Biblioteca Virtual del Sistema Sanitari Públic de Catalunya (BVSalut)

Biblioteca virtual; Recursos d’informació; Validació d’usuarisVirtual Library; Information resources; User authentication SystemBiblioteca virtual; Recursos de información; Validación de usuariosIntroducció La Biblioteca Virtual del Sistema Sanitari Públic de Catalunya (BVSalut) s’ha creat per ser el punt d’accés als recursos i als serveis bibliogràfics digitals de suport a la presa decisions per als professionals del sector públic majoritari de salut de forma equitativa i homogènia. Material i mètode Per desenvolupar el portal BVSalut es van analitzar quins serien els serveis que s’oferirien de forma virtual i quin seria el programari necessari que facilitaria la gestió, consulta i accés al portal, als serveis i als recursos bibliogràfics de forma segura per als professionals del sector públic majoritari de salut. Es va considerar que es posarien en funcionament els serveis virtuals següents: atenció a l’usuari i referència, alertes d’informació, informació especialitzada, obtenció de documents i préstec. Pel que fa al programari, es va considerar que era necessari disposar d’un gestor de continguts, un servei d’assistència a l’usuari (help desk), un programari per a la gestió del servei d’obtenció de documents, una eina de descoberta i una llista A/Z que facilités l’accés als recursos i evités els enllaços trencats. Al mateix temps, s’havia de garantir un sistema segur de validació d’usuaris que permetés als professionals de les diferents institucions poder accedir de forma segura als recursos electrònics que es posaven a la seva disposició. Concretament, es va desenvolupar un sistema de validació Single Sing‐On (SSO), que connectat a una LDAP (Lightweight Directory Access Protocol), amb la relació dels professionals i dels recursos que tenien accés, permetia que aquests professionals poguessin entrar als recursos bibliogràfics digitals de la BVSalut de forma simple i eficaç mitjançant el servidor proxy Ezproxy. Resultats S’ha donat accés als recursos bibliogràfics subvencionats per la Biblioteca de Ciències de la Salut de Catalunya a 79 entitats. Més de 40.000 professionals ja poden accedir a aquests als recursos electrònics i s’ha iniciat la redacció d’un pla estratègic, amb la col∙laboració de les biblioteques de les institucions del sector públic majoritari de salut, que facilitarà que aquests professionals també tinguin accés a serveis de suport bibliogràfic compartits. Conclusions El portal BVSalut ha permès establir un sistema homogeni d’accés als recursos i serveis bibliogràfics digitals. Progressivament s’aniran incrementant els recursos bibliogràfics i, amb la creació de la Xarxa de Biblioteques Especialitzades en Ciències de la Salut i l’aprovació de Pla estratègic, l’oferta de serveis virtuals compartits

Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis

Effect of effervescent paracetamol on blood pressure: a crossover randomized clinical trial

OBJECTIVE: To evaluate the effect of effervescent paracetamol on office and ambulatory blood pressure (BP) compared with noneffervescent paracetamol in hypertensive patients. DESIGN: This was a multicenter open crossover randomized clinical trial. SETTING: Primary care centers in Catalonia and the Basque Country. PARTICIPANTS: Inclusion criteria were office BP 150/95¿mmHg or less and daytime ambulatory BP 140/90¿mmHg or less, stable pharmacologic or nonpharmacologic antihypertensive treatment, and concomitant chronic osteoarticular pain. INTERVENTIONS: Baseline randomized assignment to 3-week periods of effervescent paracetamol (1¿g three times a day) first and noneffervescent paracetamol later, or inversely, during a 7-week study period. At the start and end of each treatment period, 24-h ambulatory BP monitoring was performed. MAIN OUTCOME MEASURES: Differences in 24-h SBP between baseline and end of both treatment periods. The main analyses were performed according to the intention-to-treat principle. RESULTS: In intention-to-treat analysis, 46 patients were analyzed, 21 were treated with paracetamol effervescent and noneffervescent later, and 25 followed the opposite sequence. The difference in 24-h SBP between the two treatments was 3.99¿mmHg (95% confidence interval 1.35-6.63; P¿=¿0.004), higher in the effervescent paracetamol treatment period. Similarly, the per-protocol analysis showed a difference in 24-h SBP between the two groups of 5.04¿mmHg (95% confidence interval 1.80-8.28; P¿=¿0.004), higher in the effervescent paracetamol treatment period. Self-reported pain levels did not differ between groups and did not vary by treatment period. No serious adverse events were reported in either study arm. CONCLUSION: Effervescent paracetamol tablets are responsible for a significant daytime and overall increase in ambulatory 24-h SBP. TRIAL REGISTRATION: NCT: 02514538 EudraCT: 2010-023485-53.Peer ReviewedPostprint (author's final draft

Impact of chronic kidney disease on the prevalence of cardiovascular disease in patients with type 2 diabetes in Spain: PERCEDIME2 study

BACKGROUND: The presence of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease (CVD) regardless of the presence of traditional cardiovascular risk factors. There is controversy about the impact of each of the manifestations of CKD on the prevalence of CVD, whether it is greater with decreased estimated glomerular filtration rate (eGFR) or increased urine albumin creatinine ratio (UACR). METHODS: This study is a national cross-sectional study performed in primary care consults. We selected participants of both sexes who were aged 40 years or older, had been diagnosed with T2DM and had complete information on the study variables recorded in their medical records. The participants were classified according to eGFR : ≥ 60; 45-59; 30-44; 60 mL/min/1.73 m(2) those with eGFR between 30-44 mL/min/m(2), (OR = 2.3; 95% CI, 1.4-3.9); and eGFR < 30 mL/min/1.73 m(2) (OR = 4.1 95% CI 1.6-10.2) showed increased likelihood of having CVD. Participants with UACR ≥ 30 mg/g compared to participants with UACR < 30 mg/g increased significantly the likelihood of having CVD, especially with UACR above 300 mg/g, (OR = 1.6; 95% CI 1.1-2.4 for UACR = 30-299 mg/g; OR = 3.9; CI 1.6-9.5 for UACR ≥ 300 mg/g). CONCLUSION: The decrease in eGFR and increase in UACR are independent risk factors that increase the prevalence of CVD in participants with T2DM and these factors are independent of each other and of other known cardiovascular risk factors. In our study the impact of mild decreased eGFR in T2DM on CVD was lower than the impact of increased UACR. It is necessary to determine not only UACR but also eGFR for all patients with T2DM, both at the time of diagnosis and during follow-up, to identify those patients at high risk of cardiovascular complications

Mitochondrial toxicity and caspase activation in HIV pregnant women.

To assess the impact of HIV-infection and highly active anti-retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV-infected and -treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome (OR: 4.81 [1.14-20.16]; P < 0.05) and decreased mtDNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase-3 activation increased 63.64 ± 45.45% in controls (P < 0.001) and 100.00 ± 47.37% in HIV-pregnancies (P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV-infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti-retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size

CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis

OBJECTIVE: Chemokines are known to play an important role in the pathophysiology of alcoholic hepatitis (AH), a form of acute-on-chronic liver injury frequently mediated by gut derived lipopolysaccharide (LPS). In our study, we hypothesise that chemokine CCL20, one of the most upregulated chemokines in patients with AH, is implicated in the pathogenesis of AH by mediating LPS induced liver injury. DESIGN: CCL20 gene expression and serum levels and their correlation with disease severity were assessed in patients with AH. Cellular sources of CCL20 and its biological effects were evaluated in vitro and in vivo in chronic, acute and acute-on-chronic experimental models of carbon tetrachloride and LPS induced liver injury. RNA interference technology was used to knockdown CCL20 in vivo. RESULTS: CCL20 hepatic and serum levels were increased in patients with AH and correlated with the degree of fibrosis, portal hypertension, endotoxaemia, disease severity scores and short term mortality. Moreover, CCL20 expression was increased in animal models of liver injury and particularly under acute-on-chronic conditions. Macrophages and hepatic stellate cells (HSCs) were identified as the main CCL20 producing cell types. Silencing CCL20 in vivo reduced LPS induced aspartate aminotransferase and lactate dehydrogenase serum levels and hepatic proinflammatory and profibrogenic genes. CCL20 induced proinflammatory and profibrogenic effects in cultured primary HSCs. CONCLUSIONS: Our results suggest that CCL20 upregulation is strongly associated with LPS and may not only represent a new potential biomarker to predict outcome in patients with AH but also an important mediator linking hepatic inflammation, injury and fibrosis in AH

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis

Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets

Integrative miRNA and Gene Expression Profiling Analysis of Human Quiescent Hepatic Stellate Cells.

Unveiling the regulatory pathways maintaining hepatic stellate cells (HSC) in a quiescent (q) phenotype is essential to develop new therapeutic strategies to treat fibrogenic diseases. To uncover the miRNA-mRNA regulatory interactions in qHSCs, HSCs were FACS-sorted from healthy livers and activated HSCs (aHSCs) were generated in vitro. MiRNA Taqman array analysis showed HSCs expressed a low number of miRNAs (n = 259), from which 47 were down-regulated and 212 up-regulated upon activation. Computational integration of miRNA and gene expression profiles revealed that 66% of qHSC-associated miRNAs correlated with more than 6 altered target mRNAs (17,28 ± 10,7 targets/miRNA) whereas aHSC-associated miRNAs had an average of 1,49 targeted genes. Interestingly, interaction networks generated by miRNA-targeted genes in qHSCs were associated with key HSC activation processes. Next, selected miRNAs were validated in healthy and cirrhotic human livers and miR-192 was chosen for functional analysis. Down-regulation of miR-192 in HSCs was found to be an early event during fibrosis progression in mouse models of liver injury. Moreover, mimic assays for miR-192 in HSCs revealed its role in HSC activation, proliferation and migration. Together, these results uncover the importance of miRNAs in the maintenance of the qHSC phenotype and form the basis for understanding the regulatory networks in HSCs

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (600 soluble proteins, our data highlight the importance of Th17 cells and Wnt/β-catenin signaling in HIV control and especially identify the IL-27/IL-27 receptor subunit alpha (IL-27RA) axis as a predictor of plasma viral load and proviral copy number in the peripheral blood. These data may provide important guidance to therapeutic approaches in the HIV cure agenda