Simulating exposure-related human mobility behavior at the neighborhood-level under COVID-19 in Porto Alegre, Brazil.

Modeling experts have been continually researching the interplay of human mobility and COVID-19 transmission since the outbreak of the pandemic. They tried to address this problem and support the control of the pandemic spreading at the national or regional levels. However, these modeling approaches had little success in producing empirically verifiable results at the neighborhood level due to a lack of data and limited representation of low spatial scales in the models. To fill this gap, this research aims to present an agent-based model to simulate human mobility choices in the context of COVID-19, based on social activities of individuals in the neighborhood. We apply the VIABLE model to the decision-making process of heterogeneous agents, who populate the system's environment. The agents adapt their mobility and activities autonomously at each iteration to improve their well-being and respond to exposure risks. The study reveals significant temporal variations in mobility choices between the groups of agents with different vulnerability levels under the Covid-19 pandemic. Agents from the same group with similar economic backgrounds tend to select the same mobility patterns and activities leading to segregation at this low scale. We calibrated the model with a focus on Porto Alegre in Brazil.

Antiproliferative Activity and VEGF Expression Reduction in MCF7 and PC-3 Cancer Cells by Paclitaxel and Imatinib Co-encapsulation in Folate-Targeted Liposomes.

Co-encapsulation of anticancer drugs paclitaxel and imatinib in nanocarriers is a promising strategy to optimize cancer treatment. Aiming to combine the cytotoxic and antiangiogenic properties of the drugs, a liposome formulation targeted to folate receptor co-encapsulating paclitaxel and imatinib was designed in this work. An efficient method was optimized for the synthesis of the lipid anchor DSPE-PEG(2000)-folic acid (FA). The structure of the obtained product was confirmed by RMN, FT-IR, and ESI-MS techniques. A new analytical method was developed and validated for simultaneous quantification of the drugs by liquid chromatography. Liposomes, composed of phosphatidylcholine, cholesterol, and DSPE-mPEG(2000), were prepared by extrusion. Their surface was modified by post-insertion of DSPE-PEG(2000)-FA. Reaction yield for DSPE-PEG(2000)-FA synthesis was 87%. Liposomes had a mean diameter of 122.85 ± 1.48 nm and polydispersity index of 0.19 ± 0.01. Lyophilized formulations remained stable for 60 days in terms of size and drug loading. FA-targeted liposomes had a higher effect on MCF7 cell viability reduction (p < 0.05) when compared with non-targeted liposomes and free paclitaxel. On PC-3 cells, viability reduction was greater (p < 0.01) when cells were exposed to targeted vesicles co-encapsulating both drugs, compared with the non-targeted formulation. VEGF gene expression was reduced in MCF7 and PC-3 cells (p < 0.0001), with targeted vesicles exhibiting better performance than non-targeted liposomes. Our results demonstrate that multifunctional liposomes associating molecular targeting and multidrug co-encapsulation are an interesting strategy to achieve enhanced internalization and accumulation of drugs in targeted cells, combining multiple antitumor strategies.

4-Nerolidylcatechol analogues as promising anticancer agents.

4-Nerolidylcatechol (1) is an isolated compound from Pothomorphe umbellata L. (Piperaceae) with promising antitumor cells properties. However it presents lability under light and room temperatures. Many efforts have been directed towards discovering anticancer agents endowed with cytotoxic activities. Here, we evaluated cytotoxic effects of 4-NRC analogues (LQFMs 2-6) and the cell death pathways induced by these compounds in multidrug-resistant K562 cells. Compounds (2-6) exhibited cytotoxic activities in a concentration-dependent manner against leukaemic cells, specially the compounds (3) and (5). Additionally, compounds (1), (3) and (5) promoted marked alterations on the cell morphology, including nuclear changes as demonstrated by Hoescht 33342 staining. Moreover, these compounds promoted apoptosis induction in K562 cells by phosphatidylserine exposure, increase of sub-G1 cells and modulation of the caspases-3/7, -8 and -9 activation. In addition, the pancaspase inhibitor z-VAD-fmk partially reduced the apoptosis induced by the compounds (1) and (5)-induced, suggesting caspase-dependent and caspase-independent cell death pathways. Compounds (1) and (5) also modified the cell cycle progression by G0/G1 and S arrest, respectively. Furthermore, compounds (1), (3) and (5) promoted mitochondrial dysfunction associated to accumulation of cytosolic cytochrome c and modulated the NF-ĸB activation. In addition, unlike their analogues, 4-NRC (1) also promoted a significant cyclin D1 inhibition. Together, these data suggest that the mechanism of cell death of 4-NRC and its analogues (3) and (5) occurs by apoptosis through mitochondrial mechanisms. Considering that LQFMs are biocompatible synthetic analogues produced by molecular simplification of (1) without the chiral centre, which is associated with the instability found in compound (1), we suggest that these compounds are promising candidates for further pre-clinical studies.

Mechanical behaviors of Flutter VRP1, Shaker, and Acapella devices.

BACKGROUND: Flutter VRP1, Shaker, and Acapella are devices that combine positive expiratory pressure (PEP) and oscillations. OBJECTIVES: To compare the mechanical performance of the Flutter VRP1, Shaker, and Acapella devices. METHODS: An experimental platform and a ventilator, used a flow generator at 5, 10, 15, 20, 26, and 32 L/min, were employed at angles of -30°, 0°, and +30° to evaluate Flutter VRP1 and Shaker, whereas Acapella was adjusted at intermediate, higher, and lower levels of resistance, including positive expiratory pressures (PEP) along with air outflow rates and oscillation frequencies. RESULTS: When the relationships between pressure amplitudes of all air flows were analyzed for the 3 devices at low and intermediate pressures levels, no statistically significant differences were observed in mean pressure amplitudes between Flutter VRP1 and Shaker devices. However, both devices had different values from Acapella, with their pressure amplitude values being higher than that of Acapella (P = .04). There were no statistically significant differences in PEP for the 3 angles or marks regarding all air flows. The expected relationships between variables were observed, with increases in PEP, compared to those of air flows and resistance. Nevertheless, there was a statistically significant difference in frequency of oscillation between these devices and Acapella, whose value was higher than those of Flutter VRP1 and Shaker devices (P = .002). At intermediate pressure levels, the patterns were the same, in comparison to low pressures, although the Acapella device showed frequencies of oscillation values lower than those of Flutter VRP1 and Shaker (P < .001). At high pressures, there were no statistically significant differences among the 3 devices for frequency of oscillations. CONCLUSIONS: The Flutter VRP1 and Shaker devices had a similar performance to that of Acapella in many aspects, except for PEP.

Net energy levels on the lipid profile of pork / Níveis de energia líquida no perfil lipídico da carne suína

ABSTRACT: This study was conducted to evaluate the effects of net energy levels on the lipid profile of adipose tissue and muscle of swines. A total of 90 animals, with initial weight of 71.94±4.43kg, were used, and distributed in a randomized block design in five net energy levels (2,300, 2,425, 2,550, 2,675, and 2,800Kcal kg-1 feed), with nine replicates and two animals per experimental unit. Lipid profiles of adipose tissue and muscle were analyzed using gas chromatography. Increasing the levels of net energy using soybean oil, improved the lipid profile of adipose tissue and muscle, increased linearly (P<0.05) the concentrations of polyunsaturated fatty acids, especially linoleic and α-linolenic acid, reduced linearly (P<0.05) the monounsaturated and saturated fatty acids and omega 6: omega 3. In adipose tissue was observed linear reduction (P<0.05) of atherogenic and thrombogenic indexes. In conclusion, increasing the level of net energy of the diet using soybean oil improved the lipid profile of adipose tissue and muscle.

RESUMO: Este estudo foi conduzido com o objetivo de avaliar o efeito dos níveis de energia líquida no perfil lipídico da gordura e carne suína. Foram utilizados 90 animais, com peso inicial de 71,94±4,43kg, distribuídos em delineamento de blocos ao acaso em cinco níveis de energia líquida (2.300, 2.425, 2.550, 2.675 e 2.800Kcal kg-1 de ração), com nove repetições e dois animais por unidade experimental. Foram analisados os perfis lipídicos da gordura subcutânea e da carne por cromatografia gasosa. O aumento do nível de energia líquida usando óleo de soja melhorou o perfil lipídico da gordura subcutânea e da carne, aumentando linearmente (P<0,05) a concentração dos ácidos graxos poli-insaturados, especialmente ácido linoleico e α-linolênico, reduzindo linearmente (P<0,05) os ácidos graxos monoinsaturados e saturados e ômega 6: ômega 3. No tecido adiposo foi observado redução linear (P<0,05) dos índices aterogênico e trombogênico. Em conclusão, o aumento do nível de energia líquida da dieta, com a utilização do óleo de soja, melhora o perfil lipídico da gordura subcutânea e da carne suína.

Grandisin induces apoptosis in leukemic K562 cells

Abstract In this study, the potential antileukemic activity of grandisin, a lignan extracted from Piper solmsianum, was evaluated against the leukemic line K562. The cytotoxicity of grandisin (0.018 to 2.365 µM) was evaluated in K562 and normal peripheral blood lymphocytes by Trypan Blue Exclusion and MTT methods after 48h exposure to the drug. In both methods, cellular viability was concentration-dependent and the IC50 values were lower than 0.85µM. Analysis of K562 cells after treatment with grandisin showed that the cell cycle was arrested in the G1 phase with a 12.31% increase, while both S and G2 phases decreased. Morphological studies conducted after the exposure of K562 to grandisin revealed changes consistent with the apoptosis process, which was confirmed by anexin V stain and caspase activation. Thus, lignan grandisin showed antileukemic activities against the K562 cell line and the cell death process occurred via apoptosis.

Avaliação técnico-econômica de suínos machos imuno e cirurgicamente castrados / Technical-economic evaluation of imuno and surgically castrated male pigs

Realizou-se este estudo com o objetivo de avaliar o desempenho técnico-econômico e determinar a lucratividade, por meio da análise de sensibilidade econômica, de suínos machos imuno (IM) e cirurgicamente castrados (MC). Foram realizados dois experimentos, em delineamento inteiramente casualizado, composto por dois tratamentos (IM e MC), com oito repetições de 10 animais cada, totalizando 160 suínos por experimento. Verificou-se que suínos IM apresentam menor consumo de ração e melhor conversão alimentar nas fases de crescimento em relação aos MC. Na fase de terminação, suínos IM apresentam melhor ganho de peso, conversão alimentar, rendimento de carcaça e porcentagem de carne em relação aos MC. A utilização de IM aumenta a lucratividade na produção de suínos. A análise de lucratividade entre suínos IM e MC deve considerar todas as fases de criação, uma vez que o desempenho diferencial dos suínos não castrados na fase de crescimento influencia economicamente os resultados da produção.

This study was conducted to evaluate the technical and economic performance and determine profitability through the economic sensitivity analysis of immune (IM) and male pigs surgically castrated (SC). Two experiments were conducted in a completely randomized design, consisting of two treatments (IM and SC) with eight replicates of 10 animals each, totaling 160 pigs per experiment. It was found that IM pigs have lower feed intake and feed conversion during the growth phases in relation to SC. In the finishing phases, IM have better weight gain, feed conversion, carcass yield and lean meat percentage in relation to SC. The use of IM increases the profitability in pig production. The analysis of profitability differential between IM and SC should consider all stages of creation, since the differential performance of not castrated pigs during growth influences economic results of production.

Restrição alimentar para suínos machos castrados e imunocastrados em terminação / Feeding restriction to finishing barrows and immunocastrated swine

O objetivo do trabalho foi avaliar o desempenho e as características quantitativas de carcaça de suínos machos castrados e imunocastrados, sob alimentação à vontade ou restrição quantitativa. Foram utilizados 240 animais, com peso inicial de 91,49±3,26kg, distribuídos em delineamento experimental de blocos ao acaso, em esquema fatorial 2x2 (dois manejos alimentares e duas categorias), com quatro repetições e 15 suínos cada. Suínos sob restrição alimentar apresentaram consumo inferior (P<0,05) em relação aos alimentados à vontade. O consumo de ração não diferiu (P>0,05) entre castrados e imunocastrados. Suínos alimentados à vontade apresentaram maior (P<0,05) ganho de peso em relação àqueles sob restrição. Os imunocastrados apresentaram ganho de peso superior (P<0,05) aos castrados. Houve interação (P<0,05) entre manejo e categorias para conversão alimentar, em que a restrição melhorou a conversão alimentar dos castrados em relação aos imunocastrados. Além disso, os imunocastrados apresentaram melhor (P<0,05) conversão alimentar em relação aos castrados, independente do manejo alimentar. Não houve interação (P>0,05) entre os fatores sobre as características de carcaça. A restrição não afetou (P>0,05) as características de carcaça. Machos imunocastrados apresentaram menor (P<0,05) espessura de toucinho e maior percentual de carne magra na carcaça. A restrição alimentar melhora a conversão alimentar de machos castrados. A restrição alimentar piora o ganho de peso e não altera as características de carcaça dos machos castrados e imunocastrados. Suínos imunocastrados apresentam desempenho superior, menor espessura de toucinho e maior percentual de carne magra em relação aos castrados.

The objective of this study was to evaluate the performance and carcass quantitative characteristics of barrows and immunocastrated swine fed ad libitum or under quantitative feeding restriction. Two hundred and forty animals were used, with initial weight of 91.49±3.26kg, distributed in a randomized blocks design, in a factorial scheme 2x2 (two management and two food categories), with four replicates of 15 pigs each. Pigs submitted to dietary restriction had lower consumption (P<0.05) than those fed ad libitum. Feed intake did not differ (P>0.05) between castrated and immunocastrated. Pigs fed ad libitum had higher (P<0.05) weight gain over those submitted to restriction. The immunocastrated showed higher weight gain (P<0.05) than castrated. There was an interaction (P<0.05) between management and categories for feed, in which the restriction improved castrated pigs. Immunocastrated had better (P <0.05) feed conversion compared to castrated, regardless of feed management. There was no interaction (P>0.05) among the factors on carcass traits. The restriction did not affect (P>0.05) carcass traits. Immunocastrated pigs had lower (P<0.05) back fat thickness and higher percentage of lean meat. Dietary restriction improves feed conversion of castrated pigs. The dietary restriction affects weight gain and does not affect carcass characteristics of barrows and immunocastrated. Immunocastrated pigs have higher performance, lower back fat thickness and a higher percentage of lean meat compared to the castrated.

Energia líquida e ractopamina para leitoas em terminação sob altas temperaturas ambientais / Net energy and ractopamine to finishing gilts under high temperature environment

O objetivo do trabalho foi avaliar níveis de energia líquida (EL) e ractopamina na dieta de leitoas em terminação sob altas temperaturas ambientais (29,5±2,3°C). Foram utilizadas 40 leitoas (peso inicial de 69,3±2,8kg) distribuídas no delineamento de bloco ao acaso em esquema fatorial 2x4 (0 e 20ppm de ractopamina e 2.300; 2.424; 2.548 e 2.668kcal de EL kg-1 de ração), com cinco repetições de um animal cada. Houve interação (P<0,05) entre EL e ractopamina, sendo que a inclusão de 20ppm em dietas com 2.548 e 2.668kcal reduziu (P<0,05) a espessura de toucinho e aumentou (P<0,05) a percentagem de carne magra das carcaças. A ractopamina melhorou (P<0,05) a conversão alimentar e a quantidade de carne magra nas carcaças (P<0,05), independente dos níveis de EL. Concluiu-se que a ractopamina na dose de 20ppm propicia benefícios no desempenho e características de carcaça de leitoas sob estresse térmico e que esse efeito é mais positivo em dietas contendo níveis energéticos mais elevados (2.548 e 2.668kcal de EL).

The objective of this paper was to assess net energy (NE) levels and ractopamine in the diet of finishing gilts maintained under high temperature environment (29.5±2.3°C). Forty gilts were used, with initial weight of 69.3±2.8kg, distributed in a randomized block design, in a factorial scheme 2x4 (0 and 20ppm of ractopamine; and 2,300; 2,424; 2,548 and 2,668kcal/kg NE kg-1 of feed), and five replications and one animal each. There was interaction (P<0.05) between NE levels and ractopamine, and the inclusion of 20ppm of ractopamine in the diets containing 2,548 and 2,668kcal reduced (P<0.05) backfat thickness and increased (P<0.05) the percentage of lean meat of carcasses. The use of ractopamine improved (P<0.05) feed gain ratio and increased (P<0.05) the amount of lean meat in carcasses. It was concluded that ractopamine at a dose of 20ppm provides benefits in performance and carcass traits of gilts under heat stress and this effect is more positive in diets containing higher energy levels (2,548 and 2,668kcal of NE kg-1).

Duração da suplementação de ractopamina em dietas para leitoas em terminação mantidas sob alta temperatura ambiente / Duration of ractopamine supplementation in diets for finishing gilts maintained under high temperature environment

Este estudo foi realizado com o objetivo de avaliar a duração da suplementação de ractopamina na dieta de leitoas em terminação, mantidas sob alta temperatura ambiente. Foram utilizadas 48 leitoas com peso inicial de 70,4±2,6kg, distribuídas no delineamento de blocos ao acaso, com seis tratamentos (suplementação de ractopamina por 0, 7, 14, 21, 28 e 35 dias pré-abate) e quatro repetições, sendo a unidade experimental constituída por dois animais. O peso final e o consumo de ração diário não foram influenciados (P>0,05) pelos tratamentos. O ganho de peso aumentou e a conversão alimentar reduziu linearmente (P<0,05) com o aumento do tempo de suplementação de ractopamina na dieta. As características quantitativas de carcaça (peso e rendimento de carcaça quente, espessura de toucinho, percentual de carne magra, profundidade de músculo e área de olho-de-lombo) não foram influenciadas (P>0,05) pela duração da suplementação de ractopamina na dieta. O peso dos pulmões, coração, fígado, rins e baço também não foi modificado (P>0,05) pelos tratamentos. Concluiu-se que a inclusão de 20ppm de ractopamina na dieta de leitoas em terminação, mantidas sob alta temperatura ambiente, durante 28 dias, maximiza a resposta de ganho de peso diário e, durante 35 dias, maximiza a resposta para conversão alimentar. Contudo, a inclusão do aditivo não altera as características quantitativas de carcaça e não afeta o desenvolvimento das vísceras.

The study was conducted to evaluate the duration of the supplementation of ractopamine in the diet of finishing gilts maintained under high temperature environment. Forty eight females, with initial weight of 70.4±2.6kg were used. The pigs were distributed in randomized blocks design of six treatments (supplementation of ractopamine for 0, 7, 14, 21, 28 and 35 days pre-slaughter) and four replications, each experimental unit consisted of two animals. The final weight and daily feed intake were not affected (P>0.05) by treatments. The weight gain increased and the feed conversion decreased linearly (P<0.05) according to the increased length of supplementation of ractopamine in the diet. The quantitative characteristics of carcass (weight and hot carcass yield, backfat thickness, percentage of lean meat, depth of muscle and loin eye area) was not influenced (P>0.05) by duration of supplementation of ractopamine in the diet. The weights of the lungs, heart, liver, kidneys and spleen were not modified (P>0.05) by treatments. It was concluded that inclusion of 20ppm of ractopamine in the diet of finishing gilts maintained under high temperature environment during 28 days maximizes the response of daily gain and during 35 days maximizes the response to feed conversion. However, the inclusion of the additive does not alter the quantitative characteristics of carcass and does not affect the development of the viscera.