CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Carbon balance in grapevines (Vitis vinifera L.): effect of environment, cultivar, and phenology on carbon gain, losses and allocation

[eng] Background and Aims Measuring the carbon assimilation and respiration during vine phenology can provide an understanding of the dynamics of carbon fluxes from different organs and their relationship. Most field studies to date do not consider the respiratory losses of different plant organs and their variability under environmental, genetic and phenological changes. The aim of this study was to investigate the effect of genotype and water regime on carbon assimilation, respiration and allocation during vine phenology. Methods and Results Field trials were carried out during 2013 and 2014 to study the effect of genotype and water status on carbon assimilation, respiratory losses from leaves, shoots, fruits and roots during the vine phenological cycle, and on biomass production. Carbon respiration varied during plant phenology and represented a significant proportion of the total vine carbon assimilation. The integrated carbon respiratory loss in leaves, fruits and roots was greater in irrigated vines than in non-irrigated vines. Tempranillo recorded the highest carbon assimilation, leaf and stem respiration, as well as the highest above-ground biomass. Garnacha showed a higher root respiration loss and allocated more biomass to the permanent organs. Accumulation of above-ground biomass was influenced by plant carbon budgets during the growing season. Conclusions Vine phenology, cultivar and plant water status affected carbon assimilation, carbon loss and carbon allocation. Non-irrigated vines had a higher respiratory carbon loss in respect to the total carbon assimilation by photosynthesis. Above- and below-ground carbon fluxes were coupled during vine phenology

Differences in water-use-efficiency between two Vitis vinifera cultivars (Grenache and Tempranillo) explained by the combined response of stomata to hydraulic and chemical signals during water stress

Knowledge about regulation of stomatal conductance is necessary to improve grapevine water use efficiency. The vast range of grapevine cultivars may allow choosing the best-performing ones to global changing conditions provided the understanding and characterization of their physiological responses. In this study, a comparison between two cultivars (Tempranillo and Grenache) with different reputation in water use efficiency was performed during two experimental years in field-conditions. Water relations, leaf gas exchange and abscisic acid (ABA) dynamics were measured at different phenological stages along the growing seasons. A clear difference in the regulation of leaf water relations was observed between cultivars under water stress conditions. Specifically, results showed that there is a clear relationship between hydraulic conductance (Kh) and stomatal regulation. However, ABA can exert a differentiating role on stomatal control during different stages within the grapevine growth period. Furthermore, this study showed that differences in osmotic adjustment could lead to substantial differentiation in the stomatal regulation and the leaf water use efficiency

Stomatal closure is induced by hydraulic signals and maintained by ABA in drought-stressed grapevine

8noWater saving under drought stress is assured by stomatal closure driven by active (ABA-mediated) and/or passive (hydraulic-mediated) mechanisms. There is currently no comprehensive model nor any general consensus about the actual contribution and relative importance of each of the above factors in modulating stomatal closure in planta. In the present study, we assessed the contribution of passive (hydraulic) vs active (ABA mediated) mechanisms of stomatal closure in V. vinifera plants facing drought stress. Leaf gas exchange decreased progressively to zero during drought, and embolism-induced loss of hydraulic conductance in petioles peaked to ∼50% in correspondence with strong daily limitation of stomatal conductance. Foliar ABA significantly increased only after complete stomatal closure had already occurred. Rewatering plants after complete stomatal closure and after foliar ABA reached maximum values did not induced stomatal re-opening, despite embolism recovery and water potential rise. Our data suggest that in grapevine stomatal conductance is primarily regulated by passive hydraulic mechanisms. Foliar ABA apparently limits leaf gas exchange over long-term, also preventing recovery of stomatal aperture upon rewatering, suggesting the occurrence of a mechanism of long-term down-regulation of transpiration to favor embolism repair and preserve water under conditions of fluctuating water availability and repeated drought events.openopenTombesi, Sergio; Nardini, Andrea; Frioni, Tommaso; Soccolini, Marta; Zadra, Claudia; Farinelli, Daniela; Poni, Stefano; Palliotti, AlbertoTombesi, Sergio; Nardini, Andrea; Frioni, Tommaso; Soccolini, Marta; Zadra, Claudia; Farinelli, Daniela; Poni, Stefano; Palliotti, Albert

Criteria for the diagnosis of extra nodal extension detected on radiological imaging in head and neck cancer: HNCIG international consensus recommendations

Extranodal extension of tumour on histopathology (pENE) is known to be a negative prognostic factor in head and neck cancer (HNC). Compelling evidence suggests that extranodal extension detected on radiological imaging (imaging-detected ENE; iENE) is also a negative prognostic factor. Furthermore, if iENE could be identified reliably before start of treatment, it could be used to guide treatment selection, as patients with iENE may be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy. There are many aspects of iENE that remain unresolved or which lack consensus – such as the criteria to best diagnose iENE and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for iENE to harmonize clinical practice and research. These recommendations have been endorsed by 19 national organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by the majority of participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading iENE.<br/