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: Right ventricular pacing (RVP) has been associated with heart failure and increased mortality. His-bundle pacing (HBP) is more physiological but requires a mapping catheter or a backup right ventricular lead and is technically challenging.', 'We sought to assess the feasibility, safety, and clinical outcomes of permanent HBP in an unselected population as compared to RVP.', 'All patients requiring pacemaker implantation routinely underwent attempt at permanent HBP using the Select Secure (model 3830) pacing lead in the year 2011 delivered through a fixed-shaped catheter (C315 HIS) at one hospital and RVP at the second hospital. Patients were followed from implantation, 2 weeks, 2 months, 1 year, and 2 years. Fluoroscopy time (FT), pacing threshold (PTh), complications, heart failure hospitalization, and mortality were compared.', 'HBP was attempted in 94 consecutive patients, while 98 patients underwent RVP. HBP was successful in 75 patients (80%). FT was similar (12.7 ± 8 minutes vs 10 ± 14 minutes; median 9.1 vs 6.4 minutes; P = .14) and PTh was higher in the HBP group than in the RVP group (1.35 ± 0.9 V vs 0.6 ± 0.5 V at 0.5 ms; P < .001) and remained stable over a 2-year follow-up period. In patients with >40% ventricular pacing (>60% of patients), heart failure hospitalization was significantly reduced in the HBP group than in the RVP group (2% vs 15%; P = .02). There was no difference in mortality between the 2 groups (13% in the HBP group vs 18% in the RVP group; P = .45).

SOLUTION: Is permanent His-bundle pacing feasible , safe , and superior to right ventricular pacing in routine clinical practice?

PROBLEM: Neurotensin-1 (NT1) receptor agonists have been proposed as putative antipsychotic drugs. Recently, brain-penetrating NT analogs produced by stability-enhancing modification of the smallest NT fragment, NT(8-13), have demonstrated antipsychotic-like efficacy after acute systemic injection in several preclinical animal tests predictive for antipsychotic efficacy. However, the evidence regarding the persistence versus tolerance of these effects after repeated administration is ambiguous. Previous studies have used compounds that nonselectively activated both NT1 and NT2 receptors or used continuous slow, central infusion of doses rather than daily acute administration, both factors which may have contributed to the ambiguity in the literature regarding the emergence of tolerance.', 'To determine if tolerance develops to the antipsychotic-like effects of NT1 receptor agonists, we investigated the effects of subchronic daily systemic administration of PD149163, a brain-penetrating NT analog with selectivity for the NT1 receptor, on amphetamine-induced locomotor activation, a classic preclinical test of antipsychotic efficacy.', 'Sprague-Dawley rats were pretreated with eight consecutive daily subcutaneous (SC) injections of PD149163 or saline. On the ninth day, rats received a pair of SC injections consisting of PD149163 or saline, followed by amphetamine (0.5 mg/kg) or saline. Locomotor activity was then measured in photobeam-equipped cages.', "The results indicated that repeated daily administration of PD149163 was able to antagonize amphetamine's locomotor-activating effect comparable to that of the first dose, despite that repeated administration of PD149163 produced an increase in baseline locomotor activity not seen after the first dose.

SOLUTION: Does the reversal of amphetamine-induced locomotor activation by a selective neurotensin-1 receptor agonist exhibit tolerance?

PROBLEM: The human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.', 'The level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(-) cells).', 'The level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P\u2009=\u20090.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(-) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(-) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(-) cells than in RECQL1(+) cells.

SOLUTION:
Is the level of RECQL1 expression a prognostic factor for epithelial ovarian cancer?