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BACKGROUND: Admixture occurs between different ethnic human populations. The global colonization in recent centuries by Europeans led to the most significant admixture in human history. While admixture may enhance genetic diversity for better fitness, it may also impact on human health by transmitting genetic variants for disease susceptibility in the admixture population. The admixture by Portuguese global exploration initiated in the 15th century has reached over 20 million of Portuguese-heritage population worldwide. It provides a valuable model to study the impact of admixture on human health. BRCA1 and BRCA2 (BRCA) are two of the important tumor suppressor genes. The pathogenic variation (PV) in BRCA is well determined to cause high risk of hereditary breast and ovarian cancer. Tracing the distribution of Portuguese BRCA PV in Portuguese-heritage population will help to understand the impact of admixture on cancer susceptibility in modern humans. In this study, we analyzed the distribution of the Portuguese-originated BRCA variation in Brazilian population, which has high degree Portuguese-heritage. METHODS: By comprehensive data mining, standardization and annotation, we generated a Portuguese-derived BRCA variation dataset and a Brazilian-derived BRCA variation dataset. We compared the two BRCA variation datasets to identify the BRCA variants shared between the two populations. RESULTS: The Portuguese-derived BRCA variation dataset consists of 220 BRCA variants including 78 PVs from 11,482 Portuguese cancer patients, 93 (42.2%) in BRCA1 and 127 (57.7%) in BRCA2. Of the 556 Portuguese BRCA PV carriers carrying the 78 PVs, 331 (59.5%) carried the three Portuguese-BRCA founder PVs of BRCA1 c.2037delinsCC, BRCA1 c.3331_3334del and BRCA2 c.156_157insAlu. The Brazilian-derived BRCA variation dataset consists of 255 BRCA PVs from 7,711 cancer patients, 136 (53.3%) in BRCA1 and 119 (46.6%) in BRCA2. We developed an open database named dbBRCA-Portuguese ( https://genemutation.fhs.um.edu.mo/dbbrca-portuguese/ ) and an open database named dbBRCA-Brazilian ( https://genemutation.fhs.um.edu.mo/dbbrca-brazilian ) to host the BRCA variation data from Portuguese and Brazilian populations. We compared the BRCA PV datasets between Portuguese and Brazilian populations, and identified 29 Portuguese-specific BRCA PVs shared between Portuguese and Brazilian populations, 14 in BRCA1 including the Portuguese founder BRCA1 c.3331_3334del and BRCA1 c.2037delinsCC, and 15 in BRCA2 including the Portuguese founder BRCA2 c.156_157insAlu. Searching the 78 Portuguese BRCA PVs in over 5,000 ancient human genomes identified evolution origin for only 8 PVs in Europeans dated between 37,470 and 3,818 years before present, confirming the Portuguese-specificity of Portuguese BRCA PVs; comparing the 78 Portuguese BRCA PVs Portuguese, 255 Brazilian BRCA PVs, and 134 African BRCA PVs showed little overlapping, ruling out the possibility that the BRCA PVs shared between Portuguese and Brazilian may also be contributed by African. CONCLUSION: Our study provides evidence that the admixture in recent human history contributed to cancer susceptibility in modern humans.
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Proteína BRCA1 , Proteína BRCA2 , Humanos , Proteína BRCA2/genética , Proteína BRCA1/genética , Portugal , Femenino , Predisposición Genética a la Enfermedad , Brasil , Variación Genética , Neoplasias de la Mama/genética , Neoplasias Ováricas/genéticaRESUMEN
Sickle cell anemia (SCA), the most common form of sickle cell disease (SCD), is a genetic blood disorder. Red blood cells break down prematurely, causing anemia and often blocking blood vessels, leading to chronic pain, organ damage, and increased infection risk. SCD arises from a single-nucleotide mutation in the ß-globin gene, substituting glutamic acid with valine in the ß-globin chain. This review examines treatments evaluated through randomized controlled trials for managing SCD, analyzes the potential of functional foods (dietary components with health benefits) as a complementary strategy, and explores the use of bioactive compounds as functional food ingredients. While randomized trials show promise for certain drugs, functional foods enriched with bioactive compounds also hold therapeutic potential. Further research is needed to confirm clinical efficacy, optimal dosages, and specific effects of these compounds on SCD, potentially offering a cost-effective and accessible approach to managing the disease.
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BACKGROUND: Sickle Cell Anemia (SCA) is a monogenic disease, although its severity and response to treatment are very heterogeneous. OBJECTIVES: This study aims to characterize a cohort of Angolan children with SCA and evaluate their response to hydroxyurea (HU) treatment and the potential side effects and toxicity. METHODS: The study enrolled 215 patients between 3 and 12 years old before and after the administration of HU, at a fix dose of 20 mg/kg/day for 12 months. RESULTS: A total of 157 patients started HU medication and 141 of them completed the 12-month treatment. After initiating HU treatment, the frequency of clinical events decreased (transfusions 53.4 %, hospitalizations 47.1 %). The response to HU medication varied among patients, with some experiencing an increase in fetal hemoglobin (HbF) of <5 %. The mean increase in HbF was 11.9 %, ranging from 1.8 % to 31 %. Responders to HU treatment were 57 %, inadequate responders 38.7 % and non-adherent 4.2 %. No clinical side effects related to HU were reported. Hematological toxicities were transient and reversible. Children naïve to HU and with lower HbF reported higher number of hospitalizations caused by malaria infection. During HU treatment, the frequency of malaria episodes did not appear to be affected by HbF levels. CONCLUSIONS: the present study provided a valuable contribution to the understanding of the clinical and laboratory profiles of Angolan children with SCA. These findings support the evidence that the implementation of prophylactic measures and treatment with HU is associated with increased survival in children with SCA.
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Anemia de Células Falciformes , Malaria , Niño , Humanos , Preescolar , Hidroxiurea/efectos adversos , Antidrepanocíticos/efectos adversos , Anemia de Células Falciformes/tratamiento farmacológico , Hemoglobina Fetal/análisis , Malaria/tratamiento farmacológicoRESUMEN
Sickle cell anemia (SCA) causes a long-standing vascular inflammation state, leading to endothelial dysfunction and chronic overexpression of several adhesion molecules, which contributes to acute and constant vaso-occlusive (VOC) episodes. It has been demonstrated that hydroxyurea (HU) can reduce VOC events, organ damage, blood transfusions, and even the adhesion properties to endothelial cells of SCA subjects. Due to VOC episodes, these patients are also more susceptible to recurrent bacterial translocation and dysbiosis. Given this, our study aimed to uncover the interplay between adhesion molecules, gut microbiome, and hydroxyurea in a population of Angolan SCA children. Serum and fecal samples were obtained before and after HU treatment in 35 children. After HU, four of these adhesion molecules were significantly reduced: sE-selectin (p = 0.002), ADAMTS13 (p = 0.023), sICAM-1 (p = 0.003), and sVCAM-1 (p = 0.018). A positive correlation was observed between the number of neutrophils and sICAM-1, platelets, and sP-selectin, and also between leukocytes, sICAM-1, and sVCAM-1. Most taxa showing a significant correlation mainly belonged to the Clostridiales order. Specifically, from the Clostridium genera, the groups g19, g21, and g34 were all negatively correlated with HbF levels; g19, g21, and g24 positively correlated with leukocytes; g19 positively with neutrophils and sVCAM-1; and g34 positively with E- and P-selectin. Serratia, an opportunistic pathogen, was positively correlated with sE-selectin and sICAM-1 levels. Additionally, a negative correlation was observed between sP-selectin and Bifidobacterium. Research studies in this area could improve our understanding and contribute to finding new prognostic biomarkers to guarantee precise SCA patient stratification and predict severe complications.
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Anemia de Células Falciformes , Microbioma Gastrointestinal , Compuestos Orgánicos Volátiles , Niño , Humanos , Hidroxiurea/uso terapéutico , Células Endoteliales , Moléculas de Adhesión Celular , Anemia de Células Falciformes/tratamiento farmacológico , SelectinasRESUMEN
Sickle cell disease (SCD) clinically manifests itself with a myriad of complications. Stroke, both ischemic and hemorrhagic, as well as silent white matter changes, occurs at a relatively high prevalence. Understanding why and in whom stroke is most likely to occur is critical to the effective prevention and treatment of individuals with SCD. Genetic studies, including genome- and exome-wide association studies (GWAS and EWAS), have found several key modifiers associated with increased stroke/stroke risk in SCD via mechanisms including Hemoglobin F (HbF) modulation, inflammation, cellular adhesion, endothelial disruption, and hemolysis. We present a review on the modifiers that have most clearly demonstrated an association to date. More studies are needed to validate other potential polymorphisms and identify new ones. Incorporating gene-focused screenings in clinical care could provide avenues for more targeted, more effective, and less toxic prevention of stroke in this population. The data from this review will be used to inform the initial GWAS performed by the International Hemoglobinopathy Research Network (INHERENT) consortium.
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Anemia de Células Falciformes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular , Humanos , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/complicaciones , Accidente Cerebrovascular/genética , Genes Modificadores , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismoRESUMEN
Parasitic infections are a common problem in developing countries and can intensify morbidity in patients with sickle cell disease (SCD), increasing the severity of anemia and the need for transfusions. It has been demonstrated that both helminths and protozoa can affect gut microbiome composition. On the other hand, the presence of specific bacterial communities can also influence parasite establishment. Considering this, our aim was to associate the presence of intestinal parasites with the results of hematological analyses and microbiome composition evaluations in a population of Angolan children with and without SCD. A total of 113 stool samples were collected, and gut microbiome analysis was performed using 16S sequencing and real-time PCR to detect eight different intestinal parasites. In our population, more than half of children (55%) had at least one parasitic infection, and of these, 43% were co-infected. Giardia intestinalis and Ascaris lumbricoides were more frequently found in children from the rural area of Bengo. Moreover, SCD children with ascariasis exhibited higher values of leukocytes and neutrophils, whereas the total hemoglobin levels were lower. In regards to the gut microbiome, the presence of intestinal parasites lowered the prevalence of some beneficial bacteria, namely: Lactobacillus, Bifidobacterium, Cuneatibacter, Bacteroides uniformis, Roseburia, and Shuttleworthia. This study presents the prevalence of several intestinal parasites in a high-risk transmission area with scarce information and opens new perspectives for understanding the interaction between parasites, the microbiome, and SCD.
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Anemia de Células Falciformes , Microbioma Gastrointestinal , Humanos , Niño , Masculino , Femenino , Preescolar , Heces/microbiología , Heces/parasitología , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/parasitología , Adolescente , AnimalesRESUMEN
BACKGROUND: In malaria-endemic areas, children presenting to hospitals with a decreased level of consciousness remain a diagnostic dilemma. The definition of cerebral malaria in a comatose child demands exclusion of other possible reasons, which requires in-depth investigations that are not easily available. The aim of this study was to investigate the frequency and clinical characteristics of PCR-confirmed malaria in a cohort of children with a decreased level of consciousness, look for potential features that would aid in differentiating children with malaria from those without, and assess the performance of traditional thick film microscopy against the cytb-qPCR-method. METHODS: A total of 345 children aged 30 days-15 years old, presenting to Hospital Pediátrico David Bernardino in Luanda, Angola, with a decreased level of consciousness (Glasgow coma scale score < 15) were prospectively enrolled during 2014-2017. Malaria was defined as a positive cytb-qPCR result on any occasion in hospital. The clinical course and laboratory parameters were compared between children with malaria and those without. The performance of thick film microscopy was analysed against the PCR method. RESULTS: 161 of 345 children (46.7%) had a positive malaria PCR test result. All cases were Plasmodium falciparum species, and 82.6% (133/161) fulfilled the WHO criteria for severe malaria. Overall, children with malaria presented to hospital with a shorter duration of symptoms and less convulsions pre-admission compared to those without malaria. The median GCS score on admission was 8, which did not differ between children with or without malaria. Clinical findings on admission were mostly similar across the whole cohort, but an infection focus outside the central nervous system was more common in malaria-negative children. Moreover, severe anaemia, thrombocytopenia, and high CRP levels occurred more frequently in children with malaria. The case fatality ratio was 28.5% (91/319) and did not differ between parasitaemic children and those without malaria, although parasitaemic children died sooner after hospital admission. When neurological sequelae were also considered, a positive malaria test was associated with a better outcome. The performance of thick film microscopy against PCR yielded a sensitivity of 96.8% and a specificity of 82.7%. CONCLUSIONS: In this cohort of children with a decreased consciousness, the frequent presence of a malarial infection could not be judged from the clinical findings on admission, but the combination of profound aneamia, thrombocytopenia, and a high CRP level increased the odds of a positive malaria test result. Mortality remained high regardless of etiology, but malaria infection associated with fewer neurological deficits at discharge. Thick film microscopy performed well compared to the cytb-qPCR method.
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Anemia , Malaria Cerebral , Malaria Falciparum , Trombocitopenia , Humanos , Niño , Lactante , Malaria Falciparum/diagnóstico , Malaria Falciparum/epidemiología , Malaria Falciparum/complicaciones , Estudios Prospectivos , Estado de Conciencia , Angola/epidemiología , Malaria Cerebral/diagnóstico , Malaria Cerebral/epidemiología , Malaria Cerebral/complicaciones , Anemia/etiología , Reacción en Cadena de la PolimerasaRESUMEN
This study aimed to synthesize the evidence on the effects of disease-modifying agents for managing sickle cell disease (SCD) in children and adolescents by means of a systematic review with network meta-analyses, surface under the cumulative ranking curve (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) (CRD42022328471). Eightteen randomized controlled trials (hydroxyurea [n = 7], l-arginine [n = 3], antiplatelets [n = 2], immunotherapy/monoclonal antibodies [n = 2], sulfates [n = 2], docosahexaenoic acid [n = 1], niprisan [n = 1]) were analyzed. SUCRA and SMAA demonstrated that hydroxyurea at higher doses (30 mg/kg/day) or at fixed doses (20 mg/kg/day) and immunotherapy/monoclonal antibodies are more effective for preventing vaso-occlusive crisis (i.e., lower probabilities of incidence of this event; 14, 25, and 30%, respectively), acute chest syndrome (probabilities ranging from 8 to 30%), and needing of transfusions (11-31%), while l-arginine (100-200 mg/kg) and placebo were more prone to these events. Therapies were overall considered safe; however, antiplatelets and sulfates may lead to more severe adverse events. Although the evidence was graded as insufficient and weak, hydroxyurea remains the standard of care for this population, especially if a maximum tolerated dose schedule is considered.
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Anemia de Células Falciformes , Hidroxiurea , Niño , Adolescente , Humanos , Hidroxiurea/uso terapéutico , Antidrepanocíticos/uso terapéutico , Metaanálisis en Red , Anemia de Células Falciformes/complicaciones , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
BACKGROUND: There is considerable research interest in the role of helminth infections in the development of allergic diseases. However, findings from previous studies are mixed. Existing systematic reviews of these studies are outdated. We performed a systematic review of the global literature on the association between helminth infections and development and clinical outcomes of allergic diseases. METHODS: We searched Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, PubMed, Global Index Medicus, Scielo, KoreaMed, Google Scholar, and Lilacs for studies published up to January 2020. We included observational epidemiological studies (cohort, case-control, and cross-sectional studies) of children and adults reporting associations between helminth infections and asthma, allergic rhinitis, eczema, and atopy. We performed random-effects meta-analysis to summarize the effect estimates. RESULTS: We included 80 studies with 99,967 participants. In the meta-analyses, we did not observe an overall association between helminth infections and allergic diseases. There was, however, evidence that Ascaris lumbricoides infections were associated with an increased risk of bronchial hyperreactivity in children (risk ratio, 1.41; 95% CI, 1.17-1.70; I2 = 50; P for I2 = .09), and were associated with an increased risk of atopy among helminth-infected adults (risk ratio, 1.37; 95% CI, 1.18-1.61; I2 = 52; P for I2 = .02). We found no study that addressed the association between helminth infection and clinical outcomes of allergic diseases. The overall strength of the underlying evidence was low to moderate. CONCLUSIONS: Helminth infections may increase the risk of bronchial hyperreactivity in children and atopy in adults. Well-designed longitudinal cohorts may help clarify potential causal associations between chronic helminth infections and allergic diseases.
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Hiperreactividad Bronquial , Helmintiasis , Helmintos , Hipersensibilidad Inmediata , Rinitis Alérgica , Adulto , Animales , Niño , Estudios Transversales , Helmintiasis/complicaciones , Helmintiasis/epidemiología , HumanosRESUMEN
Sickle cell anemia (SCA) is an inherited disease affecting the hemoglobin that is particularly common in sub-Saharan Africa. Although monogenic, phenotypes are markedly heterogeneous in terms of severity and life span. Hydroxyurea is still the most common treatment for these patients, and the response to treatment is highly variable and seems to be an inherited trait. Therefore, identifying the variants that might predict hydroxyurea response is important for identifying patients who will have a poorer or non-response to treatment, and the ones that are more prone to suffer from severe side effects. In the present pharmacogenetic study, we analyzed the exons of 77 genes described in the literature as potentially associated with hydroxyurea metabolism in Angolan children treated with hydroxyurea and evaluated the drug response considering fetal hemoglobin levels, other hematological and biochemical parameters, hemolysis, number of vaso-occlusive crises and hospitalizations. Thirty variants were identified in 18 of those genes as possibly associated with drug response, five of them in gene DCHS2. Other polymorphisms in this gene were also associated with hematological, biochemical and clinical parameters. Further research examining the maximum tolerated dose and fixed dose with a larger sample size is necessary to corroborate these findings.
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Anemia de Células Falciformes , Hidroxiurea , Humanos , Hidroxiurea/efectos adversos , Pruebas de Farmacogenómica , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/complicaciones , Hemólisis , Hemoglobina Fetal/análisisRESUMEN
Sickle cell disease (SCD) is one of the most common genetic conditions worldwide. It can contribute up to 90% of under-5 mortality in sub-Saharan Africa. Clinical manifestations are very heterogeneous, and the intestinal microbiome appears to be crucial in the modulation of inflammation, cell adhesion and induction of aged neutrophils, the main interveners of recurrent vaso-occlusive crisis. Enterocyte injury, increased permeability, altered microbial composition and bacterial overgrowth have all been documented as microbial and pathophysiologic changes in the gut microbiome of SCD patients in recent studies. Our aim was to sequence the bacterial 16S rRNA gene in order to characterize the gut microbiome of Angolan children with SCA and healthy siblings as a control. A total of 72 stool samples were obtained from children between 3 and 14 years old. Our data showed that the two groups exhibit some notable differences in microbiota relative abundance at different classification levels. Children with SCA have a higher number of the phylum Actinobacteria. As for the genus level, Clostridium cluster XI bacteria was more prevalent in the SCA children, whereas the siblings had a higher abundance of Blautia, Aestuariispira, Campylobacter, Helicobacter, Polaribacter and Anaerorhabdus. In this study, we have presented the first microbiota analysis in an Angolan paediatric population with SCD and provided a detailed view of the microbial differences between patients and healthy controls. There is still much to learn before fully relying on the therapeutic approaches for gut modulation, which is why more research in this field is crucial to making this a reality.
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Anemia de Células Falciformes , Microbioma Gastrointestinal , Microbiota , Niño , Humanos , Anciano , Preescolar , Adolescente , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Bacterias/genética , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/microbiologíaRESUMEN
BACKGROUND: Sickle Cell Anemia (SCA) is a genetic disease caused by the c.20 A > T mutation in HBB gene, generally characterized by sickle erythrocytes, chronic hemolytic anemia, and vaso-occlusive events. This study aimed to investigate genetic modulators of anemia severity, chronic hemolytic rate, and clinical manifestations in pediatric SCA patients from Angola, where the disease is a severe public health problem. METHODS AND RESULTS: The study was conducted on 200 SCA children living in Luanda or Caxito province. Their clinical phenotype was collected from patients' hospital records. Hematological and biochemical phenotypes were characterized in steady state condition. Twelve polymorphic regions in VCAM1, CD36 and NOS3 genes were genotyped using PCR, RFLP, and Sanger sequencing. CD36 gene promoter variants showed a significant impact on anemia severity. Particularly, the rs1413661_C allele was associated with lower hemoglobin levels, and increased number of hospitalizations and transfusions. This is the first report associating this SNP with SCA phenotypic heterogeneity. Moreover, the rs1041163_C allele in VCAM1 was associated with lower LDH levels; inversely the rs2070744_C allele in NOS3 was related with higher LDH levels and number of hospitalizations, being a risk factor for increased hemolytic rate. CONCLUSION: This study highlights, for the first time in the Angolan population, the importance of the genetic modifiers of vascular cell adhesion and nitric oxide metabolism in SCA pediatric phenotypic variability.
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Anemia de Células Falciformes , Hemólisis , Humanos , Anemia de Células Falciformes/genética , Eritrocitos , Alelos , HospitalizaciónRESUMEN
BACKGROUND: Studies on the electrocardiogram findings in African pregnant women are limited. There is no information available in the literature on the electrocardiographic parameters of pregnant Angolan women. OBJECTIVES: The aim of this study was to describe electrocardiographic findings in women with normal pregnancies in Bengo Province, Angola. METHODS: This is a community-based study with a cross-sectional design conducted between September 2013 and March 2014 in Bengo. The study involved 114 black pregnant women, compared with a paired control group comprising of 120 black non-pregnant women, aged 15 to 42 years. A 12-lead electrocardiogram and a rhythm strip were recorded for all participants. RESULTS: In this study, the mean age was 26.2 ± 7.3 years. Comparing pregnant women vs. non-pregnant, we found the following mean values: Heart rate (83 bpm vs. 74 bpm, p < .001), PR interval (146 ms vs. 151 ms, p = .034), QT interval (360 ms vs. 378 ms, p < .001), QTIc Fridericia (398 ms vs. 403, p = .017), QTIc Framingham (399 ms vs. 404 ms, p = .013) and T-wave axis (340 vs. 410 , p = .001).The main electrocardiographic changes found were: Sinus tachycardia (4.4% vs. 2.5%), T-wave inversion (14.9% vs. 1.7%), Minor ST segment depression (4.5% vs. 0%) and left ventricular hypertrophy (11.4% vs. 11.7%, p = .726). CONCLUSIONS: Pregnant Angolan women compared with controls, had several significantly higher values for heart rate, and significantly lower values of systolic blood pressure and diastolic blood pressure, PR interval, QT interval, QTc interval by Fridericia and Framingham and T-wave axis. Sinus tachycardia, T-wave inversion, and left ventricular hypertrophy, were the main electrocardiographic changes found.
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Electrocardiografía , Hipertrofia Ventricular Izquierda , Adolescente , Adulto , Angola , Arritmias Cardíacas , Estudios Transversales , Femenino , Humanos , Embarazo , Taquicardia Sinusal , Adulto JovenRESUMEN
Antimicrobial resistance of human pathogens, such as methicillin-resistant Staphylococcus aureus, is described by the World Health Organization as a health global challenge and efforts must be made for the discovery of new effective and safe compounds. This work aims to evaluate epigallocatechin-3-gallate (EGCG) epigenetic and modulatory drug potential against S. aureus in vitro and in vivo. S. aureus strains were isolated from commensal flora of healthy volunteers. Antibiotic susceptibility and synergistic assay were assessed through disk diffusion accordingly to EUCAST guidelines with and without co-exposure to EGCG at final concentrations of 250 µg/ml, 100 µg/ml, 50 µg/ml, and 25 µg/ml. Transcriptional expression of orfx, spdC, and WalKR was performed through qRT-PCR. A 90-day interventional study was performed with daily consumption of 225 mg of EGCG. Obtained data revealed a high prevalence of S. aureus colonization in healthcare workers and clearly demonstrated the antimicrobial and synergistic potential of EGCG as well as divergent resistant phenotypes associated with altered transcriptional expression of epigenetic and drug response modulators genes. Here, we demonstrate the potential of EGCG for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms and report divergent patterns of epigenetic modulators expression associated with phenotypic resistance profiles.
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Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Catequina/análogos & derivados , Resistencia a Medicamentos , Epigénesis Genética , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/genéticaRESUMEN
BACKGROUND: Spondylodiscitis is a severe condition where standalone antibiotic therapy resolves most cases. In refractory infections, open surgery may aid with infection debulking. However, significant morbidity can occur. Nowadays, endoscopic approaches are emerging as an alternative. However, until now, only small-scale studies exist. Being so, we carried the first systematic review on spondylodiscitis endoscopic debridement indications, technique details, and outcomes. METHODS: Search for all English written original studies approaching the spondylodiscitis endoscopic treatment was performed using PubMed and EBSCO host. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and a pre-specified protocol was registered at PROSPERO (CRD42020183657). RESULTS: Fourteen studies involving 342 participants were included for analysis. Data overall quality was fair. Indications for the endoscopic approach were poorly defined. The most consensual indication was refractory infection to conservative treatment. Spinal instability or neurological deficits were common exclusion criteria. All authors described similar techniques, and despite the frequent severe co-morbidities, procedure morbidity was low. Re-interventions were common. Microorganism identification varied from 54.2 to 90.4%. Treatment failure among studies ranged from 0 to 33%. Pain, functional status, and neurological deficits had satisfactory improvement after procedures. CONCLUSIONS: The endoscopic debridement of spondylodiscitis seems to be an effective and safe approach for refractory spondylodiscitis. A novel approach with initial endoscopic infection debulking and antibiotic therapy could improve the success of spondylodiscitis treatment.
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Discitis , Enfermedades de la Columna Vertebral , Antibacterianos/uso terapéutico , Desbridamiento/métodos , Discitis/tratamiento farmacológico , Discitis/cirugía , Endoscopía/métodos , Humanos , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Enfermedades de la Columna Vertebral/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Sickle cell anemia (SCA) is an inherited hematological disorder and a serious global health problem, especially in Sub-Saharan Africa. Although hydroxyurea (HU) is the leading treatment for patients with SCA, its effects on the gut microbiome have not yet been explored. In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment. A total of 66 stool samples were obtained and sequenced for the 16S rRNA gene (V3-V4 regions). Significant associations were observed in alpha and beta-diversity, with higher values of species richness for the children naïve for HU. We also noticed that children after HU had higher proportions of several beneficial bacteria, mostly short-chain fatty acids (SCFAs) producing species, such as Blautia luti, Roseburia inulinivorans, Eubacterium halli, Faecalibacterium, Ruminococcus, Lactobacillus rogosae, among others. In addition, before HU there was a higher abundance of Clostridium_g24, which includes C. bolteae and C. clostridioforme, both considered pathogenic. This study provides the first evidence of the HU effect on the gut microbiome and unravels several microorganisms that could be considered candidate biomarkers for disease severity and HU efficacy.
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Anemia de Células Falciformes , Microbioma Gastrointestinal , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Niño , Humanos , Hidroxiurea/uso terapéutico , Estudios Longitudinales , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: Assessing subjective social status (SSS) may be easily accommodated in the context of a Health and Demographic Surveillance System (HDSS). To our knowledge, no prior studies have examined the association of SSS and health in Angola. Subjective socioeconomic measures may provide a rapid assessment of a relevant social status construct, important for studying health inequalities. In this study, we addressed social determinants of health by examining the relationship between the subjective and objective social status, reported health and healthcare-seeking behaviour. METHODS: This research results from a cross-sectional study performed during 2015 in the Dande HDSS, in Angola. We tested the application of the MacArthur scale as a measure of SSS in a developing setting, in a sample of 12,246 households. First, we investigated its relation to objective socioeconomic indicators, and then we explored how subjective and objective social status associate with health reported needs and health-seeking behaviour of the surveyed population. Chi-square, ANOVA tests, and Receiver Operating Characteristics (ROC) Curves analysis were computed for testing relationships between subjective status ladder quartiles, sociodemographic and household characteristics. Logistic regression was used to examine the influence of subjective perception of status in self-reported health and health-seeking behaviour. RESULTS: Our findings suggest that the SSS follows a gradient distribution obtained with more objective socioeconomic indicators. Additionally, we found that subjective perception of status influence health needs reporting and health-seeking behaviour and its significant effect remained after controlling for the objective socioeconomic markers. Individuals standing in the second quartile of the social ladder have more odds of reporting illness and those in the highest quartiles of the ladder were twice more likely (OR = 2.23, 95% CI = 1.52-3.26) to seek help from formal health services than those at the bottom of the ladder. CONCLUSIONS: The MacArthur Scale is a valuable tool to measure SSS in the Dande HDSS, relevant for studying socioeconomic disparities and health inequalities. It is also an easier alternative to traditional measures such as income, usually difficult to measure in developing settings. The social perception of status should be considered as a complement with objective indicators when exploring social determinants of health.
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Distancia Psicológica , Clase Social , Angola/epidemiología , Estudios Transversales , Estado de Salud , HumanosRESUMEN
Infectious diseases during pregnancy remain a public health concern, especially in a resource-limited setting. The study aimed to determine the seroprevalence and determinants of HIV and co-infection with hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis among pregnant women attending antenatal care in Luanda, the capital city of Angola. A cross-sectional study was conducted with 1612 pregnant women screened for HIV during antenatal care. HIV-reactive were also screened for the HBV, HCV, and syphilis using immunoassay kits. A logistic regression model, adjusted odds ratios (AOR) and their 95% confidence interval (CI) were calculated with a level of significance set at 5%. The overall seroprevalence of HIV was 2.6%. About 13% of HIV-positive pregnant women were coinfected. From which, 7.5% were reactive to HBV and 5% to syphilis. There was no reactivity to HCV. Pregnant women younger aged than 25 years were significantly protected from HIV-infection (AOR, 0.43 [95% CI, 0.20-0.91], P = .026). The co-infection was 1.3 times (AOR, 0.04-41.0) in younger aged than 25 years, 7.0 times (AOR, 0.50-99.2) to residents in urbanized areas, and 1.4 times (AOR, 0.10-20.9) in pregnant women with a high educational level. In conclusion, infectious diseases are a public health burden among pregnant women in Luanda. However, include an integrated antenatal screening mainly in urbanized areas is crucial to reduce the spread of infectious diseases in different communities of Angola.
RESUMEN
The aim of this study was to explore the association between alpha-thalassemia, fetal hemoglobin, hematological indices, and clinical adverse events in Angolan sickle cell disease pediatric patients. A total of 200 sickle cell disease (SCD) children were sampled in Luanda and Caxito. A venous blood sample was collected and used for hematological analyses, fetal hemoglobin quantification, and genotyping of 3.7 kb alpha-thalassemia deletion by GAP-PCR. The frequency of the 3.7 kb alpha-thalassemia deletion in homozygosity was 12.5% and in heterozygosity was 55.0%. An increase in alpha-thalassemia frequency was observed in children older than 5 years old (11.7% vs. 13.00%). Furthermore, 3.7 kb alpha-thalassemia deletion homozygotes had a significantly higher age of the first manifestation, lower number of blood transfusions by year, higher hemoglobin, lower mean corpuscular volume, mean corpuscular hemoglobin, and lower hemolytic rate observed by a lower number of reticulocytes count. There were no differences in fetal hemoglobin between the three genotypes. Moreover, the number of stroke events, osteomyelitis, splenomegaly, splenectomy, and hepatomegaly were lower when alpha-thalassemia was co-inherited. For the first time in Angolan population, the effect of alpha-thalassemia deletion in sickle cell disease was analyzed and results reinforce that this trait influences the hematological and clinical aspects and produces a milder phenotype.
Asunto(s)
Anemia de Células Falciformes/genética , Talasemia alfa/genética , Adolescente , Anemia de Células Falciformes/epidemiología , Angola/epidemiología , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Índices de Eritrocitos , Femenino , Hemoglobina Fetal/genética , Genotipo , Hemólisis , Heterocigoto , Homocigoto , Humanos , Masculino , Talasemia alfa/epidemiologíaRESUMEN
BACKGROUND: Angola is one of the southern African countries with the highest prevalence of anaemia. Identifying anaemia determinants is an important step for the design of evidence-based control strategies. In this study, we aim at documenting the factors associated with Iron Deficiency Anaemia (IDA) in 948 children recruited at the Health Research Center of Angola study area during 2015. METHODS: Data on demographic, socio-economic and parental practices regarding water, sanitation, hygiene, malaria infection and infant and young child feeding were collected, as well as parasitological, biochemical and molecular data. Total and age-stratified multivariate multinomial regression models were fitted to estimate the magnitude of associations between anaemia and its determinants. RESULTS: Anaemia was found in 44.4% of children, of which 46.0% had IDA. Overall, regression models associated IDA with age, gender and inflammation and non-IDA with age, zinc deficiency and overload, P. falciparum infection, sickle cell trait/anaemia. Among 6-to-23-month-old children IDA was associated with continued breastfeeding and among 24-to-36-month-old children IDA was associated with stunting. Furthermore, zinc deficiency was associated with non-IDA among both age groups children. Inflammation was associated with IDA and non-IDA in either 6-to-23 and 24-to-36 months old children. CONCLUSION: The main variables associated with IDA and non-IDA within this geographic setting were commonly reported in Africa, but not specifically associated with anaemia. Additionally, the associations of anaemia with inflammation, zinc deficiency and infections could be suggesting the occurrence of nutritional immunity and should be further investigated. In age groups, zinc overload was observed to protect under 6 months children from Non-IDA, while continued breastfeeding was associated with increased IDA prevalence in 6-to-23 months children, and stunting was suggested to increase the odds of IDA in 24-to-36 month children. This site-specific aetiology profile provides an essential first set of evidences able to inform the planification of preventive and corrective actions/programs. Nevertheless, regional and country representative data is needed.