Quantitative MRI evaluation of bone marrow in sickle cell disease: relationship with haemolysis and clinical severity.

AIM: To evaluate bone marrow fat fraction using the Dixon technique (FFDix) of magnetic resonance imaging (MRI) as a potential biomarker of haemolysis and clinical severity in the overall assessment and follow-up of sickle cell disease (SCD) patients. MATERIAL AND METHODS: The present study was a cross-sectional study in which healthy individuals and SCD patients (matched for age, sex, and weight) were subjected to MRI of the lumbar spine and pelvis to quantify FFDix in the bone marrow using the Dixon technique. SCD severity was analysed by clinical and laboratory data, and an online calculator. A high degree of haemolysis was defined using the cut-off values haemoglobin (Hb) ≤10 g/dl, lactate dehydrogenase (LDH) ≥325 U/l, reticulocytes ≥3% and total bilirubin (TB) ≥1.2 mg/dl. Pearson's correlation, receiver operating characteristic (ROC) curve and binary logistic regression analysis were performed. RESULTS: Forty-eight SCD patients (26 homozygous: HbSS and 22 compound heterozygous: HbSC) and 48 healthy individuals participated in the study. FFDix was lower in SCD patients than in the control group, showing even lower values in the HbSS subtype and patients with a higher degree of haemolysis. HbSC patients with a higher degree of haemolysis using hydroxyurea (medium dosage 9.8 mg/kg/day) had lower FFDix. ROC curves and odds ratios for detecting patients with a higher degree of haemolysis at the different FFDix measurement sites demonstrated excellent performance: iliac bones (cut-off ≤16.75%, AUC = 0.824, p<0.001), femoral heads (cut-off ≤46.7%, AUC = 0.775, p=0.001), lumbar vertebrae (cut-off ≤7.8%, AUC = 0.755, p=0.002). CONCLUSION: Decreased FFDix is indicative of higher degree of haemolysis and SCD severity with great potential as a non-invasive biomarker contributing to the overall assessment and follow-up of SCD patients.

Genotoxic and mutagenic effects of methyl ether dillapiole on the development of Aedes aegypti (Diptera: Culicidae).

Dillapiole, extracted from Piper aduncum essential oil and its derivatives, has been shown to be a potential alternative to the control of Aedes aegypti, which has become resistant to synthetic insecticides. Methyl ether dillapiole (MED) and temephos (TM) were compared to complement the data on the genotoxicity and developmental changes of Ae. aegypti. Over four generations (G1 -G4 ), third stage larvae were treated with MED at 60, 80 and 100 µg/mL and TM at 0.002, 0.005 and 0.007 µg/mL for 4 h. Adult females were separated to estimate oviposition and hatching rates, and total egg length. Over the four generations, a significant reduction was recorded in oviposition and hatching rates, and in mean egg length (Tukey, P < 0.05), compared with the negative control (NC). Cytological slide preparations were done from adult oocytes and larval neuroblasts. The cumulative effects of genotoxic (bridges, budding and nuclear fragmentation) and mutagenic (micronucleus and chromosomal breakage) damage was observed in the neuroblasts and oocytes of exposed mosquitoes. Developmental changes and damage to the genome of MED-treated Ae. aegypti were greater than those caused by TM. Further studies should focus on understanding the effects of the MED molecule on Ae. aegypti.

Comparative metavirome analysis in polytransfused patients

Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirão Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.

Viral metagenomics in Brazilian multiply transfused patients with sickle cell disease as an indicator for blood transfusion safety.

BACKGROUND AND AIM: Patients with sickle cell disease (SCD) are submitted to multiple transfusions in order to increase the oxygen capacity of the blood, decrease blood viscosity, and suppress the sickling of the cells. Multiply transfused patients with SCD represent significant risk of acquiring parenterally transmitted infections. The analysis of the virome profile of high-risk multiply transfused patients with SCD can reveal the presence of parenterally transmitted viruses and therefore be used an indirect approach for evaluation of blood transfusion safety. MATERIALS AND METHODS: Blood samples were collected from 45 patients with SCD receiving multiple transfusions and analyzed by metagenomic analyses. The samples were assembled in pools f which were submitted to nucleic acids extraction and sequencing by Illumina NextSeq 550 equipment. For bioinformatic analysis, we used a specific in-house developed pipeline specialized in identification of emerging viruses. RESULTS: The virome composition of SCD patients revealed the presence of commensal viruses represented by anelloviruses and Human Pegivirus-1 (HPgV-1, GB virus C). Contaminant viral sequences belonging to human lentiviruses (rev, env genes), cytomegalovirus and murine leukemia virus were also identified and are attributed to vectors used in the laboratory practice. No novel or unsuspected pathogenic viruses were identified. CONCLUSION: This study evaluates for the first time the virome of multiply transfused patients with SCD. Exclusively genetic material of commensal viruses was annotated. Therefore, we believe that viral metagenomics applied in patients with high risk for acquiring parenterally transmitted infections can serve as a direct indicator for evaluation of transfusion safety.