In silico prediction of ADMET parameters and in vitro evaluation of antioxidant and cytotoxic activities promoted by indole-thiosemicarbazone compounds.

Cancer is a complex and multifactorial disease characterized by uncontrolled cell growth and is one of the main causes of death in the world. This work aimed to evaluate a small series of 10 different indole-thiosemicarbazone compounds as potential antitumor agents. This is a pioneering study. For this, the antioxidant and cytotoxic capacity against normal and tumor cells was evaluated. The results showed that the compounds were able to promote moderate to low antioxidant activity for the ABTS radical scavenging assay. ADMET in silico assays showed that the compounds exhibited good oral bioavailability. As for toxicity, they were able to promote low cytotoxicity against normal cells, in addition to not being hemolytic. The compounds showed promising in vitro antitumor activity against the T47D, MCF-7, Jurkat and DU-145 strains, not being able to inhibit the growth of the Hepg2 strain. Through this in vitro study, it can be concluded that the compounds are potential candidates for antitumor agents.

Interaction study with DNA/HSA, anti-topoisomerase IIα, cytotoxicity and in vitro antiproliferative evaluations and molecular docking of indole-thiosemicarbazone compounds.

In this work we will discuss the antiproliferative evaluation and the possible mechanisms of action of indole-thiosemicarbazone compounds LTs with anti-inflammatory activity, previously described in the literature. In this perspective, some analyzes were carried out, such as the study of binding to human serum albumin (HSA) and to biological targets: DNA and human topoisomerase IIα (topo). Antiproliferative study was performed with DU-145, Jukart, MCF-7 and T-47D tumor lines and J774A.1, besides HepG2 macrophages and hemolytic activity. In the HSA interaction tests, the highest binding constant was 3.70 × 106 M-1, referring to LT89 and in the fluorescence, most compounds, except for LT76 and LT87, promoted fluorescent suppression with the largest Stern-Volmer constant for the LT88 3.55 × 104. In the antiproliferative assay with DU-145 and Jurkat strains, compounds LT76 (0.98 ± 0.10/1.23 ± 0.32 µM), LT77 (0.94 ± 0.05/1.18 ± 0.08 µM) and LT87 (0.94 ± 0.12/0.84 ± 0.09 µM) stood out, due to their IC50 values mentioned above. With the MCF-7 and T-47D cell lines, the lowest IC50 was presented by LT81 with values of 0.74 ± 0.12 µM and 0.68 ± 0.10 µM, respectively, followed by the compounds LT76 and LT87. As well as the positive control amsacrine, the compounds LT76, LT81 and LT87 were able to inhibit the enzymatic action of human Topoisomerase IIα.

The Impact of Cardiovascular Risk Factors and Renal Disease on Outcomes in Patients Hospitalized with COVID-19: An Observational Study from Two Public Hospitals in Brazil

Abstract Background Cardiovascular risk factors are prognostic factors in coronavirus disease 2019 (COVID-19) and have been scarcely studied in Brazil. Objective The aim of this study was to assess the impact of cardiovascular risk factors on the outcomes of patients admitted for COVID-19. Methods From July 2020 to February 2021, 200 patients from two public hospitals were enrolled. Patients were included if they had typical symptoms or signs of COVID-19, a positive real-time polymerase chain reaction test (RT-PCR) for COVID-19, and an age above 18 years. This is a prospective, observational, and longitudinal study. Data were collected within 24 h of admission. The primary endpoint was a combination of hospital lethality, mechanical ventilation, hemodialysis, or length of hospital stay >28 days. Continuous variables were compared with the Student's t-test for independent samples or the Mann-Whitney test. For comparisons of proportions, the χ 2 test was applied. ROC curves and survival curves were constructed. Multivariate logistic regression was performed to identify independent predictors of events. The level of significance was 0.05. Results There were 98 (49%) events during the hospital course, and 72 (36%) died in the hospital. Patients with a primary endpoint were older and more likely to have a history of hypertension, diabetes, chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD). Vital signs at admission associated with events were diastolic blood pressure, respiratory rate, and oxygen saturation in ambient air (O 2 Sat). Serum creatinine >1.37 mg/dL at admission had a sensitivity of 51.6 and a specificity of 82% to predict the primary endpoint, with an area under the curve (AUC) of 0.68. In multivariate analysis, age, diabetes, CKD, and COPD were independent predictors of the primary endpoint. Age and CKD were independent predictors of in-hospital lethality. Conclusion Cardiovascular risk factors, such as diabetes and CKD, were related to a worse prognosis in patients hospitalized with COVID-19 in this sample from two public hospitals in the state of Rio de Janeiro.

Thiazolidine derivatives: In vitro toxicity assessment against promastigote and amastigote forms of Leishmania infantum and ultrastructural study.

Neglected diseases, such as Leishmaniasis, constitute a group of communicable diseases that occur mainly in tropical countries. Considered a public health problem with limited treatment. Therefore, there is a need for new therapies. In this sense, our proposal was to evaluate in vitro two series of thiazolidine compounds (7a-7e and 8a-8e) against Leishmania infantum. We performed in vitro evaluations through macrophage cytotoxicity assays (J774) and nitric oxide production, activity against promastigotes and amastigotes, as well as ultrastructural analyzes in promastigotes. In the evaluation of cytotoxicity, the thiazolidine compounds presented CC50 values between 8.52 and 126.83 µM. Regarding the evaluation against the promastigote forms, the IC50 values ranged between 0.42 and 142.43 µM. Compound 7a was the most promising, as it had the lowest IC50. The parasites treated with compound 7a showed several changes, such as cell body shrinkage, shortening and loss of the flagellum, intense mitochondrial edema and cytoplasmic vacuolization, leading the parasite to cell inviability. In assays against the amastigote forms, the compound showed a low IC50 (0.65 µM). These results indicate that compound 7a was efficient for both evolutionary forms of the parasite. In silico studies suggest that the compound has good oral bioavailability. These results show that compound 7a is a potential drug candidate for the treatment of Leishmaniasis.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of oesophageal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

Novel indole-thiazole and indole-thiazolidinone derivatives as DNA groove binders.

In this study, we report the synthesis of eight novel indole-thiazole and indole-thiazolidinone derivatives, as well as their ability to interact with DNA, analysed through the UV-vis absorption, fluorescence, circular dichroism (CD), viscosity techniques and molecular docking. The ctDNA interaction analysis demonstrated different spectroscopic effects and the affinity constants (Kb) calculated by the UV-vis absorption method were between 2.08 × 105 and 6.99 × 106 M-1, whereas in the fluorescence suppression constants (Ksv) ranged between 0.38 and 0.77 × 104 M-1 and 0.60-7.59 × 104 M-1 using Ethidium Bromide (EB) and 4',6-Diamidino-2-phenylindole (DAPI) as fluorescent probes, respectively. Most derivatives did not alter significantly the secondary structure of the ctDNA according to the CD results. None of the compounds was able to change the relative viscosity of the ctDNA. These results prove that compounds interact with ctDNA via groove binding, which was confirmed by A-T rich oligonucleotide sequence assay with compound JF-252, suggesting the importance of both the phenyl ring coupled to C-4 thiazole ring and the bromo-unsubstituted indole nucleus.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of gastric cancer.

Gastric cancer is among the ten most common types of cancer worldwide. Most cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of gastric carcinomas. The Brazilian Group of Gastrointestinal Tumors (GTG) invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy and follow-up, which was followed by presentation, discussion, and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of gastric carcinomas in several scenarios and clinical settings.

Migração e atenção primária à saúde no estado de Roraima / Migration and primary health care in the state of Roraima / Migración y atención primaria en salud en el estado de Roraima

A migração não é um fenômeno recente e muito menos restrito a uma parte do mundo. Este artigo tem por objetivo chamar atenção para o aumento significativo de demanda pelo direito à saúde no estado de Roraima e como as políticas públicas são de suma importância para ajudar na superação de uma crise humanitária. O estudo foi desenvolvido dentro de uma abordagem da pesquisa qualitativa do tipo teórica, a partir da realização de uma revisão bibliográfica referente à migração e ao direito à saúde desta população e análise de públicos e publicizados por meio do sítio eletrônico do Ministério da Saúde foram obtidos diretamente por meio de busca ativa e solicitados por meio da Lei de Acesso a Informação. Os dados da Atenção Primária apresentam uma evolução ao longo dos últimos anos. Pode-se inferir, a partir dos dados presentados pela ACNUR, bem como pelo aumento significativo de atendimentos, que o fluxo migratório teve um impacto importante nesse primeiro nível de atenção do sistema estadual de saúde. Em que pese a complexidade desse tipo de política pública, cada vez mais os dados apontam para a necessidade de um olhar atento para os fluxos migratórios internos e internacionais, na perspectiva de ações intersetoriais com o intuito de assegurar os direitos humanos, a dignidade da vida, o direito à saúde, à educação, ao trabalho e a liberdade de expressão. (AU)

Migration is not a recent phenomenon and much less restricted to one part of the world. This article is about the significant increase in demand for the right to health in the state of Roraima and how public policies are of paramount importance in helping to overcome a humanitarian crisis. The study was developed within a theoretical qualitative research approach, based on a bibliographic review regarding migration and the right to health of this population and analysis of public and published through the Ministry of Health website, were obtained directly through active search and requested through the Access to Information Act. Primary care data have evolved over the last few years. It can be inferred from the data presented by UNHCR, as well as the significant increase in attendance, that the migratory flow had an important impact on this first level of care of the state health system. Despite the complexity of this type of public policy, data increasingly point to the need for a close look at internal and international migratory flows, from the perspective of intersectoral actions to ensure human rights, the dignity of life. , the right to health, education, work and freedom of expression. (AU)

La migración no es un fenómeno reciente y mucho menos restringido a una parte del mundo. Este artículo tiene como objetivo llamar la atención sobre el aumento significativo de la demanda del derecho a la salud en el estado de Roraima y cómo las políticas públicas son de suma importancia para ayudar a superar una crisis humanitaria. El estudio se desarrolló dentro de un enfoque teórico de investigación cualitativa, basado en una revisión bibliográfica sobre la migración y el derecho a la salud de esta población y el análisis del público y publicado a través del sitio web del Ministerio de Salud, se obtuvieron directamente a través de la búsqueda activa y se solicitaron a través de la Ley de Acceso a la Información. Los datos de atención primaria han evolucionado en los últimos años. Se puede inferir de los datos presentados por ACNUR, así como del aumento significativo en la asistencia, que el flujo migratorio tuvo un impacto importante en este primer nivel de atención del sistema de salud estatal. A pesar de la complejidad de este tipo de política pública, los datos apuntan cada vez más a la necesidad de observar de cerca los flujos migratorios internos e internacionales, desde la perspectiva de acciones intersectoriales para garantizar los derechos humanos, la dignidad de la vida, el derecho a la salud, la educación, el trabajo y la libertad de expresión.

Motor neuroprosthesis for promoting recovery of function after stroke.

BACKGROUND: Motor neuroprosthesis (MN) involves electrical stimulation of neural structures by miniaturized devices to allow the performance of tasks in the natural environment in which people live (home and community context), as an orthosis. In this way, daily use of these devices could act as an environmental facilitator for increasing the activities and participation of people with stroke. OBJECTIVES: To assess the effects of MN for improving independence in activities of daily living (ADL), activities involving limbs, participation scales of health-related quality of life (HRQoL), exercise capacity, balance, and adverse events in people after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (searched 19 August 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (August 2019), MEDLINE (1946 to 16 August 2019), Embase (1980 to 19 August 2019), and five additional databases. We also searched trial registries, databases, and websites to identify additional relevant published, unpublished, and ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) and randomized controlled cross-over trials comparing MN for improving activities and participation versus other assistive technology device or MN without electrical stimulus (stimulator is turned off), or no treatment, for people after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, and assessed risk of bias of the included studies. Any disagreements were resolved through discussion with a third review author. We contacted trialists for additional information when necessary and performed all analyses using Review Manager 5. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included four RCTs involving a total of 831 participants who were more than three months poststroke. All RCTs were of MN that applied electrical stimuli to the peroneal nerve. All studies included conditioning protocols to adapt participants to MN use, after which participants used MN from up to eight hours per day to all-day use for ambulation in daily activities performed in the home or community context. All studies compared the use of MN versus another assistive device (ankle-foot orthosis [AFO]). There was a high risk of bias for at least one assessed domain in three of the four included studies. No studies reported outcomes related to independence in ADL. There was low-certainty evidence that AFO was more beneficial than MN on activities involving limbs such as walking speed until six months of device use (mean difference (MD) -0.05 m/s, 95% confidence interval (CI) -0.10 to -0.00; P = 0.03; 605 participants; 2 studies; I2 = 0%; low-certainty evidence); however, this difference was no longer present in our sensitivity analysis (MD -0.07 m/s, 95% CI -0.16 to 0.02; P = 0.13; 110 participants; 1 study; I2 = 0%). There was low to moderate certainty that MN was no more beneficial than AFO on activities involving limbs such as walking speed between 6 and 12 months of device use (MD 0.00 m/s, 95% CI -0.05 to 0.05; P = 0.93; 713 participants; 3 studies; I2 = 17%; low-certainty evidence), Timed Up and Go (MD 0.51 s, 95% CI -4.41 to 5.43; P = 0.84; 692 participants; 2 studies; I2 = 0%; moderate-certainty evidence), and modified Emory Functional Ambulation Profile (MD 14.77 s, 95% CI -12.52 to 42.06; P = 0.29; 605 participants; 2 studies; I2 = 0%; low-certainty evidence). There was no significant difference in walking speed when MN was delivered with surface or implantable electrodes (test for subgroup differences P = 0.09; I2 = 65.1%). For our secondary outcomes, there was very low to moderate certainty that MN was no more beneficial than another assistive device for participation scales of HRQoL (standardized mean difference 0.26, 95% CI -0.22 to 0.74; P = 0.28; 632 participants; 3 studies; I2 = 77%; very low-certainty evidence), exercise capacity (MD -9.03 m, 95% CI -26.87 to 8.81; P = 0.32; 692 participants; 2 studies; I2 = 0%; low-certainty evidence), and balance (MD -0.34, 95% CI -1.96 to 1.28; P = 0.68; 692 participants; 2 studies; I2 = 0%; moderate-certainty evidence). Although there was low- to moderate-certainty evidence that the use of MN did not increase the number of serious adverse events related to intervention (risk ratio (RR) 0.35, 95% CI 0.04 to 3.33; P = 0.36; 692 participants; 2 studies; I2 = 0%; low-certainty evidence) or number of falls (RR 1.20, 95% CI 0.92 to 1.55; P = 0.08; 802 participants; 3 studies; I2 = 33%; moderate-certainty evidence), there was low-certainty evidence that the use of MN in people after stroke may increase the risk of participants dropping out during the intervention (RR 1.48, 95% CI 1.11 to 1.97; P = 0.007; 829 participants; 4 studies; I2 = 0%). AUTHORS' CONCLUSIONS: Current evidence indicates that MN is no more beneficial than another assistive technology device for improving activities involving limbs measured by Timed Up and Go, balance (moderate-certainty evidence), activities involving limbs measured by walking speed and modified Emory Functional Ambulation Profile, exercise capacity (low-certainty evidence), and participation scale of HRQoL (very low-certainty evidence). Evidence was insufficient to estimate the effect of MN on independence in ADL. In comparison to other assistive devices, MN does not appear to increase the number of falls (moderate-certainty evidence) or serious adverse events (low-certainty evidence), but may result in a higher number of dropouts during intervention period (low-certainty evidence).

Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition.

Twelve 2-(quinolin-4-ylmethylene) hydrazinecarbothioamide derivatives were synthetized and their biological properties were investigated, among which, the ability to interact with DNA and BSA through UV-Vis absorption, fluorescence, Circular Dichroism, molecular docking and relative viscosity, antiproliferative activity against MCF-7 and T-47D mammary tumor cells and RAW-264.7 macrophages and inhibitory capacity of the enzyme topoisomerase IIα. In the binding study with DNA and BSA, all the compounds displayed affinity for interaction with both biomolecules, especially JF-92 (p-ethyl-substituted), with binding constant of 1.62 × 106 and 1.43 × 105, respectively, and DNA binding mode by intercalation. The IC50 values were obtained between 0.81 and 1.48 µM and topoisomerase inhibition results in 10 µM. Thus, we conclude that the reduction of the acridine to quinoline ring did not disrupt the antitumor action and that substitution patterns are important for biomolecule interaction affinity as they demonstrate the potential of these compounds for anticancer therapy.

Topoisomerase inhibition and albumin interaction studies of acridine-thiosemicarbazone derivatives.

In the present study, acridine-thiosemicarbazones (ATD) derivatives were tested for their interaction properties with BSA through UV-Vis absorption and fluorescence spectroscopic studies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated after the derivatives were added to the BSA. Values for the binding constant (Kb) ranged from 1.62 × 104 to 8.71 × 105 M-1 and quenching constant (KSV) from 3.46 × 102 to 7.83 × 103 M-1 indicating a good affinity to BSA protein. Complementary, two compounds were selected to assess their inhibition activity against topoisomerase IIα enzyme, of which derivative 3a presented the best result. Moreover, to evaluate protein-ligand interactions, as well as the antitopoisomerase potential of these compounds, tests of molecular modeling were performed between all compounds using the albumin and Topoisomerase IIα/DNA complex. Finally, in silico studies showed that all derivatives used in this research displayed good oral bioavailability potential.

Static or dynamic stretching program does not change the acute responses of neuromuscular and functional performance in healthy subjects: a single-blind randomized controlled trial / Programa de alongamento estático ou dinâmico não altera as respostas agudas do desempenho neuromuscular e funcional de sujeitos saudáveis: ensaio controlado randomizado e cego / Un programa de estiramientos estáticos o dinámicos no modifica las respuestas agudas del rendimiento neuromuscular y funcional en individuos sanos: ensayo ciego controlado de distribución aleatoria

Abstract The purpose of this study was to compare the effects of a single hamstring static or dynamic stretching session and a 10-session stretching program on the range of motion, neuromuscular performance and functional performance of healthy subjects. Forty-five, healthy, active men were divided into three groups: control; static stretching and dynamic stretching. There were no significant differences in ratings between the experimental and control groups for any of the variables (p > 0.05). It can be concluded that neither a single session of hamstring static or dynamic stretching nor a 10-session stretching program affected range of motion, neuromuscular or functional performance.

Resumo A proposta deste estudo foi comparar os efeitos de uma única sessão de alongamento estático ou dinâmico dos isquiotibias e dez sessões do programa de alongamento na amplitude de movimento e desempenho neuromuscular e funcional de indivíduos saudáveis. Quarenta e cinco homens ativos e saudáveis, foram distribuídos em três grupos: controle, alongamento estático e alongamento dinâmico. Não houve diferença significativa entre os grupos experimentais e controle para todas as variáveis (p >0,05). Pode-se concluir que nem uma única sessão de alongamento estático e dinâmico dos isquiotibiais, nem 10 sessões do programa de alongamento afetaram a amplitude de movimento e o desempenho neuromuscular e funcional.

Resumen El propósito de este estudio fue comparar los efectos de una sola sesión de estiramientos estático o dinámico en los isquiotibiales, y diez sesiones del programa de estiramiento en el rango de movimiento y rendimiento neuromuscular y funcional de individuos sanos. Cuarenta y cinco hombres activos y sanos fueron divididos en tres grupos: control, estiramiento estático y estiramiento dinámico. No hubo ninguna diferencia considerable entre los grupos experimentales y de control respecto a todas las variables (p >0,05). Se puede concluir que ni una sola sesión de estiramiento estático o dinámico de los isquiotibiales ni 10 sesiones del programa de estiramiento afectaron al rango de movimiento ni al rendimiento neuromuscular y funcional.

Synthesis, DNA and protein interactions and human topoisomerase inhibition of novel Spiroacridine derivatives.

Nine new spiroacridine derivatives were synthetized by introducing cyano-N-acylhydrazone group between the acridine and phenyl-substituted rings followed by spontaneous cyclization. The new compounds were assayed for their DNA binding properties, human topoisomerase IIα inhibition and bovine serum albumin (BSA) interaction. Besides, docking analysis were performed in order to better understanding the biomolecule-compounds interactions. All compounds interacted with BSA which was demonstrated by the fluorescence suppression constant of 104 M-1. Compounds with chloro and NO2 substituents at that para-position on phenyl ring demonstrated the best results for BSA interaction. DNA binding constant determined by UV-vis data demonstrated high values for AMTAC-11 and AMTAC-14, 1.1 × 108 M-1 and 4.8 × 106 M-1, respectively, and all others presented constant values of 105 M-1. AMTAC-06 with chloro at para-position on phenyl ring presented a topoisomerase II inhibition of 84.34% in comparison to the positive controls used. Docking studies indicated that AMTAC-06 is able to intercalate the DNA base pairs at topoisomerase IIα active site, preventing DNA connection after break, in a process known as poisoning. Topoisomerase enzyme inhibition result was correlated to BSA interaction profile, since AMTAC-06 showed the best results in both analysis. The findings obtained here proved that methoxy or chloro substitution on phenyl ring at para-position is fundamental for in vitro activity of new spiroacridine derivatives, and indicates that AMTAC-06 is a promising entity and should serve as a lead compound in the development of new DNA and protein binders, as well as human topoisomerase II inhibitors.

Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives.

The objective of this work was to obtain and evaluate anti-inflammatory in vitro, in vivo and in silico potential of novel indole-N-acylhydrazone derivatives. In total, 10 new compounds (3a-j) were synthesized in satisfactory yields, through a condensation reaction in a single synthesis step. In the lymphoproliferation assay, using mice splenocytes, 3a and 3b showed inhibition of lymphocyte proliferation of 62.7% (±3.5) and 50.7% (±2), respectively, while dexamethasone presented an inhibition of 74.6% (±2.4). Moreover, compound 3b induced higher Th2 cytokines production in mice splenocytes cultures. The results for COX inhibition assays showed that compound 3b is a selective COX-2 inhibitor, but with less potency when compared to celecoxib, and compound 3a not presented selectivity towards COX-2. The molecular docking results suggest compounds 3a and 3b interact with the active site of COX-2 in similar conformations, but not with the active site of COX-1, and this may be the main reason to the COX-2 selectivity of compound 3b. In vivo carrageenan-induced paw edema assays were adopted for the confirmation of the anti-inflammatory activity. Compound 3b showed better results in suppressing edema at all tested concentrations and was able to induce an edema inhibition of 100% after 5 h of carrageenan injection at the 30 mg kg-1 dosage, corroborating with the COX inhibition and lymphoproliferation results. I addition to our experimental results, in silico analysis suggest that compounds 3a and 3b present a well-balanced profile between pharmacodynamics and pharmacokinetics. Thus, our preliminary results revealed the potentiality of a new COX-2 selective derivative in the modulation of the inflammatory process.

Brazilian Consensus Recommendation on the Use of Polymethylmethacrylate Filler in Facial and Corporal Aesthetics.

BACKGROUND: Considering that aesthetic benefits can be obtained with the use of permanent filling materials, this work focuses on the development of a consensus regarding the facial and corporal use of polymethylmethacrylate (PMMA) filler in Brazil. METHODS: A questionnaire regarding PMMA treatment, which included items on the main indication, application site, volume of product applied, criteria for selection of the material, complications, contraindications, and individual professional experience, was distributed to the Expert Group members. In addition, the responses were summarized, constituting the starting point for the debate regarding the use of PMMA-based fillers on The First Brazilian PMMA Symposium to create a guideline to be followed in PMMA facial and corporal treatments. RESULTS: This survey involved 87,371 cases. PMMA treatment is recommended for restorative and aesthetic purposes in facial and corporal cases, particularly for facial balance. PMMA 30% filler is recommended in specific facial sites (nose, mentum, mandible angle, zygomatic arc, and malar). PMMA filler is contraindicated in other sites (lips) regardless of concentration. With regard to facial treatment, the juxtaperiostal is the application plane most recommended. For PMMA corporal application, intramuscular is the application plane most indicated, while intradermal and justadermal planes are contraindicated. The submuscular plane application is relative to PMMA filler concentration. The experts also inquired regarding the amount of PMMA recommended in each corporal site (50 mL in the calf, 100-150 mL in the gluteal region). CONCLUSION: These recommendations provide a guideline for physicians, supporting them to perform safe and efficacious treatment with PMMA fillers. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

GUIDELINE FOR THE MANAGEMENT OF BILE DUCT CANCERS BY THE BRAZILIAN GASTROINTESTINAL TUMOR GROUP.

The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.

Guideline for the management of bile duct cancers by the brazilian gastrointestinal tumor group

ABSTRACT The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.

RESUMO O Grupo Brasileiro de Tumores Gastrointestinais desenvolveu diretrizes de tratamento cirúrgico e clínico de pacientes com tumores de vias biliares. O painel multidisciplinar foi composto de especialistas nas áreas radiologia, oncologia, cirurgia, radioterapia, endoscopia e anatomia patológica. O painel utilizou literatura atual para desenvolver recomendações baseadas em evidência científica para as diferentes estratégias terapêuticas e diagnósticas dos colangiocarcinomas e tumores de vesícula biliar.

[Prevalence and factors associated with the risk of falls among the elderly registered in a primary healthcare unit of the city of Natal in the state of Rio Grande do Norte, Brazil]. / Prevalência e fatores associados ao risco de quedas em idosos adscritos a uma Unidade Básica de Saúde do município de Natal, RN, Brasil.

The scope of the study was to analyze the prevalence and factors associated with falls among the elderly registered in a Primary Healthcare Unit (PHU) in Natal, State of Rio Grande do Norte. It involved a cross-sectional study conducted with 280 elderly individuals with data collected at the primary healthcare unit. The association between falls, recurrent falls and independent variables was assessed using bivariate analysis and Poisson regression with calculation of their respective prevalence ratios. It involved predominantly elderly females (68.2%) with mean age of 71.6 years (± 6.7), literate (54.6%), non-retired (73.5%) and sedentary (87.1%). 53.6% of the elderly recorded falls and 27.8% fell twice or more. The predictive model of falls included the female gender (PR= 1.81), osteoarticular diseases (PR = 1.71) and balance impairment (PR = 0.88), while functional mobility (PR = 0.94), fear of falling (PR = 1.21) and balance deficit disorders (PR = 0.80) constituted the definitive model of recurrent falls. A higher prevalence of single fall episodes was found and the associated factors included sociodemographic, health and physical performance variables. On the other hand, the occurrence of two or more falls were only associated with physical performance variables.