Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2

The authors also thank Fundação para a Ciência e Tecnologia for the projects Research 4 COVID-19 no. 582, and RECI/BBBBQB/0230/2012. The authors also acknowledge the Solchemar company. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2 ][C1 SO3 ]2 and [HCQH2 ][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2 ][SO4 ]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2 ][GlcCOO]2 . Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra-and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.publishersversionpublishe

EDUCAÇÃO PERMANENTE EM SAÚDE: uma estratégia para a formação dos agentes comunitários de saúde

Este artigo teve por objetivo descrever e analisar o processo de educação dos Agentes Comunitários da Saúde (ACS) utilizado pelos enfermeiros na Estratégia Saúde da Família. Trata-se de uma pesquisa qualitativa, e contou com 17 sujeitos. Para a coleta de dados, utilizou-se entrevista semiestruturada, e a análise dos dados foi realizada por meio da técnica de análise de conteúdo. Identificou-se a categoria: organização do processo de educação nas unidades de saúde da família, cujas temáticas elencadas foram: enfermeiros como líderes da equipe de referência, educação permanente, metodologias tradicionais e educação centrada nas necessidades dos ACS. Através deste estudo, pudemos compreender que os enfermeiros têm pouco contato com a ferramenta da Educação Permanente, realizando as atividades de capacitação fundamentadas na metodologia tradicional de ensino, sendo necessário um investimento dos gestores no sentido de capacitá-los, no que se refere à educação permanente, possibilitando-lhes a atuação com os ACS

How to dissect viral infections and their interplay with the host-proteome by immunoaffinity and mass spectrometry: A tutorial

The capabilities of bioanalytical mass spectrometry to (i) detect and differentiate viruses at the peptide level whilst maintaining high sample throughput and (ii) to provide diagnosis and prognosis for infected patients are presented as a tutorial in this work to aid analytical chemists and physicians to gain insights into the possibilities offered by current high-resolution mass spectrometry technology and bioinformatics. From (i) sampling to sample treatment; (ii) Matrix-Assisted Laser Desorption Ionization- to Electrospray Ionization -based mass spectrometry; and (iii) from clustering to peptide sequencing; a detailed step-by-step guide is provided and exemplified using SARS-CoV-2 Spike Y839 variant and the variant of concern SARS-CoV-2 Alpha (B.1.1.7 lineage), Influenza B, and Influenza A subtypes AH1N1pdm09 and AH3N2.Highlights: - Immunohistochemistry with magnetic core nanoparticles to isolate viruses. - The use of MALDI-MS for rapid virus detection is explained in detail; - The use of ESI-MS/MS to pinpoint host-patient crosstalk is explained in detail. - The absolute quantitative MS is explained for large-scale protein quantitation.This work received financial support from PT national funds (FCT/MCTES) through the projects UIDB/50006/2020 and UIDP/50006/2020 and from PROTEOMASS Scientific Society through the projects #PM001/2019 and #PM003/2016.info:eu-repo/semantics/publishedVersio

Third post-Newtonian dynamics of compact binaries: Noetherian conserved quantities and equivalence between the harmonic-coordinate and ADM-Hamiltonian formalisms

A Lagrangian from which derive the third post-Newtonian (3PN) equations of motion of compact binaries (neglecting the radiation reaction damping) is obtained. The 3PN equations of motion were computed previously by Blanchet and Faye in harmonic coordinates. The Lagrangian depends on the harmonic-coordinate positions, velocities and accelerations of the two bodies. At the 3PN order, the appearance of one undetermined physical parameter \lambda reflects an incompleteness of the point-mass regularization used when deriving the equations of motion. In addition the Lagrangian involves two unphysical (gauge-dependent) constants r'_1 and r'_2 parametrizing some logarithmic terms. The expressions of the ten Noetherian conserved quantities, associated with the invariance of the Lagrangian under the Poincar\'e group, are computed. By performing an infinitesimal ``contact'' transformation of the motion, we prove that the 3PN harmonic-coordinate Lagrangian is physically equivalent to the 3PN Arnowitt-Deser-Misner Hamiltonian obtained recently by Damour, Jaranowski and Sch\"afer.Comment: 30 pages, to appear in Classical and Quantum Gravit

A tutorial

PM003/2016. Publisher Copyright: © 2022 The Author(s)The capabilities of bioanalytical mass spectrometry to (i) detect and differentiate viruses at the peptide level whilst maintaining high sample throughput and (ii) to provide diagnosis and prognosis for infected patients are presented as a tutorial in this work to aid analytical chemists and physicians to gain insights into the possibilities offered by current high-resolution mass spectrometry technology and bioinformatics. From (i) sampling to sample treatment; (ii) Matrix-Assisted Laser Desorption Ionization- to Electrospray Ionization -based mass spectrometry; and (iii) from clustering to peptide sequencing; a detailed step-by-step guide is provided and exemplified using SARS-CoV-2 Spike Y839 variant and the variant of concern SARS-CoV-2 Alpha (B.1.1.7 lineage), Influenza B, and Influenza A subtypes AH1N1pdm09 and AH3N2.publishersversionpublishe

Vitamin D3 as adjuvant in the treatment of type 2 diabetes mellitus: modulation of genomic and biochemical instability

Erratum in - Corrigendum: Vitamin D3 as adjuvant in the treatment of type 2 diabetes mellitus: modulation of genomic and biochemical instability. Fagundes GE, Macan TP, Rohr P, Damiani AP, Da Rocha FR, Pereira M, Longaretti LM, Vilela TC, Ceretta LB, Mendes C, Silveira PCL, Teixeira JPF, de Andrade VM. Mutagenesis. 2019 May 29;34(2):215. doi: 10.1093/mutage/gez006.Type 2 diabetes mellitus has undergone a worldwide growth in incidence in the world and has now acquired epidemic status. There is a strong link between type 2 diabetes and vitamin D deficiency. Because vitamin D has beneficial effects on glucose homeostasis, the aim of this study was to evaluate the influence of vitamin D3 supplementation on the modulation of glycaemic control and other metabolic effects, as well as modulation of genomic instability in patients with type 2 diabetes. We evaluated 75 patients with type 2 diabetes, registered in the Integrated Clinics of the University of Southern Santa Catarina. Participants received 4000 IU of vitamin D3 (25(OH)D) supplementation daily for 8 weeks. Blood samples were collected at the beginning and at the end of the supplementation, and 4 weeks after the end of supplementation. The glycidic and lipid profiles [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein and triglycerides], oxidative stress, DNA damage and 25(OH)D levels were evaluated. Vitamin D3 supplementation for 8 weeks showed enough to significantly increase blood levels of 25(OH)D. A significant difference in lipid profile was observed only in non-HDL cholesterol. Significant changes were observed in glucose homeostasis (fasting glucose and serum insulin) and, in addition, a reduction in the parameters of oxidative stress and DNA damage. There was a significant reduction in the values of 25(OH)D 4 weeks after the end of the supplementation, but levels still remained above baseline. Use of vitamin D supplementation can be an ally in the health modulation of patients with type 2 diabetes mellitusThis work was supported by grants from Conselho Nacional de Pesquisa e Desenvolvimento (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) and Programa de Pós-Graduação em Ciências da Saúde/ Universidade do Extremo Sul Catarinense.info:eu-repo/semantics/publishedVersio

Confirmation of the utility of the International Staging System and identification of a unique pattern of disease in Brazilian patients with multiple myeloma

Santa Casa São Paulo, São Paulo, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniv São Paulo, São Paulo, BrazilHEMOPE, Recife, PE, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniv Fed Bahia, BR-41170290 Salvador, BA, BrazilHosp Brigadeiro São Paulo, São Paulo, BrazilUniv Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, BrazilSch Med, Ribeirao Preto, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniv Estadual Campinas, BR-13081970 Campinas, SP, BrazilInst Nacl Canc Rio Janeiro, Rio de Janeiro, BrazilCanc Res & Biostat, Seattle, WA USACedars Sinai Outpatient Canc Ctr, Aptium Oncol Inc, Los Angeles, CA USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC

Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.Fil: López, M. Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Vinzon, Sabrina Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Nuñez, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Soto, Ariadna Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sanchez Lamas, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Afonso, María Jimena. Fundación Instituto Leloir; ArgentinaFil: Aguilar Cortes, Diana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rios, Gregorio David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Maricato, Juliana T.. Universidade Federal de Sao Paulo; BrasilFil: Torres Braconi, Carla. Universidade Federal de Sao Paulo; BrasilFil: Barbosa da Silveira, Vanessa. Universidade Federal de Sao Paulo; BrasilFil: Montes de Andrade, Tatiane. Universidade Federal de Sao Paulo; BrasilFil: Carvalho de Souza Bonetti, Tatiana. Universidade Federal de Sao Paulo; BrasilFil: Ramos Janini, Luiz M.. Universidade Federal de Sao Paulo; BrasilFil: Castello Girão, Manoel J. B.. Universidade Federal de Sao Paulo; BrasilFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Impact of dose and surface features on plasmatic and liver concentrations of biodegradable polymeric nanocapsules.

The effect of polymeric nanocapsule dose on plasmatic and liver concentrations 20 min after intravenous administration in mice was evaluated. Nanocapsules were prepared with different polymers, namely, poly(D,Llactide) (PLA), polyethylene glycol-block-poly(D,L-lactide) (PLA-PEG), and PLA with chitosan (PLA-Cs) and compared with a nanoemulsion. These formulations were labelled with a phthalocyanine dye for fluorescent detection. The nanostructures had narrow size distributions upon separation by asymmetric flow field flow fractionation with static and dynamic light scattering detection, with average hydrodynamic diameters in the 130?300 nm range, negative zeta potentials, except PLA-Cs nanocapsules, which had a positive zeta potential. Flow cytometry revealed uptake mostly by monocytes and neutrophils in mice and human blood. PLA nanocapsules and the nanoemulsion showed dose-dependent plasma concentrations, where the percentage of plasmatic fluorescence increased with increasing administered dose. In contrast, PLA-PEG nanocapsules led to a dose-independent plasmatic profile. PLA-Cs nanocapsules showed the lowest plasmatic and liver levels of fluorescence at all administered doses and significant intravenous toxicity in mice. This work demonstrates the importance of considering the nanocarrier dose when evaluating pharmacokinetic and biodistribution data and emphasizes the role of surface features in determining the plasmatic and liver concentrations of a poorly soluble lipophilic encapsulated compound