CNFD (6b,7-dihydro-5H-cyclopenta[b]naphtho[2,1-d]furan-5,6(9aH)-dione) is a semisynthetic naphthoquinone derived from lawsone that has cytotoxic action in different tumor lines and anticancer activity in vivo. Therefore, this molecule is a relevant candidate for drug development, but there is still no information on its human metabolism and systemic elimination. This study aimed to investigate the in vitro metabolism of this naphthoquinone by human liver microsomes. Initially, in order to determine the in vitro enzymatic kinetic parameters, a high performance liquid chromatography (HPLC) method to quantify the CNFD was developed and validated. In addition, the enzymatic kinetic data, the predicted pharmacokinetic in vivo parameters and the phenotyping study were presented. The main metabolism sites and metabolites have been suggested in silico. The developed HPLC method was linear, reproducible, selective, accurate, and stable. The enzymatic kinetic parameters revealed a sigmoidal profile. In vitro to in vivo extrapolation hepatic metabolic clearance was 10.39 mL min-1 kg-1 protein and the liver extraction rate was 51%. The clearance in vivo associated with a hepatic extraction ratio indicates that the hepatic metabolism is the main route of elimination. Although all cytochrome P450 enzymes evaluated metabolized CNFD, CYP2C9 and CYP3A4 showed higher metabolic capacity. For the first time, metabolism studies of CNFD were demonstrated.

Resumo Introdução O tratamento da obesidade grave é pouco estudado no Sistema Único de Saúde (SUS). Objetivo: Descrever clientela, atendimento e fatores associados à perda de peso em Centros de Referência em Obesidade (CRO), na cidade do Rio de Janeiro. Método Coorte retrospectiva baseada em registros de prontuários de 317 indivíduos com obesidade grave atendidos em três CRO-RJ entre 2011 e 2016. Foram descritas frequências e estimados riscos relativos com IC 95% para perda de ≥ 5% do peso inicial aos 6 e 12 meses de tratamento. Resultados Predominaram mulheres (76,3%), negros (69,5%), com média de 44,6 anos (DP 11,9), tratamento prévio para obesidade (62,1%), história familiar de obesidade (42,6%) e 2 ou mais comorbidades (52%). A mediana do IMC inicial foi de 51,5 kg/m2, e a do tempo de tratamento, 10 meses. Somente 14,8% perderam ≥ 5% do peso inicial após 12 meses de tratamento, sendo o risco relativo de perda de peso 78% maior entre indivíduos brancos. Predominaram tratamento dietético e mudanças de hábitos de vida, com baixo uso de medicamentos antiobesidade (14%) e cirurgia bariátrica (3%, sendo 1% no SUS). Conclusão Os resultados do tratamento sugerem necessidade de readequar práticas terapêuticas às indicadas para indivíduos com superobesidade, inclusive maior acesso à cirurgia bariátrica.

Abstract Background There are few studies on severe obesity in the Brazilian Unified Health System (SUS). Objective To describe patients, treatment approaches and factors associated with weight loss at the Obesity Reference Centers (CRO), in the city of Rio de Janeiro. Method Retrospective cohort study based on medical records of 317 patients with severe obesity admitted to three CRO-RJ, between 2011 and 2016. Frequencies were described and relative risks with 95% CI of ≥ 5% loss of body weight at 6 and 12 months of treatment were estimated. Results Patients were mainly black (69.5%), women (76.3%), mean age 44.6 years (SD 11.9), reporting ≥ 2 comorbidities (52%), previous treatment (62.1%) and family history of obesity (42.6%). The initial mean BMI was 51.5 kg/m2; average treatment time was 10 months. 14.8% lost ≥ 5% of the initial weight after 12 months of treatment and the relative risk of weight loss was 78% higher among white patients. Approaches based on diet and changes in lifestyle predominated. 14% used anti-obesity drugs and 3% underwent bariatric surgery (1% in the SUS). Conclusion Treatment results suggest the need to adjust management to follow treatment guidelines for superobesity, including bariatric surgery.

Resumen Introducción El tratamiento de la obesidad severa está poco estudiado en el SUS. Objetivo Describir la clientela, el manejo y los factores asociados con la pérdida de peso en los Centros de Referencia para la Obesidad (CRO), en la ciudad de Río de Janeiro. Método Cohorte retrospectiva basada en registros médicos de 317 individuos con obesidad severa tratados en tres CRO-RJ entre 2011 y 2016. Se describieron las frecuencias y estimaron riesgos relativos con un IC del 95% para la pérdida de ≥ 5% del peso inicial a los 6 y 12 meses de tratamiento. Resultados Predominaron las mujeres (76.3%), negros (69.5%), con una media de 44.6 años (DE 11.9), tratamiento previo (62.1%), antecedentes familiares de obesidad (42.6%) y dos o más comorbilidades (52.0%). La mediana del IMC inicial fue de 51.5 kg/m2 y el tiempo de tratamiento fue de 10 meses. Solo el 14.8% perdió ≥ 5% de su peso inicial después de 12 meses de tratamiento, con un riesgo de pérdida de peso 78% mayor entre los individuos blancos. Predominaron el tratamiento dietético y los cambios en los hábitos de estilo de vida, con un bajo uso de medicamentos contra la obesidad (14%) y cirugía bariátrica (3%, 1% en SUS). Conclusión Los resultados del tratamiento sugieren la necesidad de reajustar las prácticas terapéuticas a las indicadas en la superobesidad, incluido un mayor acceso a la cirugía bariátrica.

Resumo Introdução O tratamento da obesidade grave é pouco estudado no Sistema Único de Saúde (SUS). Objetivo: Descrever clientela, atendimento e fatores associados à perda de peso em Centros de Referência em Obesidade (CRO), na cidade do Rio de Janeiro. Método Coorte retrospectiva baseada em registros de prontuários de 317 indivíduos com obesidade grave atendidos em três CRO-RJ entre 2011 e 2016. Foram descritas frequências e estimados riscos relativos com IC 95% para perda de ≥ 5% do peso inicial aos 6 e 12 meses de tratamento. Resultados Predominaram mulheres (76,3%), negros (69,5%), com média de 44,6 anos (DP 11,9), tratamento prévio para obesidade (62,1%), história familiar de obesidade (42,6%) e 2 ou mais comorbidades (52%). A mediana do IMC inicial foi de 51,5 kg/m2, e a do tempo de tratamento, 10 meses. Somente 14,8% perderam ≥ 5% do peso inicial após 12 meses de tratamento, sendo o risco relativo de perda de peso 78% maior entre indivíduos brancos. Predominaram tratamento dietético e mudanças de hábitos de vida, com baixo uso de medicamentos antiobesidade (14%) e cirurgia bariátrica (3%, sendo 1% no SUS). Conclusão Os resultados do tratamento sugerem necessidade de readequar práticas terapêuticas às indicadas para indivíduos com superobesidade, inclusive maior acesso à cirurgia bariátrica.

Abstract Background There are few studies on severe obesity in the Brazilian Unified Health System (SUS). Objective To describe patients, treatment approaches and factors associated with weight loss at the Obesity Reference Centers (CRO), in the city of Rio de Janeiro. Method Retrospective cohort study based on medical records of 317 patients with severe obesity admitted to three CRO-RJ, between 2011 and 2016. Frequencies were described and relative risks with 95% CI of ≥ 5% loss of body weight at 6 and 12 months of treatment were estimated. Results Patients were mainly black (69.5%), women (76.3%), mean age 44.6 years (SD 11.9), reporting ≥ 2 comorbidities (52%), previous treatment (62.1%) and family history of obesity (42.6%). The initial mean BMI was 51.5 kg/m2; average treatment time was 10 months. 14.8% lost ≥ 5% of the initial weight after 12 months of treatment and the relative risk of weight loss was 78% higher among white patients. Approaches based on diet and changes in lifestyle predominated. 14% used anti-obesity drugs and 3% underwent bariatric surgery (1% in the SUS). Conclusion Treatment results suggest the need to adjust management to follow treatment guidelines for superobesity, including bariatric surgery.

Resumen Introducción El tratamiento de la obesidad severa está poco estudiado en el SUS. Objetivo Describir la clientela, el manejo y los factores asociados con la pérdida de peso en los Centros de Referencia para la Obesidad (CRO), en la ciudad de Río de Janeiro. Método Cohorte retrospectiva basada en registros médicos de 317 individuos con obesidad severa tratados en tres CRO-RJ entre 2011 y 2016. Se describieron las frecuencias y estimaron riesgos relativos con un IC del 95% para la pérdida de ≥ 5% del peso inicial a los 6 y 12 meses de tratamiento. Resultados Predominaron las mujeres (76.3%), negros (69.5%), con una media de 44.6 años (DE 11.9), tratamiento previo (62.1%), antecedentes familiares de obesidad (42.6%) y dos o más comorbilidades (52.0%). La mediana del IMC inicial fue de 51.5 kg/m2 y el tiempo de tratamiento fue de 10 meses. Solo el 14.8% perdió ≥ 5% de su peso inicial después de 12 meses de tratamiento, con un riesgo de pérdida de peso 78% mayor entre los individuos blancos. Predominaron el tratamiento dietético y los cambios en los hábitos de estilo de vida, con un bajo uso de medicamentos contra la obesidad (14%) y cirugía bariátrica (3%, 1% en SUS). Conclusión Los resultados del tratamiento sugieren la necesidad de reajustar las prácticas terapéuticas a las indicadas en la superobesidad, incluido un mayor acceso a la cirugía bariátrica.

Resumo Introdução A força extrabucal é a estratégia mais comum para corrigir a má oclusão de Classe II de Angle, restringindo e redirecionando o crescimento maxilar. Objetivo Avaliar as alterações esqueléticas decorrentes do uso do aparelho extrabucal, com ancoragens cervical e parietal, associado ao aparelho ortodôntico fixo, em pacientes em crescimento com má oclusão de Classe II (Angle) tratados na clínica de um centro de treinamento ortodôntico. Material e método As idades ao início e ao término do tratamento, o tipo de ancoragem, e os valores de algumas variáveis cefalométricas foram obtidos dos arquivos clínicos. Após a aplicação dos critérios de inclusão e exclusão, foram selecionados 56 prontuários. Em seguida, a amostra foi dividida em dois grupos, de acordo com a ancoragem: cervical (n= 30) e parietal (n=26). As diferenças entre os valores inicial (T1) e final (T2) das variáveis cefalométricas SNA, SNB, ANB, AO-BO, GoGn.SN e AFI (porcentagem da altura facial inferior em relação à altura facial total) foram avaliadas em ambos os grupos. Resultado Diferenças significativas entre T1 e T2 foram encontradas em relação às variáveis SNB e ANB em ambos os grupos. A variável AO-BO apresentou diferença estatisticamente significante apenas no grupo cervical. As demais variáveis não apresentaram diferenças significantes entre T1 e T2. Conclusão As alterações esqueléticas decorrentes do uso das ancoragens cervical e parietal foram muito semelhantes. Houve diminuição da discrepância anteroposterior entre a maxila e a mandíbula devido ao deslocamento anterior da mandíbula, sem alterações verticais significativas.

Abstract Introduction Extraoral strength is the most common strategy to correct Angle Class II malocclusion, restricting and redirecting the maxillary growth. Objective To evaluate the skeletal changes resulting from the use of headgear, with cervical and parietal anchorages, associated with a full fixed orthodontic appliance, in growing patients with Class II malocclusion (Angle) treated in the clinic of an orthodontic training center. Material and method The ages at the beginning and end of the treatment, anchorage type, and the values of some cephalometric variables were obtained from the clinical files. After applying the inclusion and exclusion criteria, 56 patient files were selected. Then, the sample was divided into two groups, according to the anchorage type: cervical (n=30) and parietal (n=26). The differences between the initial (T1) and final (T2) values of cephalometric measurements SNA, SNB, ANB, AO-BO, GoGn.SN and LHF (percentage of lower facial height to total facial height) were evaluated in both groups. Result Significant differences between T1 and T2 were found relative to SNB and ANB variables in both groups. The AO-BO variable presented a statistically significant difference only in the cervical group. The remaining variables did not show significant differences between T1 and T2. Conclusion The skeletal changes resulting from the use of cervical or parietal anchorage were very similar. There was a decrease in the sagittal discrepancy between the maxillary bones due to forward displacement of the mandible, without significant vertical changes.

RESUMO Objetivo: Avaliar as alterações dentárias e esqueléticas decorrentes do uso exclusivo do aparelho extrabucal durante 15 ± 4 meses para tratamento de pacientes com má oclusão de Classe II divisão 1 (Grupo Experimental, GE). Métodos: As diferenças entre o início (T1) e imediatamente após o término da terapia (T2) com o aparelho extrabucal de tração cervical (Grupo Experimental, GE, n = 23) foram comparadas àquelas apresentadas por um grupo composto por indivíduos não tratados (Grupo Controle, GC, n = 22), com má oclusão e faixa etária cronológica compatíveis. As variáveis cefalométricas avaliadas foram: ANB, GoGn.SN, AO-BO, S’-ENA, S’-A, S’-B, S’-Pog e S’-U6 (primeiro molar superior). Os testes de Shapiro-Wilk e Levene foram aplicados para avaliar os resultados. Resultados: Diferenças significativas entre T1 e T2 foram encontradas para as variáveis ANB, S’-U6, AO-BO, S’-ENA, S’-A, S’-B e S’-Pog, quando comparados os dois grupos. Nenhuma diferença estatisticamente significativa foi encontrada em relação ao ângulo GoGn.SN. Conclusão: O uso do aparelho extrabucal com tração cervical promoveu movimento para distal do primeiro molar superior e restringiu o deslocamento anterior da maxila, sem afetar significativamente o ângulo GoGn.SN.

ABSTRACT Objective: Evaluate dental and skeletal changes resulting from the exclusive use of the cervical headgear for 15 ± 4 months in the treatment of patients with Class II division 1 malocclusion. Methods: Differences between the beginning (T1) and immediately after the end of the therapy (T2) with the cervical headgear in growing patients (Experimental Group, EG, n = 23) were examined and compared, during compatible periods, with those presented by a group of untreated individuals (Control Group, CG, n =22) with similar malocclusions and chronological age. The cephalometric variables evaluated were: ANB, GoGn.SN, AO-BO, S'-ANS, S'-A, S'-B, S'-Pog and S'-U6 (maxillary first molar). The Shapiro-Wilk and Levene tests were used to evaluate the results. Results: Significant differences were found relative to the ANB, S'-U6, AO-BO, S'-ANS, S'-A, S'-B and S'-Pog variables between T1 and T2 when comparing both groups. No statistically significant variation was found regarding the GoGn.SN angle. Conclusions: The use of cervical headgear promoted distal movement of the maxillary first molars and restricted the anterior displacement of the maxilla, without significantly affecting the GoGn.SN angle.

ABSTRACT BACKGROUND: Urinary incontinence is a highly prevalent condition that impacts self-esteem and overall quality of life. Many non-surgical treatment options are available, ranging from pharmacological approaches to pelvic exercises. We aimed to summarize the available evidence regarding these non-surgical interventions. DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP). METHODS: A sensitive search was conducted to identify all Cochrane systematic reviews that fulfilled the inclusion criteria. Titles and abstracts were screened by two authors. RESULTS: We included 20 Cochrane systematic reviews: 4 assessing methods of vesical training, 3 evaluating pharmacological interventions, 4 studying pelvic floor muscle training approaches and 9 aimed at other alternatives (such as urethral injections, weighted vaginal cone use, acupuncture, biostimulation and radiofrequency therapy). The reviews found that the evidence regarding the benefits of these diverse interventions ranged in quality from low to high. CONCLUSIONS: This review included 20 Cochrane systematic reviews that provided evidence (of diverse quality) for non-pharmacological interventions for patients with urinary incontinence. Moderate to high quality of evidence was found favoring the use of pelvic floor muscle training among women with urinary incontinence. To establish solid conclusions for all the other comparisons, further studies of good methodological quality are needed.

Populations of Ocyurus chrysurus were compared genetically and morphometrically along the West Atlantic coast to test the null hypothesis of population homogeneity in the area. Brazilian populations were found to be differentiated in shape (canonical variates analysis; F[48,515] = 10.84, p < 0.0001). Analyses of mitochondrial DNA sequences (663 bp of the control region) did not show any differences between Brazilian populations but could detect differences between Brazilian and Caribbean (Belize) populations. The samples from Pernambuco differed significantly from the other Brazilian populations in allozyme frequencies (11 loci; F ST = 0.167; p < 0.05), but this may have resulted from the small number of samples analysed for that population. Sequence variation of Belize samples departed from neutral expectations (Fu's FS = -8.88; p < 0.001). A mismatch distribution analysis points to an ancient population expansion in that area. We conclude that the genetic data do not allow the rejection of the null hypothesis of panmixia for Brazilian yellowtail snapper populations which should be treated as a single genetic stock, with a latitudinal gradient on their morphology which probably results from phenotypic plasticity. On the other hand, there is a severe restriction to gene flow between O. chrysurus populations from the Caribbean and from the southwestern Atlantic.

OBJECTIVE: The purpose of this study was to compare the accuracy of two working cast fabrication techniques using strain-gauge analysis. METHODS: Two working cast fabrication methods were evaluated. Based on a master model, 20 working casts were fabricated by means of an indirect impression technique using polyether after splinting the square transfer copings with acrylic resin. Specimens were assigned to 2 groups (n=10): Group A (GA): type IV dental stone was poured around the abutment analogs in the conventional way; Group B (GB), the dental stone was poured in two stages. Spacers were used over the abutment analogs (rubber tubes) and type IV dental stone was poured around the abutment analogs in the conventional way. After the stone had hardened completely, the spacers were removed and more stone was inserted in the spaces created. Six strain-gauges (Excel Ltd.), positioned in a cast bar, which was dimensionally accurate (perfect fit) to the master model, recorded the microstrains generated by each specimen. Data were analyzed statistically by the variance analysis (ANOVA) and Tukey's test (α= 5%). RESULTS: The microstrain values (µepsilon) were (mean±SD): GA: 263.7±109.07µepsilon, and GB: 193.73±78.83µepsilon. CONCLUSION: There was no statistical difference between the two methods studied.