Treatment with a new peroxisome proliferator-activated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice

Trypanosoma cruzi infection induces an intense inflammatory response in diverse host tissues. The immune response and the microvascular abnormalities associated with infection are crucial aspects in the generation of heart damage in Chagas disease. Upon parasite uptake, macrophages, which are involved in the clearance of infection, increase inflammatory mediators, leading to parasite killing. The exacerbation of the inflammatory response may lead to tissue damage. Peroxisome proliferator-activated receptor gamma (PPAR\u3b3) is a ligand-dependent nuclear transcription factor that exerts important anti-inflammatory effects and is involved in improving endothelial functions and proangiogenic capacities. In this study, we evaluated the intermolecular interaction between PPAR\u3b3 and a new synthetic PPAR\u3b3 ligand, HP24, using virtual docking. Also, we showed that early treatment with HP24, decreases the expression of NOS2, a pro-inflammatory mediator, and stimulates proangiogenic mediators (vascular endothelial growth factor A, CD31, and Arginase I) both in macrophages and in the heart of T. cruzi-infected mice. Moreover, HP24 reduces the inflammatory response, cardiac fibrosis and the levels of inflammatory cytokines (TNF-\u3b1, interleukin 6) released by macrophages of T. cruzi-infected mice. We consider that PPAR\u3b3 agonists might be useful as coadjuvants of the antiparasitic treatment of Chagas disease, to delay, reverse, or preclude the onset of heart damage

A New Optical Density Granulometry-Based Descriptor for the Classification of Prostate Histological Images Using Shallow and Deep Gaussian Processes

[EN] Background and objective Prostate cancer is one of the most common male tumors. The increasing use of whole slide digital scanners has led to an enormous interest in the application of machine learning techniques to histopathological image classification. Here we introduce a novel family of morphological descriptors which, extracted in the appropriate image space and combined with shallow and deep Gaussian process based classifiers, improves early prostate cancer diagnosis. Method We decompose the acquired RGB image in its RGB and optical density hematoxylin and eosin components. Then, we define two novel granulometry-based descriptors which work in both, RGB and optical density, spaces but perform better when used on the latter. In this space they clearly encapsulate knowledge used by pathologists to identify cancer lesions. The obtained features become the inputs to shallow and deep Gaussian process classifiers which achieve an accurate prediction of cancer. Results We have used a real and unique dataset. The dataset is composed of 60 Whole Slide Images. For a five fold cross validation, shallow and deep Gaussian Processes obtain area under ROC curve values higher than 0.98. They outperform current state of the art patch based shallow classifiers and are very competitive to the best performing deep learning method. Models were also compared on 17 Whole Slide test Images using the FROC curve. With the cost of one false positive, the best performing method, the one layer Gaussian process, identifies 83.87% (sensitivity) of all annotated cancer in the Whole Slide Image. This result corroborates the quality of the extracted features, no more than a layer is needed to achieve excellent generalization results. Conclusion Two new descriptors to extract morphological features from histological images have been proposed. They collect very relevant information for cancer detection. From these descriptors, shallow and deep Gaussian Processes are capable of extracting the complex structure of prostate histological images. The new space/descriptor/classifier paradigm outperforms state-of-art shallow classifiers. Furthermore, despite being much simpler, it is competitive to state-of-art CNN architectures both on the proposed SICAPv1 database and on an external databaseThis work was supported by the Ministerio de Economia y Competitividad through project DPI2016-77869. The Titan V used for this research was donated by the NVIDIA CorporationEsteban, AE.; López-Pérez, M.; Colomer, A.; Sales, MA.; Molina, R.; Naranjo Ornedo, V. (2019). A New Optical Density Granulometry-Based Descriptor for the Classification of Prostate Histological Images Using Shallow and Deep Gaussian Processes. Computer Methods and Programs in Biomedicine. 178:303-317. https://doi.org/10.1016/j.cmpb.2019.07.003S30331717

Investigation of degradation products of cocaine and benzoylecgonine in the aquatic environment

In this work, ultra-high-performance liquid chromatography (UHPLC) coupled to a hybrid quadrupole time-of-flight mass spectrometer (QTOF MS) has allowed the discovery and elucidation of degradation products of cocaine and its main metabolite benzoylecgonine (BE) in water. Spiked surface water was subjected to hydrolysis, chlorination and photo-degradation (both ultraviolet irradiation and simulated sunlight). After degradation of cocaine, up to sixteen compounds were detected and tentatively identified (1 resulting from hydrolysis; 8 from chlorination; 7 from photo-degradation), three of which are well known cocaine metabolites (BE, norbenzoylecgonine and norcocaine). Regarding BE degradation, up to ten compounds were found (3 from chlorination; 7 from photo-degradation), including one known metabolite (norbenzoylecgonine). Since reference standards were available for the major metabolites, they could be confirmed using information on retention time and fragment ions. The other degradates resulted from chlorination, dealkylation, hydroxylation and nitration, or from a combination of these processes. Several influent and effluent sewage water, and surface water samples were then screened for the identified compounds (known and unknown) using UHPLC–tandem MS with triple quadrupole. BE, norcocaine and norbenzoylecgonine were identified in these samples as major metabolites. Four previously unreported degradates were also found in some of the samples under study, illustrating the usefulness and applicability of the degradation experiments performed in this work

Identification of new omeprazole metabolites in wastewaters and surface waters

Omeprazole is one of the world-wide most consumed pharmaceuticals for treatment of gastric diseases. As opposed to other frequently used pharmaceuticals, omeprazole is scarcely detected in urban wastewaters and environmental waters. This was corroborated in a previous research, where parent omeprazole was not detected while four transformation products (TPs), mainly resulting from hydrolysis, were found in effluent wastewaters and surface waters. However, the low abundance of omeprazole TPs in the water samples together with the fact that omeprazole suffers an extensive metabolism, with a wide range of excretion rates (between 0.01 and 30%), suggests that human urinary metabolites should be investigated in the water environment. In this work, the results obtained in excretion tests after administration of a 40 mg omeprazole dose in three healthy volunteers are reported. Analysis by liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF MS) reported low concentrations of omeprazole in urine. Up to twenty-four omeprazole metabolites (OMs) were detected and tentatively elucidated. The most relevant OM was an omeprazole isomer, which obviously presented the same exact mass (m/z 346.1225), but also shared a major common fragment at m/z 198.0589. Subsequent analyses of surface water and effluent wastewater samples by both LC-QTOF MS and LC-MS/MS with triple quadrupole revealed that this metabolite (named as OM10) was the compound most frequently detected in water samples, followed by OM14a and OM14b. Up to our knowledge, OM10 had not been used before as urinary biomarker of omeprazole in waters. On the contrary, parent omeprazole was never detected in any of the water samples. After this research, it seems clear that monitoring the presence of omeprazole in the aquatic environment should be focused on the OMs suggested in this article instead of the parent compound

Marginal mandibulectomy in the surgical treatment of tonsil and retromolar trigone tumours

Resection of the ascending ramus of the mandible can result in considerable functional and esthetic damage. AIM: To compare the survival rate and local and regional recurrence in marginal and segmental mandibulectomy for advanced tonsil and retromolar trigone tumours with no mandibular invasion. PLACE AND PERIOD: Reference Head & Neck Service, between October 1994 and December 2001. MATERIAL AND METHOD: 20 stage IV patients undergoing marginal mandibulectomy and 22 undergoing segmental mandibulectomy were compared. CASE STUDY: a contemporary cross-sectional cohort study. RESULTS: Of 20 patients undergoing marginal mandibulectomy, 35% died of the disease, 15% due to local recurrence, 15% due to regional recurrence and 5% due to local and regional recurrence. Of 22 patients undergoing segmentary mandibulectomy, 36,4% died of the disease, 31,8% due to local recurrence and 13,6% due to distant recurrence. The Kaplan-Meier analysis showed a 55% survival rate for the marginal mandibulectomy group, and a 45% survival rate for the segmental group (p= 0.8329). CONCLUSIONS: Analysis of the two groups showed that conservation of the ascending ramus of the mandible, even in advanced lesions with no mandibular involvement, does not increase the recurrence rate.A ressecção do ramo ascendente da mandíbula ocasiona um déficit funcional e estético considerável. OBJETIVO: Comparar a mandibulectomia marginal e segmentar de tumores avançados de loja amigdalina e região retromolar sem envolvimento ósseo mandibular detectado no período pré-operatório, em relação à sobrevida e recidiva loco-regional. Forma de Estudo: Estudo de coorte contemporânea com corte transversal. MATERIAL E MÉTODO: Compararam-se 20 pacientes tratados com mandibulectomia marginal e 22 tratados com mandibulectomia segmentar de outubro de 1994 a dezembro de 2001 em serviço de referência em Cirurgia de Cabeça e Pescoço. RESULTADOS: Dos 20 pacientes tratados com mandibulectomia marginal, 35% morreram com doença, 15% por recidiva local, 15% por recidiva regional e 5% por recidiva loco-regional. Dos 22 pacientes tratados com mandibulectomia segmentar 45,4% morreram pela doença, sendo 31,8% por recidiva local e 13,6% por recidiva à distância. Na análise pelo método de Kaplan-Meier o grupo tratado com mandibulectomia marginal apresentou uma taxa de 55%, e o grupo tratado com ressecção segmentar 45% com p= 0,8329. CONCLUSÕES: A análise dos dois grupos evidenciou que a conservação do ramo ascendente da mandíbula, mesmo em lesões avançadas, sem envolvimento mandibular, não aumenta o índice de recidiva.USP Departamento de Cirurgia PlásticaPUCCAMP Serviço de Cirurgia de Cabeça e PescoçoUNIFESPUSPUNICAMPHeliópolisUNICAMP Departamento de GenéticaUNIFESPSciEL

A Sociologia na Universidade de Brasília

This article analyses the development of sociological studies at UnB since the creation of the university and the commencement of social science studies. It is concerned principally with the profile of the academic staff and range of the graduate studies, and is complemented with a portrait of undergraduate courses. Highlighted is the fact that UnB’s department organizational structure, in conjunction with the university and Sociology Department’s requirement of D.Phil. degrees for academic staff has shaped a new model which is different from the typical Brazilian university’s “dual structure” approach where research and graduate studies are isolated from university’s other activities. The article’s objective is to stimulate the debate and articulate issues for discussion on the history of social science which will help focus on comparative analysis and on models for teaching and researching on sociological studies in Brazil.Cet article analyse la Sociologie à 1’Université de Brasília au moment de la création de 1’Université et des études en Sciences Sociales, en examinant surtout la carrièrre des professeurs, les cours au niveau du 3ème cycle et doctorat, en même temps qu’il ébauche un profil du cours de maitrise. On réitère 1’idée que 1’UnB, avec son organisation en départements et son exigence du titre de docteur pour le récrutement de ses professeurs, règle toujours en vigueur au Département de Sociologie, a echappé au modèle du “dualisme structurel” dominant dans d’autres institutions et qui consiste à séparer la recherche, le 30“' cycle et le doctorat des autres activités de 1’université. L’article perinet aussi un débat et stimule la reflexion sur les futures recherches pour qu’il soit possible de comparer de résultats avec d’autres institutions.Este artigo analisa o desenvolvimento da Sociologia na UnB desde a criação desta universidade e dos estudos em Ciências Sociais, detendo-se mais no exame do recrutamento do corpo docente, da consolidação de um grupo, da importância da pós-graduação, e complementando com um breve retrato do curso de graduação. E ressaltado o fato de que a UnB com sua estrutura departamental e com o requisito mínimo de doutorado para o recrutamento do corpo docente, que ainda é observado no Departamento de Sociologia, escapou do modelo, que impera em outras instituições, de “dualismo estrutural”, isolando a pesquisa e a pós-graduação do resto da universidade. O artigo se propõe a continuar e estimular o debate sobre a história das Ciências Sociais no Brasil e a levantar questões para novas pesquisas que produzam dados que possibilitem a comparação de vários casos e revelem os modelos de funcionamento e desenvolvimento do ensino e da pesquisa nestas disciplinas

Recurrent pneumonias in patient with antibody deficiency and normal immunoglobulins

The authors report the case of a 7-year-old girl, with a history of recurrent respiratory infections since five months of age. Immunological evaluation at four years of age revealed a normal level of total serum immunoglobulins, but a deficient humoral response to Streptococcus pneumoniae. Although having all normal IgG subclasses, the patient had inadequate antibody levels to all serotypes tested (1, 3, 5, 6, 9, and 14). Concurrent radiological evaluation showed diffuse atelectasis and bronchiectasis. Patient was started on IVIG, and subsequent chest CT scan revealed resolution of the above-mentioned lesions. To prevent irreversible damage to lung parenchyma, due to recurrent lower respiratory infections, it is important to identify immunocompromised individuals and treat them accordingly.É relatado o caso de uma menina de sete anos de idade com infecções de vias aéreas de repetição (otites, pneumonias e sinusites) desde os cinco meses de vida. A avaliação imunológica demonstrou produção inadequada de anticorpos ao Streptococcus pneumoniae após imunização para todos os sorotipos (1, 3, 5, 6, 9 e 14) testados, embora a paciente apresentasse níveis normais de imunoglobulinas. A avaliação radiológica, no momento da admissão, demonstrou presença de atelectasias difusas associadas a bronquiectasias. Após início do tratamento com imunoglobulina endovenosa e fisioterapia respiratória houve esvaecimento gradual até reversão das alterações radiológicas. Demonstrou-se, assim, a importância de um diagnóstico preciso para início de tratamento específico, com melhora gradual do quadro clínico e radiológico, evitando seqüelas pulmonares irreversíveis.UNIFESP-EPM Departamento de PediatriaUNIFESP-EPM Departamento de Diagnóstico por ImagemUNIFESP-EPMUniversidade de São Paulo Instituto de Ciências Biomédicas Departamento de ImunologiaUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPM Depto. de Diagnóstico por ImagemUNIFESP, EPMSciEL

A "masculinização" da produção de leite.

O fortalecimento de organizações sociais que possibilitaram fazer da produção de leite uma atividade destinada ao mercado provocou profundas mudanças na divisão sexual do trabalho. A análise sociológica das trocas intradomiciliares nos estabelecimentos rurais familiares mostra que tradições culturais, diferenças de poder entre os gêneros e contextos sociais que ampliam diferenças de acesso aos mercados entre homens e mulheres são as bases sociais e culturais de uma hierarquia estruturada segundo sexo e geração, no qual as mulheres, especialmente as mais jovens, ocupam posições de grande desvantagem. Com o fortalecimento de cooperativas, a produção de leite passou a ocupar um lugar de destaque no provimento de recursos da família, mas o domínio da atividade foi deslocado para o controle masculino. Esse foi um dos resultados não esperados da forma como as organizações conduziram o processo de modernização da produção e de reestruturação dos mercados, que reforçaram ainda mais o domínio masculino sobre a produção familiar e um aumento das desigualdades de gênero no acesso aos recursos

Application of gold nanoparticles as radiosensitizer for metastatic prostate cancer cell lines

More than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.The author is grateful for the financial support of Foundation for Science and Technology (grant reference: SFRH/BD/138271/2018).info:eu-repo/semantics/publishedVersio

CuMV VLPs Containing the RBM from SARS-CoV-2 Spike Protein Drive Dendritic Cell Activation and Th1 Polarization.

Dendritic cells (DCs) are the most specialized and proficient antigen-presenting cells. They bridge innate and adaptive immunity and display a powerful capacity to prime antigen-specific T cells. The interaction of DCs with the receptor-binding domain of the spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pivotal step to induce effective immunity against the S protein-based vaccination protocols, as well as the SARS-CoV-2 virus. Herein, we describe the cellular and molecular events triggered by virus-like particles (VLPs) containing the receptor-binding motif from the SARS-CoV-2 spike protein in human monocyte-derived dendritic cells, or, as controls, in the presence of the Toll-like receptors (TLR)3 and TLR7/8 agonists, comprehending the events of dendritic cell maturation and their crosstalk with T cells. The results demonstrated that VLPs boosted the expression of major histocompatibility complex molecules and co-stimulatory receptors of DCs, indicating their maturation. Furthermore, DCs' interaction with VLPs promoted the activation of the NF-kB pathway, a very important intracellular signalling pathway responsible for triggering the expression and secretion of proinflammatory cytokines. Additionally, co-culture of DCs with T cells triggered CD4+ (mainly CD4+Tbet+) and CD8+ T cell proliferation. Our results suggested that VLPs increase cellular immunity, involving DC maturation and T cell polarization towards a type 1 T cells profile. By providing deeper insight into the mechanisms of activation and regulation of the immune system by DCs, these findings will enable the design of effective vaccines against SARS-CoV-2