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Abstract Background Advanced chronic kidney disease (ACKD) is associated with a high risk of adverse cardiovascular and renal events and has a significant impact on quality of life and life expectancy. Several studies have identified areas for improvement in their management in primary care. Some professional and environmental factors can act as key barriers to appropriate care. Objective To analyse attitudes, subjective norms, and perceived behavioural control among primary care professionals related to the implementation of an evidence-based approach for individuals with ACKD in primary care. Methodology This was a qualitative study using an interpretative phenomenological approach based on the theory of planned behaviour. Two aspects of the evidence-based approach were explored: the implementation of clinical practice guidelines and the utilisation of electronic kidney disease records within the scope of this study. Primary care nurses and physicians participated in a previous pilot interview and five focus groups. Subsequently, a thematic analysis of the gathered data was conducted. Findings Thirty-three primary care professionals participated. The emerging themes included: experiences in the management of ACKD (highlighting a distinct profile of older, frail patients with comorbidities masking CKD and a CKD follow-up primarily focused on analytical monitoring and drug adjustment); factors in the professional environment influencing the use of scientific evidence (such as time constraints, excessive electronic health records, and unfamiliar reference guidelines); attitudes towards the application of recommendations on ACKD (recognising limitations of computer systems despite considering them as guidance); and capacities to implement evidence-based recommendations (acknowledging formative needs and challenges in coordinating care with nephrology services). Conclusions Several psychological elements identified through the TBP hinder the adequate implementation of an evidence-based approach for individuals with CKD. Attitudes have been identified as factors modulating the use of standardised electronic records. Instead, subjective norms (influences from the professional environment) and perceived behavioral control (perception of capabilities) acted as barriers to the proper application of clinical practice guidelines and standardised records. Implications for practice Strategies aimed at optimising the management of people with ACKD should focus not only on training but also on improving attitudes, organisational structures, IT systems and coordination between primary care and nephrology.

Abstract Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes’ high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using the Escherichia coli expression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is an important public health problem, occurring mainly in Latin America. The disease has a major social and economical effect, negatively impacting the life of the infected individuals, and bringing great costs to public health. An early and accurate diagnosis is essential for administration of early treatment. In addition, prognostic tests may aid disease management, decreasing hospitalization costs. However, the serological diagnostic scenario for CD still faces several challenges, making the development of new diagnostic kits a pressing matter. Facing this scenario, several researchers have expanded efforts in developing and testing new antigens, such as recombinant proteins and recombinant multiepitope proteins, with promising results. These recombinant antigens offer several advantages, such as improved sensitivity and specificity, in addition to facilitated scaling. Also, it has been possible to observe a rising number of studies using ELISA and point-of-care platforms, employing these antigens in the past few years. Among them, recombinant proteins were the most applied antigens, demonstrating great capacity to discriminate between positive and negative samples. Although fewer in number, recombinant multiepitope proteins also demonstrated an improved diagnostic performance. Indeed, a great number of studies employing these antigens showed sensitivity and specificity values above 90%, greatly impacting diagnostic accuracy. Nevertheless, despite the good results found, it is still possible to observe some bottlenecks in the development of new antigens, such as the scarcity of tests with sera from the acute phase and the variability of results in different geographic areas. In this sense, aiming to contribute to control and health programs, the continuous search for a more accurate serological diagnosis is essential, both for the acute and chronic phases of the disease.

Abstract Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors of survival in melanoma. The MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant treatment with autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 patients collected serum and stool samples before and after 2 bimonthly injections to perform metabolomics (MB) and metagenomics (MG) as prespecified exploratory analysis. Clinical outcomes are reported separately. Here we show that different microbes were associated with prognosis, with the health-related Faecalibacterium prausnitzii standing out as the main beneficial taxon for no recurrence at 2 years (p = 0.008 at baseline, nDC arm). Therapy coincided with major MB perturbations (acylcarnitines, carboxylic and fatty acids). Despite randomization, nDC arm exhibited MG and MB bias at baseline: relative under-representation of F. prausnitzii, and perturbations of primary biliary acids (BA). F. prausnitzii anticorrelated with BA, medium- and long-chain acylcarnitines. Combined, these MG and MB biomarkers markedly determined prognosis. Altogether, the host-microbial interaction may play a role in localized melanoma. We value systematic MG and MB profiling in randomized trials to avoid baseline differences attributed to host-microbe interactions.

Summary: Centriolar satellites are high-order assemblies, scaffolded by the protein PCM1, that gravitate as particles around the centrosome and play pivotal roles in fundamental cellular processes notably ciliogenesis and autophagy. Despite stringent control mechanisms involving phosphorylation and ubiquitination, the landscape of post-translational modifications shaping these structures remains elusive. Here, we report that necrosulfonamide (NSA), a small molecule known for binding and inactivating the pivotal effector of cell death by necroptosis MLKL, intersects with centriolar satellites, ciliogenesis, and autophagy independently of MLKL. NSA functions as a potent redox cycler and triggers the oxidation and aggregation of PCM1 alongside select partners, while minimally impacting the overall distribution of centriolar satellites. Additionally, NSA-mediated ROS production disrupts ciliogenesis and leads to the accumulation of autophagy markers, partially alleviated by PCM1 deletion. Together, these results identify PCM1 as a redox sensor protein and provide new insights into the interplay between centriolar satellites and autophagy.

Gender dysphoria is defined as a condition characterized by mental suffering associated with the incongruence between one’s experienced gender and their birth-assigned sex. Gender as a construct and gender dysphoria as a condition in need of multidisciplinary intervention have developed as swiftly as their visibility in society, making it mandatory to promote the literacy and education of all healthcare professionals in this area. This article aims to review information based on scientific evidence on people with gender dysphoria and its clinical approach, while contributing to a safe, inclusive, and non-discriminatory practice of healthcare.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is an important public health problem, occurring mainly in Latin America. The disease has a major social and economical effect, negatively impacting the life of the infected individuals, and bringing great costs to public health. An early and accurate diagnosis is essential for administration of early treatment. In addition, prognostic tests may aid disease management, decreasing hospitalization costs. However, the serological diagnostic scenario for CD still faces several challenges, making the development of new diagnostic kits a pressing matter. Facing this scenario, several researchers have expanded efforts in developing and testing new antigens, such as recombinant proteins and recombinant multiepitope proteins, with promising results. These recombinant antigens offer several advantages, such as improved sensitivity and specificity, in addition to facilitated scaling. Also, it has been possible to observe a rising number of studies using ELISA and point-of-care platforms, employing these antigens in the past few years. Among them, recombinant proteins were the most applied antigens, demonstrating great capacity to discriminate between positive and negative samples. Although fewer in number, recombinant multiepitope proteins also demonstrated an improved diagnostic performance. Indeed, a great number of studies employing these antigens showed sensitivity and specificity values above 90%, greatly impacting diagnostic accuracy. Nevertheless, despite the good results found, it is still possible to observe some bottlenecks in the development of new antigens, such as the scarcity of tests with sera from the acute phase and the variability of results in different geographic areas. In this sense, aiming to contribute to control and health programs, the continuous search for a more accurate serological diagnosis is essential, both for the acute and chronic phases of the disease. [ABSTRACT FROM AUTHOR]

Lipid dysregulation is associated with various disorders, including cardiovascular disease (CVD). Measuring lipid levels in cardiovascular and adipose tissues is essential for understanding the mechanisms of their regulation, defining therapeutic targets, monitoring disease severity, treatment response, and/or prognosis. This review critically examines the current status and advances in untargeted liquid chromatography-mass spectrometry workflows for tissue lipidomics, including lipid extraction, separation modes and mass spectrometric workflows, as well as their recent clinical applications to obtain novel insights into CVD and/or obesity. It also highlights current best quality control practices in the field of plasma lipidomics, including a selection of internal standards and reference materials. Key findings from recent inter-laboratory comparisons for human plasma are also summarized. Stringent quality control practices are crucial to ensure high quality, wide applicability and harmonization of lipidomics data. Their fundamentals are established in plasma lipidomics and require further development for cardiovascular and adipose tissue lipidomics. • Tissue lipidomics can provide novel insights into cardiovascular disease and obesity. • Tissue-relevant protocols include monophasic and biphasic extractions. • Solid-phase microextraction integrates sampling and extraction and reduces sampling invasiveness. • Separation and MS acquisition workflows affect lipid coverage and data quality. • Best practices in quality control procedures for tissue lipidomics are emphasized. [ABSTRACT FROM AUTHOR]

Predation pressure influences animal behaviour in relation to feeding, exposure to predators and habitat use. In the presence of a predator, prey usually decreases feeding and activity, avoiding predation-risk areas. This study evaluated the visual effects of a predator fish (red-bellied piranha Pygocentrus nattereri) on the behaviour and habitat use of Macrobrachium jelskii prawn. It was hypothesized that prawns would modify their behaviour in the presence of a predator, decreasing their general activity (foraging and locomotion) and seeking shelter more frequently. Twenty behavioural tests were carried out without and with the presence of a predator using five different M. jelskii individuals per trial. Behavioural data were collected using scan sampling with instantaneous recording of behaviours every 15 s during 5 min in each trial. The presence of the predator caused prawns to decrease their locomotion and feeding and increase environment exploration and predator inspection. Prawns used the shelter more frequently when the predator was present. Red-bellied piranha elicited anti-predator behaviour in M. jelskii. The patterns observed suggested that the most common anti-predatory behaviours exhibited by M. jelskii are beneficial as they reduce vigilance and active anti-predation strategies, such as escape. • The presence of the predator caused the prawns to decrease their locomotion and feeding. • The presence of the predator caused the prawns to increase the exploration of the environment and inspection of the predator. • Prawns using the shelter area more frequently when compared to the exposed areas of the arena when the predator was present. • Results showed that an established non-native predator elicited anti-predator behaviour in M. jelskii. [ABSTRACT FROM AUTHOR]

Este artigo analisa, qualitativamente, o emprego de um aplicativo de leitura e escrita em dispositivo móvel, especialmente em smartphones, no contexto da sala de aula. Utilizando o aplicativo Wattpad para a elaboração de uma fanfiction baseada na obra As Crônicas de Nárnia, de C. S. Lewis, nossa análise privilegiou a tecnologia em suas interações pedagógicas, especialmente no que se refere às contribuições para a formação do leitor literário, bem como outros aspectos importantes desse recurso na educação. Notamos que essa estratégia de leitura e escrita criativa oferece alternativas para que os envolvidos ampliem suas capacidades imaginativas, propiciando-lhes maior contato com o universo literário e, mais intensamente, com o mundo da criatividade - a exemplo da própria produção de fanfic -, além de ampliar as chances de formar leitores literários, posto que aproxima os participantes do hábito da leitura e da escrita. Esse debate, portanto, é resultado de diversos fatores e tendências sociais, educacionais e tecnológicas, que vão desde a necessidade do engajamento e da motivação até a aprendizagem, com ênfase para as mudanças de comportamentos em face da necessidade de atuação em um mundo cada vez mais tecnológico e digital.

It is known that conventional antigen presentation involves phagocytosis of antigens followed by its internalization in endocytic compartments and presentation of epitopes through MHC class II molecules for CD4 T cells. However, since 1976 a cross-presentation pathway has been studied, in which CD8 T cells are activated via MHC class I with antigens acquired through phagocytosis or endocytosis by dendritic cells (DCs). Among some important molecules involved in the cross-presentation, the C‐type lectin receptor of the Dectin‐1 cluster (CLECs), particularly the CLEC9A receptor, not only is expressed in dendritic cells but also presents a pivotal role in this context. In special, CLEC12A has been highlighted as a malaria pigment hemozoin (HZ) receptor. During Plasmodium infection, hemozoin crystals defend the parasite against heme toxicity within erythrocytes, as well as the released native HZ elicits pro-inflammatory responses and can induce cross-presentation. Particularly, this crystal can be synthesized from hematin anhydride and mimics the native form, and the gaps generated between the nanocrystal domains during its synthesis allow for substance coupling followed by its coating. Therefore, this study aimed to assess whether synthetic hemozoin (sHz) or hematin anhydride could be a nanocarrier and promote cross-presentation in dendritic cells. Firstly, it was verified that sHz can carry coated and coupled antigens, the compounds can associate to LAMP1-positive vesicles and decrease overall intracellular pH, which can potentially enhance the cross-presentation of ovalbumin and Leishmania infantum antigens. Thus, this study adds important data in the molecular intricacies of antigen presentation by showing not only the sHz immunomodulatory properties but also its potential applications as an antigen carrier.

Introdução: a hanseníase apresenta potencial incapacitante secundário às reações hansênicas. Existe considerável número de indivíduos com episódios recorrentes de reação durante o tratamento. Objetivo: identificar características clínicas e histopatológicas que diferenciem pacientes com reação hansênica ou não. Método: estudo prospectivo de julho/2015 a dezembro/2016, com avaliação de indivíduos com diagnóstico novo de hanseníase atendidos no serviço de dermatologia do Complexo Hospitalar Clementino Fraga, na cidade de João Pessoa, Paraíba, Brasil. Os sujeitos foram classificados segundo os critérios de Ridley-Jopling/Madrid e por classificação operacional. Realizaram exame histopatológico no momento do diagnóstico e após 12 meses, e reavaliados após 6 e 12 meses do diagnóstico. Resultados: o grupo sem reação apresentou maior número de lesões com nítida delimitação. Observou-se predomínio das formas multibacilares entre indivíduos com reação. Quanto ao grau de incapacidade, o grupo com reação apresentou maior número de indivíduos com grau de incapacidade maior que zero. No grupo sem reação, encontrou-se menor frequência de fatores predisponentes. Notou-se correlação positiva do índice baciloscópico de biópsia cutânea com a ocorrência de reações. Discussão: a ausência de delimitação periférica das lesões pode se correlacionar com o surgimento de reação hansênica. O predomínio de reação entre os indivíduos que apresentavam grau de incapacidade maior que zero sugere associação de deficiência física e doença multibacilar. A ausência de fatores predisponentes aponta menor risco de reação hansênica. Observou- se correlação positiva do índice baciloscópico da biópsia com a ocorrência das reações. Conclusão: a significativa prevalência de reações graves enfatizam a importância do estudo contínuo da hanseníase e a necessidade de identificar precocemente as características clínicas sugestivas de reações hansênicas.

A produção platônica não foi engendrada no curso de entusiásticas buscas de repleção de insaciáveis carências humanas, o desejo de sabedoria e o de imortalização (entre os deuses e, também, entre os homens)? Não estariam ambas na origem desse novo gênero de dizer em que consiste, então, a filosofia enquanto uma espécie de motor gerador de seu ser próprio? Fecundado na alma por tais forças, características da QPÓ vn otg que têm a potência de iluminá-la, divinizá-la, imortalizando-a, Plantão dá à luz magníficos Ad)VOL mais imortais que os filhos gerados carnalmente pelo homem: uma vez publicados, perduram há 25 séculos na memória cultural do Ocidente.

Child sexual abuse (CSA), the most common type of maltreatment, is any action of a sexual nature by one or more adults towards a minor without the minor’s consent. This abuse represents one of the most damaging forms of trauma, has a severe impact on mental health and psychopathology, and can lead to several disorders, including post-traumatic stress disorder (PTSD). PTSD is characterized as a disorder that encompasses physical symptoms resulting from traumatic experiences that are experienced or witnessed by the victim. This systematic review aims to understand the impact of sexual abuse on post-traumatic stress disorder in children and adolescents. Studies focusing on the relationship between these two variables were obtained through multiple databases. Of the 940 documents collected, 24 were retained for further analysis and the objectives, methodologies, results, and main conclusions were registered. One of the main conclusions was that the earlier the abuse starts and the more severe and long-lasting it is, the symptomatology of PTSD will be aggravated and remain in the long term.

Prostate cancer (PCa) is a complex disease influenced by many factors, with the genetic contribution for this neoplasia having a great role in its risk. The literature brings an increased number of Genome-Wide Association Studies (GWAS's) that attempt to elucidate the genetic associations with PCa. However, these genome studies have a considerable rate of false-positive data whose results may be biased. Therefore, we aimed to apply Bayesian approaches on significant associations among polymorphisms and PCa from GWAS's data. A literature search was performed for data published before April 20, 2024, whereby two investigators used a specific combination of keywords and Boolean operators in the search ("prostate carcinoma or prostate cancer or PCa" and "polymorphism or genetic variation" and "Genome-Wide Association Study or GWAS"). The records were retrieved, and the data were extracted with further application of two different Bayesian approaches: The False Positive Report Probability (FPRP) and the Bayesian False-Discovery Probability (BFDP), both at the prior probabilities of 10 -3 and 10 -6 . The data were considered as noteworthy at the level of FPRP <0.2 and BFDP <0.8. Besides, in-silico analyses by gene-gene network and gene enrichment were performed to evaluate the role of the noteworthy genes in PCa. As results, 13 GWAS's were included, with 2,520 values for FPRP and 1,368 values for BFDP being obtained. Our study showed an extensive number of gene variations as noteworthy candidate biomarkers for PCa risk, with highlighting for those occurred in the 8q24 locus and in the MSMB, ITGA6, SUN2, FGF10, INCENP, MLPH, and KLK3 genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study evaluates the antibiofilm action of 2.5 mg/mL peracetic acid (PA), 0.5 mg/mL cetylpyridinium chloride (CPC), and 160 mg/mL N-Acetylcysteine (NAC) against multispecies biofilm of Streptococcus mutans, Staphylococcus aureus, Candida albicans, and Candida glabrata, developed on surfaces of heat-polymerizing acrylic resin (AR) and cobaltchromium (Co-Cr) alloy., Materials and Methods: A multispecies biofilm was grown on the surface of AR and Co-Cr specimens (Ø 12×3mm). After biofilm maturation, the specimens were immersed in experimental solutions and evaluated through biofilm viability (CFU) (n&#61;9), biofilm metabolic activity (XTT) (n&#61;9), biofilm-covered areas (Live/Dead) (n&#61;2), effects on the extracellular polymeric substance (EPS) (n&#61;2) and biofilm morphology (n&#61;1). Data were analyzed by ANOVA and the Tukey post-test or Kruskal-Wallis followed by the Dunn post-test (α&#61;.05)., Results: Overall, all evaluated solutions impacted biofilm viability. PA presented wider activity by reducing CFU of all microorganisms on both surfaces, XTT (P<.001) and Live/Dead (P<.001). NAC had a notorious effect in reducing the viability of bacteria without affecting the yeasts. NAC reduced XTT on AR (P&#61;.006) and Co-Cr (P&#61;.003) but did not reduce the aggregated biofilm layer. CPC had distinct effect according to the surface, being most effective in reducing CFU on AR than the Co-Cr surface. However, it did not influence XTT, and the amount of residual aggregated biofilm., Conclusions: PA provided the greatest antibiofilm action, while CPC and NAC showed intermediate action. Nonetheless, no solution was able to completely remove the biofilm adhered to the surfaces of heat-polymerizing AR and Co-Cr alloy.

Carcinogenesis is associated with the emergence of protracted intestinal dysbiosis and metabolic changes. Increasing evidence shows that gut microbiota-related biomarkers and microbiota-centered interventions are promising strategies to overcome resistance to immunotherapy. However, current standard methods for evaluating gut microbiota composition are cost- and time-consuming. The development of routine diagnostic tools for intestinal barrier alterations and dysbiosis constitutes a critical unmet medical need that can guide routine treatment and microbiota-centered intervention decisions in patients with cancer. In this review, we explore the influence of gut microbiota on cancer immunotherapy and highlight gut-associated biomarkers that have the potential to be transformed into simple diagnostic tools, thus guiding standard treatment decisions in the field of immuno-oncology. Mechanistic insights toward leveraging the complex relationship between cancer immunosurveillance, gut microbiota, and metabolism open exciting opportunities for developing novel biomarkers in immuno-oncology.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi , is an important public health problem, occurring mainly in Latin America. The disease has a major social and economical effect, negatively impacting the life of the infected individuals, and bringing great costs to public health. An early and accurate diagnosis is essential for administration of early treatment. In addition, prognostic tests may aid disease management, decreasing hospitalization costs. However, the serological diagnostic scenario for CD still faces several challenges, making the development of new diagnostic kits a pressing matter. Facing this scenario, several researchers have expanded efforts in developing and testing new antigens, such as recombinant proteins and recombinant multiepitope proteins, with promising results. These recombinant antigens offer several advantages, such as improved sensitivity and specificity, in addition to facilitated scaling. Also, it has been possible to observe a rising number of studies using ELISA and point-of-care platforms, employing these antigens in the past few years. Among them, recombinant proteins were the most applied antigens, demonstrating great capacity to discriminate between positive and negative samples. Although fewer in number, recombinant multiepitope proteins also demonstrated an improved diagnostic performance. Indeed, a great number of studies employing these antigens showed sensitivity and specificity values above 90%, greatly impacting diagnostic accuracy. Nevertheless, despite the good results found, it is still possible to observe some bottlenecks in the development of new antigens, such as the scarcity of tests with sera from the acute phase and the variability of results in different geographic areas. In this sense, aiming to contribute to control and health programs, the continuous search for a more accurate serological diagnosis is essential, both for the acute and chronic phases of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Resende, Ribeiro, Gandra, Silva, Lopes, Barcelos, Couto, de Faria, Pereira, Xavier, Machado, da Paz, Chaves, Coelho, Giunchetti, Chávez-Fumagalli, Dutra, Gonçalves and Galdino.)

Improving the diagnostic technology used to detect tegumentary leishmaniasis (TL) is essential in view of it being a widespread, often neglected tropical disease, with cases reported from the Southern United States to Northern Argentina. Recombinant proteins, recombinant multiepitope proteins, and synthetic peptides have been extensively researched and used in disease diagnosis. One of the benefits of applying these antigens is a measurable increase in sensitivity and specificity, which improves test accuracy. The present review aims to describe the use of these antigens and their diagnostic effectiveness. With that in mind, a bibliographic survey was conducted on the PudMed platform using the search terms "tegumentary leishmaniasis" AND "diagno", revealing that recombinant proteins have been described and evaluated for their value in TL diagnosis since the 1990s. However, there was a spike in the number of publications using all of the antigens between 2013 and 2022, confirming an expansion in research efforts to improve diagnosis. Moreover, all of the studies involving different antigens had promising results, including improved sensitivity and specificity. These data recognize the importance of doing research with new technologies focused on developing quick, more effective diagnostic kits as early diagnosis facilitates treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)