TASK DEFINITION: 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.
PROBLEM: Context: Symptomatic patients with severe aortic stenosis (AS) demonstrate abnormal left ventricular (LV) mechanics. The aim of this study was to compare mechanics in asymptomatic and symptomatic patients with severe AS using two-dimensional myocardial strain imaging.', 'One hundred fifty-four patients with severe AS (aortic valve area ≤ 1.0 cm(2)) referred to a heart valve clinic from 2004 to 2011 were studied. Thirty patients were asymptomatic, with normal LV ejection fractions (≥ 55%), without other significant valvular disease or wall motion abnormalities. Thirty-two symptomatic patients who underwent early aortic valve replacement, with similar age, gender, LV ejection fraction, and aortic valve area, were selected for comparison. Both groups were also compared with 32 healthy subjects with similar age and gender distributions and normal echocardiographic results who served as controls. LV longitudinal and circumferential strain and rotation were measured using speckle-tracking software applied to archived echocardiographic studies. Conventional echocardiographic and myocardial mechanical parameters were compared among the study subgroups.', 'Patients with asymptomatic severe AS demonstrated smaller reductions in longitudinal strain, higher (supernormal) apical circumferential strain (-38 ± 6% vs -35 ± 4%, P < .05), and extreme (supernormal) apical rotation (12.2 ± 4.9° vs 2.9 ± 1.7°, P < .0005) compared with symptomatic patients. Apical rotation < 6° was the single significant predictor of symptoms in logistic regression analysis of clinical, echocardiographic, and mechanical parameters. Twelve asymptomatic patients underwent eventual aortic valve replacement and showed decreases in strain and apical rotation compared with baseline values.\Question: Are symptoms in severe aortic stenosis associated with decreased compensatory circumferential myocardial mechanics?

SOLUTION: Longitudinal strain was uniformly low in patients with severe AS and lower in those with symptoms. Compensatory circumferential myocardial mechanics (increased apical circumferential strain and rotation) were absent in symptomatic patients. Thus, myocardial mechanics may help in the follow-up of patients with severe AS and timing of valve surgery.

PROBLEM: Context: Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery.', 'In this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities.', 'We evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE.', 'The EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis (eotaxin 3, CCL26), barrier molecules (desmoglein 1, DSG1), tissue remodeling (periostin, POSTN), and mast cells (carboxypeptidase A, CPA3). PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment.\Question: Does transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveal proton pump inhibitor-reversible allergic inflammation?

SOLUTION: These findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many patients with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus might constitute a subphenotype of patients with EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE, particularly that associated with classic features of allergic inflammation, provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.

PROBLEM: Context: Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-α and IL-1β in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord.\Question: Does tanshinone IIA attenuate neuropathic pain via inhibiting glial activation and immune response?

SOLUTION:
Taken together, our study provides evidence that TIIA inhibited SNL-induced neuropathic pain through depressing microglial activation and immune response by the inhibition of mitogen-activated protein kinases (MAPKs) pathways. Our findings suggest that TIIA might be a promising agent in the treatment of neuropathic pain.