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.

Q: Context: Chronic stress is generally known to exacerbate the development of numerous neuropsychiatric diseases such as fear and anxiety disorders, which is at least partially due to the disinhibition of amygdala subsequent to the prolonged stress exposure. GABA receptor A (GABAAR) mediates the primary component of inhibition in brain and its activation produces two forms of inhibition: the phasic and tonic inhibition. While both of them are critically engaged in limiting the activity of amygdala, their roles in the amygdala disinhibition subsequent to chronic stress exposure are largely unknown.', 'We investigated the possible alterations of phasic and tonic GABAAR currents and their roles in the amygdala disinhibition subsequent to chronic stress. We found that both chronic immobilization and unpredictable stress led to long lasting loss of tonic GABAAR currents in the projection neurons of lateral amygdala. By contrast, the phasic GABAAR currents, as measured by the spontaneous inhibitory postsynaptic currents, were virtually unaltered. The loss of tonic inhibition varied with the duration of daily stress and the total days of stress exposure. It was prevented by pretreatment with metyrapone to block corticosterone synthesis or RU 38486, a glucocorticoid receptor antagonist, suggesting the critical involvement of glucocorticoid receptor activation. Moreover, chronic treatment with corticosterone mimicked the effect of chronic stress and reduced the tonic inhibition in lateral amygdala of control mice. The loss of tonic inhibition resulted in the impaired GABAergic gating on neuronal excitability in amygdala, which was prevented by metyrapone pretreatment.
Answer: Our study suggests that enduring loss of tonic but not phasic GABAAR currents critically contributes to the prolonged amygdala disinhibition subsequent to chronic stress. We propose that the preferential loss of tonic inhibition may account for the development of stress-related neuropsychiatric diseases.

A: Does chronic stress impair GABAergic control of amygdala through suppressing the tonic GABAA receptor currents?
****
Q: Context: The present study was undertaken to determine whether exposure of the sclera to prostaglandin (PG)F(2alpha) or to the PGF(2alpha) analogue latanoprost acid alters mRNA for matrix metalloproteinases.', 'Fifteen human eye bank eyes were studied. Circular pieces of sclera were either immediately preserved in a stabilization reagent or cultured in low-serum DMEM/F-12 medium. The cultures were treated for 24 hours with medium supplemented with PGF(2a), latanoprost acid, or vehicle. Total RNA was then isolated, and the expression of mRNA for matrix metalloproteinase (MMP)-1, -2, -3, -8, -9, -10, and -12 were determined by real-time PCR. All results were normalized according to the GAPDH mRNA in each sample. Altered mRNA expression after PG treatments also was evaluated with microarrays containing 19 MMP genes and 4 tissue inhibitor of matrix metalloproteinase (TIMP) genes.', 'Real-time PCR results showed that 24 hours of exposure to 100 nM PGF(2alpha) significantly increased mRNA for MMP-1 and -9 (P < 0.06 Wilcoxon test) and that exposure to 100 nM latanoprost acid significantly increased mRNA for MMP-9 (P < 0.06 Wilcoxon test). Array analysis demonstrated increases of MMP-3 and -10 mRNA after exposure to 100 nM latanoprost and further increases after exposure to 200 nM latanoprost. The array results also showed that latanoprost induced dose-dependent increases in the expression of TIMP-1, -2, and -3 mRNA in the scleral cultures.
Answer: PGF(2alpha) and latanoprost acid induce coordinated alterations of MMP gene transcription in scleral organ cultures. These results indicate that PGs can directly trigger MMP gene transcription changes within the sclera. These changes support a role for increased MMPs in the enhancement of uveoscleral outflow that occurs after topical treatment with latanoprost.

A: Do prostaglandin FP agonists alter metalloproteinase gene expression in sclera?
****
Q: Context: Hemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients.', 'We conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann–Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support.', "Median CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p = 0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p < 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02–1.19, p = 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22–1.38, p < 0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p < 0.001) that remained significant in a propensity score-adjusted model.
Answer: In critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as paracetamol, to mitigate the effects of shock and end-organ dysfunction.

A:
Is elevated serum creatine phosphokinase associated with mortality and inotropic requirement in critically injured adults?
****