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Among the three peroxisome proliferator-activated receptor (PPAR) transcription factors, PPARβ/δ is the isotype with the broadest expression pattern. In fact, the expression of PPARβ/δ is ubiquitous, albeit at levels that are tightly regulated. Herein, we reviewed its multiple functions in skin health and disease. PPARβ/δ has pro-differentiating effects in keratinocytes, regulates sebocyte differentiation, and promotes hair follicle growth in healthy skin. Furthermore, we reviewed novel insights into the roles of PPARβ/δ in skin wound healing, especially in inhibiting apoptosis and in modulating keratinocyte proliferation and migration. Therefore, PPARβ/δ represents a research target for the understanding and treatment of inflammatory skin diseases, such as psoriasis and acne vulgaris. In addition, PPARβ/δ is a tumor growth modifier. Epidemiological studies have established that tumor progression may be exacerbated by chronic low-grade inflammation, a condition promoting the production of the lipids that act as modulators of PPARβ/δ activity. The action of PPARβ/δ in skin cancer is ambivalent, which might be explained by this receptor’s putative highly context-specific behavior, which depends on a combination of factors ranging from receptor expression levels to co-regulator distribution, diversity and activity of the ligands produced, and other tissue-specific conditions. Given its diverse and crucial roles in many tissues and organs, PPARβ/δ will remain a major focus of future research.

Many types of cancer are currently treated using a combination of chemotherapeutics, but unfortunately, this strategy is considerably limited by severe side effects. The current development of nanocarriers enables the use of multiple drugs anchored on one unique platform thus enhancing the initiated therapeutic effect and minimizing the possibility of drug resistance. In this context, a graphene‐oxide‐based 2D nanoplatform is developed, which is functionalized using highly branched polyethylene‐glycol and a multimodal set of two drugs with various mechanisms of action, namely Pt‐based complex (a Pt(IV) prodrugs based on cisplatin) and doxorubicin (DOX). We performed in vitro 2D screening on two cancer cell lines, namely glioblastoma and osteosarcoma, that were selected as models of two aggressive tumors that remain a massive challenge in oncology. The therapeutic effect of the developed nano‐platform is higher at lower concentrations (15 μm of Pt‐drug, 0.6 μm DOX) compared to the impact of the free drugs. This indicates a possible positive effect of the accumulation and transport of the drugs using this nanoplatform. Results obtained on 3D cell models using MG63 osteosarcoma cells uncovered an understandable lowered diffusion profile of the developed nanoplatforms, compared to the application of free drugs.

A hanseníase é uma das enfermidades mais antigas que se tem notícia, com registros que remontam a antiguidade. Ao longo dos tempos, as pessoas com a doença foram despojadas de seus direitos humanos por meio de políticas de isolamento, exclusão e até de cunho eugênico, apartando seus filhos do convívio com pais e mães portadores. O desafio, na atualidade, é a promoção, pelas Nações que viveram a moléstia em sua história, de políticas voltadas a prevenir abusos e afronta aos direitos humanos e reparar, inclusive com indenizações, os males sofridos no apartheid histórico. Submissão: 12/09/24| Revisão: 12/09/24| Aprovação: 12/09/24

Whether the two large low-shear velocity provinces (LLSVPs) at the base of Earth's mantle are wide compact structures extending thousands of kilometers upward or bundles of distinct mantle plumes is the subject of debate. Full waveform shear wave tomography of the deep mantle beneath the Indian Ocean highlights the presence of several separate broad low-velocity conduits anchored at the core-mantle boundary in the eastern part of the African LLSVP, most clearly beneath La Réunion and Comores hot spots. The deep plumbing system beneath these hot spots may also include alternating vertical conduits and horizontal ponding zones, from 1000-km depth to the top of the asthenosphere, reminiscent of dyke and sills in crustal volcanic systems, albeit at a whole-mantle scale.

The cellar environment harbours a consortium of microorganisms on the material surfaces and in the air. Among these microorganisms, the spoilage yeast Brettanomyces bruxellensis can colonise surfaces due to its specific bioadhesive properties. In this study, air and surface samples were collected in several wineries during the winter period. B. bruxellensis was detected in the cellar environment either in the air or on the surfaces of various materials, including in tartaric acid precipitates. Difficult-to-clean tank equipment (taps, wall angles, valves) were identified as critical areas where B. bruxellensis was frequently detected. To confirm that surfaces contaminated by B. bruxellensis could be involved in wine contamination, yeast growth and volatile phenol production were monitored in wine in contact with stainless steel harbouring biofilms. The presence of bioadherent cells and biofilms in contact with the wine resulted in significant cell release into the wine, leading to population growth and the production of volatile phenols at concentrations above the olfactory detection threshold. This study demonstrates the possibility of wine spoilage by resident and adherent populations of B. bruxellensis and confirms the need to pay special attention to the hygiene of hard-to-reach areas such as valves.

Summary: Growth and differentiation factor 15 (GDF15) has recently emerged as a weight loss and insulin-sensitizing factor. Growing evidence also supports a role for GDF15 as a physiological, exercise-induced stress signal. Here, we tested whether GDF15 is required for the insulin-sensitizing effects of exercise in mice and humans. At baseline, both under a standard nutritional state and high-fat feeding, GDF15 knockout (KO) mice display normal glucose tolerance, systemic insulin sensitivity, maximal speed, and endurance running capacity when compared to wild-type littermates independent of sex. When submitted to a 4-week exercise training program, both lean and obese wild-type and GDF15 KO mice similarly improve their endurance running capacity, glucose tolerance, systemic insulin sensitivity, and peripheral glucose uptake. Insulin-sensitizing effects of exercise training were also unrelated to changes in plasma GDF15 in humans. In summary, we here show that GDF15 is dispensable for the insulin-sensitizing effects of chronic exercise.

A partir de sua crítica ao formalismo presente na filosofia de Kant, Hegel promove uma reflexão filosófica e política mediante o seu conceito de “eticidade” (Sittlichkeit). Visando compreender o referido conceito, o presente artigo terá dois objetivos fundamentais: primeiro, analisar a “vida ética”, ou seja, compreender os domínios que a marcam: o direito abstrato, a moralidade e a eticidade, e, segundo, examinar sucintamente os períodos ou etapas nas quais a eticidade se manifesta, isto é, na família, na sociedade civil e no Estado.

Objetivo: compreender as vulnerabilidades a que as mulheres com hanseníase estão expostas e quais as implicações tanto para sua saúde como para sua vida social, religiosa, política e familiar. Metodologia: Trata-se de uma revisão integrativa da literatura. A coleta de dados foi realizada no mês de abril de 2024, na base de dados do Scientific Electronic Library Online (SciELO). O descritor utilizado foi: mulheres and hanseníase. Resultados: Ao todo, 19 artigos foram selecionados. A partir da análise realizada, optou-se por produzir três categorias temáticas (vulnerabilidade, corpo e estigma) para classificar o ponto central dos artigos escolhidos. Conclusão: Necessita-se de pesquisas que possam cada vez mais elucidar quais são as necessidades de mulheres com o diagnóstico ou em tratamento da hanseníase e pensar em políticas públicas, no gerenciamento e administração da enfermidade a partir da atenção primária. Submissão: 20/05/24| Revisão: 27/05/24| Aprovação: 28/05/24

Apresentar, por meio de resenha analítica, a obra 'Consolidação, Simplificação e Revisão do Arco Normativo Infralegal da Saúde: um projeto, muitas vozes', publicado pelo CONASS e que narra a história biográfica de um projeto pioneiro e inovador da consolidação do arco normativo infralegal do Sistema Único de Saúde. Submissão: 09/05/24| Revisão: 13/05/24| Aprovação: 13/05/24

Although significant improvements have been made in the treatment of pancreatic cancer, its prognosis remains poor with an overall 5-year survival rate of less than 10%. New experimental approaches are necessary to develop novel therapeutics. In this study, the investigation of pancreatic cancer tissue growth in the chorioallantoic membrane (CAM) model and the subsequent use of indocyanine green (ICG) injections for the verification of intratumoral perfusion was conducted. ICG was injected into the CAM vasculature to visualize the perfusion of the tumor tissue. The presence of metastasis was investigated through PCR for the human-specific ALU element in the liver of the chicken embryo. Additionally, the usage of cryopreserved pancreatic tumors was established. Intratumoral perfusion of tumor tissue on the CAM was observed in recently obtained and cryopreserved tumors. ALU-PCR detected metastasis in the chick embryos’ livers. After cryopreservation, the tissue was still vital, and the xenografts generated from these tumors resembled the histological features of the primary tumor. This methodology represents the proof of principle for intravenous drug testing of pancreatic cancer in the CAM model. The cryopreserved tumors can be used for testing novel therapeutics and can be integrated into the molecular tumor board, facilitating personalized tumor treatment.

Objectives: This study aimed to analyze the knowledge of dental surgeons concerning the pharmacological effects of bisphosphonates (BP) and their impact on the health of patients undergoing oral surgery treatment. Materials and methods: A quantitative study was conducted with professionals in the Cariri region of Ceará, Brazil. The data were collected using a semi-structured questionnaire to interview the dental surgeons who met the inclusion criteria. The data were analyzed by Chi-square and Fischer's Exact tests using the SPSS program version 22.0. Results: The results indicated that most interviewed subjects have no experience with the dental treatment of individuals under treatment with bisphosphonates. When a sample of the medication was presented, a significant number of the participants (65.3%) did not recognize the drug. Among those who recognized it, 66.5% did not know how to treat bisphosphonate-using patients in the clinical routine. However, 95.1% of the professionals who recognized the need to discontinue these drugs admitted contacting the prescriber to establish the best dental conduct. Our results also showed that recently graduated professionals better understood the need to stop BP use before invasive treatment, although they did not know the protocol. Conclusion: In conclusion, a better knowledge of the pharmacological effects of BP is crucial for conducting adequate anamnesis, requesting additional tests, and performing medical monitoring, which has a significant impact on the clinical practice of dental surgeons.

A series of C2-functionalied Pt (IV) glycoconjugates based on glucosamine have been synthesised, characterised and tested as anticancer agents on a series of different 2D and 3D cancer cell lines. The carbohydrate will act as a targeted delivery system to improve the selectivity, exploiting the Warburg Effect and the GLUTs receptors that are overexpressed in most of the cancer cells. The hydroxyl at C2 of the carbohydrates does not participate in hydrogen bonding with the GLUTs receptors, making C2 an attractive position for drug conjugation as seen in literature. In this study, we use the amino functionality at the C2 position in glucosamine and Copper-catalysed Azide-Alkyne Cycloaddition “click” (CuAAC) reaction to connect the prodrug Pt (IV) scaffold to the carbohydrate. We have investigated complexes with different linker lengths, as well as acetyl protected and free derivatives. To the best of our knowledge, this study represents the first series of Pt (IV) glucosamine-conjugates functionalised at C2.

A principal motivação para este trabalho é a possibilidade de melhorar o projeto de controladores proporcionais-integrais-derivativos aplicado ao conversor boost, com incertezas paramétricas na carga, por meio de meta-heurísticas. Neste sentido, propõe-se aqui um novo procedimento para sintonia automática off-line destes controladores aplicados à regulação de tensão de conversores CC-CC do tipo boost com carga pertencente a um intervalo de incertezas. Um algoritmo de otimização por enxame de partículas é utilizado para evoluir os ganhos do controlador de forma a minimizar um erro médio quadrático da tensão de saída, respeitando limites pré-estabelecidos para margens de fase e de ganho, de frequência de cruzamento, e também para sobressinal e tempo de acomodação das respostas transitórias para variações de carga. O controlador otimizado pelo procedimento proposto fornece respostas superiores quando comparado a controladores largamente utilizados, projetados apenas para uma carga nominal. Resultados experimentais em um protótipo de 50 W, com o controle implementado em um processador digital de sinais de baixo custo, confirmam a viabilidade prática.

Uma dificuldade no projeto de controladores para conversores de potência é otimizar múltiplos objetivos de desempenho respeitando múltiplas restrições de operação, dispondo de um conjunto de poucos ganhos de controle. Este trabalho propõe um procedimento off-line de sintonia automática otimizada de controladores proporcional-integral-derivativos aplicados a conversores CC-CC. A proposta é baseada na otimização de uma função custo que visa atingir margem de fase e frequência de cruzamento desejadas, respeitando restrições de desigualdade no máximo sobressinal e no tempo de acomodação das respostas transitórias. Um algoritmo de otimização por enxame de partículas evolui os ganhos de controle até obter um mínimo da função custo, garantindo a estabilidade frente a incertezas na carga e na tensão de entrada sem violar as restrições de projeto. Os resultados para a regulação da tensão de saída de um conversor buck, descrito por um modelo de fase não mínima quando incluído o atraso na implementação do controle, mostram a superioridade do controlador proposto em comparação a um controlador obtido utilizando uma função especializada do MATLAB. Avaliações experimentais em Hardware-in-the-loop confirmam a viabilidade prática da abordagem para o controle implementado em tempo real em um processador digital de baixo custo e amplo uso.

Abstract Oestrus ovis larvae are obligate parasites of vertebrates and cause cavitary myiasis (oestrosis) in sheep and goats. It is also reported as a zoonosis causing ophthalmomyiasis and nasopharyngeal myiasis. Despite being relatively common in Brazil, epidemiological studies on O. ovis are scarce. Considering that the infestation is influenced by the climate and biomes of the studied region, we aimed to investigate the seasonal prevalence of O. ovis among slaughtered sheep in the northern region of the state of Mato Grosso, Brazil. The heads of sheep (n=697) slaughtered at a slaughterhouse in the municipality of Terra Nova do Norte (November 2011 to November 2013) were collected to count, catalog, and identify the larvae found in the upper respiratory tract. Overall, 45.77% (319/697) of the animals were infested with 2,412 recovered larvae, 96.89% (2,337/2,412) of which were identified at the species level as O. ovis. Seasonal variations in prevalence ranged from 41% (spring) to 56% (summer); however, no correlation was observed between prevalence and season, mean humidity, or temperature. In conclusion, parasitism by O. ovis in sheep in the studied area, occurs year-round, considering the occurrence of larvae (L1, L2, and L3) throughout the year, probably because of the area's environmental conditions.

Seismic anisotropy is now commonly studied on Earth and has been detected at various depths, from the crust to the top of the lower mantle, in the lowermost mantle, and in the inner core. In the mantle, observations of seismic anisotropy are often taken as an indication of past or present deformation resulting in the preferential orientation of anisotropic minerals. In the crust, it can come from stress-induced oriented cracks, compositional layering, or crystallographic preferred orientation of minerals. While many questions remain regarding the presence and interpretation of seismic anisotropy on Earth, scientists are now faced with new, exciting challenges in trying to constrain the structure of other planetary bodies. One of the goals of NASA’s InSight mission, which landed on Mars in November 2018 and includes a very broadband seismometer, is to constrain Mars interior structure. Compared to seismic studies of Earth, which benefit from the availability of a wealth of high quality data recorded on many seismic stations, difficulties with InSight stem from having only one seismic instrument and only a few high quality events. In this study, we analyzed the horizontally polarized (SH)-wave reflections generated from the shallowest crustal layer (layer 1) detected at 8 ± 2 km beneath the InSight lander site by a previous receiver function (RF) study. From Sol 105, when the first low-frequency marsquake was recorded, to Sol 1094, a total of 83 broadband and low-frequency events were detected, but only nine are rated as quality-A with constraints on both their epicentral distance and back azimuth. Of those nine events, we selected four that did not show any interference with mantle triplications generated by the olivine to the wadsleyite phase transition and that had a clear signal after the direct SH phase. A model space search approach enabled us to obtain a range of acceptable SH-wave velocities and layer thicknesses, which we then compared with the RF models of Knapmeyer-Endrun et al. (2021). We found that the acceptable SH-wave speeds are systematically lower than those from the RF study. Since this RF analysis is sensitive to vertically polarized (SV)-waves, we interpret this difference as the signature of radial anisotropy with an anisotropy coefficient ?=(???/???)2 between 0.7 and 0.9. Modeling of preferred alignment of inclusions shows that dry or fluid-filled cracks/fractures, and igneous inclusions can reproduce the observed radial anisotropy amplitude with VSV>VSH.

Abstract Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis.