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Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil.

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Resumen Se presenta el caso de una mujer de 67 años, con antecedentes de hipertensión arterial y obesidad, que acudió a urgencias por tos, fatiga, fiebre y disnea. Durante la monitorización se documentó elevación del segmento ST anterolateral e inferior y elevación de troponina; la arteriografía coronaria no evidenció lesiones significativas; en el ventriculograma y en el ecocardiograma transtorácico se documentó acinesia apical. Se confirmó RT-PCR positiva para SARS-CoV-2; se consideró como diagnóstico síndrome de takotsubo.

Abstract A 67-years-old woman with hypertension, obesity as previous diseases, presented to the emergency department due to cough, fatigue, fever, and dyspnea. ST-segment elevation was visualized during monitoring, troponin was positive, the coronary angiography was negative; the ventriculogram and transthoracic echocardiogram documented apical akinesia. The RT-PCR was positive for SARS CoV-2; the diagnosis was takotsubo-syndrome.

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Medicinal plants belonging to the Verbenaceae family demonstrated antidepressant effects in preclinical studies. Depression is one of the largest contributors to the global health burden of all countries. Plants from the Aloysia genus are traditionally used for affective disorders, and some of them have proven anxiolytic and antidepressant activity. The aim of this work was to evaluate the antidepressant effect of the ethanolic extract of Aloysia gratissima var. gratissima (Agg) and Aloysia virgata var. platyphylla (Avp) in mice. A tail suspension test (TST) and forced swimming test (FST) were conducted after three doses in a period of 24 h and after 7 days of treatment. Imipramine was used as an antidepressant drug. The main results demonstrated that Agg extract reduced the immobility time in mice treated orally for 7 consecutive days when compared to the control group (reduced by about 77%, imipramine 70%). Animals treated with three doses of Avp in a 24-h period had reduced immobility time in the FST (60%), and after 7 days of treatment the reduction was greater (Avp 50, 100, and 200 about 85%; Avp 400, 96.5%; p < 0.0001, imipramine, 77%). LCMS analysis showed the presence of verbascoside, hoffmaniaketone, and hoffmaniaketone acetate in both, A. virgata var. platyphylla and A. gratissima var gratissima. The flavonoids nepetin and 6-hydroxyluteolin were also found in Agg. Both tested extracts demonstrated promising antidepressant-like activity in mice.

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Reinforcement Learning (RL) comes with the promise of automating network management. However, due to its trial-and-error learning approach, model-based RL (MBRL) is not applicable in some network management scenarios. This paper explores the potential of using Automated Planning (AP) to achieve this MBRL in the functional areas of network management. In addition, a comparison of several integration strategies of AP and RL is depicted. We also describe an architecture that realizes a cognitive management control loop by combining AP and RL. Our experiments evaluate on a simulated environment evidence that the combination proposed improves model-free RL but demonstrates lower performance than Deep RL regarding the reward and convergence time metrics. Nonetheless, AP-based MBRL is useful when the prediction model needs to be understood and when the high computational complexity of Deep RL can not be used.

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Oxidative stress plays a key role in the initiation and progression of metabolic diseases, including obesity. Preventing the accumulation of reactive oxygen species and oxidative damage to macromolecules is a beneficial strategy for reducing comorbidities associated with obesity. Fruits from the Spondias genus are known for their antioxidant activity, but they are not available year-round due to their seasonality. In this context, we investigated the antioxidant activity and identified the chemical constituents of the aqueous extract of the stem bark of Spondias purpurea L. (EBSp). Additionally, we evaluated the effect of EBSp consumption on metabolic parameters in mice with obesity induced by a high-fat diet. Chemical analyses revealed 19 annotated compounds from EBSp, including flavan-3-ols, proanthocyanidins, methoxylated coumarin, and gallic and ellagic acids, besides other phenolic compounds. In vitro, EBSp showed antioxidant activity through the scavenging of the free radicals and the protection of macromolecules against oxidative damage. Cellular assays revealed that EBSp reduced the levels of malondialdehyde produced by erythrocytes exposed to the oxidizing agent AAPH. Flow cytometry studies showed that EBSp reduced reactive oxygen species levels in human peripheral blood mononuclear cells treated with hydrogen peroxide. Obese mice treated with EBSp (400 mg.kg-1) for 60 days showed reduced levels of malondialdehyde in the heart, liver, kidneys, and nervous system. The total cholesterol levels in mice treated with EBSp reached levels similar to those after treatment with the drug simvastatin. Together, the results show that the combination of the different phenolic compounds in S. purpurea L. bark promotes antioxidant effects in vitro and in vivo, resulting in cytoprotection in the context of oxidative stress associated with obesity and a reduction in hypercholesterolemia. From a clinical perspective, the reduction in oxidative stress in obese individuals contributes to the reduction in the emergence of comorbidities associated with this metabolic syndrome.

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Introducción: Durante el proceso de crecimiento y desarrollo una serie de hechos se suceden con mayor o menor regularidad y similitud en todos los niños desde el nacimiento hasta la adultez. Mediante la radiografía carpal se observaban un gran número de centros secundarios de osificación, considerados "indicadores de madurez", ubicados en la mano, muñeca y epífisis distales del cúbito y radio. Actualmente, los cambios morfológicos de las vértebras cervicales son considerados indicadores de la maduración ósea. Objetivo:Con el objeto de minimizar las radiaciones en pacientes niños y adolescentes al momento de determinar el grado de maduración ósea, se reemplazó la radiografía carpal por la telerradiografía lateral de cráneo, utilizada rutinariamente. Corroborando, además la edad de maduración en nuestra población. Este estudio nos permite, al momento de decidir el plan de tratamiento, el método a utilizar para la resolución del caso clínico: ortopedia, ortodoncia o ambos a la vez.Materiales y métodos: estudiotransversal sin seguimiento del paciente. Se analizaron radiografías laterales del cráneo, ortopantomografías y carpo de 318 niños y adolescentes de ambos sexos de 10 a 16 años con dentición permanente en ambos arcos dentales, con/sin la presencia del 2° molar. El biotipo facial se determinó por el cefalograma de Björk-Jarabak.Resultados: Las edades promedio en los diferentes biotipos faciales no variaron significativamente, observándose valores medios menores en varones, con biotipo dólico y meso con tendencia a braquifacial. En niñas, se observa que la mayoría están relacionadas significativamente (p<0,05) con excepción del biotipo mesofacial entre edades cronológicas con edades óseas vertebrales y edades óseas vertebrales con óseas carpales y dentarias.Mientras que en varones la excepción se da en el biotipo dólicofacial en todas las variables siendo, solamente significativo entre las variables: edades cronológicas con óseas carpales y edades óseas vertebrales con óseas carpales. Por lo tanto, podemos concluir que existe una alta correlación entre las edades óseas vertebral, carpal y dentaria en ambos sexos y biotipos faciales excepto en niñas con biotipo mesofacial

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Objective: The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. Design: A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs, and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish, and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021, the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations, although 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically in Latin American countries. The consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America.

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The electrocardiogram (ECG) is a test that will allow making life-saving decisions. It has different patterns, and differential diagnoses, like the pattern of acute coronary syndrome with an elevation of the high lateral ST segment, which is called the sign of the flag of South Africa. We present the case of a 44-year-old patient presented with typical chest pain; the ECG showed ST-segment elevation in the DI, DII, AVL - V2, and ST depression in DIII, corresponding to an acute coronary occlusion with a compromise of the lateral segment of the heart. This ECG pattern is known as the flag sign of South Africa. The early recognition allowed the decision to perform immediately pharmacological reperfusion therapy and rescue angioplasty.

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We present the case of a 61 years old man with hypothyroidism, hypertension, type 2 diabetes mellitus, and ischemic cardiopathy, who was admitted with a diagnosis of non-ST elevation myocardial infarction. The coronary angiography describes coronary ectasia with giant aneurysm and slow flow in the right coronary and aneurysm with slow flow anterior descending coronary. The echocardiogram shows contractility disorders with severely decreased left ventricular ejection fraction (20%) despite optimal medical management. This case presents a patient with ischemic heart disease and advanced heart failure secondary to coronary aneurysm, the proposed optimal treatment was a heart transplant given the disease's progression.

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This paper introduces a new solution to improve network performance by decreasing spectrum fragmentation, crosstalk interference, blocking of virtual networks, cost, and link load imbalance. These problems degrade the performance of Elastic Optical Networks with Space-Division Multiplexing. The proposed solution, called Cognitive control loop (CO-OP), is capable of identifying a set of problems and creating plans to mitigate these problems. The CO-OP comprises four functions that employ learning algorithms to identify problems and plan a series of actions to reduce or eliminate them. The results show that the CO-OP can effectively decrease up to 30% the blocking of requests and up to 50% the crosstalk occurrence compared to existing algorithms.

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Introduction: Vaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique. Methods: Adults aged 18-35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits. Results: A total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61-6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07-4.7) were associated with willingness to participate in HIV vaccine studies. Conclusion: The majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial.

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Introduction: Vaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique. Methods: Adults aged 18-35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits. Results: A total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61-6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07-4.7) were associated with willingness to participate in HIV vaccine studies. Conclusion: The majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial.

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For some ranges of its parameters and arguments, the series for Tweedie probability density functions are sometimes exceedingly difficult to sum numerically. Existing numerical implementations utilizing inversion techniques and properties of stable distributions can cope with these problems, but no single one is successful in all cases. In this work we investigate heuristically the nature of the problem, and show that it is not related to the order of summation of the terms. Using a variable involved in the analytical proof of convergence of the series, the critical parameter for numerical non-convergence ("alpha") is identified, and an heuristic criterion is developed to avoid numerical non-convergence for a reasonably large sub-interval of the latter. With these practical rules, simple summation algorithms provide sufficiently robust results for the calculation of the density function and its definite integrals. These implementations need to utilize high-precision arithmetic, and are programmed in the Python programming language. A thorough comparison with existing R functions allows the identification of cases when the latter fail, and provide further guidance to their use.

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In this work, we present a novel, efficient and green methodology for the synthesis of thioethers by the C-S cross-coupling reaction with the assistance of [Ce(l-Pro)2]2Ox as a heterogeneous catalyst in good to excellent yields. A scale-up of the protocol was explored using an unpublished methodology for the synthesis of a dapsone-precursor, which proved to be very effective over a short time. The catalyst [Ce(l-Pro)2]2Ox was recovered and it was shown to be effective for five more reaction cycles.

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Cellulose is a renewable polymer quite abundant on the Earth and very attractive for applications in the construction of eco-friendly biomedical products. The aim of this study was to investigate the chemical-physical characteristics of cotton cellulose nanofiber (CCN)/chitosan nanocomposite and its cytocompatibility with human embryonic kidney cells. First, the chemical composition, swelling ratio and surface topography of the nanocomposite were evaluated. Cytocompatibility was then assessed through spreading, proliferation and viability of cells. The experimental results showed that the CCN was an effective nanomaterial agent for increasing the roughness surface of chitosan film. Cell proliferation and changes in cell morphology indicated that the nanocomposite led to improved cell spreading and growth. Cell viability did not decrease after 24 h. However, the cell survival on the nanocomposite was affected at 72 h. The results indicate that CCN/chitosan nanocomposite could be a promising biocompatible biomaterial for biomedical applications.

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In the fog computing paradigm, fog nodes are placed on the network edge to meet end-user demands with low latency, providing the possibility of new applications. Although the role of the cloud remains unchanged, a new network infrastructure for fog nodes must be created. The design of such an infrastructure must consider user mobility, which causes variations in workload demand over time in different regions. Properly deciding on the location of fog nodes is important to reduce the costs associated with their deployment and maintenance. To meet these demands, this paper discusses the problem of locating fog nodes and proposes a solution which considers time-varying demands, with two classes of workload in terms of latency. The solution was modeled as a mixed-integer linear programming formulation with multiple criteria. An evaluation with real data showed that an improvement in end-user service can be obtained in conjunction with the minimization of the costs by deploying fewer servers in the infrastructure. Furthermore, results show that costs can be further reduced if a limited blocking of requests is tolerated.

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BACKGROUND: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. METHODS: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18-89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001-14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). FINDINGS: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001-14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53-1·70; fully adjusted OR 1·45, 95% CI 1·38-1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22-1·30; fully adjusted OR 1·18, 1·14-1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2-49·5) and lowest for women who were white with university education (29·4%, 28·2-30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%-17·2% in 1970-74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50-69 years). INTERPRETATION: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. FUNDING: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa.

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BACKGROUND/AIM: Sleep quality exerts an influence on attention level and motor skills and is associated with accidental injuries in children. The aim of this study was to evaluate the association between traumatic dental injury and sleep behaviour in children. MATERIAL AND METHODS: A cross-sectional study was conducted in a small city in southern Brazil with a representative sample of schoolchildren aged 8-10 years (n = 537). Weight and height were measured, and examinations were performed for the determination of clinical occlusion and traumatic dental injury. The parents answered the Sleep Behaviour Questionnaire and questions addressing socio-demographic characteristics. RESULTS: The prevalence of traumatic dental injury was 22% (95% CI: 19-26) and was higher among children who woke three to four times per night (PR = 3.30; 95% CI: 2.47-4.39), those who fell asleep in the parental bed (PR = 1.41; 95% CI: 1.09-1.83), those who were not in a good mood on waking up in the morning (PR = 1.30; 95% CI: 1.02-1.65), those who became sleepy while sitting and/or studying (PR = 1.57; 95% CI: 1.09-2.24) and while watching TV (PR = 1.41; 95% CI: 1.0005-1.97) and those who had bad dreams (PR = 1.35; 95% CI: 1.04-1.76). The Poisson multiple regression model with a multilevel approach revealed that the prevalence of traumatic dental injury was 1.51-fold higher among children with daytime drowsiness (PR = 1.51; 95% CI: 1.11-2.04) after adjusting for socio-demographic, occlusal and anthropometric variables. CONCLUSION: Sleep problems were associated with a higher prevalence of traumatic dental injury among the children analysed.

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Resumen La gestación en presencia de una válvula mecánica es un reto terapéutico tanto para el ginecólogo como para el cardiólogo, en vista de las complicaciones materno-fetales y mayor el riesgo de trombosis valvular. Medio siglo después del primer reporte de una gestación a término en este contexto, mucho se ha aprendido, pero persisten controversias importantes, de ahí que conocerlas sea fundamental para encontrar el tratamiento más balanceado.

Abstract Pregnancy and mechanical valves are a therapeutic challenge both for the gynaecologist and the cardiologist in view of the maternal-foetal complications, and the higher risk of valvular thrombosis. Half a century after the first report of a full term pregnancy in this context, much has been learned, but there are still significant controversies, which are essential to know about, in order to find the most balanced treatment.

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A Brazilian fox (Lycalopex vetulus) was rescued from a highway, and 16 days after maintained in captivity, the fox shed oocysts with sizes compatible with Hammondia sp. and Neospora caninum. DNA extracted from oocysts were initially tested in two PCRs targeting the internal transcribed spacer 1 (ITS-1) of the rDNA of Hammondia heydorni and the Nc-5 gene of N. caninum. A 270-bp product was visualized in the PCR for H. heydorni. No amplification was observed for N. caninum PCR. Since ITS-1-based PCR is not sufficient to differentiate Hammondia species derived from canids, oocyst DNA was examined using multilocus sequence analysis of five genetic fragments [intron 1 of the alpha tubulin gene (intron 1), internal transcribed spaces 1 and 2 (ITS-1 and ITS-2) of the rDNA, 28S rRNA gene (D2/D3 domain), and heat shock protein 70 (Hsp70)]. The Hammondia sp. oocyst from the Brazilian fox, referred here as H-FOXBR isolate, is closely related to H. heydorni and Hammondia triffittae, but differs from these parasites in three genetic markers (alpha tubulin gene, ITS-2, and 28S rRNA). As reported by other research groups, Hammondia spp. excreted by canids are genetically diverse and may encompass additional species besides H. heydorni and H. triffittae. In this study, we confirmed that H-FOXBR has significant genetic differences in comparison to H. heydorni and H. triffittae and may represent a separate species. Further studies are needed to identify the life cycle of this parasite and to characterize the parasite stages in the intermediate and definitive hosts.

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