Persistent predators: Zooarchaeological evidence for specialized horse hunting at Schöningen 13II-4.

The Schöningen 13II-4 site is a marvel of Paleolithic archaeology. With the extraordinary preservation of complete wooden spears and butchered large mammal bones dating from the Middle Pleistocene, Schöningen maintains a prominent position in the halls of human origins worldwide. Here, we present the first analysis of the complete large mammal faunal assemblage from Schöningen 13II-4, drawing on multiple lines of zooarchaeological and taphonomic evidence to expose the full spectrum of hominin activities at the site-before, during, and after the hunt. Horse (Equus mosbachensis) remains dominate the assemblage and suggest a recurrent ambush hunting strategy along the margins of the Schöningen paleo-lake. In this regard, Schöningen 13II-4 provides the first undisputed evidence for hunting of a single prey species that can be studied from an in situ, open-air context. The Schöningen hominins likely relied on cooperative hunting strategy to target horse family groups, to the near exclusion of bachelor herds. Horse kills occurred during all seasons, implying a year-round presence of hominins on the Schöningen landscape. All portions of prey skeletons are represented in the assemblage, many complete and in semiarticulation, with little transport of skeletal parts away from the site. Butchery marks are abundant, and adult carcasses were processed more thoroughly than were juveniles. Numerous complete, unmodified bones indicated that lean meat and marrow were not always so highly prized, especially in events involving multiple kills when fat and animal hides may have received greater attention. The behaviors displayed at Schöningen continue to challenge our perceptions and models of past hominin lifeways, further cementing Schöningen's standing as the archetype for understanding hunting adaptations during the European Middle Pleistocene.

How do we classify organ involvement in Chagas disease? A systematic review of organ involvement since 1909, Highlighting the urgent need for a universal classification system in Chronic Chagas disease.

Chagas disease (CD) is recognized as one of the 20 neglected tropical diseases by the World Health Organization (WHO), posing a significant global health challenge. The objective of this work was to conduct a systematic methodology review to explore the different classifications used to describe the presence and degree of organ involvement in patients with CD since the disease's description in 1909. We searched relevant electronic medical databases from their inception dates to July 2023. We also delved into historical variations and revisions of each classification, the necessary diagnostic methods, their prognostic value, and their uptake. Our study underscores the conspicuous absence of a universally accepted CD classification system for cardiac and digestive involvement, both in the context of clinical trials and within current clinical guidelines. This endeavour will facilitate cross-population comparisons if clinical manifestations and complementary test results are available for each patient, constituting a pivotal stride toward identifying precise prognoses and establishing a minimum data set requisite for a fitting CD classification, tailored to the test availability in both endemic and non-endemic regions.

A standardized clinical database for research in Chagas disease: The NHEPACHA network.

The NHEPACHA Iberoamerican Network, founded on the initiative of a group of researchers from Latin American countries and Spain, aims to establish a research framework for Chagas disease that encompasses diagnosis and treatment. For this purpose, the network has created a questionnaire to gather relevant data on epidemiological, clinical, diagnostic, and therapeutic aspects of the disease. This questionnaire was developed based on a consensus of expert members of the network, with the intention of collecting high-quality standardized data, which can be used interchangeably by the different research centers that make up the NHEPACHA network. Furthermore, the network intends to offer a clinical protocol that can be embraced by other researchers, facilitating comparability among published studies, as well as the development of therapeutic response and progression markers.

A guide for the generation of repositories of clinical samples for research on Chagas disease.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.

Physical activity levels during COVID-19 pandemic and its associated factors in patients with Chagas disease.

Background: A better understanding of the consequences of the Coronavirus Disease 2019 (COVID-19) pandemic on lifestyle of patients with Chagas disease (ChD) is of paramount importance to facilitate the implementation of intervention strategies tailored to this specific population. Objective: The present study aimed to evaluate the level of physical activity (PA) in Chagas disease (ChD) patients during the Coronavirus Disease 2019 (COVID-19) pandemic and its main associated factors. Methods: This is a cross-sectional study with 187 patients of both sexes, aged ≥18 years, followed in a national infectious disease center (Rio de Janeiro, Brazil). The level of PA was determined by the International Physical Activity Questionnaire short version and expressed in terms of total volume of physical activity (PA) (MET-minutes per week). Individuals were classified as physically active following the 2020 World Health Organization PA guideline. The exposure variables were age, sex, race, marital status, schooling, income per capita, number of rooms per domicile, number of residents per domicile, body mass index, clinical form of ChD, COVID-19 antibodies, comorbidities, self-reported anxiety, self-reported depression, self-reported fear, and self-reported sadness. The association between the exposure variables with total PA (as a continuous variable) was determined using univariate and multivariate linear regression models. Results: Mean age was 61.1 ± 11.6 years. Most (62%) were women and self-declared their race as mixed (50.8%). The percentage of physically active individuals according to was 52%. The variables independently associated with total PA levels were non-white race (Exp ß = 1.39; 95% CI 1.02 to 1.90), dyslipidemia (Exp ß = 0.73; 95% CI 0.56 to 0.95) and self-reported depression during quarantine (Exp ß = 0.71; 95% CI 0.52 to 0.96). Conclusion: Non-white race was positively associated with total levels of PA, while dyslipidemia, and self-reported depression during quarantine were negatively associated with total levels of PA. The identification of associated factors can facilitate the development of tailored strategies to increase PA levels ChD patients.

Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models.

Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

Untargeted Metabolomics Analysis Based on LC-QTOF-MS to Investigate the Phenolic Composition of Red and White Wines Elaborated from Sonicated Grapes.

Ultrasounds are considered an emerging technology in the wine industry. Concretely, in 2019, the International Organization of Vine and Wine (OIV) officially approved their use for the treatment of crushed grapes to increase the level of phenolic compound extraction. The main objective of this study was to validate an untargeted metabolomics approach as an analytical tool for identifying novel markers associated with sonication. To do so, the influence of a sonication treatment on the metabolic profile was studied in four typically commercial varietal wines, i.e., two red wines from 'Syrah' and 'Cabernet Sauvignon' grapes and two white wines from 'Macabeo' and 'Airén' grapes. A robust classification and prediction model was created employing supervised techniques such as partial least-squares discriminant analysis (PLS-DA). The findings indicated that the grapes subjected to high-power ultrasound conditions experienced cell wall disruption due to the cavitation phenomenon, resulting in significant changes in various phenolic compounds (including hydroxycinnamic acids and flavonoids) present in these wines compared to wines from non-sonicated grapes. Additionally, new metabolites were tentatively identified through untargeted metabolomics techniques. This study represents the successful application of the untargeted metabolomics approach employing a UHPLC-QTOF system to discern how grape sonication affects bioactive secondary metabolites in wines.

Emicizumab for acquired hemophilia A: Report of two cases and dosing strategies.

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by autoantibodies against FVIII. Severe AHA is life-threatening. Currently, licensed hemostatic agents for the treatment of severe AHA have short half-lives and require intravenous administration, leading to a need for hospitalization, higher costs, and negative effects on quality of life. We present two cases of severe AHA with high inhibitor titers where emicizumab was safely and effectively used with intensive immunosuppression. These reports suggest in vivo efficacy even in high inhibitor environments. The optimal dosing regimen (accelerated vs. standard loading, maintenance frequency) is unknown and we discuss the current approaches.

Chagas heart disease is associated with decreased physical activity levels: A cross-sectional analysis.

Background: Studies evaluating physical activity (PA) levels in individuals with Chagas disease (CD) are still scarce. The present study aimed to evaluate PA levels in CD individuals and examine their association with Chagas heart disease (ChHD). Methods: We included patients with CD regularly followed in a reference center for treatment of infectious diseases. PA levels were assessed using the short version of the International Physical Activity Questionnaire (IPAQ). ChHD was determined following the Brazilian Consensus on Chagas Disease. The association between ChHD and levels of PA (total, walking, moderate, and vigorous) as a continuous variable was fitted using generalized linear models. Logistic regression models were fitted to evaluate the association between ChHD and meeting WHO's PA recommendations. Results: Among the 361 participants included in the analysis (60.7 ± 10.7 years; 56.2 % women), 58.1 % (n = 210) complied with the WHO's PA recommendations. After adjustments for potential confounders, regression analyses revealed that ChHD without heart failure was significantly associated with reduced vigorous PA (Exp ß 0.32 95 % CI 0.10 to 0.98). ChHD with heart failure had significantly lower levels of total (Exp ß 0.61 95 % CI 0.44 to 0.84) and moderate (Exp ß 0.59 95 % CI 0.39 to 0.89) PA. ChHD with heart failure had a lower odd of meeting the PA recommendation in comparison to those with no cardiac involvement (OR 0.48 95 % CI 0.24 to 0.97). Conclusions: We found low levels of PA among individuals with CD. Presence of ChHD (mainly with HF) was associated with decreased levels of PA.

Association between Diet Quality and Risk of Type 2 Diabetes Mellitus in Patients with Coronary Heart Disease: Findings from the CORDIOPREV Study.

The incidence of type 2 diabetes mellitus (T2DM) is growing in Western countries. Nutritional interventions that promote high-quality dietary patterns could help reverse this trend. We aimed to evaluate whether changes in Nutrient-Rich Food Index 9.3 (NRF9.3) were related to the risk of developing T2DM in patients with coronary heart disease (CHD). The study was carried out in the context of two healthy dietary interventions (a Mediterranean and a low-fat diet). For this purpose, we evaluated all the patients in the CORDIOPREV study without T2DM at baseline. Data were obtained during the first 5 years of dietary intervention. The score was calculated using the Food Frequency Questionnaires at baseline and after 1 year of intervention. After 5 years of follow-up, 106 patients developed T2DM (incident-T2DM), while 316 subjects did not (non-T2DM). Total NRF9.3 score and changes during the first year of intervention were compared between incident-T2DM and non-T2DM. Incident-T2DM showed less improvement in NRF9.3 than non-T2DM (p = 0.010). In the multi-adjusted Cox proportional hazard study, patients with greater improvement in NRF9.3 had over 50% less risk of developing T2DM compared with the lowest tertile (HR 2.10, 95%, CI = 1.12-3.56). In conclusion, improved diet quality in terms of nutrient density after the dietary intervention was associated with a lower risk of T2DM in patients with CHD.

Effect of an exercise-based cardiac rehabilitation program on quality of life of patients with chronic Chagas cardiomyopathy: results from the PEACH randomized clinical trial.

To investigate the effect of an exercise-based cardiac rehabilitation program on the quality of life (QoL) of patients with chronic Chagas cardiomyopathy (CCC). PEACH study was a single-center, superiority randomized clinical trial of exercise training versus no exercise (control). The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction < 45%, without or with HF symptoms (CCC stages B2 or C, respectively). QoL was assessed at baseline, after three months, and at the end of six months of follow-up using the SF-36 questionnaire. Patients randomized for the exercise group (n = 15) performed exercise training (aerobic, strength and stretching exercises) for 60 min, three times a week, during six months. Patients in the control group (n = 15) were not provided with a formal exercise prescription. Both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of exercise training on QoL, considering the interaction term (group × time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using linear mixed models. Models were fitted adjusting for each respective baseline QoL value. There were significant improvements in physical functioning (ß = + 10.7; p = 0.02), role limitations due to physical problems (ß = + 25.0; p = 0.01), and social functioning (ß = + 19.2; p < 0.01) scales during the first three months in the exercise compared to the control group. No significant differences were observed between groups after six months. Exercise-based cardiac rehabilitation provided short-term improvements in the physical and mental aspects of QoL of patients with CCC.Trial registration: ClinicalTrials.gov Identifier: NCT02517632; August 7, 2015.

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

Interesting case from Argentina: Kidney transplant recipient with skin lesions-A Latin American perspective.

This is a case of a kidney transplant recipient who presented with skin lesions, low-grade fevers, and pancytopenia 2 months after his transplant.

Dietary antioxidant intake reduces carotid intima-media thickness in coronary heart disease patients: From the CORDIOPREV study.

BACKGROUND: Atherosclerosis is the leading underlying cause of coronary heart disease (CHD). In patients with CHD, intima-media thickness of common carotid arteries (IMT-CC) is a reliable, validated, and non-invasive marker of the progression of atherosclerosis. Dietary intervention may affect IMT-CC evolution through different pathways. There is a lack of clinical trials evaluating the effect of total dietary antioxidant content of diets on IMT-CC, especially in patients with CHD. OBJECTIVE: We evaluated the correlation between the diet's total antioxidant content and the changes in IMT-CC produced after 5 years of dietary intervention following two healthy diet models (Mediterranean diet and low-fat diet). We also evaluated whether the diet's total antioxidant content was related to the total redox capacity of the participants. METHODS: From the total participants of the CORDIOPREV study (clinical trial register NCT00924937), 805 participants completed the IMT-CC measurement and the dietary antioxidant evaluation at baseline and after 5 years of dietary intervention. IMT-CC was carried out by ultrasound and the dietary antioxidant evaluation was performed by the Dietary Antioxidant Index (DAI). Additionally, direct redox balance was evaluated in a subset of population by the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) by colorimetric assay. RESULTS: We observed an inverse correlation between evolution of DAI and IMT-CC after 5-years of dietary intervention. The mean of the DAI index augmented in the Mediterranean Diet group, whereas it decreased in the Low-fat group. DAI was correlated to the GSH/GSSG ratio, supporting DAI as an adequate estimator of diet's antioxidant content. When looking for individual components of the DAI that were associated to the changes in IMT-CC, an inverse correlation was found for carotenoids, vitamin E, vitamin C, and zinc and the IMT-CC. CONCLUSIONS: Our study indicates that, after five years of dietary intervention, changes in DAI inversely correlate with changes in IMT-CC in patients with CHD. Overall effect of Mediterranean diet resulted in an increase of DAI, conversely to low-fat. Specific elements included in the DAI index were inversely correlated with IMT-CC.

Drug screening and development cascade for Chagas disease: an update of in vitro and in vivo experimental models

Chagas disease is a tropical neglected disease that affects millions of people worldwide, still demanding a more effective and safer therapy, especially in its chronic phase which lacks a treatment that promotes substantial parasitological cure. The technical note of Romanha and collaborators published in 2010 aimed establish a guideline with the set of minimum criteria and decision gates for the development of new agents against Trypanosoma cruzi with the focus on developing new antichagasic drugs. In this sense, the present review aims to update this technical note, bringing the state of the art and new advances on this topic in recent years.

Inspiratory Muscle Strength in Chagas Cardiomyopathy: A Systematic Scoping Review.

The increase in inflammatory markers associated with persistent chronic fibrosing myocarditis, a characteristic of chronic Chagas disease, can result in a reduction in inspiratory muscle strength (IMS) in Chagas cardiomyopathy (CC). However, literature in this field is still scarce. This review aimed to map and summarize the evidence regarding IMS in patients with CC. The inclusion criteria included reports with adult participants with a CC diagnosis, with or without heart failure (HF). The core concept examined was the maximum inspiratory pressure evaluated in the untrained and trained groups in the pre-training period. The context was open, including but not limited to hospitals and health centers. Two authors independently identified eligible studies and extracted the data. Descriptive synthesis was used as the primary strategy for analyzing the results. Nine studies (five clinical trials, three cross-sectional, and one cohort) were included. The CC classification differed among the studies, with no mention of HF in five and no CC staging specification in six. IMS was assessed using a manovacuometer, and only six studies analyzed and interpreted the data concerning the predicted values. The CC population with HF appeared to have impaired IMS. All studies involved only Brazilian volunteers. In conclusion, randomized clinical trials evaluating IMS and the effects of inspiratory muscle training need to be conducted to better understand the prevalence and risk of inspiratory muscle weakness in the CC population, as well as the effects of training. Such studies should be conducted at different stages of CC in different populations and countries.

Predictors of Trypanosoma cruzi PCR positivity in patients with chronic Chagas disease.

BACKGROUND: A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD). OBJECTIVES: To study the association of clinical, electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD. METHODS: This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant. FINDINGS: Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 [95% confidence interval (CI) 0.30-0.93]; p = 0.03}, right bundle branch block [OR 1.78 (95% CI 1.09-2.89); p = 0.02], and history of trypanocidal treatment [OR 0.13 (95% CI 0.04-0.38); p = 0.0002]. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR. MAIN CONCLUSIONS: Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.

Exploring the Historical Background and Clinical Implications of Electrocardiogram in the Context of Chagas Disease Research.

Chagas disease (CD) remains one of the most significant endemic diseases in Latin America. Approximately 30% of individuals with CD develop the cardiac form, the main determinant of morbidity and mortality, which is characterized by typical electrocardiogram (ECG) changes caused by chronic chagasic cardiopathy (CCC). This review accentuates to how crucial it is for research teams and reference centers that treat patients with CD to standardize ECG in CCC. This was a non-systematic review of the literature. ECG is the most widely used examination in the diagnosis and evaluation of CCC, and it is also employed in epidemiological surveys, risk stratification for cardiovascular events and death, and monitoring the clinical progression of the disease. Carlos Chagas and Eurico Villela published the first work addressing CCC in 1922. Other works followed, including the study by Evandro Chagas' which was the first to perform ECG in CD, culminating in Francisco Laranja's seminal work in 1956. Since the 1980s, standardizations and ECG reading codes for CD have been established. This standardization aimed to code complex arrhythmias and characteristic ventricular conduction disorders and standardize ECG readings for clinical and epidemiological studies in CD. Nearly all existing electrocardiographic abnormalities can be found in CD, with a predominance of abnormalities in the formation and conduction of cardiac stimuli. The complex and heterogeneous substrate of CD with varied electrocardiographic manifestations poses a significant challenge when comparing studies involving patients with CCC, emphasizing the need for ECG standardization in CD.