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: Within Australian hospitals, cardiac and respiratory arrests result in a resuscitation attempt unless the patient is documented as not for resuscitation.', 'To examine the consistency of policies and documentation for withholding in-hospital resuscitation across health services.', 'An observational, qualitative review of hospital policy and documentation was conducted in June 2013 in three public and two private sector hospitals in metropolitan Melbourne. Not for resuscitation (NFR) forms were evaluated for physical characteristics, content, authorisation and decision-making. Hospital policies were coded for alerts, definition of futility and burden of treatment and management of discussions and dissent.', 'There was a lack of standardisation, with each site using its own unique NFR form and accompanying site-specific policies. Differences were found in who could authorise the decision, what was included on the form, the role of patients and families, and how discussions were managed and dissent resolved. Futility and burden of treatment were not defined independently. These inconsistencies across sites contribute to a lack of clarity regarding the decision to withhold resuscitation, and have implications for staff employed across multiple hospitals.
Answer: NFR forms should be reviewed and standardised so as to be clear, uniform and consistent with the legislative framework. We propose a two-stage process of documentation. Stage 1 facilitates discussion of patient-specific goals of care and consideration of limitations of treatment. Stage 2 serves to communicate a NFR order. Decisions to withhold resuscitation are inherently complex but could be aided by separating the decision-making process from the communication of the decision, resulting in improved end-of-life care.

SOLUTION: Does comparison of not for resuscitation ( NFR ) form across five Victorian health services?

PROBLEM: Context: p38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats.', 'Rats were divided into 4 groups: (1) the control group (daily 0.9% saline), (2) the FR group (daily FR167653, 2 mg . kg(-1) . d(-1)), (3) the MCT group (daily 0.9% saline the day after a single monocrotaline dose, 60 mg/kg), and (4) the MCT+FR group (daily FR167653, 2 mg . kg(-1) . d(-1), the day after a single MCT dose). Body weight, pulmonary artery pressure, and morphometric changes of the pulmonary artery with the histopathologic method were observed weekly for 4 weeks. Also, p38 mitogen-activated protein kinase activity and inflammatory cytokine expression in the lung were measured.', 'Four weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT+FR group was lower than in the MCT group (MCT+FR vs MCT: 24.7 +/- 1.9 vs 36.5 +/- 2.1 mm Hg; P < .05). In morphometric analysis the percentage of medial wall thickness and the percentage of muscularization in the MCT+FR group were reduced compared with those in the MCT group after 4 weeks (P < .05); however, the number of macrophages was not significantly different. p38 mitogen-activated protein kinase activity was significantly attenuated in the MCT+FR group compared with in the MCT group (7.2 +/- 0.52 vs 2.1 +/- 0.23 fold-increase, P < .05, at 1 week). Although mRNA levels of tumor necrosis factor alpha and interleukin 1beta were reduced in the MCT+FR group compared with in the MCT group (tumor necrosis factor alpha: 1.18 +/- 0.36 vs 3.05 +/- 1.12 fold-increase, P < .05, at 2 weeks; interleukin 1beta: 2.2 +/- 0.34 vs 4.4 +/- 1.09 fold-increase, P < .05, at 1 week), FR167653 did not suppress increased monocyte chemotactic protein 1 mRNA expression induced by monocrotaline (3.2 +/- 0.62 vs 3.1 +/- 0.42 fold-increase, at 1 week).
Answer: FR167653 significantly attenuates the expression of inflammatory cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38 mitogen-activated protein kinase might play a central role in the molecular events that underlie the development and progression of pulmonary hypertension.

SOLUTION: Does specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuate vascular proliferation in monocrotaline-induced pulmonary hypertension in rats?

PROBLEM: Context: Defects in phagocytic nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) function cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by dysfunctional microbicidal activity and chronic inflammation.', 'We sought to study the effect of chronic inflammation on the hematopoietic compartment in patients and mice with X-linked chronic granulomatous disease (X-CGD).', 'We used immunostaining and functional analyses to study the hematopoietic compartment in patients with CGD.', 'An analysis of bone marrow cells from patients and mice with X-CGD revealed a dysregulated hematopoiesis characterized by increased numbers of hematopoietic progenitor cells (HPCs) at the expense of repopulating hematopoietic stem cells (HSCs). In patients with X-CGD, there was a clear reduction in the proportion of HSCs in bone marrow and peripheral blood, and they were also more rapidly exhausted after in vitro culture. In mice with X-CGD, increased cycling of HSCs, expansion of HPCs, and impaired long-term engraftment capacity were found to be associated with high concentrations of proinflammatory cytokines, including IL-1β. Treatment of wild-type mice with IL-1β induced enhanced cell-cycle entry of HSCs, expansion of HPCs, and defects in long-term engraftment, mimicking the effects observed in mice with X-CGD. Inhibition of cytokine signaling in mice with X-CGD reduced HPC numbers but had only minor effects on the repopulating ability of HSCs.
Answer: Persistent chronic inflammation in patients with CGD is associated with hematopoietic proliferative stress, leading to a decrease in the functional activity of HSCs. Our observations have clinical implications for the development of successful autologous cell therapy approaches.

SOLUTION:
Does hyperinflammation in patients with chronic granulomatous disease lead to impairment of hematopoietic stem cell functions?