Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in ...inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor.
To investigate associations between the SNPs of GAL-3 gene (LGALS3) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA.
SNPs +191 and +292 in LGALS3 were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old.
GAL-3 serum levels were associated with LGALS3 +191 and +292 genotypes (p <0.0001; p = 0.0169, respectively). LGALS3 +191, AA genotype was associated with low and CC with higher levels of GAL-3. For LGALS3 +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (p = 0.0263) and +292AC/CC genotypes (p = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (p = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (p = 0.0170; p = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (p = 0.0228). LGALS3 +191 and +292 combined genotypes related to low (p = 0.0263) and intermediate expression (p = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (p = 0.0426) and FVOC ≥1 (p = 0.0012).
Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.
Sickle cell anemia (SCA) presents heterogenous clinical manifestations that cannot be explained solely by alterations to hemoglobin (Hb); other components such as endothelial adhesion, thrombosis and ...inflammation may be involved. The mannose-binding lectin (MBL) has an important role in innate immunity and inflammatory diseases. In this report, we describe an association between MBL2 polymorphism related to low production of serum MBL and the frequency of vasoocclusive events (FVOE) in children ≤ 5 years old with SCA (p = 0.0229; OR 5.55; CI 1.11-27.66). Further studies are needed to explore the role of low MBL2 in the pathophysiology of vasoocclusive events in SCA.
Background
Sickle cell anemia (SCA) is a genetic disease with great clinical heterogeneity and few viable strategies for treatment; hydroxyurea (HU) is the only widely used drug. Thus, the study of ...single nucleotide polymorphisms (SNPs) and the gene expression of MMPs 1, 2, 9, 7 and TIMPs 1 and 2, which are involved in the regulation of extracellular matrix, inflammation, and neuropathies, may provide further insights into the pathophysiology of the disease and elucidate biomarkers and molecules as potential therapeutic targets for patients with SCA.
Methods and results
We evaluated 251 young individuals with SCA from northeastern Brazil. The groups were divided according to vaso-occlusive crisis (VOC) and cerebrovascular disease (CVD), compared to control individuals. SNP detection and gene expression assays were performed by real-time PCR, TaqMan system®. Both the expression levels of MMP1 gene, and the SNP MMP1-1607 1G/2G were associated with the risk of cerebral ischemic stroke (IS), and the expression of MMP1 was also associated with a higher frequency of VOC/year. Expression levels of MMP7, TIMP1, and TIMP2 were increased in patients conditioned to IS. The SNP 372T>C (rs4898) TIMP1 T alleles were more frequent in patients with > 5 VOC events/year. The SNP rs17576 of MMP9 showed differences in gene expression levels; it was increased in the genotypes AG, and AG+GG.
Conclusion
The findings of this study, the SNPs, and expression provide initial support for understanding the role of MMPs-TIMPs in the pathophysiology of SCA in young patients.
The SOD2 polymorphism Val16Ala T→C influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD) activity with the ...vaso-occlusive crisis (VOC) and acute splenic sequestration (ASS) in children with sickle cell anemia (SCA). One hundred ninety-five children with SCA aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively). Furthermore, TC and CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively). These results suggest that the SOD2 polymorphism associated with low SOD activity could be a susceptibility factor for the occurrence of VOC and ASS.
Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial ...Doppler to identify children at risk is not universally used.
To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality.
The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme.
Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler.
The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients.
Background: Overweight and obesity are conditions associated with sedentary lifestyle and accumulation of abdominal fat, determining increased mortality, favoring chronic diseases, and increasing ...cardiovascular risk. Although the evaluation of body composition and fat distribution are highly relevant, the high cost of the gold standard techniques limits their wide utilization. Therefore, the aim of this work was to explore the relationships between simple anthropometric measures and BIA variables using multivariate linear regression models to estimate body composition and fat distribution in adults. Methods: In this cross-sectional study, sixty-eight adult individuals (20 males and 48 females) were subjected to bioelectrical impedance analysis (BIA), anthropometric measurements (waist circumference (WC), neck circumference (NC), mid-arm circumference (MAC)), allowing the calculation of conicity index (C-index), fat mass/fat-free mass (FM/FFM) ratios, body mass index (BMI) and body shape index (ABSI). Statistical analyzes were performed with the R program. Nonparametric Statistical tests were applied to compare the characteristics of participants of the groups (normal weight, overweight and obese). For qualitative variables, the Fisher’s exact test was applied, and for quantitative variables, the paired Wilcoxon signed-rank test. To evaluate the linear association between each pair of variables, the Pearson correlation coefficient was calculated, and Multivariate linear regression models were adjusted using the stepwise variable selection method, with Akaike Information Criterion (p ≤ 0.05). Results: BIA variables with the highest correlations with anthropometric measures were total body water (TBW), body fat percentage (BFP), FM, FFM and FM/FFM. The multiple linear regression analysis showed, in general, that the same variables can be estimated through simple anthropometric measures. Conclusions: The assessment of fat distribution in the body is desirable for the diagnosis and definition of obesity severity. However, the high cost of the instruments (dual energy X-ray absorptiometry, hydrostatic weighing, air displacement plethysmography, computed tomography, magnetic resonance) to assess it, favors the use of BMI in the clinical practice. Nevertheless, BMI does not represent a real fat distribution and body fat percentage. This highlights the relevance of the findings of the current study, since simple anthropometric variables can be used to estimate important BIA variables that are related to fat distribution and body composition.
The present study aimed to identify associations between extremes in body weight status (underweight and excess body weight) before a COVID-19 diagnosis and clinical outcomes in patients infected ...with SARS coronavirus type 2.
A multicenter cohort study was conducted in eight different states in northeastern Brazil. Demographic, clinical (previous diagnosis of comorbidities), and anthropometric (self-reported weight and height) data about individuals who tested positive for COVID-19 were collected. Outcomes included hospitalization, mechanical ventilation, and death. Multivariable logistic regression models, adjusted based on age, sex and previous comorbidities, were used to assess the effects of extremes in body weight status on clinical outcomes.
A total of 1308 individuals were assessed (33.6% were elderly individuals). The univariable analyses showed that only hospitalization was more often observed among underweight (3.2% versus 1.2%) and overweight (68.1% versus 63.3%) individuals. In turn, cardiovascular diseases were more often observed in all clinical outcomes (hospitalization: 19.7% versus 4.8%; mechanical ventilation: 19.9% versus 13.5%; death: 21.8% versus 14.1%). Based on the multivariable analysis, body weight status was not associated with risk of hospitalization (underweight: odds ratio OR: 1.10; 95% confidence interval CI 95%, 0.50-2.41 and excess body weight: OR: 0.81; 95 CI, 0.57-1.14), mechanical ventilation (underweight: OR: 0.92; 95% CI, 0.52-1.62 and excess weight: OR: 0.90; 95% CI, 0.67-1.19), and death (underweight: OR: 0.61; 95% CI, 0.31-1.20 and excess body weight: OR 0.88; 95% CI, 0.63-1.23).
Being underweight and excess body weight were not independently associated with clinical outcomes in patients with COVID-19 in the herein analyzed cohort. This finding indicates that the association between these variables may be confounded by both age and comorbidities.
•This is a cohort of 1308 individuals from northeastern Brazil.•Underweight and overweight individuals were more hospitalized due to COVID-19.•Body mass index categories were not independently ...associated with hospitalization, mechanical ventilation, or death.•Age and noncommunicable diseases cofounded the association between body weight status and outcomes of COVID-19.
The present study aimed to identify associations between extremes in body weight status (underweight and excess body weight) before a COVID-19 diagnosis and clinical outcomes in patients infected with SARS coronavirus type 2.
A multicenter cohort study was conducted in eight different states in northeastern Brazil. Demographic, clinical (previous diagnosis of comorbidities), and anthropometric (self-reported weight and height) data about individuals who tested positive for COVID-19 were collected. Outcomes included hospitalization, mechanical ventilation, and death. Multivariable logistic regression models, adjusted based on age, sex and previous comorbidities, were used to assess the effects of extremes in body weight status on clinical outcomes.
A total of 1308 individuals were assessed (33.6% were elderly individuals). The univariable analyses showed that only hospitalization was more often observed among underweight (3.2% versus 1.2%) and overweight (68.1% versus 63.3%) individuals. In turn, cardiovascular diseases were more often observed in all clinical outcomes (hospitalization: 19.7% versus 4.8%; mechanical ventilation: 19.9% versus 13.5%; death: 21.8% versus 14.1%). Based on the multivariable analysis, body weight status was not associated with risk of hospitalization (underweight: odds ratio OR: 1.10; 95% confidence interval CI 95%, 0.50–2.41 and excess body weight: OR: 0.81; 95 CI, 0.57–1.14), mechanical ventilation (underweight: OR: 0.92; 95% CI, 0.52–1.62 and excess weight: OR: 0.90; 95% CI, 0.67–1.19), and death (underweight: OR: 0.61; 95% CI, 0.31–1.20 and excess body weight: OR 0.88; 95% CI, 0.63–1.23).
Being underweight and excess body weight were not independently associated with clinical outcomes in patients with COVID-19 in the herein analyzed cohort. This finding indicates that the association between these variables may be confounded by both age and comorbidities.
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