frequent in the middle age group. The analyzes revealed that STOP-Bang performed better, both for the overall sample and for all age groups, followed by Berlin Questionnaire and Epworth Sleepiness Scale. Conclusion In an outpatient setting with individuals with characteristics similar to those in this study, it seems sensible to choose the STOP-Bang as a screening tool for the disease, regardless of age group. Level of evidence according the guide for authors: level 2.

Screening for obstructive sleep apnea in elderly: performance of the Berlin and STOP-Bang questionnaires and the Epworth sleepiness scale using polysomnography as gold standard.

Objectives: Obstructive sleep apnea (OSA) affects approximately one third of the population and can reach 90% prevalence in the elderly. There are screening tools to track the disease, however, their performance may differ according to population characteristics. This study aims to determine sensitivity, specificity, predictive value, likelihood ratio, and accuracy of the Berlin (BQ) and STOP-Bang (S-Bang) questionnaires and the Epworth sleepiness scale (ESS), comparing their performances, using polysomnography (PSG) as a gold standard, in a sample of elderly. Material and Methods: The study was cross-sectional, retrospective, included patients aged 60 or older who underwent PSG type 1, regardless of the BQ, S-Bang and ESS results, during the period of June 1, 2017 to April 30, 2019. OSA diagnosis was by PSG in which the hypopnea apnea index was greater than or equal to 5. Results: Sixty-two patients were evaluated; the prevalence of OSA was 72.58%. The mean age in the sample with OSA was 73.0±8.4 years and without it was 74.7±8.1 years. The sample was predominantly female, 58.1% with OSA. The BQ showed the best results for specificity, predictive value, likelihood ratio and accuracy. S-Bang had the best result for sensitivity and ESS showed the worst results. The BQ odds ratio showed that an individual with a positive BQ has 335% more chance of developing OSA. Conclusion: The QB showed the best performance in the measures for identifying OSA, for a sample of elderly individuals, with a predominance of females and a high prevalence of the disease.

Screening for obstructive sleep apnea in elderly: performance of the Berlin and STOP-Bang questionnaires and the Epworth Sleepiness Scale using polysomnography as gold standard.

Objectives: Obstructive sleep apnea (OSA) affects approximately one third of the population and can reach 90% prevalence in the elderly. There are screening tools to track the disease, however, their performance may differ according to population characteristics. This study aims to determine sensitivity, specificity, predictive value, likelihood ratio and accuracy of the Berlin (BQ) and STOP-Bang (S-Bang) questionnaires and the Epworth Sleepiness Scale (ESS), comparing their performances, using polysomnography (PSG) as a gold standard, in a sample of elderly. Methods: The study was cross-sectional, retrospective, included patients aged 60 or older who underwent PSG type 1, regardless of the BQ, S-Bang and ESS results, during the period of June 1, 2017 to April 30, 2019. OSA diagnosis was by PSG in which the hypopnea apnea index was greater than or equal to 5. Results: Sixty- two patients were evaluated; the prevalence of OSA was 72.58%. The mean age in the sample with OSA was 73.0 sd 8.4 years and without it was 74.7 sd 8.1 years. The sample was predominantly female, 58.1% with OSA. The BQ showed the best results for specificity, predictive value, likelihood ratio and accuracy. S-Bang had the best result for sensitivity and ESS showed the worst results. The BQ odds ratio showed that an individual with a positive BQ has 335% more chance of developing OSA. Conclusion: The QB showed the best performance in the measures for identifying OSA, for a sample of elderly individuals, with a predominance of females and a high prevalence of the disease.

Anti-Proliferative Effects of E2F1 Suppression in Glioblastoma Cells.

Glioblastoma (GBM) is an aggressive malignant brain tumor; surgery, radiation, and temozolomide still remain the main treatments. There is evidence that E2F1 is overexpressed in various types of cancer, including GBM. E2F1 is a transcription factor that controls the cell cycle progression and regulates DNA damage responses and the proliferation of pluripotent and neural stem cells. To test the potentiality of E2F1 as molecular target for GBM treatment, we suppressed the E2F1 gene (siRNA) in the U87MG cell line, aiming to inhibit cellular proliferation and modulate the radioresistance of these cells. Following E2F1 suppression, associated or not with gamma-irradiation, several assays (cell proliferation, cell cycle analysis, neurosphere counting, and protein expression) were performed in U87MG cells grown as monolayer or neurospheres. We found that siE2F1-suppressed cells showed reduced cell proliferation and increased cell death (sub-G1 fraction) in monolayer cultures, and also a significant reduction in the number of neurospheres. In addition, in irradiated cells, E2F1 suppression caused similar effects, with reduction of the number of neurospheres and neurosphere cell numbers relative to controls; these results suggest that E2F1 plays a role in the maintenance of GBM stem cells, and our results obtained in neurospheres are relevant within the context of radiation resistance. Furthermore, E2F1 suppression inhibited or delayed GBM cell differentiation by maintaining a reasonable proportion of CD133+ cells when grown at differentiation condition. Therefore, E2F1 proved to be an interesting molecular target for therapeutic intervention in U87MG cells.

Effect of dose and dose rate of gamma irradiation on the formation of micronuclei in bone marrow cells isolated from whole-body-irradiated mice.

It is well-known that the cytotoxicity and mutagenic effects of high dose rate (HDR) ionizing radiation (IR) are increased by increasing the dose but less is known about the effects of chronic low dose rate (LDR). In vitro, we have shown that in addition to the immediate interaction of IR with DNA (the direct and indirect effects), low doses and chronic LDR exposure induce endogenous oxidative stress. During elevated oxidative stress, reactive oxygen species (ROS) react with DNA modifying its structure. Here, BL6 mice were exposed to IR at LDR and HDR and were then sacrificed 3 hours and 3 weeks after exposure to examine early and late effects of IR. The levels of micronuclei, MN, were determined in bone marrow cells. Our data indicate that the effects of 200 mGy on MN-induction are transient, but 500 and 1000 mGy (both HDR and LDR) lead to increased levels of MN up to 3 weeks after the exposure.

Lobesia botrana: A Biological Control Approach with a Biopesticide Based on Entomopathogenic Fungi in the Winter Season in Chile.

Lobesia botrana (Denis and Shiffermüller) (Lepidoptera: Tortricidae) is one of the main pests that affect the production and export of table grapes in Chile. Because this pest has quarantine status, the fruit must be fumigated with methyl bromide, which reduces the fruit's export competitiveness in the destination market. In the present study, to help resolve this issue, six native entomopathogenic fungi were identified through multilocus analysis, including three Beauveria pseudobassiana and three Metarhizium robertsii. These fungi were evaluated in the laboratory to control L. botrana in its pupal stage in a silk cocoon and compared against a biological control product. Formulations with additional carbon sources improved the performance of the fungi. The treatments with outstanding performance contained the fungal strains B. pseudobassiana RGM 2184 and M. robertsii RGM 678. These strains were evaluated in the field during the winter season in two different regions of the country; the strains reached maximum efficacies of 80% and 88%, respectively, at 21 days post first application. Therefore, entomopathogenic fungi can contribute to reducing pupal populations in winter, thereby decreasing the moth population in spring-summer.

PARP­1 inhibition sensitizes temozolomide­treated glioblastoma cell lines and decreases drug resistance independent of MGMT activity and PTEN proficiency.

Information on the mechanisms that are associated with tumor resistance has the potential to provide the fundamental basis for novel therapeutic strategies. In glioblastoma (GBM), predictive biomarkers of cellular responses to temozolomide (TMZ) combined with poly­ADP­ribose polymerase inhibitor (PARPi) remain largely unidentified. In this context, the influence of MGMT (O6­methylguanine DNA methyltransferase) and PTEN (phosphatase and tensin homologue deleted on chromosome ten) has been studied in addition to the occurrence of synthetic lethality involving PTEN and PARPi. The present study investigated whether PARP­1 inhibition by NU1025 may increase the cytotoxicity of TMZ­induced lesions in GBM cells, and whether these mechanisms can be influenced by MGMT and PTEN status. The impact of PTEN deficiency in repair pathways, and the effects of PARP­1 inhibition and PTEN silencing, in terms of synthetic lethality, were also assessed. NU1025 combined with TMZ effectively sensitized TMZ­resistant cells (T98G PTEN­mutated and LN18 PTEN­wild­type) and TMZ­sensitive cells (U251MG PTEN­mutated), in contrast to NU1025 alone. However, the sensitizing effects were not observed in U87MG (PTEN­mutated) cells, suggesting that specific genetic alterations may influence the response to drug treatment. The sensitizing effects occurred independently of MGMT activity, which was evaluated in O6­BG­treated cells. PTEN silencing using small interfering (si)RNA did not sensitize PTEN­proficient cells to TMZ + NU1025, or NU1025 alone, indicating an absence of synthetic lethality. The responses to TMZ + NU1025 involved antiproliferative activity, G2/M arrest, double strand breaks and the induction of apoptosis. Following 20 days of recovery after three consecutive days of TMZ treatment, TMZ­resistant cells were observed. However, when TMZ was combined with NU1025, the viability of T98G and LN18 cells was extremely decreased, indicating a lethal drug combination. Therefore, independently of MGMT proficiency and PTEN status, TMZ combined with PARPi may be a promising strategy that can be used to overcome TMZ acquired resistance in GBM cells.

Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress.

The presence of glioma stem cells (GSCs), which are enriched in neurospheres, may be connected to the radioresistance of glioblastoma (GBM) due to their enhanced antioxidant defense and elevated DNA repair capacity. The aim was to evaluate the responses to different radiation qualities and to reduce radioresistance of U87MG cells, a GBM cell line. U87MG cells were cultured in a 3D model and irradiated with low (24 mGy/h) and high (0.39 Gy/min) dose rates of low LET gamma and high LET carbon ions (1-2 Gy/min). Thereafter, expression of proteins related to oxidative stress response, extracellular 8-oxo-dG, and neurospheres were determined. LD50 for carbon ions was significantly lower compared to LD50 of high and low dose rate gamma radiation. A significantly higher level of 8-oxo-dG was detected in the media of cells exposed to a low dose rate as compared to a high dose rate of gamma or carbon ions. A downregulation of oxidative stress proteins was also observed (NRF2, hMTH1, and SOD1). The NRF2 gene was knocked down by CRISPR/Cas9 in neurosphere cells, resulting in less self-renewal, more differentiated cells, and less proliferation capacity after irradiation with low and high dose rate gamma rays. Overall, U87MG glioma neurospheres presented differential responses to distinct radiation qualities and NRF2 plays an important role in cellular sensitivity to radiation.

Up to 15-Year Survival of Men and Women after Percutaneous Coronary Intervention Paid by the Brazilian Public Healthcare System in the State of Rio de Janeiro, 1999-2010. / Sobrevida em até 15 Anos de Homens e Mulheres após Intervenção Coronariana Percutânea Paga pelo Sistema Único de Saúde no Estado do Rio de Janeiro, 1999-2010.

BACKGROUND: Percutaneous coronary intervention (PCI) is the most frequently used invasive therapy for ischemic heart disease (IHD). Studies able to provide information about PCI's effectiveness should be conducted in a population of real-world patients. OBJECTIVES: To assess the survival rate of IHD patients treated with PCI in the state of Rio de Janeiro (RJ). METHODS: Administrative (1999-2010) and death (1999-2014) databases of dwellers aged ≥ 20 years old in the state of RJ submitted to one single PCI paid by the Brazilian public healthcare system (SUS) between 1999 and 2010 were linked. Patients were grouped as follows: 20-49 years old, 50-69 years old and ≥ 70 years old, and PCI in primary PCI, with stent and without stent placement (bare metal stent). Survival probabilities in 30 days, one year and 15 years were estimated by using the Kaplan-Meier method. Cox hazards regression models were used to compare risks among sex, age groups and types of PCI. Test results with a p-value < 0.05 were deemed statistically significant. RESULTS: Data of 19,263 patients (61 ± 11 years old, 63.6% men) were analyzed. Survival rates of men vs. women in 30 days, one year and 15 years were: 97.3% (97.0-97.6%) vs. 97.1% (96.6-97.4%), 93.6% (93.2-94.1%) vs. 93.4% (92.8-94.0%), and 55.7% (54.0-57.4%) vs. 58.1% (55.8-60.3%), respectively. The oldest age group was associated with lower survival rates in all periods. PCI with stent placement had higher survival rates than those without stent placement during a two-year follow-up. After that, both procedures had similar survival rates (HR 0.91, 95% CI 0.82-1.00). CONCLUSIONS: In a population of real-world patients, women had a higher survival rate than men within 15 years after PCI. Moreover, using a bare-metal stent failed to improve survival rates after a two-year follow-up compared to simple balloon angioplasty.

Up to 15-Year Survival of Men and Women after Percutaneous Coronary Intervention Paid by the Brazilian Public Healthcare System in the State of Rio de Janeiro, 1999-2010 / Sobrevida em até 15 Anos de Homens e Mulheres após Intervenção Coronariana Percutânea Paga pelo Sistema Único de Saúde no Estado do Rio de Janeiro, 1999-2010

Abstract Background: Percutaneous coronary intervention (PCI) is the most frequently used invasive therapy for ischemic heart disease (IHD). Studies able to provide information about PCI's effectiveness should be conducted in a population of real-world patients. Objectives: To assess the survival rate of IHD patients treated with PCI in the state of Rio de Janeiro (RJ). Methods: Administrative (1999-2010) and death (1999-2014) databases of dwellers aged ≥ 20 years old in the state of RJ submitted to one single PCI paid by the Brazilian public healthcare system (SUS) between 1999 and 2010 were linked. Patients were grouped as follows: 20-49 years old, 50-69 years old and ≥ 70 years old, and PCI in primary PCI, with stent and without stent placement (bare metal stent). Survival probabilities in 30 days, one year and 15 years were estimated by using the Kaplan-Meier method. Cox hazards regression models were used to compare risks among sex, age groups and types of PCI. Test results with a p-value < 0.05 were deemed statistically significant. Results: Data of 19,263 patients (61 ± 11 years old, 63.6% men) were analyzed. Survival rates of men vs. women in 30 days, one year and 15 years were: 97.3% (97.0-97.6%) vs. 97.1% (96.6-97.4%), 93.6% (93.2-94.1%) vs. 93.4% (92.8-94.0%), and 55.7% (54.0-57.4%) vs. 58.1% (55.8-60.3%), respectively. The oldest age group was associated with lower survival rates in all periods. PCI with stent placement had higher survival rates than those without stent placement during a two-year follow-up. After that, both procedures had similar survival rates (HR 0.91, 95% CI 0.82-1.00). Conclusions: In a population of real-world patients, women had a higher survival rate than men within 15 years after PCI. Moreover, using a bare-metal stent failed to improve survival rates after a two-year follow-up compared to simple balloon angioplasty.

Resumo Fundamento: A intervenção coronariana percutânea (ICP) é o tratamento invasivo mais frequentemente realizado na doença isquêmica do coração (DIC). Estudos capazes de prover informação sobre a sua efetividade são importantes. Objetivo: Avaliar a sobrevida em até 15 anos de pacientes submetidos a ICP no estado do Rio de Janeiro (ERJ). Métodos: Bases de dados administrativas (1999-2010) e de óbitos (1999-2014) dos residentes com idade ≥ 20 anos do ERJ submetidos a uma única ICP paga pelo Sistema Único de Saúde (SUS) entre 1999-2010 foram relacionadas. Os pacientes foram agrupados em 20-49, 50-69 ou ≥ 70 anos, e as ICP em primária (ICP-P), sem stent (ICP-SS) e com stent convencional (ICP-CS). As probabilidades de sobrevida em 30 dias, um ano e 15 anos foram estimadas pelo método de Kaplan-Meier. Modelos de regressão de risco de Cox foram utilizados para comparar riscos entre sexo, faixas etárias e tipos de ICP. Resultados dos testes com um valor de p < 0,05 foram considerados estatisticamente significativos. Resultados: Foram analisados os dados de 19.263 pacientes (61±11 anos, 63,6% homens). A sobrevida de homens vs. mulheres em 30 dias, um ano e 15 anos foram: 97,3% (97,0-97,6%) vs. 97,1% (96,6-97,4%), 93,6% (93,2-94,1%) vs. 93,4% (92,8-94,0%), e 55,7% (54,0-57,4%) vs. 58,1% (55,8-60,3%), respectivamente. Idade ≥ 70 anos foi associada à menor taxa de sobrevida em todos os períodos. A ICP-CS foi associada a uma sobrevida maior do que a ICP-SS até dois anos de acompanhamento, e após este período ambos os procedimentos apresentaram taxas de sobrevida semelhantes (HR 0,91, IC 95% 0,82-1,00). Conclusões: Mulheres apresentaram maiores taxas de sobrevida em 15 anos após ICP, e o uso de stent convencional não esteve associado a um aumento de sobrevida em longo prazo.

Intramuscular Gluteal Augmentation with Implants Associated with Immediate Fat Grafting.

This article presents an overview of intramuscular gluteal augmentation involving primary and secondary augmentation with implants. Although gluteal augmentation is a well-studied procedure, few reports have described the intramuscular technique or this technique in association with lipofilling. This article presents experience with a combined technique; this recent innovation combines placement of an anatomic silicone gel implant underneath the gluteus maximus and immediate fat grafting. Primary and secondary gluteal augmentations using implants resulted in satisfactory outcomes. A majority of complications were minor, predictable, and did not affect aesthetic outcome or normal postoperative recovery. Success depends on patient selection and careful intraoperative and postoperative management.

Anthropometric Profile, Serum Leptin, Antioxidant Vitamins, LEPR Q223R Polymorphism and Cardiovascular Risk Factors in Adolescents.

Cardiovascular disease (CVD) risk factors, such as bad eating habits, are typical in adolescence and lead to the consumption of meals that are not always sufficient in vitamins A, E, ß-carotene, excess calories and elevated serum leptin levels. The purpose of this research is to study the relationship between vitamin A deficiency (VAD), ß-carotene deficiency (ßcD), vitamin E deficiency (VED) and to explore the association of leptin receptor Q223R polymorphisms with obesity and other risk factors for CVD. Method: This observational study included 237 adolescents recruited from Adolescents Reference Center, Brazil. It was collected: socioeconomic and clinical data, laboratory and molecular samples. Results: The average age was 14.93 ± 2.18 years, 66.2 % were girls, 38.0 % had high levels of total cholesterol (TC) between 10-14 years Triceps (TSF) and subscapular skinfolds (SSF) measurements were inversely correlated with VAD. There was also an association between VAD, ßcD and high triglyceride (TG) levels. Adolescents with the RR genotype presented a trend toward higher levels of body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), TC, TG, low density lipoprotein (LDLC), leptin and low levels of high-density lipoprotein (HDL-c). Conclusion: The girls had higher levels of leptin than boys. Abdominal fat, ßcD and VED were observed in adolescents with VAD. Individuals with RR genotype have drawn attention to cardiovascular risk factors such as high rate of LDLC and reduced rate of HDLc. Thus, it is possible that individuals with this genotype may be more susceptible to the presence of cardiovascular risk factors.

Medium-term outcomes of 78,808 patients after heart valve surgery in a middle-income country: a nationwide population-based study.

BACKGROUND: Heart valve surgery outcomes are unknown in middle-income countries and thus cannot be used in health system decision making processes. This study estimated in-hospital mortality and medium and long-term survival. METHODS: This was a retrospective study of 78,806 patients who underwent heart valve surgery between 2001 and 2007 in Brazil. Two national databases were used, the Hospital Information System and the Mortality Information System. Kaplan-Meier survival analysis and log-rank tests were performed. Maximum and median follow-up was 7.7 and 2.8 years, respectively (0.002-7.707). RESULTS: Valve replacement accounted for 69.1% of procedures performed. Mitral stenosis, the most common valve injury, represented 38.9% of the total. In 94.7% of mitral stenosis patients, aetiology was rheumatic heart disease. In-hospital mortality was 7.6% and was higher for women, for patients who had undergone concomitant coronary artery bypass grafting (CABG) and for the elderly. Overall survival was 69.9% at the end of follow-up. Survival was worst among elderly, male and concomitant CABG patients (P<0.001). CONCLUSIONS: Rheumatic heart disease is still a major public health problem in Brazil. In-hospital mortality and global survival rates of patients who have undergone heart valve surgery were less satisfactory than those reported in high-income countries. The findings of this study can contribute to guiding decision making processes in middle-income countries similar to Brazil and others concerned with improving the quality of care.

E2F transcription factors associated with up-regulated genes in glioblastoma.

BACKGROUND: Glioblastoma is considered to the most common and malignant brain tumor in adults. Patients have a median survival of approximately one year from diagnosis due to poor response to therapy. OBJECTIVE: We applied bioinformatics approaches to predict transcription factors (TF) that are deregulated in glioblastoma in an attempt to point out molecular targets for therapy. METHODS: Up-regulated genes in glioblastoma selected from public microarray data were submitted to two TF association analyses. Thereafter, the expression levels of TF obtained in the overlap of analyses were assessed by RT-qPCR carried out in seven glioblastoma cell lines (T98, U251, U138, U87, U343, M059J, and M059K). RESULTS: E2F1 and E2F4 were highlighted in both TF analyses. However, only E2F1 was confirmed as significantly up-regulated in all glioblastoma cell lines in vitro. CONCLUSION: E2F1 is a potential common regulator of differentially expressed genes in glioblastoma, despite the genetic heterogeneity of tumor cells.

Tendências e Letalidade Hospitalar dos Procedimentos de Revascularização Miocárdica Pagos pelo SUS no Estado do Rio de Janeiro, 1999-2010 / Trends and Hospital Mortality in Myocardial Revascularization Procedures Covered by the Brazilian Unified Health System in Rio de Janeiro State from 1999 to 2010

As doenças isquêmicas do coração (DIC) são causas de morte relevantes no Estado do Rio de Janeiro (ERJ). A cirurgia de revascularização do miocárdio (CRVM) e a angioplastia coronariana (AC) objetivam reduzir agravos causados pelas DIC. É preciso conhecer a eficiência desses procedimentos para decisões clínica e gerenciais. Objetivo: Descrever evolução temporal e letalidade hospitalar de CRVM e AC de 1999 a 2010 no ERJ. Métodos: Estudo de dados referentes às CRVM e AC dos bancos de dados das Autorizações de Internação Hospitalar pagas pelo Sistema Único de Saúde, de 1999 a 2010 no ERJ, com informações sobre diagnóstico, idade, sexo, data e duração da internação, tipo de alta hospitalar. Foram realizadas estatísticas descritivas e regressão linear para análise de tendências. Resultados: Em 34 413 pacientes com média de idade 61±10 anos, foram realizados 38 509 procedimentos, sendo 66,3% AC e 65,4% homens. Ocorreu aumento anual de 15,8% das AC e de 3,2% das CRVM. O diagnóstico de DIC aguda foi registrado em 60,6% das internações relacionadas a AC e 57,9% das relacionadas a CRVM. As medianas de duração de internação foram de 2 dias nas AC e 10 nas CRVM. As letalidades hospitalares encontradas nas AC e nas CRVM foram de 1,8% e 6,8%, respectivamente, maiores nos indivíduos com 70 anos ou mais, nas mulheres e nas DIC agudas. Conclusão: Houve um aumento nos procedimentos de revascularização miocárdica no ERJ, principalmente nas AC com stent, divergindo de outras regiões do mundo. Além disso, a letalidade hospitalar após a AC e a CRVM foram superiores às encontradas em outros locais e em estudos controlados.

Background: Ischemic heart diseases (IHD) are important causes of deaths in the state of Rio de Janeiro (RJ). Coronary artery bypass grafting (CABG) and coronary angioplasty (CA) procedures aim to mitigate the effects of IHD. Awareness of the efficiency of these procedures is crucial for clinical and administrative decision making. Objective: To describe temporal evolution and hospital mortality of CABG and CA performed in RJ from 1999 to 2010. Methods: Study on data of CA and CABG, covered by the Brazilian Unified Health System in RJ from 1999 to 2010, obtained from the Authorization for Hospital Admission database, concerning diagnosis, age, sex, admission date and hospital internment duration, and type of hospital discharge. Trends analysis was performed by descriptive statistics and linear regression analysis. Results: In 34,413 patients with mean age of 61±10 years, 38,509 procedures were performed, 66.3% CA and 65.4% in men. There was an annual increase by 15.8% in CA and 3.2% in CABG. The diagnosis of acute IHD was recorded in 60.6% of admissions related to CA, and in 57.9% of admissions related to CABG. Median hospital stay was 2 days in CA and 10 days in CABG. Hospital mortality was 1.8% and 6.8% in CA and CABG, respectively, and was higher in patients aged 70 years or older, in women and in acute IHD. Conclusion: The number of myocardial revascularizations in RJ, especially CA with stent, has increased which differs from other regions of the world. In addition, post-CA and post-CABG hospital mortality was higher than that reported in other locations and controlled studies.

HEB silencing induces anti-proliferative effects on U87MG cells cultured as neurospheres and monolayers.

Glioblastoma multiforme (GBM) is a lethal tumor and novel strategies are required to overcome resistance. Transcription factor 12 (HEB) has been associated with neural and stem cell proliferation, is overexpressed in certain tumor types and is induced in irradiated U87MG cells. The present study aimed to determine whether HEB knockdown, with or without irradiation, may sensitize GBM cells. U87MG GBM and ACBRI­371 primary human astrocytes were cultured in monolayers or neurospheres. Cell proliferation and death, cell cycle and sub­G1 detection, and cluster of differentiation (CD) 133 immunofluorescence were analyzed by flow cytometry, whereas HEB protein expression was analyzed by immunocytochemistry and western blotting. Greater HEB protein expression was observed in U87MG neurospheres compared with ACBRI­371, and the two cell lines exhibited nuclear HEB expression. HEB silencing in cells grown in monolayers induced a significant reduction in proliferation and decreased the proportion of cells in G0/G1 phase. In addition, HEB silencing reduced (two­fold) the number of neurospheres compared with control scrambled (SCR) cells. HEB silencing combined with irradiation reduced U87MG cell proliferation when cultured in monolayers and reduced neurosphere cell number compared with the SCR irradiated group; however, not significantly. Differentiation of U87MG cells from neurospheres was reduced in HEB­silenced cells, whereas in irradiated cells the proportion of CD133+ cells was similar in HEB­silenced cells compared with the SCR control. These results suggest that HEB may contribute to the proliferation and maintenance of GBM cells. However, only limited effects were exerted by irradiation in HEB­silenced cells. HEB may be a potential target to decrease proliferation in U87MG GBM cells, grown as monolayers or neurospheres, and may provide important information for the development of novel strategies for cancer therapy.