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Trypanosoma cruzi is a multi-host parasite that infects dozens of mammalian species in the most variable wild environments in Americas. Between 2013 and 2018, autochthonous infections by T. cruzi were suspected in three European wolves (Canis lupus) and an orange dwarf porcupine (Coendou spinosus) from Fundação Parque Zoológico de São Paulo (FPZSP), Brazil, current Coordenadoria de Fauna Silvestre (CFS), which is inserted in a remnant of the Atlantic rainforest inside one of the biggest and most populous municipality of the world. This study aims to detect T. cruzi infections in captive mammals, triatomines and free-living opossums from surrounding areas of FPZSP/CFS. Blood samples from captive and free-living mammals from surrounding areas were collected for parasitological (direct examination and culture), serological (IFAT) and molecular diagnosis using Nested-PCR 18SrDNA followed by DNA sequence analysis. Triatomines (Panstrongylus megistus) found in FPZSP/CFS were also examined by culture of the digestive tract and PCR. Trypanosoma cruzi infection was detected in 35.7% (n = 60/168 - 106 captive and 62 free-living) of the mammals that belonged to nine different families. From captive mammals, positive T. cruzi serology was observed in 29.6% (n = 27/91). Twenty-six positive hemocultures were obtained, from which parasite isolation was achieved in 69.2%, while positive PCR was observed in 40% of them, including nine free-living individuals that were also positive in hemoculture. Of 28 individuals in which T. cruzi characterization was successful, 89.3% were genotyped as DTU TcI, 7.2% as TcII and 3.5% as TcI/TcII mixed infection. Besides, 29 of 30 collected triatomines were infected, and infection by T. cruzi DTU TcI was confirmed in 16 of them. The confirmed autochthonicity of at least 68.9% of cases demonstrates that captive mammals from FPZSP are immersed in the T. cruzi enzootic cycle that involves the vector species P. megistus, and the reservoir hosts C. spinosus and Didelphis aurita from the wild surrounding areas.

Background Trypanosoma cruzi is a multi-host parasite that infects dozens of mammalian species in the most variable wild environments in Americas. Between 2013 and 2018, autochthonous infections by T. cruzi were suspected in three European wolves (Canis lupus) and an orange dwarf porcupine (Coendou spinosus) from Fundação Parque Zoológico de São Paulo (FPZSP), Brazil, current Coordenadoria de Fauna Silvestre (CFS), which is inserted in a remnant of the Atlantic rainforest inside one of the biggest and most populous municipality of the world. This study aims to detect T. cruzi infections in captive mammals, triatomines and free-living opossums from surrounding areas of FPZSP/CFS. Methodology/Principal Findings Blood samples from captive and free-living mammals from surrounding areas were collected for parasitological (direct examination and culture), serological (IFAT) and molecular diagnosis using Nested-PCR 18SrDNA followed by DNA sequence analysis. Triatomines (Panstrongylus megistus) found in FPZSP/CFS were also examined by culture of the digestive tract and PCR. Trypanosoma cruzi infection was detected in 35.7% (n = 60/168 - 106 captive and 62 free-living) of the mammals that belonged to nine different families. From captive mammals, positive T. cruzi serology was observed in 29.6% (n = 27/91). Twenty-six positive hemocultures were obtained, from which parasite isolation was achieved in 69.2%, while positive PCR was observed in 40% of them, including nine free-living individuals that were also positive in hemoculture. Of 28 individuals in which T. cruzi characterization was successful, 89.3% were genotyped as DTU TcI, 7.2% as TcII and 3.5% as TcI/TcII mixed infection. Besides, 29 of 30 collected triatomines were infected, and infection by T. cruzi DTU TcI was confirmed in 16 of them. Conclusions/Significance The confirmed autochthonicity of at least 68.9% of cases demonstrates that captive mammals from FPZSP are immersed in the T. cruzi enzootic cycle that involves the vector species P. megistus, and the reservoir hosts C. spinosus and Didelphis aurita from the wild surrounding areas.

Determination of potentially-reversible factors contributing to exertional dyspnea remains an unmet clinical need in chronic thromboembolic pulmonary hypertension (CTEPH). Therefore, we aimed to evaluate the influence of inspiratory muscle weakness (IMW) on exercise capacity and dyspnea during effort in patients with CTEPH. We performed a prospective cross-sectional study that included thirty-nine consecutive patients with CTEPH (48 ± 15 yrs, 61% female) confirmed by right heart catheterization that underwent an incremental cardiopulmonary exercise test, 6-minute walk test and maximum inspiratory pressure (MIP) measurement. MIP < 70%pred was found in 46% of patients. On a multiple linear regression analysis, MIP was independently associated with 6MWD and [Formula: see text]. Patients with MIP < 70% presented greater [Formula: see text] than those with MIP ≥ 70%. Additionally, they also presented stronger sensations of dyspnea throughout exercise, even when adjusted for ventilation. At rest and at different levels of exercise, mean inspiratory flow (VT/TI) was significantly higher in patients with MIP < 70%. In conclusion, IMW is associated with a rapid increase of dyspnea, higher inspiratory load and poor exercise capacity in patients with CTEPH.

It has been proposed that copy number variations (CNVs) are associated with increased risk of autism spectrum disorder (ASD) and, in conjunction with other genetic changes, contribute to the heterogeneity of ASD phenotypes. Array comparative genomic hybridization (aCGH) and exome sequencing, together with systems genetics and network analyses, are being used as tools for the study of complex disorders of unknown etiology, especially those characterized by significant genetic and phenotypic heterogeneity. Therefore, to characterize the complex genotype-phenotype relationship, we performed aCGH and sequenced the exomes of two affected siblings with ASD symptoms, dysmorphic features, and intellectual disability, searching for de novo CNVs, as well as for de novo and rare inherited point variations-single nucleotide variants (SNVs) or small insertions and deletions (indels)-with probable functional impacts. With aCGH, we identified, in both siblings, a duplication in the 4p16.3 region and a deletion at 8p23.3, inherited by a paternal balanced translocation, t(4, 8) (p16; p23). Exome variant analysis found a total of 316 variants, of which 102 were shared by both siblings, 128 were in the male sibling exome data, and 86 were in the female exome data. Our integrative network analysis showed that the siblings' shared translocation could explain their similar syndromic phenotype, including overgrowth, macrocephaly, and intellectual disability. However, exome data aggregate genes to those already connected from their translocation, which are important to the robustness of the network and contribute to the understanding of the broader spectrum of psychiatric symptoms. This study shows the importance of using an integrative approach to explore genotype-phenotype variability.