The usefulness of patient-reported outcome measures in decision making in Chagas cardiomyopathy: a scoping review.

Chagas cardiomyopathy (ChC) presents many biopsychosocial complexities, highlighting the need to have patient self-report questions. This study demonstrates the scope of the use of patient-reported outcome measures (PROMs) in patients with ChC and highlights the main research gaps. This is a scoping review and the search strategy was performed in the Online Medical Literature Analysis and Retrieval System (MEDLINE), Excerpta Medica database (EMBASE), Accumulated Index of Nursing and Allied Health Literature (CINAHL), Cochrane Central, Latin American Literature and Caribbean in Health Sciences (LILACS) and Diagnostic Test Accuracy (DITA). The search identified 4484 studies and 20 studies met the inclusion criteria. The Short-Form of 36 items (SF-36) had potential prognostic value and the ability to identify systolic dysfunction. The Human Activity Profile was able to screen for functional impairment, and the New York Heart Association showed potential prognostic value. The SF-36 and Minnesota Living with Heart Failure Questionnaire were responsive to interventions. The pharmaceutical care affected adherence to treatment as assessed by the Morisky score and also for SF-36. Despite the increased use of PROMs, there are still a large number of gaps in the literature, and further studies using PROMs are needed.

Recurrent Chagas' disease meningomyelitis in an HIV-infected patient.

Chagas' disease reactivation leading to monophasic acute or subacute meningoencephalitis or space-occupying lesions is a well-described AIDS-defining condition in Latin America. We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas' disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic disease.

WEIRD-Confucian comparisons: Ongoing cultural biases in psychology's evidence base and some recommendations for improving global representation.

The realization that most behavioral science research focuses on cultures labeled as WEIRD-Western, educated, industrialized, rich, and democratic (Arnett, 2008; Henrich et al., 2010; Thalmayer et al., 2021)-has given an impetus to extend the research to more diverse populations. Confucian East Asian societies have relatively strong social and technological infrastructure to advance science and thus have gained much prominence in cross-cultural studies. This has inadvertently fostered another bias: the dominance of WEIRD-Confucian comparisons and a tendency to draw conclusions about "non-WEIRD" cultures in general based on data from Confucian societies. Here, analyzing 1,466,019 scientific abstracts and, separately, coverage of 60 large-scale cross-cultural psychological projects (Nsamples = 2,668 from Ncountries = 153 covering nparticipants = 3,722,940), we quantify the dominance of Confucian over other non-WEIRD cultures in psychological research. Our analysis also reveals the underrepresentation of non-European Union postcommunist societies and the almost total invisibility of Pacific Island, Caribbean, Middle African, and Central Asian societies within the research database of psychology. We call for a shift in cross-cultural studies toward midsize (7+ countries) and ideally large-scale (50+ countries) cross-cultural studies, and we propose mitigations that we believe could aid the inclusion of diverse researchers as well as participants from underrepresented cultures in our field. People in all world regions and cultures deserve psychological knowledge that applies to them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessment of health-related quality of life in patients with Chagas cardiomyopathy using Minnesota living with heart failure questionnaire: A validation study.

OBJECTIVE: Chagas cardiomyopathy (ChC) is the most severe clinical form of Chagas disease and, in association with psychosocial factors, can compromise the health-related quality of life (HRQoL) of affected patients. To date, there is no specific instrument to assess the HRQoL of these patients, and the Minnesota Living with Heart Failure Questionnaire (MLwHFQ), specific for heart failure, is being used both in research and current clinical practice. Therefore, we aimed to verify the validity of the MLwHFQ in the assessment of HRQoL of patients with ChC. METHODS: Fifty patients with ChC (50.6 ± 10.1 years, NYHA I-III) were evaluated. The MLwHFQ, Short-Form of Health Survey (SF-36), Beck Depression Inventory (BDI), and Human Activity Profile (HAP) were applied. All patients underwent echocardiography and Cardiopulmonary Exercise Testing (CPET). RESULTS: The MLwHFQ score correlated with almost all SF-36 domains (with r-value ranging from -0.38 to -0.69), except pain (p = 0.118). The MLwHFQ score also correlated with the BDI score (r = 0.748; p < 0.001), HAP score (r = -0.558; p = 0.001), peak oxygen uptake (r = -0.352; p = 0.01), and left ventricular ejection fraction (r = -0.329; p = 0.021). There was no significant difference in the score found on the MLwHFQ among NYHA classes (p = 0.101), as well as between patients with systolic dysfunction (n = 30) and preserved cardiac function (n = 20) (p = 0.058). Similarly, there was no significant difference in the score found on the physical (p = 0.423) and mental (p = 0.858) components of SF-36 between patients with systolic dysfunction and preserved cardiac function (p = 0.271 and p = 0.609, respectively). There was also no difference in the mental component of SF-36 among NYHA classes (p = 0.673). However, the HRQoL using the physical component of SF-36 was worse in advanced NYHA classes (p = 0.014). CONCLUSION: MLwHF correlated with most SF-36 HRQoL domains, depressive symptoms, physical activity, and systolic function and seems to be valid in assessing the HRQoL of ChC patients.

Functional predictors of poor outcomes in Chagas cardiomyopathy: The value of end-tidal carbon dioxide at peak exercise.

BACKGROUND: Functional impairment can be detected from the onset of heart disease in patients with Chagas cardiomyopathy (ChC) and the prognostic value of the end-tidal carbon dioxide at peak exercise (PETCO2 peak) should be investigated. OBJECTIVE: To verify the prognostic value of PETCO2 peak in patients with ChC. METHODS: Seventy-six patients with ChC (49.2 ± 9.8 years, NYHA I-III) were evaluated by echocardiography and Cardiopulmonary Exercise Testing. Patients were followed up to four years and the end-point was defined as cardiovascular death, stroke, or cardiac transplantation. RESULTS: At the end of the follow-up period (29.0 ± 16.0 months), 16 patients (21%) had experienced adverse events. The area under the receiver operating characteristic (ROC) curve to identify the risk of adverse events by PETCO2 peak in patients with ChC was 0.83 (95% CI: 0.69 to 0.97), and the value of 32 mmHg was the optimal cut point (70% of sensitivity and 85% of specificity). In the Kaplan-Meier diagram, there was a significant difference (p<0.001) between patients with reduced (≤ 32 mmHg) and preserved PETCO2 peak (>32 mmHg). In the final Cox multivariate model, only reduced PETCO2 peak (HR 4.435; 95% CI: 1.228 to 16.016, p = 0.023) and VO2peak (HR 0.869; 95% CI: 0.778 to 0.971, p = 0.013) remained as independent predictors of poor outcome in ChC patients. CONCLUSION: Reduced PETCO2 peak and VO2peak demonstrated valuable prognostic value in patients with ChC. The cutoff points for both functional variables can be used during risk stratification and may help in the development of therapeutic strategies in ChC patients.

Development of SEDDS formulation containing caffeine for dermal delivery.

OBJECTIVE: The objective of this work was to develop a self-emulsifying drug delivery system (SEDDS) containing caffeine for the treatment of cellulite. METHODS: SEDDS were prepared using the solution method. 0.5% (w/v) caffeine was added to the previously selected excipients. The system was characterized by droplet size, zeta potential, emulsification time and long-term stability. In vitro release and skin permeation were investigated using Franz-type diffusion cells. The cytotoxicity was evaluated on normal human keratinocytes. RESULTS: Caffeine SEDDS were thermodynamically stable, with a zeta potential less than - 22 mV and droplet size around 30 nm, and were long-term stable. The permeation study showed that the formulation promoted caffeine accumulation in the skin layers, suggesting an increase in local circulation. Cytotoxicity studies on HaCaT cells were not conclusive as the surfactant used indicated false-positive results due to its high molar mass. CONCLUSION: It was possible to obtain a stable SEDDS that could cause an increase in blood flow in the applied area, resulting in cellulite reduction.

OBJECTIF: L'objectif de ce travail était de développer un système d'administration de médicaments auto-émulsifiants (SEDDS) contenant de la caféine pour le traitement de la cellulite. MÉTHODES: Les SEDDS ont été préparés par la méthode en solution. 0,5 % (p/v) de caféine a été ajouté aux excipients préalablement sélectionnés. Le système a été caractérisé par la taille des gouttelettes, le potentiel zêta, le temps d'émulsification et la stabilité à long terme. La libération in vitro et la perméation cutanée ont été étudiées dans des cellules de diffusion de type Franz. La cytotoxicité était évaluée sur des kératinocytes humains normaux. RÉSULTATS: Les SEDDS de caféine étaient thermodynamiquement stables, avec un potentiel Zeta inférieur à -22 mV et une taille de gouttelettes d'environ 30 nm, et stables à long terme. L'étude de perméation a montré que les formulations favorisent l'accumulation de caféine dans les couches de la peau, suggérant une augmentation de la circulation locale. Les études de cytotoxicité sur les cellules HaCaT n'ont pas été concluantes car le surfactant utilisé indique des résultats faussement positifs dus à une masse molaire élevée. CONCLUSION: Il a été possible d'obtenir un SEDDS stable qui peut provoquer une augmentation du flux sanguin dans la zone appliquée, entraînant une réduction de la cellulite.

Reliability and validity of specific quality of life assessment questionnaires related to chronic venous insufficiency: a systematic review.

This systematic review aimed to discuss the main findings regarding the reliability and validity of health-related quality of life questionnaires for chronic venous insufficiency. Searches were performed on the MEDLINE, CINAHL, Web of Science, LILACS, and Scopus databases. The search terms used were related to "venous insufficiency", and "quality of life". The CIVIQ-20 and CIVIQ-14 instruments had adequate internal consistency and both were able to discriminate disease severity. The VEINES-QoL showed adequate internal consistency but was not able to discriminate disease severity. Most studies did not demonstrate a correlation between VEINES-QoL and the mental component of the SF-36. The AVVQ had inadequate reliability but its validity was also doubtful when compared to the SF-36. The VARIShort demonstrated good internal consistency, reproducibility, and validity, but only the original study was included. For venous leg ulcers, the CCVUQ showed adequate reliability and validity when compared to VLU-QoL.

Esta revisão sistemática objetivou discutir os principais achados sobre a confiabilidade e validade dos questionários de qualidade de vida relacionada à saúde na insuficiência venosa crônica. A busca foi realizada nas bases de dados MEDLINE, CINAHL, Web of Science, LILACS e Scopus. Os termos de busca foram relacionados a "insuficiência venosa" e "qualidade de vida". O Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ)-20 e o CIVIQ-14 apresentaram consistência interna adequada e foram capazes de discriminar a gravidade da doença. O Venous Insufficiency Epidemiological and Economic Study ­ Quality of Life (VEINES-QoL) apresentou consistência interna adequada, mas não foi capaz de discriminar a gravidade da doença. A maioria dos estudos não demonstrou associação do VEINES-QoL com o componente mental do Short Form Health Survey (SF-36). O Aberdeen Varicose Vein Questionnaire (AVVQ) apresentou confiabilidade inadequada e validade duvidosa quando comparado ao SF-36. O VARIShort demonstrou consistência interna, reprodutibilidade e validade boas, mas apenas o estudo original foi incluído. Na úlcera venosa, o Charing Cross Venous Ulcer Questionnaire (CCVUQ) apresentou confiabilidade e validade adequadas quando comparado ao Venous Leg Ulcer Quality of Life (VLU-QoL).

Studying the Dynamics of Chromatin-Binding Proteins in Mammalian Cells Using Single-Molecule Localization Microscopy.

Single-molecule localization microscopy (SMLM) allows the super-resolved imaging of proteins within mammalian nuclei at spatial resolutions comparable to that of a nucleosome itself (~20 nm). The technique is therefore well suited to the study of chromatin structure. Fixed-cell SMLM has already allowed temporal "snapshots" of how proteins are arranged on chromatin within mammalian nuclei. In this chapter, we focus on how recent developments, for example in selective plane illumination, 3D SMLM, and protein labeling, have led to a range of live-cell SMLM studies. We describe how to carry out single-particle tracking (SPT) of single proteins and, by analyzing their diffusion parameters, how to determine whether proteins interact with chromatin, diffuse freely, or do both. We can study the numbers of proteins that interact with chromatin and also determine their residence time on chromatin. We can determine whether these proteins form functional clusters within the nucleus as well as whether they form specific nuclear structures.

Impairments in ankle range of motion, dorsi and plantar flexors muscle strength and gait speed in patients with chronic venous disorders: A systematic review and meta-analysis.

OBJECTIVE: To verify the differences in ankle range of motion (ROM), muscle strength of dorsi and plantar flexors, and gait speed among healthy subjects, and patients with chronic venous disorders (CVD) with and without venous leg ulcer. METHODS: A systematic review and meta-analysis (http://osf.io/b7n3k) were conducted following a search of MEDLINE, Web of Science, CINAHL, LILACS, Scopus, and EMBASE databases. RESULTS: Eight papers were included. The ankle ROM was significantly lower both in dorsiflexion and plantar flexion in patients with venous leg ulcer when compared to healthy individuals and CVD patients without venous leg ulcer. The muscle strength of the plantar flexors and gait speed were reduced in CVD patients when compared to healthy ones. CONCLUSION: Impaired muscle strength and gait speed can be detected in CVD patients compared to healthy individuals, and ankle ROM tends to be reduced in CVD patients even in the absence of venous leg ulcers.

Outside the "Cultural Binary": Understanding Why Latin American Collectivist Societies Foster Independent Selves.

Cultural psychologists often treat binary contrasts of West versus East, individualism versus collectivism, and independent versus interdependent self-construal as interchangeable, thus assuming that collectivist societies promote interdependent rather than independent models of selfhood. At odds with this assumption, existing data indicate that Latin American societies emphasize collectivist values at least as strongly as Confucian East Asian societies, but they emphasize most forms of independent self-construal at least as strongly as Western societies. We argue that these seemingly "anomalous" findings can be explained by societal differences in modes of subsistence (herding vs. rice farming), colonial histories (frontier settlement), cultural heterogeneity, religious heritage, and societal organization (relational mobility, loose norms, honor logic) and that they cohere with other indices of contemporary psychological culture. We conclude that the common view linking collectivist values with interdependent self-construal needs revision. Global cultures are diverse, and researchers should pay more attention to societies beyond "the West" and East Asia. Our contribution concurrently illustrates the value of learning from unexpected results and the crucial importance of exploratory research in psychological science.

Differences in health-related quality of life in patients with mild and severe chronic venous insufficiency: A systematic review and meta-analysis.

OBJECTIVE: Chronic venous insufficiency (CVI) has a broad spectrum of clinical expression, ranging from mild to severe cases, which negatively impacts the health-related quality of life (HRQoL). However, the comparison in HRQoL between mild and severe CVI has not yet been systematically discussed, which could assist in the adoption of preventive strategies METHODS: A systematic review and meta-analysis was conducted (protocol register https://osf.io/mr4aj/) following a search of the MEDLINE, CINAHL, Web of Science, LILACS, and Scopus databases, using the terms related to CVI and HRQoL. Observational studies that assessed the HRQoL in individuals with CVI in different degrees of severity were included, without date restriction RESULTS: We retrieved 4750 titles and abstracts and 9 were included in this review. The HRQoL was worse in patients with severe CVI compared to mild patients at Short-form of Health Survey (SF-36) (mean difference 11.02, 95% CI from 8.62 to 13.43; p<0.001), Chronic Venous Insufficiency Quality Of Life Questionnaire (CIVIQ-14) (mean difference 13.07; 95% CI from 11.33 to 14.82; p<0.001) and Aberdeen Varicose Veins Questionnaire (mean difference 7.7; 95% CI: -12.82 to -2.58; p=0.003), especially in the physical domains. There was no difference in the HRQoL between severe and mild patients at CIVIQ-20 (p=0.09) CONCLUSION: The HRQoL was worse in the physical domains in patients with severe CVI when compared to mild patients. However, the heterogeneity of the results was high and the data should be interpreted with caution.

Who Can Buffer Marginalization Risk? Affect Experience, Affect Valuation, and Social Marginalization in Japan and Brazil.

Previous research has associated social marginalization with the rejection of mainstream cultural values. Since cultural values reflect affect valuation, the present research investigates the relationships between social marginalization and ideal/actual affect in two different non-WEIRD cultures, Brazil and Japan. As a social marginalization index, we used the NEET-Hikikomori Risk Scale (NHR). We predicted that cultural differences would emerge in the valuation of affective states. Affect valuation theory suggests that in East Asia, individuals are encouraged to pursue and value low arousal positive emotions (LAP: e.g., calmness, serenity) over high arousal positive emotions (HAP: e.g., excitement, elation, etc.) as they can harm social relationships in these societies. In contrast, Latin American cultures value HAP over LAP, because social relationships are promoted through vibrant positive emotional expression in these cultures. Hence, we hypothesized that individuals' ideal affect, actual affect, and the discrepancy between ideal and actual affect would be associated with higher risk of social marginalization. Participants from Japan (N = 54) and Brazil (N = 54) reported their ideal affect and actual affect and completed the NEET-Hikikomori Risk Scale (NHR). Regression analyses showed that actual HAP and the discrepancy between ideal and actual HAP were negatively associated with NHR in Brazil, but no association was found in the Japanese data. The other variables, including ideal affect, were only minorly or not significantly associated with NHR. Though the study has limitations regarding its small sample size, we can explore future perspectives and discuss the relationships between emotion and cultural marginalization. Socioecological factors that promote actual HAP in Brazilians may encourage other mainstream cultural ideals, which buffers against cultural marginalization.

Cultural differences in music features across Taiwanese, Japanese and American markets.

BACKGROUND: Preferences for music can be represented through music features. The widespread prevalence of music streaming has allowed for music feature information to be consolidated by service providers like Spotify. In this paper, we demonstrate that machine learning classification on cultural market membership (Taiwanese, Japanese, American) by music features reveals variations in popular music across these markets. METHODS: We present an exploratory analysis of 1.08 million songs centred on Taiwanese, Japanese and American markets. We use both multiclass classification models (Gradient Boosted Decision Trees (GBDT) and Multilayer Perceptron (MLP)), and binary classification models, and interpret their results using variable importance measures and Partial Dependence Plots. To ensure the reliability of our interpretations, we conducted a follow-up study comparing Top-50 playlists from Taiwan, Japan, and the US on identified variables of importance. RESULTS: The multiclass models achieved moderate classification accuracy (GBDT = 0.69, MLP = 0.66). Accuracy scores for binary classification models ranged between 0.71 to 0.81. Model interpretation revealed music features of greatest importance: Overall, popular music in Taiwan was characterised by high acousticness, American music was characterised by high speechiness, and Japanese music was characterised by high energy features. A follow-up study using Top-50 charts found similarly significant differences between cultures for these three features. CONCLUSION: We demonstrate that machine learning can reveal both the magnitude of differences in music preference across Taiwanese, Japanese, and American markets, and where these preferences are different. While this paper is limited to Spotify data, it underscores the potential contribution of machine learning in exploratory approaches to research on cultural differences.

Cross-cultural adaptation of a quality of life questionnaire for individuals with oral potentially malignant disorders in the Brazilian context.

The aim of this article is to describe the cross-cultural adaptation of a quality of life (QoL) questionnaire for individuals with potentially malignant oral diseases (OPMD) in the Brazilian context. This methodological study consisted of the following stages of content validation process: (1) Conceptual and item equivalence: stage during which a comprehensive literature review on the construct was performed; (2) Semantic equivalence. The extensive literature review showed that the questionnaire enables evaluation of QoL, and that domains and items are also considered and relevant to the Brazilian context. Semantic equivalence was evaluated as satisfactory by a committee of judges. The scope of the domains was analyzed according to the agreement rate and presented results equal to or greater than 84%. The general Content Validity Calculation (CVC) was 0.84 for clarity and 0.92 for representativeness. Of the 20 items, 18 presented CVC values above 0.8. The indicators for content validation, pre-test and operational equivalence indicate that the Brazilian version of the OPMD QoL questionnaire is a promising instrument and a tool that seems valid to evaluate the quality of life of people with oral potentially malignant disorders. As a next step, it is important to measure equivalences to evaluate the psychometric properties of this instrument.

Este artigo objetiva adaptar transculturalmente um questionário de qualidade de vida para indivíduos com doenças orais potencialmente malignas para o contexto brasileiro. Este estudo metodológico consistiu nas seguintes etapas do processo de validação de conteúdo: (1) Equivalência conceitual e de itens - etapa em que foi realizada uma ampla revisão da literatura sobre o construto; (2) Equivalência semântica. A extensa revisão da literatura mostrou que o questionário permite avaliar a QV e que os domínios e itens também são considerados e relevantes para o contexto brasileiro. A equivalência semântica foi avaliada pelo comitê de juízes de forma satisfatória. A análise do escopo dos domínios foi realizada pela taxa de concordância e apresentou resultados iguais ou superiores a 84%. Para a análise de clareza e representatividade, o resultado do cálculo geral do Cálculo de Validade de Conteúdo (CVC) foi de 0,84 e 0,92 respectivamente. Dos 20 itens, 18 apresentaram valores de IVC acima de 0,8. Os indicadores de validação de conteúdo, pré-teste e equivalência operacional indicam que a versão brasileira do QoL-OPMD é um instrumento promissor e que parece válido para avaliar a qualidade de vida de pessoas com doenças orais potencialmente malignas. Como próximo passo, é importante avaliar as propriedades psicométricas desse instrumento.

Risk factors for common mental disorders in health care workers in the city of Diamantina, state of Minas Gerais.

INTRODUCTION: The increased prevalence of mental health symptoms in primary care workers in recent years is a major cause of concern, and highlights the need to identify modifiable risk factors for mental health disorders in this population. OBJECTIVES: To analyze the prevalence of common mental disorders and associated factors in primary care workers in the city of Diamantina, state of Minas Gerais. METHODS: This was a cross-sectional, exploratory study involving 203 workers in different sectors of primary health care. Participants completed the Self-Report Questionnaire (20 item version), the Job Stress Scale (JSS), and a form with questions regarding sociodemographic factors, occupational characteristics, lifestyle and habits. RESULTS: The prevalence of common mental disorders in the sample was 20.2%. These disorders were significantly associated (p ≤ 0.05) with younger age, poor self-assessed health, poor sleep quality and physically demanding work. CONCLUSIONS: Poor working conditions may directly and indirectly affect the occurrence of mental health disorders by influencing lifestyle and habits. The restructuring of organizational norms, together with worker support policies, may positively contribute to the mental health of workers.

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells.

Trypanosoma cruzi, the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi, which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans-sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin-like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle-free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC-MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain-derived EVs caused higher infection of LLC-MK2 cells than Y strain-derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host-parasite interaction.

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells

Trypanosoma cruzi, the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi, which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans-sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin-like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle-free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC-MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain-derived EVs caused higher infection of LLC-MK2 cells than Y strain-derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host-parasite interaction.

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells

Trypanosoma cruzi, the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi, which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans-sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin-like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle-free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC-MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain-derived EVs caused higher infection of LLC-MK2 cells than Y strain-derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host-parasite interaction.

Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response.

Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and remained at normal levels shortly after treatment in 76% and 96% of cases, respectively. Plasmin-antiplasmin complexes (PAP) were altered before treatment in 32% of G1 patients but normalized in 94% of cases several months after treatment. None of the patients with normal F1+2 values during follow-up had a positive qRT-PCR result, but 3/24 patients (13%) with normal ETP values did. In a percentage of chronic T. cruzi infected patients treated with benznidazole, altered coagulation markers returned into normal levels. F1+2, ETP and PAP could be useful markers for assessing sustained response to benznidazole.

Effect of processing, post-harvest irradiation, and production system on the cytotoxicity and mutagenicity of Vitis labrusca L. juices in HTC cells.

The juices of grapes (Vitis labrusca L.) are similar to the fruit itself because the main constituents of the fruit are present in the juice. However, their quality characteristics may be modified by the harsh technological processes used for the production of integral food, such as production systems of raw materials and post-harvest treatment of grapes with ultraviolet (UV) irradiation. Therefore, the present study analyzed juices produced naturally (by liquefying the fruit) or by the technological process of extraction by steam distillation (90°C) of grapes from organic and conventional production systems that were untreated or treated with UV type C (65.6 J/m² for 10 minutes). Using cultures of Rattus norvegicus hepatoma cells (HTC) in vitro, cytotoxic effects were assayed by the MTT test and by calculating the cytokinesis blocked proliferation index (CBPI), and mutagenic effects were measured by the cytokinesis block micronucleus assay. The results of the MTT assay and the CBPIs indicated that none of the juices were cytotoxic, including those that induced cell proliferation. The results of the micronucleus assay showed that none of the juices were mutagenic. However, the average number of micronuclei was lower in the juices produced from organic grapes, and cell proliferation, soluble acids and phenolic compounds were significantly higher. Compared with the natural juices, the integral juices of conventional grapes showed a higher average number of micronuclei as well as lower stimulation of cell proliferation and lower levels of bioactive compounds. The results demonstrate a beneficial effect of UV-C irradiation of post-harvest grapes in stimulating the synthesis of nutraceutical compounds without generating cytotoxic or mutagenic substances. Taken together, our findings support the consumption of grape juice and the application of food production techniques that enhance its nutritional value and promote its production, marketing and consumption.