OBJECTIVEThis study determined the effects of insulin versus liraglutide therapy on liver fat in patients with type 2 diabetes inadequately controlled with oral agents therapy, including metformin. RESEARCH DESIGN AND METHODSThirty-five patients with type 2 diabetes inadequately controlled on metformin monotherapy or in combination with other oral antidiabetic medications were randomized to receive insulin glargine or liraglutide therapy for 12 weeks. The liver proton density fat fraction (PDFF) was measured by MRS. The mean liver PDFF, the total liver volume, and the total liver fat index were measured by MRI. The Student t test, the Fisher exact test, and repeated-measures ANOVA were used for statistical analysis. RESULTSInsulin treatment was associated with a significant improvement in glycated hemoglobin (7.9% to 7.2% [62.5 to 55.2 mmol/mol], P = 0.005), a trend toward a decrease in MRS-PDFF (12.6% to 9.9%, P = 0.06), and a significant decrease in liver mean MRI-PDFF (13.8% to 10.6%, P = 0.005), liver volume (2,010.6 to 1,858.7 mL, P = 0.01), and the total liver fat index (304.4 vs. 209.3 % · mL, P = 0.01). Liraglutide treatment was also associated with a significant improvement in glycated hemoglobin (7.6% to 6.7% [59.8 to 50.2 mmol/mol], P < 0.001) but did not change MRS-PDFF (P = 0.80), liver mean MRI-PDFF (P = 0.15), liver volume (P = 0.30), or the total liver fat index (P = 0.39). CONCLUSIONSThe administration of insulin glargine therapy reduced the liver fat burden in patients with type 2 diabetes. However, the improvements in the liver fat fraction and glycemia control were not significantly different from those in the liraglutide group.To reduce the risk of long-term microvascular and macrovascular complications, diabetes therapy should aim for tight glucose control as assessed by glycated hemoglobin (HbA 1c ) below 7% (53 mmol/mol) while minimizing hypoglycemia (1,2). However, most patients still do not achieve glycemic targets and thus require

MIST for respiratory distress syndrome management in moderate and late preterm infants was associated with a significant reduction of MV exposure and pneumothorax occurrence.

Background When designing and developing patient decision aids, guidelines recommend involving patients and stakeholders. There are myriad ways to do this. We aimed to describe how such involvement occurs by synthesizing reports of patient decision aid design and development within a user-centered design framework and to provide context by synthesizing reports of user-centered design applied to other personal health tools. Methods We included articles describing at least one development step of 1) a patient decision aid, 2) user- or human-centered design of another personal health tool, or 3) evaluation of these. We organized data within a user-centered design framework comprising 3 elements in iterative cycles: understanding users, developing/refining prototype, and observing users. Results We included 607 articles describing 325 patient decision aid projects and 65 other personal health tool projects. Fifty percent of patient decision aid projects reported involving users in at least 1 step for understanding users, 35% in at least 1 step for developing/refining the prototype, and 84% in at least 1 step for observing users’ interaction with the prototype. In comparison, other personal health tool projects reported 91%, 49%, and 92%, respectively. A total of 74% of patient decision aid projects and 92% of other personal health tool projects reported iterative processes, both with a median of 3 iterative cycles. Preliminary evaluations such as usability or feasibility testing were reported in 66% of patient decision aid projects and 89% of other personal health tool projects. Conclusions By synthesizing design and development practices, we offer evidence-based portraits of user involvement. Those wishing to further align patient decision aid design and development with user-centered design methods could involve users earlier, design and develop iteratively, and report processes in greater detail.

Mitochondria are organelles that govern energy supply and control cell death. Mitochondria also express bacterial features, such as the presence of inner membrane cardiolipin and a circular genome rich in hypomethylated CpG motifs. While mitochondrial extrusion by damaged organs or activated cells is thought to trigger innate immunity, it is unclear whether extracellular mitochondria also stimulate an adaptive immune response. We describe the development of novel assays to detect autoantibodies specific to two distinct components of the mitochondrion: the mitochondrial outer membrane and mitochondrial DNA. Antibodies to these two mitochondrial constituents were increased in both human and murine systemic lupus erythematosus (SLE), compared to controls, and were present at higher levels than in patients with antiphospholipid syndrome or primary biliary cirrhosis. In both bi- and multi-variate regression models, antibodies to mitochondrial DNA, but not whole mitochondria, were associated with increased anti-dsDNA antibodies and lupus nephritis. This study describes new and optimized methods for the assessment of anti-mitochondrial antibodies, and demonstrates their presence in both human and murine SLE. These findings suggest that different mitochondrial components are immunogenic in SLE, and support the concept that extracellular mitochondria may provide an important source of circulating autoantigens in SLE.

BACKGROUND: Whereas platelet transfusion is a common medical procedure, inflammation still occurs in a fraction of transfused individuals despite the absence of any apparent infectious agents. Platelets can shed membrane vesicles, called extracellular vesicles (EVs), some of which contain mitochondria (mito+EV). With its content of damage-associated molecular pattern (DAMP), the mitochondrion can stimulate the innate immune system. Mitochondrial DNA (mtDNA) is a recognized DAMP detected in the extracellular milieu in numerous inflammatory conditions and in platelet concentrates. We hypothesized that platelet-derived mitochondria encapsulated in EVs may represent a reservoir of mtDNA. STUDY DESIGN AND METHODS:Herein, we explored the implication of mito+EVs in the occurrence of mtDNA quantified in platelet concentrate supernatants that induced or did not induce transfusion adverse reactions. ABBREVIATIONS: DAMP = damage-associated molecular pattern; EVs = extracellular vesicles; FNHTRs = febrile nonhemolytic transfusion reactions; mito+EV = extracellular vesicles that contain mitochondria; mtDNA = mitochondrial DNA; PC = platelet concentrate; PS = phosphatidylserine; qPCR = quantitative polymerase chain reaction; sCD40L = soluble CD40 ligand; sCD62P = soluble CD62P. From the

Objective To determine whether vitamin D3 supplementation improves insulin sensitivity, using the hyperinsulinemic-euglycemic clamp. Design This single-centre, double-blind, placebo-controlled trial randomised 96 participants at high risk of diabetes or with newly diagnosed type 2 diabetes to vitamin D3 5000 IU daily or placebo for 6 months. Methods We assessed at baseline and 6 months: (1) primary aim: peripheral insulin sensitivity (M-value using a 2-h hyperinsulinemic-euglycemic clamp); (2) secondary aims: other insulin sensitivity (HOMA2%S, Matsuda) and insulin secretion (insulinogenic index, C-peptide area under the curve, HOMA2-B) indices using a 2-h oral glucose tolerance test (OGTT); β-cell function (disposition index: M-value × insulinogenic index); fasting and 2-h glucose post OGTT; HbA1c; anthropometry. Results Baseline characteristics were similar between groups (% or mean ± s.d.): women 38.5%; age 58.7 ± 9.4 years; BMI 32.2 ± 4.1 kg/m2; prediabetes 35.8%; diabetes 20.0%; 25-hydroxyvitamin D (25(OH)D) 51.1 ± 14.2 nmol/L. At 6 months, mean 25(OH)D reached 127.6 ± 26.3 nmol/L and 51.8 ± 16.5 nmol/L in the treatment and placebo groups, respectively (P < 0.001). A beneficial effect of vitamin D3 compared with placebo was observed on M-value (mean change (95% CI): 0.92 (0.24–1.59) vs −0.03 (−0.73 to 0.67); P = 0.009) and disposition index (mean change (95% CI): 267.0 (−343.4 to 877.4) vs −55.5 (−696.3 to 585.3); P = 0.039) after 6 months. No effect was seen on other outcomes. Conclusions In individuals at high risk of diabetes or with newly diagnosed type 2 diabetes, vitamin D supplementation for 6 months significantly increased peripheral insulin sensitivity and β-cell function, suggesting that it may slow metabolic deterioration in this population.

Background. High-quality health decisions are often defined as those that are both evidence informed and values congruent. A values-congruent decision aligns with what matters to those most affected by the decision. Values clarification methods are intended to support values-congruent decisions, but their effects on values congruence are rarely evaluated. Methods. We tested 11 strategies, including the 3 most commonly used values clarification methods, across 6 between-subjects online randomized experiments in demographically diverse US populations ( n1 = 1346, n2 = 456, n3 = 840, n4 = 1178, n5 = 841, n6 = 2033) in the same hypothetical decision. Our primary outcome was values congruence. Decisional conflict was a secondary outcome in studies 3 to 6. Results. Two commonly used values clarification methods (pros and cons, rating scales) reduced decisional conflict but did not encourage values-congruent decisions. Strategies using mathematical models to show participants which option aligned with what mattered to them encouraged values-congruent decisions and reduced decisional conflict when assessed. Limitations. A hypothetical decision was necessary for ethical reasons, as we believed some strategies may harm decision quality. Later studies used more outcomes and covariates. Results may not generalize outside US-based adults with online access. We assumed validity and stability of values during the brief experiments. Conclusions. Failing to explicitly support the process of aligning options with values leads to increased proportions of values-incongruent decisions. Methods representing more than half of values clarification methods commonly in use failed to encourage values-congruent decisions. Methods that use models to explicitly show people how options align with their values offer more promise for helping people make decisions aligned with what matters to them. Decisional conflict, while arguably an important outcome in and of itself, is not an appropriate proxy for values congruence.

The mitochondrion supplies energy to the cell and regulates apoptosis. Unlike other mammalian organelles, mitochondria are formed by binary fission and cannot be directly produced by the cell. They contain numerous copies of a compact circular genome that encodes RNA molecules and proteins involved in mitochondrial oxidative phosphorylation. Whereas, mitochondrial DNA (mtDNA) activates the innate immune system if present in the cytosol or the extracellular milieu, it is also the target of circulating autoantibodies in systemic lupus erythematosus (SLE). However, it is not known whether mitochondrial RNA is also recognized by autoantibodies in SLE. In the present study, we evaluated the presence of autoantibodies targeting mitochondrial RNA (AmtRNA) in SLE. We quantified AmtRNA in an inducible model of murine SLE. The AmtRNA were also determined in SLE patients and healthy volunteers. AmtRNA titers were measured in both our induced model of murine SLE and in human SLE, and biostatistical analyses were performed to determine whether the presence and/or levels of AmtRNA were associated with clinical features expressed by SLE patients. Both IgG and IgM classes of AmtRNA were increased in SLE patients ( n = 86) compared to healthy controls ( n = 30) ( p < 0.0001 and p = 0.0493, respectively). AmtRNA IgG levels correlated with anti-mtDNA-IgG titers ( r s = 0.54, p < 0.0001) as well as with both IgG and IgM against β-2-glycoprotein I (anti-β 2 GPI; r s = 0.22, p = 0.05), and AmtRNA-IgG antibodies were present at higher levels when patients were positive for autoantibodies to double-stranded-genomic DNA ( p < 0.0001). AmtRNA-IgG were able to specifically discriminate SLE patients from healthy controls, and were negatively associated with plaque formation ( p = 0.04) and lupus nephritis ( p = 0.03). Conversely, AmtRNA-IgM titers correlated with those of anti-β 2 GPI-IgM ( r s = 0.48, p < 0.0001). AmtRNA-IgM were higher when patients were positive for anticardiolipin antibodies (aCL-IgG: p = 0.01; aCL-IgM: p = 0.002), but AmtRNA-IgM were not associated with any of the clinical manifestations assessed. These findings identify mtRNA as a novel mitochondrial antigen target in SLE, and support the concept that mitochondria may provide an important source of circulating autoantigens in SLE.