BackgroundChronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin ...America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected.Methodology/principal findingsWe describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10-9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis.Conclusions/significanceWe suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.
Intestinal parasites are the causative agents of common infections responsible for significant public health problems in developing countries and generally linked to lack of sanitation, safe water, ...and improper hygiene. More than two billion people throughout the world live with unrelenting illness due to intestinal parasitic infections (IPIs). The purposes of this study are to assess knowledge, attitudes, and practices on IPIs and investigate the relationship with prevalence of intestinal parasites among a low-income group of inhabitants from two communities of the Travessão District area, Campos dos Goytacazes, north of Rio de Janeiro State, Brazil. The two communities are known as “Parque Santuário,” which is an urban slum with miserable living conditions, and “Arraial,” where the socioeconomic and educational levels are better, neither having a sanitary infrastructure with an excreta collection system. Questionnaires revealed that both communities had local and specific codification to denominate the intestinal parasites and present correct knowledge on the theme but ignored some aspects of IPI transmission, with the Arraial population being better informed (p < 0.05). The overall prevalence of IPIs in Parque Santuário (49.7%) was greater than in Arraial (27.2%) (p < 0.001; prevalence ratio/95% confidence interval 1.83/1.50-2.23). This study reports the real IPI situation in the Travessão District and also reinforces the need to continue the investigation on the impact of combined prophylactic methods, educational measures, and socioeconomic and sanitary improvements by governmental authorities and the local popular organization.
IntroductionThe aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals.Methods and ...analysisA prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed.Ethics and disseminationEthical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences.
Although inhaled glucocorticosteroids are recommended for persistent asthma, their long-term effect on recent onset, mild, persistent asthma has yet to be established.
We did a randomised, ...double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids. Patients aged 5–66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications. The daily budesonide dose was 400 μg, or 200 μg for children younger than 11 years. The primary outcome was time to first severe asthma-related event, and analysis was by intention to treat.
198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation; hazard ratio 0·56 (95% CI 0·45–0·71, p<0·0001). Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo. Compared with placebo, budesonide increased postbronchodilator forced expiratory volume in 1 s (FEV
1) from baseline by 1·48% (p<0·0001) after 1 year and by 0·88% (p=0·0005) after 3 years (expressed as percent of the predicted value). The corresponding increase in prebronchodilator FEV
1 was 2·24% after 1 year and 1·71% after 3 years (p<0·0001 at both timepoints). The effect of treatment on all outcome variables was independent of the baseline lung function (prebronchodilator or postbronchodilator) or baseline medication. In children younger than 11 years, 3-year growth was reduced in the budesonide group by 1·34 cm. The reduction was greatest in the first year of treatment (0·58 cm) than years 2 and 3 (0·43 cm and 0·33 cm, respectively)
Long-term, once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset.
Polyvalent anti-
Bitis and anti-
Naja antivenom IgY antibodies were prepared using
B. arietans,
B. nasicornis,
B. rhinoceros,
N. melanoleuca, and
N. mossambica venoms to immunize chickens. Blood and ...eggs were collected before and during the 10-month immunization period; the sera and yolk extracts were then prepared and assayed for the presence of antivenom antibodies by ELISA and Western blot methods. ELISA Antivenom antibody titers, referred to as U-ELISA/ml of serum or egg yolk extracts, absent in pre-immunization sera or yolk, increased sharply during the 4
weeks after immunization, reaching a plateau thereafter. Yolk extracts with high antivenom titers, as detected by ELISA were used to isolate and purify IgY. Purified IgY preparations recognized venom protein bands from 10 to 20
kDa to 60 and 70
kDa, as shown by Western blot. Recovery of antivenom antibodies from the whole yolk was over 80%. Final preparations exhibited high antivenom activity (>100,000 U-ELISA/ml) as well as efficacy in neutralizing venom lethality (1440
μg of IgY neutralize 62.2 LD
50 of venom), and were free of toxic products, pyrogen or bacterial and fungal contaminations.
The upgrade of the CMS experiment for the high luminosity operation of the LHC comprises the replacement of the current endcap calorimeter by a high granularity sampling calorimeter (HGCAL). The ...electromagnetic section of the HGCAL is based on silicon sensors interspersed between lead and copper (or copper tungsten) absorbers. The hadronic section uses layers of stainless steel as an absorbing medium and silicon sensors as an active medium in the regions of high radiation exposure, and scintillator tiles directly readout by silicon photomultipliers in the remaining regions. As part of the development of the detector and its readout electronic components, a section of a silicon-based HGCAL prototype detector along with a section of the CALICE AHCAL prototype was exposed to muons, electrons and charged pions in beam test experiments at the H2 beamline at the CERN SPS in October 2018. The AHCAL uses the same technology as foreseen for the HGCAL but with much finer longitudinal segmentation. The performance of the calorimeters in terms of energy response and resolution, longitudinal and transverse shower profiles is studied using negatively charged pions, and is compared to GEANT4 predictions. This is the first report summarizing results of hadronic showers measured by the HGCAL prototype using beam test data.
The incorporation of zinc onto biomaterials may improve their biological properties, since it is an essential trace element, involved in bone remodelling. The in-vivo biocompatibility of previously ...characterised hydroxyapatite granules incorporated with 5% zinc (ZnHA) was evaluated using a subcutaneous grafting test. Granules produced from powders of ZnHA or stoichiometric HA were subcutaneously grafted onto Balb/c mice, and histomorphometrical analysis was performed at 7, 14, 21, 28 or 60 days after grafting. HA and ZnHA induced a similar foreign body reaction, with formation of granulome and the presence of a fibrous capsule. Granulocytes were virtually absent, and agranulocytes decreased with time. ZnHA treated samples presented faster reduction on multinucleated giant cells and increase on observed angiogenesis, compared to HA. ZnHA granules were therefore concluded to be biocompatible. Further study is needed on its potential use for bone therapy.
The Compact Muon Solenoid Collaboration is designing a new high-granularity endcap calorimeter, HGCAL, to be installed later this decade. As part of this development work, a prototype system was ...built, with an electromagnetic section consisting of 14 double-sided structures, providing 28 sampling layers. Each sampling layer has an hexagonal module, where a multipad large-area silicon sensor is glued between an electronics circuit board and a metal baseplate. The sensor pads of approximately 1 cm\(^2\) are wire-bonded to the circuit board and are readout by custom integrated circuits. The prototype was extensively tested with beams at CERN's Super Proton Synchrotron in 2018. Based on the data collected with beams of positrons, with energies ranging from 20 to 300 GeV, measurements of the energy resolution and linearity, the position and angular resolutions, and the shower shapes are presented and compared to a detailed Geant4 simulation.
Background The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study enrolled 7241 patients aged 5 to 66 years with recent-onset, mild persistent asthma to assess early ...intervention with the inhaled corticosteroid budesonide on long-term asthma control. Objective The open-label phase of the START study was included to determine the effect on lung function and asthma control of adding budesonide to the reference group patients who had not initially received inhaled corticosteroids. Methods Patients were randomized to double-blind treatment with budesonide, 200 μg (those aged <11 years) or 400 μg once daily, or placebo plus the usual asthma therapy for 3 years, after which all patients received 2 years of open-label treatment with budesonide once daily. Results During the full 5-year study period, postbronchodilator FEV1 percent predicted decreased, irrespective of randomized treatment during the double-blind phase, by an average of 2.22% (SE, 0.15%). However, patients with inhaled budesonide in the double-blind phase had a significantly lower risk (odds ratio, 0.61; P < .001) of a severe asthma-related event during the full 5-year study period than those in the reference group. Moreover, patients in the reference group used more additional asthma medications during both the open-label and double-blind phases. Conclusions In mild persistent asthma early intervention with inhaled budesonide was associated with improved asthma control and less additional asthma medication use.
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