Dibucaine in Ionic-Gradient Liposomes: Biophysical, Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of dibucaine.Fil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Prieto, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Feas, Daniela Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Ribeiro, Lígia N.M.. Universidade Estadual de Campinas; BrasilFil: Silva, Camila M.G.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Guilherme, Viviane A.. Universidade Estadual de Campinas; BrasilFil: Dantzger, Darlene D.. Universidade Estadual de Campinas; BrasilFil: Machado, Daisy. Universidade Estadual de Campinas; BrasilFil: Alonso, Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

Managing Organizational Learning with Focus on The Theory U

The learning of the organization's employees and their perception can instruct the managerial adaptations in search of innovation of the processes. This study focuses on the Theory U, with the objective of studying the perception of stakeholders in the face of learning in the corporation. Its specific objectives are: (1) To raise stakeholders' perceptions regarding the learning tools and practices in the organization; (2) To characterize the possibility of organizational learning in the application of the Theory U; (3) Propose measures to modernize organizational learning tools and practices. The scenario is a military corporation in the Capital of Rondônia, Brazilian Amazon. The study of case method is applied, with procedures in search of qualitative and quantitative results. The collection of the stakeholders' perception was done through ethical protocol; interviews and in loco observation. A report was generated that points out the existence of a confrontation between corporate interests, indicating that managers do not promote the means to bring knowledge to their employees in the institution, while they become sceptical about their reality due to the emergence of a confrontation between theory and practice. The result suggests modernizing the organizational environment to support learning demands. It points that the tools and practices should be reoriented with the purpose of innovating the environment with organizational learning resizing, from now on to be integrative with new technologies, with collaborative focus, through redesigns of processes and procedures following advanced technological standards. This research is a contribution of the academy to managers who potentialize their stakeholders through organizational learning with innovative practices

Banana as adjunct in beer production: applicability and performance of fermentative parameters

Traditionally, the raw materials for beer production are barley, hops, water, and yeast, but most brewers use also different adjuncts. During the alcoholic fermentation, the contribution of aroma compounds from other ingredients to the final beer flavor depends on the wort composition, on the yeast strain, and mainly on the process conditions. In this context, banana can also be a raw material favorable to alcoholic fermentation being rich in carbohydrates and minerals and providing low acidity. In this work, the objective was to evaluate the performance of wort adjusted with banana juice in different concentrations. For this, static fermentations were conducted at 15 °C at pilot scale (140 L of medium). The addition of banana that changed the concentration of all-malt wort from 10 °P to 12 and 15 °P were evaluated (°P is the weight of the extract or the sugar equivalent in 100 g solution, at 20 °C). The results showed an increase in ethanol production, with approximately 0.4 g/g ethanol yield and 0.6 g/L h volumetric productivity after 84 h of processing when concentrated wort was used. Thus, it was concluded that banana can be used as an adjunct in brewing methods, helping in the development of new products as well as in obtaining concentrated worts.Fundação para a Ciência e a Tecnologia (FCT)EMATER-MGJohnson-DiverseyFapesp (Fundação de Amparo à Pesquisa do Estado de São Paulo/Brasil)Wallerstein Industrial & CommercialNovozymesCAPES (Coordenação para Aperfeiçoamento do Ensino Superior/ Brasil)Malteria do ValeGRICES (Gabinete de Relações Internacionais da Ciência e do Ensino Superior/Portugal

Cardiorespiratory andmetabolic responses and reference equation validation to predict peak oxygen uptake for the incremental shuttle waking test in adolescent boys

Background Previous studies speculated that the Incremental Shuttle Walking Test (ISWT) is a maximal test in children and adolescents, however comparison between ISWT with cardiopulmonary exercise test has not yet performed. Furthermore, there is no regression equation available in the current literature to predict oxygen peak consumption (VO2 peak) in this population. This study aimed to assesses and correlate the cardiorespiratory responses of the ISWT with the cardiopulmonary exercise (CEPT) and to develop and validate a regression equation to predict VO2 peak in healthy sedentary adolescent boys. Methods Forty-one participants were included in the study. In the first stage, the VO2 peak, respiratory exchange ratio (R peak), heart rate max (HR max) and percentage of predicted HR max (% predicted HR max) were evaluated in CEPT and ISWT (n = 26). Second, an equation was developed (n = 29) to predict VO2 peak. In both phases, the VO2 peak, respiratory exchange ratio R and hearth rate (HR) were evaluated. In the third stage, the validation equation was performed by another 12 participants. Results Similar results in VO2 peak (P>0.05), R peak (P>0.05) and predicted maximum HR (P>0.05) were obtained between the ISWT and CEPT. Both tests showed moderate significant correlations of VO2 peak (r = 0.44, P = 0.002) e R peak (r = -0.53, P < 0.01), as well as the agreement of these measurements by Bland-Altman analysis (VO2 peak, bias = -0.13; R peak, bias = 0.0). Distance walked was the variable that explained 42.5% (R2 = 0.425, p = 0.0001) of the variance in VO2 peak. The equation was VO2 peak (predicted) = 20.94 + (0.02 x distance walked). The results obtained by the equation were not significantly different compared to the values obtained by the gas analyzer and the Bland-Altman analysis showed agreement (bias = 1.6). Conclusion The ISWT produced maximal cardiorespiratory responses comparable to the CEPT, and the developed equation showed viability for the prediction of VO2 peak in healthy sedentary adolescent boys.Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq)Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)Funda??o de Amparo ? Pesquisa do estado de Minas Gerais (FAPEMIG

Photobiomodulation reduces the cytokine storm syndrome associated with Covid-19 in the zebrafish model

Although the exact mechanism of the pathogenesis of COVID-19 is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red PBM as an attractive therapy to downregulate the cytokine storm caused by COVID-19 from a zebrafish model. RT-PCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that rSpike was responsible for generating systemic inflammatory processes with significantly increased pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a, coa1) mRNA markers, with a pattern like those observed in COVID-19 cases in humans. On the other hand, PBM treatment decreased the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most impacted metabolic pathways between PBM and the rSpike-treated groups were related to steroid metabolism, immune system, and lipids metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19, and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials.publishedVersio

Synthetic Peptides Mimic gp75 from Paracoccidioides brasiliensis in the Diagnosis of Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease, endemic in Latin America, caused by the thermal dimorphic fungus Paracoccidioides brasiliensis. Although some fungal antigens have already been characterized and used for serological diagnosis, cross-reactions have been frequently observed. Thus, the examination of fungal forms in clinical specimens or isolation of P. brasiliensis by culture is still the most frequent method for the diagnosis of this mycosis. In this study, a random peptide phage display library was used to select mimotopes of P. brasiliensis, which were employed as antigens in an indirect enzyme-linked immunosorbent assay. The protective monoclonal antibody against experimental PCM (anti-gp75) was used as molecular target to screen a phage display library. That approach led to a synthetic peptide named P2, which was synthesized and tested against PCM patients’ sera to check whether it was recognized. There was significant recognition of P2 by sera of untreated PCM patients when compared with normal human sera. Sera from treated PCM group, patients with other mycosis or co-infected with HIV had much lower recognition of P2 than untreated patient group. The test showed a sensitivity of 100 and 94.59% of specificity in relation to human sera control. These data indicate a potential use of P2 as diagnostic tool in PCM. Its application for serological diagnosis of PCM may contribute to the development and standardization of simpler, faster and highly reproducible immunodiagnostic tests at low cost

Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function

We designed and synthesized synI, which is ~21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems  </p

β-Cyclodextrins alter the energy metabolism-related enzyme activities in rats

Abstract Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been previously evaluated. In vivo studies evaluated the function of cyclodextrins as active compounds. Despite the use of cyclodextrins as active compounds, the effects of cyclodextrins on hepatic and renal tissues remain to be fully elucidated. The primary objective of this study was to evaluate the effects of β- cyclodextrins, methyl-β-cyclodextrin (M-β- cyclodextrins), and (2-hydroxypropyl)-β-cyclodextrin (HP-β-cyclodextrins) on enzyme activities regulating the maintenance of energy homeostasis in the kidney and liver tissues in relation to toxicity. Serum levels of liver and kidney markers were measured, and oxidative stress parameters were assessed. After 60-day treatments, we observed that the administration of β-cyclodextrins and M-β-cyclodextrins inhibited the hepatic activity of pyruvate kinase, an irreversible enzyme within the glycolytic pathway. Additionally, administration of HP-β-cyclodextrins inhibited creatine kinase activity and increased the total sulfhydryl content in kidneys. Here, we demonstrated for the first time that β-cyclodextrins, M-β-cyclodextrins, and HP-β-cyclodextrins cause bioenergetic dysfunction in renal and hepatic tissues. These findings suggest that understanding the balance between cyclodextrins’ efficacy and adverse effects is essential for better accepting their use in medicine

Global and regional ecological boundaries explain abrupt spatial discontinuities in avian frugivory interactions

Species interactions can propagate disturbances across space via direct and indirect effects, potentially connecting species at a global scale. However, ecological and biogeographic boundaries may mitigate this spread by demarcating the limits of ecological networks. We tested whether large-scale ecological boundaries (ecoregions and biomes) and human disturbance gradients increase dissimilarity among plant-frugivore networks, while accounting for background spatial and elevational gradients and differences in network sampling. We assessed network dissimilarity patterns over a broad spatial scale, using 196 quantitative avian frugivory networks (encompassing 1496 plant and 1004 bird species) distributed across 67 ecoregions, 11 biomes, and 6 continents. We show that dissimilarities in species and interaction composition, but not network structure, are greater across ecoregion and biome boundaries and along different levels of human disturbance. Our findings indicate that biogeographic boundaries delineate the world’s biodiversity of interactions and likely contribute to mitigating the propagation of disturbances at large spatial scales.The authors acknowledge the following funding: University of Canterbury Doctoral Scholarship (L.P.M.); The Marsden Fund grant UOC1705 (J.M.T., L.P.M.); The São Paulo Research Foundation - FAPESP 2014/01986-0 (M.G., C.E.), 2015/15172-7 and 2016/18355-8 (C.E.), 2004/00810-3 and 2008/10154-7 (C.I.D., M.G., M.A.P.); Earthwatch Institute and Conservation International for financial support (C.I.D., M.G., M.A.P.); Carlos Chagas Filho Foundation for Supporting Research in the Rio de Janeiro State – FAPERJ grant E-26/200.610/2022 (C.E.); Brazilian Research Council grants 540481/01-7 and 304742/2019-8 (M.A.P.) and 300970/2015-3 (M.G.); Rufford Small Grants for Nature Conservation No. 22426–1 (J.C.M., I.M.), No. 9163-1 (G.B.J.) and No. 11042-1 (MCM); Universidade Estadual de Santa Cruz (Propp-UESC; No. 00220.1100.1644/10-2018) (J.C.M., I.M.); Fundação de Amparo à Pesquisa do Estado da Bahia - FAPESB (No. 0525/2016) (J.C.M., I.M.); European Research Council under the European Union’s Horizon 2020 research and innovation program (grant 787638) and The Swiss National Science Foundation (grant 173342), both awarded to C. Graham (D.M.D.); ARC SRIEAS grant SR200100005 Securing Antarctica’s Environmental Future (D.M.D.); German Science Foundation—Deutsche Forschungsgemeinschaft PAK 825/1 and FOR 2730 (K.B.G., E.L.N., M.Q., V.S., M.S.), FOR 1246 (K.B.G., M.S., M.G.R.V.) and HE2041/20-1 (F.S., M.S.); Portuguese Foundation for Science and Technology - FCT/MCTES contract CEECIND/00135/2017 and grant UID/BIA/04004/2020 (S.T.) and contract CEECIND/02064/2017 (L.P.S.); National Scientific and Technical Research Council, PIP 592 (P.G.B.); Instituto Venezolano de Investigaciones Científicas - Project 898 (V.S.D.)