TASK DEFINITION: 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.
PROBLEM: Angiotensin II (Ang II) signaling has been implicated in cardiac arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which regulates similar targets as CaMKII has recently been shown to be redox-sensitive as well.', 'This study aims to investigate the distinct molecular mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the individual contribution of PKA vs. CaMKII.', 'Isolated ventricular cardiac myocytes from rats and mice were used. Ang II exposure resulted in increased NOX2-dependent ROS generation assessed by expression of redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell patch clamp measurements showed that Ang II significantly increased peak Ca and Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/-)). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak INa and ICa were also absent. In contrast, genetic knockout of CaMKIIδ (CaMKIIδ(-/-)) did not influence the Ang II-dependent increase in peak ICa and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark measurements) in a CaMKIIδ-, but not PKA-dependent manner. Surprisingly, only the increase in diastolic SR Ca leak was absent in gp91phox(-/-)myocytes suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII- but not on NOX2. Finally, we show that Ang II increased the propensity for cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on NOX2.

SOLUTION: Does nADPH oxidase 2 mediate angiotensin II-dependent cellular arrhythmias via PKA and CaMKII?

PROBLEM: The dietary determinants of adolescent blood pressure (BP) are not well understood. We determined the association between major dietary patterns and BP in a sample of Iranian adolescents.', "This cross-sectional study was conducted among a representative sample (n\xa0=\xa0557) of Shirazi adolescents aged 12-19\xa0years. Participants' systolic and diastolic BP was measured using a validated oscillometric BP monitor. Usual dietary intakes during the past 12\xa0months were assessed using a valid and reproducible 168-item semiquantitative food frequency questionnaire through face-to-face interviews. Principal component factor analysis was used to identify major dietary patterns based on a set of 25 predefined food groups.", 'Overall, three major dietary patterns were identified, among which only the Western pattern (abundant in soft drinks, sweets and desserts, salt, mayonnaise, tea and coffee, salty snacks, high-fat dairy products, French fries, and red or processed meats) had a significant association with BP. After adjusting for potential confounders in the analysis of covariance models, multivariable adjusted means of the systolic and mean BP of subjects in the highest tertile of the Western pattern score were significantly higher than those in the lowest tertile (for systolic BP: mean difference 6.9\xa0mmHg, P\xa0=\xa00.001; and for mean BP: mean difference 4.2\xa0mmHg, P\xa0=\xa00.003). A similar but statistically insignificant difference was observed in terms of diastolic BP.

SOLUTION: Is a Western dietary pattern associated with higher blood pressure in Iranian adolescents?

PROBLEM: Concomitant thyroid nodules are the most common reason for false-positive ultrasonography (US) results in primary hyperparathyroidism. The aims of this prospective clinical study were to evaluate false-positive US results according to the characteristics of concomitant thyroid nodules and to determine which characteristics of thyroid nodules are important.', 'This prospective study included 120 consecutive patients with primary hyperparathyroidism. The patients were divided into 2 groups according to preoperative US results. Group 1 consisted of 32 patients with false-positive US results and group 2 consisted of 88 patients with true-positive US results.', 'The risk for false-positive US result was increased 25-fold for patients with parathyroid adenoma weight of more than 500 mg (odds ratio [OR], 25; 95% confidence interval [CI], 8.6-74.5), 75-fold for more than 1 posteriorly located thyroid (OR, 75; 95% CI, 19.3-293.4), 358-fold for the presence of exophytic thyroid nodules (OR, 358; 95% CI, 42.3-3036), and 423-fold for the presence of posteriorly located thyroid nodules (OR, 423; 95% CI, 49-3662).

SOLUTION:
Do the characteristics of concomitant thyroid nodules cause false-positive ultrasonography results in primary hyperparathyroidism?