Given a passage with a context and an answer, 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: Context: Kisspeptin and naloxone stimulate the reproductive axis while morphine inhibits its function. We have investigated the effect of central injection of kisspeptin-10 on mean plasma testosterone concentration in morphine or naloxone pretreated rats.', 'In this experimental study, 60 male Wistar rats that were divid- ed into 12 groups (n=5 per group) received saline, kisspeptin (1 nmol, ICV), naloxone (2 mg/kg, subcutaneously), morphine (5 or 10 mg/kg, sc) or co-administrations of kisspeptin, morphine and naloxone at 09:00 - 09:30. In the co-administrated groups, kisspeptin was injected 15 minutes following morphine or naloxone injections. Blood samples were collected 60 minutes following injections via the tail vein. Plasma testosterone concentration was measured by a rat testosterone ELISA kit.', 'Central injection of kisspeptin or subcutaneous injection of naloxone significantly increased the mean plasma testosterone concentration compared to saline while subcutaneous injections of different doses of morphine (5 or 10 mg/kg) significantly decreased testosterone compared to saline. The results revealed that morphine significantly attenuated the testosterone increase after kisspeptin injection compared to kisspeptin while a stimulatory additive effect was observed in the kisspeptin/naloxone group compared to either naloxone or kisspeptin.
Answer: Morphine and kisspeptin systems may interact with each other to control the hypothalamic-pituitary-gonadal (HPG) axis.

A: Does morphine attenuate testosterone response to central injection of kisspeptin in male rats?
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Q: Context: To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA).', "We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with ≥1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models.", 'Of 113\u2005677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6\u2005months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6\u2005months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged ≥50\u2005years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3\u2005years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively.
Answer: Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.

A: Are longer durations of antitumour necrosis factor treatment associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis?
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Q: Context: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD).', 'Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The association between SNPs and susceptibility to IPD and IMD, mortality and pneumococcal serotypes was investigated.', '372 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were included. We included 406 cases with meningococcal meningitis, 272 with meningococcal bacteremia, and 672 controls. The NFKBIE SNP was associated with increased risk of pneumococcal meningitis (aOR 1.68; 95% CI: 1.20-2.36), but not bacteremia (aOR 1.08; 95% CI: 0.86-1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality.
Answer: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis.

A:
Does genetic Variation in NFKBIE be Associated With Increased Risk of Pneumococcal Meningitis in Children?
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