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: 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: Primary pneumonic plague is a rare but often fatal form of Yersinia pestis infection that results from direct inhalation of bacteria and is potentially transmissible from person to person. We describe a case of primary pneumonic plague in a wildlife biologist who was found deceased in his residence 1 week after conducting a necropsy on a mountain lion.', "To determine cause of death, a postmortem examination was conducted, and friends and colleagues were interviewed. Physical evidence was reviewed, including specimens from the mountain lion and the biologist's medical chart, camera, and computer. Human and animal tissues were submitted for testing. Persons in close contact (within 2 meters) to the biologist after he had developed symptoms were identified and offered chemoprophylaxis.", 'The biologist conducted the necropsy in his garage without the use of personal protective equipment. Three days later, he developed fever and hemoptysis and died approximately 6 days after exposure. Gross examination showed consolidation and hemorrhagic fluid in the lungs; no buboes were noted. Plague was diagnosed presumptively by polymerase chain reaction and confirmed by culture. Tissues from the mountain lion tested positive for Y. pestis, and isolates from the biologist and mountain lion were indistinguishable by pulsed-field gel electrophoresis. Among 49 contacts who received chemoprophylaxis, none developed symptoms consistent with plague.\Question: Do primary pneumonic plague contracted from a mountain lion carcass?

SOLUTION: The biologist likely acquired pneumonic plague through inhalation of aerosols generated during postmortem examination of an infected mountain lion. Enhanced awareness of zoonotic diseases and appropriate use of personal protective equipment are needed for biologists and others who handle wildlife.

PROBLEM: Context: Significant improvement in myocardial recovery has been shown previously with interventions to decrease reactive oxygen species after ischemia/hypoxia. We investigated whether co-administration of N-acetylcysteine (NAC, a scavenger for reactive oxygen species) and N (G)-monomethyl-L: -arginine (L-NMMA, a non-selective nitric oxide synthase inhibitor) results in better hemodynamic recovery.', 'Controlled, block-randomized study.', 'University research laboratory.', 'Mixed breed piglets (1-4d, 1.6-2.4 kg).', 'Acutely instrumented piglets received normocapnic alveolar hypoxia (10-15% oxygen) for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). After reoxygenation, hypoxic-reoxygenated piglets were given either saline (controls), NAC [30 mg/kg bolus + 20 mg/(kg h) infusion], NMMA [0.1 mg/kg bolus + 0.1 mg/(kg h) infusion] or NAC + L-NMMA via intravenous infusion in a blinded, randomized fashion (n = 8/group). Sham-operated piglets had no hypoxia-reoxygenation (n = 5).', 'Both cardiac index and stroke volume of hypoxia-reoxygenation controls remained depressed during reoxygenation (vs. normoxic baseline, p < 0.05). Post-resuscitation treatment with L-NMMA alone did not improve systemic hemodynamic recovery, but caused pulmonary hypertension (vs. controls). In contrast, treating the piglets with either NAC or NAC + L-NMMA improved cardiac index and stroke volume, with no effect on heart rate and blood pressure (vs. controls). These treatments also decreased various oxidative stress markers in myocardial tissues (vs. controls). However, there was no significant difference between NAC- and NAC + L-NMMA groups in all examined parameters.\Question: Does post-resuscitation NOS inhibition improve hemodynamic recovery of hypoxic newborn pigs?

SOLUTION:
Post-resuscitation administration of NAC improved cardiac function and reduced oxidative stress in newborn pigs with hypoxia-reoxygenation insult. Low-dose, non-selective inhibitor of nitric oxide synthase activity did not provide any further beneficial effect.