Practical application of the ATOM study: Treatment efficacy of antihypertensive drugs in monotherapy or combination (ATOM metaanalysis according to PRISMA statement); tables for the use of antihypertensive drugs in monotherapy or combination

Background: The response to antihypertensive drugs is predictable. The absence of precise prescription recommendations to treat arterial hypertension (HT) lead to use drugs unable to reduce blood pressure (BP) to target values. We published ATOM study, in which we found significant differences in the ability to reduce BP between the different drugs. The objective of the study was to determine the expected decrease in blood pressure with the use of commercialized doses of the drugs commonly used in the treatment of HT in clinical practice, to avoid the use of drugs or combinations that even with the best response, are unable to obtain the necessary BP decrease to reach the goal. Methods: The analysis was based on the results of the ATOM study. To convert the mean doses of the different drugs and combinations in commercialized doses, the conclusions of the study by Law et al have been applied. Results: Based on the results, two tables were drawn, one for systolic BP and the other for diastolic BP, where the doses of the different drugs and combinations are classified according to the BP decrease that can be expected from them. In order to favor the use of the tables in clinical practice, the different drugs have been grouped in intervals of 10 millimeters of mercury (mmHg) for the decrease of the systolic BP and of 5 mmHg for the diastolic BP. Conclusions: Recommendations for the use of antihypertensive treatments should not be limited to pharmacological families. They should also consider differences between drugs or specific combinations. From the data of the ATOM study we have implemented tables that express the effect of the drugs commonly used in clinical practice and that should allow the clinicians to choose with care the treatment to use

An approach to the spatial distribution of fishing effort in the Gulf of Cadiz.

The spatial distribution of the fishing effort exerted by the trawl fleet of Isla Cristina port (Huelva, Spain) is simulated by means of an application (FAST) for Geographic Information Systems (ArcView), which can offer results just with limited input data. The simulation were carried out with three input variables: depth, distance from fishing grounds to port and the fishing laws in force in the area. The results obtained from two simulations tested match up the effort distribution detected in the area for both the fleet as a whole and a given segment of the same.Postprin

Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples

Copy number variants (CNVs) conferring risk of schizophrenia present incomplete penetrance, suggesting the existence of second genetic hits. Identification of second hits may help to find genes with rare variants of susceptibility to schizophrenia. The aim of this work was to search for second hits of moderate/high risk in schizophrenia carriers of risk CNVs and resequencing of the relevant genes in additional samples. To this end, ten patients with risk CNVs at cytobands 15q11.2, 15q11.2-13.1, 16p11.2, or 16p13.11, were subjected to whole-exome sequencing. Rare single nucleotide variants, defined as those absent from main public databases, were classified according to bioinformatic prediction of pathogenicity by CADD scores. The average number of rare predicted pathogenic variants per sample was 13.6 (SD 2.01). Two genes, BFAR and SYNJ1, presented rare predicted pathogenic variants in more than one sample. Follow-up resequencing of these genes in 432 additional cases and 432 controls identified a significant excess of rare predicted pathogenic variants in case samples at SYNJ1. Taking into account its function in clathrin-mediated synaptic vesicle endocytosis at presynaptic terminals, our results suggest an impairment of this process in schizophrenia

Imputation of the Date of HIV Seroconversion in a Cohort of Seroprevalent Subjects: Implications for Analysis of Late HIV Diagnosis

Objectives. Since subjects may have been diagnosed before cohort entry, analysis of late HIV diagnosis (LD) is usually restricted to the newly diagnosed. We estimate the magnitude and risk factors of LD in a cohort of seroprevalent individuals by imputing seroconversion dates. Methods. Multicenter cohort of HIV-positive subjects who were treatment naive at entry, in Spain, 2004–2008. Multiple-imputation techniques were used. Subjects with times to HIV diagnosis longer than 4.19 years were considered LD. Results. Median time to HIV diagnosis was 2.8 years in the whole cohort of 3,667 subjects. Factors significantly associated with LD were: male sex; Sub-Saharan African, Latin-American origin compared to Spaniards; and older age. In 2,928 newly diagnosed subjects, median time to diagnosis was 3.3 years, and LD was more common in injecting drug users. Conclusions. Estimates of the magnitude and risk factors of LD for the whole cohort differ from those obtained for new HIV diagnoses

Ceramide Metabolism and Parkinson’s Disease—Therapeutic Targets

Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson’s disease.This study was partially supported by grants from the Xunta de Galicia (Consellería de Economía e Industria: IN607A2018/3 & IN607D 2020/09), and Science Ministry of Spain (RTI2018-102165-B-I00 & RTC2019-007373-1). Furthermore, this study was also supported by grants from the INTERREG Atlantic Area (EAPA_791/2018_ NEUROATLANTIC project), INTERREG V A España Portugal (POCTEP) (0624_2IQBIONEURO_6_E) and the European Regional Development Fund (ERDF). Work in AGM lab is supported by grant IT-1106-16 from “Departamento de Educación, Universidades e Investigación” (Gobierno Vasco, Gasteiz-Virtoria, Spain). Moreover, M. Aramburu-Núñez (IFI18/00008) is recipient of iPFIS contract, and Sobrino (CPII17/00027) is recipient of a research contract from the Miguel Servet Program from the Instituto de Salud Carlos III. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

INFORME CAMPAÑA ARSA 0297

Durante los días 19 al 26 de Febrero del 1997 se ha llevado a cabo la campaña de la serie "Arrastre Suratlántica" (ARSA 0297). La zona prospectada ha correspondido a la zona de plataforma y talud continental de la parte española del Golfo de Cádiz, comprendida entre el meridiano 7º 20’ W, o la frontera con Portugal, el paralelo 36º 15’ N, entre las isóbatas de 15 y 800 metros, siendo su límite inferior la distancia de 6 millas a la costa. La campaña se realizó a bordo del B/O "Cornide de Saavedra", siendo el objetivo previsto la estimación de los índices de abundancia (número y biomasa), de las especies demersales de mayor interés pesquero, así como de la fauna asociada a ellas

Overall and cause-specific mortality in HIV-positive subjects compared to the general population

Poster Session – Abstract P179INTRODUCTION: Emerging non-AIDS related causes of death have been observed in HIV-positive subjects in industrialized countries. We aimed to analyze overall and cause-specific excess of mortality of HIV-positive patients compared to the general population and to assess the effect of prognostic factors. MATERIAL AND METHODS: We used generalized linear models with Poisson error structure to estimate overall and cause-specific excess of mortality in HIV-positive patients from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS), compared to Spanish general population and to assess the impact of multiple risk factors. We investigated differences between short-term and long-term risk factors effects on excess of mortality. Multiple Imputation by Chained Equations was used to deal with missing data. RESULTS: In 9162 patients there were 363 deaths, 16.0% were non-AIDS malignancies, 10.5% liver and 0.3% cardiovascular related. Excess mortality was 1.20 deaths per 100 person years (py) for all-cause mortality, 0.16 for liver, 0.10 for non-AIDS malignancies and 0.03 for cardiovascular. Short-term (first-year follow-up) excess Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27 (95% CI 3.06-6.01) and 1.47 (95% CI 0.95-2.27) for HCV coinfection; long-term (subsequent follow-up) eHR for baseline AIDS was 0.88 (95% CI 0.58-1.35) and 4.48 (95% CI 2.71-7.42) for HCV coinfection. Lower CD4 count and higher viral load at entry, lower education, being male and over 50 years were predictors for overall excess mortality. Excess of liver mortality was higher in patients with CD4 counts at entry below 200 cells compared to those above 350 (eHR: 6.49, 95% CI 1.21-34.84) and in HCV-coinfected patients (eHR: 3.85, 95% CI 0.85- 17.37), although it was borderline significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.4-12.85) and HCV coinfected (eHR: 5.81, 95% CI 2.6-13) showed a higher risk of non-AIDS malignancies mortality excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25-35.73). CONCLUSIONS: Our results show overall, liver, non-AIDS malignancies and cardiovascular excess of mortality associated with being HIV-positive, despite improvements in HIV disease management and antiretroviral therapies. Differential short-term and long-term effect of AIDS before entry and HCV coinfection was found for overall mortality.S

Comparison of oxidative stress markers in HIV-infected patients on efavirenz or atazanavir/ritonavir-based therapy

INTRODUCTION: Chronic low-grade inflammation and immune activation may persist in HIV patients despite effective antiretroviral therapy (ART). These abnormalities are associated with increased oxidative stress (OS). Bilirubin (BR) may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UGT1A1, thus increasing unconjugated BR levels, a distinctive feature of this drug. We compared changes in OS markers in HIV patients on ATV/r versus efavirenz (EFV)-based first-line therapies. MATERIALS AND METHODS: Cohort of the Spanish Research Network (CoRIS) is a multicentre, open, prospective cohort of HIV-infected patients naïve to ART at entry and linked to a biobank. We identified hepatitis C virus/hepatitis B virus (HCV/HBV) negative patients who started first-line ART with either ATV/r or EFV, had a baseline biobank sample and a follow-up sample after at least nine months of ART while maintaining initial regimen and being virologically suppressed. Lipoprotein-associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in paired samples. Marker values at one year were interpolated from available data. Multiple imputations using chained equations were used to deal with missing values. Change in the OS markers was modelled using multiple linear regressions adjusting for baseline marker values and baseline confounders. Correlations between continuous variables were explored using Pearson's correlation tests. RESULTS: 145 patients (97 EFV; 48 ATV/r) were studied. Mean (SD) baseline values for OS markers in EFV and ATV/r groups were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO [74.3 (48.2) and 93.9 (64.3) µg/L] and OxLDL [76.3 (52.3) and 82.2 (54.4) µg/L]. After adjustment for baseline variables patients on ATV/r had a significant decrease in Lp-PLA2 (estimated difference -16.3 [CI 95%: -31.4, -1.25; p=0.03]) and a significantly lower increase in OxLDL (estimated difference -21.8 [-38.0, -5.6; p<0.01] relative to those on EFV, whereas no differences in MPO were found. Adjusted changes in BR were significantly higher for the ATV/r group (estimated difference 1.33 [1.03, 1.52; p<0.01]). Changes in BR and changes in OS markers were significantly correlated. CONCLUSIONS: In virologically suppressed patients on stable ART, OS was lower in ATV/r-based regimens compared to EFV. We hypothesize these changes could be in part attributable to increased BR plasma levels.S

Estradiol, acting through estrogen receptor alpha, restores dimethylarginine dimethylaminohydrolase activity and nitric oxide production in oxLDL-treated human arterial endothelial cells

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. ADMA accumulation, mainly due to a decreased dimethylarginine dimethylaminohydrolase (DDAH) activity, has been related to the development of cardiovascular diseases. We investigate whether estradiol prevents the alterations induced by oxidized low density lipoprotein (oxLDL) on the DDAH/ADMA/NO pathway in human umbilical artery endothelial cells (HUAEC). HUAEC were exposed to estradiol, native LDL (nLDL), oxLDL and their combinations for 24h. In some experiments, cells were also exposed to the unspecific estrogen receptor (ER) antagonist ICI 182780, or the specific ERα antagonist MPP. ADMA concentration was measured by HPLC and concentration of NO by amperometry. Protein expression and DDAH activity were measured by immunoblotting and an enzymatic method, respectively. oxLDL, but not to nLDL, increased ADMA concentration with a concomitant decrease of DDAH activity. oxLDL reduced eNOS protein and NO production. Estradiol alone had no effects on DDAH/ADMA/NO pathway, but increased the attenuated endothelial NO production induced by oxLDL by restoring the DDAH activity. ICI 182780 and MPP completely abolished these effects of estradiol on oxLDL-exposed cells. In conclusion, estradiol restores DDAH activity ADMA levels and NO production impaired by oxLDL in HUAEC acting through ERα