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.

Input: Consider Input: Context: This study was conducted to quantify the effect of multidisciplinary care (MDC) on amputation-free survival (AFS) and wound healing within a chronic critical limb ischemia (CLI) population.', 'We performed a retrospective, single-center cohort study of consecutive CLI patients presenting to the Vascular Surgery Service. Patients who received initial and follow-up wound care from the MDC were compared with patients who received standard wound care (SWC). The MDC team consisted of vascular, plastic, and podiatric surgeons who jointly managed wound care and directed any other consults or services as deemed necessary. SWC consisted of an inconsistent mix of providers without a defined manager, including nurses, wound care midlevel providers, general surgeons, internists, or the patients themselves. The referring physician determined the allocation of patients. The primary outcome variable was AFS, with a secondary evaluation of wound healing. The effects of baseline demographics, comorbid medical conditions, laboratory values, ischemic lesion severity and location, Rutherford classification, and participation in MDC were assessed. Significant univariate predictors (P < .10) of AFS were entered into a multivariate Cox regression model and assessed at an α = .05.', 'Between August 2010 and June 2012, 146 CLI patients (91 male [63%]) were evaluated by the Vascular Surgery Service and were followed up for a median of 539 days (interquartile range 314-679 days). Ischemic tissue loss was present in 85 patients (38 at Rutherford category 5, and 47 at Rutherford category 6). Within this cohort, 51 (60%) had MDC, and 34 (40%) had SWC. Fifty-eight patients (68%) underwent revascularization (open in 17, endovascular in 35, and hybrid in 6), 14 (8%) were managed with primary major amputation, and 13 (15%) declined revascularization. AFS was superior for patients in the MDC arm vs the SWC arm (593.3 ± 53.5 days vs 281.0 ± 38.2 days; log-rank, P = .02). Wound-healing times favored the MDC arm over the SWC arm (444.5 ± 33.2 days vs 625.2 ± 126.5 days), although this was not statistically significant (log-rank, P = .74). Multivariate modelling revealed that independent predictors of major amputation or death, or both, were nonrevascularized patients (hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.78-8.02; χ(2), P < .01), treatment by SWC (HR, 2.664; 95% CI, 1.23-5.77; χ(2), P = .012), and baseline nonambulatory status (HR, 1.89; 95% CI, 1.17-2.85; χ(2), P < .01).
Answer: MDC pathways for the management of a population of CLI patients improved AFS by greater than twofold and should be the standard of care for the CLI population. Baseline nonambulatory status and unrevascularized patients also predict worse AFS. Wound healing remains prolonged regardless of preoperative or postoperative wound care. Future study is required to evaluate the costs and functional outcomes for MDC in the management of CLI.

Output: Does multidisciplinary care improve amputation-free survival in patients with chronic critical limb ischemia?


Input: Consider Input: Context: Allopregnanolone (ALLO) is a physiologically relevant neurosteroid modulator of GABA(A) receptors, and it exhibits a psychopharmacological profile that closely resembles the post-ingestive effects of ethanol. The 5alpha-reductase inhibitor finasteride (FIN), which inhibits biosynthesis of ALLO and structurally related neurosteroids, was previously demonstrated to reduce the maintenance of limited-access ethanol consumption. The primary aim of the current work was to determine whether FIN would reduce the acquisition of drinking in ethanol-naïve mice.', 'Male C57BL/6J (B6) mice were acclimated to a reverse light/dark schedule, and were provided ad libitum access to chow and water. Following habituation to vehicle injections (VEH; 20% w/v beta-cyclodextrin; i.p.) administered 22-hour prior to drinking sessions with water only, mice were divided into 3 treatment groups: vehicle control (VEH), 50 mg/kg FIN (FIN-50), and 100 mg/kg FIN (FIN-100). Twenty-two hours after the first treatment, mice were permitted the inaugural 2-hour limited access to a 10% v/v ethanol solution (10E) and water. The acquisition of 10E consumption and underlying drinking patterns were assessed during FIN treatment (7 days) and subsequent FIN withdrawal (13 days) phases.', 'FIN dose-dependently blocked the acquisition of 10E drinking and prevented the development of ethanol preference, thereby suggesting that the GABAergic neurosteroids may be important in the establishment of stable drinking patterns. FIN-elicited reductions in 10E intake were primarily attributable to selective and marked reductions in bout frequency, as no changes were observed in bout size, duration, or lick rates following FIN treatment. FIN-treated mice continued to exhibit attenuated ethanol consumption after 2 weeks post-treatment, despite a full recovery in brain ALLO levels. A second study confirmed the rightward and downward shift in the acquisition of ethanol intake following 7 daily FIN injections. While there were no significant group differences in brain ALLO levels following the seventh day of ethanol drinking, ALLO levels were decreased by 28% in the FIN-50 group.
Answer: Although the exact mechanism is unclear, FIN and other pharmacological interventions that modulate the GABAergic system may prove useful in curbing ethanol intake acquisition in at-risk individuals.

Output: Does inhibition of 5alpha-reduced steroid biosynthesis impede acquisition of ethanol drinking in male C57BL/6J mice?


Input: Consider Input: Context: Declines in skeletal muscle structure and function are found in various clinical populations, but the intramuscular proteolytic pathways that govern declines in these individuals remain relatively poorly understood. The nematode Caenorhabditis elegans has been developed into a model for identifying and understanding these pathways. Recently, it was reported that UNC-105/degenerin channel activation produced muscle protein degradation via an unknown mechanism.', 'Generation of transgenic and double mutant C.\u2009elegans, RNAi, and drug treatments were utilized to assess molecular events governing protein degradation. Western blots were used to measure protein content. Cationic dyes and adenosine triphosphate (ATP) production assays were utilized to measure mitochondrial function.', 'unc-105 gain-of-function mutants display aberrant muscle protein degradation and a movement defect; both are reduced in intragenic revertants and in let-2 mutants that gate the hyperactive UNC-105 channel. Degradation is not suppressed by interventions suppressing proteasome-mediated, autophagy-mediated, or calpain-mediated degradation nor by suppressors of degenerin-induced neurodegeneration. Protein degradation, but not the movement defect, is decreased by treatment with caspase inhibitors or RNAi against ced-3 or ced-4. Adult unc-105 muscles display a time-dependent fragmentation of the mitochondrial reticulum that is associated with impaired mitochondrial membrane potential and that correlates with decreased rates of maximal ATP production. Reduced levels of CED-4, which is sufficient to activate CED-3 in vitro, are observed in unc-105 mitochondrial isolations.
Answer: Constitutive cationic influx into muscle appears to cause caspase degradation of cytosolic proteins as the result of mitochondrial dysfunction, which may be relevant to ageing and sarcopenia.


Output: Does degenerin channel activation cause caspase-mediated protein degradation and mitochondrial dysfunction in adult C. elegans muscle?