Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection

<p>Abstract</p> <p>Background</p> <p>It has been well documented over past decades that interaction of pathogens with the extracellular matrix (ECM) plays a primary role in host cell attachment and invasion. Adherence to host tissues is mediated by surface-exposed proteins expressed by the microorganisms during infection. The mechanisms by which pathogenic leptospires invade and colonize the host remain poorly understood since few virulence factors contributing to the pathogenesis of the disease have been identified. Whole-genome sequencing analysis of <it>L. interrogans </it>allowed identification of a repertoire of putative leptospiral surface proteins.</p> <p>Results</p> <p>Here, we report the identification and characterization of a new leptospiral protein that exhibits extracellular matrix-binding properties, called as Lsa21 (leptospiral surface adhesin, 21 kDa). Compatible with its role in adhesion, the protein was shown to be surface-exposed by indirect immunofluorescence. Attachment of Lsa21 to laminin, collagen IV, and plasma fibronectin was specific and dose dependent. Laminin oxidation by sodium metaperiodate reduced the protein-laminin interaction in a concentration-dependent manner, indicating that laminin sugar moieties are crucial for this interaction. The gene coding for Lsa21 is present in pathogenic strains belonging to the <it>L. interrogans </it>species but was not found in the saprophytic <it>L. biflexa </it>serovar Patoc strain Patoc 1. Loss of gene expression occurs upon culture attenuation of pathogenic strains. Environmental factors such as osmolarity and temperature affect Lsa21 expression at the transcriptional level. Moreover, anti-Lsa21 serum labeled liver and kidney tissues of human fatal cases of leptospirosis.</p> <p>Conclusion</p> <p>Our data suggest a role of Lsa21 in the pathogenesis of leptospirosis.</p

Directed differentiation of human induced pluripotent stem cells into functional cholangiocyte-like cells

The difficulty in isolating and propagating functional primary cholangiocytes is a major limitation in the study of biliary disorders and the testing of novel therapeutic agents. To overcome this problem, we have developed a platform for the differentiation of human pluripotent stem cells (hPSCs) into functional cholangiocyte-like cells (CLCs). We have previously reported that our 26-d protocol closely recapitulates key stages of biliary development, starting with the differentiation of hPSCs into endoderm and subsequently into foregut progenitor (FP) cells, followed by the generation of hepatoblasts (HBs), cholangiocyte progenitors (CPs) expressing early biliary markers and mature CLCs displaying cholangiocyte functionality. Compared with alternative protocols for biliary differentiation of hPSCs, our system does not require coculture with other cell types and relies on chemically defined conditions up to and including the generation of CPs. A complex extracellular matrix is used for the maturation of CLCs; therefore, experience in hPSC culture and 3D organoid systems may be necessary for optimal results. Finally, the capacity of our platform for generating large amounts of disease-specific functional cholangiocytes will have broad applications for cholangiopathies, in disease modeling and for screening of therapeutic compounds.This work was funded by ERC starting grant Relieve IMDs (L.V., N.R.F.H.), the Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V., N.R.F.H., F.S.), the Evelyn trust (N.R.F.H.) and the EU Fp7 grant TissuGEN (M.C.d.B.). F.S. was supported by an Addenbrooke's Charitable Trust Clinical Research Training Fellowship and a joint MRC-Sparks Clinical Research Training Fellowship

High prevalence of ST121 in community-associated methicillin-susceptible Staphylococcus aureus lineages responsible for skin and soft tissue infections in Portuguese children

In order to evaluate the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal, we analyzed a collection of 38 S. aureus isolates recovered from 30 children attending the pediatric emergency department of a central hospital in Lisbon due to skin and soft tissue infections. Molecular characterization identified seven clonal lineages among the 35 methicillin-susceptible S. aureus (MSSA) isolates, of which the major lineage PFGE A/t159/ST121 included 63% of the isolates. The three MRSA isolates belonged to the Pediatric clone PFGE D/t535/ST5-IV (n = 2) and to the European CA-MRSA clone PFGE G/t044/ST80-IVc (n = 1). All isolates harbored several virulence factors, namely, leukocidins. Panton-Valentine leukocidin (PVL) was produced by isolates from five MSSA lineages and by the ST80 MRSA. Of interest, this is the first reported isolation of CA-MRSA ST80 in Portugal

Exercise inhibits the effects of smoke-induced COPD involving modulation of STAT3

Purpose . Evaluate the participation of STAT3 in the e ff ects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods . C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary in fl ammation, systemic in fl ammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results . AE inhibited smoke-induced accumulation of total cells ( p <0 001 ), lymphocytes ( p <0 001 ), and neutrophils ( p <0 001 ) in BAL, as well as BAL levels of IL- 1 β ( p <0 001 ), CXCL1 ( p <0 001 ), IL-17 ( p <0 001 ), and TNF- α ( p <0 05 ), while increased the levels of IL-10 ( p <0 001 ). AE also inhibited smoke-induced increases in total leukocytes ( p <0 001 ), neutrophils ( p <0 05 ), lymphocytes ( p <0 001 ), and monocytes ( p <0 01 ) in blood, as well as serum levels of IL-1 β ( p <0 01 ), CXCL1 ( p <0 01 ), IL-17 ( p <0 05 ), and TNF- α ( p <0 01 ), while increased the levels of IL-10 ( p <0 001 ). AE reduced smoke-induced emphysema ( p <0 001 ) and collagen fi ber accumulation in the airways ( p <0 001 ). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells ( p <0 001 ), peribronchial leukocytes ( p <0 001 ), and parenchymal leukocytes ( p <0 001 ). Conclusions .AE reduces smoke-induced COPD phenotype involving STAT3

Employment and sociodemographic characteristics: a study of increasing precarity in the health districts of Belo Horizonte, Brazil

<p>Abstract</p> <p>Background</p> <p>The fundamental importance of human resources for the development of health care systems is recognized the world over. Health districts, which constitute the middle level of the municipal health care system in the city of Belo Horizonte, Brazil, deal with demands from all parts of the system. This research seeks to provide the essential features required in order to understand the phenomenon of increase in precarity of employment in these health districts.</p> <p>Methods</p> <p>The legal and human resource management documents used by the Municipal Health Secretariat of the City of Belo Horizonte were adopted as the corpus for this research. In order to analyse the changes in employment (2002–2006), the data were collected from ArteRH, a computerized database dealing specifically with data related to human resources, which began operating in 2001. The workers were classified into permanent and non-permanent groups, and their contractual rights were described. Employment dynamics and changes were examined, concentrating on the incorporation of workers and on their social and employment rights during the period under study. The comparative data for the two groups obtained were presented in frequency distribution tables according to type of employment, sex, age group, level of education and wages from 2002 to 2006.</p> <p>Results</p> <p>There was a clear difference between the permanent worker and non-permanent worker groups as regards existing guaranteed employment rights and social security. The increase in the number of non-permanent workers in the workforce, the growing proportion of older workers among the permanently employed and the real wage reductions during the period from 2002 to 2006 are indicative of the process of growing precarity of employment in the group studied.</p> <p>Conclusion</p> <p>It is a plausible supposition that the demand for health reforms, along with the legal limits imposed on financial expenditure, gave rise to the new types of contract and the present employment situation in the health districts in Belo Horizonte.</p

The nurse in the management of materials in teaching hospitals

OBJECTIVETo present the nurse's integration within materials management of six teaching hospitals of Paraná - Brazil, and to describe the activities performed by nurses within this process.METHODA study of a qualitative approach and descriptive nature, conducted in teaching hospitals in Paraná, between June and August of 2013. The data collection was conducted through semi-structured interviews with eight nurses who worked in materials management; data were analyzed using content analysis.RESULTSThese showed that nurses perform ten categories of activities, distributed into four of the five steps of the materials management process.CONCLUSIONThe nurse, in performing of these activities, in addition to favoring the development of participative management, contributes to the organization, planning, and the standardization of the hospital supply process, giving greater credibility to the work with professionals who use the materials, and to the suppliers

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Genetic variability in five populations of Partamona helleri (Hymenoptera, Apidae) from Minas Gerais State, Brazil

Partamona is a Neotropical genus of stingless bees that comprises 33 species distributed from Mexico to southern Brazil. These bees are well-adapted to anthropic environments and build their nests in several substrates. In this study, 66 colonies of Partamona helleri from five localities in the Brazilian state of Minas Gerais (São Miguel do Anta, Teixeiras, Porto Firme, Viçosa and Rio Vermelho) were analyzed using nine microsatellite loci in order to assess their genetic variability. Low levels of observed (Ho = 0.099-0.137) and expected (H e = 0.128-0.145) heterozygosity were encountered and revealed discrete genetic differentiation among the populations (F ST = 0.025). AMOVA further showed that most of the total genetic variation (94.24%) in P. helleri was explained by the variability within local populations