Objective. To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). Methods. Prospectively collected data on
Increased evidence suggests an accelerated macrovascular disease in systemic sclerosis (SSc). Brachial artery flow-mediated vasodilation (FMD) and carotid intima-media thickness (IMT) are two indicators of subclinic cardiovascular disease and are frequently used as surrogate measures of subclinic atherosclerosis. The aim of this study was to evaluate macrovascular involvement in SSc. We studied 35 SSc patients (6 males and 29 females; 11 with diffuse and 24 with limited disease) and 20 healthy controls. Brachial artery FMD was assessed by method described by Celermajer in all patients and 13 control subjects. IMT was measured using high-resolution B-mode ultrasonography in patients and controls. Traditional risk factors for atherosclerosis (hypertension, dyslipidemia, and smoke) were also assessed. FMD was significantly impaired (3.41% +/- 4.56% versus 7.66% +/- 4.24%; P < 0.037) and IMT was significantly elevated compared with healthy controls (0.93 +/- 0.29 mm versus 0.77 +/- 0.13 mm; P < 0.005). FMD was not significantly different in SSc with increased IMT compared with those with normal IMT). No correlation was found between risk factors for atherosclerosis and the impairment of FMD or IMT in SSc patients. The impairment of endothelial function and structural changes of large vessels are evident in SSc, but do not seem associated with traditional risk factors for atherosclerosis. Prospective studies including also clinical outcomes are needed to assess the features and significance of macrovacular involvement in SSc.
Objective To identify the main computed tomography (CT) features that may help distinguishing a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc) from COVID-19 pneumonia. Methods This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Results Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p < 0.0001) and signs of fibrosis in GGO in the lower lobes (p < 0.0001) remained independently associated with COVID-19 pneumonia or SSc-ILD, respectively. A predictive score was created which resulted positively associated with the COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). Conclusion The CT differential diagnosis between COVID-19 pneumonia and SSc-ILD is possible through the combination the proposed score and the radiologic expertise. The presence of consolidation in the lower lobes may suggest a COVID-19 pneumonia while the presence of fibrosis inside GGO may indicate a SSc-ILD.
B chromosomes (Bs) have been found in 55 out of 4629 living species of mammals. The summarized data show great variability in types of mammalian Bs, including differences in size, shape and molecular composition. This variability extends to the origin, mode of transmission and population dynamics. In general, B chromosomes in mammals do not differ from Bs found in other animal or plant species, but some peculiarities do exist. Most species in which Bs are found are widespread. Some data support the view that Bs may contribute to the successful expansion of some of these species, but it is possible that Bs are just more easily scored in them due to their frequent occurrence. Most of these species are also characterized by cycling fluctuations of abundance and characteristic social organization that produce conditions favorable for Bs to spread. All areas of research on Bs in mammals suffer from lack of data, emphasizing the necessity for intensified research on the molecular structure and ways of maintenance of Bs in populations.
BackgroundThe treatment of ILD remains a challenge for the rheumatologist. Recent studies suggested a potential short-term benefit of rituximab (RTX) on connective tissue diseases developing ILD.ObjectivesTo compare RTX effects on ILD in patients with systemic sclerosis (SSc), mixed connective tissue disorder (MCTD) and anti-synthetase (SYN).MethodsMulticentre retrospective assessment of the effects of RTX on ILD comparing three patient populations: SSc (n=23), MCTD (n=6) and SYN (n=15). All underwent high-resolution computed tomography (HRCT) at baseline and lung function tests (LFTs) at baseline and at 1 and 2 years of follow-up. The primary outcomes were the mean change in predicted forced vital capacity (FVC) value and the percentage of responders defined by an increase in FVC of 10% or greater.ResultsIn SYN patients, although the change of FVC from baseline to 2 years was not statistically significant, a trend of improvement was observed (table 1). In SSc, discrepancies were observed with a trend of improvement at 1 year but a decline at 2 years. In MCTD, FVC remained table at 1 and 2 years of follow-up. In SYN patients, the percentage of responders for FVC was greater than in SSc (33.3% vs 9.5%) (p=0.1) and than in MCTD patients (33.3% vs 16.7%) (p=0.15). At baseline, SSc and MCTD patients had a higher FVC when compared to SYN population (table 1) and this finding may partially explain the major percentage of responders in SYN than in SSc. The percentage of responders in DLCO (gain ≥15%) was similar in SYN and SSc populations (27.3% and 23.8% respectively). Some patients received DMARDs and/or immunosuppressive treatment previously or/and concurrently to RTX; although this did not influence our findings, these treatments may influence the effects of RTX. RTX showed a satisfactory safety profile.ConclusionsOur data obtained in routine care provide for the first time outcomes in LFTs after 2 years of follow-up. The main results show a good safety profile supporting future development. We also observed a promising trend of improvement in the SYN group and indicate that the drug may provide a stabilization of the involvement of the lung in SSc and MCTD. Future trials on homogenous groups of patients are warranted to determine how rituximab may be positioned in the treatment of CTD-ILD, but the SYN group should be prioritized.AcknowledgementsEULAR scintific travel bursaryDisclosure of InterestG. Lepri: None declared, J. Avouac: None declared, P. Airò: None declared, F. Anguita Santos: None declared, S. Bellando Randone: None declared, J. Blagojevic: None declared, O. Distler Grant/research support from: received research funding from, 4D Science, Actelion, Active Biotec, Bayer-Schering, Biogen, Biovitrium, BMS, Boehringer Ingelheim Pharma, EpiPharm, Ergonex, GSK, Inventiva, Medac, Novartis, Pfizer, Pharmacyclics, Roche/Genentech, Sanofi/Genzyme, Serodapharm, Sinoxa and United BioSource Corporation., F. J. Garcìa Hernàndez: None declared, J. A. Gonzalez Nieto: None declared, S. Guiducci: None declared, S. Jordan: ...
BackgroundThe oesophagus is the first gastrointestinal (GI) tract involved in systemic sclerosis (SSc), followed by the anorectum.ObjectiveEvaluation of oesophageal and anorectal involvement and their correlations in patients with very early diagnosis of SSc (VEDOSS).Patients and methods59 patients with VEDOSS, evaluated with oesophageal and anorectal manometry and investigated with lung function tests and chest HRCT. Demographic data, oesophageal and anorectal symptoms, Raynaud's phenomenon, autoantibodies, videocapillaroscopy patterns, puffy fingers and digital ulcers were recorded for all patients.ResultsIn 4 patients oesophageal manometry and in 17 patients anorectal manometry was not performed because of scarce tolerance. Oesophageal peristalsis was absent in 14 patients; its pressure and speed were significantly lower in 41 patients (p<0.001 and p=0.005, respectively). The maximum pressure and mean pressure (Pmax and Pm) of lower oesophageal sphincter were significantly lower (p=0.012 and p=0.024, respectively). Patients with a diffusing capacity of the lung for carbon monoxide<80% presented a hypotonic lower oesophageal sphincter (p=0.008) and an abnormal peristalsis (p<0.001); patients with a diffusing capacity of the lung for carbon monoxide>80% showed only an abnormal peristalsis (<0.001). The anal resting pressure (ARP) at 4.3 cm and 2 cm from anal edge and the anal canal Pm were significantly decreased (p<0.001 and p=0.010, respectively). The maximum voluntary contraction was significantly abnormal in its Pmax and Pm (p=0.017 and p=0.005) and in its duration (p=0.001). In patients with a positive HRCT, the ARP and the canal Pmax and Pm were significantly lower; patients with negative HRCT presented only an abnormal ARP.ConclusionsIn patients with VEDOSS, oesophageal and anorectal disorders are frequently detected, showing that very early SSc is characterised by GI involvement.
We have previously suggested a model for the eukaryotic genome based on the structure of the bacterial nucleoid where active RNA polymerases cluster to loop the intervening DNA. This organization of polymerases into clusters – which we call transcription ‘factories’ – has important consequences. For example, in the nucleus of a HeLa cell the concentration of soluble RNA polymerase II is ∼1 mM, but the local concentration in a factory is 1000-fold higher. Because a promoter can diffuse ∼100 nm in 15 s, one lying near a factory is likely to initiate; moreover, when released at termination, it will still lie near a factory, and the movement and modifications (e.g. acetylation) accompanying elongation will leave it in an ‘open’ conformation. Another promoter out in a long loop is less likely to initiate, because the promoter concentration falls off with the cube of the distance from the factory. Moreover, a long tether will buffer it from transcription-induced movement, making it prone to deacetylation, deposition of HP1 (heterochromatin protein 1), and incorporation into heterochromatin. The context around a promoter will then be self-sustaining: productive collisions of an active promoter with the factory will attract factors increasing the frequency of initiation, and the longer an inactive promoter remains inactive, the more it becomes embedded in heterochromatin. We review here the evidence that different factories may specialize in the transcription of different groups of genes.
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