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In Brazil, where Chagas disease is endemic, the most frequent form of transmission of the parasite is the oral route, associated with greater severity and worse response to benznidazole (BZ), the drug used in its treatment. This study aimed to evaluate the impact of gastrointestinal infection (GI) and BZ treatment on the parasitological and histopathological parameters in mice inoculated with a strain of T. cruzi II. Swiss mice were inoculated by GI and intraperitoneal (IP) routes with 2x106 culture-derived metacyclic trypomastigotes of the Y strain (TcII) of T. cruzi and were treated with BZ in the acute phase of the infection. Fresh blood examination, qPCR, histopathological and biochemical evaluations (enzymatic dosages and oxidative stress-OS) were performed. BZ treatment of uninfected animals caused changes in the liver, increased the activity of aspartate aminotransferase and alanine aminotransferase enzymes and OS, showing that the drug alone affects this organ. Inflammation and necrosis in the cardiac tissue were less intense and deaths occurred later in animals inoculated via the GI route than the animals inoculated via the IP route. BZ reduced the intensity of tissue lesions and avoided lethality in animals inoculated via the GI route, and decreased parasitemia and OS in those inoculated via both routes. Although BZ alone caused liver damage, it was less intense than that caused by both routes of inoculation. Infection with the Y strain of T. cruzi II via the GI route proved to be less virulent and pathogenic and responded better to treatment than the infection acquired via the IP route.
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SARS-CoV-2 is the virus responsible for a respiratory disease called COVID-19 that devastated global public health. Since 2020, there has been an intense effort by the scientific community to develop safe and effective prophylactic and therapeutic agents against this disease. In this context, peptides have emerged as an alternative for inhibiting the causative agent. However, designing peptides that bind efficiently is still an open challenge. Here, we show an algorithm for peptide engineering. Our strategy consists of starting with a peptide whose structure is similar to the interaction region of the human ACE2 protein with the SPIKE protein, which is important for SARS-COV-2 infection. Our methodology is based on a genetic algorithm performing systematic steps of random mutation, protein-peptide docking (using the PyRosetta library) and selecting the best-optimized peptides based on the contacts made at the peptide-protein interface. We performed three case studies to evaluate the tool parameters and compared our results with proposals presented in the literature. Additionally, we performed molecular dynamics (MD) simulations (three systems, 200 ns each) to probe whether our suggested peptides could interact with the spike protein. Our results suggest that our methodology could be a good strategy for designing peptides.
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COVID-19 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2 , Péptidos/farmacologíaRESUMEN
BACKGROUND: Rhodnius robustus and Rhodnius pictipes are vectors of Trypanosoma cruzi, the etiologic agent of Chagas disease (CD), that are found in the Brazilian Amazon region. Susceptibility to infection and vector competence depend on the parasite-vector relationship. Our objective was to evaluate the interaction between T. cruzi and these two triatomine vectors in pure and mixed experimental infections of T. cruzi strains from the same or different geographic regions. METHODS: Fifth-instar nymphs of R. robustus and R. pictipes were fed on mice infected with four T. cruzi strains, namely genotypes TcIAM, TcIMG, TcIIPR, and TcIVAM, respectively, from the Brazilian states of Amazonas, Minas Gerais and Paraná. Over a period of 120 days, excreta were examined every 20 days to assess vector competence, and intestinal contents (IC) were examined every 30 days to determine susceptibility to infection. RESULTS: The highest positive rate in the fresh examination (%+FE, 30.0%), the highest number of parasitic forms (PF, n = 1969) and the highest metacyclogenesis rate (%MC, 53.8%) in the excreta were recorded for R. robustus/TcIVAM. Examination of the IC of R. pictipes revealed a higher number of PF in infections with TcIAM (22,680 PF) and TcIIPR (19,845 PF) alone or in association (17,145 PF), as well as a %+FE of 75.0% with TcII, in comparison with the other genotypes. The highest %MC (100%) was recorded for the mixed infections of TcIAM with TcIIPR or TcIVAM in the IC of R. pictipes. CONCLUSIONS: Overall, both species were found to be susceptible to the T. cruzi strains studied. Rhodnius robustus showed vector competence for genotypes TcIVAM and TcIAM+TcIVAM and R. pictipes for TcIAM+TcIVAM and TcIAM+TcIIPR; there was elimination of infective forms as early as at 20 days. Our results suggest that both the genetics of the parasite and its geographic origin influence the susceptibility to infection and vector competence, alone or in association.
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Enfermedad de Chagas , Kinetoplastida , Rhodnius , Triatominae , Trypanosoma cruzi , Trypanosomatina , Animales , Enfermedad de Chagas/parasitología , Ratones , Rhodnius/parasitología , Triatominae/parasitología , Trypanosoma cruzi/genéticaRESUMEN
Strains of Trypanosoma cruzi, etiological agent of Chagas disease, are classified into different discrete typing units that may present distinct dynamics of infection and susceptibility to benznidazole (BZ) treatment. Mice that were orally inoculated with T. cruzi IV strains exhibited a more intense course of infection compared with intraperitoneally inoculated mice, reflected by higher parasite loads. We evaluated the efficacy of BZ treatment in Swiss mice that were inoculated with T. cruzi IV strains from the Western Brazilian Amazon. The mice were orally (OR) or intraperitoneally (IP) inoculated with 2 × 106 culture-derived metacyclic trypomastigotes of the AM14, AM16, AM64, and AM69 strains of T. cruzi that were obtained from two outbreaks of orally acquired acute Chagas disease in the state of Amazonas, Brazil. The animals were treated with BZ (100 mg/kg/day for 20 days). Fresh blood examination, hemoculture, conventional and quantitative real-time polymerase chain reaction were performed to monitor the therapeutic effects of BZ. Significant reductions in five of 24 parameters of parasitemia and parasite load were found in different tissues in the OR group, indicating worse response to BZ treatment compared with the IP group, in which significant reductions in nine of those 24 parameters were observed. The cure rates in the OR groups ranged from 18.2% (1/11) to 75.0% (9/12) and in the IP groups from 58.3% (7/12) to 91.7% (11/12), for the AM14 and AM69 strains, respectively. These findings indicate that treatment with BZ had fewer beneficial effects with regard to reducing parasitemia and parasite load in different tissues of mice that were OR inoculated with four TcIV strains compared with IP inoculation. Therefore, the route of infection with T. cruzi should be considered when evaluating the therapeutic efficacy of BZ in patients with Chagas disease.
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Enfermedad de Chagas/parasitología , Nitroimidazoles/uso terapéutico , Tripanocidas/uso terapéutico , Trypanosoma cruzi/clasificación , Pared Abdominal/parasitología , Animales , Brasil/epidemiología , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/epidemiología , Esófago/parasitología , Corazón/parasitología , Ratones , Nitroimidazoles/farmacología , Carga de Parásitos , Parasitemia/tratamiento farmacológico , Parasitemia/epidemiología , Parasitemia/parasitología , Estómago/parasitología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacosRESUMEN
BACKGROUND: Trypanosoma cruzi is the etiological agent of Chagas disease (CD) or American trypanosomiasis, an important public health problem in Latin America. Benznidazole (BZ), a drug available for its treatment, has limited efficacy and significant side effects. Essential oils (EOs) have demonstrated trypanocidal activity and may constitute a therapeutic alternative. Our aim was to evaluate the efficacy of the EOs of clove (CEO - Syzygium aromaticum) and ginger (GEO - Zingiber officinale), administered alone and in combination with BZ, in Swiss mice infected with T. cruzi. METHODS: The animals were inoculated with 10,000 blood trypomastigotes of the Y strain of T. cruzi II by gavage and divided into four groups (n = 12 to 15): 1) untreated control (NT); 2) treated with BZ; 3) treated with CEO or GEO; and 4) treated with BZ + CEO or GEO. The treatments consisted of oral administration of 100 mg/kg/day, from the 5th day after parasite inoculation, for 20 consecutive days. All groups were submitted to fresh blood examination (FBE), blood culture (BC), conventional PCR (cPCR) and real-time PCR (qPCR), before and after immunosuppression with cyclophosphamide. RESULTS: Clove and ginger EOs, administered alone and in combination with BZ, promoted suppression of parasitemia (p < 0.0001), except for the animals treated with CEO alone, which presented a parasitemia curve similar to NT animals. However, there was a decrease in the BC positivity rate (p < 0.05) and parasite load (< 0.0001) in this group. Treatment with GEO alone, on the other hand, besides promoting a decrease in the BC positivity rate (p < 0.05) and parasite load (p < 0.01), this EO also resulted in a decrease in mortality rate (p < 0.05) of treated mice. CONCLUSIONS: Decreased parasite load, as detected by qPCR, was observed in all treatment groups (BZ, CEO, GEO and BZ + EOs), demonstrating benefits even in the absence of parasitological cure, thus opening perspectives for further studies.
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Antiprotozoarios/administración & dosificación , Nitroimidazoles/administración & dosificación , Aceites Volátiles/administración & dosificación , Aceites de Plantas/administración & dosificación , Syzygium/química , Trypanosoma cruzi/efectos de los fármacos , Zingiber officinale/química , Animales , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Quimioterapia Combinada , Humanos , Masculino , Ratones , Carga de Parásitos , Trypanosoma cruzi/genética , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/fisiologíaRESUMEN
Bioinformatics is a fast-evolving research field, requiring effective educational initiatives to bring computational knowledge to Life Sciences. Since 2017, an organizing committee composed of graduate students and postdoctoral researchers from the Universidade Federal de Minas Gerais (Brazil) promotes a week-long event named Summer Course in Bioinformatics (CVBioinfo). This event aims to diffuse bioinformatic principles, news, and methods mainly focused on audiences of undergraduate students. Furthermore, as the advent of the COVID-19 global pandemic has precluded in-person events, we offered the event in online mode, using free video transmission platforms. Herein, we present and discuss the insights obtained from promoting the Online Workshop in Bioinformatics (WOB) organized in November 2020, comparing it to our experience in previous in-person editions of the same event.
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The aim of the present study was to evaluate the genetic diversity of Ehrlichia canis in naturally infected dogs from six mesoregions of Rio de Janeiro state. E. canis was diagnosed with a real-time polymerase chain reaction (qPCR) targeting a 93 base pair (bp) fragment of the 16S rDNA gene. To evaluate the genetic diversity of the parasite, we amplified a positive sample from each mesoregion by distinct conventional PCR assays with targets in the gp19 (414 bp), gp36 (814 bp), and p28 (843 bp) genes. A total of 267 samples were collected from dogs in Rio de Janeiro state. Among the samples analyzed, 42.3% (n = 113/267) were 16S rDNA-qPCR positive. When performing PCR for the gp19 and gp36 genes, 100% (n = 113/113) and 5.3% (n = 6/113) of the samples amplified fragments of 414 bp and 814 bp, respectively. The six PCR-positive samples for the gp36 gene also amplified the p28 gene fragment. The characterization based on the gp19 gene demonstrated that it is highly conserved. In protein analysis (TRP36), all samples showed a tandem repeat protein (TRP) that comprised 11 replicates. Seven high-entropy amino acid sites were distributed throughout the gp36 gene. Eleven high-entropy amino acid sites were found throughout the p28 gene. There is a positive selection pressure in both genes (p ≤ 0.05). Comparing and characterizing an organism are useful for providing important information about the host's immune response and identifying new antigenic targets, as well as essential characteristics for the development of vaccines and new diagnostic tools.
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Enfermedades de los Perros/microbiología , Ehrlichia canis/genética , Ehrlichia canis/aislamiento & purificación , Ehrlichiosis/veterinaria , Animales , Proteínas Bacterianas/genética , Brasil , Perros , Ehrlichia canis/clasificación , Ehrlichiosis/microbiología , Variación Genética , FilogeniaRESUMEN
This cross-sectional, observational, and descriptive study aims to investigate the epidemiology of Ehrlichia canis in healthy owned dogs from the Southeastern region of Rio de Janeiro, Brazil. Blood samples were collected from 390 households dogs. During the visits, an epidemiological questionnaire was filled out concerning the dogs' characteristics as well as the environments in which they lived. The variables were analyzed using a bivariate test, while the correlation analysis between the variables was performed via a phi test. The variables that had p-values lower than 0.2 in the bivariate analysis and had a low or moderate correlation were selected for the multivariate analysis. The model that had the lowest Akaike information criterion (AIC) value was retained. Among the 390 blood samples tested, 24.8% were considered positive for E. canis. The parsimonious logistic regression model presented an AIC value of 408.75 and showed three variables that favored the presence of E. canis DNA in the tested dogs: the animal's access to urban streets and neighborhoods (odds ratio [OR] = 1.91; p-value = 0.02; confidence interval [CI]: 1.14 - 3.18), tick infestation (OR = 2.01; p-value = 0.006; CI: 1.22 - 3.32), and poor hygienic conditions (OR = 2.19; p-value = 0.002; CI: 1.31 - 3.67). The model was considered well-calibrated based on the Hosmer-Lemeshow test (p = 0.39). According to the present study, dogs that have access to the street and neighborhood, are infested with ticks, and live under poor hygienic conditions are more likely to be infected with E. canis in the state of Rio de Janeiro, Brazil.
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Infecciones Asintomáticas/epidemiología , Enfermedades de los Perros/epidemiología , Ehrlichia canis/aislamiento & purificación , Ehrlichiosis/veterinaria , Infestaciones por Garrapatas/veterinaria , Animales , Proteínas de la Membrana Bacteriana Externa/análisis , Brasil/epidemiología , Estudios Transversales , Enfermedades de los Perros/microbiología , Perros , Ehrlichiosis/epidemiología , Ehrlichiosis/microbiología , Femenino , Masculino , Análisis Multivariante , Reacción en Cadena de la Polimerasa/veterinaria , Infestaciones por Garrapatas/epidemiología , Infestaciones por Garrapatas/parasitologíaRESUMEN
After obtaining certification of the absence of transmission of the Trypanosoma cruzi by Triatoma infestans in 2006, other native species of protozoan vectors have been found in human dwellings within municipalities of the State of Paraná, Southern Brazil. However, the spatial distribution of T. cruzi vectors and how climatic and landscape combined variables explain the distribution are still poorly understood. The goal of this study was to predict the potential distribution of T. cruzi vectors as a proxy for Chagas disease transmission risk using Ecological Niche Models (ENMs) based on climatic and landscape variables. We hypothesize that ENM based on both climate and landscape variables are more powerful than climate-only or landscape-only models, and that this will be true independent of vector species. A total of 2,662 records of triatomines of five species were obtained by community-based entomological surveillance from 2007 to 2013. The species with the highest number of specimens was Panstrongylus megistus (73%; n = 1,943), followed by Panstrongylus geniculatus (15.4%; 411), Rhodnius neglectus (6.0%; 159), Triatoma sordida (4.5%; 119) and Rhodnius prolixus (1.1%; 30). Of the total, 71.9% were captured at the intradomicile. T. cruzi infection was observed in 19.7% of the 2,472 examined insects. ENMs were generated based on selected climate and landscape variables with 1 km2 spatial resolution. Zonal statistics were used for classifying the municipalities as to the risk of occurrence of synanthropic triatomines. The integrated analysis of the climate and landscape suitability on triatomines geographical distribution was powerful on generating good predictive models. Moreover, this showed that some municipalities in the northwest, north and northeast of the Paraná state have a higher risk of T. cruzi vector transmission. This occurs because those regions present high climatic and landscape suitability values for occurrence of their vectors. The frequent invasion of houses by infected triatomines clearly indicates a greater risk of transmission of T. cruzi to the inhabitants. More public health attention should be given in the northern areas of the State of Paraná, which presents high climate and landscape suitabilities for the disease vectors. In conclusion, our results-through spatial analysis and predictive maps-showed to be effective in identifying areas of potential distribution and, consequently, in the definition of strategic areas and actions to prevent new cases of Chagas' disease, reinforcing the need for continuous and robust surveillance in these areas.
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Enfermedad de Chagas/transmisión , Transmisión de Enfermedad Infecciosa , Insectos Vectores/crecimiento & desarrollo , Panstrongylus/crecimiento & desarrollo , Rhodnius/crecimiento & desarrollo , Triatoma/crecimiento & desarrollo , Trypanosoma cruzi/aislamiento & purificación , Animales , Brasil/epidemiología , Enfermedad de Chagas/epidemiología , Clima , Estudios Transversales , Entomología , Geografía , Humanos , Insectos Vectores/parasitología , Panstrongylus/parasitología , Rhodnius/parasitología , Medición de Riesgo , Análisis Espacial , Triatoma/parasitologíaRESUMEN
Hemoparasitic diseases are prominent in domestic animals, particularly in Brazil, a tropical country with a wide range of vectors. This study investigated the epidemiology of Babesia vogeli in the whole blood of dogs from the southeastern region of Rio de Janeiro, Brazil. Whole blood samples from 390 dogs were screened for the presence of B. vogeli DNA by qPCR using the heat shock protein 70â¯kDa (hsp70) gene of B. vogeli. Characteristics related to the host and its environment were collected using a questionnaire. Bivariate analysis was used to evaluate each factor individually. A phi correlation test was used to verify collinearity. The variables with pâ¯<â¯.1 and a low or moderate correlation with the other variables were selected for the multivariate analysis. Multiple models were created, and the best logistic regression model was chosen using the Akaike Information Criterion (AIC). The final model was used to determine which variables were closely related to B. vogeli infections in dogs. Of the 390 dog blood samples, 15.66% were positive for B. vogeli. The variables cat contact, age, shelter, street or woods access, tick infestation and fur lengthwere included in the final model. Per the logistic regression analysis, three variables explained B. vogeli detection in dogs: age (odds ratio [OR]â¯=â¯2.12; p-value <.05; confidence interval [CI]: 1.13-3.96), tick infestation (ORâ¯=â¯2.08; p-value <.05; CI: 1.10-3.93) and shelter (ORâ¯=â¯2.22; p-value <.05; CI: 1.16-4.26). These variables were determined to be associated with B. vogeli detection in domiciled dogs in the southeastern region of Rio de Janeiro, Brazil. These data indicate that the age of the animal, the presence of ticks and the lack of shelter directly affect the epidemiology of B. vogeli.
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Babesia/genética , Babesiosis/epidemiología , Enfermedades de los Perros/epidemiología , Infestaciones por Garrapatas/parasitología , Factores de Edad , Animales , Babesia/aislamiento & purificación , Brasil/epidemiología , ADN Protozoario/genética , Enfermedades de los Perros/parasitología , Perros/parasitología , Femenino , Proteínas HSP70 de Choque Térmico/genética , Modelos Logísticos , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Infestaciones por Garrapatas/epidemiología , Garrapatas/parasitologíaRESUMEN
Chlorhexidine is an antiseptic and disinfectant used in surgical and clinical practice since 1954 and is available in aqueous or alcoholic solutions 0.5%-4.0% and has a broad-spectrum activity. Despite their widespread use, allergic reactions with chlorhexidine are rarely reported. We describe a case of anaphylaxis with chlorhexidine during a septoplasty, turbinectomy, and maxillary sinusectomy. The patient presented with periorbital edema, hives, hypotension, and wheezing. Immediately after the diagnosis of anaphylaxis promethazine, hydrocortisone, and epinephrine were administered with immediate clinical improvement. This case highlights the importance of assessing whether there is a previous clinical history of hypersensitivity to chlorhexidine in patients who will undergo surgical procedures.
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A new epidemiological view of American trypanosomiasis or Chagas disease has been formulated in recent decades. Oral transmission of the etiological agent of Chagas disease, Trypanosoma cruzi, has been the most common form of transmission. The T. cruzi discrete typing units TcI and TcIV have been involved in tens outbreaks of acute cases of Chagas disease in the Brazilian Amazon region. We investigated the intensity of infection in mice that were orally inoculated (OR group) with four strains of TcIV that were isolated from two outbreaks of acute Chagas disease that was orally acquired in the state of Amazonas, Brazil. We compared the OR group with mice that were intraperitoneally inoculated (IP group). Blood samples were analyzed by fresh blood examination, hemoculture, and conventional and qualitative real-time polymerase chain reaction (PCR). Samples of different tissues were analyzed by quantitative real-time PCR. The OR group exhibited a higher maximum peak of parasitemia, greater rates of positivity, and higher parasite loads in different tissues during acute infection compared with the IP group, indicating a greater intensity of orally acquired infection. Mice that were orally inoculated with TcIV strains that were obtained from two outbreaks of orally acquired Chagas disease in Amazonas, Brazil, exhibited a more intense course of infection compared with intraperitoneally inoculated mice, reflected by higher levels of parasitemia and parasite loads.
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Enfermedad de Chagas/parasitología , Enfermedad de Chagas/transmisión , Parasitemia/parasitología , Trypanosoma cruzi/aislamiento & purificación , Administración Oral , Animales , Brasil/epidemiología , Enfermedades Transmisibles/epidemiología , Brotes de Enfermedades , Femenino , Humanos , Inyecciones Intraperitoneales , Ratones , Carga de Parásitos , Reacción en Cadena en Tiempo Real de la Polimerasa , Trypanosoma cruzi/patogenicidadRESUMEN
In breast cancer patients, primary chemotherapy is associated with the same survival benefits as adjuvant chemotherapy. Residual tumors represent a clinical challenge, as they may be resistant to additional cycles of the same drugs. Our aim was to identify differential transcripts expressed in residual tumors, after neoadjuvant chemotherapy, that might be related with tumor resistance. Hence, 16 patients with paired tumor samples, collected before and after treatment (4 cycles doxorubicin/cyclophosphamide, AC) had their gene expression evaluated on cDNA microarray slides containing 4,608 genes. Three hundred and eighty-nine genes were differentially expressed (paired Student's t-test, pFDR<0.01) between pre- and post-chemotherapy samples and among the regulated functions were the JNK cascade and cell death. Unsupervised hierarchical clustering identified one branch comprising exclusively, eight pre-chemotherapy samples and another branch, including the former correspondent eight post-chemotherapy samples and other 16 paired pre/post-chemotherapy samples. No differences in clinical and tumor parameters could explain this clustering. Another group of 11 patients with paired samples had expression of selected genes determined by real-time RT-PCR and CTGF and DUSP1 were confirmed more expressed in post- as compared to pre-chemotherapy samples. After neoadjuvant chemotherapy some residual samples may retain their molecular signature while others present significant changes in their gene expression, probably induced by the treatment. CTGF and DUSP1 overexpression in residual samples may be a reflection of resistance to further administration of AC regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Resistencia a Antineoplásicos/genética , Expresión Génica/efectos de los fármacos , Adulto , Anciano , Biomarcadores de Tumor/genética , Factor de Crecimiento del Tejido Conjuntivo/biosíntesis , Factor de Crecimiento del Tejido Conjuntivo/efectos de los fármacos , Factor de Crecimiento del Tejido Conjuntivo/genética , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Fosfatasa 1 de Especificidad Dual/biosíntesis , Fosfatasa 1 de Especificidad Dual/efectos de los fármacos , Fosfatasa 1 de Especificidad Dual/genética , Femenino , Perfilación de la Expresión Génica , Humanos , MAP Quinasa Quinasa 4/metabolismo , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasia Residual , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genéticaRESUMEN
This is the first report of a natural infection in the saffron finch Sicalis flaveola (Linnaeus, 1766) captured in Brazil, with the establishment of a new host record for the acuarioid nematode Acuaria mayori Lent, Freitas and Proença, 1945, previously referred in Cyanocorax chrysops (Vieillot, 1818) from Paraguay and Sporophila caerulescens caerulescens (Vieillot, 1823) and C. cyanomelas (Wied, 1821) from Brazil and Myarchus nuttingi (Ridgway, 1883) from Costa Rica.