TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Population-based studies of associations between subclinical hypercortisolism and risk for disease states, such as type 2 diabetes mellitus, have been difficult to assess because of imprecise measures of glucocorticoid exposure. Alternative measures (salivary cortisol and adrenal gland volume) have not been systematically compared with 24-h urine free cortisol (UFC) in a healthy population.', 'Our objectives were: 1) to determine whether 24-h UFC and total daily salivary cortisol correlated with each other, adrenal gland volume, and salivary cortisol after dexamethasone suppression and 2) to evaluate the association of adrenal gland volume with salivary cortisol after dexamethasone suppression.', 'This was a cross-sectional study of 20 healthy, premenopausal African-American women aged 18-45 yr.', 'Salivary cortisol was assessed at six time points throughout the day simultaneous with 24-h UFC collection. Adrenal gland volume was measured by computed tomography scan. Dexamethasone-suppressed salivary cortisol was measured at 0800 h after administration of 0.5 mg dexamethasone at 2300 h the prior evening.', 'Dexamethasone-suppressed salivary cortisol levels correlated strongly with individual, timed salivary cortisol measurements, total daily salivary cortisol (rs=0.75; P=0.0001; n=20), and adrenal gland volume (rs=0.66; P=0.004; n=17). Total daily salivary cortisol and adrenal gland volume also correlated (rs=0.46; P=0.04; n=19). In contrast, 24-h UFC levels did not correlate with any of the other hypothalamic-pituitary-adrenal axis measures.\Question: Do adrenal gland volume and dexamethasone-suppressed cortisol correlate with total daily salivary cortisol in African-American women?

SOLUTION: A dexamethasone suppression test or adrenal gland volume may be alternative measures for characterizing subtle subclinical hypercortisolism in healthy adults.

PROBLEM: Context: To determine GJB2 allelic mutant and estimate probability of hereditary hearing loss in newborn with GJB2 heterozygous mutation in Beijing.', 'We performed genetic testing for sequencing of GJB2 gene for searching GJB2 allelic mutant in 915 newborn who received newborn deafness gene screening (GJB2 c. 235delC, GJB2 c. 299_300delAT, GJB2 c. 176191del16, GJB2 c. 35delG) in Beijing Tongren hospital, and the mutation were classified to pathogenic mutation,undefined variant and polymorphism.', 'Four hundred (43.72%, 400/915) newborn were detected to carry at least one mutation allele in GJB2. 3 (0.33%, 3/915) newborn had pathogenic mutations (c. 94C>T, c. 380G>T, c. 344T>G); 62 (6.76%, 62/915) newborn carried 14 undefined variant, 36 newborn had c. 109G>A (58.06%, 36/62),13 newborn had c. 368C>A (20.97%,13/62), six (c. 268C>G, c. 282C>T, c. 294G>C, 456C>T, c. 501G>A, c. 587T>C) are novel; 335 (36.61%, 335/915) newborn were polymorphism.\Question: Do [ The sequencing analyze of 915 newborn with GJB2 heterozygous mutation in Beijing ]?

SOLUTION: The probability of hereditary hearing loss is 7.09% in newborn with GJB2 heterozygous mutation in Beijing. It is noteworthy that c. 109G>A, c. 368C>A occupy a high proportion.

PROBLEM: Context: The mechanism by which low dose methotrexate (MTX, the gold standard treatment for rheumatoid arthritis) exerts its anti-inflammatory effect in rheumatoid arthritis (RA) patients is still debated. Lately, the MTX immunosuppressive effect has been related to apoptosis, especially in active RA patients, with ROS involvement.', 'In the present research we investigated MTX oxidative effect and its ability to modulate immune balance in active versus non-active RA patients.', 'Our results show that MTX induces IL-10 secretion (a TH2 cytokine) and significantly reduces TH1 profile in Peripheral Mononuclear Cells (PMNC) derived from active RA patients (n=28). Additionally, we found that MTX modulates the immune status towards TH2 dominance by decreasing the IL-12R and the CXCR3 receptors typical for the TH1 population. Moreover, MTX was found to inhibit the production of nitric oxide (NO) in these patients, a phenomenon that might contribute to MTX action toward cytokine homeostasis. A significant correlation was found between MTX IL-10 induction and NO inhibition in active RA patients.\Question: Does methotrexate selectively modulate TH1/TH2 balance in active rheumatoid arthritis patients?

SOLUTION:
Our data suggest that, in active RA patients, apoptosis induction by MTX may be primarily due to IL-10 production via modulation of oxidative stress, which may restore the critically important immune balance. These findings may contribute to determining which group of RA patients may better respond to MTX therapy.