Simuladores en odontología y la formación de habilidades clínicas: un diálogo permanente / Simulators in dentistry and clinical skill training: a permanent dialogue

El avance tecnológico evidencia el gran desarrollo de los simuladores en la educación odontológica. Con el transcurrir de los años, el uso de simuladores como herramienta educativa para el logro de competencias en estudiantes de preclínica ha tenido una creciente incorporación en los planes de estudio. Por ello, el presente artículo tiene como objetivo revisar la historia de los simuladores en la educación odontológica e identificar las habilidades desarrolladas con el uso de simuladores en estudiantes universitarios de pregrado a nivel mundial. Al respecto, se realizó una búsqueda de artículos científicos indexados en bases de datos como Medline, Scopus, LILACS, SciELO, Google académico y Redalyc; se desarrolló la búsqueda bibliográfica hasta enero 2021 y se consideró las siguientes palabras clave: simulación, educación en odontología, estudiantes de odontología, educación basada en competencias. En los resultados se identificó cuatro etapas relevantes como una manera interactiva para explicar la historia de la simulación en odontología, cada una de estas etapas estuvo determinada por el impacto tecnológico de cada época, la necesidad de entrenamiento de los estudiantes y la integración en los planes de estudio. Con esta revisión, se concluyó que existe evidencia que el uso de simuladores durante la formación preclínica universitaria desarrolla habilidades en el estudiante de odontología, y que estas habilidades clínicas están relacionadas con el tipo de simulador usado durante su formación de pregrado.

Technological advance shows the great development of simulators in dental education. The use of simulators as an educational tool to achieve competencies in preclinical students has been increasingly incorporated into the study plans. Therefore, this article aims to review the history of simulators in dental education and identify the skills developed with the use of simulators in undergraduate university students worldwide. In this regard, a search was carried out for scientific articles indexed in databases such as Medline, Scopus, LILACS, SciELO, Academic Google and Redalyc; the bibliographic search was carried out until January 2021 and the following keywords were considered: simulation, dental education, dentistry students, competency-based education. In the results, four relevant stages were identified as an interactive way to explain the history of simulation in dentistry, each of these stages was determined due to the technological impact of each era, the need for training of the students and the integration into the study plans. It was concluded that there is evidence that the use of simulators during preclinical university training develops skills in dental students, these are related to the type of simulator used during their undergraduate training.

Extinction of herbivorous dinosaurs linked to Early Jurassic global warming event.

Sauropods, the giant long-necked dinosaurs, became the dominant group of large herbivores in terrestrial ecosystems after multiple related lineages became extinct towards the end of the Early Jurassic (190-174 Ma). The causes and precise timing of this key faunal change, as well as the origin of eusauropods (true sauropods), have remained ambiguous mainly due to the scarce dinosaurian fossil record of this time. The terrestrial sedimentary successions of the Cañadón Asfalto Basin in central Patagonia (Argentina) document this critical interval of dinosaur evolution. Here, we report a new dinosaur with a nearly complete skull that is the oldest eusauropod known to date and provide high-precision U-Pb geochronology that constrains in time the rise of eusauropods in Patagonia. We show that eusauropod dominance was established after a massive magmatic event impacting southern Gondwana (180-184 Ma) and coincided with severe perturbations to the climate and a drastic decrease in the floral diversity characterized by the rise of conifers with small scaly leaves. Floral and faunal records from other regions suggest these were global changes that impacted the terrestrial ecosystems during the Toarcian warming event and formed part of a second-order mass extinction event.

Evaluation of the biocompatibility of a PVA/SA scaffold with a human gingival fibroblast (HGF) by using electrochemical impedance spectroscopy.

The biocompatibility of human gingival fibroblasts (HGF) was evaluated in different concentrations of poly(vinyl alcohol) and sodium alginate (PVA/SA) nanofibres (3.5 wt% 4 wt% and 5 wt%). The PVA/SA nanofibres were deposited on the surface of an electrode microchip by using the electrospinning technique. Electrochemical impedance spectroscopy (EIS) was applied to measure the dielectric properties of each system. In order to provide a detailed analysis as well as a right physical interpretation of the EIS results, the data was fitted with an electric equivalent circuit based on the EIS and the microscopic assessments. The results registered three different time constants (TCs) of the PVA/SA scaffold which indicated different layers at different depths of the scaffold. The TCs changed their dielectric properties depending on the PVA/SA concentration. The 4 wt% system showed the highest biocompatibility properties, given that its resistance and electrochemical capacitance show the formation of a mature-stage cell interaction of HGF. The EIS data offers an exhaustive analysis of the biological activity of the cell response in real time to determine its biocompatibility features. Fluorescence analysis demonstrated a heterogeneous growth of the HGF on the PVA/SA scaffold surface.

Inequalities in health? An update on the effect of social deprivation for patients with breast cancer in South East Wales.

BACKGROUND: Breast cancer, historically a disease of more affluent women, has increased in incidence for women from areas of greater social deprivation, yet prognosis is worse for these women. This study identifies differences in presentation, treatment and prognostic factors between the socioeconomic groups. METHODS: Patient data obtained from the prospectively maintained Welsh national Cancer Network Information System Cymru, for an 11-year period, were categorised according to Welsh Index of Multiple Deprivation quintiles. Quintiles were compared for differences in variables relating to patient characteristics, detection of cancer, tumour biology and treatment. RESULTS: 1570 patients were included. Analysis showed that in the more socially deprived quintiles, there are proportionally fewer women being diagnosed through the NHS breast cancer screening programme and as a consequence greater numbers of women from poorer areas being diagnosed outwith the screening age parameters. Screen detection is strongly associated with better prognosis in terms of Nottingham Prognostic Index. Similarly, increasing levels of social deprivation are associated with higher incidence of oestrogen receptor negative and triple negative tumours, both features associated with a shorter disease free and overall survival. Other variables of tumour biology, rates and type of surgical and adjuvant treatment were similar across social deprivation quintiles. CONCLUSION: There is a trend of reduced early detection of breast cancer in South East Wales in those patients living in areas of higher social deprivation. Given that there is equity in access to treatment within NHS, which is free for patients at the point of care, further study is warranted to address this existing disparity. Population cancer surveillance will need to inform both public health and NHS service responses, to continue to achieve improvements. Health trends may yet alter depending on current and future shifts in governmental health policy.

Comparison of liposomal drug formulations for transdermal iontophoretic drug delivery.

This study was aimed to evaluate the in vitro transdermal direct/pulsed current iontophoretic delivery of an amphiphilic model compound from various lipid vesicle-encapsulated formulations compared to free-drug formulation. Conventional, pegylated, ultradeformable liposomes (transfersomes) and ethosomes loaded with a negatively charged drug diclofenac sodium (DS) were prepared and characterized. All the liposomes possessed an average size of ≈100-150nm and negative zeta potential. No changes in colloidal stability were detected after 8h incubation of any vesicle formulation under constant or pulsed iontophoretic current. DS was released from all the liposome formulations with a similar, limited rate (≈50% in 24h), leading therefore to significantly lower transdermal fluxes across full-thickness porcine skin compared to the respective free drug formulation. From the tested lipid vesicle formulations, the transfersomes resulted in the highest passive flux and the ethosomes in the highest iontophoretic flux under direct constant current treatment. Higher negative surface charge of the vesicle led to better transport efficiency due to the higher mobility of the drug carrier under electric field. Pulsed current iontophoresis had no advantage over constant current treatment in combination with any type of lipid vesicular nanocarriers, in contrast to what has been described earlier with drug-loaded polymeric nanocarriers.

Predicting patterns of long-term adaptation and extinction with population genetics.

Population genetics struggles to model extinction; standard models track the relative rather than absolute fitness of genotypes, while the exceptions describe only the short-term transition from imminent doom to evolutionary rescue. But extinction can result from failure to adapt not only to catastrophes, but also to a backlog of environmental challenges. We model long-term adaptation to long series of small challenges, where fitter populations reach higher population sizes. The population's long-term fitness dynamic is well approximated by a simple stochastic Markov chain model. Long-term persistence occurs when the rate of adaptation exceeds the rate of environmental deterioration for some genotypes. Long-term persistence times are consistent with typical fossil species persistence times of several million years. Immediately preceding extinction, fitness declines rapidly, appearing as though a catastrophe disrupted a stably established population, even though gradual evolutionary processes are responsible. New populations go through an establishment phase where, despite being demographically viable, their extinction risk is elevated. Should the population survive long enough, extinction risk later becomes constant over time.

Transdermal iontophoresis of flufenamic acid loaded PLGA nanoparticles.

The objective of this study was to test in vitro a drug delivery system that combines nanoencapsulation and iontophoresis for the transdermal delivery of lipophilic model drug using poly(lactic-co-glycolic acid) (PLGA) as the carrier polymer. Negatively charged fluorescent nanoparticles loaded with negatively charged flufenamic acid were prepared. The colloidal properties of the particles were stable under iontophoretic current (constant, pulsed and alternating) profiles and in contact with skin barrier. The release of the drug from the particles was not affected by iontophoresis and remained always limited (≈50%), leading to significantly lower transdermal fluxes across human epidermis and full thickness porcine skin compared to respective free drug formulation. From nanoparticles, pulsed current profile resulted in comparable or higher fluxes compared to constant current profile although fluorescence imaging was not able to confirm deeper distribution of nanoparticles in skin. Based on our results, there is no clear advantage with respect to drug permeation from nanoencapsulating flufenamic acid into PLGA nanoparticles compared to free drug formulation, either in passive or iontophoretic delivery regimens. However, pulsed current iontophoresis could be an effective alternative instead of traditional constant current iontophoresis to enhance transdermal permeation of drugs from nanoencapsulated formulations.

Carboxylated nanodiamonds inhibit γ-irradiation damage of human red blood cells.

Nanodiamonds when carboxylated (cNDs) act as reducing agents and hence could limit oxidative damage in biological systems. Gamma (γ)-irradiation of whole blood or its components is required in immunocompetent patients to prevent transfusion-associated graft versus host disease (TA-GVHD). However, γ-irradiation of blood also deoxygenates red blood cells (RBCs) and induces oxidative damage, including abnormalities in cellular membranes and hemolysis. Using atomic force microscopy (AFM) and Raman spectroscopy, we examined the effect of cNDs on γ-irradiation mediated deoxygenation and morphological damage of RBCs. γ-Radiation induced several morphological phenotypes, including stomatocytes, codocytes and echinocytes. While stomatocytes and codocytes are reversibly damaged RBCs, echinocytes are irreversibly damaged. AFM images show significantly fewer echinocytes among cND-treated γ-irradiated RBCs. The Raman spectra of γ-irradiated RBCs had more oxygenated hemoglobin patterns when cND-treated, resembling those of normal, non-irradiated RBCs, compared to the non-cND-treated RBCs. cND inhibited hemoglobin deoxygenation and morphological damage, possibly by neutralizing the free radicals generated during γ-irradiation. Thus cNDs have the therapeutic potential to preserve the quality of stored blood following γ-irradiation.

Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders.

BACKGROUND: Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy. However, recently developed super-resolution microscopes provide sufficient spatial resolution to effectively image platelet granules. When combined with automated image analysis, these methods provide a quantitative, unbiased, rapidly acquired dataset that can readily and reliably reveal differences in platelet granules between individuals. OBJECTIVE: To demonstrate the ability of structured illumination microscopy (SIM) to efficiently differentiate between healthy volunteers and three patients with Hermansky-Pudlak syndrome. METHODS: Blood samples were taken from three patients with Hermansky-Pudlak syndrome and seven controls. Patients 1-3 have gene defects in HPS1, HPS6 and HPS5, respectively; all controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets fixed, stained for CD63 and processed for analysis by immunofluorescence microscopy, using a custom-built SIM microscope. RESULTS: SIM can successfully resolve CD63-positive structures in fixed platelets. A determination of the number of CD63-positive structures per platelet allowed us to conclude that each patient was significantly different from all of the controls with 99% confidence. CONCLUSIONS: A super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers. CD63 is a useful marker for predicting Hermansky-Pudlak syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders.

Safety and efficacy of factor XI (FXI) concentrate use in patients with FXI deficiency: a single-centre experience of 19 years.

AIM: Factor XI (FXI) concentrate is a pooled human plasma-derived factor concentrate used as replacement therapy for patients with FXI deficiency, which provides a predictable response and consistent haemostatic cover in emergency or elective situations. It has previously been implicated in adverse events such as thrombosis and inhibitor formation, with rare case reports of fatal incidents. We sought to establish the incidence of such complications in a retrospective case series between 1994 and 2012 at the Haemophilia Comprehensive Care Centre at Royal Free Hospital, London, UK. METHODS: Patients who received FXI concentrate had their medical records reviewed to extract information and specific adverse events recorded such as failure of treatment with further bleeding, suspected viral transfusion transmitted infection (TTI), thrombosis or inhibitor formation. RESULTS: Eighty-six patients received 242 treatment episodes of FXI concentrate. Ninety percent of treatment episodes were covered with BPL FXI concentrate and 10% with LFB Hemoleven. Twelve (5%) adverse events were recorded, with eight (3.3%) of all treatment episodes were related to persistent bleeding postconcentrate infusion and there were 4 (1.7%) non-bleeding adverse events. No viral TTIs were identified. There were two recorded inhibitors, one thrombotic event (central retinal artery occlusion) and one transfusion reaction. No patient suffering an adverse event resulted in long-term morbidity. CONCLUSION: Our experience of FXI concentrate use demonstrates infrequent minor adverse events related to its administration and is a safe product to use.

Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international, retrospective, 10-year survey.

Sparse data are available on presentation and management of acute coronary syndromes (ACS), including unstable angina and non-ST- and ST-elevation myocardial infarction, among persons with haemophilia (PWH). The aim of this study was to determine demographics, bleeding disorder characteristics, cardiovascular risk factors (CRFs), interventions, haemostatic protocol, revascularization outcomes and complications among PWH with ACS. Members of an international consortium comprising >2000 adult PWH retrospectively completed case report forms for episodes of ACS in a >10-year follow-up period (2003-2013). Twenty ACS episodes occurred among 19 patients [rate, 0.8% (95% CI 0.4, 1.2)]. Seven patients (37%) were aged <50 years; 10 (53%) had ≥3 CRFs. In 5/20 episodes (25%), the initial ACS management protocol was altered because of the bleeding disorder. None of the eight patients with severe haemophilia underwent coronary artery bypass grafting (CABG), compared with 54.5% of patients with non-severe disease (P = 0.02). Revascularization with percutaneous coronary intervention (PCI) or CABG was rated successful in 13/13 cases, with no excessive bleeding during initial management. During chronic exposure to antiplatelet agents, secondary haemophilia prophylaxis was more prevalent in patients with severe haemophilia compared with non-severe haemophilia (85.7% vs. 30%, P = 0.05). No ACS-related deaths occurred during initial management, but one patient with severe haemophilia A died of undetermined cause 36 months after the ACS event while on aspirin therapy. ACS occurs even among relatively younger PWH, typically in association with multiple CRFs. Revascularization with PCI/CABG is feasible, and antiplatelet agents plus secondary prophylaxis appears to be well tolerated in selected PWH with ACS.

An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B.

BACKGROUND: Factor IX (FIX) is important in the coagulation cascade, being activated to FIXa on cleavage. Defects in the human F9 gene frequently lead to hemophilia B. OBJECTIVE: To assess 1113 unique F9 mutations corresponding to 3721 patient entries in a new and up-to-date interactive web database alongside the FIXa protein structure. METHODS: The mutations database was built using MySQL and structural analyses were based on a homology model for the human FIXa structure based on closely-related crystal structures. RESULTS: Mutations have been found in 336 (73%) out of 461 residues in FIX. There were 812 unique point mutations, 182 deletions, 54 polymorphisms, 39 insertions and 26 others that together comprise a total of 1113 unique variants. The 64 unique mild severity mutations in the mature protein with known circulating protein phenotypes include 15 (23%) quantitative type I mutations and 41 (64%) predominantly qualitative type II mutations. Inhibitors were described in 59 reports (1.6%) corresponding to 25 unique mutations. CONCLUSION: The interactive database provides insights into mechanisms of hemophilia B. Type II mutations are deduced to disrupt predominantly those structural regions involved with functional interactions. The interactive features of the database will assist in making judgments about patient management.

Above- and below-ground methane fluxes and methanotrophic activity in a landfill-cover soil.

Landfills are a major anthropogenic source of the greenhouse gas methane (CH(4)). However, much of the CH(4) produced during the anaerobic degradation of organic waste is consumed by methanotrophic microorganisms during passage through the landfill-cover soil. On a section of a closed landfill near Liestal, Switzerland, we performed experiments to compare CH(4) fluxes obtained by different methods at or above the cover-soil surface with below-ground fluxes, and to link methanotrophic activity to estimates of CH(4) ingress (loading) from the waste body at selected locations. Fluxes of CH(4) into or out of the cover soil were quantified by eddy-covariance and static flux-chamber measurements. In addition, CH(4) concentrations at the soil surface were monitored using a field-portable FID detector. Near-surface CH(4) fluxes and CH(4) loading were estimated from soil-gas concentration profiles in conjunction with radon measurements, and gas push-pull tests (GPPTs) were performed to quantify rates of microbial CH(4) oxidation. Eddy-covariance measurements yielded by far the largest and probably most representative estimates of overall CH(4) emissions from the test section (daily mean up to ∼91,500µmolm(-2)d(-1)), whereas flux-chamber measurements and CH(4) concentration profiles indicated that at the majority of locations the cover soil was a net sink for atmospheric CH(4) (uptake up to -380µmolm(-2)d(-1)) during the experimental period. Methane concentration profiles also indicated strong variability in CH(4) loading over short distances in the cover soil, while potential methanotrophic activity derived from GPPTs was high (v(max)∼13mmolL(-1)(soil air)h(-1)) at a location with substantial CH(4) loading. Our results provide a basis to assess spatial and temporal variability of CH(4) dynamics in the complex terrain of a landfill-cover soil.

The role of recombinant factor VIIa for obstetric block in women with severe factor XI deficiency.

Regional blocks like spinal, epidural and combined spinal epidural (CSE) are relatively contraindicated in individuals with bleeding disorders. Consequently pregnant women with severe factor XI (FXI) deficiency are often denied this option during labour and caesarean section. We describe three women with severe FXI deficiency in whom regional block was performed with low-dose recombinant factor VIIa (rFVIIa) for their operative procedures during delivery. All women achieved haemostasis and had uncomplicated regional block, delivery and surgical procedures. The point of care device--rotational thromboelastometry (ROTEM) was used to monitor the patients' coagulation and determine the dose of rFVIIa to achieve in vitro haemostasis in these women that was then subsequently used in vivo. Low-dose rFVIIa seems to be effective and safe in the management of delivery and enables provision of regional blocks in women with severe FXI deficiency.

DRB1*1532, a new DR15 allele, identified in a Mexican unrelated donor from Veracruz, Mexico.

DRB1*1532 allele was identified in a Mexican unrelated marrow donor from the Gulf of Mexico.

Quantifying methane oxidation in a landfill-cover soil by gas push-pull tests.

Methane (CH(4)) oxidation by aerobic methanotrophs in landfill-cover soils decreases emissions of landfill-produced CH(4) to the atmosphere. To quantify in situ rates of CH(4) oxidation we performed five gas push-pull tests (GPPTs) at each of two locations in the cover soil of the Lindenstock landfill (Liestal, Switzerland) over a 4 week period. GPPTs consist of the injection of a gas mixture containing CH(4), O(2) and noble gas tracers followed by extraction from the same location. Quantification of first-order rate constants was based upon comparison of breakthrough curves of CH(4) with either Ar or CH(4) itself from a subsequent inactive GPPT containing acetylene as an inhibitor of CH(4) oxidation. The maximum calculated first-order rate constant was 24.8+/-0.8 h(-1) at location 1 and 18.9+/-0.6 h(-1) at location 2. In general, location 2 had higher background CH(4) concentrations in vertical profile samples than location 1. High background CH(4) concentrations in the cover soil during some experiments adversely affected GPPT breakthrough curves and data interpretation. Real-time PCR verified the presence of a large population of methanotrophs at the two GPPT locations and comparison of stable carbon isotope fractionation of CH(4) in an active GPPT and a subsequent inactive GPPT confirmed that microbial activity was responsible for the CH(4) oxidation. The GPPT was shown to be a useful tool to reproducibly estimate in situ rates of CH(4) oxidation in a landfill-cover soil when background CH(4) concentrations were low.

Identification of B*9550, a novel B*15 allele, in a Mexican bone marrow donor from Veracruz State.

Human leukocyte antigen-B*9550 is a novel allele identified in a Mexican Mestizo bone marrow donor from Veracruz.

Effects of environmental enrichment on the amyotrophic lateral sclerosis mouse model.

The manner in which an animal's environment is furnished may have significant implications for animal welfare as well as research outcomes. We evaluated four different housing conditions to determine the effects of what has been considered standard rodent enrichment and the exercise opportunities those environments allow on disease progression in the amyotrophic lateral sclerosis mouse model. Forty-eight copper/zinc superoxide dismutase mice (strain: B6SJL-TgN [SOD1-G931]1Gur) (SOD1) and 48 control (C) (strain: B6SJL-TgN[SOD1]2Gur) male mice were randomly assigned to four different conditions where 12 SOD1 and 12 C animals were allotted to each condition (n = 96). Conditions tested the effects of standard housing, a forced exercise regime, access to a mouse house and opportunity for ad libitum exercise on a running wheel. In addition to the daily all-occurrence behavioural sampling, mice were weighed and tested twice per week on gait and Rotor-Rod performance until the mice reached the age of 150 days (C) or met the criteria for our humane endpoint (SOD1). The SOD1 mice exposed to the forced exercise regime and wheel access did better in average lifespan and Rotor-Rod performance, than SOD1 mice exposed to the standard cage and mouse house conditions. In SOD1 mice, stride length remained longest throughout the progression of the disease in mice exposed to the forced exercise regime compared with other SOD1 conditions. Within the control group, mice in the standard cage and forced exercise regime conditions performed significantly less than the mice with the mouse house and wheels on the Rotor-Rod. Alpha motor neuron counts were highest in mice with wheels and in mice exposed to forced exercise regime in both mouse strains. All SOD1 mice had significantly lower alpha neuron counts than controls (P < 0.05). These data show that different enrichment strategies affect behaviour and disease progression in a transgenic mouse model, and may have implications for the effects of these strategies on experimental outcomes.

Factor XI deficiency.

Although factor XI (FXI) deficiency has a particularly high incidence in Ashkenazi Jews, it is now frequently diagnosed in other ethnic groups. This review gives an overview of the basic pathophysiology, clinical manifestations, and management of FXI deficiency. The correlation between FXI levels and the bleeding phenotype is much less clear than in the haemophilias, and consequently the bleeding risk can be difficult to predict. Two well-characterized mutations in the F11 gene are responsible for the majority of Jewish cases, but new mutations are becoming increasingly recognized. The publication of the crystal structure has greatly enhanced our understanding of the structure-function relationship in FXI. The impact of recent studies on our understanding of the role of FXI in coagulation is discussed.

Anti-beta1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease.

Chronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against the C-terminal region of the ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with the second extracellular loop of beta1-adrenergic receptor (beta1-AR, peptide H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human beta1-AR, the aim of this study was to investigate further the physical interaction between cChHD IgGs and the human beta1-AR. Immunofluorescence assays demonstrated the binding of these antibodies to the receptor expressed on stably transfected cells, together with a beta1-AR agonist-like effect. In addition, immunoadsorption of the serum samples from cChHD patients with a commercially available matrix, containing peptides representing the first and the second extracellular loop of the beta1-AR, completely abolished reactivity against the H26R peptide and the physiological response to the receptor. The follow-up of this specificity after in vitro immunoadsorption procedures suggests that this treatment might be used to diminish significantly the serum levels of anti-beta1-AR antibodies in patients with Chagas heart disease.