Given a passage, 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]: We recently proposed the existence of neurotoxic interactions between the cannabinoid type 1 (CB(1)) receptor and transient receptor potential vanilloid 1 (TRPV1) channels in rat mesencephalic cultures. This study seeks evidence for the mediator(s) and mechanisms underlying the neurotoxic interactions between CB(1) receptors and TRPV1 in vitro and in vivo.', 'The mediator(s) and mechanism(s) for the interactions between CB(1) receptors and TRPV1 were evaluated by cell viability assays, immunocytochemistry, Fura-2 calcium imaging, mitochondrial morphology assay, ELISA and Western blot assay in vitro in neuron-enriched mesencephalic cultures. Injections into the substantia nigra and subsequent cell counts were also used to confirm these interactions in vivo.', 'The neurotoxic interactions were mediated by 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), an endogenous TRPV1 agonist. CB(1) receptor agonists (HU210 and WIN55,212-2) increased the level of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a downstream metabolite of 12(S)-HPETE, which stimulates TRPV1-mediated death of mesencephalic neurons, both in vitro and in vivo. The neurotoxicity was mediated by increased intracellular Ca(2+) concentration ([Ca(2+)](i)) through TRPV1, consequently leading to mitochondrial damage and was attenuated by baicalein, a 12-lipoxygenase inhibitor.
[A]: Are interactions between CB ( 1 ) receptors and TRPV1 channels mediated by 12-HPETE cytotoxic to mesencephalic dopaminergic neurons?


[Q]: Patients with diabetes are at greater risk of cardiovascular events. Insulin resistance (IR) and hyperinsulinaemia are both related to an increased cardiovascular risk, but whether IR predicts coronary heart disease (CHD) independently of other risk factors in patients with type 2 diabetes (T2D) is a topic of considerable controversy. The aim of the present study was to evaluate the prospective relationship of fasting insulin, HOMA-IR, fasting plasma glucose (FPG) and 2-h post-load glucose (2hPG) load with CHD incidence among such patients.', 'A total of 2607 patients with T2D were enrolled in a community-dwelling cohort and followed for an average of 7.2 years. Conventional CHD risk factors, FPG, 2hPG, fasting insulin levels and HOMA-IR index were measured at baseline. Cox regression hazard ratios (HRs) were used to assess CHD risk.', "A total of 299 'hard' CHD events were registered (in 114 women and 185 men). Increasing levels of fasting insulinaemia were positively associated with CHD incidence. This correlation persisted after controlling for gender, body mass index, blood pressure, lipid profile, medication use and HbA1c [HR for each increase in quartile (fully adjusted model): 1.18 (95% CI: 1.06-1.32); P<0.01]. 2hPG showed a non-linear association with incident CHD [HR of highest vs lowest quartile: 1.64 (95% CI: 1.03-2.61)]. Fasting glycaemia was not associated with CHD risk, whereas HOMA-IR had a direct and independent correlation with CHD risk [HR for each one-quartile increase: 1.19 (95% CI: 1.07-1.34); P<0.01].
[A]: Do fasting hyperinsulinaemia and 2-h glycaemia predict coronary heart disease in patients with type 2 diabetes?


[Q]: The aim was to review different approaches for the derivation of threshold values and to discuss their strengths and limitations in the context of minimum provider volumes.', "The following methods for the calculation of threshold values are compared and discussed: The value of acceptable risk limit, the value of acceptable risk gradient, the benchmark value proposed by Budtz-Jørgensen and Ulm's breakpoint model. The latter is extended to account for two different breakpoints. The methods are applied to German quality assurance data concerning total knee replacement.", 'The discussed methods for calculating threshold values differ in the kind of information that has to be specified beforehand. For the value of acceptable risk limit approach an absolute number, the acceptable risk, has to be predetermined. The value of acceptable risk gradient approach and the method of Budtz-Jørgensen require the specification of a relative change expressed in gradient and in odds, respectively. On the other hand, the threshold value according to the method of Ulm is defined as a parameter of a statistical model and no a priori specification is required.
[A]:
Are flexible regression models useful tools to calculate and assess threshold values in the context of minimum provider volumes?