Antimicrobial properties of membrane-active dodecapeptides derived from MSI-78

Antimicrobial peptides (AMPs) are a class of broad-spectrum antibiotics known by their ability to disrupt bacterial membranes and their low tendency to induce bacterial resistance, arising as excellent candidates to fight bacterial infections. In this study we aimed at designing short 12-mer AMPs, derived from a highly effective and broad spectrum synthetic AMP, MSI-78 (22 residues), by truncating this peptide at the N- and/or C-termini while spanning its entire sequence with 1 amino add (aa) shifts. These designed peptides were evaluated regarding antimicrobial activity against selected gram-positive Staphylococcus strains and the gram-negative Pseudomonas aeruginosa (P. aeruginosa). The short 12-mer peptide CEM1 (GIGMFLKKAKICF) was identified as an excellent candidate to fight P. aeruginosa infections as it displays antimicrobial activity against this strain and selectivity, with negligible toxicity to mammalian cells even at high concentrations. However, in general most of the short 12-mer peptides tested showed a reduction in antimicrobial activity, an effect that was more pronounced for gram-positive Staphylococcus strains. Interestingly, CEM1 and a highly similar peptide differing by only one aa-shift (CEM2: IGKFLKKAKICFG), showed a remarkably contrasting AMP activity. These two peptides were chosen for a more detailed study regarding their mechanism of action, using several biophysical assays and simple membrane models that mimic the mammalian and bacterial lipid composition. We confirmed the correlation between peptide helicity and antimicrobial activity and propose a mechanism of action based on the disruption of the bacterial membrane permeability barrier

Nonadherence to treatment recommendations is a factor contributing to the clinical failure of daptomycin: Cohort study in Brazil

To evaluate the clinical outcomes of daptomycin therapy and adherence to treatment recommendations, a retrospective cohort study was conducted with patients that received daptomycin during the period of the study. The adherence and nonadherence to clinical guidelines were assessed through organism identification, dose and time of treatment, management of bacteremia, and vancomycin treatment failure. A multiple logistic regression model analyzed the association between independent variables and clinical success (dependent variable), considering 5% of statistical significance. The study presented 52 patients who received daptomycin for the treatment of bacteremia (21.1%) or infections (osteomyelitis [63.5%], synovial fluid [15.4%]). Most patients (86.5%) received daptomycin as the second line of treatment, and 51.9% achieved clinical success. The patients had a better chance of clinical success when they followed the guideline indications (OR = 16.86; 95% CI = 1.45-195.88) and the medication was prescribed by a specialist in infectious diseases (OR = 4.84; 95% CI = 1.11- 21.09). The study demonstrated lower clinical success than that described in the literature because of patients who were not eligible according to the clinical guidelines. Adherence to recommendations and appropriate prescription of reserve antibiotics is important in limiting early resistance, and avoiding clinical failure and unnecessary expenditure

Main variables that are influenced by the anthropic activity resulting from the soybean production in the municipalities of Mato Grosso

This study aimed to identify how the main variables that are influenced by the anthropic activity resulting from the soybean production in the Mato Grosso Municipalities cluster among themselves. Factor analysis method was used to identify underlying dimensions that can account for the shared variation of observed variables. The factorial analysis proposes to reduce the number of variables by the extraction of independent factors, so that a better explanation of the relationship between the original variables occurs, avoiding correlational problems and reducing the relevance of endogeneity. Three dimensions were identified, each with a different combination of variables. Based on the results from principal components modelling it is fair to state that the impacts of the anthropic activity resulting from soybean production in the Mato Grosso municipalities can be analyzed according to three main domains: production impacts, socioeconomic impacts and demographic impacts. The main contribution of this paper is that it offers a useful framework of analysis for both public and private decision-makers regarding the influence of soybean production on economic, social, environmental, and cultural factors

Metabolic risk is associated with sociodemographic characteristics in adolescents from both rural and urban regions from southern Brazil

Background: The prevalence of several cardiovascular metabolic disorders are increasingly cause for concern in adolescents worldwide. Given the complex interrelations between metabolic risk (MR) and sociodemographic variables, the present study aims to examine the association between the presence of MR with sociodemographic characteristics (sex, skin color, residential area, and parental socioeconomic status) in adolescents from Southern Brazil. Methods: Cross-sectional study conducted with 1,152 adolescents (507 males) aged between 12 and 17 years. MR was assessed using a continuous score (cMetS; sum of Z-scores of the following variables: waist circumference, systolic blood pressure (SBP), glucose, high-density lipoprotein cholesterol [HDL-C, inverse], triglycerides [TG], and estimated cardiorespiratory fitness [CRF, inverse]). Poisson regression was used to examine associations between sociodemographic variables with the dichotomized cMetS and separate metabolic variables. The results were expressed with prevalence ratios (PR) and 95% confidence intervals (CI). Results: The presence of MR (evaluated by the cMetS) was observed in 8.7% of adolescents. Higher MR was less prevalent among non-white adolescents (PR: 0.96; 95% CI: 0.93; 0.99). Adolescents living in rural areas had a lower prevalence of the following metabolic variables; low HDL-C (PR: 0.95; 95% CI: 0.94; 0.97), elevated TG (PR: 0.95; 95% CI: 0.92; 0.99), elevated glucose (PR: 0.96; 95% CI: 0.95; 0.98), and low CRF levels (PR: 0.88; 95% CI: 0.85; 0.92). Whereas, SBP was higher in those living in rural areas (PR: 1.11; 95% CI: 1.05; 1.17). In girls, there was a higher prevalence of raised TG (PR: 1.06; 95% CI: 1.02; 1.10) and lower levels of CRF (PR: 1.20; 95% CI: 1.16; 1.24), but a lower prevalence of elevated glucose (PR: 0.97; 95% CI: 0.97; 0.99). Conclusion: Higher MR prevalence was lower in those self-reporting non-white skin color and selected MR factors were less prevalent in those living in rural areas. The identification of groups at higher MR is important for early prevention and monitoring strategies for both Type 2 diabetes and later cardiovascular disease. Future studies should be conducted to assess the socio-cultural aspects of the relationships between MR and socio-cultural and lifestyle variables

Entomological survey in the state of Piauí, Northeastern Brazil, reveals intradomiciliary colonization of Triatoma brasiliensis macromelasoma

This survey aimed to assess the presence of triatomine vectors of Chagas disease within the rural communities of São João do Piauí, Northeast Brazil. Intradomiciliary and peridomiciliary collection strategies were implemented wherein 279 specimens of Triatoma brasiliensis macromelasoma, both nymph and adult were found in 15 (50%) of the studied homes. Of the intradomiciliary insects, 73 (67.6%) were identified as nymph instars (1st instar [N1]= 6, N2= 14, N3= 28, N4= 7 and N5= 18). In the studied communities, a continuous interaction between triatomine bugs and humans could be shown. It is therefore urgent that suitable strategies for the control of the triatomine vector are implemented in this area

Perfil de medicamentos envueltos en errores de administración: conocer para prevenir

OBJECTIVES: To describe the pharmacological characteristics of medicines involved in administration errors and determine the frequency of errors with potentially dangerous medicines and low therapeutic index, in clinical units of five teaching hospitals, in Brazil. METHODS: Multicentric study, descriptive and exploratory, using the non-participant observation technique (during the administration of 4958 doses of medicines) and the anatomical therapeutic chemical classification (ATC). RESULTS: Of that total, 1500 administration errors were identified (30.3%). The administration of pharmacological groups - ATC (cardiovascular system, nervous system, alimentary tract and metabolism system and anti-infectives for systemic use) showed a higher frequency of errors. In 13.0% of errors were involved potentially dangerous medicines and in 12.2% medicines with low therapeutic index. CONCLUSION: The knowledge of the pharmacological profile could be an important strategy to be used in the prevention medication errors in health institutions.OBJETIVOS: Descrever as características farmacológicas dos medicamentos envolvidos em erros de administração e determinar a frequência desses erros com medicamentos potencialmente perigosos e de baixo índice terapêutico em unidades de clínica médica de cinco hospitais de ensino brasileiros. MÉTODOS: Estudo multicêntrico, descritivo/exploratório utilizando a técnica de observação não participante durante a administração de 4958 doses de medicamentos e a classificação anatômica terapêutica química (ATC). RESULTADOS: Dentre esse total, foram identificados 1500 erros de administração de medicamentos (30,3%). A administração dos fármacos dos grupos ATC - sistema cardiovascular, sistema nervoso, trato alimentar e metabolismo e antinfecciosos de uso sistêmico apresentou maior frequência de erros. Em 13,0% dos erros estavam envolvidos medicamentos potencialmente perigosos e em 12,2% medicamentos de baixo índice terapêutico. CONCLUSÃO: O conhecimento do perfil farmacológico pode ser uma importante estratégia a ser utilizada na prevenção de erros de medicação em instituições de saúde.OBJETIVOS: Describir las características farmacológicas de los medicamentos envueltos en errores de administración y determinar la frecuencia de esos errores en medicamentos potencialmente peligrosos y en los de bajo índice terapéutico, en unidades de clínica médica de cinco hospitales de enseñanza brasileños. MÉTODOS: Estudio multicéntrico, descriptivo-exploratorio utilizando la técnica de observación no participante (durante la administración de 4.958 dosis de medicamentos) y la clasificación anatómica terapéutica química (ATC). RESULTADOS: Fueron identificados 1500 errores de administración de medicamentos (30,3%). La administración de los fármacos de los grupos ATC (sistema cardiovascular, sistema nervioso, sistema digestivo y metabolismo, y, anti-infecciosos) de uso sistémico presentó mayor frecuencia de errores. En 13,0% de los errores estaban envueltos medicamentos potencialmente peligrosos y en 12,2% medicamentos de bajo índice terapéutico. CONCLUSIÓN: El conocimiento del perfil farmacológico puede ser una importante estrategia para prevenir los errores de medicación en las instituciones de salud.FAPESPCNPqCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Práticas de amamentação no município de Ouro Preto, MG, Brasil

OBJETIVO: Conhecer a freqüência e a duração mediana das práticas de aleitamento materno em crianças de 0-24 meses no município de Ouro Preto, MG. MÉTODOS: Estudo epidemiológico tipo transversal em amostra estratificada de 229 crianças provenientes de 1.800 domicílios, visitados em 1996 e sorteados por conglomerado em três estágios. A freqüência e a duração mediana das práticas foram calculadas mediante tábua de vida. RESULTADOS: A duração mediana da amamentação foi de 198 dias, sendo de 71 dias para a amamentação exclusiva somada à predominante e 17 dias para a amamentação exclusiva. CONCLUSÃO: Embora a maioria das mães amamente seus filhos ao nascer, a introdução de outros alimentos ainda é bastante prematura, fato que justifica a necessidade de intervenções para prevenir o desmame parcial e/ou total precoce.OBJECTIVE: To identify the frequency and median duration of breast-feeding in children aged 0-24 months in the city of Ouro Preto, Brazil. METHODS: A cross-sectional study was carried out to identify the median duration of breastfeeding in children aged 0-24 months. A sample of 229 children from 1800 households was drawn by clusters at three different occasions and stratified according to the area (urban or rural). The frequency and median duration of breast-feeding were calculated using the life table technique. RESULTS: A median duration of 198 days was found for breast-feeding as a whole: 71 days for the group of exclusive plus mainly breastfeeding and 17 days for exclusive breastfeeding. CONCLUSION: The current pattern of breast-feeding is of a short-term practice. This evidence suggests the need for intervention programs to promote breast-feeding for longer periods and delay the introduction of food supplementation, preventing the early weaning

An Inherited Small Microdeletion at 15q13.3 in a Patient\ud with Early- Onset Obsessive-Compulsive Disorder

Copy number variations (CNVs) have been previously associated with several different neurodevelopmental psychiatric\ud disorders, such as autism, schizophrenia, and attention deficit hyperactivity disorder (ADHD). The present study consisted of\ud a pilot genome-wide screen for CNVs in a cohort of 16 patients with early-onset obsessive-compulsive disorder (OCD) and\ud 12 mentally healthy individuals, using array-based comparative genomic hybridization (aCGH) on 44K arrays. A small rare\ud paternal inherited microdeletion (,64 kb) was identified in chromosome 15q13.3 of one male patient with very early onset\ud OCD. The father did not have OCD. The deletion encompassed part of the FMN1 gene, which is involved with the\ud glutamatergic system. This finding supports the hypothesis of a complex network of several genes expressed in the brain\ud contributing for the genetic risk of OCD, and also supports the glutamatergic involvement in OCD, which has been\ud previously reported in the literature.We wish to thank the patients and heathy controls who volunteered to participate in this study.This study was supported by grants to Dras Cappi and Brentani from the Foundation for Research Support of the State of São Paulo (FAPESP); grant number: 2008/11537-7, and from the Brazilian National Council for Scientific and Technological Development (CNPq; protocol number MCT/CNPq 14/2008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78

Intervenção psicoeducativa em grupo de mães adolescentes: um relato de experiência

Studies concerning teenage mothers have increasingly become a focus of attention in the field of psychology. The number of girls becoming mothers at ages of between ten and fourteen years is constantly growing, which seems to necessitate a review of how this phase of life is affected by the family environment. Mothers, in particular, are influential in their children’s lives, furnishing notions concerning the concept of a good life and providing guidelines to avoid dangerous situations and early pregnancy, within a progressive educational process beginning at an early age. Considering the variables that affect the way that the family functions, and the growing number of adolescents that become mothers, and hence initiate a new family group, the main objectives of this work are to evaluate the parental abilities of teenage mothers, provide guidance to prevent inadvertent pregnancy, and suggest correlations with the current environment within which adolescents find themselves, from a Developmental Psychology perspective.Los estudios con madres adolescentes se han convertido en un foco creciente dentro de la psicología. En este contexto, existe un número cada vez mayor de niñas que llegan a ser madres con edades entre diez y catorce años, lo que parece una señal para rever como este ciclo está directamente relacionado a los patrones de desarrollo familiar. Las madres, especialmente, poseen un papel significativo en la vida de los hijos, influenciándolos con su concepción de lo que sería una buena vida y mostrando como evitar envolverse en comportamientos de riesgos, de gravidez precoz, todo esto por medio de de un proceso gradual de educación, comenzando a una edad temprana. Al considerar algunas variables que actúan sobre el funcionamiento familiar, además de la incidencia del crecimiento de las adolescentes que se convierten en madres y que tienden a comenzar un nuevo grupo familiar, este trabajo tuvo como objetivos: evaluar las a habilidades y responsabilidades de las madres adolescentes; dar orientación y prevenir gravidez indeseada y favorecer correlaciones con el ciclo vital en que se encuentran partiendo de la perspectiva de la Psicología del Desarrollo.Estudos com mães adolescentes têm se configurado um foco crescente dentro da Psicologia. Neste contexto, há um número cada vez maior de meninas que se tornam mães com idade entre dez e quatorze anos, o que parece apontar para a necessidade de se rever como esta fase do ciclo vital está diretamente relacionada a padrões do desenvolvimento familiar. As mães, em especial, têm papel significativo nas vidas dos filhos, influenciando suas idéias sobre o que seria uma boa vida e como evitar envolverem-se em comportamentos de risco e gravidez precoce, por meio de um processo de educação gradual e que começa desde a mais tenra idade. Considerando algumas variáveis que atuam sobre o funcionamento da família, e, com a emergência cada vez maior de adolescentes que se tornam mães e, portanto, tendem a iniciar um novo grupo familiar, este trabalho teve como principais objetivos avaliar as habilidades parentais de mães adolescentes, orientar a prevenção da gravidez indesejada e propiciar algumas correlações com a fase do ciclo vital em que se encontram, a partir da perspectiva da Psicologia do Desenvolvimento