Nanopartículas de quitosana/tripolifosfato como sistema de liberação para o herbicida Paraquat : preparo, caracterização, interação com substâncias húmicas e avaliação da atividade biológica

Orientador: Leonardo Fernandes FracetoTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: Os defensivos agrícolas tornaram-se alguns dos mais importantes compostos utilizados no mundo e são os principais responsáveis pelo aumento da produção agrícola. O Paraquat, um herbicida não seletivo de contato utilizado em diversas culturas no mundo, apresenta alta toxicidade para os seres vivos e considerável persistência no solo, o que fez com que ele fosse banido em alguns países. Embora os defensivos agrícolas possuam uma importante função no aumento da produção de alimentos, através do controle de pragas, eles podem gerar sérios impactos ambientais, através da contaminação dos recursos hídricos e do solo. Com o crescimento da nanotecnologia, diversos mecanismos estão sendo estudados a fim de minimizar estes danos, tais como o desenvolvimento de sistemas de liberação modificada, utilizando polímeros biodegradáveis, o qual permite um aumento no desempenho/eficiência do produto. Estudos indicam que a matéria orgânica natural presente no solo, sedimento e água podem interagir com os defensivos agrícolas e nanopartículas e consequentemente modificar o destino destas substâncias no ambiente. A presente Tese tem como objetivo principal mostrar resultados do desenvolvimento e caracterização de nanopartículas poliméricas de quitosana/tripolifosfato para liberação modificada do herbicida Paraquat, bem como, estudar a estabilidade e a toxicidade deste sistema nanoparticulado com a presença ou ausência de matéria orgânica natural (na forma de substâncias húmicas). A atividade herbicida e a sorção do herbicida nanoparticulado no solo também foram avaliados. Nanopartículas de quitosana/tripolifosfato (com ou sem Paraquat) foram preparadas pelo método de gelificação iônica e apresentaram tamanho médio, índice de polidispersão e potencial zeta de ~ 300 nm, 0,250 e 45 mV, respectivamente. A eficiência de encapsulação do Paraquat foi de 62,6 ± 0,7 % e as nanopartículas apresentaram-se esféricas e com boa estabilidade coloidal. A cinética de liberação e o ensaio de sorção no solo mostraram que as nanopartículas retardaram a difusão e a liberação do herbicida e o modelo matemático que melhor descreveu a cinética de sorção foi o de pseudo-segunda ordem. Ensaios de citotoxicidade, genotoxicidade e ecotoxicidade indicaram que a associação do Paraquat às nanopartículas reduziram o efeito tóxico, uma vez que menos herbicida foi liberado para o ambiente em função do tempo, e ainda assim a atividade herbicida foi preservada ou aumentada. A presença de substâncias húmicas naturais não alterou os parâmetros físico-químicos estudados; entretanto, mostrou que pode reduzir a genotoxicidade e a ecotoxicidade do herbicida quando associado às nanopartículas, através de modificações na dinâmica do sistema. Este trabalho possui resultados inovadores e promissores que abrem novas discussões e perspectivas para o desenvolvimento de sistemas de liberação modificada para defensivos agrícolasAbstract: Agrochemicals have become one of the most important compounds used in the world and are the main responsible for the increase in agricultural production. Paraquat, a non-selective herbicide used in several crops in the world, has high toxicity to living beings and considerable persistence in the soil, which led to its banishment in some countries. Although agrochemicals have an important function in increasing food production by minimizing pests, they can cause serious environmental impacts through contamination of soil and water resources. With the nanotechnology growth, several mechanisms have been studied in order to minimize these damages, such as the development of modified release systems using biodegradable polymers, which allows an increase in performance/efficiency of the product. Studies indicate that the natural organic matter present in the soil, sediment and water can interact with agrochemicals and nanoparticles, and therefore, modify the destination of these substances in the environment. The purpose of the present Thesis is to show results of the development and characterization of chitosan/trypolyphosphate polymeric nanoparticles for modified release of the Paraquat herbicide, as well as to study the stability and toxicity of this nanoparticles with the presence or absence of natural organic matter (mainly in the form of humic substances). Herbicide activity and sorption of the nanoparticulate herbicide in the soil were also evaluated. Chitosan/Trypolyphosphate nanoparticles (with or without Paraquat) have been prepared by ionic gelation method and presented average size, polydispersity index and zeta potential of ~ 300 nm, 0.250 and 45 mV, respectively. The Paraquat encapsulation efficiency was 62.6 ± 0.7 % and the nanoparticles showed themselves spherical and good colloidal stability. The release kinetics and sorption test in the soil showed that the nanoparticles modified the diffusion and release of herbicide and the mathematical model that best described the sorption kinetics was pseudo-second order. Cytotoxicity, genotoxicity and ecotoxicity tests indicated that the association of Paraquat with the nanoparticles reduced the toxic effect, since less herbicide was released into the environment as function of time, but even so, the herbicidal activity was preserved or enhanced. The presence of humic substances in the medium altered the dynamic equilibrium of the herbicide in solution, and diminished the toxicity of the nanoparticle/paraquat system. This study has innovative and promising results that open new discussions and perspectives for the development of modified release systems for agrochemicalsDoutoradoBioquimicaDoutor em Biologia Funcional e Molecula

Produção do Pinus taeda L. em povoamento desbastado na região dos Campos de Cima da Serra, Rio Grande do Sul

This work was carried out with the objective of studying the yield of Pinus taeda L., planted in an initial spacing of 3 x 2 m, located in Canela, Rio Grande do Sul state. The amostral population was submitted to one and two selective thinning, beyond a control sample, without thinning. The selective low thinning was conducted with reduction of the basal area to levels of 28 m2/ha. At age 17, the total yield of the control sample, without thinning, was 886.3 m3ha-1; with one thinning at age 11 the yield was 756.6 m3ha-1, resulting in losses of yield of 14.6% compared to the control; with two selective at ages 11 and 15, the yield was 732.9 m3ha-1, resulting in losses of yield in relation with the control sample, without thinning, of 17.3%. The selective thinning allowed a significant gain in diameter, up to age 17, with the execution of a selective thinning at age 11 an average diameter of 33.4 cm; with two selective thinning at ages 11 and 15 an average diameter of 33.5 cm; and an average diameter of 24.3 cm in the control sample, without thinning.Este trabalho foi realizado com o objetivo de estudar a produção do Pinus taeda L., implantado num espaçamento inicial de 3 x 2 m, localizado em Canela, estado do Rio Grande do Sul. A população amostral foi submetida a um e dois desbastes seletivos, além da manutenção de uma testemunha, sem desbaste. Os desbastes foram realizados por baixo com redução da área basal para níveis de 28 m2ha-1. Aos 17 anos, a produção total das parcelas testemunhas, sem desbaste, foi de 886,3 m3ha-1; com a realização de um desbaste aos 11 anos, de 756,6 m3ha-1, tendo resultado perdas de produção em relação a testemunha de 14,6 %; com dois desbastes aos 11 e 15 anos, a produção foi de 732,9 m3ha-1, tendo provocado perdas de produção em relação à testemunha, sem desbaste, de 17,3 %. Os desbastes executados permitiram um ganho significativo em diâmetro, até os 17 anos de idade, com a execução de um desbaste aos 11 anos obteve-se um diâmetro médio de 33,4 cm; com dois desbastes aos 11 e 15 anos, um diâmetro médio de 33,5 cm; e, um diâmetro médio de 24,3 cm na testemunha, sem desbaste

Yield of Pinus taeda L. in thinned stand in the Campos de Cima da Serra region, Rio Grande do Sul

Este trabalho foi realizado com o objetivo de estudar a produ\ue7\ue3o do Pinus taeda L., implantado num espa\ue7amento inicial de 3 x 2 m, localizado em Canela, estado do Rio Grande do Sul. A popula\ue7\ue3o amostral foi submetida a um e dois desbastes seletivos, al\ue9m da manuten\ue7\ue3o de uma testemunha, sem desbaste. Os desbastes foram realizados por baixo com redu\ue7\ue3o da \ue1rea basal para n\uedveis de 28 m2ha-1. Aos 17 anos, a produ\ue7\ue3o total das parcelas testemunhas, sem desbaste, foi de 886,3 m3ha-1; com a realiza\ue7\ue3o de um desbaste aos 11 anos, de 756,6 m3ha-1, tendo resultado perdas de produ\ue7\ue3o em rela\ue7\ue3o a testemunha de 14,6 %; com dois desbastes aos 11 e 15 anos, a produ\ue7\ue3o foi de 732,9 m3ha-1, tendo provocado perdas de produ\ue7\ue3o em rela\ue7\ue3o \ue0 testemunha, sem desbaste, de 17,3 %. Os desbastes executados permitiram um ganho significativo em di\ue2metro, at\ue9 os 17 anos de idade, com a execu\ue7\ue3o de um desbaste aos 11 anos obteve-se um di\ue2metro m\ue9dio de 33,4 cm; com dois desbastes aos 11 e 15 anos, um di\ue2metro m\ue9dio de 33,5 cm; e, um di\ue2metro m\ue9dio de 24,3 cm na testemunha, sem desbaste.This work was carried out with the objective of studying the yield of Pinus taeda L., planted in an initial spacing of 3 x 2 m, located in Canela, Rio Grande do Sul state. The amostral population was submitted to one and two selective thinning, beyond a control sample, without thinning. The selective low thinning was conducted with reduction of the basal area to levels of 28 m2/ha. At age 17, the total yield of the control sample, without thinning, was 886.3 m3ha-1; with one thinning at age 11 the yield was 756.6 m3ha-1, resulting in losses of yield of 14.6% compared to the control; with two selective at ages 11 and 15, the yield was 732.9 m3ha-1, resulting in losses of yield in relation with the control sample, without thinning, of 17.3%. The selective thinning allowed a significant gain in diameter, up to age 17; with the execution of a selective thinning at age 11 an average diameter of 33.4 cm; was obtained with two selective thinning at ages 11 and 15 an average diameter of 33.5 cm; and an average diameter of 24.3 cm in the control sample, without thinning

Covid-19 vaccination priorities defined on machine learning

OBJECTIVE: Defining priority vaccination groups is a critical factor to reduce mortality rates. METHODS: We sought to identify priority population groups for covid-19 vaccination, based on in-hospital risk of death, by using Extreme Gradient Boosting Machine Learning (ML) algorithm. We performed a retrospective cohort study comprising 49,197 patients (18 years or older), with RT-PCR-confirmed for covid-19, who were hospitalized in any of the 336 Brazilian hospitals considered in this study, from March 19th, 2020, to March 22nd, 2021. Independent variables encompassed age, sex, and chronic health conditions grouped into 179 large categories. Primary outcome was hospital discharge or in-hospital death. Priority population groups for vaccination were formed based on the different levels of in-hospital risk of death due to covid-19, from the ML model developed by taking into consideration the independent variables. All analysis were carried out in Python programming language (version 3.7) and R programming language (version 4.05). RESULTS: Patients’ mean age was of 60.5 ± 16.8 years (mean ± SD), mean in-hospital mortality rate was 17.9%, and the mean number of comorbidities per patient was 1.97 ± 1.85 (mean ± SD). The predictive model of in-hospital death presented area under the Receiver Operating Characteristic Curve (AUC - ROC) equal to 0.80. The investigated population was grouped into eleven (11) different risk categories, based on the variables chosen by the ML model developed in this study. CONCLUSIONS: The use of ML for defining population priorities groups for vaccination, based on risk of in-hospital death, can be easily applied by health system managers

Physico-chemical characterization of inclusion complex between hydroxymethylnitrofurazone and hydroxypropyl-beta-cyclodextrin

Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-beta-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (deltaGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Fatores associados ao tempo de permanência hospitalar de mulheres submetidas à cesariana

OBJECTIVE: To evaluate whether age group, complications or comorbidities are associated with the length of hospitalization of women undergoing cesarean section. METHODS: A cross-sectional study was carried out between June 2012 and July 2017, with 64,437 women undergoing cesarean section and who did not acquire conditions during their hospital stay. Hospital discharge data were collected from national health institutions, using the Diagnosis-Related Groups system (DRG Brasil). The DRG referring to cesarean section with additional complications or comorbidities (DRG 765) and cesarean section without complications or associated comorbidities (DRG 766) were included in the initial diagnosis. The influence of age group and comorbidities or complications present at admission on the length of hospital stay was assessed based on the means of the analysis of variance. The size of the effect was verified by Cohen’s D, which allows evaluating clinical relevance. The criticality levels were identified using the Duncan test. RESULTS: The longest length of hospital stay was observed in the age group from 15 to 17 years old and among those aged 45 years old or more. The hospital stay of women with complications or comorbidities at the time of admission was also longer. Moreover, it was noted that the increase in criticality level was associated with an increase in the mean length of hospital stay. CONCLUSIONS: The length of hospital stay of women is higher among those belonging to the age group ranging from 15 to 17 years old and for those aged 45 years old or more. The presence of associated comorbidities, such as eclampsia, pre-existing hypertensive disorder with superimposed proteinuria and gestational hypertension (induced by pregnancy) with significant proteinuria increase the length of hospital stay. This study enabled the construction of distinct criticality level profiles based on the combination of age groups and the main comorbidities, which were directly related to the length of hospital stay.OBJETIVO: Avaliar se grupo etário, complicações ou comorbidades estão associados ao tempo de internação de mulheres submetidas à cesariana. MÉTODOS: Estudo transversal realizado entre junho de 2012 e julho de 2017, com 64.437 mulheres submetidas à cesariana e que não apresentaram condições adquiridas durante o tempo de permanência hospitalar. Os dados foram coletados a partir da alta hospitalar nas instituições nacionais de saúde, utilizando o sistema Diagnosis-Related Groups [Grupos de Diagnósticos Relacionados] (DRG Brasil). Foram incluídos os DRG referentes à cesariana com complicações ou comorbidades adicionais ao diagnóstico inicial (DRG 765) e cesariana sem complicações ou comorbidades associadas (DRG 766). A influência do grupo etário e comorbidades ou complicações presentes na admissão sobre o tempo de permanência hospitalar foi avaliada por meio da análise de variância. O tamanho do efeito foi verificado pelo d de Cohen, que permite avaliar a relevância clínica. Os níveis de criticidade foram identificados utilizando o teste de Duncan. RESULTADOS: O maior tempo de permanência hospitalar foi observado nos grupos etários de 15 a 17 anos e 45 anos ou mais. Mulheres que apresentaram complicações ou comorbidades presentes à admissão também apresentaram maior tempo de permanência hospitalar. Quantos aos níveis de criticidade, notou-se que seu aumento estava associado ao aumento na média do tempo de permanência hospitalar. CONCLUSÕES: O tempo de permanência hospitalar de mulheres é maior entre aquelas pertencentes aos grupos etários de 15 a 17 anos e 45 anos ou mais. A presença de comorbidades associadas, como a eclâmpsia, o distúrbio hipertensivo pré-existente com proteinúria superposta e a hipertensão gestacional (induzida pela gravidez) com proteinúria significativa aumentam o tempo de permanência hospitalar. Este estudo possibilitou a construção de perfis distintos de níveis de criticidade a partir da combinação de grupos etários e das principais comorbidades, os quais se apresentaram diretamente relacionados ao tempo de permanência hospitalar

Challenging the tradition of a fishmeal producing countryan economic overview of the fishing activity of Piura, Peru

Piura is a region in northern Peru that stands out for its artisanal fisheries, export-oriented processing industry that focuses on products for direct human consumption (DHC), and marine gastronomy. We characterized the Piura region’s fisheries sector value chain for 2014 using primary and secondary information. This resulted in the estimation of indicators for production, value added (VA) and employment. Piura reported landings of 732,000 t of fish and invertebrates that generated U$D 1,771 million of income, U$D 700 million of VA and 49,000 jobs. The main supply chains of Piura’s landings were: (1) Industrial production and export of DHC products mainly sourced from artisanal fisheries (82% landings, 59% of AV, and 46% of employment), and (2) Supply of fresh seafood for domestic consumption (13% landings, 36% of AV, and 52% of employment). This region does not follow the national pattern for Peru. The latter is characterized by the massive industrial extraction of anchoveta for fishmeal and fish oil production (IHC). Finally, given that Peruvian artisanal fisheries have a long way to go before achieving sustainability, we discussed our findings within a broader governance framework seeking to strengthen participatory governance to prevent potential future collapses and increase the competitiveness of the economic activities characterized throughout this research.Publisher PDFPeer reviewe