Percorrer por autor "Vasconcelos, J."
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- Genetic variability and disease severity in a cohort of Angolan sickle cell disease patientsPublication . Brito, Miguel; Ferreira, J.; Capriello, I.; Ginete, Catarina; Delgadinho, Mariana; Sebastião, Cruz; Mendes, M.; Quinto, F.; Mavunza, F.; Vasconcelos, J.; Cogle, A.Purpose: Sickle Cell Anaemia (SCA) is an inherited autosomal and lethal blood disorder caused by a mutation in the HBB gene that promotes haemoglobin (Hb) polymerization and consequent sickling of red blood cells (RBCs) in hypoxia. Regardless of being a monogenic disease, SCA has a remarkably high clinical heterogeneity in its phenotypic expression. Several factors have been shown to modulate the clinical manifestations of SCA, namely genetic markers such as α-thalassaemia and β-globin cluster haplotypes, that can modulate biological parameters like the degree of haemolytic anaemia or the levels of foetal haemoglobin (HbF).
- Gut microbiota impact on Angolan children with sickle cell diseasePublication . Brito, Miguel; Delgadinho, Mariana; Ginete, Catarina; Mendes, Joana; Vasconcelos, J.; Santos, BrígidaIntroduction: Clinical manifestations of Sickle cell disease (SCD) are very heterogeneous, and the intestinal microbiome appears to be crucial in the modulation of inflammation, cell adhesion, and induction of aged neutrophils, which are 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 research studies. Microbiota analysis in SCD populations will be essential to demonstrate the importance of specific bacteria and their function in this disease and provide new insights for attenuating symptoms and new drug targets. Purpose: Given this, our aim is to sequence by NGS bacterial 16S RNA gene in order to characterize the gut microbiome of SCD children and healthy siblings, as a control.
- Preliminary findings from the follow-up of pregnant sickle cell disease patients in Luanda, AngolaPublication . Brito, Miguel; Ginete, Catarina; Ferreira, J.; Delgadinho, Mariana; Sebastião, Cruz; Mateus, A.; Mendes, M.; Quinto, F.; Simão, F.; Fernandes, F.; Vasconcelos, J.Background: In Angola, the prevalence of Sickle Cell Disease (SCD) is almost 2%, and the carriers reach 21% of the population. Although its presentation tends to be very heterogeneous, chronic hemolytic anemia, frequent painful crises, and extensive organ damage are common features of these patients. Pregnancy in SCD patients is associated with an increase in severe outcomes, namely, a high risk of eclampsia and pre-eclampsia, stroke, and even death. Therefore, it is crucial to maintain continuous medical surveillance during pregnancy, especially in women with previous strokes. Moreover, health services in low- and middle-income countries are generally not prepared to follow these patients. Aims: We aim to present the preliminary findings from the cohort study conducted at the Lucrecia Paim Maternity Hospital (Luanda, Angola), which aims to determine pregnancy complications in SCD women, especially those responsible for maternal death, and, by supporting the obstetric consultations in this hospital, contribute to the reduction of mortality and morbidity rates. Methods: Pregnancy monitoring includes analysis of clinical history and incidents (number of hospitalizations, blood transfusions, strokes, and other clinical complications), hematological and biochemical analysis, transcranial Doppler to assess cerebral hemodynamics and genetic analysis (confirmation of the diagnosis, genotyping of four SNPs in the β-cluster to assess the haplotype, and evaluation of the presence of the 3.7kb deletion of the α-globin gene). Results: To date, 61 women are being followed in the obstetric consultations, with ages from 18 to 40 years old (mean 26.1±5.4). There are no records of previous strokes, although 83.9% of the patients have been previously transfused (47 out of 56), 98.2% have been hospitalized (55 out of 56) due to SCD complications and 19.6% (10 out of 54) had at least one miscarriage. At the first appointment, total hemoglobin values ranged from 4.70 to 10.40 g/dL (n=52, mean 7.18±1.30), erythrocytes from 1.46 to 5.42 x1012/L (n=52, mean 2.46±0,72), white blood cells count from 1.67 to 61.88 x109/L (n=51, mean 12.20±8.69), platelets from 24.2 to 710.0 x109/L (n=52, mean 272.2±155.9), and lactate dehydrogenase (LDH) from 263.3 to 2836.7 (n=50, mean 708.1±450.46). The CAR/CAR haplotype, which is usually associated with a more severe prognosis, is the most prevalent in this population (57.7%, 30 out of 52), followed by the CAR/SEN haplotype (25.0%, 13 out of 52). In this population, 17.3% (9 out of 52) are homozygous for the 3.7kb α-thalassemia deletion and 44.2% (23 out of 52) are carriers. This deletion influences hematological and clinical aspects of sickle cell disease patients, resulting in less severe phenotypes. TCD time-averaged mean of the maximum velocity (TAMMx) at the middle cerebral arteries ranged between 41 to 132 cm/s (n=61, mean 84cm/s), and peak systolic velocity (PSV) from 61 to 180 cm/s (mean 129 cm/s). At the basilar artery level, TAMMx obtained were between 29 to 102 cm/s (n=60, mean 52 cm/s) and PSV ranged from 43 to 141 cm/s (mean 78 cm/s). Summary - Conclusion: The main goal of this project is to study pregnancy-related complications and outcomes by giving support to an Angolan cohort of SCD pregnant women. We also intend to obtain TCD reference values of cerebral blood flow velocities in pregnant women with SCD as a risk predictor of vascular events as there are no values in the literature for this specific population.
- The effect of hydroxyurea in the gut microbiome of Angolan children with sickle cell diseasePublication . Delgadinho, Mariana; Ginete, Catarina; Fernandes, C.; Santos, Brígida; Vasconcelos, J.; Brito, MiguelPurpose: Sickle cell disease (SCD) is one of the most prevalent genetic disorders, affecting around 20 to 25 million individuals throughout the world. In Sub-Saharan Africa, where it is more prevalent, it can contribute to up to 80% of under-5 mortality. Clinical manifestations of SCD are very heterogeneous and the intestinal microbiome has recently been reported to be crucial in the modulation of inflammation, cell adhesion, and induction of aged neutrophils, which are key interveners of recurrent vaso-occlusive crises. Since gut bacteria can regulate aged neutrophils, defects in either the integrity of the intestinal walls or a chronic disequilibrium of the microbiota are very likely to emerge in SCD patients. Moreover, it has been suggested that Hydroxyurea (HU), the most common treatment for SCD, shows a multimodal action and may reduce microbiome dysbiosis and aged neutrophils. In this context, we aimed to understand how SCD and HU treatment modulates the microbiome and if these changes could be related to disease severity.
- The gut microbiome and hydroxyurea effect on sickle cell disease children from AngolaPublication . Brito, Miguel; Delgadinho, Mariana; Ginete, Catarina; Santos, Brígida; Vasconcelos, J.Background: Sickle cell disease (SCD) is an inherited hematological disorder and a serious global health problem, affecting between 20 and 25 million people worldwide. In Sub-Saharan Africa, where it is more prevalent, it contributes up to 90% of under-5 mortality. Although hydroxyurea (HU) is the leading treatment for these patients, its effects on the gut microbiome have not yet been explored. Some studies reported that gastroenteritis events were less frequent in SCA children taking HU and it also significantly improved the survival from pneumococcal infections. HU may have a protective effect, not only by improving several hematological parameters but also by lowering the risk of some bacterial infections. Aims: 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 and comparing it with a control group of healthy siblings. Results: A total of 113 fecal samples were obtained and sequenced by NGS for the 16S rRNA gene (V3-V4 regions), which corresponded to 40 children in the control and before HU groups and 33 after HU, aged between 4-12 years old. Our findings revealed that these three groups exhibit some notable differences, especially within Lachnospiraceae and Ruminococcaceae family. After HU treatment there was an increase of several beneficial bacteria, such as: Blautia coccoides (p=0.009), Blautia luti (p<0.001), Blautia faecis (p=0.008), Bifidobacterium longum (p=0.011), Dorea formicigenerans (p<0.001), Dorea massiliensis (p=0.003), Eubacterium halii (p=0.004), Elusimicrobium spp (p=0.032), Ruminococcus callidus (p=0.037), Ruminococcus faecis (p=0.012), Roseburia spp (p=0.050) and Subdoligranulum variabile (p=0.009). Most of those OTUs are SCFAs producing species, having butyrate or propionate as end-products of bacterial metabolism, both exhibiting anti-inflammatory properties. Moreover, children before HU had a higher abundance of bacteria considered pathogenic, like E. coli (p=0.001), Clostridiun_g24 (p=0.039), and H. influenzae (p=0.050). Conclusion: Overall, this study provides the first evidence of the HU effect on the gut microbiome and provides a rationale for further research for developing treatments to reduce gut microbiota-driven inflammation, which may attenuate the dysbiosis and chronic symptoms experienced by these patients.