BackgroundRheumatoid Arthritis (RA) is a chronic systemic inflammatory disorder associated with increased mortality, in particular from cardiovascular (CV) disease, infections and cancer. We recently ...demonstrate a incidence mortality rate (IMR) in 654 RA patients enrolled over a 6 year period in a South-Italian tertiary Rheumatology Centre lower than that reported in the Norfolk Arthritis Registry.1 ObjectivesThe present study is devoted to investigate differences in IMR between our series and other European tertiary centre cohorts. Furthermore we evaluated the role, if any, of Anticarbamylated protein antibodies (anti-CarP Ab) in modulating the low IMR detected in our patients.MethodsClinical charts of patients consecutively admitted to our centre, from January 1st, 2008 to December 31st, 2014 were reviewed. IMRs and causes of death as assessed at December 31st 2015, were registered. Sera collected at the time of admission to our centre in 61 patients representative of our RA cohort were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab detected in our series were compared with those reported in the Better Anti-rheumatic Farmaco-therapy (BARFOT) cohort, the Leiden Early Arthritis Clinic cohort (Leiden EAC) and a Spanish cohort.2 3 ResultsSix hundred and eight patients were observed for a median of 3.51 years. All causes and cause-specific IMRs were significantly lower in our cohort with respect to the BARFOT and the Spanish cohort, while only all causes and CV IMRs were significantly lower in our series with respect to the Leiden EAC. These discrepancies might depend on demographic and clinical differences among the various cohorts. Nevertheless, we failed to find putative differences with respect to each North European cohort, but we detected a significantly lower prevalence of anti-CarP Ab in our series with respect to that reported in the other European cohorts considered (table 1).ConclusionsIn conclusion, we confirm that the mortality rate in our South Italian RA cohort is lower than that detected in patients from both North and South European countries.We detected a very low prevalence of anti-CarP Ab in our sample representative of the entire cohort. Whether this is the aspect underpinning the low mortality rate detected in our series, awaits to be furtherly investigated.Abstract AB0216 – Table 1References1 Iacono D, et al. Mortality in Italian patients with rheumatoid arthritis: evidence for a low mortality rate from cancer and infections in patients followed up at a tertiary center. Open Access Rheumatol2017.2 Ajeganova S, et al. Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts. Ann Rheum Dis2016.3 Vidal-Bralo L, et al. Anti-carbamylated protein autoantibodies associated with mortality in Spanish rheumatoid arthritis patients. PLoS One2017.Disclosure of InterestNone declared
We summed estimates of the carbon balance of forests, grasslands, arable lands and peatlands to obtain country-specific estimates of the terrestrial carbon balance during the 1990s. Forests and ...grasslands were a net sink for carbon, whereas croplands were carbon sources in all European countries. Hence, countries dominated by arable lands tended to be losing carbon from their terrestrial ecosystems, whereas forest-dominated countries tended to be sequestering carbon. In some countries, draining and extraction of peatlands caused substantial reductions in the net carbon balance. Net terrestrial carbon balances were typically an order of magnitude smaller than the fossil fuel-related carbon emissions. Exceptions to this overall picture were countries where population density and industrialization are small. It is, however, of utmost importance to acknowledge that the typically small net carbon balance represents the small difference between two large but opposing fluxes: uptake by forests and grasslands and losses from arable lands and peatlands. This suggests that relatively small changes in either or both of these large component fluxes could induce large effects on the net total, indicating that mitigation schemes should not be discarded a priori. In the absence of carbon-oriented land management, the current net carbon uptake is bound to decline soon. Protecting it will require actions at three levels; a) maintaining the current sink activity of forests, b) altered agricultural management practices to reduce the emissions from arable soils or turn into carbon sinks and c) protecting current large reservoirs (wetlands and old forests), since carbon is lost more rapidly than sequestered.
The VSiPMT (Vacuum Silicon PhotoMultiplier Tube) is an innovative design for a hybrid photodetector. The idea, born with the purpose to use a SiPM for large detection volumes, consists in replacing ...the classical dynode chain with a special SiPM. In this configuration, we match the large sensitive area of a photocathode with the performances of the SiPM technology, which therefore acts like an electron detector and so like a current amplifier. The excellent photon counting capability, fast response, low power consumption and the stability are among the most attractive features of the VSiPMT.We now present the progress on the realization of a 1-in. prototype and the preliminary tests we are performing on it.
•The VSiPMT is a new high gain photodetector with very good photon counting capability.•Simulations to realize a good focusing system have been done.•A test bench was set up to verify the simulations.•A 1-in. VSiPMT prototype has been realized and tested, with good results.•A 1-in. industrial prototype has been realized by Hamamatsu and is now under test.
BackgroundAnxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general ...population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited.AimsTo assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries.MethodsPeople aged 18–65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-International Neuropsychiatric Interview. Demographic and medical record data were collected.ResultsA total of 3170 people with type 2 diabetes (56.2% women; with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%; however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India.ConclusionsOur international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted.
SINEUPs are natural and synthetic antisense long non-coding RNAs (lncRNAs) selectively enhancing target mRNAs translation by increasing their association with polysomes. This activity requires two ...RNA domains: an embedded inverted SINEB2 element acting as effector domain, and an antisense region, the binding domain, conferring target selectivity. SINEUP technology presents several advantages to treat genetic (haploinsufficiencies) and complex diseases restoring the physiological activity of diseased genes and of compensatory pathways. To streamline these applications to the clinic, a better understanding of the mechanism of action is needed. Here we show that natural mouse SINEUP AS Uchl1 and synthetic human miniSINEUP-DJ-1 are N6-methyladenosine (m6A) modified by METTL3 enzyme. Then, we map m6A-modified sites along SINEUP sequence with Nanopore direct RNA sequencing and a reverse transcription assay. We report that m6A removal from SINEUP RNA causes the depletion of endogenous target mRNA from actively translating polysomes, without altering SINEUP enrichment in ribosomal subunit-associated fractions. These results prove that SINEUP activity requires an m6A-dependent step to enhance translation of target mRNAs, providing a new mechanism for m6A translation regulation and strengthening our knowledge of SINEUP-specific mode of action. Altogether these new findings pave the way to a more effective therapeutic application of this well-defined class of lncRNAs.
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In this study, Pierattini and colleagues show that antisense long non-coding SINEUP RNAs require m6A-modified residues to exert their activity as enhancers of translation. These results are important to unveil the details of the molecular mechanism of SINEUPs to streamline their use as therapeutics to treat unmet medical needs.
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