Infections with Avian Pathogenic and Fecal Escherichia coli Strains Display Similar Lung Histopathology and Macrophage Apoptosis

The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC) and avian fecal (Afecal) Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic Afecal strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.). Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE), terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas

Mammographic over-screening: Evaluation based on probabilistic linkage of records databases from the breast cancer information system (SISMAMA)

The Brazilian Ministry of Health recommends biennial mammographic screening for women aged between 50 and 69 years. Since screening is opportunistic in the country, the actual periodicity varies. This study sought to test a methodology for estimating over-screening due to excessive periodicity, defined as a smaller than recommended interval between exams, and its association with socio-demographic characteristics. A cohort of women who underwent mammography in 2010, and whose result was normal, was assembled through probabilistic linkage SISMAMA records based on a set of personal identifiers. We used data from women living in the micro health region of Juiz de Fora/Lima Duarte/Bom Jardim, Minas Gerais State, Brazil, who were followed in the System until the end of 2012. The rate of over-screening was 150/1,000 women/year (95%CI: 144.9-155.9), affecting 21% of women. Over-screening increased by 24% during Pink October campaigns (adjusted HR = 1.24; 95%CI: 1.15-1.35). The shorter the time passed since the last mammogram, the greater the odds of over-screening. Compared with women who had never had a mammogram prior to 2010, women who had had one in the previous 2 years were two times more likely to be over-screened (adjusted HR = 2.01; 95%CI: 1.74-2.31) whilst those who had had a mammogram ≤ 1 year previously were three times more likely to be over-screened (adjusted HR = 3.27; 95%CI: 2.87-3.73). Over-screening was substantial in this population, excessively exposing women to the risks of screening with no additional benefits and overestimating mammogram coverage. The methodology proved to be successful and should be applied to representative populations in order to guide breast cancer control policies

Inequities in access to mammographic screening in Brazil

Our objectives with this study were to describe the spatial distribution of mammographic screening coverage across small geographical areas (micro-regions) in Brazil, and to analyze whether the observed differences were associated with spatial inequities in socioeconomic conditions, provision of health care, and healthcare services utilization. We performed an area-based ecological study on mammographic screening coverage in the period of 2010-2011 regarding socioeconomic and healthcare variables. The units of analysis were the 438 health micro-regions in Brazil. Spatial regression models were used to study these relationships. There was marked variability in mammographic coverage across micro-regions (median = 21.6%; interquartile range: 8.1%-37.9%). Multivariable analyses identified high household income inequality, low number of radiologists/100,000 inhabitants, low number of mammography machines/10,000 inhabitants, and low number of mammograms performed by each machine as independent correlates of poor mammographic coverage at the micro-region level. There was evidence of strong spatial dependence of these associations, with changes in one micro-region affecting neighboring micro-regions, and also of geographical heterogeneities. There were substantial inequities in access to mammographic screening across micro-regions in Brazil, in 2010-2011, with coverage being higher in those with smaller wealth inequities and better access to health care

Conservation and divergence within the clathrin interactome of <i>Trypanosoma cruzi</i>

Trypanosomatids are parasitic protozoa with a significant burden on human health. African and American trypanosomes are causative agents of Nagana and Chagas disease respectively, and speciated about 300 million years ago. These parasites have highly distinct life cycles, pathologies, transmission strategies and surface proteomes, being dominated by the variant surface glycoprotein (African) or mucins (American) respectively. In African trypanosomes clathrin-mediated trafficking is responsible for endocytosis and post-Golgi transport, with several mechanistic aspects distinct from higher organisms. Using clathrin light chain (TcCLC) and EpsinR (TcEpsinR) as affinity handles, we identified candidate clathrin-associated proteins (CAPs) in Trypanosoma cruzi; the cohort includes orthologs of many proteins known to mediate vesicle trafficking, but significantly not the AP-2 adaptor complex. Several trypanosome-specific proteins common with African trypanosomes, were also identified. Fluorescence microscopy revealed localisations for TcEpsinR, TcCLC and TcCHC at the posterior region of trypomastigote cells, coincident with the flagellar pocket and Golgi apparatus. These data provide the first systematic analysis of clathrin-mediated trafficking in T. cruzi, allowing comparison between protein cohorts and other trypanosomes and also suggest that clathrin trafficking in at least some life stages of T. cruzi may be AP-2-independent