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    Tensions and challenges concerning ethics on video research with young children - experiences from an international collaboration among seven countries

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    Abstract This article and the four videos linked to this article are a result of the earliest experiences in establishing an international research collaboration among seven countries in the Project Social and emotional experiences in transition through the early years. We draw attention to the complex issues surrounding the many processes, beliefs and attitudes about infants in research that permeated our processes of gaining ethical approval for the international study and which posed many challenges for our project. Through a process of reflective analysis, we have identified a range of ethical tensions and issues which the different countries involved in this international study faced in gaining ethical approval from their institutional ethical committees for their collaborative participation. More specifically, we identify one persistent tension concerning the use of video data in research on young children. This tension is a result of diverse interpretations of international ethical codes, alongside local restrictions and ethics review processes. It illuminates various positions concerning the protection of infants’ privacy versus the benefits of using non-anonymous video data both in joint analysis, and even further, in open publishing. Such positions have been widely debated in research with adults, whereupon many of the ethically challenging questions have been dealt with through processes of acquiring informed consents from the participants. In case of infants, however, the role and nature of informed consents is different from research with adults, as is the role of the adult in using infant ‘data’ in research. For most cases, informed consents are acquired from the parents or the legal guardians that are not necessarily present on a day-to-day basis in the actual data collection process in early years educational settings. The question of children’s own assents for study is widely debated and this is no less so in the project we present in this paper. On the basis of the experiences in this international collaboration, and the challenges and tensions identified in between diverse cultural context and ethical review boards and practices, we propose that more dialogue in relation to research ethics on video research is needed within the diverse research communities and contexts, both locally and internationally. The dialogue is important to include also the representatives from the ethical committees, as the new (open) mediums for publishing are becoming more relevant and promising. Most important, ultimately, is the dialogue among the research participants, including where possible infants as contributors in their own right (as opposed to vulnerable subjects), and researchers in all phases of the research process

    Diagnosis of acute canine leptospirosis using multiple laboratory tests and characterization of the isolated strains

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    Abstract Background Dogs presenting with acute leptospirosis may present non-specific clinical and laboratory findings, and the definitive diagnosis may require additional confirmatory tests, including bacterial culture, for the direct or indirect identification of the pathogen. The present study describes the diagnosis of leptospirosis in suspected dogs based on the use of multiple diagnostic tests, including serological, molecular and bacteriological tests, along with the characterization of the recovered leptospiral strains. Results Urine, serum and blood samples were collected from 33 dogs with suspected clinical leptospirosis treated at the University of São Paulo Veterinary Hospital Service (Hovet FMVZ-USP) between 2013 and 2016. Only dogs with high blood urea nitrogen and creatinine levels in association with multiple clinical manifestations of the disease were included. Leptospiral culture, PCR and serology (Microscopic agglutination test - MAT) were performed in blood and urine samples taken from all suspected dogs at clinical presentation, and an additional prospective MAT titration was performed in seven dogs. Infection could be identified exclusively by PCR in 10 dogs (30.3%), exclusively by MAT in four dogs (12.1%) and by both tests in four dogs, totaling 18 dogs (54.5–95%CI: 37.6–71.5). Six out of eight MAT-confirmed cases presented with the highest titers against the Icterohaemorrhagiae serogroup. Leptospires were recovered from urine samples from two PCR-positive dogs, and both strains could be characterized by Multilocus Sequence Analysis and serogrouping as L. interrogans serogroup Icterohaemorrhagiae. Both isolates were shown to be pathogenic in the hamster model. Conclusions The simultaneous use of MAT and PCR was able to increase the diagnosis of leptospirosis in clinically suspected cases. Despite the increasing incidence of new serovars affecting dogs being reported in different locations, our results suggest that leptospiral strains belonging to the Icterohaemorrhagiae serogroup are still a major causative agent of canine leptospirosis in São Paulo, Brazil

    Unilateral diaphragm paralysis: a dysfunction restricted not just to one hemidiaphragm

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    Abstract Background Most patients with unilateral diaphragm paralysis (UDP) have unexplained dyspnea, exercise limitations, and reduction in inspiratory muscle capacity. We aimed to evaluate the generation of pressure in each hemidiaphragm separately and its contribution to overall inspiratory strength. Methods Twenty-seven patients, 9 in right paralysis group (RP) and 18 in left paralysis group (LP), with forced vital capacity (FVC) < 80% pred, and 20 healthy controls (CG), with forced expiratory volume in 1 s (FEV1) > 80% pred and FVC > 80% pred, were evaluated for lung function, maximal inspiratory (MIP) and expiratory (MEP) pressure measurements, diaphragm ultrasound, and transdiaphragmatic pressure during magnetic phrenic nerve stimulation (PdiTw). Results RP and LP had significant inspiratory muscle weakness compared to controls, detected by MIP (− 57.4 ± 16.9 for RP; − 67.1 ± 28.5 for LP and − 103.1 ± 30.4 cmH2O for CG) and also by PdiTW (5.7 ± 4 for RP; 4.8 ± 2.3 for LP and 15.3 ± 5.7 cmH2O for CG). The PdiTw was reduced even when the non-paralyzed hemidiaphragm was stimulated, mainly due to the low contribution of gastric pressure (around 30%), regardless of whether the paralysis was in the right or left hemidiaphragm. On the other hand, in CG, esophagic and gastric pressures had similar contribution to the overall Pdi (around 50%). Comparing both paralyzed and non-paralyzed hemidiaphragms, the mobility during quiet and deep breathing, and thickness at functional residual capacity (FRC) and total lung capacity (TLC), were significantly reduced in paralyzed hemidiaphragm. In addition, thickness fraction was extremely diminished when contrasted with the non-paralyzed hemidiaphragm. Conclusions In symptomatic patients with UDP, global inspiratory strength is reduced not only due to weakness in the paralyzed hemidiaphragm but also to impairment in the pressure generated by the non-paralyzed hemidiaphragm

    Physician’s sociodemographic profile and distribution across public and private health care: an insight into physicians’ dual practice in Brazil

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    Abstract\ud \ud Background\ud The intertwined relation between public and private care in Brazil is reshaping the medical profession, possibly affecting the distribution and profile of the country’s medical workforce. Physicians’ simultaneous engagement in public and private services is a common and unregulated practice in Brazil, but the influence played by contextual factors and personal characteristics over dual practice engagement are still poorly understood. This study aimed at exploring the sociodemographic profile of Brazilian physicians to shed light on the links between their personal characteristics and their distribution across public and private services.\ud \ud \ud Methods\ud A nation-wide cross-sectional study using primary data was conducted in 2014. A representative sample size of 2400 physicians was calculated based  on the National Council of Medicine database registries; telephone interviews were conducted to explore physicians’ sociodemographic characteristics and their engagement with public and private services.\ud \ud \ud Results\ud From the 2400 physicians included, 51.45% were currently working in both the public and private services, while 26.95% and 21.58% were working exclusively in the private and public sectors, respectively. Public sector physicians were found to be younger (PR 0.84 [0.68–0.89]; PR 0.47 [0.38–0.56]), less experienced (PR 0.78 [0.73–0.94]; PR 0.44 [0.36–0.53]) and predominantly female (PR 0.79 [0.71–0.88]; PR 0.68 [0.6–0.78]) when compared to dual and private practitioners; their income was substantially lower than those working exclusively for the private (PR 0.58 [0.48–0.69]) and mixed sectors (PR 0.31 [0.25–0.37]). Conversely, physicians from the private sector were found to be typically senior (PR 1.96 [1.58–2.43]), specialized (PR 1.29 [1.17–1.42]) and male (PR 1.35 [1.21–1.51]), often working less than 20 h per week (PR 2.04 [1.4–2.96]). Dual practitioners were mostly middle-aged (PR 1.3 [1.16–1.45]), male specialists with 10 to 30 years of medical practice (PR 1.23 [1.11–1.37]).\ud \ud \ud Conclusion\ud The study shows that more than half of Brazilian physicians currently engage with dual practice, while only one fifth dedicate exclusively to public services, highlighting also substantial differences in socio-demographic and work-related characteristics between public, private and dual-practitioners. These results are consistent with the international literature suggesting that physicians’ sociodemographic characteristics can help predict dual practice forms and prevalence in a country.This study was financially supported by Fundação Faculdade de Medicina\ud (FFM), Conselho Regional de Medicina do Estado de São Paulo (Cremesp)\ud and Conselho Federal de Medicina (CFM), agreement (#0075/2015), which\ud also contributed by making their database fully available. This study was also\ud funded by the UK Medical Research Concil (MRC/R022747/1) and the\ud Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; project\ud number 17/50356-7). Alex Jones Flores Cassenote was given a PhD Student\ud scholarship from FAPESP (proc. 2013/18158–0)

    Immunohistological features related to functional impairment in lymphangioleiomyomatosis

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    Abstract\ud \ud Background\ud Lymphangioleiomyomatosis (LAM) is a low-grade neoplasm characterized by the pulmonary infiltration of smooth muscle-like cells (LAM cells) and cystic destruction. Patients usually present with airway obstruction in pulmonary function tests (PFTs). Previous studies have shown correlations among histological parameters, lung function abnormalities and prognosis in LAM. We investigated the lung tissue expression of proteins related to the mTOR pathway, angiogenesis and enzymatic activity and its correlation with functional parameters in LAM patients.\ud \ud \ud Methods\ud We analyzed morphological and functional parameters of thirty-three patients. Two groups of disease severity were identified according to FEV1 values. Lung tissue from open biopsies or lung transplants was immunostained for SMA, HMB-45, mTOR, VEGF-D, MMP-9 and D2-40. Density of cysts, density of nodules and protein expression were measured by image analysis and correlated with PFT parameters.\ud \ud \ud Results\ud There was no difference in the expression of D2-40 between the more severe and the less severe groups. All other immunohistological parameters showed significantly higher values in the more severe group (p ≤ 0.002). The expression of VEGF-D, MMP-9 and mTOR in LAM cells was associated with the density of both cysts and nodules. The density of cysts and nodules as well as the expression of MMP-9 and VEGF-D were associated with the impairment of PFT parameters.\ud \ud \ud Conclusions\ud Severe LAM represents an active phase of the disease with high expression of VEGF-D, mTOR, and MMP-9, as well as LAM cell infiltration. Our findings suggest that the tissue expression levels of VEGF-D and MMP-9 are important parameters associated with the loss of pulmonary function and could be considered as potential severity markers in open lung biopsies of LAM patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP): responsible for financial support to tissue processing and immunohistological analysis, statistical analysis and pulmonary meetings participations

    In silico epitope mapping and experimental evaluation of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) as a malaria vaccine candidate

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    Abstract\ud \ud Background\ud Technical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda. The immunogenicity of the M2 domain of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) antigen cloned from the Plasmodium yoelii murine parasite, has been previously demonstrated.\ud \ud \ud Results\ud Detailed epitope mapping of MAEBL through immunoinformatics identified several MHCI, MHCII and B cell epitopes throughout the peptide, with several of these lying in the M2 domain and being conserved between P. vivax, P. yoelii and Plasmodium falciparum, hinting that the M2-MAEBL is pan-reactive. This hypothesis was tested through functional assays, showing that P. yoelii M2-MAEBL antisera are able to recognize and inhibit erythrocyte invasion from both P. falciparum and P. vivax parasites isolated from Thai patients, in ex vivo assays. Moreover, the sequence of the M2-MAEBL is shown to be highly conserved between P. vivax isolates from the Amazon and Thailand, indicating that the MAEBL antigen may constitute a vaccine candidate outwitting strain-specific immunity.\ud \ud \ud Conclusions\ud The MAEBL antigen is promising candidate towards the development of a malaria vaccine.This work was supported by Fundação de Amparo à Pesquisa do Estado de\ud São Paulo (FAPESP—Grant # 2012/16525-2), Instituto Nacional de Ciência e\ud Tecnologia de Vacinas (INCTV) and the Conselho Nacional de Desenvolvimento\ud Científco e Tecnológico (CNPq). RBM was supported by a CAPES\ud fellowship. JAL and NB were sponsored by FAPESP fellowships. CC was supported\ud by a CNPq fellowship. PC, MVGL, MUF and FTMC are CNPq research\ud fellows in productivity. This study and RS and BR received funding from SIgN\ud under the Agency for Science, Technology and Research (A*STAR, Singapore)

    Colon epithelial cells luminal environment and physiopathological consequences: impact of nutrition and exercise

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    Abstract\ud The colonic epithelial cells represent a border between the colon luminal content, containing notably bacteria and a complex mixture of compounds, and the “milieu interieur” as defined by the French physiologist Claude Bernard. The physical-chemical composition of the luminal content, including luminal pH and bacterial metabolite, that obviously is not constant, is modified for instance according to the diet. Data obtained recently indicate that physical exercise may also modify the colonic luminal content. Evidence has indicated that modification of the luminal content characteristics has, indeed, consequences for the colonic epithelial cells, notably in terms of energy metabolism and DNA integrity. Although such alterations impact presumably the homeostatic process of the colonic epithelium renewal and the epithelial barrier function, their contribution to pathological processes like mucosal inflammation, pre-neoplasia, and neoplasia remains partly elusive. Open questions remain regarding the individual and collective roles of luminal changes, particularly in a long-term perspective. These questions are related particularly to the capacity of the bacterial metabolites to cross the mucus layer before entering the colonocytes, to the concentrations of metabolites in proximity of the colonic crypt stem cells, and to the capacity of colonocytes to detoxicate deleterious compounds, to take up and utilize beneficial compounds

    Abatacept blocks anti-citrullinated protein antibody and rheumatoid factor mediated cytokine production in human macrophages in IDO-dependent manner

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    Abstract\ud \ud Background\ud The anti-inflammatory effect of abatacept is most pronounced in patients with high-titer autoantibodies (including anticitrullinated protein antibodies [ACPA] and rheumatoid factor [RF]). Considering that autoantibodies trigger inflammatory cytokine production by monocytes and that abatacept binds to monocytes, influencing their functional state, we hypothesized that abatacept may effectively inhibit the production of several different cytokines by ACPA- or RF-challenged monocytes.\ud \ud \ud Methods\ud Peripheral blood CD68+ monocytes stimulated with macrophage colony-stimulating factor for 24 h were exposed to random immunoglobulin G alone (negative control), purified ACPA, purified RF, or lipopolysaccharide (positive control) in cell culture plates coated with citrullinated vimentin (to allow ACPA immune complex formation). Stimulations were done in the presence or absence of abatacept or tumor necrosis factor (TNF) antibody (adalimumab) with or without indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyl-d-tryptophan. Supernatants were analyzed for key proinflammatory cytokines TNF-α, interleukin (IL)-1β, IL-6, IL-8, and chemokine (C-C motif) ligand 2 (CCL2) after 24 h.\ud \ud \ud Results\ud Exposure to ACPA or RF significantly induced the production of TNF-α (20-fold and 27-fold, respectively), IL-1β (each 4-fold), IL-6 (12-fold and 11-fold, respectively), IL-8 (43-fold and 30-fold, respectively), and CCL2 (each 4-fold) in human monocytes. Abatacept inhibited this autoantibody-mediated upregulation of cytokines, reducing TNF-α by > 75%, IL-1β by > 65%, IL-6 and IL-8 by > 80%, and CCL2 by > 60%. In contrast, a TNF inhibitor did not influence autoantibody-induced proinflammatory cytokine production. IDO inhibition reversed the effect of abatacept and again permitted the induction of cytokine production by ACPA and RF.\ud \ud \ud Conclusions\ud These data show that abatacept interferes with autoantibody-mediated cytokine production by monocytes through induction of IDO. This inhibitory effect on the production of several effector cytokines in RA may explain the fast anti-inflammatory effect of abatacept as well as its preferential efficacy in patients with high-titer ACPA and RF.This study was supported by the Deutsche Forschungsgemeinschaft (CRC1181),\ud the Bundesministerium für Bildung und Forschung (BMBF; project\ud METARTHROS), and the Innovative Medicines Initiative-funded project RTCure

    Dietary patterns are influenced by socio-demographic conditions of women in childbearing age: a cohort study of pregnant women

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    Abstract\ud \ud Background\ud Women’s health during their reproductive years and whilst pregnant has implications for their children’s health, both in utero and during childhood. Associations of women’s pre-pregnancy dietary patterns (DP) with maternal socio-demographic characteristics and nutrient intake were investigated in ProcriAr cohort study in São Paulo/Brazil, 2012.\ud \ud \ud Methods\ud The DPs of 454 women were investigated by principal component factor analysis, using dietary information from a validated 110-item food frequency questionnaire. Multiple linear regression models identified independent associations between DPs and maternal socio-demographic characteristics and Spearman’s correlation determined associations between DPs and nutrients intake.\ud \ud \ud Results\ud Participants’ mean age was 26.1 years (standard deviation = 6.3), 10.3% had more than 8 years of formal education, 30% were migrants from outside of the Southeast of Brazil, 48% were employed, 13% were smokers, and 51% were overweight/obese. Four DPs were derived: ‘Lentils, whole grains and soups,’ ‘Snacks, sandwiches, sweets and soft drinks,’ ‘Seasoned vegetables and lean meats,’ and ‘Sweetened juices, bread and butter, rice and beans’. The ‘Lentils, whole grains and soups’ score was positively related to maternal age, being non-smoker and born in the South, North or Midwest of Brazil. The ‘Snacks, sandwiches, sweets and soft drinks’ score was positively related to higher maternal education, and negatively related to age, lack of formal work and being born in the Northeast region. The ‘Seasoned vegetables and lean meats’ score was positively related to higher maternal education. The ‘Sweetened juices, bread and butter, rice and beans’ score was positively related to unemployment and to no family history of hypertension, and negatively related to maternal overweight and obesity. Dietary intake of fruits and vegetables, foods that require preparation, nutrients from one-carbon metabolism, protein, iron, calcium and vitamin D were correlated with the ‘Seasoned vegetables and lean meats’. Dietary intake of sugar-sweetened and alcoholic beverages, industrialized and takeaway foods, and foods rich in sugar, energy, fat, and synthetic folate were correlated with the ‘Snacks, sandwiches, sweets and soft drinks’.\ud \ud \ud Conclusions\ud Findings from this study add perspectives to be considered in the implementation of health interventions, which could improve women’s nutritional status and provide an adequate environment for the developing fetus.This study was supported by the Sao Paulo Research Foundation (SRDMS, grant number 2009/17315-9) and by the National Council for Scientific and Technological Development (SRDMS, grant number 2008/57717-6). Juliana A. Teixeira is supported by the Sao Paulo Research Foundation (2014/12647-1). Sao Paulo Research Foundation and National Council for Scientific and Technological Development had no role in the design, analysis or writing of this article

    Correction to: Rate and determinants of non-adherence to a gluten-free diet and nutritional status assessment in children and adolescents with celiac disease in a tertiary Brazilian referral center: a cross-sectional and retrospective study

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    Correction Unfortunately, after publication of this article [1], it was noticed that the names of the second and third authors were incorrectly displayed, respectively, as Glauce Hiromi Yonaminez and Carla Aline Satiro. The correct names are Glauce Hiromi Yonamine and Carla Aline Fernandes Satiro and can be seen in the corrected author list above. The original article has also been updated to correct this error

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