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: Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated.', 'We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies.
Answer: These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

SOLUTION: Are cognitive-behavioral phenotypes of Williams syndrome associated with genetic variation in the GTF2I gene , in a healthy population?

PROBLEM: Context: Preconditioning neurons with noninjurious hypoxia (hypoxic preconditioning, HPC) or the anesthetic isoflurane (APC) induces tolerance of severe ischemic stress. The mechanisms of both types of preconditioning in the hippocampus require moderate increases in intracellular Ca and activation of protein kinase signaling. The authors hypothesized that the expression of signal transduction genes would be similar after APC and HPC.', 'Hippocampal slice cultures prepared from 9-day-old rats were preconditioned with hypoxia (5 min of 95% nitrogen/5% carbon dioxide) or 1% isoflurane in air/5% carbon dioxide for 1 h. A day later, cultures were subjected to 10 min oxygen and glucose deprivation (simulated ischemia). Intracellular Ca, measured in CA1 neurons at the completion of preconditioning, and cell death in CA1, CA3, and dentate regions was assessed 48 h after simulated ischemia. Message RNA encoding 119 signal transduction genes was quantified with rat complimentary DNA microarrays from pre-oxygen-glucose deprivation samples.', 'Both APC and HPC increased intracellular Ca approximately 50 nm and decreased CA1, CA3, and dentate neuron death by about 50% after simulated ischemia. Many signaling genes were increased after preconditioning, with hypoxia increasing more apoptosis/survival genes (8 of 10) than isoflurane (0 of 10). In contrast, isoflurane increased more cell cycle/development/growth genes than did hypoxia (8 of 14 genes, vs. 1 of 14).
Answer: Despite sharing similar upstream signaling and neuroprotective outcomes, the genomic response to APC and HPC is different. Increased expression of antiapoptosis genes after HPC and cell development genes after APC has implications both for neuroprotection and long-term effects of anesthetics.

SOLUTION: Does expression of signal transduction genes differ after hypoxic or isoflurane preconditioning of rat hippocampal slice cultures?

PROBLEM: Context: Depression predicts prognosis in many cardiac conditions, including congestive heart failure (CHF). Despite heightened cardiac risk in patients with comorbid atrial fibrillation (AF) and CHF, depression has not been studied in this group. This substudy, from the AF-CHF Trial of rate- versus rhythm-control strategies, investigated whether depression predicts long-term cardiovascular mortality in patients with left ventricular ejection fraction <or=35%, CHF symptoms, and AF history who receive optimal medical care.', 'Depression symptoms (Beck Depression Inventory-II) were assessed in 974 participants (833 men), with 32.0% showing elevated scores (Beck Depression Inventory-II >or=14). Over a mean follow-up of 39 months, there were 246 cardiovascular deaths (111 presumed arrhythmic; 302 all-cause deaths). Cox proportional hazards models adjusted for other prognostic factors (including age, marital status, cause of CHF, creatinine level, left ventricular ejection fraction, paroxysmal AF, previous AF hospitalization, previous electrical conversion, and baseline medications) showed that elevated depression scores significantly predicted cardiovascular mortality (primary outcome), arrhythmic death, and all-cause mortality. The adjusted hazard ratios were 1.57 (95% confidence interval 1.20 to 2.07, P<0.001), 1.69 (95% confidence interval 1.13 to 2.53, P=0.01), and 1.38 (95% confidence interval 1.07 to 1.77, P=0.01), respectively. The risks associated with depression and marital status were additive, with the highest risk in depressed patients who were unmarried.
Answer: Elevated depression symptoms are related to cardiovascular mortality even after adjustment for other prognostic indicators in patients with comorbid AF and CHF who receive optimized treatment. Unmarried patients are also at increased risk. Mechanisms and treatment options deserve additional study.

SOLUTION:
Do elevated depression symptoms predict long-term cardiovascular mortality in patients with atrial fibrillation and heart failure?