JAK2V617F allele burden is associated with thrombotic mechanisms activation in polycythemia vera and essential thrombocythemia patients

The clinical courses of polycythemia vera (PV) and essential thrombocythemia (ET) are characterized by thrombohemorrhagic diathesis. Several groups have suggested an association between JAK2V617F mutation and thrombosis. We hypothesized a relationship between JAK2V617F allele burden, cellular activation parameters, and thrombosis. We evaluated a group of PV and ET patients using flow cytometry: platelet CD62P, CD63, and dense granules, platelet-leukocyte aggregates (PLA), leukocyte CD11b and monocyte tissue factor (TF) expression. All patients had increased baseline platelet CD62P and CD63 expression (p 50 % presented higher levels of leukocyte activation. In ET, thrombosis was associated with JAK2V617F mutation (p < 0.05, χ (2) = 5.2), increased monocyte CD11b (p < 0.05) and with platelet-PMN aggregates (p < 0.05). In ET patients, hydroxyurea does not significantly reduce the activation parameters. Our data demonstrate that JAK2V617F allele burden is directly correlated with activation parameters that drive mechanisms that favor thrombosis.info:eu-repo/semantics/publishedVersio

Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease

<p>Abstract</p> <p>Background</p> <p>The search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis.</p> <p>Methods</p> <p>We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records.</p> <p>Results</p> <p>Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis.</p> <p>Conclusions</p> <p>We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.</p

Delays in access to care for abortion-related complications: the experience of women in Northeast Brazil.

Around 18 million unsafe abortions occur in low and middle-income countries and are associated with numerous adverse consequences to women's health. The time taken by women with complications to reach facilities where they can receive appropriate post-abortion care can influence the risk of death and the extent of further complications. All women aged 18+ admitted for abortion complications to public-sector hospitals in three capital cities in the Northeastern Brazil between August-December 2010 were interviewed; medical records were extracted (N = 2,804). Nearly all women (94%) went straight to a health facility, mainly to a hospital (76.6%); the rest had various care-seeking paths, with a quarter visiting 3+ hospitals. Women waited 10 hours on average before deciding to seek care. 29% reported difficulties in starting to seek care, including facing challenges in organizing childcare, a companion or transport (17%) and fear/stigma (11%); a few did not initially recognize they needed care (0.4%). The median time taken to arrive at the ultimate facility was 36 hours. Over a quarter of women reported experiencing difficulties being admitted to a hospital, including long waits (15%), only being attended after pregnant women (8.9%) and waiting for a bed (7.4%). Almost all women (90%) arrived in good condition, but those with longer delays were more likely to have (mild or severe) complications. In Brazil, where access to induced abortion is restricted, women face numerous difficulties receiving post-abortion care, which contribute to delay and influence the severity of post-abortion complications

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

A study on the construct validity of the Parent-Child Conflict Tactics Scale (CTSPC) in an urban population in Northeast Brazil

The Parent-Child Conflict Tactics Scale (CTSPC) is one of the most widely used instruments in the world for investigating domestic violence against children, but targeted use has proven inadequate given the phenomenon's complexity. This study focused on the factor structure of CTSPC scales in an urban population in Northeast Brazil. We conducted a cross-sectional study in a cohort of 1,370 children in Salvador, Bahia State. Factor analysis with promax oblique rotation was performed, and the Kuder-Richardson coefficient was calculated. Factor analysis showed a different distribution of items in the factors as compared to the original instrument. Violence showed a gradual profile in each factor. The Kuder-Richardson coefficient was 0.63 for factor 1, 0.59 for factor 2, and 0.42 for factor 3. The items behaved differently from the original instrument, corroborating international studies. These findings support proposing a resizing of the CTSPC