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.

Input: Consider Input: Context: Transport across the blood-brain barrier (BBB) is an important mediator of beta-amyloid (A) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors responsible for the transport of A in the BBB is the low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at the cell surface, which prevents endocytic transport of ligands. Previously, we reported a strong inverse correlation between LRP1 shedding in the brain and A transit across the BBB. Several proteases contribute to the ectodomain shedding of LRP1 including the -secretase, a desintegrin and metalloproteinase domain containing protein 10 (ADAM10).", 'The role of ADAM10 in the shedding of LRP1 and A BBB clearance was assessed through pharmacological inhibition of ADAM10 in an in vitro model of the BBB and through the use of ADAM10 endothelial specific knock-out mice. In addition, an acute treatment paradigm with an ADAM10 inhibitor was also tested in an AD mouse model to assess the effect of ADAM10 inhibition on LRP1 shedding and Abrain accumulation.', 'In the current studies, inhibition of ADAM10 reduced LRP1 shedding in brain endothelial cultures and increased A42 transit across an in vitro model of the BBB. Similarly, transgenic ADAM10 endothelial knockout mice displayed lower LRP1 shedding in the brain and significantly enhanced A clearance across the BBB compared to wild-type animals. Acute treatment with the ADAM10-selective inhibitor GI254023X in an AD mouse model substantially reduced brain LRP1 shedding and increased A40 levels in the plasma, indicating enhanced A transit from the brain to the periphery. Furthermore, both soluble and insoluble A40 and A42 brain levels were decreased following GI254023X treatment, but these effects lacked statistical significance.\Question: Does inhibition of ADAM10 promote the clearance of A across the BBB by reducing LRP1 ectodomain shedding?

Output: These studies demonstrate a role for ADAM10 in the ectodomain shedding of LRP1 in the brain and the clearance of A across the BBB, which may provide a novel strategy for attenuating A accumulation in the AD brain.

Input: Consider Input: Context: Recent studies have implicated central nicotinic cholinergic receptor systems in the reinforcing properties of alcohol. In laboratory animals, mecamylamine, a central nicotinic receptor antagonist, reduces the consumption of and preference for alcohol. This study investigated the effect of mecamylamine on the subjective responses to alcohol in humans. It was hypothesized that mecamylamine (7.5 and 15 mg) would attenuate the stimulant-like subjective effects of alcohol (0.8 g/kg) and decrease the self-reported desire to consume additional alcohol beverages.', 'Fourteen male and 13 female nonsmokers participated in 6 laboratory sessions. During each session, subjects received, in randomized order under double-blinded conditions, a capsule containing mecamylamine (7.5 or 15 mg) or placebo followed by a beverage containing alcohol (0.8 g/kg) or placebo. Physiologic and subjective-effect measures were taken at 30-min intervals for 2 hr after beverage consumption.', 'Mecamylamine attenuated the stimulant and euphoric effects of alcohol and reduced the self-reported desire to consume additional alcohol beverages. This effect was most pronounced in men, even though women exhibited greater physiologic reactions to mecamylamine.\Question: Does mecamylamine attenuate the subjective stimulant-like effects of alcohol in social drinkers?

Output: These findings suggest that nicotinic cholinergic receptors are involved in mediating some of the stimulant-like effects of alcohol.

Input: Consider Input: Context: Palliative sedation therapy (PST) is indicated for and used to control refractory symptoms in cancer patients undergoing palliative care. We aimed to evaluate whether PST has a detrimental effect on survival in terminally ill patients.', 'This multicenter, observational, prospective, nonrandomized population-based study evaluated overall survival in two cohorts of hospice patients, one submitted to palliative sedation (A) and the other managed as per routine hospice practice (B). Cohorts were matched for age class, gender, reason for hospice admission, and Karnofsky performance status.', 'Of the 518 patients enrolled, 267 formed cohort A and 251 cohort B. In total, 25.1% of patients admitted to the participating hospices received PST. Mean and median duration of sedation was 4 (standard deviation 6.0) and 2 days (range 0-43), respectively. Median survival of arm A was 12 days [90% confidence interval (CI) 10-14], while that of arm B was 9 days (90% CI 8-10) (log rank = 0.95, P = 0.330) (unadjusted hazard ratio = 0.92, 90% CI 0.80-1.06).\Question: Does palliative sedation therapy hasten death : results from a prospective multicenter study?
Output: PST does not shorten life when used to relieve refractory symptoms and does not need the doctrine of double effect to justify its use from an ethical point of view.