TASK DEFINITION: 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.
PROBLEM: 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.

SOLUTION: Does long-term NSAID treatment directly decrease COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis?

PROBLEM: Context: The aim of this study was to determine the effects of exogenous expression of the catalytic subunit of telomerase (hTERT) on the lifespan, growth characteristics, and tumorigenicity of normal human ovarian surface epithelial (OSE) cells.', 'Low-passage primary cultures of normal human OSE cells were transfected with hTERT and the resulting cell lines were characterized.', 'The ectopic expression of hTERT stabilized the telomeres of the OSE cultures above 8 kb. The hTERT-transfected OSE cell lines grew beyond the normal lifespan seen in OSE cells and propagated in culture for more than 40 passages before senescing. Moreover, the hTERT-transfected cells demonstrated extensive proliferative capacity as evidenced by their ability to continuously grow even when seeded at low dilutions. The morphologic features and normal differentiation patterns seen in normal OSE cells were likewise retained by the hTERT-transfected cells. In addition, the cultures remained responsive to physiologic concentrations of epidermal growth factor and transforming growth factor-beta. Changes associated with neoplastic transformation like anchorage-independent growth, tumorigencity and karyotypic instability were not observed.
Answer: We were able to show that the ectopic expression of hTERT in normal human OSE: 1) resulted in cultures with greater growth potential and longer lifespan and 2) did not induce a transformed phenotype previously seen in viral oncogene-transfected OSE cells. The established cell lines would not only provide sufficient material for comprehensive studies to investigate the normal physiology of OSE cells, but could also help in the understanding of the early steps of ovarian carcinogenesis.

SOLUTION: Does telomerase prolong the lifespan of normal human ovarian surface epithelial cells without inducing neoplastic phenotype?

PROBLEM: Context: Dairy foods help achieve essential nutrient adequacy. This role may be conflicted where so-called chronic diseases prevail. We have examined associations between dairy intake and mortality where dairy foods have not been traditional.', 'A representative Taiwanese cohort of 3810 subjects, aged 19-64 years, derived from the Nutrition and Health Survey in Taiwan (NAHSIT, 1993-1996) was linked to death registration (1993-2008). Participants were categorized by 4 dairy weekly intake frequencies from 0 to >7 times. Mortality hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional-hazards models.', 'Nonconsumers of dairy products included 30.7% of the men and 22.1% of the women. Adverse sociodemographic and personal behaviors were generally significantly associated with lower dairy consumption. After adjustment for covariates, together with body mass index (BMI) and supplement use, those with 3-7 times/week intakes had an HR (95% CI) for all-cause mortality of 0.61 (0.39-0.96) with a significant dose-response trend (p = 0.043). Similarly, the HR for cardiovascular disease (CVD) mortality with dairy weekly intake frequency >7 was 0.14 (0.02-0.97) with a significant linear trend (p = 0.007). For stroke, the corresponding HR (95% CI) was 0.03 (0.00-0.28) with a linear trend. By age and with adjustment for dietary quality, food, and calcium or vitamin D intake, significance and dose-response relationships remained. Dairy intake and cancer mortality were not associated.
Answer: In a Chinese food culture, a dairy foods intake in adults up to 7 times a week does not increase mortality and may have favorable effects on stroke.

SOLUTION:
Is optimal dairy intake predicated on total , cardiovascular , and stroke mortalities in a Taiwanese cohort?