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: Women have poorer outcomes after vascular surgery as compared to men as shown by studies recently. Frailty is also an independent risk factor for postoperative morbidity and mortality. This study examines the interplay of gender and frailty on outcomes after infrainguinal vascular procedures.', 'The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all patients who underwent infrainguinal vascular procedures from 2005-2012. Frailty was measured using a modified frailty index (mFI; derived from the Canadian Study of Health and Aging). Univariate and multivariate analysis were performed to investigate the association of preoperative frailty and gender, on postoperative outcomes.', 'Of 24,645 patients (92% open, 8% endovascular), there were 533 deaths (2.2%) and 6198 (25.1%) major complications within 30 d postoperatively. Women were more frail (mean mFI = 0.269) than men (mean mFI = 0.259; P < 0.001). Women and frail patients (mFI>0.25) were more likely to have a major morbidity (P < 0.001) or mortality (P < 0.001) with the highest risk in frail women. On multivariate logistic regression analysis, female gender and increasing mFI were independently significantly associated with mortality (P < 0.05) as well as major complications. The interaction of gender and frailty in multivariate analysis showed the highest adjusted 30-d mortality and morbidity in frail females at 2.8% and 30.1%, respectively and that was significantly higher (P < 0.001) than nonfrail males, nonfrail females and frail males.
Answer: Female gender and frailty are both associated with increased risk of complications and death following infrainguinal vascular procedures with the highest risk in frail females. Further studies are needed to explore the mechanisms of interaction of gender and frailty and its effect on long-term outcomes for peripheral vascular disease.

SOLUTION: Do gender and frailty predict poor outcomes in infrainguinal vascular surgery?

PROBLEM: Context: Increased oxidative stress and myocyte apoptosis co-exist in the remote non-infarcted myocardium (RM) following a large myocardial infarction. We proposed that these phenomena are causally related.', 'On day 3 after induction of myocardial infarction, Sprague-Dawley rats were randomized to receive probucol and pyrrolidine dithiocarbamate (MI-T), or vehicle only (MI) for 7 weeks. Control rats (C) received vehicle. At 7 weeks, lipidperoxidation within the RM was assessed by measuring thiobarbituric acid reactive substances, which were significantly increased in MI vs. C, while MI-T was not different from C. There was a significant increase in cardiac myocytes positive for in situ TdT-UTP nick-end labeling within the RM in MI vs. C, which was inhibited in MI-T. Furthermore, internucleosomal DNA fragmentation was clearly demonstrated on agarose gels from RM in the MI group, while it was much less apparent on gels from RM in the C and MI-T groups. Western blot analysis showed a significant increase in p53, Bax and caspase-3 protein expression within the RM of MI vs. C, all of which were inhibited in the MI-T group. Furthermore, there was evidence for an increase in caspase-3 activity within the RM from MI vs. C, which was normalized in the MI-T group.
Answer: Long-term treatment with the antioxidants probucol and pyrrolidine dithiocarbamate attenuates oxidative stress, myocyte apoptosis, caspase-3 like activity and the expression of p53, bax and caspase-3 within RM in rats after a large myocardial infarction.

SOLUTION: Do antioxidants attenuate myocyte apoptosis in the remote non-infarcted myocardium following large myocardial infarction?

PROBLEM: Context: The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites.', 'The effects of tacrolimus and TGF-beta1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated.', 'The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-beta production of skin cells was analyzed.', 'Tacrolimus and TGF-beta1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-beta receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased.
Answer: The synergism between TGF-beta1 and tacrolimus leads to the generation of LCs, reduced expression of costimulatory and MHC II molecules, and reduced stimulatory activity. Shifting the balance of the dendritic cell population to LCs might be of major importance for the therapeutic effect of tacrolimus.

SOLUTION:
Do tacrolimus and TGF-beta act synergistically on the generation of Langerhans cells?