The optical field angle distortion calibration feasibility study for the Hubble Space Telescope fine guidance sensors

The results of an analytical study to investigate the feasibility of calibrating the Hubble Space Telescope's (HST's) fine guidance sensors (FGSs) within HST mission accuracy limits are presented. The study has two purposes: (1) to determine the mathematical feasibility of the optical field angle distortion (OFAD) calibration algorithm and (2) to confirm that the OFAD, plate scale, and FGS-to-FGS alignment calibration algorithms produced a calibration of the FGSs that satisfied mission requirements. The study concluded that the mathematical specification of the OFAD algorithm is adequate and permits a determination of the FGS calibration parameters (accurate to better than 0.003 arc-second) sufficient to meet the mission requirements. The algorithms implemented, the characteristics of the simulated data and procedures for data analysis, and the study's results are discussed. In addition, several useful techniques for improving the stability and accuracy of the OFAD solution are outlined

Endothelial cells, endoplasmic reticulum stress and oxysterols

Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress

Ethical issues associated with in-hospital emergency from the medical emergency team's perspective: a national survey

Medical Emergency Teams (METs) are frequently involved in ethical issues associated to in-hospital emergencies, like decisions about end-of-life care and intensive care unit (ICU) admission. MET involvement offers both advantages and disadvantages, especially when an immediate decision must be made. We performed a survey among Italian intensivists/anesthesiologists evaluating MET's perspective on the most relevant ethical aspects faced in daily practice

Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study

AIM To report adalimumab (Ada) efficacy on articulargastrointestinal disease and health-related quality of life (HRQoL) in patients with enteropathic spondyloarthritis (ES). METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes (PROs) of the HRQoL questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor (TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests: (1) Ankylosing Spondylitis Disease Activity Score- C-Reactive Protein (ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) for articular activity; (2) Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and partial Mayo (pMayo) score for gastrointestinal symptoms and activity; and (3) Health Assessment Questionnaire (HAQ), Patient Global Assessment (PGA) and Short Form-36 health survey (SF-36) questionnaires for PROs of the HRQoL. RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQoL scores, showed a significant improvement having been achieved at the earliest (6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES. CONCLUSION Ada treatment, upon multidisciplinary (gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQoL in patients affected by ES

Successful Invasions of Short Internally Deleted Elements (SIDEs) and Its Partner CR1 in Lepidoptera Insects

Although DNA transposons often generated internal deleted derivatives such as miniature inverted-repeat transposable elements, short internally deleted elements (SIDEs) derived from nonlong terminal-repeat retrotransposons are rare. Here, we found a novel SIDE, named Persaeus, that originated from the chicken repeat 1 (CR1) retrotransposon Zenon and it has been found widespread in Lepidoptera insects. Our findings suggested that Persaeus and the partner Zenon have experienced a transposition burst in their host genomes and the copy number of Persaeus and Zenon in assayed genomes are significantly correlated. Accordingly, the activity though age analysis indicated that the replication wave of Persaeus coincided with that of Zenon. Phylogenetic analyses suggested that Persaeus may have evolved at least four times independently, and that it has been vertically transferred into its host genomes. Together, our results provide new insights into the evolution dynamics of SIDEs and its partner non-LTRs

Comparative genomics of tadpole shrimps (Crustacea, Branchiopoda, Notostraca): Dynamic genome evolution against the backdrop of morphological stasis

This analysis presents five genome assemblies of four Notostraca taxa. Notostraca origin dates to the Permian/Upper Devonian and the extant forms show a striking morphological similarity to fossil taxa. The comparison of sequenced genomes with other Branchiopoda genomes shows that, despite the morphological stasis, Notostraca share a dynamic genome evolution with high turnover for gene families' expansion/contraction and a transposable elements content comparable to other branchiopods. While Notostraca substitutions rate appears similar or lower in comparison to other branchiopods, a subset of genes shows a faster evolutionary pace, highlighting the difficulty of generalizing about genomic stasis versus dynamism. Moreover, we found that the variation of Triops cancriformis transposable elements content appeared linked to reproductive strategies, in line with theoretical expectations. Overall, besides providing new genomic resources for the study of these organisms, which appear relevant for their ecology and evolution, we also confirmed the decoupling of morphological and molecular evolution

Niemann-Pick B-lymphocytes show autophagic stress features

Niemann-Pick disease (NPD) type A and B are lysosomal storage disorders (LSD) due to the lack of acid sphingomyelinase (ASM) activity (Schuchman et al., 2001). The enzyme defect results in a pathological accumulation of sphingomyelin (SM) within lysosomes. In many LSD, an accumulation of undegraded substrates in lysosomes due to deficiency of specific lysosomal enzymes impairs the autophagic process (Settembre et al., 2008), but an imbalance of the of autophagic process in NPB cells has never been shown. The purpose of this study is to examine the autophagic response in NPB B lymphocytes by means of flow cytometry, confocal microscopy and western blot techniques. EBV-transformed B Lymphocytes from patients with Niemann-Pick type B were treated with nocodazole (NZ) and wortmannin (WM), two autophagy inhibitors, and rapamicyn (RM), an autophagic inductor. Furthermore we starved cells using a serum-free medium to activate the autophagic process. NPD lymphocytes treated by NZ and RM showed an opposite trend than the expected results for normal cells, in Acridine Orange, Lysotracker Green and CD63 staining, clearly suggesting an impairment of this cellular pathway. Instead, starved cells highlighted a normal behaviour for these markers, indicating a residual ability to enter the process. In conclusion such results suggest the involvement of autophagy and the impairment of lysosomal network before and during NPB cells response to the above-mentioned stimuli. These scenario characterize an imbalance between formation and degradation of autophagic vacuoles (autophagic stress)

POS1061 THE ITALIAN PROSPECTIVE SIRENA STUDY: FOCUS ON EARLY PSORIATIC ARTHRITIS COHORT AND GENDER DIFFERENCES

Background:Limited data on early Psoriatic Arthritis (PsA) are available1,2.Objectives:To describe baseline data of PsA patients naive to any DMARDs.Methods:SIRENA study is an Italian, prospective Registry of Spondyloarthritis patients diagnosed according to ASAS criteria and naïve to any DMARDs. Data on demographic and clinical characteristics of PsA cohort were collected and analysed, also by gender.Results:203/350 (58%) subjects included in SIRENA Registry had PsA (mean age 51.9 years) and in 190/203 (94%) CASPAR classification criteria were fulfilled. In 70% of patients the diagnosis was performed within 24 months from symptom onset. At baseline, 194/203 (95.6%) had mainly peripheral manifestations, 74.4% of patients had skin psoriasis, 40% nail psoriasis, 39.3% clinical enthesitis and 25.9% dactylitis. Mean SJC66 and TJC68 were, respectively, 3 and 7.2; mean PhGA was 46.3; 14.7% of patients were in MDA.The higher tender joint count in women (mean TJC68 9.3 in women vs 5.3 in men) resulted in a higher disease activity according to DAPSA (high disease activity: 11.5% women vs 4.1% men), a higher joint VAS score (mean score 47.1 women vs 39.8 men) and a lower prevalence of MDA (8.3% women vs 20% men). We observed a higher prevalence of moderate or severe psoriasis in men (BSA≥3%: 37% men vs 27.8% women) while all PROs collected (PtGA, pain VAS score, sleep VAS score, BASFI, BASDAI, HAQ-DI, WPAI) were worse in women.The most common comorbidities were cardiometabolic (35.5%), endocrine (9.4%), and gastrointestinal disorders (7.4%). Cardiometabolic disorders were more frequently reported by men, endocrine and gastrointestinal disorders by women; depression exclusively by women.Conclusion:This analysis provides real-life data in a cohort of early PsA subjects. Relevant gender differences were observed, with women showing a higher disease activity and more joint pain and men having more severe psoriasis. Women also perceived a worse disease burden.References:[1]Theander E, et al. Ann Rheum Dis 2014; 73:407–413.[2]Nas K, et al. Mod Rheumatol 2017; 27(2):345-349.Table 1.Baseline dataPsAAll patients (n=203)Women (n=98)Men (n=105)Age (years), mean (SD)51.9 (13.1)51.1 (13.2)52.7 (13.0)Men, n (%)105 (51.7)0 (0)105 (100)BMI (kg/m2), mean (SD)25.9 (4.4)25.4 (4.9)26.4 (3.9)BMI categories^, n (%) Obese40 (21.2)20 (22.2)20 (20.2) Overweight44 (23.3)15 (16.7)29 (29.3) Under/normal weight105 (55.6)55 (61.1)50 (50.5)Comorbidities > 5%*, n (%) Cardiometabolic72 (35.5)28 (28.6)44 (41.9) Endocrine disease19 (9.4)15 (15.3)4 (3.8) Gastrointestinal15 (7.4)10 (10.2)5 (4.8) Depression/Anxiety8 (3.9)8 (8.2)0 (0) Hepatic diseases7 (3.5)1 (1.0)6 (5.7)Clinical assessmentCRP (mg/dl), median (min-max)0.40 (0 – 7.12)0.31 (0 - 5.40)0.49 (0 - 7.12)SJC66, mean (SD)3.0 (4.0)3.2 (4.0)2.7 (4.0)TJC68, mean (SD)7.2 (8.8)9.3 (10.3)5.3 (6.6)Dactylitis, n/tot assessed (%)35/135 (25.9)12/63 (19.1)23/72 (31.9)Enthesitis, n/tot assessed (%)66/168 (39.3)39/80 (48.8)27/88 (30.7)Psoriasis skin, n (%)151 (74.4)68 (69.4)83 (79.1)Psoriasis nails, n/tot assessed (%)62/155 (40.0)29/75 (38.7)33/80 (41.3)Fibromyalgia, n (%)6 (3.0)5 (5.2)1 (1.0)VAS, mean (SD) [range: 0-100] PhGA score46.3 (25.8)51.2 (25.4)41.7 (25.4) Joint score43.3 (26.8)47.1 (25.2)39.8 (27.8) Skin score20.3 (24.0)17.8 (23.1)22.6 (24.8)DAPSA, mean (SD)22.3 (14.1)26.8 (15.4)18.7 (11.9)DAPSA categories^, n (%)High disease activity13 (7.4)9 (11.5)4 (4.1)Moderate disease activity83 (47.2)43 (55.1)40 (40.8)Low disease activity71 (40.3)24 (30.8)47 (48.0)Remission9 (5.1)2 (2.6)7 (7.1)MDA°, n (%)23 (14.7)6 (8.3)17 (20.0)BSA categories, n (%) 3-10% (moderate psoriasis)35 (24.6)13 (21.2)22 (27.1) >10% (severe psoriasis)12 (8.5)4 (6.6)8 (9.9)* A patient could report one or more comorbidities. ^The sum does not add up to the total because of some missing values. ° According to Coates et al. (Ann Rheum Dis. 2010;69: 48).Disclosure of Interests:Alen Zabotti: None declared, Michele Maria Luchetti Speakers bureau: Honorary fees for conferences and workshops by Janssen, Abbvie, Novartis, Lilly, Celgene, Pfizer, Carlo Selmi Speakers bureau: Honoraria and/or speaker bureau from AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer, Sanofi-Regeneron, Grant/research support from: Research support from Amgen, Janssen, Novartis, Pfizer, Roberta Ramonda Speakers bureau: Honoraria and speaker fees from Novartis, Abbvie, Pfizer, MSD, Janssen, Rosa Daniela Grembiale: None declared, Lorenzo Dagna Consultant of: Consultation honoraria from Abbvie, Amgen, Biogen, Celltrion, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Salvatore D'Angelo Speakers bureau: Consulting fees and/or speakers bureau from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi and UCB, Giacomo Cafaro: None declared, Salvatore De Vita: None declared, Mara Felicetti: None declared, Silvia Marelli Employee of: Janssen-Cilag SpA, Daniela Frigerio Employee of: Janssen-Cilag SpA, Ennio Favalli Speakers bureau: Consulting fees and/or speaking engagements from AbbVie, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Pfizer, Galapagos, Sanofi-Genzyme, and UCB