Surveillance of avian influenza and Newcastle disease viruses in backyard poultry raised near migratory bird sites in Mato Grosso state, Brazil.

The Pantanal and Cerrado biomes in the state of Mato Grosso contain migratory bird sites in the municipalities of Cáceres and Araguaiana, respectively. The levels of avian influenza (AI) and Newcastle disease (ND) viral activity in backyard poultry at these sites are unknown owing to a lack of studies. Considering the risk of introduction of AI and ND to Brazil from migratory birds, as well as the importance of active surveillance in the detection and prevention of diseases for official control, monitoring in these poultry populations is faster, more practical and cheaper for official service veterinarians. The objective of this study was to verify the presence of AI and ND viral activity in backyard poultry reared near these migratory bird sites in the years 2016 and 2019. Serum samples and cloacal and tracheal swab samples collected from chickens, turkeys, quails, ducks and geese were evaluated by indirect diagnostic methods including enzyme-linked immunosorbent assay and haemagglutination inhibition tests and direct detection of viral sequences using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). No positive samples were detected by qRT-PCR.The frequencies of birds seropositive for AI and ND were 0.7% and 19.6% in 2016 and 0.5% and 17.2% in 2019, respectively, in Araguaiana and 0.8% and 32.3% in 2016 and 7.0% and 38.1% in 2019, respectively, in Cáceres. Antibodies belonging to AI subtypes H1, H4, H6 and H14 were identified in Cáceres in 2019. Spatial analysis showed an agglomeration of farms with seropositive poultry within the urban area of Cáceres, suggesting AI and ND virus activity in this area. This study showed no circulation of the notifiable AI subtypes H5 and H7 or the ND virus in backyard poultry raised around migratory bird sites in the state of Mato Grosso. The results of the present study support evidence indicating that the circulation of strains with low pathogenicity in urban areas enables backyard poultry to serve as a source of infection for other birds; thus, increased surveillance is necessary in this population.

Les biomes du Pantanal et du Cerrado dans l'état du Mato Grosso contiennent deux sites accueillant des oiseaux migrateurs, situés respectivement dans les comtés de Cáceres et d'Araguaiana. Faute d'études de terrain, le niveau d'activité virale de l'influenza aviaire et de la maladie de Newcastle chez les volailles de basse-cour de ces deux sites était jusqu'à présent inconnu. Compte tenu du risque d'introduction au Brésil de l'influenza aviaire et de la maladie de Newcastle par les oiseaux migrateurs, et de l'importance de la surveillance active pour détecter et prévenir ces maladies dans le cadre des activités de lutte conduites par les Services vétérinaires, il est plus pratique, moins onéreux et plus rapide pour les vétérinaires des services officiels d'axer la surveillance sur les populations de volailles de basse-cour. Les auteurs présentent les résultats d'une étude conduite en 2016 et en 2019 pour déterminer le niveau de circulation des virus de l'influenza aviaire et de la maladie de Newcastle chez les volailles de basse-cour élevées à proximité des sites d'oiseaux migrateurs. Des échantillons sériques et des écouvillons cloacaux et trachéaux prélevés sur des poulets, des dindes, des cailles, des canards et des oies ont été soumis à des méthodes de diagnostic indirectes telles que les épreuves immuno-enzymatique et d'inhibition de l'hémagglutination, et à une méthode de détection directe des séquences virales par amplification en chaîne par polymérase quantitative en temps réel couplée à une transcription inverse (qRT-PCR). Aucun échantillon positif n'a été détecté par qRT-PCR. Les taux de séropositivité respectivement à l'influenza aviaire et à la maladie de Newcastle étaient, chez les volailles prélevées à Araguaiana, de 0,7 % et 19,6 % en 2016, et de 0,5 % et 17,2 % en 2019 ; chez les volailles prélevées à Cáceres, ils étaient de 0,8 % et 32,3 % en 2016, et de 7,0 % et 38,1 % en 2019. Les anticorps détectés à Cáceres en 2019 appartenaient aux sous-types H1, H4, H6 et H14 du virus de l'influenza aviaire. L'analyse spatiale a révélé une concentration importante d'élevages ayant des volailles séropositives dans la zone urbaine de Cáceres, indiquant une activité des virus de l'influenza aviaire et de la maladie de Newcastle dans cette région. Aucune circulation des sous-types H5 et H7 à déclaration obligatoire du virus de l'influenza aviaire ni du virus de la maladie de Newcastle n'a été mise en évidence chez les volailles de basse-cour élevées autour des sites d'oiseaux migrateurs dans l'état du Mato Grosso. Les résultats de cette étude étayent les données d'après lesquelles les volailles de basse-cour des zones urbaines deviennent des sources d'infection pour d'autres espèces d'oiseaux à la faveur d'une circulation de souches faiblement pathogènes ; il est donc nécessaire de renforcer la surveillance dans cette population.

Los biomas de Pantanal y Cerrado, situados en el estado de Mato Grosso, albergan espacios frecuentados por aves migratorias en los municipios de Cáceres y Araguaiana, respectivamente. Debido a la falta de estudios al respecto, se desconocen los niveles de actividad de los virus de la influenza aviar (IA) y de la enfermedad de Newcastle (EN) en las aves de corral caseras de estas zonas. Teniendo en cuenta el riesgo de introducción en el Brasil de la IA y la EN por conducto de aves migratorias, así como la importancia de una vigilancia activa para la detección y prevención de enfermedades con fines de control oficial, para los veterinarios de los servicios públicos resulta más rápido, práctico y barato vigilar esas poblaciones de aves de corral. Los autores describen un estudio encaminado a comprobar, en los años 2016 y 2019, la actividad de los virus de la IA y la EN en bandadas caseras de aves de corral criadas cerca de los antedichos espacios de aves migratorias. Tras obtener muestras séricas e hisopados cloacales y traqueales de pollos, pavos, codornices, patos y gansos, se analizaron las muestras con técnicas de diagnóstico indirecto (ensayo inmunoenzimático y prueba de inhibición de la hemaglutinación) y de detección directa de secuencias víricas (retrotranscripción acoplada a reacción en cadena de la polimerasa cuantitativa en tiempo real: qRT-PCR). No se detectó ninguna muestra positiva por qRT-PCR. En cuanto a las tasas de seropositividad para la IA y la EN, en Araguaiana resultaron positivas el 0,7% y el 19,6%, respectivamente, de las aves analizadas en 2016, por un 0,5% y un 17,2% en 2019, mientras que en Cáceres lo fueron el 0,8% y el 32,3% en 2016 y el 7,0% y el 38,1% en 2019. En 2019 se identificaron en Cáceres anticuerpos correspondientes a los subtipos H1, H4, H6 y H14 del virus de la influenza aviar. El análisis espacial puso de relieve una aglomeración de fincas con aves de corral seropositivas en la zona urbana de Cáceres, hecho indicativo de que en la zona hay actividad de los virus de la IA y la EN. El estudio no evidenció circulación alguna de los subtipos H5 y H7 del virus de la IA, que son de declaración obligatoria, ni del virus de la EN en las aves de corral caseras criadas en los alrededores de los espacios del estado de Mato Grosso que albergan aves migratorias. Los resultados del estudio parecen avalar los datos que indican que la circulación de cepas poco patógenas en zonas urbanas hace de las bandadas caseras una posible fuente de infección para otras aves, razón por cual es tanto más necesario redoblar la vigilancia de estas poblaciones de aves de corral.

Spatial distribution and risk factors for equine infectious anaemia in the state of Mato Grosso, Brazil.

The prevalence of equine infectious anaemia (EIA) in the three biomes of the state of Mato Grosso (Amazon, Cerrado and Pantanal) was estimated. Serum samples were collected from 3,858 equines in 1,067 herds between Septemberand December 2014. The agar gel immunodiffusion (AGID) assay was used to detect EIA virus antibodies, and if a herd contained a seropositive animal itwas classified as a focus. The prevalence rates were 17.2% (95% confidence interval [CI]: 14.9-19.8%) for herds and 6.6% (95% CI: 5.8-7.5%) for animals. The Pantanal region showed the highest prevalence rates: 36.1% (95% CI: 30.8-41.7%) for herds and 17.0% (95% CI: 14.7-19.6%) for animals. The spatial distribution of relative risk was calculated according to the kernel density, which revealed three major clusters with the highest prevalence rates occurring in the north-western(Amazon biome), north-eastern (Cerrado biome) and southern (Pantanal biome)regions. A high spatial correlation was found among ranches, with high intra-herd prevalence rates located in the Amazon and Cerrado biomes, but the highest spatial correlation with EIA foci was found in the Pantanal biome. Variables related to ranch management, reflecting human influence, were associated with positive equines. Based on the results, it can be concluded that EIA is present in all biomes of the state, and that the risk factors are associated with human interference in the transmission process. Given this situation, the EIA control programme should be re-evaluated and more prophylactic measures should be adopted to control the disease.

Les auteurs présentent les résultats d'une estimation de la prévalence de l'anémie infectieuse des équidés (AIE) dans les trois biomes de l'état du Mato Grosso (l'Amazonie, le Cerrado et le Pantanal) réalisée de septembre à décembre2014 à partir d'échantillons de sérum collectés chez 3 858 équidés dans1 067 troupeaux. La méthode d'immunodiffusion sur gélose était utilisée pour détecter les anticorps anti-AIE. En cas de test positif chez un individu, le troupeau était classé comme un foyer. La prévalence par troupeau était de 17,2 % (intervalle de confiance à 95 % [IC 95 %] de 14,9 à 19,8) tandis que la prévalence individuelle était de 6,6 % (IC 95 % de 5,8 à 7,5). La prévalence la plus élevée était enregistrée dans la région du Pantanal : 36,1 % (IC 95 % de 30,8 à 41,7) par troupeaux et17,0 (IC 95 % de 14,7 à 19,6) à l'échelle des individus. La distribution spatiale du risque relatif estimée par noyau montre trois grappes de prévalence élevée dans le nord-ouest (biome de l'Amazonie), le nord-est (biome du Cerrado) et le sud (biome du Pantanal). Si une corrélation spatiale forte est observée dans les élevages des biomes de l'Amazonie et du Cerrado où la prévalence intra-troupeau est élevée, la corrélation spatiale la plus élevée avec les foyers d'AIE se trouve dans le biome du Pantanal. Une association a été constatée entre les équidés testés positifs et les variables descriptives liées aux pratiques d'élevage, ce qui traduit l'importance de l'influence humaine. À partir de ces résultats, on peut conclure que l'AIE est présente dans l'ensemble des biomes de l'état et que les facteurs de risque sont associés à l'interférence humaine dans le processus de transmission. Ainsi, une réévaluation du programme de lutte contre l'AIE serait indiquée avec plus de mesures prophylactiques afin de contrôler la maladie.

Los autores describen el proceso seguido para estimar la prevalencia de anemia infecciosa equina en los tres biomas presentes en el estado de Mato Grosso (Amazonia, Cerrado y Pantanal). Entre septiembre y diciembre de 2014 se extrajeron muestras a 3.858 equinos de 1.067 rebaños, a las que se aplicó la técnica de inmunodifusión en gel de agar para detectar anticuerpos contra el virus de la anemia infecciosa equina: todo rebaño en el que hubiera un animal seropositivo era considerado un foco. La tasa de prevalencia de rebaños infectados resultó del 17,2% (intervalo de confianza [IC] al 95%: 14,9­19,8) y la de individuos infectados del 6,6% (IC 95%: 5,8­7,5). Las tasas más elevadas se observaron en la región de Pantanal: un 36,1% (IC 95%: 30,8­41,7) de prevalencia de rebaño y un 17,0% (IC 95%: 14,7­19,6) de prevalencia individual. La distribución espacial del riesgo relativo se determinó con arreglo a la densidad kernel, proceso que reveló la presencia de tres grandes conglomerados: las mayores tasas de prevalencia se situaban en las regiones del noroeste (en el caso del bioma amazónico), el noreste (biomade Cerrado) y el sur (bioma de Pantanal). Se observó que existía una estrecha correlación espacial entre explotaciones, y aunque en los biomas de la Amazonia y Cerrado había elevadas tasas de prevalencia intrarrebaño, fue en el bioma de Pantanal donde se observó la correlación espacial más estrecha con los focos de anemia infecciosa equina. La presencia de equinos seropositivos venía asociada a variables relacionadas con la gestión de las explotaciones, hecho que pone de relieve la influencia humana en la cuestión. A tenor de los resultados, cabe concluir que la anemia infecciosa equina está presente en todos los biomas del estado y que los factores de riesgo guardan relación con la interferencia humana en el proceso de transmisión. Ante tal situación, convendría evaluar de nuevo el programa de lucha contra la anemia infecciosa y poner mayor acento en las medidas profilácticas para combatir la enfermedad.

Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions.

BACKGROUND: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). PATIENTS AND METHODS: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected. RESULTS: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had <10 pg mutated genomes/µl with allelic fractions below 0.25%. Patients treated first line with TKIs based exclusively on EGFR positivity in blood had an ORR of 72% and a median PFS of 11 months. Of 105 patients screened after progression to EGFR-TKIs, sensitizing mutations were found in 56.2% and the p.T790M resistance mutation in 35.2%. CONCLUSIONS: Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

A survey of tick-borne pathogens in dogs and their ticks in the Pantanal biome, Brazil.

Tick and blood samples collected from domestic dogs in the Brazilian Pantanal were tested by molecular methods for the presence of tick-borne protozoa and bacteria. Among 320 sampled dogs, 3.13% were infected by Babesia vogeli (Piroplasmida: Babesiidae), 8.75% by Hepatozoon canis (Eucoccidiorida: Hepatozoidae), 7.19% by Anaplasma platys (Rickettsiales: Anaplasmataceae), and 0.94% by an unclassified Anaplasma sp. In three tick species collected from dogs, the following tick-borne agents were detected: (a) B. vogeli, An. platys and Ehrlichia canis (Rickettsiales: Anaplasmataceae), infecting Rhipicephalus sanguineus sensu lato (Ixodida: Ixodidae) ticks; (b) H. canis, an unclassified Anaplasma sp. and Rickettsia amblyommii (Rickettsiales: Rickettsiaceae), infecting Amblyomma cajennense sensu lato (Ixodida: Ixodidae) ticks, and (c) Rickettsia sp. strain Atlantic rainforest, an emerging human pathogen, infecting Amblyomma ovale ticks. Molecular analysis, based on a mitochondrial gene, revealed that the Am. cajennense s.l. ticks of the present study corresponded to Amblyomma sculptum, a member of the Am. cajennense species complex, and that Rh. sanguineus s.l. belonged to the tropical lineage. Whereas dogs are exposed to a number of tick-borne bacterial and protozoan agents in the Pantanal biome, humans are potentially exposed to infection by spotted fever group rickettsiae (e.g. R. amblyommii and Rickettsia sp. strain Atlantic rainforest) because both Am. sculptum and Am. ovale are among the most important human-biting ticks in Brazil.

Development and evaluation of a loop-mediated isothermal amplification assay for detection of Ehrlichia canis DNA in naturally infected dogs using the p30 gene.

Canine monocytic ehrlichiosis (CME) is a common tick-borne disease caused by the rickettsial bacterium Ehrlichia canis (Rickettsiales: Anaplasmataceae). In view of the different stages and variable clinical signs of CME, which can overlap with those of other infections, a conclusive diagnosis can more readily be obtained by combining clinical and hematological evaluations with molecular diagnostic methods. In this study, a loop-mediated isothermal amplification (LAMP) assay targeting the p30 gene of E. canis was developed. The assay was developed using DNA extracted from E. canis-infected cultures of the macrophage cell line DH82 and samples from dogs testing positive for E. canis DNA by PCR. The LAMP assay was compared to a p30-based PCR assay, using DNA extracted from EDTA-anticoagulated blood samples of 137 dogs from an endemic region in Brazil. The LAMP assay was sensitive enough to detect a single copy of the target gene, and identified 74 (54.0%) E. canis DNA-positive samples, while the p30 PCR assay detected 50 positive samples (36.5%) among the field samples. Agreement between the two assays was observed in 42 positive and 55 negative samples. However, 32 positive samples that were not detected by the PCR assay were identified by the LAMP assay, while eight samples identified as E. canis-positive by PCR showed negative results in LAMP. The developed E. canis LAMP assay showed the potential to maximize the use of nucleic acid tests in a veterinary clinical laboratory, and to improve the diagnosis of CME.

Molecular characterization of Babesia vogeli in dogs from Belém, northern Brazil.

Babesiosis is an infectious hemolytic disease that occurs worldwide, and is caused by a protozoan of the Babesia genus (Apicomplexa). Little is known about this genus; therefore, this study conducted a molecular characterization of Babesia spp in naturally infected dogs in northern Brazil. Blood samples were collected from 172 dogs from metropolitan Belém, and screened for Babesia spp using semi-nested polymerase chain reactions. Subsequently, 18S rDNA gene fragments were amplified and sequenced. Alignments of the 27 nucleotide sequences returned fragments measuring 1023 bp in size, which did not include any polymorphic sites (100% identity). This genotype was very similar to the 18S rDNA gene in B. vogeli. This study provides an important molecular characterization of the parasite responsible for canine babesiosis in naturally infected dogs in metropolitan Belém. In addition, the 18S rDNA gene in B. vogeli may represent the most common genotype occurring in South America.

Adjuvant therapy with cetuximab for locally advanced squamous cell carcinoma of the oropharynx: results from a randomized, phase II prospective trial.

BACKGROUND: Cetuximab combined with radiotherapy (RT) is a treatment option for head and neck cancer. The objectives of this randomized, phase II trial were to evaluate the efficacy and safety of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in patients with oropharyngeal cancer. PATIENTS AND METHODS: Ninety-one patients with stage III-IV M0 oropharyngeal tumors were randomly assigned to the treatment with accelerated concomitant boost RT (69.9 Gy) + cetuximab or the same treatment with the addition of 12 consecutive weeks of cetuximab maintenance therapy. The primary end point was locoregional control (LRC) at 1 year. RESULTS: LRC at 1 year was superior among patients in the experimental arm, treated with cetuximab maintenance (59% versus 47%). However, LRC was similar between both arms after 2 years of follow-up, as a result of increased locoregional recurrences after the first year in the maintenance group. Patients treated with adjuvant cetuximab do recover very soon from toxic effect after combined treatment. CONCLUSIONS: Twelve weeks of cetuximab maintenance therapy after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma is feasible and improves clinical outcomes measured at 1 year. This improvement is not maintained after the second year suggesting that epidermal growth factor receptor blockade is not sufficient to completely eliminate the minimal residual disease.

First molecular description of autochthonous urban cases of canine visceral leishmaniasis in the city of Belém, Pará, Brazil.

Leishmaniasis is an anthropozoonosis transmitted by vectors, with dogs being the main domestic reservoirs. Brazil is one of the countries most affected by this disease, and it has been described in humans and dogs in every region in the country. In the northern region leishmaniasis cases in humans have been described in more than 100 municipalities in the State, including the capital, Belém. This study involves two cases of canine visceral leishmaniasis in which the animals developed clinical signs compatible with the disease in urban areas in Belém, the Pará state capital. The diagnosis was confirmed via polymerase chain reaction (PCR) to detect SSUr-rDNA and kDNA of Leishmania sp. and Leishmania infantum, respectively. In one of the cases the animal died and in the other the animal underwent treatment with medicines prescribed for dogs. Through this treatment, parasitemia in the second animal has been kept under control and is being monitored through molecular tests. Previously, no canine cases had been notified from urban neighborhoods in the city of Belém, but only on the island of Cotijuba, at a distance of 29 kilometers from the city. Cases of canine and human leishmaniasis have been recorded close to the capital, Belém, which has areas of conserved vegetation and where the presence of disease vectors has been described. Thus, as has been done in several other Brazilian cities, this study uses clinical and laboratory findings to confirm the presence of autochthonous cases of canine visceral leishmaniasis in the city of Belém.

Gradual Correction of Valgus Deformities of the Tibia Using a Monolateral External Fixator.

Objective: To present a review of patients subjected to gradual correction of a valgus deformity of the tibia using a monolateral external fixator. Method: This retrospective review included patients from January 2012 to May 2022 who met the following inclusion criteria: deviation of mechanical axis of the limb due to valgus deformity of the tibia; tibial deformity in the coronal plane on radiographic examination; a documented outpatient pre-operative evaluation by an orthopaedic surgeon and age between 10 and 70 years. The following exclusion criteria were applied: the presence of another tibia deformity preventing gradual correction using the proposed assembly; skin conditions incompatible with the surgical procedure; inadequate pre- or post-operative radiological evaluation; and insufficient information in the medical records. Results: The mean age of patients with a valgus deformity of the tibia was 30.8 ± 15.9 years. These patients had a body mass index (BMI) of 26.1 ± 5.5 kg/m2. A congenital or developmental aetiology was attributed to 58.3% of the cases. Most commonly, the deformity was found in the middle third of the tibia with a mean deformity of 14.7 ± 6.6 degrees. The total external fixator time ranged from 73 to 229 days (average 149.7 ± 36.1 days). The mean medial proximal and lateral distal tibial angles differed significantly for pre- and post-operative measurements (p ≤ 0.05). There were complications in eight cases; five cases of pin site infections, two cases of medial cortical fracture and one case of peroneal nerve neuropraxia. Conclusion: The proposed correction technique produces a satisfactory angular correction and with similar outcomes as described in the literature. How to cite this article: Motta DP, Faria JLR, Couto A, et al. Gradual Correction of Valgus Deformities of the Tibia Using a Monolateral External Fixator. Strategies Trauma Limb Reconstr 2023;18(2):123-132.

Prospective Pilot study of Quality of Life in patients with severe late-radiation-toxicity treated by Low hyperbaric-oxigen-therapy.

Background/purpose: The aim of this study is to assess for the first time the immediate and long term impact on quality-of-life of HBO treatments(HBOT) at 1.45 ATA (Absolute Atmospheric Pressure) Medical Hyperbaric chamber. Methods: Patients over 18 years-old, suffering of grade 3 Common Terminology Criteria for Adverse Events (CTCAE) 4.0 radiation induced late toxicity and progressing to standard support therapy were included in this prospective study. HBOT was given daily, sixty minutes per session by a Medical Hyperbaric Chamber Biobarica System at 1.45 ATA at 100% O2. Forty sessions were prescribed for all patients given in 8 weeks. Patients reported outcomes (PROs) was assessed by the QLQ-C30 questionnaire, before starting, in the last week of the treatment, as well as during follow up. Results: Between February-2018/June-2021, 48 patients fulfilled the inclusion criteria. A total of 37 patients (77%) completed the treatment prescribed HBOT sessions. Patients with anal fibrosis (9/37) and brain necrosis (7/37) were the most frequently treated. The most common symptoms were pain (65%) and bleeding (54%). In addition, thirty out of the 37 patients who completed the pre- and post-treatment Patients Reported Outcomes (PROs) assessment also completed the follow up European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire C30 (EORTC-QLQ-C30), and were evaluated in the present study. Mean follow up was 22,10 (6-39) months.The Median score of the EORTC-QLQ-C30, at the end of HBOT and during follow-up, was improved in all assessed domains, except in the cognitive aspect (p = 0.106). Conclusions: HBOT at 1.45 ATA is a feasible and well tolerated treatment, improving long term quality of life in terms of physical function, daily activities and general health subjective state of patients suffering severe late radiation-induced toxicity.

Use of a generalized additive model for a spatial analysis of bovine brucellosis risk in the state of Mato Grosso in 2002 and 2014.

Diseases that affect cattle represent obstacles to the development of livestock activity. Brucellosis is a significant such disease because it is transmissible, has a chronic nature, and causes health and economic damages to the herd and rural producer. Data from surveys performed in 2002 and 2014 were compared to identify the spatial distribution of bovine brucellosis and to evaluate clusters of outbreaks and areas of greater risk to have infected cattle in the state of Mato Grosso, Brazil. The present study analyzed the data obtained in the aforementioned investigations with a statistical model based on a spatial point process called a generalized additive model (GAM). The analysis made it possible to identify the regions of highest and lowest risk in the state of Mato Grosso. Of the 1001 properties analyzed in 2002, 198 were in areas with high-odds ratio, and 121 were in a low-odds ratio area. Of the 1248 properties sampled in 2014, 119 were in a high-odds ratio area, and 162 were in a low-odds ratio area. Areas with high-odds ratio are more likely to have infected cattle and can be considered to be at higher risk for the disease. The results of the present study highlight the reduction in foci, prevalence, and its relationship with the spatial distribution of bovine brucellosis. The study results should help the official defense service of Mato Grosso direct its activities according to the profile of each region.

Phoretic mites (Rhinoseius spp.) in Apodiformes from Cerrado and Pantanal Biomes in midwestern Brazil.

Nasal mites are commonly found in hummingbirds (Apodiformes). In most cases, endoparasitic mites were reported to parasitize the respiratory system, particularly the anterior nasal chambers, larynx, trachea, lungs, and the air and conjunctival sacs. However, some mites are only carried by hummingbirds, because flowers serving as a nutrient source for these small mites, such as for Apodiformes, a tropical nectar-feeding in their natural habitat. From August 2012 to May 2014, humminbirds were captured using mist nets, and examined for the presence of nasal mites (identified according to specific keys) in the Pantanal, and Cerrado biomes, from the Mato Grosso state, midwestern Brazil. Overall, 76 Apodiform specimens, from the Trochilidae family were captured, and 20 female nasal mites, identified as being from the Rhinoseius genus, were collected from eight hosts (10.5%), of the following species: Amazilia fimbriata, Amazilia versicolor, Eupetonema macroura, and Thalurania furcata. The Rhinoseius spp. has been reported on, in many ecosystems in the Americas, including Brazil, however, this is the first report on Apodiformes from the Pantanal biome. Phoretic mites are not responsible for direct damage to the population of Apodiformes, as they are not pathogenic. However, they compete for food with hummingbirds and decrease the quantity of food available in the environment. They also affect the reproductive dynamics of plants, feed on pollen, and interfere with the intricacies of the biodiversity where they live.

Chromosomal effects of rapid gene evolution in Drosophila melanogaster.

Rapid adaptive fixation of a new favorable mutation is expected to affect neighboring genes along the chromosome. Evolutionary theory predicts that the chromosomal region would show a reduced level of genetic variation and an excess of rare alleles. We have confirmed these predictions in a region of the X chromosome of Drosophila melanogaster that contains a newly evolved gene for a component of the sperm axoneme. In D. simulans, where the novel gene does not exist, the pattern of genetic variation is consistent with selection against recurrent deleterious mutations. These findings imply that the pattern of genetic variation along a chromosome may be useful for inferring its evolutionary history and for revealing regions in which recent adaptive fixations have taken place.

Antiaversive effects of cannabinoids: is the periaqueductal gray involved?

Cannabinoids play an important role in activity-dependent changes in synaptic activity and can interfere in several brain functions, including responses to aversive stimuli. The regions responsible for their effects, however, are still unclear. Cannabinoid type 1 (CB1) receptors are widely distributed in the central nervous system and are present in the periaqueductal gray (PAG), a midbrain structure closely involved in responses related to aversive states. Accordingly, exposure to stressful stimuli increases endocannabinoid (eCB) levels in the PAG, and local administration of CB1 agonists or drugs that facilitate eCB-mediated neurotransmission produces antinociceptive and antiaversive effects. To investigate if these drugs would also interfere in animal models that are sensitive to anxiolytic drugs, we verified the responses to intra-PAG injection of CB1 agonists in rats submitted to the elevated plus-maze, the Vogel punished licking test, or contextual aversive conditioning model. The drugs induced anxiolytic-like effects in all tests. The same was observed with the transient receptor potential vanilloid type 1 (TRPV1) antagonist capsazepine and with cannabidiol, a nonpsychotomimetic phytocannabinoid that produces anxiolytic-like effects after systemic administration in humans and laboratory animals. These results, therefore, suggest that the PAG could be an important site for the antiaversive effects of cannabinoids.

Activation of CB1 cannabinoid receptors in the dorsolateral periaqueductal gray reduces the expression of contextual fear conditioning in rats.

RATIONALE: Conditioned fear to context causes freezing and cardiovascular changes in rodents and has been used to measure anxiety. It also activates the dorsolateral column of the periaqueductal gray (dlPAG). Microinjections of cannabinoid agonists into the dlPAG produced anxiolytic-like effects in the elevated plus maze, but the effects of these treatments on fear conditioning remains unknown. OBJECTIVE: The objective of this study was to verify if intra-dlPAG injection of the CB1 cannabinoid receptor agonist anandamide (AEA) or the anandamide transport inhibitor AM404 would attenuate behavioral (freezing) and cardiovascular (increase of arterial pressure and heart rate) responses of rats submitted to a contextual fear-conditioning paradigm. MATERIALS AND METHODS: Male Wistar rats with cannulae aimed at the dlPAG were re-exposed to a chamber where they had received footshocks 48 h before. Fifteen minutes before the test, the animals received a first intra-dlPAG injection of vehicle or AM251, a CB1 receptor antagonist (100 pmol/200 nl), followed 5 min later by vehicle, AEA (5 pmol/200 nl) or AM404 (50 pmol/200 nl). Freezing and cardiovascular responses were recorded for 10 min. RESULTS: Freezing and cardiovascular responses were reduced by administration of either AEA or AM404 into the dlPAG before re-exposition to the aversively conditioned context. These effects were abolished when the animals were locally pretreated with AM251. The latter drug, even at a higher dose (300 pmol), was ineffective when administered alone into the dlPAG. CONCLUSION: The results suggest that facilitation of endocannabinoid-mediated neurotransmission in the dlPAG, through activation of local CB1 receptors, attenuates the expression of contextual fear responses.

Hepatic injury induced by thioacetamide causes aortic endothelial dysfunction by a cyclooxygenase-dependent mechanism.

Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation and cirrhotic cardiomyopathy. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include vascular dysregulations. AIM: The present study tested the hypothesis that the systemic vascular hyporesponsiveness in thioacetamide (TAA)-induced liver injury model is dependent on nitric oxide (NO) and cyclooxygenase (COX) derivatives. MAIN METHODS: Wistar rats were treated with TAA for eight weeks to induce liver injury. KEY FINDINGS: The maximal contractile response in concentration-effect curves to phenylephrine was decreased in aorta from TAA-treated rats, but no differences were found in aorta without endothelium, suggesting an endothelium-dependent mechanism in decreased contractile response. There was no difference in the contractile response with and without L-NAME (N(ω)-nitro-l-arginine methyl ester) in rats with liver injury, showing that the TAA treatment impairs NO synthesis. Pre-incubation of the aorta with indomethacin, a COX-inhibitor, normalized the reduced contractile response to phenylephrine in arteries from TAA group. Also, COX-2 and iNOS (inducible nitric oxide syntase) protein expression was increased in aorta from TAA group compared to control group. Animals submitted to TAA treatment had a reduction in systolic blood pressure. Our findings demonstrated that liver injury induced by TAA caused a decrease in aortic contractile response by a COX-dependent mechanism but not by NO release. Also, it was demonstrated an inflammatory process in the aorta of TAA-treated rats by increased expression of COX-2 and iNOS. SIGNIFICANCE: Therefore, there is an essential contribution of COX-2 activation in extra-hepatic vascular dysfunction and inflammation present in cirrhosis induced by TAA.

Metabolomics as a promising tool for early osteoarthritis diagnosis.

Osteoarthritis (OA) is the main cause of disability worldwide, due to progressive articular cartilage loss and degeneration. According to recent research, OA is more than just a degenerative disease due to some metabolic components associated to its pathogenesis. However, no biomarker has been identified to detect this disease at early stages or to track its development. Metabolomics is an emerging field and has the potential to detect many metabolites in a single spectrum using high resolution nuclear magnetic resonance (NMR) techniques or mass spectrometry (MS). NMR is a reproducible and reliable non-destructive analytical method. On the other hand, MS has a lower detection limit and is more destructive, but it is more sensitive. NMR and MS are useful for biological fluids, such as urine, blood plasma, serum, or synovial fluid, and have been used for metabolic profiling in dogs, mice, sheep, and humans. Thus, many metabolites have been listed as possibly associated to OA pathogenesis. The goal of this review is to provide an overview of the studies in animal models and humans, regarding the use of metabolomics as a tool for early osteoarthritis diagnosis. The concept of osteoarthritis as a metabolic disease and the importance of detecting a biomarker for its early diagnosis are highlighted. Then, some studies in plasma and synovial tissues are shown, and finally the application of metabolomics in the evaluation of synovial fluid is described.

The Endocannabinoid System and Anxiety.

The medical properties of Cannabis sativa is known for centuries. Since the discovery and characterization of the endogenous cannabinoid system, several studies have evaluated how cannabinoid compounds and, particularly, how the modulation of the endocannabinoid (eCB) system influences a wide range of functions, from metabolic to mental disorders. Cannabinoids and eCB system often exert opposite effects on several functions, such as anxiety. Although the mechanisms are not completely understood, evidence points to different factors influencing those effects. In this chapter, the recent advances in research about the relationship between eCB system and anxiety disorders in humans, as well as in animal models, will be discussed. The recent data addressing modulation of the eCBs in specific brain areas, such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of stria terminalis, hippocampus, and dorsal periaqueductal gray, will be summarized. Finally, data from animal models addressing the mechanisms through which the eCB system modulates anxiety-related behavior dependent on stressful situations, such as the involvement of different receptors, distinct eCBs, modulation of neurotransmitters release, HPA axis and immune system activation, and plastic mechanisms, will also be discussed.

Seroprevalence of Toxoplasma gondii antibodies in cats and pigs from rural Western Amazon, Brazil.

Antibodies to Toxoplasma gondii were assayed in sera of 63 cats and 80 pigs from 71 farms located at Rondônia State, Western Amazon, Brazil, by the modified agglutination test (MAT) and the indirect immunofluorescent antibody test (IFAT). Antibodies (MAT > or = 1: 25) were found in 55 of 63 cats (87.3%) with titers of 1:25 in 2, 1:50 in 2, 1:100 in 7, 1:200 in 1, 1:400 in 2, 1:800 in 9, 1:1,600 in 6, and 1:3,200 or higher in 26 cats. By IFAT, antibodies were found in 55 cats (87.3%) with titers of 1:25 in 2, 1:50 in 1, 1:100 in 4, 1:200 in 4, 1: 400 in 1, 1:800 in 13, 1:1,600 in 12, and 1:3,200 or higher in 18 cats. In pig sera, by MAT, antibodies were found in 30 of 80 pigs (37.5%) with titers of 1:25 in 2, 1:50 in 3, 1:100 in 2, 1:200 in 8, 1:400 in 3, 1:800 in 5, 1:1,600 in 3, and 1:3,200 or higher in 4 pigs. By using the IFAT (titers > or = 1:64), antibodies were found in 35 (43.7%) pigs. The ingestion of undercooked tissues of infected pigs can be a source of T. gondii infection for humans and cats. However, the high seroprevalence of T. gondii in cats from the Amazon seems most likely to be indicative of high contamination of the environment by oocysts.

First record of Pseudoryzomys simplex (Cricetidae, Sigmodontinae) in a flooded area of the Pantanal, Brazil.

Pseudoryzomys simplex is a small to medium sized terrestrial rodent confined to lowland open areas with strong seasonal rainfall throughout the Chaco, Cerrado and Caatinga. Despite its extensive range, the species is difficult to trap. In this report we provide the first record of P. simplex in the Pantanal, where three specimens were collected in a pasture of exotic grass. The specimens are morpometrically similar to the population from Paraguay (Chaco). In this sense, our report shows how interesting a taxonomic review of the species would be to better understand the real significance of the geographic variation herein observed.