DHA and EPA in Sickle Cell Disease Favor Clinical Improvement and Contribute to Better Quality of Life: A Qualitative Systematic Review.

BACKGROUND: Sickle cell disease is a severe genetic disorder, and searching for therapeutic strategies is indispensable for prolonged and improved life for people affected by this condition. OBJECTIVE: This qualitative systematic review aimed to highlight the therapeutic potential of omega- 3 (n-3) in people with sickle cell disease. METHODS: The search was performed by combining sickle cell disease and n-3 descriptors in DeCS/ MeSH databases, including Scopus, PubMed, ScienceDirect, Web of Science, and Virtual Health Library. The risk of bias assessment in the primary studies was performed using the Cochrane risk of bias tool for randomized controlled trials. The evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. RESULTS: From the 187 records identified, seven were selected for data collection. Based on the evidence, n-3 supplementation contributes to lower activation of pro-inflammatory biomarkers, improves the concentration of docosahexaenoic and eicosapentaenoic acids in the erythrocyte membrane, provides better hemostatic response, and helps in vaso-occlusive crisis, pain episodes, and hospitalization reduction. CONCLUSION: The findings suggest that n-3 adjuvant therapy favors the clinical and general aspects of people with sickle cell disease.

Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group.

Background: There is limited data on the prevalence and risk factors for long COVID and few prospective studies with appropriate control groups and adequate sample sizes. We performed a prospective study to determine the prevalence and risk factors for long COVID. Methods: We recruited individuals aged ≥15 years who were clinically suspected of having an acute SARS-CoV-2 infection from September 2020 to April 2021. We collected nasopharyngeal swabs three to five days following symptom onset for analysing using reverse transcriptase polymerase chain reaction (RT-PCR). We also collected clinical and sociodemographic characteristics from both SARS-CoV-2 positive and negative participants using structured questionnaires. We followed-up the participants via telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life. Results: We followed 814 participants (412 COVID-19 positive and 402 COVID-19 negative persons). Most (n = 741/814) had mild symptoms. Both groups had similar sociodemographic and clinical characteristics, except for the hospitalization rate (15.8% in the COVID-19 positive vs 1.5% in the COVID-19 negative group). One month after disease onset, 122/412 (29.6%) individuals in the COVID-19 positive (long COVID) and 24 (6%) in the COVID-19 negative group reported residual symptoms. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms in the acute phase. Compared to recovered individuals, older age and having more than five symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID, with 57 (55.9%) reporting an impact in at least one dimension of the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) questionnaire. Conclusions: In this prospective study consisting predominantly of individuals with mild disease, the persistence of symptoms after an acute respiratory illness was associated with a diagnosis of COVID-19. Polysymptomatic acute disease and older age were risk factors for long COVID.

An evaluation of ticagrelor for the treatment of sickle cell anemia.

INTRODUCTION: Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the evidence demonstrating that ticagrelor-mediated inhibition of platelet activation and aggregation have beneficial effects in the treatment of thrombotic conditions, clinical studies have been conducted to evaluate the use of this drug for the treatment of sickle cell disease (SCD), demonstrating satisfactory tolerability and safety. AREAS COVERED: Clinical investigation has characterized the pharmacokinetic and pharmacodynamical profile, as well as the efficacy and safety of ticagrelor to prevent painful vaso-occlusive crisis (painful episodes and acute chest syndrome) in SCD patients. EXPERT OPINION: While phase 1 and 2 clinical trials demonstrated satisfactory tolerability and safety, the conclusion of phase 3 clinical trials is crucial to prove the efficacy of ticagrelor as a therapeutic option for the treatment of SCD. Thus, it is expected that ticagrelor, especially in combination with other drugs, will improve the clinical profile and quality of life of patients with SCD.

Effect of N(Epsilon)-(carboxymethyl)lysine on Laboratory Parameters and Its Association with ß S Haplotype in Children with Sickle Cell Anemia.

The present study aimed to investigate the association of N ε -carboxymethyllysine (CML) with laboratory parameters and ß S haplotypes in pediatric sickle cell anemia (SCA) patients with or without hydroxyurea (HU) therapy. We included 55 children with SCA (SCAtotal), where 27 were on HU treatment (SCA-HU+) and 28 without HU treatment (SCA-HU-). Laboratory characteristics were determined using electronic methods while CML was measured using competitive ELISA. ß S haplotypes were determined by RFLP-PCR. Significant increases in MCV and MCH and significant decreases in leukocytes, eosinophils, basophils, atypical lymphocytes, lymphocytes, and monocytes were found in SCA-HU+ compared to SCA-HU-. SCA-HU+ presented significant reduction in aspartate transaminase and lactate dehydrogenase and increase in creatinine levels compared to SCA-HU-. CML levels were significantly higher in both SCA-HU+ and SCA-HU- compared to the healthy control. In addition, a negative correlation was found between CML and alanine transaminase in SCA-HU+ and SCAtotal (p < 0.01). A significant association was found between CML levels and ß S haplotypes. The results suggest that CML has a role to play in SCA complications, independent of HU therapy.

Correction: Multi-Method Approach for Characterizing the Interaction between Fusarium verticillioides and Bacillus thuringiensis Subsp. Kurstaki.

[This corrects the article DOI: 10.1371/journal.pone.0092189.].

Genetic Polymorphisms Associated with Environmental Exposure to Polycyclic Derivatives in African Children.

BACKGROUND: The nonracial leukopenia may be a result of exposure to polycyclic derivatives (benzene-toluene-xylene (BTX)) and may arise from a possible change in the bone marrow microenvironment. The present study sought to evaluate the association of genetic polymorphisms in xenobiotic-metabolizing enzymes with hematological and biochemical profiles. METHODS: We evaluated 89 African descendant children, exposed indirectly to benzene derivatives. Laboratory parameters were investigated by automated methods and genetic polymorphisms by PCR-RFLP and PCR multiplex. RESULTS: Children with leukopenia had significantly decreased white blood cells (WBCs) and platelet counts, which is not consistent with benign leukopenia. In the same group, we have found that carriers of the CYP2E1 variant allele had decreased WBC and lymphocytes. Those with NQO1 variant allele had decreased WBC, neutrophil, eosinophil, monocyte, and lymphocyte counts. Carriers of the MPO variant allele had decreased WBC, neutrophil, eosinophil, basophil, monocyte, lymphocyte, and platelet counts and an elevated free iron level. Children with GSTT and GSTM null exhibited decreased WBC, neutrophil, basophil, and lymphocyte counts. Our multivariate analysis model reveals that females were independently associated with leukopenia. CONCLUSION: Our results suggest that the polymorphisms investigated were associated with hematological changes in the studied population. These alterations could be heightened by exposure to benzene derivatives.

Evaluation of Cardiometabolic Parameters among Obese Women Using Oral Contraceptives.

BACKGROUND: Combined oral contraceptive (COC) use has been associated with an unfavorable impact on carbohydrate and lipid metabolism in diverse populations of normal weight and obese women. The present study aimed to evaluate the cardiometabolic and inflammatory profiles of women in northeastern Brazil with respect to COC use and obesity. METHODS: We performed a cross-sectional study to verify cardiovascular parameters, including blood pressure (BP), fasting serum glucose, lipid, and inflammatory profile, in a population of women aged 15-45 years, considering obesity and COC use. Our sample consisted of 591 women, 481 women who were COC users, and 110 age-matched women who were COC non-users, classified as obese and non-obese according to BMI. RESULTS: COC use and obesity were associated with increased systolic (p ≤ 0.001) and diastolic BP (p = 0.001), blood glucose (p ≤ 0.001), total cholesterol (p = 0.008), low-density lipoprotein cholesterol (p ≤ 0.001), very low-density lipoprotein cholesterol (p ≤ 0.001), triglycerides (p ≤ 0.001), ferritin (p = 0.006), C-reactive protein (CRP) (p ≤ 0.001), and nitric oxide metabolites (p ≤ 0.001), as well as decreased high-density lipoprotein cholesterol (HDL-c) (p ≤ 0.001) in comparison to controls. CRP and HDL-c levels in obese COC users were determined to be outside reference range values. The odds of having lower levels of HDL-c and elevated CRP increased among obese COC users. COC use was independently associated with low levels of HDL-c, especially second-generation progestins (p < 0.001; OR = 8.976; 95% CI 2.786-28.914). CONCLUSION: Obesity and COC use were associated with alterations in lipid and inflammatory cardiometabolic parameters, particularly increased CRP levels and decreased HDL-c, which are considered markers of cardiovascular disease (CVD) risk. Given the need to prevent unintended pregnancy among obese women, together with weight loss counseling, it is important to evaluate the most effective and safest contraceptive methods to avoid the potential risk of developing CVD.

Hemoglobin Variant Profiles among Brazilian Quilombola Communities.

Brazilian Quilombolas are communities composed of African-derived populations that have their territories guaranteed by the Brazilian Constitution. The present study investigated the hemoglobin (Hb) variants among these population groups. This study was conducted in a total of 2843 individuals of Brazilian Quilombola communities of the Bahia, Pará, and Piauí states. All the participants had their Hb profiles evaluated. The Hb S (HBB: c.20A>T) variant was described in all the studied localities. However, the individuals in Bahia State had the highest frequency of the Hb C (HBB: c.19G>A) variant; individuals from Piauí State had a higher frequency of the Hb D-Punjab (HBB: c.364G>C) variant compared to the other states, and individuals from Pará State only carried the Hb S variant. The present study revealed a specific distribution of Hb variants that could represent different waves of African influence in these Brazilian populations.

Risk factors for Toxocara spp. seroprevalence and its association with atopy and asthma phenotypes in school-age children in a small town and semi-rural areas of Northeast Brazil.

Toxocara canis, Toxocara cati, are roundworms that live in the intestines of dogs and cats, respectively, and are predominantly agents of human toxocariasis. Studies have suggested that Toxocara spp. seroprevalence increases levels of total and aeroallergen-specific IgE (sIgE), asthma prevalence and asthma morbidity. Nevertheless, other work reported a negative association between Toxocara spp. seropositivity with skin hypersensititity and a positive association with sIgE. The objective of the present study was to evaluate risk factors for acquiring Toxocara spp. infection and to investigate possible significant association between its seroprevalence with atopy and asthma. Students from elementary schools, residents in a small town and its surroundings of Northeast Brazil, underwent blood sampling to measure levels of anti-Toxocara spp. IgG, peripheral blood eosinophils, and specific IgE to aeroallergens. We used univariable and multivariable logistic regression analyses to assess possible risk factors for Toxocara spp. seropositivity and its association with atopy, wheeze/asthma with asthma phenotypes, in a sample of 791 elementary school children aged 6-13 years. Toxocara spp. seroprevalence reached 63.6%; 49.9% had sIgE; 7.2% and 3.3% had atopic wheeze/asthma and non-atopic wheeze/asthma respectively. Risk factors associated with Toxocara spp. seropositivity were: contact with dogs (adj. OR 2.33; 95% CI=1.70-3.19) and cats (adj. OR 3.09; 95% CI=2.10-4.55), and male sex (adj. OR 2.21; 95% CI=1.62-3.02). The presence of anti-Toxocara IgG was statistically associated with blood eosinophils >4% and >10% (adj. OR 1.84; 95% CI=1.33-2.55 and adj. OR 2.07; 95% CI=1.45-2.97, respectively), and atopy (adj. OR 2.00; 95% CI=1.49-2.68), but it was not associated with wheeze/asthma. Concluding, the results obtained in this study showing the association of Toxocara spp. seroprevalence with sIgE may suggest a possible immunological cross-reactivity between IgE epitopes from Toxocara spp. and aeroallergens.

Data on prevalence and risk factors associated with Toxocara spp infection, atopy and asthma development in Northeast Brazilian school children.

In the present article, we provide shortly, data on risk factors for acquiring Toxocara spp. infection and investigate possible associations between this infection with atopy and asthma in school children of a small town and its semi-rural areas of Northeast Brazil. The data set are composed by demographic, social and home environment variables. The detection of anti-Toxocara spp. IgG and specific IgE to aeroallergens was determined by ELISA and ImmunocAP/Phadiatrope systems, respectively. The data presented in this article are related to the article entitled "Risk factors for Toxocara spp. seroprevalence and its association with atopy and asthma phenotypes in school-age children in a small town and semi-rural areas of Northeast Brazil" (M.B. Silva, A.L. Amor, L.N. Santos, A.A. Galvão, A.V. Oviedo Vera, E.S. Silva et al., 2016) [1].

Outcome of B-Cell Acute Lymphoblastic Leukemia in Brazilian Children: Immunophenotypical, Hematological, and Clinical Evaluation.

The aim of this study is to investigate the clinical, hematological, and immunophenotypic characteristics of Brazilian children with B-cell acute lymphoblastic leukemia (B-ALL) to identify prognostic biomarkers of the disease. Thirty-three children newly diagnosed with B-ALL were followed between March 2004 and December 2009. Information about the demographic profile, diagnosis, immunophenotype, clinical manifestations, and disease outcome were gathered from the patients' medical records. Of the 33 patients with B-ALL, 18 were male and 15 female. Eighteen patients were classified as high risk; 13 as low risk, and 2 as true low risk. The frequencies of cluster of differentiation (CD)10, CD19, and CD20 antigens were 69.7%, 81.8%, and 18.2%, respectively. Six patients (18.2%) had aberrant expression of myeloid antigens. At diagnosis, patients immunopositive for CD20 had elevated white blood cell counts (P = 0.018) and lower platelet counts (P = 0.017). The 6-year overall survival was 67.5%± 3.47%. Our results demonstrate the distinct immunophenotypic and prognostic characteristics of patients with B-ALL, which can be related to the Brazilian racial admixture. Consequently, these results will most likely aid in the selection of additional prognostic markers and their use in monitoring the clinical manifestations and treatment response among B-ALL patients.

Multi-method approach for characterizing the interaction between Fusarium verticillioides and Bacillus thuringiensis subsp. Kurstaki.

Bacterial antagonists used as biocontrol agents represent part of an integrated management program to reduce pesticides in the environment. Bacillus thuringiensis is considered a good alternative as a biocontrol agent for suppressing plant pathogens such as Fusarium. In this study, we used microscopy, flow cytometry, indirect immunofluorescence, and high performance liquid chromatography to determine the interaction between B. thuringiensis subsp. kurstaki LFB-FIOCRUZ (CCGB) 257 and F. verticillioides MRC 826, an important plant pathogen frequently associated with maize. B. thuringiensis showed a strong in vitro suppressive effect on F. verticillioides growth and inhibited fumonisin production. Flow cytometry analysis was found to be adequate for characterizing the fungal cell oscillations and death during these interactions. Further studies of the antagonistic effect of this isolate against other fungi and in vivo testing are necessary to determine the efficacy of B. thuringiensis subsp. kurstaki in controlling plant pathogens. This is the first report on the use of flow cytometry for quantifying living and apoptotic F. verticillioides cells and the B. thuringiensis Cry 1Ab toxin.

Determinação de HbA1c por CLAE: interferência de variantes de hemoglobinas S e C e alta concentração de HbF / HbA1c determination by HPLC: interference of hemoglobin variants HbS, HbC and HbF high concentration

INTRODUÇÃO: O diabetes mellitus (DM) é considerado um problema importante de saúde pública; possui prevalência elevada e nos últimos anos observa-se aumento progressivo na sua incidência. OBJETIVO: verificar possíveis variações na concentração de hemoglobina (Hb) glicada (HbA1c) na presença de Hbs S e C e avaliar o impacto da redução da HbA1c na avaliação clínica e no monitoramento do paciente diabético. MATERIAL E MÉTODOS: Foram incluídos no estudo, 150 indivíduos diabéticos oriundos da cidade de Salvador, Bahia, de ambos os gêneros, com idade média de 56 anos. Foram determinadas a glicemia de jejum e a HbA1c por metodologia de oxidase-peroxidase e cromatografia líquida de alta eficiência (CLAE), respectivamente. RESULTADOS: Foram observadas variações na concentração da HbA1c em função da presença de variantes de Hb, como 7,85%, AA; 7,30%, AS e 7,15%, AC. DISCUSSÃO E CONCLUSÃO: A metodologia analítica a ser utilizada para determinação de HbA1c deve ser escolhida com base nas características gerais da população atendida e nas comorbidades associadas, pois a presença de Hbs S e C ocasiona reduções significativas de glicação. Essa redução pode levar a interpretações clínicas inadequadas relativas ao controle glicêmico dos pacientes.

INTRODUCTION: Diabetes mellitus (DM) is considered an important public health problem. It is highly prevalent and its incidence has progressively increased in recent years. OBJECTIVE: To verify possible variations of glycated hemoglobin (HbA1c) concentration in the presence of Hb S and Hb C and to evaluate the impact of HbA1c reduction on clinical evaluation and monitoring of diabetic patients. MATERIAL AND METHODS: This study comprised 150 diabetic individuals from Salvador city, Bahia, from both genders and average age of 56 years old. Fast blood glucose and HbA1c were determined by oxidase-peroxidase and high-performance liquid chromatography (HPLC) methods, respectively. RESULTS: There were variations in the concentration of HbA1c in the presence of hemoglobin variants such as AA (7.85%), AS (7.30%), and AC (7.15%). DISCUSSION AND CONCLUSION: The analytical method used to determine HbA1c needs to be chosen according to the general population characteristics and associated comorbidities, since the presence of hemoglobin S and C causes significant reductions in hemoglobin glycation, which may lead to clinical misinterpretation of patients' glycemic control.

Chromatographic method for the determination of aflatoxin M1 in cheese, yogurt, and dairy beverages.

The aim of this work was to develop and validate a method to determine aflatoxin M1 (AFM1) in cheese, yogurt, and dairy beverages. The method consisted of aqueous methanol extraction, immunoaffinity column purification and isolation, RPLC separation, and fluorescence detection. The four types of cheese samples were classified according to moisture and fat content. The mean recoveries were 71% for cheese at spiked levels from 100 to 517 ng/kg, and 76% for yogurt and dairy beverages spiked at levels from 66 to 260 ng/kg. The mean RSDs were 5.9% for cheese, and 10% for yogurt and dairy beverages. The LOD was 3 ng/kg and the LOQ was 10 ng/kg for all test commodities. To test the applicability of the developed method, a small survey of the presence of AFM1 in cheese, yogurt, and dairy beverages purchased in Ribeirão Preto-SP, Brazil, was conducted. AFM1 was detected (> 3 ng/kg) in all samples. Twenty cheese samples (83%) were contaminated with AFM1 in the range of 13-304 ng/kg. In yogurt and dairy beverages, the contamination was lower (13-22 ng/kg) in five samples (42%). The results indicated that the method is adequate for the determination of AFM1 in these four types of cheese, as well as in yogurt and dairy beverages.

BCL11A is a major HbF quantitative trait locus in three different populations with beta-hemoglobinopathies.

Increased HbF levels or F-cell (HbF containing erythrocyte) numbers can ameliorate the disease severity of beta-thalassemia major and sickle cell anemia. Recent genome-wide association studies reported that single nucleotide polymorphisms (SNPs) in BCL11A gene on chromosome 2p16.1 were correlated with F-cells among healthy northern Europeans, and HbF among Sardinians with beta-thalassemias. In this study, we showed that SNPs in BCL11A were associated with F-cell numbers in Chinese with beta-thalassemia trait, and with HbF levels in Thais with either beta-thalassemia or HbE trait and in African Americans with sickle cell anemia. Taken together, the data suggest that the functional motifs responsible for modulating F-cells and HbF levels reside within a 3 kb region in the second intron of BCL11A.

Methylenetetrahydrofolate reductase polymorphisms in myeloid leukemia patients from Northeastern Brazil

Methylenetetrahydrofolate reductase (MTHFR: EC 1.5.1.20) polymorphisms are associated to acute lymphoid leukemia in different populations. We used the polymerase chain reaction and the restriction fragment length polymorphism method (PCR-RFLP) to investigate MTHFR C677T and A1298C polymorphism frequencies in 67 patients with chronic myeloid leukemia (CML), 27 with acute myeloid leukemia FAB subtype M3 (AML-M3) and 100 apparently healthy controls. The MTHFR mutant allele frequencies were as follows: CML = 17.2 percent for C677T, 21.6 percent for A1298C; AML-M3 = 22.2 percent for C677T, 24.1 percent for A1298C; and controls = 20.5 percent for C677T, 21 percent for A1298C. Taken together, our results provide evidence that MTHFR polymorphisms have no influence on the development of CML or AML-M3.