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.
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Question: In chronic pain, increased activity from intact or damaged peripheral nerve endings results in an enhanced response in central pain transmission systems, a mechanism known as central sensitization. Central sensitization can also be invoked in human experimental models. Therefore, these models may be useful to characterize novel analgesics in humans. The anticonvulsant gabapentin has demonstrated efficacy in patients with neuropathic pain, but its mode of action remains unclear. This study examined the effects of gabapentin on signs of central sensitization (brush and pinprick hyperalgesia) in a human model of capsaicin-evoked pain, using a gabapentin dosing regimen similar to that used in the clinic. The aims were to determine whether gabapentin, dosed in a manner similar to that used in the clinic, affected the various components of central sensitization and to assess the utility of this model for characterizing novel analgesics.', 'Intradermal capsaicin (100 microg/20 microl) was administered in the volar forearm of 41 male human volunteers to induce pain and clinical signs of central sensitization. Gabapentin (titrated to 2,400 mg daily) or placebo was given orally for 15 days in a randomized, double-blind, parallel-group design. The capsaicin test was conducted at baseline and after gabapentin or placebo. Endpoints were the size of areas of brush-evoked allodynia (with cotton gauze) and pinprick hyperalgesia (with von Frey filament), and the intensity of ongoing brush- and pinprick-evoked pain.', 'Gabapentin significantly reduced the area of brush allodynia compared with placebo (P </= 0.05) and insignificantly attenuated the area of pinprick hyperalgesia. Gabapentin had no significant effect on spontaneous and evoked pain intensity.

Answer: Does chronic oral gabapentin reduce elements of central sensitization in human experimental hyperalgesia?


Question: The major immuno-modulating effects of Ganoderma lucidum include mitogenicity and activation of immune effector cells such as T cells, macrophages and natural killer cells resulting in the production of cytokines.', 'The purpose of this study was to evaluate the expression of CD40 and CD80 by G. lucidum-treated human peripheral blood mononuclear cells.', 'Monocytes were isolated and incubated at 37 C and 5% CO2 for 24 h and 48 h in the presence or absence of different concentrations of G. lucidum. Cells were then incubated with labelled monoclonal antibodies against CD14, CD40 and B7-1(CD80) molecules utilizing standard protocols, and analyzed by flow cytometry.', 'The results showed that incubation of monocytes with G. lucidum led to marked enhancement of CD40 and B7-1 expression in a dose- and time- dependent manner (p<0.001). G. lucidum was more effective in enhancing the expression of CD80 and CD40 molecules of cells obtained from females than male donors (p<0.001).

Answer: Does ganoderma lucidum induce the expression of CD40/CD86 on peripheral blood monocytes?


Question: Aging and chronic alcohol consumption are both modifiers of DNA methylation, but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression.', 'Old (18\xa0months) and young (4\xa0months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloric Lieber-DeCarli control diet for 5\xa0weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new liquid chromatography-tandem mass spectrometry method. Hepatic mRNA expression of the Tet enzymes were measured via quantitative real-time polymerase chain reaction.', 'In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22\xa0±\xa00.01 vs. 0.29\xa0±\xa00.06%, p\xa0=\xa00.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24\xa0±\xa00.02 vs. 0.29\xa0±\xa00.06%, p\xa0=\xa00.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction \xa0=\xa00.009). Expression of Tet2 and Tet3 was decreased in the old mice relative to the young (p\xa0<\xa00.005).

Answer:
Do aging and alcohol interact to alter hepatic DNA hydroxymethylation?