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: Aging is associated with reduced secretion of, and down-regulation of receptors for, progesterone (P); yet, P's effects when administered to younger and older animals have not been systematically investigated. Some of P's antianxiety effects may be due to its conversion to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) and its subsequent actions as a positive modulator at GABAA receptor complexes (GBRs).", 'We investigated whether P administration can decrease anxiety behavior of progestin receptor (PR) knockout (PRKO) or wild-type control mice.', 'P (10 mg/kg) or vehicle (propylene glycol) were administered subcutaneously to intact, female or male wild-type or PRKO mice that were either 9-12 or 18-24 months of age. Behavior in tasks that assess spontaneous activity (activity monitor and roto-rod), free exploration of a novel environment (open field, elevated plus maze, and elevated zero maze), and conflict behavior (mirror chamber, dark-light transition, and punished drinking) were examined 1 h after injection.', 'P significantly decreased anxiety behavior of both PRKO and wild-type mice. P did not alter motor behavior but increased central entries in the open field, time in the open quadrants of the elevated zero maze, time in the mirrored chamber, time in the light compartment of the dark-light transition, and punished drinking in young and old mice. P-administered mice had higher levels of hippocampal 3alpha,5alpha-THP and GABA-stimulated chloride flux than did vehicle-administered PRKO or wild-type mice.\Question: Do progesterone 's effects to reduce anxiety behavior of aged mice require actions via intracellular progestin receptors?

SOLUTION: The effects of P to decrease anxiety behavior of younger and older mice do not require classic PRs and may involve actions of 3alpha,5alpha-THP at GBRs.

PROBLEM: Context: Endothelial Microparticles (EMP) are small fragments of endothelial cell membrane shed during apoptosis or activation. Our group has previously reported elevations of EMP in patients with coronary artery disease (CAD), thrombotic thrombocytopenic purpura (TTP), pre-eclampsia, multiple sclerosis (MS), and severe hypertension (HTN). In the present study, we evaluate the possible relationship between EMP levels and the angiographic severity and characteristics of coronary obstructive lesions.', 'We studied a total of 43 patients undergoing coronary angiography. Fifteen had presented with acute myocardial infarction (MI), 20 with unstable anginas (UA), 5 with stable angina (SA) and 3 with congestive heart failure. Coronary angiography was reviewed and coronary lesions were classified using the Ambrose classification. Coronary stenoses were classified as high and low risk. High-risk included lesions with eccentric appearance (type II), presence of thrombi, or multiple irregularities. Low-risk lesions were defined as concentric or type I. Lesions were also analyzed by degree of stenosis and history of acute coronary syndrome (ACS). EMP in plasma was assayed by flow cytometry.', 'EMP in eccentric type II or multiple irregular lesions (high-risk) were 2.5-fold higher than in type I or concentric (low-risk) lesions, p<0.05. Lesions with thrombi had three-fold higher EMP than those without (p=0.05). Mild stenosis (>20%-<45%) had three-fold higher EMP than more severe (>45%), and five-fold higher than those without stenosis (p<0.01). Among patients with type II lesions, those with first ACS episode had four-fold higher EMP levels than those with recurrent ACS (p<0.01).\Question: Do endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes?

SOLUTION: High EMP was associated with high-risk angiographic lesions including eccentric type II, multiple irregular, and lesions with thrombi. Mild to moderate stenosis was associated with higher EMP levels than severe stenosis. EMP may be a useful marker in detecting endothelial injury and risk of ACS as defined by angiography.

PROBLEM: Context: Several case-control studies examined an association between schizophrenia and the 40-bp variable number tandem repeat (VTNR) polymorphism in the 3'-UTR of the dopamine transporter gene (SLC6A3). The results of these studies have been equivocal due to small sample size and low power. This meta-analysis has the aim to evaluate the collective evidence for an association between the VTNR polymorphism and schizophrenia.", 'Different meta-analyses were performed, sequentially considering the 9- and 10-repeat alleles and different genotypes (genotypes 9/9, 9/10, 10/10) as risk factors for schizophrenia. Analyses of the alleles included 659 cases and 563 controls from six case-control studies.', 'The pooled OR from each analysis approximated 1.0, and none were significant. Lack of significance attributable to the negative effects of single large studies or to heterogeneity between the studies was excluded.\Question: Does meta-analysis show schizophrenia is not associated with the 40-base-pair repeat polymorphism of the dopamine transporter gene?

SOLUTION:
Despite over 90% power to detect a significant odds ratio as small as 1.3, no association was observed. Considering the cumulative evidence from six case-control studies and results from additional family-based studies, it seems unlikely that the 40-base-pair VTNR polymorphism of the SLC6A3 gene influences risk for schizophrenia.