Chemical characterization and antibacterial activities of Brazilian propolis extracts from Apis mellifera bees and stingless bees (Meliponini).

The aim of this study was to evaluate the physicochemical composition and antibacterial activity of Brazilian propolis extracts from different types, concentrations, and extraction solvents and from different regions in Brazil. A total of 21 samples were analyzed, comprising 14 samples from Apis mellifera (12 green, 1 brown, and 1 red) and 7 samples from stingless bees (3 mandaçaia, 2 jataí, 1 hebora, and 1 tubuna). The analyses performed were dry extract, total phenolic content (TPC) and antioxidant activity (DPPH and ABTS). The antibacterial activity was performed by Determination of Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC). The results showed that very low levels of phenolic compounds and antioxidant activity decreased the antimicrobial activity of the propolis extracts from tubuna and jataí. However, there was no correlation between the increase in propolis concentration in the extract, and the increase in antimicrobial activity. The highest TPC and antioxidant activity was obtained for green propolis extract made with 70% raw propolis that presented similar antibacterial activity to the samples formulated with 30% or less raw propolis. The aqueous propolis extract showed lower antimicrobial activity compared to the alcoholic extracts, indicating that ethanol is a better solvent for extracting the active compounds from propolis. It was observed that the MIC (0.06 to 0.2 mg/mL) and MBC (0.2 to 0.5 mg/mL) values for Gram-negative bacteria were higher compared to Gram-positive bacteria (MIC 0.001-0.2 mg/mL, and the MBC 0.02-0.5 mg/mL). The propolis extracts that exhibited the highest antimicrobial activities were from stingless bees hebora from the Distrito Federal (DF) and mandaçaia from Santa Catarina, showing comparable efficacy to samples 5, 6, and 7, which were the green propolis from the DF. Hence, these products can be considered an excellent source of bioactive compounds with the potential for utilization in both the pharmaceutical and food industries.

Charge Regulation Triggers Condensation of Short Oligopeptides to Polyelectrolytes.

Electrostatic interactions between charged macromolecules are ubiquitous in biological systems, and they are important also in materials design. Attraction between oppositely charged molecules is often interpreted as if the molecules had a fixed charge, which is not affected by their interaction. Less commonly, charge regulation is invoked to interpret such interactions, i.e., a change of the charge state in response to a change of the local environment. Although some theoretical and simulation studies suggest that charge regulation plays an important role in intermolecular interactions, experimental evidence supporting such a view is very scarce. In the current study, we used a model system, composed of a long polyanion interacting with cationic oligolysines, containing up to 8 lysine residues. We showed using both simulations and experiments that while these lysines are only weakly charged in the absence of the polyanion, they charge up and condense on the polycations if the pH is close to the pKa of the lysine side chains. We show that the lysines coexist in two distinct populations within the same solution: (1) practically nonionized and free in solution; (2) highly ionized and condensed on the polyanion. Using this model system, we demonstrate under what conditions charge regulation plays a significant role in the interactions of oppositely charged macromolecules and generalize our findings beyond the specific system used here.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study.

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Protein-folding chaperones predict structure-function relationships and cancer risk in BRCA1 mutation carriers.

Predicting the risk of cancer mutations is critical for early detection and prevention, but differences in allelic severity of human carriers confound risk predictions. Here, we elucidate protein folding as a cellular mechanism driving differences in mutation severity of tumor suppressor BRCA1. Using a high-throughput protein-protein interaction assay, we show that protein-folding chaperone binding patterns predict the pathogenicity of variants in the BRCA1 C-terminal (BRCT) domain. HSP70 selectively binds 94% of pathogenic BRCA1-BRCT variants, most of which engage HSP70 more than HSP90. Remarkably, the magnitude of HSP70 binding linearly correlates with loss of folding and function. We identify a prevalent class of human hypomorphic BRCA1 variants that bind moderately to chaperones and retain partial folding and function. Furthermore, chaperone binding signifies greater mutation penetrance and earlier cancer onset in the clinic. Our findings demonstrate the utility of chaperones as quantitative cellular biosensors of variant folding, phenotypic severity, and cancer risk.

Protein-Folding Chaperones Predict Structure-Function Relationships and Cancer Risk in BRCA1 Mutation Carriers.

Identifying pathogenic mutations and predicting their impact on protein structure, function and phenotype remain major challenges in genome sciences. Protein-folding chaperones participate in structure-function relationships by facilitating the folding of protein variants encoded by mutant genes. Here, we utilize a high-throughput protein-protein interaction assay to test HSP70 and HSP90 chaperone interactions as predictors of pathogenicity for variants in the tumor suppressor BRCA1. Chaperones bind 77% of pathogenic BRCA1-BRCT variants, most of which engaged HSP70 more than HSP90. Remarkably, the magnitude of chaperone binding to variants is proportional to the degree of structural and phenotypic defect induced by BRCA1 mutation. Quantitative chaperone interactions identified BRCA1-BRCT separation-of-function variants and hypomorphic alleles missed by pathogenicity prediction algorithms. Furthermore, increased chaperone binding signified greater cancer risk in human BRCA1 carriers. Altogether, our study showcases the utility of chaperones as quantitative cellular biosensors of variant folding and phenotypic severity. HIGHLIGHTS: Chaperones detect an abundance of pathogenic folding variants of BRCA1-BRCT.Degree of chaperone binding reflects severity of structural and phenotypic defect.Chaperones identify separation-of-function and hypomorphic variants. Chaperone interactions indicate penetrance and expressivity of BRCA1 alleles.

Nivel de conocimiento sobre profilaxis antibiótica de endocarditis infecciosa en estudiantes de Odontología de Lima / Knowledge about antibiotic prophylaxis of infective endocarditis in dental students in Lima

Introducción: La endocarditis infecciosa es una condición severa que puede presentarse luego de procedimientos odontológicos invasivos, principalmente en pacientes portadores de válvulas cardiacas protésicas y enfermedad cardiaca reumática y congénita. Es importante identificar el nivel de conocimientos de los estudiantes de Odontología para establecer reformas en el plan de estudios de la carrera. Objetivo: Determinar el nivel de conocimiento sobre profilaxis antibiótica de endocarditis infecciosa previa a procedimientos odontológicos en estudiantes de último año de Odontología de Lima. Material y métodos: Estudio analítico y transversal, cuya muestra estuvo constituida por 117 estudiantes del último año de la carrera de Odontología de la Universidad Nacional Mayor de San Marcos (UNMSM), la Universidad Nacional Federico Villareal (UNFV) y la Universidad Peruana Cayetano Heredia (UPCH), de Lima, Perú, durante el año 2014. El instrumento de evaluación fue una encuesta de 20 preguntas cerradas sobre epidemiología y etiopatogenia de endocarditis infecciosa e indicación y farmacología de la profilaxis antibiótica previa a procedimientos odontológicos. Los resultados fueron catalogados en 3 niveles: bajo, regular y alto. Resultados: El 53,84 por ciento de los internos presentó un nivel de conocimiento bajo, mientras el 32,47 por ciento un nivel regular y el 13,69 por ciento un nivel alto. El nivel de respuesta promedio fue 10,1 ± 2,95 [IC95 por ciento(9,57-10,65)]. Por universidad, los internos de la UNMSM tuvieron un nivel de conocimiento promedio de 11 ± 2,60 [IC95 por ciento (9,84-12,15)], los de UNFV tuvieron 8,8 ± 3,36 [IC95 por ciento (7,74 - 9,86)] y los de UPCH tuvieron 10,7 ± 2,41 [IC95 por ciento (10,08-11,39)]; p=0,002. Conclusiones: El nivel de conocimiento sobre profilaxis antibiótica de endocarditis infecciosa en estudiantes de último año de Odontología de Lima es predominantemente bajo(AU)

Introduction: Infective endocarditis is a severe condition that can occur after invasive dental procedures, mainly in patients with prosthetic heart valves and rheumatic and congenital heart disease. It is important to identify the level of knowledge of dental students to establish reforms in the curriculum of the career. Objective: To determine the level of knowledge about antibiotic prophylaxis of infective endocarditis prior to dental procedures in last-year dental students of Lima. Material and methods: Analytical and cross-sectional study whose sample was made up of 117 last-year dental students of the National University of San Marcos (UNMSM), the National University Federico Villareal (UNFV) and the Peruvian University Cayetano Heredia (UPCH) from Lima, Peru, during the year 2014. The evaluation instrument was a survey of 20 closed questions on epidemiology and etiopathogenesis of infective endocarditis and indication and pharmacology of antibiotic prophylaxis prior to dental procedures. The results were cataloged in 3 levels: low, regular and high. Results: The results show that 53,84 percent of the interns presented a low level of knowledge, while 32,47 percent had a regular level and 13,69 percent a high level. The average response level was 10,1 ± 2,95 [95 percent CI (9,57-10,65)]. By university, UNMSM interns had an average level of knowledge of 11 ± 2,60 [95 percent CI (9,84-12,15)], UNFV had 8,8 ± 3,36 [95 percent CI (7,74-9,86)] and those of UPCH had 10,7 ± 2,41 [95 percent CI (10,08-11,39)]; p=0.002. Conclusions: The level of knowledge about antibiotic prophylaxis of infective endocarditis in last- year dental students in Lima is predominantly low(AU)

Management of hepatitis C infection with direct action antiviral drugs (DAA)

Several new direct action antiviral drugs (DAA) against the HCV virus (HCV) are approved and marketed. The combination of DAA with pegylated interferon and ribavirin (PR) is only recommended to patients with tolerance to interferon (IFN). IFN-free treatments are now considered elective drugs for patients with chronic HCV. More than 90% of patients infected with HCV genotype 1 or 4 (fewer with other genotypes) show sustained virological response, when treated with sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the combination of paritaprevir with ritonavir, ombitasvir and dasabuvir, with or without ribavirin. The safety and efficacy of DAA therapy in HIV-HCV confection is now comparable with HCV monoinfection. DAA drugs are also efficient in patients with previous interferon/ribavirin, or protease inhibitors, treated patients as well as with hepatic transplanted patients. The goal of this review is to clarify the current stage of DAA drugs already approved and available by January-2016. Another objective is to discuss the main drugs regimen recommended by international medical associations and drugs regulatory agencies, including Brazil's Health Ministry. In this review, the authors make an approach about: adverse effects of DAA; interactions with other drugs, efficacy in patients with compensated cirrhosis or comorbidities, different genotypes or subtypes, as well as the development of resistance associated to viral mutants and their possible clinical importance

Prevalence and risk factors associated with Toxocara canis infection in children.

The objective of this study was to determine seroprevalence and identify risk factors associated with Toxocara canis infection. A clinical and epidemiological questionnaire and body mass index were used to assess the risk factors associated with human toxocariasis in 108 children with an age range of 2-16 years. Antibodies against Toxocara canis were detected using an ELISA test kit. Chi-square analysis and odds ratio (OR) were used to identify risk factors associated with Toxocara canis seropositivity. The prevalence of antibodies against Toxocara canis was greater (P = 0.02) in males than females (28.84% and 16.07%, resp.). Chi-square analysis and odds ratio revealed just one variable with P < 0.05, and OR > 1.0 was associated with seropositivity: the possession of dogs under one year old (OR = 1.78). Although not significant, the OR values suggest that other factors may be epidemiologically important for Toxocara presence such as not washing hands before meals, malnutrition, obesity, and use of public parks. Children in the age group >12 and <16 years old had higher seroprevalence to Toxocara canis (17.59%) than the >2 and <11 years old age group (4.62%). Toxocariosis infection needs to be prevented by pet deworming and hygienic measures after contact with dogs.

Conocimientos, prácticas y actitudes sobre alimentación normal en el primer año de vida de los estudiantes de medicina de la Universidad del Valle de Cali, Colombia / Knowledge, attitudes and practices about normal feeding in the first year of life, in the medical students from the Universidad del Valle in Cali, Colombia

Introducción: La alimentación constituye una prioridad en el niño menor de un año. Los profesionales de la salud son una fuente importante de educación sobre alimentación para padres y cuidadores de lactantes, por lo que la formación en esta área de dichos profesionales es trascendental para las instituciones de educación superior, siendo importante evaluar los conocimientos que tienen los estudiantes de medicina en ésta área. Objetivo: Determinar los conocimientos, prácticas y actitudes (CAP) en estudiantes de medicina matriculados en la Universidad del Valle sobre alimentación normal durante el primer año de vida. Metodología: Se realizó un estudio de prevalencia observacional, descriptivo, tipo encuesta que incluyó 105 estudiantes matriculados en el año 2005 en Medicina y Cirugía en la Universidad del Valle (Univalle). Resultados: 46,7% de los estudiantes encuestados posee un conocimiento insuficiente (< 60% de respuestas correctas) sobre alimentación en el primer año de vida, 51,4% posee un nivel aceptable, 1,9% bueno y ninguno muy bueno. Hay menor nivel de conocimiento significativamente entre los estudiantes de cuarto año, pero no en los del quinto ni sexto año. No se encontró diferencias significativas en los estudiantes de sexto año de la Univalle comparados con otras universidades. Conclusiones: Se debe mejorar el conocimiento global sobre alimentación normal en el primer año de vida en los estudiantes de debido a la importancia de su formación para suministrar a los padres y/o cuidadores información relacionada con la alimentación del niño.

Introduction: The nutrition supply is a priority in the child under one year. Health professionals are an important source of nutrition education for parents and caregivers of infants, so training in this area of such professionals is critical to higher education institutions and it is important to assess the knowledge students have medicine in this area. Objective: To determine knowledge, attitudes and practices (KAP) about normal feeding during the first year of life, in medical students enrolled at the Universidad del Valle from Cali, Colombia. Methodology: An observational study of prevalence, descriptive survey included 105 such students enrolled in 2005 in Medicine and Surgery at the Universidad del Valle. Results: 46.7% of the students have insufficient knowledge (<60% correct) on feeding in the first year of life, 51.4% have an acceptable level, 1.9% good and no good. There are significantly lower level of knowledge among seniors, but not in the fifth or sixth year. No significant differences were found among students in sixth year of the Univalle compared with other universities. Conclusions: We must improve the global knowledge on normal diet in the first year of life in students due to the importance of providing training for parents and/or caregivers information about infant feeding.

Estimated risks of water and saliva contamination by phthalate diffusion from plasticized polyvinyl chloride.

Phthalates are additives commonly used to convert hard polyvinyl chloride (PVC) resins into flexible and workable plastics employed in the production of chewable rubber toys and other soft-plastic products. In theory, phthalates can diffuse in small quantities to the surface of a product, and from there they can enter the environment and the human body. The purpose of this study was to determine the diffusion of phthalates from plasticized PVC in water and artificial saliva; to determine the migration of di(2-ethylhexyl) (DEHP) phthalate in human saliva using gas chromatography; to compare the experimental values with theoretical values calculated using a model based on the principles of molecular diffusion in fluids; and to use the experimental values to estimate daily doses of DEHP received by Mexican children and infants using plastic and soft-plastic products (e.g., pacifiers, chewable toys, and bottles). Our findings indicated phthalate diffusion of 0.36 microg/cm2 per hour and 4.10 microg/cm2 per hour, respectively, in water and artificial saliva. The average value of phthalate diffusion in vivo was 6.04 microg/cm2 per hour. The daily oral phthalate exposure in Mexican infants and toddlers from oral use of rubber toys and soft-plastic products is 18.12 microg/kg. These daily doses are considerably lower than the maximum daily phthalate intake recommended by an international public health committee.

Objetivos de Desarrollo del Milenio: Cochabamba situación actual, evaluación y perspectivas / Objectives of Development of the Millenium: Cochabamba present situation, evaluation and perspective

Situación del Departamento. Seleccion de indicadores para el seguimiento a los ODM. Los ODM en el Departamento de Cochabamba. Conclusiones y Perspectivas. Bibliografía. Anexos

Análisis de Equidad de Género en Bolivia

Libro que proporciona información de carácter comparativo sobre la situación y evolución de las mujeres bolivianas desde un enfoque de sus relaciones de género, contemplando temas que permitan determinar su grado de desarrollo económico, político, social y cultural como resultado del proceso de implementación de políticas públicas durante la década comprendida entre los años 1992 y 2002

Dificultades en los métodos de estudio de exposiciones ambientales y defectos del tubo neural / Methodological challenges to assess environmental exposure related to neural tube defects

Objetivo. Discutir las actitudes en la evaluación de las exposiciones ambientales como factores de riesgo para defectos de riesgo del tubo neural, al tiempo que se presentan los principales factores estudiados hasta la fecha. Resultados. Las exposiciones ambientales se citan muy a menudo como causa de malformaciones congénitas; sin embargo, ha sido difícil establecer esta asociación en los estudios de poblaciones humanas, debido a problemas en su diseño y conducción. Lo anterior es particularmente marcado en el caso del estudio de los defectos del cierre del tubo neural (DTN), que es una de las principales malformaciones y que incluye anencefalia, espina bífida y encefalocele, y su asociación con exposiciones ambientales. Las dificultades en los métodos surgen de: a) la medida de frecuencia para realizar comparaciones espacio-temporales; b) la clasificación y heterogeneidad de las malformaciones; c) la consideración de los factores relacionados con la madre, el padre y el producto, de manera conjunta, y d) la evaluación de las exposiciones ambientales. Conclusiones. Hipotéticamente las exposiciones ambientales tanto del padre como de la madre pueden producir daño genético antes y/o después de la concepción por la acción directa sobre el embrión o sobre el complejo fetoplacentario, de tal manera que en la evaluación de exposiciones ambientales: a) deben tomarse en cuenta las exposiciones maternas y paternas; b) debe considerarse el periodo crítico de exposición, esto es, tres meses anteriores a la concepción para el padre y un mes alrededor de la concepción para la madre; c) en la medida de lo posible, la evaluación de la exposición deberá ser cuantitativa, evitando clasificar a los grupos únicamente como expuestos y no expuestos, y d) es recomendable emplear marcadores biológicos de exposición siempre que sea posible, así como utilizar marcadores biológicos que permitan clasificar a la población en grupos con distinta susceptibilidad genética

El diseño de casos y controles en la investigación / The case control design in medical research

Presentamos un marco teórico-práctico de la metodología de los estudios de casos y controles incluyendo diseño y análisis. El propósito es mostrar elementos conceptuales prácticos al personal de salud interesado en la investigación, que provengan del área clínica, de servicios de salud o que se encuentren en una etapa de formación académica. Hacemos referencia a la versatilidad en la aplicación de este tipo de diseño en la investigación en salud. En el diseño destacamos los aspectos más importantes en la selección de los casos y los controles y hacemos consideraciones sobre la determinación de tamaño de muestra. Mostramos algunos aspectos del análisis estadístico con ejemplos concretos, con estimación de razones de momios y sus intervalos de confianza, así como los métodos para evaluar si una asociación encontrada puede estar afectada por la presencia de una covariable o factor confusor, para lo cual se revisa la prueba de homogeneidad y la prueba de Mantel-Haeszel ajustada. Por último revisamos el análisis de regresión logística que permite el ajuste simultáneo por varios factores de interés en este tipo de estudios

El análisis de la desnutrición como causa múltiple de muerte / Malnutrition as a cause of death

Con el objeto de describir la frecuencia de la desnutricón como causa múltiple de muerte, se realizó un análisis de los certificados de defunción de los niños menores de cinco años que fallecieron en los meses de abril y mayo de 1985 en el Distrito Federal, México. Mediante un diseño de mortalidad proporcional e incluyendo todas las causas listadas en el certificado de defunción, se estudió la asociación entre desnutrición e infección. Se encontró que la frecuencia de la enfermedad infecciosa como causa básica de muerte fue casi ocho veces mayor cuando coexistió la desnutrición como causa múltiple que cuando no se reportó como tal, resultando estadísticamente significativa la diferencia (RM = 7.9, IC 95 por ciento 5.0 - 12.7, p = 0.00000). Se discute la relevancia de estudiar otras causas consignadas en el certificado de defunción, principalmente aquellas que son frecuentes entre la población pero que no se registran comúnmente como causa básica de muerte

With the purpose of describing the role of malnutrition at death time, an analysis of multiple causes of death in children under five years-old was performed on deaths which ocurred during April and May 1985 in Mexico City. A proportional mortality analysis was done taking in consideration all the causes listed on the death certificate, not only the underlying causes. The number of deaths associated to malnutrition was greater by multiple cause than by underlying cause (OR = 7.9, 95% CI 5.0 - 12.7, p = 0.00000). The importance of considering multiple causes of death, mainly when there are frequent diseases which are some times recorded as underlying cause of death, is also discussed.

Años de vida potencial perdidos en México: aplicaciones en la planeación de los servicios de salud / Years of potential life lost in Mexico: applications in health care services planning

Durante el proceso de planeación de los servicios de salud se requiere de información consistente que permita sustentar las decisiones referentes a la asignación de recursos, en función de las variaciones locales y regionales de salud. En el presente trabajo se utilizó el Indice de Años de Vida Potencialmente Perdidos (IAVPP) para priorizar la necesidad entre las entidades federativas del país. Se hace un intento de reconocer la situación actual del país mediante el contraste del IAVPP y la Inversión Pública Federal en Salud per cápita (IPFS) para cada entidad federativa, mediante la aplicación del método propuesto por Stone. Los resultados observados muestran diferencias notables, tanto en las necesidades como en la distribución de los recursos. Las razones de recursos-necesidad presentan una gama de entre 0.21 para el estado de Oaxaca y 3.79 para el D.F. Tomando en cuenta sólo los estados extremos, los que tuvieron menor asignación de recursos respecto a su necesidad relativa fueron: O axaca, Puebla, Hidalgo y México; las entidades con mayores recursos fueron del Distrito Federal, Quintana Roo, Baja California Sur y Tamaulipas. La proposición del uso estos indicadores en la asignación de recursos busca, en términos de equidad, la distribución desigual de los recursos, asignando más a quien más lo necesita