Teleconsultations in oral medicine: dentist perception during the COVID-19 pandemic in Brazil.

BACKGROUND: The aim of this study was to describe the perception of dentists from the North macroregion of Minas Gerais, Brazil, users of telediagnosis in Oral Medicine, during the COVID-19 pandemic. MATERIAL AND METHODS: This is a cross-sectional and descriptive study. Data collection was carried out online, between May and October 2022. The information was transferred to the Statistical Package for the Social Sciences for Windows (SPPS)® version 24. RESULTS: The sample consisted of 255 dentists, predominantly female. Regarding perception, a significant percentage (47.8%) of respondents agreed that they would like to use telediagnosis frequently, more than half (60.6%) agreed that the technology is easy to use, only a small percentage (8.8%) needed technical support to use it and almost half (48.2%) mentioned the desire to continue using it after the pandemic. When asked if patients felt confident and comfortable when passing on information, more than half disagreed or remained neutral (58.4%), a similar result was found in relation to confidence in the application of the instrument by professionals. CONCLUSIONS: It is concluded that, during the pandemic, telediagnosis in Oral Medicine was an easy and adequate tool. However, professionals must be trained and prepared to be comfortable and ready for use.

From Psoriasis to Psoriatic Arthritis: Ultrasound Insights Connecting Psoriasis with Subclinical Musculoskeletal Inflammation and the Path to Psoriatic Arthritis.

PURPOSE OF REVIEW: This review summarizes the literature about the transition from psoriasis to psoriatic arthritis (PsA), focusing on musculoskeletal ultrasound (MSUS) for detecting subclinical inflammation and its role in diagnosis and triage of high-risk patients. RECENT FINDINGS: MSUS effectively detects subclinical musculoskeletal inflammation in patients with psoriasis; however, some of these lesions are non-specific and can be found in healthy individuals. Preliminary evidence suggest that subclinical sonographic findings may predict progression to PsA in psoriasis patients. MSUS can also improve referrals' accuracy and its integration in the PsA classification criteria may improve early PsA detection. MSUS is a valuable tool for detecting subclinical abnormalities in psoriasis patients, which indicate an increased likelihood of progressing to PsA. Its integration into referral protocols and clinical use could improve PsA diagnosis. We propose an MSUS-inclusive algorithm for PsA referrals and triage, which requires validation. The potential of early intervention in reducing PsA progression in psoriasis patients with subclinical inflammation remains to be established.

Undernutrition, and overweight and obesity: the two faces of malnutrition in Brazil, analysis of the Global Burden of Disease, 1990 to 2019.

OBJECTIVES: The objective of this study was to analyse the global burden of disease attributable to undernutrition and high body mass index (BMI) in Brazil and its 27 states, as well as its association with the socio-demographic index (SDI) from 1990 to 2019. STUDY DESIGN: This is an epidemiological time-series study. METHODS: This study analysed the undernutrition and high BMI estimated by the Global Burden of Disease study conducted from 1990 to 2019 for Brazil and its states, using the following metrics: absolute number of deaths, standardised mortality rate, and disability-adjusted life years (DALYs). This study also analysed the correlation between the percentage variation of mortality rates and SDI. RESULTS: A decrease in the number of deaths (-75 %), mortality rate (-75.1 %), and DALYS (-72 %) attributable to undernutrition was found in Brazil and in all regions. As regarding the high BMI, an increase in the number of deaths was found (139.6 %); however, the mortality rate (-9.7) and DALYs (-6.4 %) declined in all regions, except in the North and Northeast regions, which showed an increase. A strong correlation was identified between undernutrition and high BMI with SDI. CONCLUSION: Our study observed a double burden of malnutrition in Brazil, with a reduction in the burden of diseases due to malnutrition in Brazil and variation in the burden due to high BMI according to the socioeconomic status of the region. Public policies are necessary in order to guarantee the human right to a healthy and sustainable diet, together with food and nutrition security and a diminishing of social inequality.

Mortality by avoidable causes in Brazil from 1990 to 2019: data from the Global Burden of Disease Study.

OBJECTIVES: The aim of this study was to analyse the trends of avoidable mortality in Brazil from 1990 to 2019 and its correlation with sociodemographic indexes (SDIs). STUDY DESIGN: Epidemiological mortality trends. METHODS: This study analysed data from the Global Burden of Disease database. The list of causes of avoidable death, as proposed by Nolte and McKee, was applied and included 32 causes. The current study used age-standardised mortality rates and the rates of change, in addition to a correlation analysis between avoidable death and the SDI. RESULTS: Mortality rates decreased from 343.90/100,000 inhabitants in 1990 to 155.80/100,000 inhabitants in 2019. Infectious diseases showed the largest decline in mortality rates, but notable decreases were also found for diarrhoeal diseases (-94.9%), maternal conditions (-66.5%) and neonatal conditions (-60.5%). Mortality rates for non-communicable diseases (NCDs) also decreased (-48%) but maintained a similar absolute number of deaths in 2019 compared with 1990. Decreased mortality rates were also found for ischaemic heart disease (-49.1%), stroke (-61.4%) and deaths due to adverse effects caused by medical treatments (-26.2%). Avoidable mortality rates declined in all of the 27 Brazilian states, and a high correlation was found between deaths and SDI (R = -0.74; P < 0.000001). CONCLUSIONS: A reduction in avoidable deaths was found throughout Brazil over the study period, although major regional inequalities were revealed. Richer states presented the best overall reduction in mortality rates. The biggest decreases in mortality were seen in maternal and paediatric infectious diseases in the poorest states due to the expansion of the Primary Health System and improvements in sanitation. Today, NCDs predominate and efforts should be made to formulate public policies for the prevention and control of NCDs.

Spatial association of homicide rate with violence, sociodemographic, and public security factors: global burden of disease study 2018 for municipalities in Brazil.

OBJECTIVES: To analyse spatial-temporal changes and spatial association of homicide rates with violence, sociodemographic, public security and human rights indicators in Brazilian municipalities. STUDY DESIGN: An ecological study using homicide estimates from the Global Burden of Disease and population from the Brazilian Ministry of Health, 2000 to 2018. The explanatory variables come from the systems of mortality, notifications of violence and security, and the Brazilian Institute of Geography and Statistics. METHODS: Moran indices and maps identified clusters of high and low risk for homicides in three trienniums (p < 0.05). Multivariate linear and spatial regressions estimated explanatory factors' contributions for the last triennium. RESULTS: Municipalities with high rates of homicides (>34/100,000) doubled, reaching 21.5 %. Those rates were concentrated in big cities, and increased in smaller municipalities. Increases in critical areas were found in the Northeast and North regions: more than 40 % in the states of Sergipe, Bahia, Ceará, Rio Grande do Norte and Roraima. Decreases occurred in the Southeast and Midwest regions: more than 35 % in São Paulo and Rio de Janeiro states. The spatial model, with an 18.9 % higher R2 (0.706), showed a positive association for records of violence, Blacks, low-level education, municipalities >50,000 inhabitants and municipalities with homicide and municipal police. CONCLUSIONS: An increase in and the interiorisation of homicide risk areas in Brazil was observed, with displacement among regions (from the Southeast to the North/Northeast). The level of violence was the main explanatory factor for homicides. Territorial space proved to be important to understand and prevent lethal crime.

Chagas disease deaths detected among garbage codes registered in mortality statistics in Brazil: a study from the buRden of ChAgas dISEase in the contemporary world (RAISE) project.

OBJECTIVES: The objective of this study was to identify Brazil's most critical garbage codes (GCs) reclassified to Chagas disease (ChD) in mortality data and their proportions. We also estimated the potential impact of misclassification on the number of deaths attributed to ChD. STUDY DESIGN: Population-based descriptive study. METHODS: We used the Mortality Information System (SIM; in Portuguese) data before and after routine GC investigation in 2015-2019 to evaluate ChD deaths detected among them. We identified priority GCs, which contributed more than 0.1 % to the percentage of total ChD deaths registered. Spearman's correlation was used to evaluate the association between the reclassification of priority GCs and ChD prevalence. Then, we applied the GC correction factors to estimate the number of deaths attributed to ChD. RESULTS: 22,154 deaths were reported as ChD in the study period. Among them, 1004 deaths originally listed as priority GCs were deaths reclassified to ChD after an investigation in the SIM final database. Unspecific cardiomyopathy (10.2 %), unspecific heart diseases (4.7 %), and heart failure (2.8 %) were GCs with the highest proportions of reclassification to ChD in Brazil. Higher ChD prevalence at the state level was associated with a higher proportion of GC deaths reclassified as ChD. When applying correction factors identified after investigation, we estimated an increase of 26.4 % in registered ChD deaths, mostly in states with higher endemicity. CONCLUSIONS: GCs might conceal deaths due to ChD, particularly in Brazil's states with higher endemicity. The approach suggested in this study may offer an alternative method for estimating ChD-related deaths in endemic countries.

Burden of non-communicable diseases and the achievement of the sustainable development goals in 2030 in Mercosur countries.

OBJECTIVES: The aims of this article were to analyse the burden of NCDs and their RFs in the Mercosur countries between 1990 and 2019 and to project mortality trends for 2030. STUDY DESIGN: Epidemiological study of time series. METHODS: The present study used data from the Global Burden of Disease study. The absolute number of deaths, mortality rates, disability-adjusted life years, years of life lost, years lived with disability and the burden of premature mortality by NCD attributable to the RFs were evaluated. Projections were made up to 2030. Age-standardised rates were used to draw comparisons by years and by countries. The analysis was conducted using the RStudio software. RESULTS: Between 1990 and 2019, a decrease was found in the premature mortality rates caused by NCDs in all the countries, except for Paraguay, which remained stable. When analysing premature mortality rates due to NCDs up to 2030, it was predicted that none of the countries would achieve the sustainable development goal of a one-third reduction in premature mortality by NCDs. Regarding the impacts of the RFs for NCDs, smoking, dietary risks, high blood pressure (BP) and high body mass index (BMI) were the main risks attributable to premature deaths due to NCDs. CONCLUSIONS: The results showed that mortality rates are declining in Mercosur countries; however, none of the countries are predicted to achieve the sustainable development goal of a one-third reduction in mortality due to NCDs by 2030. In addition to access to adequate treatment, progress is required in public regulation actions to reduce RFs, such as smoking, dietary risks, high BP and high BMI.

Cardiovascular mortality in Brazil during the COVID-19 pandemic: a comparison between underlying and multiple causes of death.

OBJECTIVES: The COVID-19 pandemic has differentially impacted cardiovascular disease (CVD) mortality worldwide. Causes of death misclassification may be one of the reasons. We evaluated the impact of the pandemic on CVD mortality in Brazil, comparing underlying causes (UCs) and multiple causes (MCs) of death. STUDY DESIGN: Ecological time-series study. METHODS: An ecological, time-series study was conducted analysing age-standardised death rates for CVD, from epidemiological week (EW) 10/2020 to 39/2021, using data from the Mortality Information System, Brazil. CVD was defined using the International Classification of Diseases (ICD-10) coding, if reported as UC or MC of death. Observed and expected data (mean for the same EW, 2017-2019) were compared. Risk ratios (RiRs) were analysed, and 95% confidence intervals (CIs) were calculated. RESULTS: Age-standardised mortality rate for CVD as UC of death was 165.8 (95%CI: 165.4-166.3) per 100,000 inhabitants, similar to what was expected (165.6/100,000, 95%CI: 165.2-166.1, RiR = 1.00). There was increased out-of-hospital mortality (RiR = 1.18; 95%CI: 1.17-1.19) and deaths of ill-defined causes (RiR = 1.43; 95%CI: 1.42-1.44). The increase in out-of-hospital deaths was more pronounced in the North (RiR = 1.33; 95%CI 1.30-1.36) region, with a less resilient health system. Conversely, as MCs of death, there was a 10% increase in CVD mortality (observed: 243.2 [95%CI: 242.7-243.7], expected: 221.6 [95%CI: 221.1-222.1] per 100,000). An increase also occurred in the North and Central West regions (RiR = 1.16; 95%CI: 1.15-1.18), among men (RiR = 1.11; 95%CI: 1.11-1.12) and individuals aged ≥60 years (RiR = 1.11; 95%CI: 1.10-1.11). CONCLUSIONS: During the pandemic, mortality rates for CVD as MCs of death increased in Brazil, whereas as UC mortality rates did not change. Higher out-of-hospital mortality, misclassification, and competing causes of death may explain this pattern.

Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicenter randomized Phase II non-inferiority clinical trial.

BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.

Natural vertical infection by dengue virus serotype 4, Zika virus and Mayaro virus in Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus.

Vertical transmission to progeny ensures the maintenance of arboviruses in their natural vectors. This mechanism is largely reported for dengue virus (DENV) and yellow fever virus (YFV). Few studies have addressed this mechanism for Zika virus (ZIKV), Mayaro virus (MAYV) and other arboviruses. The present study investigated the natural infection rate by arboviruses in 4490 Aedes (Stegomyia) aegypti and 296 Aedes (Stegomyia) albopictus (Diptera: Culicidae) reared from eggs collected with ovitraps in Cuiabá, Mato Grosso State, from February to July, 2017. After viral RNA extraction and reverse transcriptase-polymerase chain reaction protocols for 10 flaviviruses and five alphaviruses, nucleotide sequencing and three passages in C6/36 cells, eight pools of Ae. aegypti positive for DENV-4 genotype II, seven for ZIKV Asian genotype and two for MAYV genotype L were found. In addition, two Ae. albopictus pools were positive for DENV-4 genotype II and two were positive for ZIKV Asian genotype. Infection was confirmed by viral isolation in all positive pools for DENV-4 and for MAYV and in eight of nine for ZIKV. This mechanism may contribute to the spread of arboviruses during epidemics and also to their maintenance in natural vectors during interepidemic periods.

Incidence of cardiovascular risk factors in female patients with systemic lupus erythematosus: a 3-year follow-up cohort.

Objectives To evaluate the incidence and variability of traditional coronary artery disease (CAD) risk factors in a cohort of lupus patients and to investigate if prednisone use predicts an increase in the number of risk factors. Methods A total of 151 women, 37.8 ± 11.1 (mean ± SD) years old at baseline, were reevaluated after a median period of 39 (interquartile range 36.5-42.0) months. The cumulative incidence of traditional risk factors, the incidence rate (with 95% confidence interval) of hypertension, diabetes, dyslipidemia and hypertriglyceridemia, and the frequency of the risk factors' disappearance were calculated. Metabolic syndrome (MetS) and Framingham risk score (FRS) were computed. Logistic regression was used to investigate if maximum or cumulative prednisone dose used during follow-up predicted an increase in the cardiometabolic risk factors' number. Results The cumulative incidence of risk factors varied from 39.1% (abdominal obesity) to zero (smoking), and the incidence rate varied from 133.2 (87.8-178.6) per 1000 person-years (dyslipidemia) to 10.4 (1.3-19.5) per 1000 person-years (diabetes). The cumulative incidence for MetS was 18.8%, and 11.7% of 143 patients with low FRS at baseline (T1) were classified in the high-risk category at the end of the study (T2). Dyslipidemia was the most variable risk factor, with 43.5% disappearance at T2. The maximum prednisone dose used during follow-up was borderline ( p = 0.050) for prediction of an increase in the number of cardiometabolic risk factors in an adjusted model for antimalarial use, modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and age. Conclusion The authors described high incidence and variability of CAD risk factors in female lupus patients, with higher prednisone dose being borderline for an increase in the number of cardiometabolic risk factors.

Relationship between heart rate variability and subclinical thyroid disorders of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44-56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (ß: -0.070; 95% confidence interval (95%CI): -0.014 to -0.009) and low-frequency (LF) (ß: -0.242, 95%CI: -0.426 to -0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.

Relationship between heart rate variability and subclinical thyroid disorders of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44-56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (β: -0.070; 95% confidence interval (95%CI): -0.014 to -0.009) and low-frequency (LF) (β: -0.242, 95%CI: -0.426 to -0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.

The Effects of Weight and Waist Change on the Risk of Long-Term Mortality in Older Adults- The Bambuí (Brazil) Cohort Study of Aging.

OBJECTIVE: We aimed to investigate the risk of long-term mortality associated with weight and waist circumference (WC) change among older adults, particularly the overweight and obese ones. DESIGN: Cohort Study. SETTING: The Bambuí (Brazil) Cohort Study of Aging. PARTICIPANTS: Community-dwelling elderly (n=1138). MEASUREMENTS: Weight and WC were reassessed three years after baseline. Mortality risk associated with a 5% weight/WC loss and gain was compared to that of weight/WC stability by Cox models adjusted for clinical, behavioral and social known risk factors for death (age, gender, BMI, smoking, diabetes, total cholesterol, hypertension, Chagas disease, major electrocardiographic changes, physical activity, B-type natriuretic peptide, C-reactive protein, creatinine, education and household income). RESULTS: Female sex was predominant (718; 63.1%). Mean age was 68 (6.7) years. Weight stability (696; 61.1%) was more common than weight loss (251; 22.1%) or gain (191; 16.8%). WC remained stable in 422 (37.3%), decreased in 418 (37.0%) and increased in 291 (25.7%) participants. There were 334 (29.3%) deaths over a median follow-up time of 8.0 (6.4-8.0) years from weight/WC reassessment. Weight loss (HR 1.69; 95% CI 1.30-2.21) and gain (HR 1.37; 95% CI 1.01-1.85) were associated with increased mortality, except in those who were physically active in which weight gain was associated with decreased mortality. Results were similar for participants who were overweight/obese or with abdominal obesity at baseline (HR 1.41; 95%CI 1.02-1.97 and HR 2.01; 95%CI 1.29-3.12, for weight loss and gain, respectively). WC change was not significantly associated with mortality. CONCLUSION: Although weight loss has been recommended for adults with excessive weight regardless of age, weight change might be detrimental in older adults. Rather than weight loss, clinical interventions should target healthy lifestyle behaviors that contribute to weight stability, particularly physical activity in overweight and obese older adults.

Adipokines, tumor necrosis factor and its receptors in female patients with systemic lupus erythematosus.

OBJECTIVES: To analyze the association of adipokines and tumor necrosis factor α (TNFα) and its receptors with characteristics of systemic lupus erythematosus (SLE) and to investigate the correlation between adipokines and the TNF system. METHODS: One hundred and thirty-six SLE women, aged ≥18 years old, were assessed. TNFα, soluble TNFα receptors 1 (sTNFR1) and 2 (sTNFR2) and adipokines were analyzed by ELISA kits. RESULTS: The median (IQR) of age was 41.5 (33.0-49.7) years old and of disease duration 11.3 (7.8-15.8) years. The median (IQR) of disease activity was 0 (0-4) and of damage index was 2 (1-3). Higher levels of sTNFR1 and sTNFR2 were associated with nephritis (p < 0.001 for both), and sTNFR1 (p = 0.025) and TNFα (p = 0.014) were positively associated with arthritis. Higher sTNFR1 levels were found in participants that were not using antimalarial drugs (p = 0.04). Independent correlation was found between sTNFR1 (ß = 0.253; p = 0.003) and sTNFR2 (ß = 0.297; p < 0.001) levels and disease activity and damage index (sTNFR1: ß = 0.367; p < 0.001; sTNFR2: ß = 0.335; p < 0.001). Higher adiponectin levels were independently associated with nephritis (p = 0.009) and antimalarial drugs use (p = 0.015). There was a positive correlation between leptin and sTNFR2 levels (p = 0.002) and between resistin levels and sTNFR1 (p < 0.001) and sTNFR2 (p < 0.001). CONCLUSION: The correlation between adipokines and TNF system allows a better understanding of the role of adipokines in the inflammatory response in SLE patients.

Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease.

BACKGROUND: Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups. METHODS: This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) who were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy patients (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS. RESULTS: A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-γ, IL-6, IL-10 and TNF-α and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be the most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status. CONCLUSIONS: Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments.

Human Mesenchymal Stromal Cells Transplantation May Enhance or Inhibit 4T1 Murine Breast Adenocarcinoma through Different Approaches.

The use of Mesenchymal Stromal Cells (MSCs) aiming to treat cancer has shown very contradictory results. In an attempt to clarify the contradictory results reported in the literature and the possible role of human fallopian tube Mesenchymal Stromal Cells (htMSCs) against breast cancer, the aim of this study was to evaluate the clinical effect of htMSCs in murine mammary adenocarcinoma using two different approaches: (1) coinjections of htMSCs and 4T1 murine tumor cell lineage and (2) injections of htMSCs in mice at the initial stage of mammary adenocarcinoma development. Coinjected animals had a more severe course of the disease and a reduced survival, while tumor-bearing animals treated with 2 intraperitoneal injections of 10(6) htMSCs showed significantly reduced tumor growth and increased lifespan as compared with control animals. Coculture of htMSCs and 4T1 tumor cells revealed an increase in IL-8 and MCP-1 and decreased VEGF production. For the first time, we show that MSCs isolated from a single source and donor when injected in the same animal model and tumor can lead to opposite results depending on the experimental protocol. Also, our results demonstrated that htMSCs can have an inhibitory effect on the development of murine mammary adenocarcinoma.

Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.