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: Islet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.', 'Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.
Answer: In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular islet autoreactivity may be required. Monitoring cellular immune reactivity can be useful to identify factors influencing graft survival and to assess efficacy of immunosuppression.

SOLUTION: Does cellular islet autoimmunity associate with clinical outcome of islet cell transplantation?

PROBLEM: Context: Tinnitus can adversely affect patients' quality of life. Transcutaneous electrical nerve stimulation (TENS) may be effective in the management of tinnitus. No study has investigated the efficacy of TENS for the management of tinnitus by means of quality of life measures. In this study, we evaluated the efficacy of TENS for the management of tinnitus symptoms by using the visual analogue scale (VAS), tinnitus handicap inventory test, Nottingham health profile (NHP) and short form-36 (SF-36) questionnaires.", 'Twenty-two patients were included in this study (male/female, 16/6; mean age, 48.04 +/- 15.57 years). Nine patients had unilateral and 13 patients had bilateral tinnitus.', 'After TENS, improvement measured by VAS was only marginally significant (p = 0.059). However, after TENS, there were statistically significant improvements regarding tinnitus severity scores, tinnitus handicap inventory scores, NHP fatigue, social isolation and emotional problems scores, and many parameters measured by the SF-36 (physical functioning, general health, vitality, social functioning, role limitations due to emotional problems, and mental health)(p < 0.05).
Answer: Transcutaneous electrical nerve stimulation is a useful method to improve the quality of life of patients with tinnitus.

SOLUTION: Does treatment of tinnitus with transcutaneous electrical nerve stimulation improve patients ' quality of life?

PROBLEM: Context: Impaired resolution of acute inflammation results in development of chronic inflammatory disorders such as atherosclerosis, asthma and arthritis. Clearance of apoptotic neutrophils by M2 macrophages, the process termed efferocytosis, is critical for complete resolution of inflammation as it prevents secondary necrosis caused by disgorgement of toxic contents from apoptotic cells in the inflamed site. In the present study, we investigated the effect of docosahexaenoic acid (DHA) on efferocytosis.', 'To determine the effect of DHA on efferocytosis, murine macrophage-like RAW264.7 cells were co-incubated with apoptotic Jurkat T cells, and efferocytosis was assessed by flow cytometry. The expression and production of M1 and M2 markers were determined by RT-PCR, ELISA and flow cytometry. To demonstrate the involvement of peroxisome proliferator-activated receptor (PPAR) in DHA-mediated effects, siRNA against PPAR was utilized. The expression of PPAR was examined by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry. The PPAR activation was measured by the electrophilic gel shift assay.', 'DHA enhanced the efferocytic ability of RAW264.7 cells, and induced their M2 polarization. Notably, knockdown of PPAR abolished the stimulatory effect of DHA on M2 polarization as well as efferocytosis. Furthermore, lipopolysaccharide-induced production of pro-inflammatory cytokines was significantly inhibited by DHA, suggesting that DHA alters the macrophage phenotype in favor of M2 while it suppresses M1 polarization.
Answer: These findings indicate that DHA can promote resolution of inflammation by facilitating efferocytosis through M2 macrophage polarization. Therefore, DHA may have a therapeutic potential in the management of inflammatory diseases which are related to impaired resolution of inflammation.

SOLUTION:
Does docosahexaenoic acid induce M2 macrophage polarization through peroxisome proliferator-activated receptor activation?