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Cystic fibrosis carriership and tuberculosis: hints toward an evolutionary selective advantage based on data from the Brazilian territory
Abstract
Background
The reason why Cystic Fibrosis (CF) is the most common fatal genetic disease among Caucasians has been incompletely studied. We aimed at deepening the hypothesis that CF carriers have a relative protection against Mycobacterium tuberculosis (Mtb) infection.
Methods
Applying spatial epidemiology, we studied the link between CF carriership rate and tuberculosis (TB) incidence in Brazil. We corrected for 5 potential environmental and 2 immunological confounders in this relation: monthly income, sanitary provisions, literacy rates, racial composition and population density along with AIDS incidence rates and diabetes mellitus type 2. Smoking data were incomplete and not available for analysis.
Results
A significant, negative correlation between CF carriership rate and TB incidence, independent of any of the seven confounders was found.
Conclusion
We provide exploratory support for the hypothesis that carrying a single CFTR mutation arms against Mtb infections
Molecular signatures of neutrophil extracellular traps in human visceral leishmaniasis
Abstract\ud
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Background\ud
Infections with parasites of the Leishmania donovani complex result in clinical outcomes that range from asymptomatic infection to severe and fatal visceral leishmaniasis (VL). Neutrophils are major players of the immune response against Leishmania, but their contribution to distinct states of infection is unknown. Gene expression data suggest the activation of the NETosis pathway during human visceral leishmaniasis. Thus, we conducted an exploratory study to evaluate NET-related molecules in retrospective sera from VL patients, asymptomatic individuals and uninfected endemic controls.\ud
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Results\ud
We demonstrate that VL patients and asymptomatic individuals exhibit differential regulation of molecules associated with neutrophil extracellular traps (NET). These differences were observed at the transcriptional level of genes encoding NET-associated proteins; in quantifications of cell free DNA and metalloproteinase 9; and in enzymatic activity of DNAse and elastase. Moreover, multivariate analysis resulted in class-specific signatures, and ROC curves demonstrate the ability of these molecules in discriminating asymptomatic infection from uninfected controls.\ud
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Conclusion\ud
Molecules that are associated with NETs are differentially regulated between distinct states of infection with L. infantum, suggesting that NETs might have distinct roles depending on the clinical status of infection. Although unlikely to be exclusive for VL, these signatures can be useful to better characterize asymptomatic infections in endemic regions of this disease.This work was supported by Fundação Carlos Chagas Filho de Amparo à Pesquisa\ud
do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento\ud
Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de\ud
Pessoal de Nível Superior (CAPES). LGG and GRG were supported by scholarships\ud
from the Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP\ud
(2011/23819-0 and 2014/25856-8; 2013/00382-0, respectively)
Anti-Toxoplasma gondii antibodies in patients with beta-hemoglobinopathies: the first report in the Americas
Abstract\ud
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Background\ud
In Brazil, there have been no previous studies of Toxoplasma gondii infection in sickle cell anemia patients and carriers of severe forms of beta-thalassemia. This study evaluated T. gondii infection in patients with beta-hemoglobinopathies.\ud
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Methods\ud
A total of 158 samples, 77 (48.7%) men and 81 (51.3%) women, were evaluated. Three groups were formed: G1 (85 patients with sickle cell disease); G2 (11 patients with homozygous beta-thalassemia; G3 (62 patients with heterozygous beta-thalassemia). ELISA was employed to identify anti-T. gondii IgM and IgG antibodies, and molecular analysis was performed to determine beta-hemoglobin mutations. Fisher’s exact test was used to compare frequencies of anti-T. gondii IgM and IgG antibodies in respect to gender and age.\ud
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Results\ud
Anti-T. gondii IgG antibodies were found in 43.5% of individuals in G1, 18.1% in G2 and 50% in G3. All samples from G1 and G2 were seronegative for anti-T. gondii IgM antibodies, but 3.2% from G3 were seropositive. Considering anti-T. gondii IgG antibodies, no statistical significant differences were found between these groups nor in seroprevalence between genders within each group. Despite this, comparisons of the mean ages between G1, G2 and G3 were statistically significant (G2 vs. G1: p value = 0.0001; G3 vs. G1: p-value <0.0001; G3 vs. G2: p-value = 0.0001).\ud
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Conclusion\ud
A comparison by age of patients with sickle cell anemia showed a trend of lower risk of infection among younger individuals. Therefore, this study demonstrates that T. gondii infection occurs in patients with beta-thalassemia and sickle cell anemia in Brazil as seen by the presence of anti-T. gondii IgM and IgG antibodies.This study was supported by grants from the FAPERP (Fundação de Apoio\ud
à Pesquisa e Extensão de São José do Rio Preto) to CCBM and to MNF\ud
and by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo,\ud
Brazil) 2011/15570-1 to GCSC; 2012/07716-9 to LCM; 2014/01706-7 to MNF;\ud
2015/04677-0 to CCBM). The opinions, assumptions, and conclusions or\ud
recommendations expressed in this material are responsibility of the authors\ud
and do not necessarily refect the views of FAPESP. The funders had no role in\ud
study design, data collection and analysis, decision to publish, or preparation\ud
of the manuscript
Text mining and semantics: a systematic mapping study
Abstract\ud
As text semantics has an important role in text meaning, the term semantics has been seen in a vast sort of text mining studies. However, there is a lack of studies that integrate the different research branches and summarize the developed works. This paper reports a systematic mapping about semantics-concerned text mining studies. This systematic mapping study followed a well-defined protocol. Its results were based on 1693 studies, selected among 3984 studies identified in five digital libraries. The produced mapping gives a general summary of the subject, points some areas that lacks the development of primary or secondary studies, and can be a guide for researchers working with semantics-concerned text mining. It demonstrates that, although several studies have been developed, the processing of semantic aspects in text mining remains an open research problem.The authors would like to thank the financial support of grant #132666/2016-2,\ud
National Council for Scientific and Technological Development (CNPq); grants\ud
#2013/14757-6, #2014/08996-0, and #2016/07620-2, São Paulo Research\ud
Foundation (FAPESP); and Coordination for the Improvement of Higher\ud
Education Personnel (CAPES)
Erratum to: Combined effect of pulse density and grid cell size on predicting and mapping aboveground carbon in fast-growing Eucalyptus forest plantation using airborne LiDAR data
This research was funded through a Ph.D. scholarship from the National\ud
Council of Technological and Scientifc Development - CNPq via the Science\ud
Without Borders Program (Process 249802/2013-9) and by the State of São\ud
Paulo Research Foundation-FAPESP (Process 12/03176-0)
Interaction between saliva’s adenosine and tick parasitism: effects on feeding and reproduction
Abstract\ud
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Background\ud
It has recently been demonstrated that saliva from Rhipicephalus sanguineus ticks contains adenosine (ADO) and prostaglandin E2 (PGE2), two non-protein molecules that have significant immunomodulatory properties. These molecules can inhibit cytokine production by dendritic cells (DCs), while also reducing the expression of CD40 in these cells. However, more studies are needed for a better understanding of their participation in the feeding of ticks in vivo. This work, therefore, evaluated the importance of ADO during tick infestations. Mice were infested with adult ticks (3 couples/mouse), and their skin was collected at the tick-infested site (3rd and 7th day), and mRNA for receptors of ADO was quantified by real-time PCR.\ud
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Results\ud
Tick infestation increased by four and two times the expression of the A2b and A3v1 receptors on day 3, respectively, while expression of other ADO receptors was unaltered. In addition, we treated mice (n = 10/group) daily with 8-(p-Sulfophenyl)theophylline, 8-pSPT, 20 mg/kg, i.p.), a non-selective antagonist of ADO receptors, and evaluated the performance of ticks during infestations. Female ticks fed on 8-pSPT-treated mice presented a reduction in their engorgement, weight and hatching rates of egg masses, and survival times of larvae compared to the same parameters presented by ticks in the control group. To investigate if these 8-pSPT-treated mice presented altered immune responses, we performed three tick infestations and collected their lymph node cells to determine the percentages and activation state of DCs and cytokine production by lymphocytes by flow cytometry (Cytometric Bead Array technique, CBA). Our data showed that 8-pSPT-treated mice presented an increase in the percentage of DCs as well as of their stimulatory and co-stimulatory molecules (CD40, CD80 and MHCII). Regarding production of T cell cytokines, we observed a significant increase in the levels of IL-2 and a significant decrease in IL-10, IL-17, TNF-α and IFN-γ cytokines.\ud
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Conclusions\ud
These results suggest that ADO produced by ticks helps them feed and reproduce and that this effect may be due to modulation of host DCs and T cells.This work was supported by the Conselho Nacional de Desenvolvimento\ud
Científico e Tecnológico (CNPq), fellowship numbers 301,663/2007–6,\ud
308,815/2010–6 and 308,280/2013–0 and São Paulo Research Foundation\ud
(FAPESP) grant agreement number 2011/00905–8 and fellowship number\ud
2010/11285–8. The funders had no role in study design, data collection and\ud
analysis, decision to publish or preparation of the paper
Patients’ perception regarding the influence of individual and social vulnerabilities on the adherence to tuberculosis treatment: a qualitative study
Abstract\ud
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Background\ud
Tuberculosis remains an important disease which mainly affects the majority of vulnerable individuals in society, who are subjected to poor living conditions and difficulties to access the services of public health. Under these circumstances, the present study aims to understand patients’ perception in relation to the influence of individual and social vulnerabilities on the adherence to tuberculosis treatment.\ud
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Methods\ud
A qualitative descriptive cross sectional study was conducted in one large municipality at the state of Paraíba, Northeast of Brazil. The study subjects, who were residents of the study site, covered all tuberculosis cases diagnosed between March and June 2015. The sample was defined by the criteria of response saturation. All interviews were audio recorded, and data analysis was developed through the hermeneutic dialectic method and the theory of Generative Route Sense. The project was approved by the Research Ethics Committee of the University of São Paulo (USP).\ud
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Results\ud
A total of 13 individuals were interviewed and the responses were identified into two analytical categories: the difficulties they had and the enabling factors they could mention during their tuberculosis treatment. Patients brought up social exclusion as an obstacle to treatment adherence, which, along with stigmatization, weakened their link with family members and health professionals. Moreover, economic precariousness was a major hindrance to the maintenance of a proper diet and transportation access to health centers. However, social support and directly observed treatment helped to break down barriers of prejudice and to promote individual and family empowerment. Finally, patients also reported that their will to live and faith gave them the strength to continue with the treatment.\ud
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Conclusions\ud
According to patients in this study, social support and the strengthening of links with family members and health professionals may reduce social exclusion and other difficulties they face, thus encouraging them to the adhere to tuberculosis treatment
Putative progressive and abortive feline leukemia virus infection outcomes in captive jaguarundis (Puma yagouaroundi)
Abstract\ud
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Background\ud
Feline leukemia virus (FeLV) is an exogenous gammaretrovirus of domestic cats (Felis catus) and some wild felids. The outcomes of FeLV infection in domestic cats vary according to host susceptibility, virus strain, and infectious challenge dose. Jaguarundis (Puma yagouaroundi) are small wild felids from South and Central America. We previously reported on FeLV infections in jaguarundis. We hypothesized here that the outcomes of FeLV infection in P. yagouaroundi mimic those observed in domestic cats. The aim of this study was to investigate the population of jaguarundis at Fundação Parque Zoológico de São Paulo for natural FeLV infection and resulting outcomes.\ud
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Methods\ud
We investigated the jaguarundis using serological and molecular methods and monitored them for FeLV-related diseases for 5 years. We retrieved relevant biological and clinical information for the entire population of 23 jaguarundis held at zoo. Post-mortem findings from necropsies were recorded and histopathological and immunohistopathological analyses were performed. Sequencing and phylogenetic analyses were performed for FeLV-positive samples. For sample prevalence, 95% confidence intervals (CI) were calculated. Fisher’s exact test was used to compare frequencies between infected and uninfected animals. P-values <0.05 were considered significant.\ud
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Results\ud
In total, we detected evidence of FeLV exposure in four out of 23 animals (17%; 95% CI 5–39%). No endogenous FeLV (enFeLV) sequences were detected. An intestinal B-cell lymphoma in one jaguarundi was not associated with FeLV. Two jaguarundis presented FeLV test results consistent with an abortive FeLV infection with seroconversion, and two other jaguarundis had results consistent with a progressive infection and potentially FeLV-associated clinical disorders and post-mortem changes. Phylogenetic analysis of env revealed the presence of FeLV-A, a common origin of the virus in both animals (100% identity) and the closest similarity to FeLV-FAIDS and FeLV-3281 (98.4% identity), originally isolated from cats in the USA.\ud
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Conclusions\ud
We found evidence of progressive and abortive FeLV infection outcomes in jaguarundis, and domestic cats were probably the source of infection in these jaguarundis.This work was supported by grants of Coordination for the Improvement of Higher Education Personnel (CAPES) and the Post-Graduate Pro-Rector from USP in Brazil and the International Relations Office from the University of Zurich in Switzerland. Partial writing of this manuscript work was also supported by the São Paulo Research Foundation (Fapesp) (grant 2013/12253–0). The funding bodies had no specific role in the design of the study, collection, analysis, and interpretation of data
Is hematoxylin-eosin staining in rectal mucosal and submucosal biopsies still useful for the diagnosis of Hirschsprung disease?
Abstract\ud
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Background\ud
Hematoxylin-eosin (HE) staining of a full-thickness rectal wall fragment is classically used for the diagnosis of Hirschsprung disease (HD). However, this technique requires large fragments for a better diagnosis. Additionally, the histochemical and immunohistochemical methods of staining small fragments of rectal mucosal and submucosal biopsies are not available in all centers. Therefore, the possibility of diagnosing HD through HE staining in these biopsies could be a valuable alternative for centers that do not have more specific techniques. The objectives of the current investigation were to evaluate the concordance of the results obtained by HE staining and the calretinin method with acetylcholinesterase (AChE) activity in fragments of mucosa and submucosa in the diagnosis of HD.\ud
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Methods\ud
For this study, 50 cases from our laboratory were selected. The tissue material was embedded in paraffin. Sixty levels of each fragment were utilized for HE, and the other 3 levels were used for calretinin. These slides were analyzed under the microscope, photographed and classified as either positive for HD when no ganglion cells were found with nerve trunks present or as negative when ganglion cells were found. The results from reading the slides were compared with those of AChE.\ud
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Results\ud
Of the 50 cases evaluated by the HE technique, only 5 contradicted the diagnosis based on AChE, with a Kappa value of 0.800 and an accuracy of 90%. In the comparison between calretinin and AChE, 8 cases were discordant, with a Kappa value of 0.676 and an accuracy of 84%.\ud
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Conclusions\ud
The concordance of results from AChE and HE methods was satisfactory, allowing for the potential use of the HE method for fragments of mucosa and submucosa as a valid alternative in the diagnosis of HD. The immunohistochemical technique of calretinin did not show good agreement with the AChE activity in our study
Effects of virtual rehabilitation versus conventional physical therapy on postural control, gait, and cognition of patients with Parkinson’s disease: study protocol for a randomized controlled feasibility trial
Abstract\ud
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Background\ud
There is an association among postural instability, gait dysfunction, and cognitive impairment in subjects with Parkinson’s disease (PD). Difficulty in dividing attention, response inhibition, and visuospatial attention deficiencies may contribute to the impairment of motor performance during daily activities. There are strong evidences that physical therapy can prevent physical and cognitive decline in individuals with PD. Recently, the European Physiotherapy Guideline (EPG) was developed based on randomized clinical trials about the effectiveness of the physical therapy to improve the functional deficiencies of individuals with PD. The EPG did not include the use of promising new intervention as virtual reality in PD due the lack of studies about its safety, feasibility and effectiveness. Therefore, this study protocol had as objective to evaluate the feasibility, safety and effectiveness of a physical therapy program-based on the European Physiotherapy Guideline (EPG) compared to Kinect-based training on postural control, gait, cognition, and quality of life (QoL) of Individuals with PD. \ud
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Methods/design\ud
A single-blind, parallel, randomized, controlled feasibility trial will be conducted with a sample of 32 individuals diagnosed with idiopathic PD. Participants will be allocated into control group (CG) and experimental group (EG). The intervention of the CG will be conventional physical therapy, and the intervention of the EG will be a supervised practice of five Kinect games. Both groups will perform 14 sessions of 1 h each one, twice a week over 7 weeks. Process outcomes will be safety, feasibility, adherence, and acceptability. Safety will be assessed by the proportion of participants who experienced intervention-related adverse events or any serious adverse event during the study period. Feasibility will be assessed through the scores of the games recorded in all training sessions. Adherence will be assessed through the participant’s attendance. Acceptability will be the motivation of the participants regarding the interventions. Clinical outcomes will be (1) postural control, (2) cognitive function, (3) balance, (4) gait, and (5) QoL. Individuals will be assessed pre- and post-interventions and after 30 days by a blinded evaluator.\ud
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Discussion\ud
This protocol will clarify if an intervention based on Kinect games will be feasible, safe, and acceptable for individuals with PD compared to conventional physical therapy. We will verify whether the proposed interventions can improve clinical outcomes as postural control, gait, cognition, and QoL of individuals with PD. Our hypothesis is that both Kinect games and conventional physical therapy will be feasible, safe, and acceptable for individuals with PD and will promote positive clinical effects. The results of this feasibility study will be used to design a future definitive clinical trial.\ud
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Trial registration\ud
Unique identification number in WHO Trial Registration: U1111-1171-0371. Brazilian Clinical Trial Registration Number \ud
RBR-27kqv5\ud
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, registration date: February, 2016.This study was supported by Fundação de Amparo à Pesquisa do Estado de\ud
São Paulo (FAPESP), process number 2014/22348-1. This funding source had\ud
no role in the design of this study. It will also not participate in the\ud
execution, analyses, interpretation of the data, or decision to submit results