[Mortality and disability-adjusted life years in motorcyclists in Latin America and the Caribbean during the first decade of action for road safetyMortalidad y años de vida ajustados por discapacidad de los motociclistas en América Latina y el Caribe en la primera década de seguridad vial]. / Mortalidade e anos de vida ajustados por incapacidade de motociclistas na América Latina e Caribe na primeira década de segurança viária.

Objective: To identify the temporal trend in mortality and years of life lost to death or disability (DALY) due to motorcycle accidents in males from Latin America and the Caribbean from 2010 to 2019, using estimates produced by the Global Burden of Disease (GBD) study. Method: In this ecological study, the time series was analyzed using a piecewise linear regression model (joinpoint) to estimate and test the annual percent change and the average annual percent change with a 95% confidence interval. Results: The super-region defined by GBD 2019 as Latin America and the Caribbean ranked first globally in mortality and DALY for male motorcyclists aged 15-49 in 2019. Rates increased significantly from 2010 to 2013, with a significant reduction in both after this period. During the analyzed decade, the Tropical Latin America sub-region (Brazil and Paraguay) had the highest mortality and DALY rates in the population of interest; nevertheless, this was the only sub-region achieving a significant reduction in these rates. The Caribbean sub-region (Bermuda, Dominica, Suriname, Guyana, Belize, Bahamas, Puerto Rico, Saint Lucia, Dominican Republic, Haiti, Saint Kitts and Nevis, U.S. Virgin Islands, Grenada, Trinidad and Tobago, Barbados, Saint Vincent and the Grenadines, Antigua and Barbuda, Cuba e Jamaica) showed a significant increase in both rates over the same period, while Andean Latin America (Ecuador, Bolivia and Peru) and Central Latin America (Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Nicaragua, Panama, Honduras, and Venezuela) remained stable. Conclusions: The data underscore the importance of developing surveillance actions aimed at preventing motorcycle accidents, since the observed declining rates are still insufficient to address the morbidity and mortality associated with road accidents as a public health problem.

Objetivo: Determinar la tendencia temporal de la mortalidad y los años de vida perdidos por muerte o ajustados por discapacidad (AVAD) de hombres por accidentes de motocicleta en América Latina y el Caribe en el período 2010-2019, a partir de las estimaciones del estudio de la carga mundial de enfermedades (CME). Métodos: En este estudio ecológico se analizaron las series temporales mediante el modelo de regresión lineal segmentada (joinpoint), con cálculo y comprobación del cambio porcentual anual y del cambio porcentual anual promedio, con un intervalo de confianza del 95%. Resultados: La región de América Latina y el Caribe definida por el estudio de la CME ocupó el primer lugar a nivel mundial en mortalidad y AVAD de motociclistas varones de 15 a 49 años en el 2019. Las tasas tuvieron un notable aumento del 2010 al 2013, y ambas registraron una reducción importante después de ese período. En la década analizada, la subregión de América Latina Tropical (Brasil y Paraguay) presentó las mayores tasas de mortalidad y de AVAD en la población de estudio, pero fue la única con una reducción importante de las mismas. La subregión del Caribe (Antigua y Barbuda, Bahamas, Barbados, Belice, Bermudas, Cuba, Dominica, Granada, Guyana, Haití, Islas Vírgenes de Estados Unidos, Jamaica, Puerto Rico, República Dominicana, Saint Kits y Nevis, San Vicente y las Granadinas, Santa Lucía, Suriname, y Trinidad y Tabago) mostró un aumento importante de ambas tasas, mientras que América Latina Andina (Bolivia, Ecuador y Perú) y América Latina Central (Colombia, Costa Rica, El Salvador, Guatemala, Honduras, México, Nicaragua, Panamá y Venezuela) se mantuvieron estables. Conclusiones: Los datos refuerzan la importancia de las actividades de vigilancia destinadas a prevenir los accidentes de motocicleta, puesto que la reducción observada de las tasas aún es insuficiente para abordar la morbimortalidad por accidentes de tráfico como problema de salud pública.

Mining increases the prevalence of avian haemosporidian parasites in Northeast Amazonia.

Studies contrasting parasite prevalence and host-parasite community structure between pristine and disturbed environments will improve our understanding of how deforestation affects disease transmission and parasite extinction. To determine how infection rates of a common and diverse group of avian blood parasites (Plasmodium and Haemoproteus) respond to changes in avian host composition after mining, we surveyed 25 bird communities from pristine forests (two forest types: plateau and hillside) and reforested sites in Northeast Amazonia. Infection rates and both parasite and avian host community structure exhibited considerable variation across the deforestation gradient. In opposition to the emerging pattern of lower avian haemosporidian prevalence in disturbed tropical forests in Africa, we show that secondary forests had higher haemosporidian prevalence in one of the largest mining areas of Amazonia. The dissimilarity displayed by bird communities may explain, in part, the higher prevalence of Haemoproteus in reforested areas owing to the tolerance of some bird species to open-canopy forest habitat. On the other hand, deforestation may cause local extinction of Plasmodium parasites due to the loss of their avian hosts that depend on closed-canopy primary forest habitats. Our results demonstrate that forest loss induced by anthropogenic changes can affect a host-parasite system and disturb both parasite transmission and diversity.

Brazilian malaria molecular targets (BraMMT): selected receptors for virtual high-throughput screening experiments.

BACKGROUND: Owing to increased spending on pharmaceuticals since 2010, discussions about rising costs for the development of new medical technologies have been focused on the pharmaceutical industry. Computational techniques have been developed to reduce costs associated with new drug development. Among these techniques, virtual high-throughput screening (vHTS) can contribute to the drug discovery process by providing tools to search for new drugs with the ability to bind a specific molecular target. OBJECTIVES: In this context, Brazilian malaria molecular targets (BraMMT) was generated to execute vHTS experiments on selected molecular targets of Plasmodium falciparum. METHODS: In this study, 35 molecular targets of P. falciparum were built and evaluated against known antimalarial compounds. FINDINGS: As a result, it could predict the correct molecular target of market drugs, such as artemisinin. In addition, our findings suggested a new pharmacological mechanism for quinine, which includes inhibition of falcipain-II and a potential new antimalarial candidate, clioquinol. MAIN CONCLUSIONS: The BraMMT is available to perform vHTS experiments using OCTOPUS or Raccoon software to improve the search for new antimalarial compounds. It can be retrieved from www.drugdiscovery.com.br or download of Supplementary data.

Observational study of multiple myeloma in Latin America.

Relatively little is known about the outcomes of multiple myeloma in Latin America, a world region where incorporation of novel agents is generally slow. In the current retrospective-prospective study, we aimed to describe the patterns of care and treatment results in five Latin American countries. Between April 2007 and October 2009, patients who had been diagnosed from January 2005 to December 2007 were registered at 23 institutions from Argentina, Brazil, Chile, Mexico, and Peru. We divided patients into two cohorts, according to transplantation eligibility, and analyzed them with regard to first-line treatment and overall survival (OS). We analyzed a total of 852 patients, 46.9 % of whom were female. The median follow-up was 62 months. Among transplantation-ineligible patients (N = 461), the mean age was 67.4 years, approximately one third of patients received a thalidomide-based treatment in the first line, and the median OS was 43.0 months. Transplantation-eligible patients (N = 391) had a mean age of 54.7 years and a median OS of 73.6 months. Autologous transplantation was performed in 58.6 % of the patients for whom this procedure was initially planned and in only 26.9 % of the overall patients. Our long-term results reflect the contemporary literature for patients with multiple myeloma treated with autologous transplantation and thalidomide-based regimens in clinical trials and observational studies. However, further efforts are needed to approve and incorporate novel agents in Latin American countries, as well as to increase access to transplantation, in order to achieve the expected improvements in patient outcomes.

Successful application of virtual screening and molecular dynamics simulations against antimalarial molecular targets.

The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001) against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC) were established for each molecular target. The AUC values obtained for plasmepsin-IV, plasmepsin-II, and falcipain-II were 0.64, 0.92, and 0.94, respectively. All docking simulations were carried out using AutoDock Vina software. The ligand Tx001 exhibited a better interaction with PfATP6 than with the reference compound (-12.2 versus -6.8 Kcal/mol). The Tx001-PfATP6 complex was submitted to molecular dynamics simulations in vacuum implemented on an NAMD program. The ligand Tx001 docked at the same binding site as thapsigargin, which is a natural inhibitor of PfATP6. Compound TX001 was evaluated in vitro with a P. falciparum strain (W2) and a human cell line (WI-26VA4). Tx001 was discovered to be active against P. falciparum (IC50 = 8.2 µM) and inactive against WI-26VA4 (IC50 > 200 µM). Further ligand optimisation cycles generated new prospects for docking and biological assays.

Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study.

PURPOSE: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). DESIGN: Prospective, double-masked, randomized clinical trial. PARTICIPANTS: Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging. METHODS: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. MAIN OUTCOME MEASURES: Change in area of GA at 26 weeks. RESULTS: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55 ± 0.94 and 2.02 ± 0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19 ± 0.12 and 0.18 ± 0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37 ± 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 ± 0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. CONCLUSIONS: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Antimalarial activity of 4-metoxychalcones: docking studies as falcipain/plasmepsin inhibitors, ADMET and lipophilic efficiency analysis to identify a putative oral lead candidate.

Herein, we report the antimalarial activity of nine 4-methoxychalcone derivatives 1a-i and an initial analysis of their ADMET properties. All compounds showed potent activity against the P. falciparum chloroquine-resistant clone W2, with IC50 values ranging from 1.96 µM to 10.99 µM, with moderate or low cytotoxicity against the HeLa cell line. The compound 1a (IC50 = 2.06 µM) had the best selectivity index (9.0). All the sulfonamide 4-metychalcone derivatives synthesized had cLogP values between 2 and 5 (mean value 3.79) and molecular weights (MWs) below 500. The substitution of the pyrrolidine group in 1i by a morpholine group in 1a reduced the cLogP value from 3.05 in compound 1i to 2.34 in compound 1a. Indeed, compound 1a had the highest LipE value. The binding free energy of compound 1a showed it to be the most optimal chalcone derivative for plasmepsin-2 (-7.3 Kcal/mol). The physicochemical properties and LipE analysis of the dataset allowed us to establish that compound 1a is the highest quality compound of the series and a potential oral lead candidate.

Discriminant Analysis of Brazilian Stingless Bee Honey Reveals an Iron-Based Biogeographical Origin.

Stingless bee honey (SBH) is gaining attention due to its nutritional, sensorial, and medicinal characteristics. This study focuses on the combination of physicochemical properties, antioxidant capacity, mineral profile, and mass spectrometry-based fingerprints, using a chemometric approach to differentiate SBH (n = 18) from three different Brazilian biogeographical zones (Caatinga, Cerrado, and Atlantic Forest). The physicochemical properties of SBH varied, resulting in a wide range of water activity, moisture, total soluble solids, pH, and total and free acidity. The Caatinga honey showed the highest and the lowest contents of phenolics and flavonoids, respectively. The antioxidant free-radical scavenging assays demonstrated that the Brazilian SBH has a high antioxidant potential. The mineral profile of honey samples from the Atlantic Forest revealed higher contents of Ca and Fe while the Cerrado and Caatinga honey showed the highest P contents. Partial Least-Squares Discriminant Analysis (PLS-DA) analysis separated the samples into three groups based on the biogeographical zones of harvest. The main separation factors between groups were the m/z 326 ion and the Fe content. Univariate analysis confirmed that Fe content is important for SBH discrimination. The present results indicate that the origin of SBH can be determined on the basis of mineral profile, especially Fe content.

In vitro and in silico assessment of new beta amino ketones with antiplasmodial activity.

BACKGROUND: Based on the current need for new drugs against malaria, our study evaluated eight beta amino ketones in silico and in vitro for potential antimalarial activity. METHODS: Using the Brazilian Malaria Molecular Targets (BraMMT) and OCTOPUS® software programs, the pattern of interactions of beta-amino ketones was described against different proteins of P. falciparum and screened to evaluate their physicochemical properties. The in vitro antiplasmodial activities of the compounds were evaluated using a SYBR Green-based assay. In parallel, in vitro cytotoxic data were obtained using the MTT assay. RESULTS: Among the eight compounds, compound 1 was the most active and selective against P. falciparum (IC50 = 0.98 µM; SI > 60). Six targets were identified in BraMMT that interact with compounds exhibiting a stronger binding energy than the crystallographic ligand: P. falciparum triophosphate phosphoglycolate complex (1LYX), P. falciparum reductase (2OK8), PfPK7 (2PML), P. falciparum glutaredoxin (4N0Z), PfATP6, and PfHT. CONCLUSIONS: The physicochemical properties of compound 1 were compatible with the set of criteria established by the Lipinski rule and demonstrated its potential as a drug prototype for antiplasmodial activity.

Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs.

BACKGROUND: The resistance against antimalarial drugs represents a global challenge in the fight and control of malaria. The Brazilian biodiversity can be an important tool for research and development of new medicinal products. In this context, toxinology is a multidisciplinary approach on the development of new drugs, including the isolation, purification, and evaluation of the pharmacological activities of natural toxins. The present study aimed to evaluate the cytotoxicity, as well as the antimalarial activity in silico and in vitro of four compounds isolated from Rhinella marina venom as potential oral drug prototypes. METHODS: Four compounds were challenged against 35 target proteins from P. falciparum and screened to evaluate their physicochemical properties using docking assay in Brazilian Malaria Molecular Targets (BraMMT) software and in silico assay in OCTOPUS® software. The in vitro antimalarial activity of the compounds against the 3D7 Plasmodium falciparum clones were assessed using the SYBR Green I based assay (IC50). For the cytotoxic tests, the LD50 was determined in human pulmonary fibroblast cell line using the [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. RESULTS: All compounds presented a ligand-receptor interaction with ten Plasmodium falciparum-related protein targets, as well as antimalarial activity against chloroquine resistant strain (IC50 = 3.44 µM to 19.11 µM). Three of them (dehydrobufotenine, marinobufagin, and bufalin) showed adequate conditions for oral drug prototypes, with satisfactory prediction of absorption, permeability, and absence of toxicity. In the cell viability assay, only dehydrobufotenin was selective for the parasite. CONCLUSIONS: Dehydrobufotenin revealed to be a potential oral drug prototype presenting adequate antimalarial activity and absence of cytotoxicity, therefore should be subjected to further studies.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective.

PURPOSE: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. METHODS: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. RESULTS: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. CONCLUSIONS: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation.

BACKGROUND: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. METHODS: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. RESULTS: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p=0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. CONCLUSION: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

Effectiveness of monthly and fortnightly anti-VEGF treatments for age-related macular degeneration.

PURPOSE: To study the efficacy and safety of treatments with ranibizumab and bevacizumab for exudative age-related macular degeneration. METHODS: A parallel randomized clinical trial was conducted to compare the efficacy and safety of three regimens (bevacizumab every month, bevacizumab every 2 weeks, and ranibizumab every month), followed by as-needed retreatments, for 1 year, in previously untreated individuals with age-related macular degeneration. The primary outcome was change in visual acuity and in central macular thickness after 1 year of follow-up. Subjects were assigned randomly to one of the three groups in a 1:1:1 ratio, and investigators and examiners were blinded to the randomization results. RESULTS: We included 15 patients in each group. After 1 year of follow-up, we found statistically significant improvements in visual acuity and central macular thickness reduction in all groups. However, we found no statistically significant differences between the three groups. CONCLUSIONS: The bi-weekly follow-up was effective and we found no significant differences in efficacy or safety between the treatments with ranibizumab and bevacizumab.

Structure and Distribution of Centromeric Retrotransposons at Diploid and Allotetraploid Coffea Centromeric and Pericentromeric Regions.

Centromeric regions of plants are generally composed of large array of satellites from a specific lineage of Gypsy LTR-retrotransposons, called Centromeric Retrotransposons. Repeated sequences interact with a specific H3 histone, playing a crucial function on kinetochore formation. To study the structure and composition of centromeric regions in the genus Coffea, we annotated and classified Centromeric Retrotransposons sequences from the allotetraploid C. arabica genome and its two diploid ancestors: Coffea canephora and C. eugenioides. Ten distinct CRC (Centromeric Retrotransposons in Coffea) families were found. The sequence mapping and FISH experiments of CRC Reverse Transcriptase domains in C. canephora, C. eugenioides, and C. arabica clearly indicate a strong and specific targeting mainly onto proximal chromosome regions, which can be associated also with heterochromatin. PacBio genome sequence analyses of putative centromeric regions on C. arabica and C. canephora chromosomes showed an exceptional density of one family of CRC elements, and the complete absence of satellite arrays, contrasting with usual structure of plant centromeres. Altogether, our data suggest a specific centromere organization in Coffea, contrasting with other plant genomes.

Análise ergonômica do trabalho de policiais civis da polícia especializada do Ceará: um estudo de caso / Ergonomic analysis of the work of civilian policemen of the specialized police of Ceará: a case study / Análisis ergonómico del trabajo de los policías civiles de la policía especializada de Ceará: un estudio de caso

Introdução: a dinâmica laboral, os fatores ambientais e a individualidade de enfrentamento nos postos de trabalho podem influenciar o surgimento de alterações físicas e psicológicas nos indivíduos. Objetivo: identificar os riscos ergonômicos de policiais de uma Unidade Especializada da Polícia Civil do Estado do Ceará. Métodos: trata de um estudo de caso no qual foi realizada uma Análise Ergonômica do Trabalho, de forma qualitativa e multidisciplinar, de três policiais civis, considerando quatro posições diferentes: posição ortostática com seu equipamento de proteção individual e de exercício laboral; posição de prontidão de tiro; posição de descanso, alerta em operação e fora da operação; e posição ortostática em operação. A análise foi realizada por meio de cinco etapas: análise da demanda; análise da tarefa; análise da atividade; diagnóstico; e recomendações, sendo avaliados o peso dos equipamentos, sobrecargas musculares e articulares e compensações posturais oriundas do exercício das atividades laborais. Resultados: foi detectada elevada carga de peso dos equipamentos, levando a desvios posturais. Os policiais também apresentaram condutas posturais viciosas na execução das atividades. Conclusão: alterações e vícios posturais precisam ser solucionadas visando o cuidado com a saúde dos policiais, de modo a evitar afastamentos para tratamento de saúde. Recomendações foram propostas.

Introduction: the labor dynamics, the environmental factors and the individuality of confrontation at workstations may influence the emergence of physical and psychological alterations in individuals. Objective: to identify the ergonomic risks of policemen of a Specialized Unit of the Civil Police of the State of Ceará. Methods: this is a case study in which a qualitative and multidisciplinary Ergonomic Analysis of Work was carried out on three civilian policemen, considering four different positions: orthostatic position with their individual protection equipment and work exercise; shooting readiness position; resting position, alert in operation and out of operation; and orthostatic position in operation. The analysis was conducted through five stages: demand analysis; task analysis; activity analysis; diagnosis; and recommendations, evaluating the weight of the equipment, muscle and joint overloads and postural compensations arising from the exercise of labor activities. Results: a high weight load of the equipment was detected, leading to postural deviations. The policemen also presented vicious postural behaviors in the execution of their activities. Conclusion: postural alterations and addictions need to be solved in order to take care of the policemen's health, so as to avoid absence for health treatment. Recommendations were proposed.

Introducción: la dinámica laboral, los factores ambientales y la individualidad del enfrentamiento en los puestos de trabajo pueden influir en la aparición de alteraciones físicas y psicológicas en los individuos. Objetivo: identificar los riesgos ergonómicos de los policías de una Unidad Especializada de la Policía Civil del Estado de Ceará. Método: se trata de un estudio de caso en el que se realizó un Análisis Ergonómico del Trabajo cualitativo y multidisciplinar a tres policías civiles, considerando cuatro posiciones diferentes: posición ortostática con su equipo de protección individual y ejercicio de trabajo; posición de preparación para el tiro; posición de descanso, alerta en operación y fuera de operación; y posición ortostática en operación. El análisis se realizó a través de cinco etapas: análisis de la demanda; análisis de la tarea; análisis de la actividad; diagnóstico; y recomendaciones, evaluando el peso del equipo, las sobrecargas musculares y articulares y las compensaciones posturales derivadas del ejercicio de las actividades laborales. Resultados: se detectó una elevada carga de peso del equipo, lo que provocó desviaciones posturales. Los policías también presentaron comportamientos posturales viciosos en la ejecución de sus actividades. Conclusión: las alteraciones posturales y las adicciones necesitan ser solucionadas para cuidar de la salud de los policías, de forma a evitar ausencias para tratamiento sanitario. Se propusieron recomendaciones.

Mortalidade e anos de vida ajustados por incapacidade de motociclistas na América Latina e Caribe na primeira década de segurança viária / Mortality and disability-adjusted life years in motorcyclists in Latin America and the Caribbean during the first decade of action for road safety / Mortalidad y años de vida ajustados por discapacidad de los motociclistas en América Latina y el Caribe en la primera década de seguridad vial

RESUMO Objetivo. Identificar a tendência temporal da mortalidade e dos anos de vida perdidos por morte ou incapacidade (DALY) de homens por acidente motociclístico na América Latina e Caribe no período de 2010 a 2019, utilizando estimativas do estudo Global Burden of Disease (GBD). Métodos. Este estudo ecológico analisou a série temporal pelo modelo de regressão linear segmentada (joinpoint), estimando-se e testando-se a variação percentual anual e a variação percentual anual média, com intervalo de confiança de 95%. Resultados. A grande região da América Latina e Caribe definida pelo GBD ocupou o primeiro lugar global em mortalidade e DALY de motociclistas homens de 15 a 49 anos em 2019. As taxas aumentaram significativamente de 2010 a 2013, havendo redução significativa de ambas após esse período. Durante a década analisada, a sub-região da América Latina Tropical (Brasil e Paraguai) apresentou as maiores taxas de mortalidade e DALY na população em estudo, porém foi a única com redução significativa das mesmas; a sub-região do Caribe (Bermudas, Dominica, Suriname, Guiana, Belize, Bahamas, Porto Rico, Santa Lúcia, República Dominicana, Haiti, São Cristóvão e Névis, Ilhas Virgens/EUA, Granada, Trinidad e Tobago, Barbados, São Vicente e Granadinas, Antígua e Barbuda, Cuba e Jamaica) apresentou aumento significativo de ambas as taxas, enquanto América Latina Andina (Equador, Bolívia e Peru) e América Latina Central (Colômbia, Costa Rica, El Salvador, Guatemala, México, Nicarágua, Panamá, Honduras e Venezuela) permaneceram estáveis. Conclusões. Os dados reforçam a importância das ações de vigilância destinadas à prevenção de acidentes motociclísticos, uma vez que os resultados de queda nas taxas ainda são insuficientes frente à morbimortalidade no trânsito como problema de saúde pública.

ABSTRACT Objective. To identify the temporal trend in mortality and years of life lost to death or disability (DALY) due to motorcycle accidents in males from Latin America and the Caribbean from 2010 to 2019, using estimates produced by the Global Burden of Disease (GBD) study. Method. In this ecological study, the time series was analyzed using a piecewise linear regression model (joinpoint) to estimate and test the annual percent change and the average annual percent change with a 95% confidence interval. Results. The super-region defined by GBD 2019 as Latin America and the Caribbean ranked first globally in mortality and DALY for male motorcyclists aged 15-49 in 2019. Rates increased significantly from 2010 to 2013, with a significant reduction in both after this period. During the analyzed decade, the Tropical Latin America sub-region (Brazil and Paraguay) had the highest mortality and DALY rates in the population of interest; nevertheless, this was the only sub-region achieving a significant reduction in these rates. The Caribbean sub-region (Bermuda, Dominica, Suriname, Guyana, Belize, Bahamas, Puerto Rico, Saint Lucia, Dominican Republic, Haiti, Saint Kitts and Nevis, U.S. Virgin Islands, Grenada, Trinidad and Tobago, Barbados, Saint Vincent and the Grenadines, Antigua and Barbuda, Cuba e Jamaica) showed a significant increase in both rates over the same period, while Andean Latin America (Ecuador, Bolivia and Peru) and Central Latin America (Colombia, Costa Rica, El Salvador, Guatemala, Mexico, Nicaragua, Panama, Honduras, and Venezuela) remained stable. Conclusions. The data underscore the importance of developing surveillance actions aimed at preventing motorcycle accidents, since the observed declining rates are still insufficient to address the morbidity and mortality associated with road accidents as a public health problem.

RESUMEN Objetivo. Determinar la tendencia temporal de la mortalidad y los años de vida perdidos por muerte o ajustados por discapacidad (AVAD) de hombres por accidentes de motocicleta en América Latina y el Caribe en el período 2010-2019, a partir de las estimaciones del estudio de la carga mundial de enfermedades (CME). Métodos. En este estudio ecológico se analizaron las series temporales mediante el modelo de regresión lineal segmentada (joinpoint), con cálculo y comprobación del cambio porcentual anual y del cambio porcentual anual promedio, con un intervalo de confianza del 95%. Resultados. La región de América Latina y el Caribe definida por el estudio de la CME ocupó el primer lugar a nivel mundial en mortalidad y AVAD de motociclistas varones de 15 a 49 años en el 2019. Las tasas tuvieron un notable aumento del 2010 al 2013, y ambas registraron una reducción importante después de ese período. En la década analizada, la subregión de América Latina Tropical (Brasil y Paraguay) presentó las mayores tasas de mortalidad y de AVAD en la población de estudio, pero fue la única con una reducción importante de las mismas. La subregión del Caribe (Antigua y Barbuda, Bahamas, Barbados, Belice, Bermudas, Cuba, Dominica, Granada, Guyana, Haití, Islas Vírgenes de Estados Unidos, Jamaica, Puerto Rico, República Dominicana, Saint Kits y Nevis, San Vicente y las Granadinas, Santa Lucía, Suriname, y Trinidad y Tabago) mostró un aumento importante de ambas tasas, mientras que América Latina Andina (Bolivia, Ecuador y Perú) y América Latina Central (Colombia, Costa Rica, El Salvador, Guatemala, Honduras, México, Nicaragua, Panamá y Venezuela) se mantuvieron estables. Conclusiones. Los datos refuerzan la importancia de las actividades de vigilancia destinadas a prevenir los accidentes de motocicleta, puesto que la reducción observada de las tasas aún es insuficiente para abordar la morbimortalidad por accidentes de tráfico como problema de salud pública.

New Drugs and New Posterior Delivery Methods in CME.

PURPOSE: To discuss the characteristics, indications and adverse events (AEs) of sustained-release corticosteroid devices for the treatment of cystoid macular edema (CME). RECENT FINDINGS: Ozurdex® is approved for the treatment of diabetic macular edema (DME), retinal vein occlusion related-CME and noninfectious posterior uveitis (NIPU). It releases dexamethasone over a maximum period of 6 months making repeated intravitreal injections necessary for recurrent CME. Iluvien® releases fluocinolone for up to 36 months and is effective for the treatment of chronic DME. Retisert® (Bausch & Lomb, Rochester, NY) also releases fluocinolone, and is approved for chronic NIPU. Both Iluvien® and Retisert® are non-biodegradable devices and are highly associated with cataract and glaucoma. SUMMARY: Long-acting intraocular corticosteroid formulations offer a more predictable drug-release profile and reduced dosing frequency in comparison to conventional formulations of the same compounds but the risk-benefit ratio must be taken into consideration previous to the implantation of those devices.

In vitro and in silico assessment of new beta amino ketones with antiplasmodial activity

ABSTRACT Background: Based on the current need for new drugs against malaria, our study evaluated eight beta amino ketones in silico and in vitro for potential antimalarial activity. Methods: Using the Brazilian Malaria Molecular Targets (BraMMT) and OCTOPUS® software programs, the pattern of interactions of beta-amino ketones was described against different proteins of P. falciparum and screened to evaluate their physicochemical properties. The in vitro antiplasmodial activities of the compounds were evaluated using a SYBR Green-based assay. In parallel, in vitro cytotoxic data were obtained using the MTT assay. Results: Among the eight compounds, compound 1 was the most active and selective against P. falciparum (IC50 = 0.98 µM; SI > 60). Six targets were identified in BraMMT that interact with compounds exhibiting a stronger binding energy than the crystallographic ligand: P. falciparum triophosphate phosphoglycolate complex (1LYX), P. falciparum reductase (2OK8), PfPK7 (2PML), P. falciparum glutaredoxin (4N0Z), PfATP6, and PfHT. Conclusions: The physicochemical properties of compound 1 were compatible with the set of criteria established by the Lipinski rule and demonstrated its potential as a drug prototype for antiplasmodial activity.

Tendência temporal dos homicídios no Brasil no período de 2000-2019 / Temporal trend of homicides in Brazil in the period 2000-2019

Objetivo: descrever a tendência temporal da mortalidade por homicídios no Brasil e Regiões de 2000 a 2019. Métodos: trata-se de estudo ecológico de análise de série temporal por meio de dados extraídos do Sistema de Informações de Mortalidade correspondentes às mortes provocadas por agressões (CID X85-Y09), intervenções legais (CID Y35-Y36) e óbitos por eventos de intenção não determinada, (CID Y10-Y34) ocorridas em BR e regiões Norte, Nordeste, Sudeste, Sul e Centro-Oeste, no período de 2000 a 2019. A tendência temporal foi calculada utilizando o Joinpoint Regression Program versão 4.9.0.0, obtendo-se as variações percentuais anuais e variações percentuais anuais médias, com intervalo de confiança de 95%. Resultados: houve redução significativa dos óbitos por homicídios após 2017, além de aumento significativo das mortes por intervenção legal de 2000 a 2019, em todas as unidades territoriais estudadas, acompanhado de redução daquelas por agressões no Brasil e Sudeste e aumento nas regiões Norte e Nordeste, ambos significativos estatisticamente. Houve aumento substancial dos óbitos por eventos de intenção não determinada a partir de 2017, em todas as regiões, significativos para Brasil, Norte e Sudeste. Observou-se inexistência de ponto de inflexão em 2017 no Sudeste relativo aos homicídios estimados, evidenciando o elevado ocultamento dos homicídios no período por falhas nas notificações. Conclusões: torna-se essencial, para a integridade e correção dos dados contidos nos sistemas de informações, o compartilhamento destas entre os atores envolvidos na produção daqueles.

Objective to describe the temporal trend of homicide mortality in Brazil and the Regions from 2000 to 2019. Methods: this is an ecological study of time series analysis based on data extracted from the Mortality Information System corresponding to deaths caused by aggression (CID X85-Y09), legal interventions (CID Y35-Y36), and deaths due to undetermined intentions (CID Y10-Y34) occurring in BR and the North, Northeast, Southeast, South, and Center-West regions, in the period from 2000 to 2019. The temporal trend was calculated using Joinpoint Regression Program version 4.9.0.0, obtaining the annual percentage changes and mean annual percentage changes, with a 95% confidence interval. Results: there was a significant reduction in deaths from homicide after 2017, in addition to a significant increase in deaths from legal intervention from 2000 to 2019 in all territorial units studied, accompanied by a reduction in those from aggression in Brazil and the Southeast and an increase in the North and Northeast regions, both statistically significant. There was a substantial increase in deaths from events of undetermined intention as of 2017 onwards in all regions, significant for Brazil, North, and Southeast. There was no inflection point in 2017 in the Southeast regarding estimated homicides, evidencing the high concealment of homicides in the period due to failures in notifications. Conclusions: it is essential for the integrity and correction of the data contained in the information systems that these are shared among the actors involved in their production.

Docking, QM/MM, and molecular dynamics simulations of the hexose transporter from Plasmodium falciparum (PfHT).

Malaria is the most prevalent parasitic disease in the world. Currently, an effective vaccine for malaria does not exist, and chemotherapy must be used to treat the disease. Because of increasing resistance to current antimalarial drugs, new treatments must be developed. Among the many potential molecular targets, the hexose transporter of Plasmodium falciparum (PfHT) is particularly promising because it plays a vital role in glucose transport for the parasite. Thus, this study aims to determine the three-dimensional structure of PfHT and to describe the intermolecular interactions between active glycoside derivatives and PfHT. Such information should aid in the development of new antimalarial drugs. The receptor PfHT was constructed from primary sequences deposited in the SWISS MODEL database. Next, molecular docking simulations between O-(undec-10-en)-l-D-glucose and the constructed active site models were performed using Autodock Vina. The glycoside derivative-PfHT complexes were then refined using the hybrid QM/MM (PM3/ff03) method within the AMBER package. The models were then evaluated using Ramachandran plots, which indicated that 93.2% of the residues in the refined PfHT models (P5) were present in favorable regions. Furthermore, graphical plots using ANOLEA showed that the potential energies of interaction for atoms unbonded to P5 were negative. Finally, the O-(undec-10-en)-l-D-glucose-PfHT complex was evaluated using 20-ns Molecular Dynamics simulations with an ff03 force field. Docking and QM/MM studies revealed the amino acids essential for molecular recognition of and activity on glycosides. Inhibition of glucose transporters may prevent the development and metabolism of P. falciparum, so a description of the receptor's structure is a critical step towards rational drug design.