In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
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Question: Context: Severity of rheumatoid arthritis and progression of radiographic joint damage have decreased over the last decades.', 'To examine whether this trend is attributable to an underlying trend towards milder disease or to improved treatment.', 'The study used an inception cohort of patients with early rheumatoid arthritis seen at the Wichita Arthritis Center, Wichita, Kansas, USA, since 1973 and monitored prospectively since their first clinic visit through clinical, radiographic, laboratory, demographic and self-reported data. The radiographic disease progression in patients with disease onset in the 1970s, 1980s and 1990s was compared using a multivariate regression model for longitudinal data. The analysis was adjusted for differences in baseline predictors, type of disease-modifying antirheumatic drugs (DMARDs) and steroid use.', '418 patients with rheumatoid arthritis with radiographic follow-up were included. Patients in earlier decades used fewer DMARDs, had longer disease durations and higher tender joint counts at their first visit. Other important predictors of disease progression did not differ significantly between decades of disease onset. The unadjusted rates of radiographic progression differed between decades (analysis of variance, p = 0.01), with a significant trend towards less radiographic progression in more recent times (trend, p<0.001). However, after adjusting for DMARD use, steroid use and baseline predictors, differences between decades vanished (analysis of variance, p = 0.40) and the trend towards less radiographic progression disappeared (trend, p = 0.45).\Question: Are progression of radiographic joint damage in different eras : trends towards milder disease in rheumatoid arthritis attributable to improved treatment?

Answer: These results suggest that the observed trend towards milder disease in rheumatoid arthritis is attributable to more effective antirheumatic treatment and not to a secular trend.


Question: Context: Platelets are a natural source of growth factors, cytokines and chemokines, that regulate angiogenesis and inflammation. It has been suggested that differential release of pro- and anti-angiogenic growth factors from platelet α-granules by protease-activated receptors (PAR) 1 and 4 may be important for the regulation of angiogenesis. We aimed to compare the releasates of unstimulated platelets with PAR-1- and PAR-4-stimulated platelets.', "The release of β-thromboglobulin, platelet factor (PF)-4, thrombospondin, platelet-derived growth factor (PDGF)-A/B, regulated and normal T-cell expressed and secreted (RANTES/CCL5), endostatin, CXCL12, and vascular endothelial growth factor (VEGF) was measured with enzyme-linked immunosorbent assay (ELISA). Mass spectrometry (MS)-based quantitative proteomics identified 93 proteins from platelets stimulated with PAR-1 and PAR-4. A strong correlation between the factors released after either stimulus was observed (Spearman's r 0.94, P < 0.001). Analysis with ELISA showed that stimulation with PAR-1 or PAR-4 lead to non-differential release of β-thromboglobulin, PF-4, thrombospondin, PDGF-A/B, RANTES/CCL5, endostatin, CXCL12, and VEGF. Release of thrombospondin was slightly lower after PAR-1 stimulation (7.2 μg/mL), compared with PAR-4 induced release (9.8 μg/mL; P < 0.05).\Question: Does quantitative proteomics analysis reveal similar release profiles following specific PAR-1 or PAR-4 stimulation of platelets?

Answer: Both ELISA on established α-granule proteins and MS-based quantitative proteomics showed that the most abundant α-granule proteins are released in similar quantities from platelets after stimulation with either PAR-1 or PAR-4. Our findings provide evidence against the hypothesis that PAR-1 and PAR-4 stimulation of platelets trigger differential release of alpha-granule, but further studies are needed to draw conclusions for physiological conditions.


Question: Context: Phosphodiesterase 2A (PDE2A) is an evolutionarily conserved enzyme that catalyzes the degradation of the cyclic nucleotides, cyclic adenosine monophosphate, and/or cyclic guanosine monophosphate. Recent studies reported the expression of PDE2A in the dorsal horn of the spinal cord, pointing to a potential contribution to the processing of pain. However, the functions of PDE2A in spinal pain processing in vivo remained elusive.', 'Immunohistochemistry, laser microdissection, and quantitative real-time reverse transcription polymerase chain reaction experiments were performed to characterize the localization and regulation of PDE2A protein and messenger RNA in the mouse spinal cord. Effects of the selective PDE2A inhibitor, BAY 60-7550 (Cayman Chemical, Ann Arbor, MI), in animal models of inflammatory pain (n = 6 to 10), neuropathic pain (n = 5 to 6), and after intrathecal injection of cyclic nucleotides (n = 6 to 8) were examined. Also, cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in spinal cord tissues were measured by liquid chromatography tandem mass spectrometry.', 'The authors here demonstrate that PDE2A is distinctly expressed in neurons of the superficial dorsal horn of the spinal cord, and that its spinal expression is upregulated in response to hind paw inflammation. Administration of the selective PDE2A inhibitor, BAY 60-7550, increased the nociceptive behavior of mice in animal models of inflammatory pain. Moreover, BAY 60-7550 increased the pain hypersensitivity induced by intrathecal delivery of cyclic adenosine monophosphate, but not of cyclic guanosine monophosphate, and it increased the cyclic adenosine monophosphate levels in spinal cord tissues.\Question: Does phosphodiesterase 2A localized in the spinal cord contribute to inflammatory pain processing?

Answer:
Our findings indicate that PDE2A contributes to the processing of inflammatory pain in the spinal cord.