Canine visceral leishmaniasis: study of methods for the detection of IgG in serum and eluate samples

The Brazilian Ministry of Health recommends the culling and euthanasia of dogs with a positive serological test for canine visceral leishmaniasis (CVL). In the Municipality of Rio de Janeiro, the technique used for the diagnosis of CVL is the indirect fluorescent antibody test (IFAT), using blood samples eluted on filter paper (eluate). A dog survey was conducted over a period of one year in the region of Carapiá, in order to evaluate the diagnosis of CVL in this region. All animals underwent clinical examination, and blood samples (serum and eluate) were collected for analysis by enzyme immunoassay (ELISA) and IFAT. A skin biopsy was obtained for parasitological examination (culture). A total of 305 animals were studied and Leishmania chagasi was isolated from nine animals. Sensitivity and specificity were 100% and 96.6% for ELISA, respectively, 100% and 65.5% for IFAT (cut-off at a 1:40 dilution), 100% and 83.4% for IFAT (cut-off at a 1:80 dilution), and 22.2% and 97.0% for eluate IFAT. In conclusion, ELISA was the best tool for the diagnosis of CVL among the serological techniques tested. The present results suggest the need for a better evaluation of filter paper IFAT as the only diagnostic method for CVL in the Municipality of Rio de Janeiro.O Ministério da Saúde recomenda a eutanásia de cães sororreatores como controle da leishmaniose visceral canina (LVC). No Município do Rio de Janeiro, a técnica utilizada para o diagnóstico da LVC é o teste de imunofluorescência indireta (IFI), utilizando amostras de sangue eluídas em papel de filtro (eluato). Um levantamento, durante um ano, foi conduzido na região de Carapiá, a fim de avaliar o diagnóstico da LVC nesta região. Todos os animais foram submetidos a exame clínico e coleta de sangue (soro e eluato) para realização do ensaio imunoenzimático (ELISA) e imunofluorescência indireta (IFI). Biópsia de pele foi obtida para o exame parasitológico (cultura). Foram avaliados 305 (89,4%) animais de uma população de 341 cães e Leishmania chagasi foi isolada de nove animais. A sensibilidade e especificidade do ELISA foram de 100% e 96,6%, na IFI (ponto de corte 1:40) de 100% e 65,5%, na IFI (ponto de corte 1:80) de 100% e 83,4% e na IFI (eluato) de 22,2% e 97,0%, respectivamente. A partir dos resultados obtidos podemos concluir que entre as técnicas sorológicas empregadas, o teste de ELISA apresentou-se como a melhor ferramenta para o diagnóstico da LVC. Os resultados sugerem a necessidade de uma melhor avaliação do teste de IFI realizada com eluato, como único método de diagnóstico para LVC no município do Rio de Janeiro

Rapid Sampling of Molecular Motions with Prior Information Constraints

Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT). Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complementary tool for molecular dynamics, Normal Mode Analysis, and other prevalent techniques for predicting motion in proteins. We applied our framework to three different model systems. We show that a limited set of experimentally motivated constraints may effectively bias the simulations toward diverse predicates in an outright fashion, from distance constraints to enforcement of loop closure. In particular, our analysis sheds light on mechanisms of protein domain swapping and on the role of different residues in the motion

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: a report of the international immuno-oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Presence of depressive symptoms in patients with a first episode of acute Coronary Syndrome

AIM: to compare possible differences regarding the presence of depressive symptoms according to the clinical diagnosis of Acute Coronary Syndrome, gender and age, one week before the first cardiac event. METHOD: cross-sectional, descriptive and exploratory study, which used the Beck Depression Inventory. The sample consisted of 253 patients. RESULTS: it was found that patients with a clinical diagnosis of unstable angina, female and under 60 years of age reported the presence of depressive symptoms more frequently. CONCLUSION: a high percentage of patients presented depressive symptoms at the time of hospitalization for the first episode of Acute Coronary Syndrome, and this prevalence was significantly higher among women, under 60 years of age, with unstable angina. These results should provide support for the care in the hospitalization, discharge and planning of the rehabilitation of these patients, as it is known that depression impairs the control of coronary disease

Comportamento da pressão arterial em homens pré-hipertensos participantes em um programa regular de natação

INTRODUÇÃO: A natação tem sido recomendada como tipo de atividade física para a prevenção, tratamento e controle da hipertensão arterial. OBJETIVO: Analisar os efeitos da prática regular de natação sobre a pressão arterial de adultos pré-hipertensos. MÉTODOS: A amostra foi composta por 36 homens pré-hipertensos divididos em dois grupos: Experimental - GE (n=24, 40,60±9,36 anos) e Controle - GC (n=12, 40,57±8,05 anos). O GE realizou um programa regular de natação, com três sessões semanais de 45 min, durante 12 semanas, enquanto o GC não alterou seus hábitos alimentares e permaneceu sem praticar atividade física no período. O procedimento estatístico utilizado para verificar as diferenças entre as médias antes e depois de 12 semanas do programa regular de natação foi o teste-t de Student. O estudo admitiu o nível de p < 0.05 para a significância estatística. RESULTADOS: O grupo GE apresentou diferenças estatisticamente significativas nas variáveis analisadas quando comparadas com o GC, tanto na pressão arterial sistólica, PAS (Δ = - 5,89 mmHg, p = 0,00), como na pressão arterial diastólica, PAD (Δ = - 5,15mmHg, p = 0,00). CONCLUSÃO: Os resultados mostram que um programa regular de natação provoca reduções significativas na pressão arterial em repouso em homens pré-hipertensos