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: Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs.', 'To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after 2 hours of hemorrhagic shock, mice that received SRBCs were given a coinfusion of haptoglobin, hemopexin, or albumin.', 'Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh packed red blood cells, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects.\Question: Does haptoglobin or Hemopexin Therapy prevent Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells?

SOLUTION: In mice, the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis after prolonged hypotension.

PROBLEM: Context: Glucocorticoids (GCs) are highly effective in the treatment of asthma. However, some individuals have GC-insensitive asthma.', 'To evaluate the functional response to steroids of bronchoalveolar lavage (BAL) cells from sites of airway inflammation from patients with GC-insensitive versus GC-sensitive asthma. As well, to attempt to define the functional role of glucocorticoid receptor (GCR)beta (a splicing variant, and dominant negative inhibitor of, the classic GCRalpha) in controlling GCRalpha nuclear translocation and transactivation at a molecular level.', 'Fiberoptic bronchoscopy with collection of BAL fluid was performed on seven patients with GC-sensitive asthma and eight patients with GC-insensitive asthma. GCRalpha cellular shuttling in response to 10(-6) M dexamethasone treatment and GCRbeta expression were analyzed in BAL cells by immunofluorescence staining. The effects of overexpression and silencing of GCRbeta mRNA on GCRalpha function were assessed.', 'Significantly reduced nuclear translocation of GCRalpha in response to steroids was found in BAL cells from patients with GC-insensitive asthma. BAL macrophages from patients with GC-insensitive asthma had significantly increased levels of cytoplasmic and nuclear GCRbeta. It was demonstrated that GCRalpha nuclear translocation and its transactivation properties were proportionately reduced by level of viral transduction of the GCRbeta gene into the DO-11.10 cell line. RNA silencing of GCRbeta mRNA in human BAL macrophages from patients with GC-insensitive asthma resulted in enhanced dexamethasone-induced GCRalpha transactivation.\Question: Does increased glucocorticoid receptor beta alter steroid response in glucocorticoid-insensitive asthma?

SOLUTION: GC insensitivity is associated with loss of GCRalpha nuclear translocation in BAL cells and elevated GCRbeta, which may inhibit GCRalpha transactivation in response to steroids.

PROBLEM: Context: Replacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (Poliorix™, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China.', 'In pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N=541) or OPV (N=535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N=470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study.', 'Study A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and ≥ 98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in ≥ 94.7% IPV and ≥ 96.1% OPV recipients at 18-24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration.\Question: Is primary and booster vaccination with an inactivated poliovirus vaccine ( IPV ) immunogenic and well-tolerated in infants and toddlers in China?

SOLUTION:
Trivalent IPV is non-inferior to OPV in terms of seroprotection (in the Chinese vaccination schedule) in infant and toddlers, with a clinically acceptable safety profile.