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The article by Arlet et al., “Use of hydroxyurea in French-speaking Sub-Saharan Africa”, provides valuable insights into sickle cell disease management in Sub-Saharan Africa (SSA), particularly regarding hydroxyurea (HU) demonstrated efficacy and persistent accessibility challenges in the region. Despite its significant burden, SCD remains insufficiently addressed in many health systems worldwide, reflected in the 515,000 births recorded with the condition in 2021 [2], 75% of which occurred in SSA [2] – a region where limited access, lack of professional training, and poor awareness among patients and healthcare providers create substantial obstacles to the widespread use of HU in clinical practice [1]. [...]between 2000 and 2021, 29,400 deaths were recorded in this age group [2], making the disease the 11th leading cause of death among children under five in SSA, surpassing even measles and malnutrition [3].

Key aspects of 36 mosquito-borne arboviruses indigenous to Africa are summarized, including lesser or poorly-known viruses which, like Zika, may have the potential to escape current sylvatic cycling to achieve greater geographical distribution and medical importance. Major vectors are indicated as well as reservoir hosts, where known. A series of current and future risk factors is addressed. It is apparent that Africa has been the source of most of the major mosquito-borne viruses of medical importance that currently constitute serious global public health threats, but that there are several other viruses with potential for international challenge. The conclusion reached is that increased human population growth in decades ahead coupled with increased international travel and trade is likely to sustain and increase the threat of further geographical spread of current and new arboviral disease.

The mechanism of the antimicrobial peptide daptomycin is reviewed and discussed. Daptomycin is a last-resort antibiotic in current use against drug-resistant bacterial infections. Many models have been proposed for its function, most based on the observation that it increases membrane permeability and causes leakage of contents, such as ions and small molecules from bacterial cells and lipid vesicles. However, daptomycin is actually not efficient at permeabilizing or translocating across membranes, contrary to many well-known antimicrobial peptides. There is strong evidence that daptomycin binds preferentially to membranes in active division regions of bacterial cells and that it causes large membrane reorganization in terms of the distribution of lipids and proteins, both in cells and in model membranes. Those observations support the alternative hypothesis for the mechanism of daptomycin that its primary effect is in inducing membrane reorganization and that other events, such as increased membrane leakage and depolarization, are secondary consequences, not essential to its function.Graphic Abstract

ABSTRACT Objective: to construct and validate the Educational Content Validation Instrument in Health. Method: methodological study that includes the establishment of the conceptual structure; definition of objectives and population; construction of items and response scale; selection and arrangement of items; instrument structuring; opinion of experts; pre-test and content validation. Results: an instrument with 15 items was constructed and, after expert evaluation, eighteen items were obtained, divided into three domains: objectives (four), structure/presentation (nine), and relevance (two). Six items were modified since they presented a percentage of agreement below 0.8. Items of the total instrument presented good internal consistency (0.877) regarding domains. Conclusion: an Educational Content Validation Instrument in Health was elaborated and validated, presenting good reliability, and may contribute to the practice of researchers and health professionals in the development of educational content. RESUMEN Objetivo: construir y validar el Instrumento de Validación de Contenido Educativo en Salud. Método: estudio metodológico contemplando el establecimiento de la estructura conceptual; definición de los objetivos y población; construcción de los ítems y escala de respuesta; selección y organización de los ítems; estructura del instrumento; opinión de expertos; pre-test y validación de contenido. Resultados: se construyó un instrumento con quince ítems y después de la evaluación de expertos, se obtuvieron dieciocho ítems, divididos en tres áreas: objetivos (cuatro), estructura/presentación (nueve) y relevancia (dos). Seis ítems fueron modificados, pues presentaron un porcentaje de concordancia inferior a un 0,8. Los ítems del instrumento total presentaron una buena consistencia interna (0,877) en cuanto a sus dominios. Conclusión: fue elaborado y validado el Instrumento de Validación de Contenido Educativo en Salud, que presentó buena confiabilidad, contribuyendo a la práctica de investigadores y profesionales de las áreas de salud en la elaboración de contenidos educativos. RESUMO Objetivo: construir e validar o Instrumento de Validação de Conteúdo Educativo em Saúde. Método: estudo metodológico contemplando estabelecimento da estrutura conceitual; definição dos objetivos e população; construção dos itens e escala de resposta; seleção e organização dos itens; estruturação do instrumento; opinião de especialistas; pré-teste e validação de conteúdo. Resultados: construiu-se instrumento com quinze itens e após avaliação dos especialistas obtiveram-se dezoito itens, divididos em três domínios: objetivos (quatro), estrutura/apresentação (nove) e relevância (dois). Seis itens foram modificados, pois apresentaram percentual de concordância inferior a 0,8. Itens do instrumento total apresentaram boa consistência interna (0,877) quanto aos seus domínios. Conclusão: foi elaborado e validado Instrumento de Validação de Conteúdo Educativo em Saúde, que apresentou boa confiabilidade, podendo contribuir para a prática de pesquisadores e profissionais das áreas de saúde na elaboração de conteúdos educativos.

A key point of immunity against protozoan Leishmania parasites is the development of an optimal T cell response, which includes a low apoptotic rate, high proliferative activity and polyfunctionality. During acute infection, antigen-specific T cells recognize the pathogen resulting in pathogen control but not elimination, promoting the development and the maintenance of a population of circulating effector cells that mount rapid response quickly after re-exposure to the parasite. However, in the case of visceral disease, the functionality of specific T cells is lost during chronic infection, resulting in inferior effector functions, poor response to specific restimulation, and suboptimal homeostatic proliferation, a term referred to as T cell exhaustion. Multiple factors, including parasite load, infection duration and host immunity, affect T lymphocyte exhaustion. These factors contribute to antigen persistence by promoting inhibitory receptor expression and sustained production of soluble mediators, influencing suppressive cell function and the release of endogenous molecules into chronically inflamed tissue. Together, these signals encourage several changes, reprogramming cells into a quiescent state, which reflects disease progression to more severe forms, and development of acquired resistance to conventional drugs to treat the disease. These points are discussed in this review.

Traffic congestion is a major concern in urban centers, as it can affect society, the environment, and the economy. There are many studies on the use of computational intelligence (CI) to improve mobility in urban centers. Some of these researches focus on developing strategies for traffic light programming, since traffic coordination is complex due to its many parameters, variables, and dynamic behavior, and also an inefficient traffic control plan can lead to increased delays and contribute to traffic congestion. Although there are many works in the literature on strategies for traffic control, there are still some contributions and gaps to be filled, especially because some studies do not consider the automatic optimization of traffic signals in real time, that is, according to the demand of vehicles on the roads, considering multiple objectives and the use of a network of intersections in their experiments. In addition, some of the proposed models are not independent of simulation to evaluate the solutions of CI algorithms, resulting in a more complex deployment in real situations. In this context, this paper presents a new method to optimize traffic light plan in a network of intersections and in real time, called Active Control of Traffic Signals (ACTS) associated with the Non-Dominated Sorting Genetic Algorithm, considering multiple objectives in the optimization process (minimizing the average delay time and the number of vehicles stops per cycle). To test the applicability of the model, a real dataset of vehicle demand collected by the Company of Transport and Traffic of Belo Horizonte (BHTrans) is loaded into the AIMSUN simulator, then the method is applied and compared with the current traffic control plan used by BHTrans. The results show that the ACTS method reduces the average vehicle delay by almost half compared to the results obtained with the current solution used by BHTrans. In real life, this means less time spent in traffic, which promotes faster traffic flow, reducing traffic congestions.

The mechanism of the all-or-none release of the contents of phospholipid vesicles induced by the antimicrobial peptide cecropin A was investigated. A detailed experimental study of the kinetics of dye release showed that the rate of release increases with the ratio of peptide bound per vesicle and, at constant concentration, with the fraction of the anionic lipid phosphatidylglycerol in neutral, phosphatidylcholine membranes. Direct measurement of the kinetics of peptide binding and dissociation from vesicles revealed that the on-rate is almost independent of vesicle composition, whereas the off-rate decreases by orders of magnitude with increasing content of anionic lipid. A simple, exact model fits all experimental kinetic data quantitatively. This is the first time that an exact kinetic model is implemented for a peptide with an all-or-none mechanism. In this model, cecropin A binds reversibly to vesicles, which at a certain point enter an unstable state. In this state, a pore probably opens and all vesicle contents are released, consistent with the all-or-none mechanism. This pore state is a state of the whole vesicle, but does not necessarily involve all peptides on that vesicle. No peptide oligomerization on the vesicle is involved; alternative models that assume oligomerization are inconsistent with the experimental data. Thus, formation of well-defined, peptide-lined pores is unlikely.

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Additionally, steroids have been associated with a relatively low toxicity and high bioavailability. Nowadays, multiple steroidal derivatives are clinically available for the treatment of numerous diseases. Moreover, different structural modifications on their skeleton have been explored, aiming to develop compounds with new and improved pharmacological properties. Thus, steroidal arylidene derivatives emerged as a relevant example of these modifications. This family of compounds has been mainly described as 17β-hydroxysteroid dehydrogenase type 1 and aromatase inhibitors, as well as neuroprotective and anticancer agents. Besides, due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems. In fact, starting from arylidenesteroids, it was possible to develop bioactive steroidal pyrazolines, pyrazoles, pyrimidines, pyridines, spiro-pyrrolidines, amongst others. Most of these products have also been studied as anti-inflammatory and anticancer agents, as well as 5α-reductase and aromatase inhibitors. This work aims to provide a comprehensive overview of steroidal arylidene derivatives described in the literature, highlighting their bioactivities and importance as synthetic intermediates for other pharmacologically active compounds.

The biological maturation (BM) analyzed by peak height velocity (PHV) and bone age (BA), and lean body mass has been associated with the strength and muscle power of young athletes. However, the ability of BM (PHV and BA) and LM markers to predict muscle strength and power in young athletes remains uncertain. The Aim was determine the predicting power of BM markers (PHV and BA) and LM in relation to muscle power of upper and lower limbs and muscle strength of upper limbs in adolescent athletes at puberty. Ninety-two adolescent athletes (both sexes; age 12.4 ± 1.02 years) were assessed for body composition by dual-energy X-ray absorptiometry (DXA). Power of upper limbs (ULP), force handgrip (HG), vertical jump (VJ) and countermovement jump (CMJ) were recorded. BM was predicted by mathematical models to estimate PHV and BA. Multilayer artificial neural network analyses (MLP's) were used to determine the power of prediction of LM, PHV and BA on muscle power and strength of upper- and lower-limbs of the athletes. LM, BA and PHV were associated with HG (r>0.74, p0.60, p0.55, p0.53, p0.60, p<0.05) with BA and with PHV (r<0.83, p 72% of probability to predict the muscle power of upper- and lower-limbs, and the strength of the upper limbs; whereas PHV provides > 43% and bone age >64% in both female and male adolescent athletes. We identified that, like PHV and BA, LM is a strong predictor of low cost of both upper limbs muscle strength and upper and lower limbs power in adolescent athletes.

Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery; however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable self-assembled monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpG-AuNPs were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor growth, and promoted survival in mice when compared to treatments with free CpG.