instruction:
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.
question:
Context: To simultaneously study the effect of a selective cyclooxygenase-2 (COX-2) inhibitor and that of a classic non-steroidal anti-inflammatory drug (NSAID) on the expression of pro-inflammatory genes in the cartilage of patients with severe knee osteoarthritis (OA) and in cultured human OA chondrocytes.', 'A 3-month clinical trial was carried out on 30 patients with severe knee OA scheduled for knee replacement surgery. Patients were randomized into two groups: patients treated with celecoxib (CBX) and patients treated with aceclofenac (ACF). OA patients who did not want to be treated served as the control group. After surgery, cartilage was processed for molecular biology studies. We also employed cultured chondrocytes from different OA patients to examine NSAID effects on pro-inflammatory gene expression in cells stimulated with interleukin (IL)-1beta.', 'Both CBX and ACF inhibited COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and inducible nitric oxide synthase (iNOS) synthesis in the articular cartilage of OA patients. In cultured chondrocytes, both NSAID decreased COX-2 and mPGES-1 synthesis and prostaglandin E2 (PGE2) release induced by IL-1beta, while no effect was observed on nitric oxide or iNOS synthesis. In OA patients, only CBX decreased tumor necrosis factor alpha and IL-1beta expression in the cartilage, while both NSAID diminished IL-1beta induced cytokine synthesis in cultured OA chondrocytes.
Answer: Both NSAID diminished PGE2 release and induced a decrease in COX-2 and mPGES-1 synthesis in the cartilage from OA patients and in OA chondrocytes. These data suggest that prolonged therapy with PGE2 blocking agents decreases PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating COX-2 and mPGES-1 synthesis in the cartilage. However, CBX and ACF seem to have a different anti-inflammatory profile in controlling pro-inflammatory gene expression in the cartilage.
answer:
Does long-term NSAID treatment directly decrease COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis?


question:
Context: Although diabetic patients often have gastrointestinal complications, the gastric mucosal function in diabetes has not been well documented.', 'To investigate the effect of fasting on the gastric mucosa in C57BL/KsJ-db +/+ db (db/db) mice, genetically non-insulin-dependent diabetic animals.', 'Blood glucose levels, gastric mucosal morphology, and the amount of gastric mucin were examined before and after 18 h of fasting with free access to water in db/db mice and their non-diabetic littermates (db/m).', 'Although 18 h of fasting reduced the blood glucose levels of both db/db and db/m mice, fasting decreased the amount of gastric adherent mucin and caused haemorrhagic gastric lesions only in db/db mice. After fasting, oral administration of ethanol induced much more severe gastric damage in db/db than in db/m mice. The above fasting-induced gastric damage such as haemorrhagic lesions, loss of the mucin, and the increased sensitivity to ethanol worsened as the duration of diabetes became longer. Glucose ingestion in drinking water during the fasting counteracted the fall in blood glucose and prevented the decrease in the amount of gastric mucin and the formation of gastric mucosal lesions in db/db mice.
Answer: These findings indicate that fasting-induced glucose deficit causes gastric mucosal lesions and increases the susceptibility of gastric mucosa to noxious agents owing to the loss of mucus glycoprotein in db/db mice. Prolonged diabetes is likely to augment the severity of fasting-induced impairment of the gastric mucosal function.
answer:
Does fasting induce impairment of gastric mucosal integrity in non-insulin-dependent diabetic ( db/db ) mice?


question:
Context: To ensure that clinical practice guidelines (CPGs) form a sound basis for decision-making in health care, it is necessary to be able to reliably assess and ensure their quality. This results in the need to assess the content of guidelines systematically, particularly with regard to the validity of their recommendations.The aim of the present analysis was to determine the suitability and applicability of frequently used assessment tools for evidence syntheses with regard to the assessment of guideline content.', 'We conducted a systematic comparison and analysis of established tools for the assessment of evidence syntheses (guidelines, systematic reviews, health technology assessments). The tools analyzed were: ADAPTE, AGREE II, AMSTAR, GLIA and the INAHTA checklist. We analyzed methodological steps related to the assessment of the reliability and validity of guideline recommendations. Data were extracted and analyzed by two persons independently of one another.', 'Widely used tools for the methodological assessment of evidence syntheses are not suitable for a comprehensive content-related assessment. They remain mostly at the level of assessment of the documentation of processes. Some tools assess selected content-related aspects, but operationalization is either unspecific or lacking.
Answer: None of the tools analyzed enables the structured and comprehensive assessment of the content of guideline recommendations with special regard to their reliability and validity. All tools contribute towards the judicious use of evidence syntheses by supporting their systematic development or assessment. However, further progress is needed, particularly with regard to the assessment of content quality. This includes comprehensive operationalization and documentation of the assessment process to ensure reliability and validity, and therefore to enable the effective use of trustworthy guidelines in the health care system.
answer:

Are tools for assessing the content of guidelines needed to enable their effective use -- a systematic comparison?