Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Depression is the most common psychiatric comorbidity in epilepsy patients. The lack of success with current pharmacological interventions for this patient population, highlights the importance of optimizing non-pharmacological neuromodulatory treatments such as vagus nerve stimulation (VNS). Studies on the antidepressant effect of VNS in epilepsy patients may be confounded by concurrent anti-epileptic drug therapy. To date, studies in epilepsy models overcoming this problem are lacking.', 'We investigated whether VNS affects anhedonia, a key symptom of major depression, in the kainic acid rat model for temporal lobe epilepsy.', 'Anhedonia was assessed in kainic acid (KA) and saline (SAL) injected rats using the saccharin preference test (SPT). To exclude differences in taste perception, the quinine aversion test (QAT) was performed. Both groups were randomly subdivided in a VNS and a SHAM group, yielding 4 experimental arms: KA-VNS, KA-SHAM, SAL-VNS and SAL-SHAM. Both VNS groups received 2 weeks of VNS, while the SHAM groups were not stimulated. Thereafter, the SPT and QAT were repeated.', 'Saccharin preference was significantly reduced in the KA compared to the SAL rats (P\xa0<\xa00.05), without differences in quinine aversion. Two weeks of VNS significantly increased the saccharin preference in the KA-VNS group (P\xa0<\xa00.05), while it had no effect on quinine aversion. No effects of VNS or SHAM were found in the other groups.
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The tumor necrosis factor (TNF) gene is located within the highly polymorphic major histocompatibility complex region, exhibiting the -308 GA promoter region polymorphism and six microsatellites (TNFa-f) spanning the region nearby the TNF locus.', 'In the present study, we evaluated the frequency of -308 GA and TNFa-e polymorphisms and respective haplotypes (in chromosomal sequence: TNFd-TNFe-308GA-TNFc-TNFa-TNFb), in 222 patients with AIDS, 52 of whom exhibited cytomegalovirus retinitis, and in 202 healthy HIV-negative individuals.', 'TNF microsatellite and single nucleotide polymorphism typings were performed by PCR followed by polyacrylamide gel electrophoresis.', 'The TNF-308A allele and the 4-3-G-2-7-1 haplotype were associated with susceptibility to AIDS, whereas the TNFb4 allele and the 3-3-G-1-11-4 haplotype were associated with protection against AIDS development. The TNFc2 allele and the 4-1-G-2-2-1 haplotype, which contains the TNFc2 allele, were associated with cytomegalovirus retinitis.
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Glucocorticoids (GCs), including the synthetic GC derivate dexamethasone, are widely used as immunomodulators. One of the numerous side effects of dexamethasone therapy is hypertension arising from reduced release of the endothelium-derived vasodilator nitric oxide (NO).', 'Herein, we described the role of dexamethasone and its glucocorticoid receptor (GR) in the regulation of NO synthesis in vitro using the mouse myocardial microvascular endothelial cell line, MyEND. GC treatment caused a firm decrease of extracellular NO levels, whereas the expression of endothelial NO synthase (eNOS) was not affected. However, GC application induced an impairment of tetrahydrobiopterin (BH4 ) concentrations as well as GTP cyclohydrolase-1 (GTPCH-1) expression, both essential factors for NO production upstream of eNOS. Moreover, dexamethasone stimulation resulted in a substantially decreased GR gene and protein expression in MyEND cells. Importantly, inhibition of proteasome-mediated proteolysis of the GR or overexpression of an ubiquitination-defective GR construct improved the bioavailability of BH4 and strengthened GTPCH-1 expression and eNOS activity.

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