A survey on cell nuclei instance segmentation and classification: Leveraging context and attention.

Nuclear-derived morphological features and biomarkers provide relevant insights regarding the tumour microenvironment, while also allowing diagnosis and prognosis in specific cancer types. However, manually annotating nuclei from the gigapixel Haematoxylin and Eosin (H&E)-stained Whole Slide Images (WSIs) is a laborious and costly task, meaning automated algorithms for cell nuclei instance segmentation and classification could alleviate the workload of pathologists and clinical researchers and at the same time facilitate the automatic extraction of clinically interpretable features for artificial intelligence (AI) tools. But due to high intra- and inter-class variability of nuclei morphological and chromatic features, as well as H&E-stains susceptibility to artefacts, state-of-the-art algorithms cannot correctly detect and classify instances with the necessary performance. In this work, we hypothesize context and attention inductive biases in artificial neural networks (ANNs) could increase the performance and generalization of algorithms for cell nuclei instance segmentation and classification. To understand the advantages, use-cases, and limitations of context and attention-based mechanisms in instance segmentation and classification, we start by reviewing works in computer vision and medical imaging. We then conduct a thorough survey on context and attention methods for cell nuclei instance segmentation and classification from H&E-stained microscopy imaging, while providing a comprehensive discussion of the challenges being tackled with context and attention. Besides, we illustrate some limitations of current approaches and present ideas for future research. As a case study, we extend both a general (Mask-RCNN) and a customized (HoVer-Net) instance segmentation and classification methods with context- and attention-based mechanisms and perform a comparative analysis on a multicentre dataset for colon nuclei identification and counting. Although pathologists rely on context at multiple levels while paying attention to specific Regions of Interest (RoIs) when analysing and annotating WSIs, our findings suggest translating that domain knowledge into algorithm design is no trivial task, but to fully exploit these mechanisms in ANNs, the scientific understanding of these methods should first be addressed.

Lavandula pedunculata Polyphenol-Rich Extracts Obtained by Conventional, MAE and UAE Methods: Exploring the Bioactive Potential and Safety for Use a Medicine Plant as Food and Nutraceutical Ingredient.

Nowadays, plant-based bioactive compounds (BCs) are a key focus of research, supporting sustainable food production and favored by consumers for their perceived safety and health advantages over synthetic options. Lavandula pedunculata (LP) is a Portuguese, native species relevant to the bioeconomy that can be useful as a source of natural BCs, mainly phenolic compounds. This study compared LP polyphenol-rich extracts from conventional maceration extraction (CE), microwave and ultrasound-assisted extraction (MAE and UAE). As a result, rosmarinic acid (58.68-48.27 mg/g DE) and salvianolic acid B (43.19-40.09 mg/g DE) were the most representative phenolic compounds in the LP extracts. The three methods exhibited high antioxidant activity, highlighting the ORAC (1306.0 to 1765.5 mg Trolox equivalents (TE)/g DE) results. In addition, the extracts obtained with MAE and CE showed outstanding growth inhibition for B. cereus, S. aureus, E. coli, S. enterica and P. aeruginosa (>50%, at 10 mg/mL). The MAE extract showed the lowest IC50 (0.98 mg DE/mL) for angiotensin-converting enzyme inhibition and the best results for α-glucosidase and tyrosinase inhibition (at 5 mg/mL, the inhibition was 87 and 73%, respectively). The LP polyphenol-rich extracts were also safe on caco-2 intestinal cells, and no mutagenicity was detected. The UAE had lower efficiency in obtaining LP polyphenol-rich extracts. MAE equaled CE's efficiency, saving time and energy. LP shows potential as a sustainable raw material, allowing diverse extraction methods to safely develop health-promoting food and nutraceutical ingredients.

Condições de trabalho na atenção primária à saúde na pandemia de COVID-19: um panorama sobre Brasil e Portugal / Working conditions in primary health care in the COVID-19 pandemic: an overview of Brazil and Portugal

Resumo A pandemia de COVID-19 pressiona os sistemas públicos de saúde no mundo desde 2020. Este artigo pretende discutir as condições de trabalho na atenção primária à saúde (APS) no Brasil, dialogando também com os cuidados de saúde primários (CSP) em Portugal no cenário pandêmico. Para isso, apresentam-se dados da pesquisa "Condições de trabalho dos profissionais de saúde no contexto da COVID-19 no Brasil", para posterior discussão com o relatório das Unidades de Saúde Familiar - Associação Nacional (USF-AN) sobre os CSP em Portugal. No Brasil, no recorte amostral de 3.895 profissionais de saúde da APS, foram percebidos: múltiplos vínculos trabalhistas, falta de apoio institucional e de treinamentos específicos, convívio com fake news e falta de coesão política entre as autoridades sanitárias, com alterações significativas na saúde mental desses trabalhadores. Em Portugal, destacaram-se o aumento da carga horária de trabalho e presença de síndrome de burnout entre os profissionais das USFs. A pandemia impactou de forma significativa a saúde e o cotidiano de trabalho dos profissionais de saúde na APS e nos CSP. Porém, o contexto brasileiro foi mais adverso devido às fake news e às divergências na condução do combate à pandemia, pela atuação e negacionismo do governo federal.

Abstract The COVID-19 pandemic has put pressure on public health systems worldwide since 2020. This article aims to discuss working conditions in Primary Health Care (PHC) in Brazil, while dialoguing with primary health care (CSP, Cuidados de Saúde Primários) in Portugal in the pandemic scenario. For that purpose, data from the study "Working conditions of health professionals in the context of COVID-19 in Brazil" are presented, for further discussion with the report produced by "Family Health Units - National Association (USF-AN, Unidades de Saúde Familiar - Associação Nacional)" on the CSP in Portugal. In Brazil, regarding the sample of 3,895 PHC health professionals, it was observed: multiple employment relationships, lack of institutional support and specific training, living with fake news and the lack of political cohesion between health authorities, with significant changes in these workers' mental health. In Portugal, the increase in the workload and the presence of Burnout Syndrome among FHU professionals was emphasized. The pandemic had a significant impact on the health and daily work of health professionals in PHC and CSP. However, the Brazilian context was more adverse due to fake news and divergences regarding conducts related to the fight against the pandemic, due to the actions and denialism by the federal government.

Emerging Applications of Chlorella sp. and Spirulina (Arthrospira) sp.

Chlorella sp. and Spirulina (Arthrospira) sp. account for over 90% of the global microalgal biomass production and represent one of the most promising aquiculture bioeconomy systems. These microorganisms have been widely recognized for their nutritional and therapeutic properties; therefore, a significant growth of their market is expected, especially in the nutraceutical, food, and beverage segments. However, recent advancements in biotechnology and environmental science have led to the emergence of new applications for these microorganisms. This paper aims to explore these innovative applications, while shedding light on their roles in sustainable development, health, and industry. From this state-of-the art review, it was possible to give an in-depth outlook on the environmental sustainability of Chlorella sp. and Spirulina (Arthrospira) sp. For instance, there have been a variety of studies reported on the use of these two microorganisms for wastewater treatment and biofuel production, contributing to climate change mitigation efforts. Moreover, in the health sector, the richness of these microalgae in photosynthetic pigments and bioactive compounds, along with their oxygen-releasing capacity, are being harnessed in the development of new drugs, wound-healing dressings, photosensitizers for photodynamic therapy, tissue engineering, and anticancer treatments. Furthermore, in the industrial sector, Chlorella sp. and Spirulina (Arthrospira) sp. are being used in the production of biopolymers, fuel cells, and photovoltaic technologies. These innovative applications might bring different outlets for microalgae valorization, enhancing their potential, since the microalgae sector presents issues such as the high production costs. Thus, further research is highly needed to fully explore their benefits and potential applications in various sectors.

Effect from dinoponeratoxin M-PONTXDq3a arginine and lysine substituted analogues against Staphylococcus aureus strains.

The growing incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections is associated with increased mortality rates, which has generated interest in the development of antimicrobial peptides (AMP), such as those found in the giant ant Dinoponera quadríceps. In order to improve the net positive charge and the antibacterial activity of the AMP, amino acids with positive side chain single substituted analogues have been proposed, mainly arginine or lysine. The present work aims to study the antimicrobial activity of the analogues of M-PONTX-Dq3a, a 23 amino acid AMP identified in the D. quadriceps venom. M-PONTX-Dq3a[1-15], a fragment containing the 15 central amino acids, and eight derivatives of single arginine or lysine substituted analogues were proposed. The antimicrobial activity of peptides was evaluated against Staphylococcus aureus ATCC 6538 P (MSSA) and ATCC 33591 (MRSA) strains, followed by minimum inhibitory concentration (MIC), minimum lethal concentration (MLC), and minimum biofilm inhibitory concentration (MBIC) measurement. The membrane permeability was then assessed via crystal violet assay and flow cytometry analysis. The effect of exposure time on microbial viability (Time-Kill) was evaluated. Finally, ultrastructural alterations were evaluated through scanning electron microscopy (SEM). Both arginine-substituted peptides [Arg]3M-PONTX-Dq3a[1-15] and [Arg]4M-PONTX-Dq3a[1-15], showed lowest MIC and MLC values (each 0.78 µM). In the biofilm formation assays, the peptide [Arg]3M-PONTX-Dq3a [1-15] showed MBIC of 3.12 µM against the two tested strains. Both peptides were able to alter the membrane permeability approximately by 80%. The treatment with MIC was able to eliminate bacteria after 2 h of contact on the other hand, treatment with half of the MIC, the population of both bacterial strains remained constant for up to 12 h, indicating a possible bacteriostatic effect. The SEM results showed that the treatment with the lowest concentration (0.78 µM) of both peptides caused disruption of the cell membrane, destabilization of the intercellular interaction and the CLM of [Arg]4M-PONTX-Dq3a [1-15] resulted in the complete eradication of the bacteria. Thus, this study describes two AMPs active against MSSA and MRSA and also inhibits the biofilm formation of these stains. This study finds [Arg]3M-PONTX-Dq3a[1-15] and [Arg]4M-PONTX-Dq3a[1-15] as alternative substances to treat resistant and/or biofilm-forming strains.

Functionalized Cyclopentenones with Low Electrophilic Character as Anticancer Agents.

In this study were synthesized non-Michael acceptor cyclopentenones (CP) from biomass derivative furfural as anticancer agents. Cyclic enones, both from natural sources and synthetic analogues, have been described as cytotoxic agents. Most of these agents were unsuccessful in becoming valuable therapeutic agents due to toxicity problems derived from unselective critical biomacromolecule alkylation. This may be caused by Michael addition to the enone system. Ab initio studies revealed that 2,4-substituted CPs are less prone to Michael additions, and as such were tested three families of those derivatives. We prepare the new CPs from furfural through a tandem furan ring opening/Nazarov electrocyclization and further functionalization. Experimentally the 2,4-substituted CPs exhibited no reactivity towards sulphur nucleophiles, while maintaining cytotoxicity against HT-29, MCF-7, NCI-H460, HCT-116 and MDA-MB 231 cells lines. Moreover, the selected CP are non-toxic against healthy HEK 293T cell lines and present proper calculated drug-like properties.

Food Wastes and Microalgae as Sources of Bioactive Compounds and Pigments in a Modern Biorefinery: A Review.

The United Nations 2030 Agenda for Sustainable Development has created more pressure on countries and society at large for the development of alternative solutions for synthetic and fossil fuel derived products, thus mitigating climate change and environmental hazards. Food wastes and microalgae have been studied for decades as potential sources of several compounds that could be employed in various fields of application from pharmaceutical to textile and packaging. Although multiple research efforts have been put towards extracting rich compounds (i.e., phenolic compounds, tocopherols, and tocotrienols) from these sources, they still remain overlooked as two major sources of bioactive compounds and pigments, mainly due to inefficient extraction processes. Hence, there is a growing need for the development of optimized extraction methods while employing non-organic solvent options following the main principles of green chemistry. This review will focus on delivering a clear and deep analysis on the existing procedures for obtaining bioactive compounds and pigments from food wastes derived from the most consumed and produced fruit crops in the world such as apples, oranges, cherries, almonds, and mangoes, and microalgal biomass, while giving light to the existing drawbacks in need to be solved in order to take full advantage of the rich properties present in these two major biorefinery sources.

Inflammation and mitochondria in the pathogenesis of chronic Chagas disease cardiomyopathy.

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is a neglected disease affecting around 6 million people. About 30% of CD patients develop chronic Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy that occurs decades after the initial infection, while most infected patients (60%) remain asymptomatic in the so-called indeterminate form (IF). Death results from heart failure or arrhythmia in a subset of CCC patients. Myocardial fibrosis, inflammation, and mitochondrial dysfunction are involved in the arrhythmia substrate and triggering events. Survival in CCC is worse than in other cardiomyopathies, which may be linked to a Th1-T cell rich myocarditis with abundant interferon (IFN)-γ and tumor necrosis factor (TNF)-α, selectively lower levels of mitochondrial energy metabolism enzymes in the heart, and reduced levels of high-energy phosphate, indicating poor adenosine triphosphate (ATP) production. IFN-γ and TNF-α signaling, which are constitutively upregulated in CD patients, negatively affect mitochondrial function in cardiomyocytes, recapitulating findings in CCC heart tissue. Genetic studies such as whole-exome sequencing (WES) in nuclear families with multiple CCC/IF cases has disclosed rare heterozygous pathogenic variants in mitochondrial and inflammatory genes segregating in CCC cases. In this minireview, we summarized studies showing how IFN-γ and TNF-α affect cell energy generation, mitochondrial health, and redox homeostasis in cardiomyocytes, in addition to human CD and mitochondria. We hypothesize that cytokine-induced mitochondrial dysfunction in genetically predisposed patients may be the underlying cause of CCC severity and we believe this mechanism may have a bearing on other inflammatory cardiomyopathies.

Ultrasound-assisted extraction of bioactive pigments from Spirulina platensis in natural deep eutectic solvents.

Spirulina platensis biopigments have been documented as a potential source of nutritional, physiological, and pharmacological purposes due to the presence of bioactive pigments, total phenolic content (TPC) and the consequent antioxidant activity that these compounds present. Bioextracts market has increased in the last decades and is a key option for replacing fossil-derived products and promote the transition for a bio-based economy. To take advantage of these compounds more effectively, optimized extraction processes must be researched and used in biomass sources. The present study focused on optimizing the ultrasound-assisted extraction (UAE) using response surface methodology. Three factor and three level Box-Behnken design was used to optimize the extraction of bioactive pigments, and to investigate the effects of three independent variables, x 1: extraction temperature (40-60 °C), x 2: extraction cycle time (20-40 min), and x 3: solvent-to-biomass ratio (50-70 mL/mg) on total pigment yield, antioxidant assay, and TPC (dependent variables). A second-order polynomial model was used for predicting the responses. Statistically, the model was validated using an analysis of variance. Results revealed that ultrasound-assisted temperature, time, and solvent-to-biomass ratio had a significant (p < 0.05) influence on the total pigment yield, while temperature and solvent-to-biomass ratio had a significant influence in the antioxidant activity, and temperature significantly influenced the total pigment yield. For total pigment yield, antioxidant activity, and total phenol content, the R 2 values of the models generated were 0.8627, 0.8460, and 0.9003, respectively, indicating that the models developed based on second-order polynomials were satisfactorily accurate for analyzing interactions between parameters. Desirability functions showed that the optimal extraction parameters were temperature: 60 °C, extraction cycle time: 20 min; and a solvent-to-biomass ratio of 70 mL/mg. Under optimal conditions, experimental values for total pigment yield, total phenol content expressed as gallic acid equivalent (GAE), and antioxidant activity expressed as Trolox equivalent (TRE) were: 165.19 ± 1.01 mg/g Dry Matter (DM), 36.50 ± 0.98 mg GAE/g DM, and 37.98 ± 0.58 mg TRE/g DM, respectively. The experimental values showed a good agreement with the predicted values with residual standard low 1% under optimum conditions. This optimized ultrasound-assisted method in natural eutectic solvents is effective and scalable to a green extraction of the bioactive pigments from Spirulina platensis with potential application to food, pharmaceutical, functional materials, and packaging.

A vida cotidiana do neoliberalismo: os cuidados de saúde à população em situação de rua no Rio de Janeiro / The everyday life of neoliberalism: The provision of health care for unhoused people in Rio de Janeiro

Resumo O crescimento do neoliberalismo nas políticas sociais brasileiras vem resultando em retrocessos nos indicadores sociais, nas condições de trabalho e no desempenho dos serviços de saúde. Não obstante, sabe-se pouco sobre como o neoliberalismo age nas práticas concretas e relações de cuidado. Este artigo visa contribuir para a análise dos impactos da neoliberalização da saúde no Brasil, com foco na capilarização do neoliberalismo no cotidiano do cuidado, bem como pensar formas de resistência ao neoliberalismo na saúde. Partimos da crítica marxista e feminista da vida cotidiana, que considera a interdependência entre o global e o local nas políticas e práticas de saúde. Utilizamos resultados de pesquisa qualitativa sobre o cuidado de saúde à população em situação de rua no Rio de Janeiro, como forma de ilustrar o impacto do neoliberalismo no cotidiano dos serviços de saúde e suas consequências nas percepções de profissionais de saúde e usuários. Observamos que atitudes individuais e coletivas dos profissionais de saúde evidenciam formas de resistência à racionalidade neoliberal hegemônica. A lente da vida cotidiana permite observar tanto a reprodução do global neoliberal, quanto atitudes que potenciam transformações e revelam a persistência de um cuidado empático enquanto um ato de resistência ao neoliberalismo.

Abstract The growth of neoliberalism in Brazilian social policies has resulted in setbacks in social indicators, in working conditions and performance of health services. Nonetheless, little is known about how neoliberalism acts in concrete practices and care relationships. This article aims to contribute to the analysis of the impacts of neoliberalization of health in Brazil, focusing on the capillarization of neoliberalism in daily care., and to reflect about forms of resistance to neoliberalism in health. We draw on the Marxist and feminist critique of everyday life, which considers the interdependence between the global and the local in health policies and practices. We consider results of a qualitative research on health care for the unhoused population in Rio de Janeiro, as a way of illustrating the impact of neoliberalism in the daily life of health services and its consequences on the perceptions of health professionals and users. We observed that individual and collective attitudes of health professionals show forms of resistance to hegemonic neoliberal rationality. The lens of everyday life allows us to observe both the reproduction of neoliberal global dynamics, as well as attitudes that can enable transformations and the persistence of an empathic approach to care as an act of resistance to neoliberalism.

Reescrever saúde global / Rewriting global health

Resumo O conceito de saúde global popularizou-se mesmo com suas origens sendo alvo de um escrutínio crítico: nomeadamente, suas origens na medicina colonial, suas ligações com a proteção do comércio internacional e da exploração capitalista, seus pressupostos orientalistas. Até que ponto o conceito é, ainda, adequado ou proveitoso? Será possível reescrever a saúde global de forma a reconhecer e contrariar as suas múltiplas violências? Reflito sobre a potencialidade do conceito de saúde global a partir de uma ética da escrita que pretende ser analítica (respeitante à sua capacidade para refletir as tensões sociais, a multiplicidade de experiências, as justificações e reivindicações dos atores, a opressão e o potencial não realizado); crítica (respeitante à sua capacidade de identificar a contradição entre aquilo que os arranjos sociais ostensivamente proclamam e o que produzem de facto); e política (respeitante ao seu potencial emancipatório e de reparação das injustiças históricas). Identifico cinco vertentes importantes para um esforço de reescrever o conceito de saúde global: o global como planetário; o global como coletivo; o global como público; o global como periférico; e o global como cotidiano.

Abstract The concept of global health has become popular even though its origins have come under critical scrutiny: namely, its origins in colonial medicine, its links to the protection of international trade and capitalist exploitation and its Orientalist assumptions. To what extent is the concept still adequate or useful? Is it possible to rewrite global health while recognizing and tackling its multiple forms of violence? I reflect on the potentiality of the concept of global health based on an ethics of writing that intends to be analytical (concerning its ability to reflect social tensions, the multiplicity of experiences, the social actors' justifications and claims, the oppression, and the unrealized potential); critical (concerning its ability to identify the contradiction between what social arrangements ostensibly proclaim and what they actually produce); and political (concerning its potential for emancipation and for the reparation of historical injustices). Five important aspects are identified toward rewriting the concept of global health: the global as planetary; the global as collective; the global as public; the global as peripheral; and the global as everyday.

Chitosan microparticles loaded with essential oils inhibit duo-biofilms of Candida albicans and Streptococcus mutans

Abstract Oral candidiasis is a common fungal infection that affects the oral mucosa, and happens when Candida albicans interacts with bacteria in the oral microbiota, such as Streptococcus mutans, causing severe early childhood caries. C. albicans and S. mutans mixed biofilms are challenging to treat with conventional antimicrobial therapies, thus, new anti-infective drugs are required. Objective This study aimed to test a drug delivery system based on chitosan microparticles loaded with geranium and lemongrass essential oils to inhibit C. albicans and S. mutans mixed biofilms. Methodology Chitosan microparticles loaded with essential oils (CM-EOs) were obtained by spray-drying. Susceptibility of planktonic were performed according CLSI at 4 to 2,048 µg/mL. Mixed biofilms were incubated at 37ºC for 48 h and exposed to CM-EOs at 256 to 4,096 µg/mL. The antimicrobial effect was evaluated using the MTT assay, with biofilm architectural changes analyzed by scanning electron microscopy. RAW 264.7 cell was used to evaluate compound cytotoxicity. Results CM-EOs had better planktonic activity against C. albicans than S. mutans. All samples reduced the metabolic activity of mixed C. albicans and S. mutans biofilms, with encapsulated oils showing better activity than raw chitosan or oils. The microparticles reduced the biofilm on the slides. The essential oils showed cytotoxic effects against RAW 264.7 cells, but encapsulation into chitosan microparticles decreased their toxicity. Conclusion This study demonstrates that chitosan loaded with essential oils may provide an alternative method for treating diseases caused by C. albicans and S. mutans mixed biofilm, such as dental caries.

Uma leitura crítica das emergências em saúde global: o caso da epidemia de zika de 2016 / A critical view of the global health emergencies: the 2016 zika epidemic case

Resumo O estudo da definição de agendas e prioridades da saúde global tem sido, nos últimos anos, uma das prioridades de uma literatura crítica que visa identificar as dimensões políticas da governança global em saúde, e que enfatiza os pontos de tensão, exclusão e desigualdade. O presente ensaio se posiciona nesta leitura crítica da saúde global, focando a construção da categoria de emergência de importância internacional. Considerando em específico o caso do surto de zika e de síndromes congênitas no Brasil, em 2016, explora as condições que possibilitam a construção de uma emergência. Questionamos os fatores e condições em torno desse evento de saúde pública que eventualmente foram considerados no processo decisório, e que vão além dos dados materiais mais objetivos relativos à epidemiologia do zika, à sua morbi-mortalidade ou à sua associação com as malformações congênitas. Concluímos que o contexto securitário e a crescente importância do risco na saúde global são condições importantes para entender as declarações de emergência.

Abstract The study of global health agenda-setting and issue-prioritization has been one of the key aspects of a critical literature that, in recent years, has aimed to identify the political dimensions of global health governance and to shed light on points of tension, exclusion, and inequality. This essay speaks to this critical global health literature, focusing on the construction of the category of emergencies of international concern. Considering the case of the outbreak of zika and congenital syndrome in Brazil in 2016, it explores the conditions enabling the construction of an emergency. We question the factors and conditions around this public health event that were considered during the decision-making process and that transcended material, more objective data regarding zika's epidemiology, its morbimortality, or its association with congenital malformations. We conclude that the securitized context and the growing relevance of risk to global health are important conditions for understanding emergency declarations.

Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms.

Chagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) ≥ 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.

Rational design of a trypanocidal peptide derived from Dinoponera quadriceps venom.

Chagas disease is caused by the parasite Trypanosoma cruzi and affects millions of people worldwide, having no effective cure. The main sanitary emergency is related to patients with chronic infection, which accumulate comorbidities causing patient death. However, actual chemotherapeutic treatments do not effectively address the chronic forms of the disease. Invertebrates are a relevant source of antimicrobial peptides (AMPs) as part of the innate immune system for their protection. The AMP M-PONTX-Dq3a, isolated from the Dinoponera quadriceps ant venom, has shown very effective antimicrobial and trypanocidal activities. Although M-PONTX-Dq3a has better activity that the current therapies, the peptide length has limited its possibilities to reach clinical application. In this investigation, we aimed to dissect the trypanocidal effect of M-PONTX-Dq3a fragments and to study the activity of substituted analogs, to improve not only peptide trypanocidal activity and bioavailability, but also production costs. Our studies have led to the identification of two smaller peptides, M-PONTX-Dq3a [1-15] and [Lys]3-M-PONTX-Dq3a [3-153-15 with similar trypanocidal activities that the parent peptide has against the three forms of T. cruzi benznidazole-resistant Y strain. Both peptides represent promising candidates to develop novel and effective trypanocidal bio-therapeutic agents, opening new avenues for the treatment of chronic patients.

Glycidamide and cis-2-butene-1,4-dial (BDA) as potential carcinogens and promoters of liver cancer - An in vitro study.

Acrylamide and furan are environmental and food contaminants that are metabolized by cytochrome P450 2E1 (CYP2E1), giving rise to glycidamide and cis-2-butene-1,4-dial (BDA) metabolites, respectively. Both glycidamide and BDA are electrophilic species that react with nucleophilic groups, being able to introduce mutations in DNA and perform epigenetic remodeling. However, whereas these carcinogens are primarily metabolized in the liver, the carcinogenic potential of acrylamide and furan in this organ is still controversial, based on findings from experimental animal studies. With the ultimate goal of providing further insights into this issue, we explored in vitro, using a hepatocyte cell line and a hepatocellular carcinoma cell line, the putative effect of these metabolites as carcinogens and cancer promoters. Molecular alterations were investigated in cells that survive glycidamide and BDA toxicity. We observed that those cells express CD133 stemness marker, present a high proliferative capacity and display an adjusted expression profile of genes encoding enzymes involved in oxidative stress control, such as GCL-C, GSTP1, GSTA3 and CAT. These molecular changes seem to be underlined, at least in part, by epigenetic remodeling involving histone deacetylases (HDACs). Although more studies are needed, here we present more insights towards the carcinogenic capacity of glycidamide and BDA and also point out their effect in favoring hepatocellular carcinoma progression.

Whey Protein Supplementation Is Superior to Leucine-Matched Collagen Peptides to Increase Muscle Thickness During a 10-Week Resistance Training Program in Untrained Young Adults.

The purpose of this study was to investigate the effects of supplementation of whey protein (WP) versus leucine-matched collagen peptides (CP) on muscle thickness MT and performance after a resistance training (RT) program in young adults. Twenty-two healthy untrained participants were randomly assigned to either a WP (n = 11) or leucine-matched CP (n = 11) group and then submitted to a supervised 10-week RT program (3 days/week). The groups were supplemented with an equivalent amount of WP (35 g, containing 3.0 g of leucine) and CP (35 g, containing 1.0 g of leucine and 2.0 g of free leucine) during the intervention period (after each workout and in the evening on nontraining days). MT of the vastus lateralis and biceps brachii, isokinetic peak torque and mean power output of the elbow flexors, and peak power output of the lower body were assessed before and after the RT program. The WP group experienced a greater (interaction, p < .05) increase in the vastus lateralis (effect size, WP = 0.68 vs. CP = 0.38; % Δ, WP = 8.4 ± 2.5 vs. CP = 5.6 ± 2.6%) and biceps brachii muscle thickness (effect size, WP = 0.61 vs. CP = 0.35; % , WP = 10.1 ± 3.8 vs. CP = 6.0 ± 3.2%), with a similar increase in muscle performance (peak torque, mean power output, and peak power output) between groups (time p < .05). Supplementation with WP was superior to leucine content-matched CP supplementation in increasing muscle size, but not strength and power, after a 10-week RT program in young adults.

Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).

OBJECTIVES: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. METHODS: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. RESULTS: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. CONCLUSIONS: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.

Effects of Photobiomodulation/Laser Therapy Combined With Resistance Training on Quadriceps Hypertrophy and Strength, and Postural Balance in Older Women: A Randomized, Triple-Blinded, Placebo-Controlled Study.

BACKGROUND AND PURPOSE: Physical and therapeutic strategies to maintain and rehabilitate skeletal muscle mass, strength, and postural balance are clinically relevant to improve the health, well-being, and quality of life of older adults. The purpose of this study was to investigate the effects of photobiomodulation (PBM)/laser therapy combined with a resistance training (RT) program on quadriceps hypertrophy and strength, and postural balance in older women. METHODS: In a randomized, triple-blinded, placebo-controlled design, twenty-two older women (age 66.6 ± 5.2 years) were engaged in a supervised 10-wk RT program (2 times per week) involving unilateral leg extension exercise, in which each leg of the same participant was randomly assigned to receive active (λ = 808 nm, optical output = 100 mW, total energy = 42 J) or placebo laser PBM immediately before the RT sessions. Maximal dynamic strength by unilateral knee extension 1-repetition maximum (1RM), muscle hypertrophy by vastus lateralis muscle thickness, and postural balance by one-legged stance test on a force platform were assessed before and after the training program. RESULTS: Significance statistical analysis revealed a similar improvement (time P = .003) from pre- to posttraining for muscle hypertrophy and strength, and postural balance between active and placebo laser conditions. However, clinical interpretation for muscle hypertrophy showed a moderate effect (effect size [ES] = 0.58) for the active laser and a small effect (ES = 0.38) for the placebo laser. Clinical difference was not noticed between conditions for other analyzed variables. CONCLUSIONS: These findings indicate that RT alone can be clinically important for counteracting the deleterious effects of aging on muscle size, strength, and balance, and that applying laser PBM therapy before the RT sessions may further improve gains in muscle hypertrophy.