E-Volve: understanding the impact of mutations in SARS-CoV-2 variants spike protein on antibodies and ACE2 affinity through patterns of chemical interactions at protein interfaces.

Background: The SARS-CoV-2 pandemic reverberated, posing health and social hygiene obstacles throughout the globe. Mutant lineages of the virus have concerned scientists because of convergent amino acid alterations, mainly on the viral spike protein. Studies have shown that mutants have diminished activity of neutralizing antibodies and enhanced affinity with its human cell receptor, the ACE2 protein. Methods: Hence, for real-time measuring of the impacts caused by variant strains in such complexes, we implemented E-Volve, a tool designed to model a structure with a list of mutations requested by users and return analyses of the variant protein. As a proof of concept, we scrutinized the spike-antibody and spike-ACE2 complexes formed in the variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), by using contact maps depicting the interactions made amid them, along with heat maps to quantify these major interactions. Results: The results found in this study depict the highly frequent interface changes made by the entire set of mutations, mainly conducted by N501Y and E484K. In the spike-Antibody complex, we have noticed alterations concerning electrostatic surface complementarity, breaching essential sites in the P17 and BD-368-2 antibodies. Alongside, the spike-ACE2 complex has presented new hydrophobic bonds. Discussion: Molecular dynamics simulations followed by Poisson-Boltzmann calculations corroborate the higher complementarity to the receptor and lower to the antibodies for the K417T/E484K/N501Y (Gamma) mutant compared to the wild-type strain, as pointed by E-Volve, as well as an intensification of this effect by changes at the protein conformational equilibrium in solution. A local disorder of the loop α1'/ß1', as well its possible effects on the affinity to the BD-368-2 antibody were also incorporated to the final conclusions after this analysis. Moreover, E-Volve can depict the main alterations in important biological structures, as shown in the SARS-CoV-2 complexes, marking a major step in the real-time tracking of the virus mutant lineages. E-Volve is available at http://bioinfo.dcc.ufmg.br/evolve.

Well Defined Poly(Methyl Methacrylate)-Fe3O4/Poly(Vinyl Pivalate) Core-Shell Superparamagnetic Nanoparticles: Design and Evaluation of In Vitro Cytotoxicity Activity Against Cancer Cells.

The objective of this work is to develop and characterize polymeric nanoparticles with core-shell morphology through miniemulsion polymerization combined with seeded emulsion polymerization, aiming at the application in the treatment of vascular tumors via intravascular embolization. The synthesis of the core-shell nanocomposites was divided into two main steps: (i) Formation of the core structure, consisting of poly(methyl methacrylate)/magnetic oxide coated with oleic acid (OM-OA) via miniemulsion and (ii) shell structure produced through seeded emulsion polymerization of vinyl pivalate. Nanocomposites containing about 8 wt.% of OM-OA showed high colloidal stability, mean diameter of 216.8 nm, spherical morphology, saturation magnetization (Ms) of 4.65 emu·g-1 (57.41 emu·g-1 of Fe3O4), preserved superparamagnetic behavior and glass transition temperature (Tg) of 111.8 °C. TEM micrographs confirmed the obtaining of uniformly dispersed magnetic nanoparticles in the PMMA and that the core-shell structure was obtained by seeded emulsion with Ms of 1.35 emu·g-1 (56.25 emu·g-1 of Fe3O4) and Tg of 114.7 °C. In vitro cytotoxicity assays against murine tumor of melanoma (B16F10) and human Keratinocytes (HaCaT) cell lines were carried out showing that the core-shell magnetic polymeric materials (a core, consisting of poly(methyl methacrylate)/Fe3O4 and, a shell, formed by poly(vinyl pivalate)) presented high cell viabilities for both murine melanoma tumor cell lines, B16F10, and human keratinocyte cells, HaCaT.

Implantable Medical Devices and Tissue Engineering: An Overview of Manufacturing Processes and the Use of Polymeric Matrices for Manufacturing and Coating their Surfaces.

Medical devices are important diagnosis and therapy tools for several diseases which include a wide range of products. Technological advances in this area have been proposed to reduce adverse complication incidences. New technologies and manufacturing processes, as well as the development of new materials or medical devices with modified surface and the use of biodegradable polymeric devices such as a substrate for cell culture in the field of tissue engineering, have attracted considerable attention in recent years by the scientific community intended to produce medical devices with superior properties and morphology. This review article focused on implantable devices, addresses the major advances in the biomedical field related to the devices manufacture processes such as 3D printing and hot melting extrusion, and the use of polymer matrices composed of copolymers, blends, nanocomposites or grafted with antiproliferative drugs for manufacturing and/or coating the devices surface.

Transition to the ovulatory season in mares: An investigation of antral follicle receptor gene expression in vivo.

The inability to obtain in vivo samples of antral follicle wall layers without removing the ovaries or sacrificing the animals has limited more in-depth studies on folliculogenesis. In this study, a novel ultrasound-guided follicle wall biopsy (FWB) technique was used to obtain in vivo follicle wall layers and follicular fluid samples of growing antral follicles. The expression of proliferative, hormonal, angiogenic, and pro-/antiapoptotic receptors and proteins in the follicular wall among three follicle classes were compared during the spring transitional anovulatory (SAN) and spring ovulatory (SOV) seasons in mares. The main findings observed in the granulosa, theca interna, and/or all follicle layers during the SOV season compared with the SAN season were (a) small-sized follicles (10-14 mm) had greater epidermal growth factor receptor (EGFR) and Bcl-2 expression; (b) medium-sized follicles during the expected deviation/selection diameter (20-24 mm) had greater expression of EGFR, Ki-67, luteinizing hormone receptor (LHR), and Bcl-2; and (c) dominant follicles (30-34 mm) had greater EGFR, Ki-67, vascular endothelial growth factor, LHR, and Bcl-2 expression. Estradiol related receptor alpha expression and intrafollicular estradiol concentration increased, along with an increase in follicle diameter in both seasons. In this study, the application of the FWB technique allowed a direct comparison of different receptors' expression among follicles in different stages of development and between two seasons using the same individuals, without jeopardizing their ovarian function. The successful utilization of the FWB technique and the mare as an experimental animal offer a great combination for future folliculogenesis studies on mechanisms of follicle selection, development, and ovulation in different species, including women.

Taxa de recuperação e características morfológicas de embriões muares (Equus caballus x Equus asinus) / Recovery rate and morphologic features of cross bred embryos (Equus caballus x Equus asinus)

A Transferência de Embrião (TE) contribuiu efetivamente para a produção de equinos e outras espécies. O mercado de muares tem apresentado um contínuo crescimento, entretanto, a aplicação das biotecnologias para a produção desses animais ainda é escassa. O presente estudo avaliou a taxa de recuperação embrionária e as características dos embriões provenientes do cruzamento de éguas com jumentos. Os embriões foram recuperados entre os dias 6 e 9 após a ovulação, dessa forma foi realizada a avaliação da taxa de recuperação embrionária e avaliação das características relacionadas com a idade, morfologia e diâmetro embrionário. A taxa de recuperação embrionária total foi de 55,9% (71/127), e não apresentou diferença para as colheitas realizadas em diferentes dias (D6-D9). Foram recuperados embriões nos estágios de mórula, blastocisto inicial, blastocisto e blastocisto expandido. O tamanho dos embriões variou entre 147-1688μm e a média do diâmetro de todos os embriões recuperados foi de 438,04μm. A recuperação de embriões muares pode ser realizada entre os dias 6 e 9 após a ovulação, e propicia a recuperação de embriões nos primeiros estágios de desenvolvimento.(AU)

Production biotechnologies, particularly embryo transfer (ET) has constantly been contributed to reproduce horses and other species. The mules market has shown continuous growth, however, the biotechnology for mule assisted reproduction is still scarce. The aim of this study was to evaluate the embryo recovery rate and the features of the embryos from mares bred with donkeys. The embryos recovery attempts were performed on days 6 to 9 after ovulation, in order to evaluate the embryo recovery rate and the features related to age, morphology and embryonic diameter in each day. The overall embryo recovery rate was 55,9% (71/127), and there was no significant difference (p>0,05) on different days (D6-D9). Embryos were recovered in stages of mórula, early blastocyst, blastocyst and expanded blastocyst. The diameter of the embryos ranged from 147-1688μm and the mean diameter of all the embryos collected was 438,04μm. The collection of hybrid embryos might be performed between days 6 and 9 after ovulation, and provides recovery of embryos in the early stages of development.(AU)

Educação em saúde: agentes comunitários de saúde e estudantes de medicina no controle da dengue / Health education: community health workers and medical students inthe control of dengue epidemics / Educación en salud: agentes comunitarios de salud y estudiantes de medicina en el control del dengue

A Estratégia Saúde da Família, uma das mais bem sucedidas iniciativas para reorganização da AtençãoBásica no Brasil, traz como diferencial o Agente Comunitário de Saúde (ACS), trabalhador da saúde queatua como interlocutor, facilitando o acesso da comunidade a ações promotoras de saúde. No entanto, épouco conhecido o processo de orientação e formação destes trabalhadores para tratar de epidemias, como adengue. Neste contexto, salienta-se a importância da aproximação entre estudantes de Medicina e ACS paraque haja o fortalecimento não só da educação permanente destes trabalhadores, mas também da formaçãoacadêmica dos futuros médicos. O método adotado foi o grupo focal com seis agentes de uma UnidadeBásica de Saúde (UBS) no município de Jataí, Goiás, Brasil. O grupo focal foi conduzido por estudantes docurso de Medicina da Universidade Federal de Goiás, tendo como instrumento roteiro condutor elaboradopor professores e estudantes. Este roteiro foi construído com enfoque em Educação em Saúde, para garantira possibilidade de elaboração de futuras estratégias de ação pelos estudantes, contribuindo para a formaçãotransdisciplinar dos alunos. Em seguida, foi feita a Análise de Conteúdo para análise e interpretação dosdados. Os estudantes observaram que os agentes acreditam que as estratégias comunicacionais adotadassão efetivas e acessíveis. Entretanto, constataram que há falhas comunicacionais a serem sanadas, pois acomunidade continua relutante em por em prática seus conhecimentos, encontrando assim um desafioa ser trabalhado com os agentes comunitários ao longo de sua formação acadêmica, em busca de novasestratégias de ação para o combate da doença. Os alunos já começaram a elaborar suas estratégias de ação,com base em conhecimentos construídos sobre comunicação e saúde coletiva. Acredita-se que este trabalhoé de grande importância para desenvolver habilidades comunicacionais nos estudantes e para fortalecerseu compromisso com a responsividade social.(AU)

The Family Health Strategy represents one of the most successful initiatives for reorganization of primarycare in Brazil. It brings, as differential, the Community Health Workers (CHW), who acts facilitatingcommunity access to effective professional care in the form of health-promoting actions. However, the wayworkers receive training to manage epidemics, as dengue, is almost unknown. In this context, this projectaddresses the importance of bringing together medical students and CHW in order to strengthening not onlycontinuing education of CHW, but also the experienced learning of future physicians. The method adoptedwas the conduction of a focus group with six workers in a primary health care center in a mid-size town ofBrazilian midwest. The focus group was conducted by the tutor and students previously trained on dengueprevention and management. Students identified communicational gaps based on what was told by CHW ascorrect actions related to dengue control, allowing them to start developing action strategies. This approachnot only contributed for continuing education of workers but also became a effective transdisciplinary andinterprofessional education opportunity for the students involved in the process. CHWs believed theircommunication strategies about dengue are effective and affordable, however the students detected somecommunication failures and created opportunities to address these misconceptions. Students have alreadystarted developing their strategies based on knowledge acquired on public health and experienced practicesin the medical school. We believe that this project also offers a great importance for the development ofstudents'communication skills and increase their commitment and social accountability.

La Estrategia Salud de la Familia, una de las más exitosas iniciativas para la reorganización de la AtenciónBásica en Brasil, trae como diferencial el Agente Comunitario de Salud (ACS), trabajador de la salud queactúa como interlocutor, facilitando el acceso de la comunidad a acciones promotoras de salud. Sin embargo,es poco conocido el proceso de orientación y formación de estos trabajadores para tratar de epidemias,como el dengue. En este contexto, se destaca la importancia del acercamiento entre estudiantes de Medicinay ACS para que haya el fortalecimiento no sólo de la educación permanente de estos trabajadores, sinotambién de la formación académica de los futuros médicos. El método adoptado fue el grupo focal conseis agentes de una Unidad Básica de Salud (UBS) en el municipio de Jataí, Goiás, Brasil. El grupo focalfue conducido por estudiantes del curso de Medicina de la Universidad Federal de Goiás, teniendo comoinstrumento un guión conductor elaborado por profesores y estudiantes. Este itinerario fue construidocon enfoque en Educación en Salud, para garantizar la posibilidad de elaboración de futuras estrategias deacción por los estudiantes, contribuyendo a la formación transdisciplinaria de los alumnos. A continuación,se hizo el Análisis de Contenido para análisis e interpretación de los datos. Los estudiantes observaron quelos agentes creen que las estrategias comunicacionales adoptadas son efectivas y accesibles. Sin embargo,constataron que hay fallas comunicacionales a ser sanadas, pues la comunidad continúa reticente en poneren práctica sus conocimientos, encontrando así un desafío a ser trabajado con los agentes comunitarios a lolargo de su formación académica, en busca de nuevas estrategias de acción para desarrollar el combate dela enfermedad. Los alumnos ya comenzaron a elaborar sus estrategias de acción, con base en conocimientosconstruidos sobre comunicación y salud colectiva. Se cree que este trabajo es de gran importancia paradesarrollar habilidades comunicacionales en los estudiantes y para fortalecer su compromiso con laresponsividad social.

Surtos de dermatite ulcerativa causados por espinhos de Mimosa setosa, M. debilis e M. pudica (Fabaceae) em equinos / Ulcerative dermatitis outbreaks caused by thorns of Mimosa setosa, M. debilis and M. pudica (Fabaceae) in horses

Descrevem-se, na pele de equídeos, lesões de natureza mecânico-traumática causadas por espinhos de Mimosa spp. Dentre as três espécies da planta identificadas como responsáveis pelas lesões, M. setosa estava presente em maior quantidade (80%) e M. debilis e M. pudica encontravam-se em menor proporção na pastagem. Ocorreram três surtos de dermatite ulcerativa em períodos chuvosos de abril a maio de 2013, dezembro de 2013 a fevereiro de 2014 e abril a maio deste mesmo ano. Vinte e cinco equinos do Setor de Reprodução Animal da Universidade Federal Rural do Rio de Janeiro apresentaram, na pele, lesões ulcerativas com contornos irregulares, exsudato hemorrágico, recobertas por crostas. As lesões localizavam-se sobretudo nas regiões de quartela, boleto, articulação escapulo-umeral, lábios superior e inferior, focinho, narinas, bochechas e chanfro. Sete animais foram biopsiados e o exame histopatológico revelou ulceração da epiderme e infiltrado inflamatório constituído por macrófagos e neutrófilos, delimitado por tecido de granulação subjacente. Em alguns casos, foram observados microespículos das referidas plantas (tricomas hirsutos) em meio à reação inflamatória. O diagnóstico de dermatite cutânea causada pela ação traumática da planta baseou-se na presença de Mimosa spp. na pastagem, nas características e localização das lesões na pele dos equinos, nos achados histopatológicos e na recuperação após a retirada dos animais do pasto.(AU)

Mechanic natural skin lesions in horses caused by thorns of Mimosa spp. are described. Between the three plant species identified as responsible for the lesions, Mimosa setosa was present in greater quantity (80%) in the pasture, whilst M. debilis and M. pudica existed in lower proportion. Three ulcerative dermatitis outbreaks were observed during rainy periods of April to May 2013, December 2013 to February 2014 and April to May of the same year. Twenty-five horses from the Sector of Animal Reproduction, Federal Rural University of Rio de Janeiro, showed ulcerative skin lesions with irregular borders, hemorrhagic exudate, sometimes covered with scabs, located mainly in the regions of the pastern, fetlock, scapular-humeral joints, upper and lower lips, nose, nostrils, cheeks and chamfer. Seven horses were biopsied and histopathological examination revealed ulceration of the skin with inflammatory infiltrate by macrophages and neutrophils, delimited by granulation tissue. In some cases, microspicules of these plants (hirsute trichomes) were found throughout the inflammatory reaction. The diagnosis of skin dermatitis, caused by traumatic action of the plants, was based on the presence of Mimosa spp. in the pasture, on the characteristic clinic-pathological features and on recovery of the horses after their removal from the pasture. This appears to be the first report of the occurrence of ulcerative dermatitis caused by Mimosa setosa, as dermatitis caused by the others has been described before.(AU)