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: The measurement of affective symptoms in older persons who decline cognitively is uncertain. The authors investigated whether mood variability predicts dementia in patients with age-related macular degeneration (AMD).', 'Three-year observational study after a clinical trial.', 'Community follow-up of outpatients ascertained from retina clinics.', 'One hundred sixty patients with AMD.', "Geriatric Depression Scale (GDS) administered every 2 weeks for 6 months to subjects; Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to subjects' knowledgeable informants.", 'Twenty-three subjects (14.4%) declined cognitively. Age, education, baseline GDS score > or =5, and variability in GDS scores (i.e., fluctuations between adjacent time points) were associated with cognitive decline. For GDS variability, each 1 unit increase in the residual standard deviation (SD) of the GDS increased the risk for cognitive decline by 93% (IDR = 1.92; 95% CI [1.27-2.91]). Thus, subjects with a residual SD of 1 were nearly twice as likely to become demented as subjects with no variability in GDS scores. The risk for subjects with SDs of 2 increased more than threefold (IDR = 3.68; 95% CI [1.61-8.47]). A multiple regression analysis showed that GDS variability was a significant risk factor for dementia after controlling for significant covariates.\Question: Does variability in depressive symptoms predict cognitive decline in age-related macular degeneration?

SOLUTION: These data suggest a useful approach to conceptualizing and measuring depressive symptoms in older persons. Variability in self-reported mood may be an early sign of dementia and may offer new insights into the neurobiological mechanisms linking depression and cognition

PROBLEM: Context: Hypercontracture is an important mechanism of myocyte death during reperfusion. cGMP modulates the sensitivity of contractile myofilaments to Ca2+, and increasing cGMP concentration during the last minutes of anoxia prevents reoxygenation-induced hypercontracture in isolated cardiomyocytes. The purpose of this study was to determine whether stimulation of particulate guanylyl cyclase with the natriuretic peptide urodilatin, given at the time of reperfusion, reduces myocardial necrosis in the rat heart submitted to transient ischemia.', 'Isolated rat hearts (n = 38) were submitted to either 40 or 60 min of no-flow ischemia and 2 h of reperfusion, and were allocated to receive or not receive 0.05 microM urodilatin during the first 15 min of reperfusion or non-reperfusion treatment.', 'A marked reduction in myocardial cGMP concentration was observed in control hearts during reperfusion after 40 or 60 min of ischemia. Urodilatin significantly attenuated cGMP depletion during initial reperfusion, markedly improved contractile recovery after 40 min of ischemia (P < 0.0309), and reduced reperfusion-induced increase in left ventricular end-diastolic pressure (P = 0.0139), LDH release (P = 0.0263), and contraction band necrosis (P = 0.0179) after 60 min of ischemia. The beneficial effect of urodilatin was reproduced by the membrane permeable cGMP analog 8-Bromo-cGMP.\Question: Does urodilatin limit acute reperfusion injury in the isolated rat heart?

SOLUTION: These results indicate that reduced cGMP concentration may impair myocyte survival during reperfusion. Stimulation of particulate guanylyl cyclase may appear as a new strategy to prevent immediate lethal reperfusion injury.

PROBLEM: Context: Central nervous system (CNS) trauma and neurodegenerative disorders trigger a cascade of cellular and molecular events resulting in neuronal apoptosis and regenerative failure. The pathogenic mechanisms and gene expression changes associated with these detrimental events can be effectively studied using a rodent optic nerve crush (ONC) model. The purpose of this study was to use a mouse ONC model to: (a) evaluate changes in retina and optic nerve (ON) gene expression, (b) identify neurodegenerative pathogenic pathways and (c) discover potential new therapeutic targets.', 'Only 54% of total neurons survived in the ganglion cell layer (GCL) 28 days post crush. Using Bayesian Estimation of Temporal Regulation (BETR) gene expression analysis, we identified significantly altered expression of 1,723 and 2,110 genes in the retina and ON, respectively. Meta-analysis of altered gene expression (≥1.5, ≤-1.5, p\u2009<\u20090.05) using Partek and DAVID demonstrated 28 up and 20 down-regulated retinal gene clusters and 57 up and 41 down-regulated optic nerve clusters. Regulated gene clusters included regenerative change, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. Expression of selected genes (Vsnl1, Syt1, Synpr and Nrn1) from retinal and ON neuronal clusters were quantitatively and qualitatively examined for their relation to axonal neurodegeneration by immunohistochemistry and qRT-PCR.\Question: Does optic nerve crush induce spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice?

SOLUTION:
A number of detrimental gene expression changes occur that contribute to trauma-induced neurodegeneration after injury to ON axons. Nrn1 (synaptic plasticity gene), Synpr and Syt1 (synaptic vesicle fusion genes), and Vsnl1 (neuron differentiation associated gene) were a few of the potentially unique genes identified that were down-regulated spatially and temporally in our rodent ONC model. Bioinformatic meta-analysis identified significant tissue-specific and time-dependent gene clusters associated with regenerative changes, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. These ONC induced neuronal loss and regenerative failure associated clusters can be extrapolated to changes occurring in other forms of CNS trauma or in clinical neurodegenerative pathological settings. In conclusion, this study identified potential therapeutic targets to address two key mechanisms of CNS trauma and neurodegeneration: neuronal loss and regenerative failure.