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3% to 0.3%), and A4 (-24.2% to -18.1%), with no clear dose response. In Study 2, participants with baseline A4 >2x ULN (n=5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤2x ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%). For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal. For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal. Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life. In this first-in-human, placebo-controlled study, 502 healthy non-pregnant women were randomized 1111 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3), or placebo. Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4-53.2%) vs placebo (0-15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with pre-vaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8-14-fold and 12-21-fold at day (D)8 and persisted 5-6-fold and 6-8-fold higher until D91 in the RSVPreF3 groups vs 1-fold in placebo. Comparisons at D8 and D31 showed that the higher dose levels were significantly more immunogenic than the lowest one. The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women. The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women. To explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease. Furthermore, to explore characteristics of patients with/without physical consultations in the clinic, and impact of early versus established disease. Patients with rheumatoid arthritis(RA)/psoriatic arthritis(PsA)/axial spondyloarthritis(AxSpA) prospectively followed in the nationwide DANBIO-registry answered online questionnaires and reported patient reported outcomes (PROs) in June and November 2020. Patient characteristics, disease activity and physical consultations in the clinic before and during the pandemic were identified in DANBIO (all patients and subgroup with early disease (disease duration ≤2 years)). In individual patients, changes in PROs before and during the pandemic were calculated. Characteristics of patients with/without physical consultations were described (age/gender/educational level/con was high and the PROs and remission rates remained stable despite remarkable reduction in physical consultations, also in patients with early disease. Characteristics of patients with/without physical consultations appeared similar. Digital pitting scars (DPS) are frequent, but little studied in SSc to date. An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to 1) examine DPS prevalence, 2) whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene), and 3) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with 1) functional impairment, 2) structural microvascular disease, 3) and mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia, and mortality. 9671 patients were included with reported DPS at any time point (n = 4924) or 'never' DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. https://www.selleckchem.com/products/o-pentagalloylglucose.html DPS were associated with longer disease and Raynaud's duration (both P = <0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P = <0.001) and joint synovitis (P = <0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (OR) with DUs 22.03 (19.51 to 24.87), active digital ischaemia 6.30 (5.34 to 7.42), and death 1.86 (1.48 to 2.36). DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimise the therapeutic strategy. DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimise the therapeutic strategy.Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating "evolutionary strata" of various ages. While the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around one hundred candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost.
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