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: Abnormalities of serum sodium are common after subarachnoid hemorrhage (SAH) and have been linked to poor outcome. This study analyzed whether abnormal serum sodium levels are associated with cardiac outcomes and mortality after subarachnoid hemorrhage (SAH).', "In a prospective cohort study of SAH patients, the primary predictor variable was subjects' sodium level. Hypernatremia was defined as sodium >143 mmol/L and hyponatremia was <133 mmol/L. Cardiac troponin I (cTi) was measured and echocardiography was performed on three study days. Dichotomous outcome variables were cTi > 1.0 microg/L, left-ventricular ejection fraction (LVEF) <50%, presence (vs absence) of regional wall motion abnormalities (RWMA) of the LV, pulmonary edema, and death. Additional analyses studied the degree of hypernatremia and sodium supplementation, and the temporal relationship between hypernatremia and cardiac outcomes.", 'The study included 214 subjects. Forty-eight subjects (22%) were hypernatremic on at least one study day, and 45 (21%) were hyponatremic. After multivariate adjustment, hypernatremia was an independent predictor of LVEF <50% (OR 4.7, CI 1.3-16.2, p = 0.015), elevated cTi (OR 3.7, CI 1.2-11.9, p = 0.028), and pulmonary edema (OR 4.1 CI 1.4-1.5, p = 0.008). It was not, however a statistically significant predictor of mortality (p = 0.075).\Question: Does hypernatremia predict adverse cardiovascular and neurological outcomes after SAH?

SOLUTION: In the acute period after SAH, hypernatremia is associated with adverse cardiac outcomes and death. SAH patients with hypernatremia should be monitored for evidence of cardiac dysfunction.

PROBLEM: Context: Protein kinase D (PKD or PKD1) is a serine/threonine protein kinase that has been shown to play a role in a variety of cellular processes; however, the function of PKD1 in the skin has not been fully investigated. The balance between proliferation and differentiation processes in the predominant cells of the epidermis, the keratinocytes, is essential for normal skin function.', 'To investigate the effect of PKD1 deficiency on proliferation and differentiation of epidermal keratinocytes.', 'We utilized a floxed PKD1 mouse model such that infecting epidermal keratinocytes derived from these mice with an adenovirus expressing Cre-recombinase allowed us to determine the effect of PKD1 gene loss in vitro. Proliferation and differentiation were monitored using qRT-PCR, Western blot, transglutaminase activity assays, [3H]thymidine incorporation into DNA and cell cycle analysis.', 'A significant decrease in PKD1 mRNA and protein levels was achieved in adenoviral Cre-recombinase-infected cells. Deficiency of PKD1 resulted in significant increases in the mRNA and protein expression of various differentiation markers such as loricrin, involucrin, and keratin 10 either basally and/or upon stimulation of differentiation. PKD1-deficient keratinocytes also showed an increase in transglutaminase expression and activity, indicating an anti-differentiative role of PKD1. Furthermore, the PKD1-deficient keratinocytes exhibited decreased proliferation. However, PKD1 loss had no effect on stem cell marker expression.\Question: Does protein kinase D1 deficiency promote differentiation in epidermal keratinocytes?

SOLUTION: Cre-recombinase-mediated knockdown represents an additional approach demonstrating that PKD1 is an anti-differentiative, pro-proliferative signal in mouse keratinocytes.

PROBLEM: Context: Proliferative vitreoretinopathy (PVR) is a blinding disorder that develops after a retinal tear or detachment. Activation of the retinal pigmented epithelium (RPE) is implicated in PVR; however, the mechanisms leading to enhanced RPE proliferation, migration, and contraction remain largely unknown. This study utilized an in vitro model of PVR to investigate the role of acetylation in RPE activation and its contribution to the progression of this disease.', 'ARPE-19 cells, primary cultures of porcine RPE, and induced pluripotent stem cell-derived RPE (iPS-RPE) were utilized for cellular and molecular analyses. Cells treated with transforming growth factor beta 2 (TGF2; 10ng/mL) alone or in the presence of the broad-spectrum histone deacetylase (HDAC) inhibitor, trichostatin A (TSA; 0.1M), were assessed for contraction and migration through collagen contraction and scratch assays, respectively. Western blotting and immunofluorescence analysis were performed to assess -smooth muscle actin (-SMA) and -catenin expression after TGF2 treatment alone or in combination with TSA.', 'TGF2 significantly increased RPE cell contraction in collagen matrix and this effect was inhibited in the presence of TSA (0.1M). In agreement with these data, immunofluorescence analysis of TSA-treated iPS-RPE wounded monolayers revealed decreased -SMA as compared with control. Scratch assays to assess wound healing revealed TSA inhibited TGF2-mediated iPS-RPE cell migration.\Question: Does trichostatin A inhibit Retinal Pigmented Epithelium Activation in an In Vitro Model of Proliferative Vitreoretinopathy?

SOLUTION:
Our findings indicate a role of acetylation in RPE activation. Specifically, the HDAC inhibitor TSA decreased RPE cell proliferation and TGF2-mediated cell contraction and migration. Further investigation of pharmacological compounds that modulate acetylation may hold promise as therapeutic agents for PVR.