Saliency-driven system models for cell analysis with deep learning.

Background and objectivesSaliency refers to the visual perception quality that makes objects in a scene to stand out from others and attract attention. While computational saliency models can simulate the expert's visual attention, there is little evidence about how these models perform when used to predict the cytopathologist's eye fixations. Saliency models may be the key to instrumenting fast object detection on large Pap smear slides under real noisy conditions, artifacts, and cell occlusions. This paper describes how our computational schemes retrieve regions of interest (ROI) of clinical relevance using visual attention models. We also compare the performance of different computed saliency models as part of cell screening tasks, aiming to design a computer-aided diagnosis systems that supports cytopathologists.MethodWe record eye fixation maps from cytopathologists at work, and compare with 13 different saliency prediction algorithms, including deep learning. We develop cell-specific convolutional neural networks (CNN) to investigate the impact of bottom-up and top-down factors on saliency prediction from real routine exams. By combining the eye tracking data from pathologists with computed saliency models, we assess algorithms reliability in identifying clinically relevant cells.ResultsThe proposed cell-specific CNN model outperforms all other saliency prediction methods, particularly regarding the number of false positives. Our algorithm also detects the most clinically relevant cells, which are among the three top salient regions, with accuracy above 98% for all diseases, except carcinoma (87%). Bottom-up methods performed satisfactorily, with saliency maps that enabled ROI detection above 75% for carcinoma and 86% for other pathologies.ConclusionsROIs extraction using our saliency prediction methods enabled ranking the most relevant clinical areas within the image, a viable data reduction strategy to guide automatic analyses of Pap smear slides. Top-down factors for saliency prediction on cell images increases the accuracy of the estimated maps while bottom-up algorithms proved to be useful for predicting the cytopathologist's eye fixations depending on parameters, such as the number of false positive and negative. Our contributions are: comparison among 13 state-of-the-art saliency models to cytopathologists' visual attention and deliver a method that the associate the most conspicuous regions to clinically relevant cells

Determination of βS haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

βS haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5%) were identified with genotype CAR/CAR, 9 (19.1%) CAR/BEN, 6 (12.8%) CAR/CAM, 1 (2.1%) BEN/BEN, 2 (4.3%) CAR/Atp, 1 (2.1%) BEN/Atp and 1 (2.1%) with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte

Primary healthcare and the construction of thematic health networks: what role can they play?

The enhancement of primary healthcare has been a core strategy for the empowerment of the Brazilian Unified Health System (SUS). Recent guidelines issued by OPAS and the Ministry of Health highlight the role it has played as a thematic communication network center, a regulating agent for the access and use of services required for comprehensive healthcare. Sponsored by PPSUS/Fapesp, this study examines the possibilities of the primary healthcare network exercising such a strategic function. Life narratives involving 15 regular users were produced in two cities of ABC Paulista, which have adopted the Family Health Strategy for the organization of their primary healthcare networks. The study presents three main findings: the primary healthcare network serves as an outpost of SUS by producing user values even for high complexity service users; the primary network is perceived is a place for simple care needs; there is shared impotence between users and teams when it comes to the network functioning as the coordinator of care, indicating that it does not possess the technological, operational and organizational material conditions or symbolic conditions (values, meanings, and representations) to be in a central position in the coordination of thematic healthcare networks.O fortalecimento da atenção básica tem sido valorizado como estratégia central para a construção do SUS. Diretrizes recentes emanadas pela OPAS e pelo MS destacam seu papel como centro de comunicação de redes temáticas, como reguladora do acesso e utilização dos serviços necessários para a integralidade do cuidado. O presente estudo, financiado com recursos PPSUS/Fapesp, problematiza as possibilidades da rede básica exercer tal função estratégica. Foram produzidas narrativas de vida de 15 usuários altamente utilizadores de serviços de saúde em dois municípios do ABC paulista, que adotaram a Estratégia de Saúde da Família para organização de suas redes básicas. O estudo apresenta três achados principais: a rede básica funciona como posto avançado do SUS, produzindo valores de uso mesmo para os pacientes utilizadores de serviços de alta complexidade; a rede básica é vista como lugar de coisas simples; há uma impotência compartilhada entre usuários e equipes quando se trata da rede básica funcionar como coordenadora do cuidado, indicando como ela não reúne condições materiais (tecnológicas, operacionais, organizacionais) e simbólicas (valores, significados e representações) de deter a posição central da coordenação das redes temáticas de saúde.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina PreventivaInstituto Superior de Ciências do Trabalho e da Empresa Instituto Universitário de Lisboa Faculdade de Ciências Médicas Departamento de Saúde ColetivaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Saúde ColetivaUNIFESP, EPM, Depto. de Medicina PreventivaSciEL

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.Laboratório Central de Saúde Pública de Pernambuco Setor de VirologiaUniversidade Federal de Pernambuco Programa de Pós-Graduação em Medicina TropicalFiocruz Centro de Pesquisa Aggeu MagalhãesCentro de Testagem e Aconselhamento Herbert de SouzaUniversidade Federal de São Paulo (UNIFESP) Laboratório de RetrovirologiaUNIFESP, Laboratório de RetrovirologiaSciEL

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel