Obesity is considered a global public health problem. Cesarean section has been associated with high body mass index (BMI) and increased obesity throughout life. However, this association has been ...challenged by some studies. This study aims to assess the causal effect of cesarean section on the BMI of children aged 1-3 years. This is a cohort study of 2,181 children aged 1-3 years, born in 2010, obtained from the BRISA Birth Cohort, in São Luís, state of Maranhão, Brazil. Sociodemographic variables, maternal characteristics, type of childbirth, morbidity, anthropometric measurements, and BMI were assessed. Marginal structural models with a counterfactual approach were used to check the causal effect of the type of childbirth on obesity, weighted by the inverse probability of selection and exposure. Out of the 2,181 children assessed (52% female), 50.6% were born by cesarean section, 5.9% of the newborn infants were large for gestational age, and 10.7% of them had excess weight. No causal effect of cesarean section on BMI was observed (coefficient = -0.004; 95%CI: -0.136; 0.127; p = 0.948). Cesarean section did not have a causal effect on the BMI of children aged 1-3 years.
The toxicity of cadmium and chromium to Pseudokirchneriella subcapitata and Microcystis aeruginosa was evaluated through algal growth rate during 96h exposure bioassays. Free metal ion concentrations ...were obtained using MINEQL super(+) 4.61 and used for IC50 determination. Metal accumulations by the microorganisms were determined and they were found to be dependent on the concentration of Cd super(2+) and Cr super(6+). IC50 for P. subcapitata were 0.60 mu mol L super(-1) free Cd super(2+) and 20 mu mol L super(-1) free Cr super(6+), while the IC50 values for M. aeruginosa were 0.01 mu mol L super(-1) Cd super(2+) and 11.07 mu mol L super(-1) Cr super(6+) times P. subcapitata accumulated higher metal concentrations (0.001 -0.05 mu mol Cd mg super(-1) dry wt. and 0.001 -0.04 mu mol Cr mg super(-1) dry wt) than the cyanobacteria (0.001 -0.01 mu mol Cd mg super(-1) dry wt and 0.001 -0.02 mu mol Cr mg super(-1) dry wt). Cadmium was more toxic than chromium to both the microorganisms.
A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y ...challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log
10
mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naïve baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α
+
and IFN-γ
+
produced by CD4
+
and CD8
+
T-cells along with increasing levels of IL-10
+
CD4
+
T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naïve baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8
+
memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.
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•Recombinase Polymerase Amplification (RPA) is a simple and accurate tool for fast detection of Schistosoma mansoni DNA.•RPA targeting the S. mansoni mitochondrial minisatellite ...region (SmMIT-RPA) can be used to detect infected snails.•SmMIT-RPA detects S. mansoni early pre-patent infections in laboratory snails.•SmMIT-RPA is a sensitive and specific tool for S. mansoni snail xenomonitoring.
Improvements in diagnostics for schistosomiasis in both humans and snail hosts are priorities to be able to reach the World Health Organization (WHO) goal of eliminating the disease as a public health problem by 2030. In this context, molecular isothermal amplification tests, such as Recombinase Polymerase Amplification (RPA), are promising for use in endemic areas at the point-of-need for their accuracy, robustness, simplicity, and time-effectiveness. The developed recombinase polymerase amplification assay targeting the Schistosoma mansoni mitochondrial minisatellite region (SmMIT-RPA) was used to detect S. mansoni DNA from both laboratory and field Biomphalaria snails. Laboratory snails were experimentally infected and used at one, seven, and 28 days post-exposure (dpe) to 10 S. mansoni miracidia to provide samples in the early pre-patent infection stage. Field samples of Biomphalaria spp. were collected from the Mucuri Valley and Jequitinhonha Valley regions in the state of Minas Gerais, Brazil, which are endemic for S. mansoni. The sensitivity and specificity of the SmMIT-RPA assay were analysed and compared with existing loop-mediated isothermal amplification (LAMP), PCR-based methods, parasitological examination of the snails, and nucleotide sequencing. The SmMIT-RPA assay was able to detect S. mansoni DNA in the experimentally infected Biomphalaria glabrata as early as one dpe to 10 miracidia. It also detected S. mansoni infections (55.5% prevalence) in the field samples with the highest accuracy (100% sensitivity and specificity) compared with the other molecular tests used as the reference. Results from this study indicate that the SmMIT-RPA assay is a good alternative test to be used for snail xenomonitoring of S. mansoni due to its high sensitivity, accuracy, and the possibility of detecting early pre-patent infection. Its simplicity and portability also make it a suitable methodology in low-resource settings.
A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar ...epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19).
This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality.
Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints.
Administration of NAC in high doses did not affect the evolution of severe COVID-19.
Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).
Abstract
The SARS‐CoV‐2 (COVID‐19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in ...blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi‐omics platform to investigate COVID‐19‐infected lung tissues. Five tissue‐profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi‐omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS‐CoV‐2 on the lungs.
To externally validate community-acquired pneumonia (CAP) tools on patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia from two distinct countries, and compare their performance ...with recently developed COVID-19 mortality risk stratification tools.
We evaluated 11 risk stratification scores in a binational retrospective cohort of patients hospitalized with COVID-19 pneumonia in São Paulo and Barcelona: Pneumonia Severity Index (PSI), CURB, CURB-65, qSOFA, Infectious Disease Society of America and American Thoracic Society Minor Criteria, REA-ICU, SCAP, SMART-COP, CALL, COVID GRAM and 4C. The primary and secondary outcomes were 30-day in-hospital mortality and 7-day intensive care unit (ICU) admission, respectively. We compared their predictive performance using the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, likelihood ratios, calibration plots and decision curve analysis.
Of 1363 patients, the mean (SD) age was 61 (16) years. The 30-day in-hospital mortality rate was 24.6% (228/925) in São Paulo and 21.0% (92/438) in Barcelona. For in-hospital mortality, we found higher AUCs for PSI (0.79, 95% CI 0.77–0.82), 4C (0.78, 95% CI 0.75–0.81), COVID GRAM (0.77, 95% CI 0.75–0.80) and CURB-65 (0.74, 95% CI 0.72–0.77). Results were similar for both countries. For the 1%–20% threshold range in decision curve analysis, PSI would avoid a higher number of unnecessary interventions, followed by the 4C score. All scores had poor performance (AUC <0.65) for 7-day ICU admission.
Recent clinical COVID-19 assessment scores had comparable performance to standard pneumonia prognostic tools. Because it is expected that new scores outperform older ones during development, external validation studies are needed before recommending their use.
Sickle cell disease (SCD), the most common monogenic disease worldwide, is marked by a phenotypic variability that is, to date, only partially understood. Because inflammation plays a major role in ...SCD pathophysiology, we hypothesized that single nucleotide polymorphisms (SNP) in genes encoding functionally important inflammatory proteins might modulate the occurrence of SCD complications. We assessed the association between 20 SNPs in genes encoding Toll-like receptors (TLR), NK cell receptors (NKG), histocompatibility leukocyte antigens (HLA), major histocompatibility complex class I polypeptide-related sequence A (MICA) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and the occurrence of six SCD clinical complications (stroke, acute chest syndrome (ACS), leg ulcers, cholelithiasis, osteonecrosis, or retinopathy). This study was performed in a cohort of 500 patients. We found that the
4696480
3804099
, and HLA-G,
9380142
genotypes were more frequent in patients who had fewer complications. Also, in logistic regression, the HLA-G
9380142
allele increased the risk of cholelithiasis (
vs.
, OR 1.57, 95%CI 1.16-2.15;
vs.
, OR 2.47, 95%CI 1.34-4.64;
= 0.02). For SNPs located in the
loci, in logistic regression, the A allele in three SNPs was associated with a lower frequency of retinopathy, namely,
2246809 (
vs.
: OR 0.22, 95%CI 0.09-0.50;
vs.
: OR 0.47, 95%CI 0.31-0.71;
= 0.004, for patients of same origin),
2617160 (
vs.
: OR 0.67, 95%CI 0.48-0.92;
vs.
: OR 0.45, 95%CI 0.23-0.84;
= 0.04), and
2617169 (
vs.
: OR 0.33, 95%CI 0.13-0.82;
vs.
: OR 0.58, 95%CI 0.36-0.91,
= 0.049, in patients of same SCD genotype). These results, by uncovering susceptibility to, or protection against SCD complications, might contribute to a better understanding of the inflammatory pathways involved in SCD manifestations and to pave the way for the discovery of biomarkers that predict disease severity, which would improve SCD management.
This work aimed to carry out phytochemical prospecting and evaluate the antioxidant potential of
, a species of Malpighiaceae family that has not yet been studied.In qualitative analyses of ...hydroethanolic extracts of leaves and stems were detected the presence of flavonoids, alkaloidsand terpenes. The histochemical evaluation evidenced a greater distribution of these compounds in the tissues of leaf when compared with those of stem. The analysis by mass spectrometry allowed the identification of prenylated xanthones and glycoside flavonoids that have not yet been reported in the literature. The antioxidant activity of the stem extract was considered moderate (IAA = 0.79), but the leaves presented a strong antioxidant activity (IAA = 1.6). In this work we present information about the phytochemicals of
, showing that the species is promising in obtaining compounds with medicinal potential mainly antioxidant potential.
We investigated the genetic composition of six Canis remains from western Iberia, directly radiocarbon dated to 7,903–7,570 years (cal BP). They were identified as dogs via their archaeological and ...depositional context, osteometry, and a high percentage of aquatic diet shared with humans. For comparison, genetic data were obtained from an additional 37 Iberian dog remains from the Neolithic to Late Antiquity, as well as two Palaeolithic and a Chalcolithic Canis identified as wolves. Previous data indicated that dog mtDNA haplogroup A (HgA) is prevalent in extant European dogs (>50%), in the Near East and Asia, but rare or absent (<10%) in European Canis older than 3,000 years (cal BP). We found a high frequency (83%) of dog HgA in Mesolithic Iberian dog remains. This is the first report of a high frequency of dog HgA in pre-Neolithic Europe. We show that, contrary to the current view, Canis with HgA did not necessarily arrive in Europe from East-Asia. This phylogeographical difference in HgA frequency demonstrates that genetic differentiation was high prior to, or as a consequence of, domestication which may be linked with pre-Neolithic local processes for Iberian wolf domestication. Our results emphasize that knowledge of both ancient wolves' and early dogs’ genetic profiles from the European periphery should improve our understanding of the evolution of the European dog.
•We studied the oldest Portuguese dog remains (n = 6), dated to the Mesolithic .•High frequency of dog haplogroup A is reported for pre-Neolithic Iberia.•Dog haplogroup A did not necessarily arrive in Europe from the East.•Pre-Neolithic local processes for an Iberian wolf domestication is suggested.
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