TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: Developmental dyslexia (DD) is a complex heritable condition associated with impairments in multiple neurocognitive domains. Substantial heritability has been reported for DD and related phenotypes, and candidate genes have been identified. Recently, a candidate gene for human cognitive processes, that is, GRIN2B, has been found to be associated significantly with working memory in a German DD sample. In this study, we explored the contribution of six GRIN2B markers to DD and key DD-related phenotypes by association analyses in a sample of Italian nuclear families. Moreover, we assessed potential gene-by-environment interactions on DD-related phenotypes.', 'We carried out a family-based association study to determine whether the GRIN2B gene influences both DD as a categorical trait and its related cognitive traits in a large cohort of 466 Italian nuclear families ascertained through a proband affected by DD. Moreover, we tested the role of the selected GRIN2B markers and a set of commonly described environmental moderators using a test for GE interaction in sib pair-based association analysis of quantitative traits in 178 Italian nuclear families.', 'Evidence for a significant association was found with the categorical diagnosis of DD, performance intelligence quotient, phonemic elision, and auditory short-term memory. No significant gene-by-environment effects were found.
Answer: Our results add further evidence in support of GRIN2B contributing toward DD and deficits in DD. More specifically, our data support the view that GRIN2B influences DD as a categorical trait and its related quantitative phenotypes, thus shedding further light on the etiologic basis and the phenotypic complexity of this disorder.

SOLUTION: Does gRIN2B mediate susceptibility to intelligence quotient and cognitive impairments in developmental dyslexia?

PROBLEM: Context: In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity.', 'To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL.', 'Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results.', 'Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P<001). Multiple hierarchical linear regression analyses showed a statistically significant (P<001) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P<005) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score.
Answer: Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis.

SOLUTION: Is itching a significant problem and a mediator between disease severity and quality of life for patients with psoriasis : results from a randomized controlled trial?

PROBLEM: Context: Clonidine prolongs the duration of sensory and motor block induced by bupivacaine, and this association, in constant infusion by the epidural route, is used for postoperative analgesia. After a near-fatal intravenous bolus of bupivacaine in dogs, clonidine improves ventricular electrophysiologic parameters, but probably worsens bupivacaine-induced bradycardia and depression of the myocardial contractility. The current study, using a rodent animal model, evaluated the influence of clonidine pretreatment on the systemic toxic effects of bupivacaine overdose induced by a constant intravenous infusion.', 'Twenty Wistar male rats were anesthetized with thiopental, and controlled ventilation was started with an equal mixture of O2 and N2O. Electrocardiogram (ECG), electroencephalogram (EEG), and invasive arterial blood pressure were continuously recorded. Clonidine (5 micrograms/kg) or saline was injected intravenously in a randomized fashion. After 15 min, an intravenous infusion of bupivacaine was started at 2 mg.kg-1 x min-1. The time of occurrence of the bupivacaine-induced toxic events was recorded and the doses were calculated. Ten (five in each group) additional rats, pretreated according to the same protocol, were killed at the time of the first dysrhythmia, for blood sampling and plasma bupivacaine concentration measurement.', 'Clonidine reduced heart rate and arterial blood pressure before bupivacaine infusion (P < 0.05). The threshold doses at the first QRS modification (11.3 +/- 5.6 vs. 2.1 +/- 0.9 mg/kg) and the first dysrhythmia (40.6 +/- 15.3 vs. 8.48 +/- 3.7 mg/kg), the increase in EEG total spectral power (33.3 +/- 21.9 vs. 8.2 +/- 5.1 mg/kg), the 25 and 50% reduction in baseline mean arterial pressure and heart rate, the isoelectric EEG (58.6 +/- 14 vs. 22 +/- 6.6 mg/kg), and the final systole (99 +/- 16 vs. 51.8 +/- 14.5 mg/kg) were significantly greater in the clonidine group than in the saline group (P < 0.01). The time between the first dysrhythmia and 50% reduction of baseline mean arterial blood pressure was not different between the groups. In the additional series, the first dysrhythmia occurred later (10.9 +/- 4.5 vs. 3.2 +/- 1.0 min, P < 0.01) and plasma bupivacaine levels were greater (18.7 +/- 8.0 vs. 7.8 +/- 3.2 micrograms/ml, P < 0.01) in the clonidine group than in the saline group.
Answer: In this model, clonidine given prophylactically delays the toxic manifestations of bupivacaine overdose and does not accentuate the subsequent hypotension.

SOLUTION:
Does clonidine pretreatment reduce the systemic toxicity of intravenous bupivacaine in rats?