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: Recent studies have indicated a protective role of physiological autophagy in ischemic heart disease. However, the underlying mechanisms of autophagy regulation after ischemia are poorly understood. Exosomes are nano-sized vesicles released from cells that play critical roles in mediating cell-to-cell communication through the transfer of microRNAs. In this study, we observed that miR-30a was highly enriched in exosomes from the serum of acute myocardial infarction (AMI) patients in vivo and culture medium of cardiomyocytes after hypoxic stimulation in vitro. We also found that hypoxia inducible factor (HIF)-1 regulates miR-30a, which efficiently transferred via exosomes between cardiomyocytes after hypoxia. Inhibition of miR-30a or release of exosomes increased the expression of the core autophagy regulators beclin-1, Atg12, and LC3II/LC3I, which contributed to maintaining the autophagic response in cardiomyocytes after hypoxia. Taken together, the present study showed that exosomes from hypoxic cardiomyocytes regulate autophagy by transferring miR-30a in a paracrine manner, which revealed a new pathway of autophagy regulation that might comprise a promising strategy to treat ischemic heart disease.

SOLUTION: Does exosomal transfer of miR-30a between cardiomyocytes regulate autophagy after hypoxia?

PROBLEM: The antidepressant drug fluoxetine (FLU) is considered in the group of selective serotonine re-uptake inhibitors. Its distribution in brain and binding to human brain glutathione S-transferase- (GST-) have been shown. FLU can cross blood brain barrier and placenta, accumulate in fetus and may cause congenital malformations.', 'To elucidate the interaction of placental GST- with FLU.', 'First, concentration-dependent inhibition of human placental GST- was evaluated by using different FLU concentrations and then 0.3125, 0.625, 1.25, 2.5 and 5mM FLU concentrations were chosen and tested while keeping GSH concentration constant and 1-chloro-2,4-dinitrobenzene (CDNB) concentration varied and vice versa. The data were evaluated with different kinetic models and Statistica 9.00 for Windows.', 'The Vm, at variable [CDNB] (14216U/mg protein) was 3 times higher than the Vm obtained at variable [GSH] (494U/mg protein). On the other hand, the Km for CDNB was 10 times higher than the Km for GSH (1.990.36mM versus 0.210.06mM). The IC50 value for FLU was 8.6mM. Both at constant [CDNB] and variable [GSH] and at constant [GSH] and variable [CDNB] the inhibition types were competitive with the Ki values of 5.624.37 and 8.091.27mM, respectively.

SOLUTION: Does fluoxetine-induced toxicity result in human placental glutathione S-transferase- ( GST- ) dysfunction?

PROBLEM: The possibility of ignition of polyvinylchloride (PVC) tracheal tubes by a CO2 laser is of concern in patients undergoing CO2 laser surgery of the airway. The authors analyzed the ignition of PVC tracheal tubes by a CO2 laser beam to determine what variables were involved, and then designed a study to determine how they affect the incidence of such fires.', 'For the analysis, PVC tracheal tubes were enclosed in a clear plexiglass enclosure and a laser beam was focused on the tubes. The enclosure contained one of three different gas combinations. A high-speed camera photographed the tubes during the analysis and showed that tracheal tube perforation always preceded ignition in all three gas combinations. These results led to the hypothesis that intraluminal gauge pressure (IGP) may be an important variable, because it would affect the flow of O2 across the perforation. This hypothesis was tested by aiming a CO2 laser beam at PVC tracheal tubes and varying IGP in 0.25-cm H2O increments, from 0.25 to 28 cm H2O, while nitrogen or helium containing O2 at 40, 50, or 60% flowed through the tubes. To simulate the clinical effect of IGP on PVC tracheal tube ignition, we used a mechanical lung model connected to an anesthesia breathing circuit with a standing bellows ventilator in which 60% He and 40% O2 flowed through a PVC tracheal tube. Laser beam exposure was started at three different times during the respiratory cycle: at the start of inspiration, at the end of inspiration, or at the end of expiration. Also, for each condition, trials were made at baseline circuit pressure (2.5 cm H2O) and at 5.0 cm H2O by the addition of 2.5 cm H2O positive end-expiratory pressure (PEEP) applied to the circuit.', 'The incidence of tracheal tube ignition decreased as IGP increased. The IGP at which ignition did not occur (which increased as O2 concentration increased) did not differ between N2 and He at 40% O2, but was twice as high with N2 as with He at O2 of 50% and 60%. Fires never occurred when PEEP was added to the system and, when PEEP was not added, always started during the last 2 s of end expiration (when airway pressure is lowest), regardless of when the laser beam was activated.

SOLUTION:
Does positive end-expiratory pressure lower the risk of laser-induced polyvinylchloride tracheal-tube fires?