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IL-33 promotes type 2 immunity, epithelial repair, and tissue fibrosis by activating group 2 innate lymphoid cells (ILC2). ILC2 lack all known surface markers of mature T, B, NK, and myeloid cell lineages (Linneg), express the IL-33 receptor ST2, and release type 2 cytokines which contribute to cholangiocyte proliferation and activation of hepatic stellate cells. This pathway results in massive proliferation of the extrahepatic bile duct (EHBD) but also exacerbates liver fibrosis, suggesting that there may be tissue-specific subpopulations of IL-33-induced ILC. To determine the tissue-specific subsets of ILC in the hepatobiliary system, we analyzed CD45+Linneg mononuclear cells from IL-33 treated adult Balb/c mouse liver or EHBD by single cell RNA sequencing. Principal component analysis identified 6 major CD45+Linneg cell classes, two of which were restricted to the EHBD. One of these classes, biliary immature myeloid (BIM) cells, was predicted to interact with ILC2 by a network of shared receptor-ligand pairs. BIM highly expressed Gp49 and ST2 receptors on the cell surface while lacking surface expression of markers for mature myeloid cells. In conclusion, single cell RNA sequencing identified IL-33 responsive cell groups regionally confined to the liver or extrahepatic bile duct, including a novel population of CD45+Linneg Gp49-expressing mononuclear cells., Competing Interests: The authors have declared that no competing interests exist.

Axial symptoms emerge in a significant proportion of patients with Parkinson's disease (PD) within 5 years of deep brain stimulation (STN-DBS). Lowering the stimulation frequency may reduce these symptoms. The objectives of the current study were to establish the relationship between gait performance and STN-DBS frequency in chronically stimulated patients with PD, and to identify factors underlying variability in this relationship. Twenty-four patients treated chronically with STN-DBS (>4 years) were studied off-medication. The effect of stimulation frequency (40-140 Hz, 20 Hz-steps, constant energy) on gait was assessed in 6 sessions spread over 1 day. Half of the trials/session involved walking through a narrow doorway. The influence of stimulation voltage was investigated separately in 10 patients. Gait was measured using 3D motion capture and axial symptoms severity was assessed clinically. A novel statistical method established the optimal frequency(ies) for each patient by operating on frequency-tuning curves for multiple gait parameters. Narrowly-tuned optimal frequencies (20 Hz bandwidth) were found in 79% of patients. Frequency change produced a larger effect on gait performance than voltage change. Optimal frequency varied between patients (between 60 and 140 Hz). Contact site in the right STN and severity of axial symptoms were independent predictors of optimal frequency ( P = 0.009), with lower frequencies associated with more dorsal contacts and worse axial symptoms. We conclude that gait performance is sensitive to small changes in STN-DBS frequency. The optimal frequency varies considerably between patients and is associated with electrode contact site and severity of axial symptoms. Between-subject variability of optimal frequency may stem from variable pathology outside the basal ganglia.

Objective: To investigate the relation between donor characteristics and TRALI incidence., Background: Transfusion-related acute lung injury (TRALI) is a potentially fatal complication of transfusion. In pre-clinical studies and several clinical studies, TRALI has been related to loss of product quality during red blood cell (RBC) storage, called the "storage lesion". Donor characteristics, as for example age, genetics and life style choices influence this "storage lesion". We hypothesized that donor sex, age and blood type is related to TRALI incidence., Methods/materials: We performed a secondary analysis of two cohort studies, designed to identify TRALI risk factors by matching TRALI patients to transfused controls. We obtained donor sex, age and blood type from the Dutch Blood Bank Sanquin and investigated TRALI incidence in patients who were exposed to a certain donor characteristic. We used Kruskal-Wallis testing to compare the number of transfused products and Chi 2 testing to compare proportions of TRALI patients and transfused control., Results: After implementation of the male-donor only plasma strategy, patients received more transfusion products from male donors. However, we did not detect a relation between TRALI incidence and donor sex. Both TRALI patients and transfused controls received mainly products from donors over 41 years old, but donor age did not influence TRALI risk. Donor blood type, the transfusion of blood type-compatible and blood type-matched products also had no influence on TRALI incidence., Conclusion: We conclude that in two cohorts of TRALI patients, donor age, donor sex and donor blood type are unrelated to TRALI., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: The purpose of this study was to evaluate relationships between behavioral and psychosocial constructs, A1C, and diabetes-dependent quality of life (DQoL) among low-socioeconomic status, ethnically diverse young adults with diabetes., Methods: Using baseline data of 81 participants in the Resilient, Empowered, Active Living (REAL) randomized controlled trial, behavioral, cognitive, affective, and experiential variables were correlated with A1C and DQoL while adjusting for demographic characteristics, and these relationships were examined for potential effect modification., Results: The data indicate that depressive symptoms and satisfaction with daily activities are associated with both A1C and DQoL, while diabetes knowledge and participation in daily activities are associated with neither A1C nor DQoL. Two constructs, diabetes distress and life satisfaction, were associated with DQoL and were unrelated to A1C, while 2 constructs, self-monitoring of blood glucose and medication adherence, were associated with A1C but unrelated to DQoL. These relationships were largely unchanged by adjusting for demographic characteristics, while numerous effect modifications were found., Conclusion: The data suggest that when tailoring interventions, depressive symptoms and satisfaction with daily activities may be particularly fruitful intervention targets, as they represent modifiable risk factors that are associated with both A1C and DQoL.

Endocrine Society guideline recommendations on diabetes technology in adults originate from the 2016 guideline titled "Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline." Society recommendations on diabetes technology in children are contained in the 2011 guideline titled "Continuous Glucose Monitoring: An Endocrine Society Clinical Practice Guideline." The field of diabetes technology is a rapidly advancing one, with new devices released annually and data from clinical trials published frequently. This report describes the most recent findings since the 2011 and 2016 guidelines were written, combining summaries of new literature with the authors' clinical experience of new devices. Although we describe what we believe to be important scientific and technological updates since these guidelines were published, we are not advancing formal additions or amendments to previously offered recommendations.

Background: The majority of therapies have generally targeted fasting glucose control, and current mealtime insulin therapies have longer time action profiles than that of endogenously secreted insulin. The primary purpose of this study was to assess both glucose time-in-range (TIR: 70-180 mg/dL) and postprandial glucose excursions (PPGE) in 1-4 h using a real-time continuous glucose monitor (CGM) with Technosphere insulin (TI) versus insulin aspart in patients with type 1 diabetes (T1DM) on multiple daily injections (MDI)., Research Design and Methods: This pilot, investigator-led, collaborative, open-label, multicenter, clinical research trial enrolled 60 patients with T1DM with HbA1c levels ≥6.5% and ≤10%. Individuals were randomized to treatment with titrated TI (n = 26) or titrated insulin aspart (n = 34), stratified by baseline HbA1c levels (≤8% or >8%). All were required to wear a real-time CGM throughout the trial. All patients in the TI group were advised to take supplemental inhalations at 1 and 2 h after meals if indicated based on postprandial glucose (PPG) values. The coprimary outcomes were assessed both in the full intent-to-treat population and in those individuals randomized to TI who were compliant with supplemental doses ≥90% of the time (n = 15). The CGM data were analyzed using linear regression models., Results: Overall, those treated with TI versus aspart achieved comparable TIR, but less time spent in hypoglycemia (<60 and <50 mg/dL, both P < 0.05). In the TI-compliant group (n = 15), TIR was significantly greater (62.5% ± 2.6% vs. 53.8% ± 1.7%, P = 0.009) and time in hyperglycemia >180 mg/dL was lower (34.2% ± 2.7% vs. 41.0% ± 1.7%, P = 0.045) as compared with the aspart group. PPG was also significantly lower in the TI cohort at 60 and 90 min postmeal, and PPGE were lower in the TI-compliant group as compared with the aspart group over 1-4-h postmeal (P < 0.05). In addition, there was weight gain in the aspart group compared with weight loss in the TI group (P = 0.006) despite higher prandial TI insulin dose., Conclusions: We conclude that using TI appropriately at mealtimes with supplemental dosing improves prandial glucose (TIR and 1-4 h) control without any increase in time in hypoglycemia or weight gain in patients with T1DM on MDI. The study results support a larger study using a treat-to-target design to confirm these findings. Clinical trial reg. no. NCT03143816, clinicaltrials.gov .

Objectives: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO')., Background: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion., Methods: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale., Results: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [β 0·4(-0·1-1·0)], positive fluid balance [β 0·9(0·4-1·5)] and history of renal failure [β 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [β 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [β 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved., Conclusion: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes., (© 2017 British Blood Transfusion Society.)

Objective: The objective of this study was to evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 and 2 inhibitor sotagliflozin compared with placebo when combined with optimized insulin in adults with type 1 diabetes (T1D)., Research Design and Methods: In a double-blind, 52-week, international phase 3 trial, adults with T1D were randomized to placebo ( n = 258) or once-daily oral sotagliflozin 200 mg ( n = 261) or 400 mg ( n = 263) after 6 weeks of insulin optimization. The primary outcome was change in HbA 1c from baseline to 24 weeks. The first secondary end point was a composite of the proportion of patients with HbA 1c <7.0%, no episode of severe hypoglycemia, and no episode of diabetic ketoacidosis (DKA) at week 24. Fasting glucose, weight, insulin dose, and safety end points were assessed through 52 weeks., Results: At 24 weeks, placebo-adjusted changes in HbA 1c from baseline (7.8%) were -0.37% and -0.35% with sotagliflozin 200 and 400 mg, respectively ( P < 0.001), and differences were maintained at 52 weeks. At 52 weeks, greater proportions of sotagliflozin-treated patients (200 mg: 25.67%; 400 mg: 26.62%) than placebo-treated patients (14.34%; P ≤ 0.001) met the composite end point, and sotagliflozin 400 mg reduced fasting plasma glucose (-0.87 mmol/L; P = 0.008), weight (-2.92 kg; P < 0.001), and total daily insulin dose (-8.2%; P = 0.001). In a 24-week continuous glucose monitoring (CGM) substudy, postprandial glucose decreased ( P ≤ 0.009) and CGM demonstrated up to 3 h more time in the target range of 3.9-10.0 mmol/L with sotagliflozin. Treatment satisfaction increased and diabetes distress decreased with sotagliflozin ( P < 0.05 vs. placebo). The frequency of documented hypoglycemia was lower with sotagliflozin, and severe hypoglycemia occurred by week 52 in 13 patients (5.0%), 13 patients (5.0%), and 6 patients (2.3%) treated with placebo and sotagliflozin 200 and 400 mg, respectively. DKA occurred in 0 of 258 patients, 6 of 261 patients (2.3%), and 9 of 263 patients (3.4%) in these respective groups., Conclusions: In a 1-year study, sotagliflozin was associated with statistically significant HbA 1c reductions. More episodes of DKA and fewer episodes of documented and severe hypoglycemia were observed in patients using sotagliflozin relative to those receiving placebo (ClinicalTrials.gov, NCT02421510)., (© 2018 by the American Diabetes Association.)

Objective: Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D)., Research Design and Methods: The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo ( n = 268), sotagliflozin 200 mg ( n = 263), or sotagliflozin 400 mg ( n = 262) after 6 weeks of insulin optimization. The primary end point was HbA 1c change from baseline at 24 weeks. HbA 1c , weight, and safety were also assessed through 52 weeks., Results: From a mean baseline of 7.57%, placebo-adjusted HbA 1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P < 0.001). Among patients with a baseline HbA 1c ≥7.0%, an HbA 1c <7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively ( P ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were -1.08 mmol/L for fasting plasma glucose, -4.32 kg for weight, and -15.63% for bolus insulin dose and -11.87% for basal insulin dose (all P < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo ( P < 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo., Conclusions: In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA 1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941)., (© 2018 by the American Diabetes Association.)

Objective: To compare the effectiveness of two interventions to reduce diabetes distress (DD) and improve glycemic control among adults with type 1 diabetes (T1D)., Research Design and Methods: Individuals with T1D ( n = 301) with elevated DD and HbA 1c were recruited from multiple settings and randomly assigned to OnTrack, an emotion-focused intervention, or to KnowIt, an educational/behavioral intervention. Each group attended a full-day workshop plus four online meetings over 3 months. Assessments occurred at baseline and 3 and 9 months. Primary and secondary outcomes were change in DD and change in HbA 1c , respectively., Results: With 12% attrition, both groups demonstrated dramatic reductions in DD (effect size d = 1.06; 78.4% demonstrated a reduction of at least one minimal clinically important difference). There were, however, no significant differences in DD reduction between OnTrack and KnowIt. Moderator analyses indicated that OnTrack provided greater DD reduction to those with initially poorer cognitive or emotion regulation skills, higher baseline DD, or greater initial diabetes knowledge than those in KnowIt. Significant but modest reductions in HbA 1c occurred with no between-group differences. Change in DD was modestly associated with change in HbA 1c ( r = 0.14, P = 0.01), with no significant between-group differences., Conclusions: DD can be successfully reduced among distressed individuals with T1D with elevated HbA 1c using both education/behavioral and emotion-focused approaches. Reductions in DD are only modestly associated with reductions in HbA 1c . These findings point to the importance of tailoring interventions to address affective, knowledge, and cognitive skills when intervening to reduce DD and improve glycemic control., (© 2018 by the American Diabetes Association.)

Background: Gestational tight glycemic control is critical for women with type 1 diabetes (T1D). Limited data exist on the adoption and retention of diabetes technologies among women in different parity strata., Methods: We compared T1D management between T1D Exchange clinic registry participants (mean age 28 ± 9 years, 84% white non-Hispanic, and median T1D duration 13 years) who were pregnant at enrollment or year 1 follow-up ("recently pregnant" between 2010 and 2013, n = 214), ever (but not recently) pregnant (n = 1540), and never pregnant (n = 2586). We examined self-reported maternal and fetal outcomes in 130 women who delivered a baby within the last year., Results: Recently pregnant women had the lowest hemoglobin A1c (6.5% pregnant vs. 7.8% ever pregnant vs. 8.0% never pregnant, P < 0.001). Recently pregnant women reported the highest use of continuous subcutaneous insulin infusion (74% vs. 60% vs. 58%, adjusted P < 0.001) and continuous glucose monitor (CGM) (36% vs.17% vs. 12%, adjusted P < 0.001) therapies compared with ever or never pregnant women, respectively, after adjusting for age, diabetes duration, and socioeconomic status. Among women 18-25 years old, CGM use was highest among recently pregnant women (adjusted P = 0.0022). Never pregnant women 26-45 years old had a higher use of CGM compared with younger counterparts (adjusted P < 0.001). Adverse maternal and fetal outcomes were common., Conclusions: Despite high uptake levels of advanced diabetes technologies among pregnant women, rates of adverse maternal and fetal outcomes remain high. More studies are needed to determine how these technologies could be best used in pregnancy and postpartum to improve health outcomes among women with T1D.

Background: Red blood cell (RBC) transfusion has been related to thromboembolic events. Microvesicles in the RBC product may support coagulation because they have procoagulant effects in vitro. We investigated whether transfusion of RBCs containing extracellular vesicles promotes coagulation in human recipients. As transfusion is mostly administered to ill patients, we used a model of endotoxemia., Study Design and Methods: Eighteen healthy volunteers were randomized to receive either saline or fresh (2 days stored) or stored autologous (35 days stored) RBC transfusion (Dutch Trial Register: NTR4455). Two hours after infusion of lipopolysaccharide (LPS, from Escherichia coli, 2 ng/kg body weight), subjects received either saline or fresh or stored RBCs. Blood was sampled every 2 hours up to 8 hours after LPS infusion. Vesicles were measured with a flow cytometer (A50-Micro, Apogee Flow Systems)., Results: LPS resulted in increased thrombin generation compared to baseline. During storage, the total number of extracellular vesicles increased from 1.4 × 10 8 /mL (interquartile range [IQR], 8.3 × 10 7 -1.9 × 10 8 /mL) in the fresh product to 1.7 × 10 10 /mL (IQR, 7.9 × 10 9 -2.3 × 10 10 /mL; p < 0.01) in the stored product (p < 0.001). Vesicles appeared to be mostly RBC derived., Conclusion: After transfusion, extracellular vesicles from stored RBC products, but not from fresh products, could be detected in the circulation of healthy volunteers. However, infusion of stored RBC extracellular vesicles did not augment thrombin generation compared to endotoxemic controls. Also, levels of d-dimer and thrombin-antithrombin complex were unaffected. In conclusion, transfusion of autologous RBCs containing high levels of extracellular vesicles does not enhance coagulation in human volunteers with endotoxemia., (© 2018 AABB.)

Aims: Patients with a type-2-diabetes (T2D) phenotype positive for glutamic acid decarboxylase antibodies (GADA) represent the majority of cases of latent autoimmune diabetes of the adult (LADA). The GLP-1 receptor agonist dulaglutide, recently introduced for treatment of T2D, has yet to be evaluated in LADA patients. Our primary objective was to evaluate the effect of dulaglutide on glycaemic control (HbA1c) in GADA-positive LADA vs GADA-negative T2D patients., Methods: A post-hoc analysis was performed using data from 3 randomized phase 3 trials (AWARD-2,-4,-5; patients with GADA assessment) which were part of the dulaglutide clinical development programme in T2D. LADA patients were identified by GADA ≥5 IU/mL (ELISA). Changes in HbA1c during 12 months of treatment with dulaglutide or comparator were analysed using mixed-effect model repeated measures., Results: Of 2466 adults tested for GADA (dulaglutide, 1710; glargine, 298; sitagliptin, 294; placebo, 164), 2278 (92.4%) were GADA-negative and 188 (7.6%) were GADA-positive, including 58 GADA-high patients (> 200 IU/mL) and 130 GADA-low patients (≤200 and ≥5 IU/mL). Overall, baseline parameters were comparable between the groups. Dulaglutide resulted in comparable HbA1c reductions in GADA-negative (LS mean change [95%CI], -1.09% [-1.15, -1.03]) and GADA-positive patients (-0.94% [-1.15, -0.72]) at 12 months. HbA1c reductions were numerically, but not statistically, significantly larger in GADA-low patients (-1.02% [-1.26, -0.78]) vs GADA-high patients (-0.72% [-1.21,-0.24]) at 12 months. Similar outcomes were observed at 3 and 6 months., Conclusions: These data are the first to indicate that dulaglutide was effective in reducing HbA1c in LADA patients., (© 2018 John Wiley & Sons Ltd.)

Background: Disciplines involved in diagnosing transfusion-related acute lung injury (TRALI) report according to a "one-hit" theory. However, studies showed that patients with an underlying condition are at increased risk of the development of TRALI. We investigated whether accumulating evidence on the "two-hit" theory has changed the practice of reporting TRALI., Materials and Methods: Departments of haematology, haemovigilance, transfusion medicine, intensive care and anaesthesiology from all Dutch hospitals with at least five beds equipped for mechanical ventilation were invited to participate in an online survey. Using clinical vignettes with conjoint analysis we investigated the effect of patients' age, admission diagnosis, type and number of transfusions and presence of risk factors for acute lung injury on TRALI reporting. A positive β-coefficient indicated a higher likelihood of reporting TRALI., Results: We received 129 questionnaires (response rate 74%). Respondents were more likely to report TRALI in younger patients, if symptoms developed within 2 hours of transfusion and if patients had received multiple transfusions. Sepsis and the presence of a risk factor for acute lung injury reduced the inclination to report. Transfusion medicine physicians and haemovigilance staff no longer took the age of transfusion products into account in their diagnostic considerations on TRALI., Discussion: We conclude that the multidisciplinary team involved in TRALI reporting, still considers TRALI a "one-hit" event, despite accumulating evidence that supports the "two-hit" theory. These results suggest that the patients most at risk of developing TRALI are not reported to the blood bank.

Objective: The impact of weight loss intervention on disability-free life expectancy in adults with diabetes is unknown. We examined the impact of a long-term weight loss intervention on years spent with and without physical disability., Research Design and Methods: Overweight or obese adults with type 2 diabetes age 45-76 years ( n = 5,145) were randomly assigned to a 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Physical function was assessed annually for 12 years using the 36-Item Short Form Health Survey. Annual incidence of physical disability, mortality, and disability remission were incorporated into a Markov model to quantify years of life spent active and physically disabled., Results: Physical disability incidence was lower in the ILI group (6.0% per year) than in the DSE group (6.8% per year) (incidence rate ratio 0.88 [95% CI 0.81-0.96]), whereas rates of disability remission and mortality did not differ between groups. ILI participants had a significant delay in moderate or severe disability onset and an increase in number of nondisabled years ( P < 0.05) compared with DSE participants. For a 60-year-old, this effect translates to 0.9 more disability-free years (12.0 years [95% CI 11.5-12.4] vs. 11.1 years [95% CI 10.6-11.7]) but no difference in total years of life. In stratified analyses, ILI increased disability-free years of life in women and participants without cardiovascular disease (CVD) but not in men or participants with CVD., Conclusions: Long-term lifestyle interventions among overweight or obese adults with type 2 diabetes may reduce long-term disability, leading to an effect on disability-free life expectancy but not on total life expectancy., (© 2018 by the American Diabetes Association.)

With the enormous growth in the development and utilization of solar-energy resources, the proliferation of waste solar panels has become problematic. While current research into solar panels has focused on how to improve the efficiency of the production capacity, the dismantling and recycling of end-of-life (EOL) panels are seldom considered, as can be seen, for instance, in the lack of dedicated solar-panel recycling plants. EOL solar-panel recycling can effectively save natural resources and reduce the cost of production. To address the environmental conservation and resource recycling issues posed by the huge amount of waste solar panels regarding environmental conservation and resource recycling, the status of the management and recycling technologies for waste solar panels are systemically reviewed and discussed in this article. This review can provide a quantitative basis to support the recycling of PV panels, and suggests future directions for public policy makers. At present, from the technical aspect, the research on solar panel recovery is facing many problems, and we need to further develop an economically feasible and non-toxic technology. The research on solar photovoltaic panels' management at the end of life is just beginning in many countries, and there is a need for further improvement and expansion of producer responsibility., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To assess the efficacy of a manualized occupational therapy (OT) intervention (Resilient, Empowered, Active Living with Diabetes [REAL Diabetes]) to improve glycemic control and psychosocial well-being among ethnically diverse young adults with low socioeconomic status (SES) who have type 1 or type 2 diabetes., Research Design and Methods: Eighty-one young adults (age 22.6 ± 3.5 years; hemoglobin A 1c [HbA 1c ] = 10.8%/95 mmol/mol ± 1.9%/20.8 mmol/mol) were randomly assigned to the REAL Diabetes intervention group (IG) or an attention control group (CG) over 6 months. IG participants received biweekly sessions guided by a manual composed of seven content modules; CG participants received standardized educational materials and biweekly phone calls. Blinded assessors collected data at baseline and 6 months. The primary outcome was HbA 1c ; secondary outcomes included diabetes self-care, diabetes-related quality of life (QOL), diabetes distress, depressive symptoms, and life satisfaction. Change scores were analyzed using Wilcoxon rank sum tests., Results: Intent-to-treat analyses showed that IG participants showed significant improvement in HbA 1c (-0.57%/6.2 mmol/mol vs. +0.36%/3.9 mmol/mol, P = 0.01), diabetes-related QOL (+0.7 vs. +0.15, P = 0.04), and habit strength for checking blood glucose (+3.9 vs. +1.7, P = 0.05) as compared with CG participants. There was no statistically significant effect modification by sex, ethnicity, diabetes type, recruitment site, or SES. No study-related serious adverse events were reported., Conclusions: The REAL Diabetes intervention improved blood glucose control and diabetes-related QOL among a typically hard-to-reach population, thus providing evidence that a structured OT intervention may be beneficial in improving both clinical and psychosocial outcomes among individuals with diabetes., (© 2018 by the American Diabetes Association.)

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Introduction: Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management., Methods: We conducted an open-label, non-randomized, controlled, before-and-after 1-year study of this continuous care intervention (CCI) and usual care (UC). Primary outcomes were glycosylated hemoglobin (HbA 1c ), weight, and medication use. Secondary outcomes included fasting serum glucose and insulin, HOMA-IR, blood lipids and lipoproteins, liver and kidney function markers, and high-sensitivity C-reactive protein (hsCRP)., Results: 349 adults with T2D enrolled: CCI: n = 262 [mean (SD); 54 (8) years, 116.5 (25.9) kg, 40.4 (8.8) kg m 2 , 92% obese, 88% prescribed T2D medication]; UC: n = 87 (52 (10) years, 105.6 (22.15) kg, 36.72 (7.26) kg m 2 , 82% obese, 87% prescribed T2D medication]. 218 participants (83%) remained enrolled in the CCI at 1 year. Intention-to-treat analysis of the CCI (mean ± SE) revealed HbA 1c declined from 59.6 ± 1.0 to 45.2 ± 0.8 mmol mol -1 (7.6 ± 0.09% to 6.3 ± 0.07%, P < 1.0 × 10 -16 ), weight declined 13.8 ± 0.71 kg (P < 1.0 × 10 -16 ), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (P < 1.0 × 10 -16 ). Insulin therapy was reduced or eliminated in 94% of users; sulfonylureas were entirely eliminated in the CCI. No adverse events were attributed to the CCI. Additional CCI 1-year effects were HOMA-IR - 55% (P = 3.2 × 10 -5 ), hsCRP - 39% (P < 1.0 × 10 -16 ), triglycerides - 24% (P < 1.0 × 10 -16 ), HDL-cholesterol + 18% (P < 1.0 × 10 -16 ), and LDL-cholesterol + 10% (P = 5.1 × 10 -5 ); serum creatinine and liver enzymes (ALT, AST, and ALP) declined (P ≤ 0.0001), and apolipoprotein B was unchanged (P = 0.37). UC participants had no significant changes in biomarkers or T2D medication prescription at 1 year., Conclusions: These results demonstrate that a novel metabolic and continuous remote care model can support adults with T2D to safely improve HbA 1c , weight, and other biomarkers while reducing diabetes medication use. CLINICALTRIALS., Gov Identifier: NCT02519309., Funding: Virta Health Corp.

Transfusion Related Acute Lung Injury (TRALI) is one of the leading causes of mortality and morbidity following blood transfusion. The mechanisms behind the disease are not yet fully understood but seem to involve many different activating pathways and donor factors, in synergy with patient susceptibility. Studies have focused mostly on neutrophil activation, as aggregates of neutrophils and edema in lungs are found in post-mortem histological sections. This review aims to highlight the role of the endothelium in TRALI, as activated endothelium is the main promoter of leukocyte transmigration, and creates the barrier between blood and tissue. Since recent evidence suggests that a strong endothelial barrier prevents leukocyte transmigration and vascular leakage, we suggest that strengthening this barrier may be key to TRALI prevention., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Many then believed CGM would revolutionise the use of intensive insulin therapy in diabetes; however, progress towards that vision has been gradual. Although increasing, the proportion of individuals using CGM rather than conventional systems for self-monitoring of blood glucose on a daily basis is still low in most parts of the world. Barriers to uptake include cost, measurement reliability (particularly with earlier-generation systems), human factors issues, lack of a standardised format for displaying results and uncertainty on how best to use CGM data to make therapeutic decisions. This scientific statement makes recommendations for systemic improvements in clinical use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and health outcomes for more people with diabetes.

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long-term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long-term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow-up continued for a median of 11.3 years at 16 academic centers. A total of 5145 persons aged 45 to 76 years with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self-report and confirmed with central adjudication of medical records. The baseline mean age of participants was 59 years, 60% were women, 63% were white, and the mean BMI was 36 kg/m 2 . Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. A total of 731 participants had a confirmed incident fracture (358 in DSE versus 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR 1.39; 95% CI, 1.02 to 1.89). An intensive lifestyle intervention resulting in long-term weight loss in overweight/obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Objective: To examine the relationship between objectively assessed moderate-to-vigorous intensity physical activity (MVPA) and 4-year weight loss (WL) and WL maintenance among individuals with diabetes enrolled in the Look AHEAD trial., Methods: MVPA was measured in a subgroup of lifestyle intervention participants with accelerometry data at baseline and at 1 and 4 years (n = 553; age: 59.7 ± 6.8 y; BMI: 35.5 ± 5.9 kg/m 2 ). Minutes per week of bout-related MVPA were calculated (≥ 3 metabolic equivalents, ≥ 10-min bouts), and adherence to the national physical activity (PA) recommendation for WL maintenance (≥ 250 min/wk) was assessed., Results: Independent of 1-year WL, 4-year MVPA (β = -0.003, SE = 0.002, P = 0.006), but not 1-year MVPA (β = 0.0001, SE = 0.001, P = 0.50), was significantly associated with 4-year WL. Compared with "nonmaintainers" (≥ 10% WL at year 1, but < 10% at year 4; n = 132), WL maintainers (≥ 10% WL at years 1 and 4; n = 103) had higher MVPA at year 1 (253.4 ± 251.8 vs. 163.9 ± 158.2 min/wk, P = 0.002) and year 4 (155.3 ± 180.6 vs. 111.4 ± 154.5 min/wk, P = 0.046). Although 38.8% and 22.3% of WL maintainers engaged in ≥ 250 min/wk at years 1 and 4, respectively, many engaged in < 150 min/wk (year 1: 41%, year 4: 61%)., Conclusions: Higher weekly MVPA is associated with greater long-term WL and weight maintenance; however, many individuals are able to maintain ≥ 10% WL while engaging in little MVPA., (© 2017 The Obesity Society.)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide. Detection of heterozygously deficient females can be difficult as residual activity in G6PD-sufficient red blood cells (RBCs) can mask deficiency. In this study, we compared accuracy of 4 methods for detection of G6PD deficiency in females. Blood samples from females more than 3 months of age were used for spectrophotometric measurement of G6PD activity and for determination of the percentage G6PD-negative RBCs by cytofluorometry. An additional sample from females suspected to have G6PD deficiency based on the spectrophotometric G6PD activity was used for measuring chromate inhibition and sequencing of the G6PD gene. Of 165 included females, 114 were suspected to have heterozygous deficiency. From 75 females, an extra sample was obtained. In this group, mutation analysis detected 27 heterozygously deficient females. The sensitivity of spectrophotometry, cytofluorometry, and chromate inhibition was calculated to be 0.52 (confidence interval [CI]: 0.32-0.71), 0.85 (CI: 0.66-0.96), and 0.96 (CI: 0.71-1.00, respectively, and the specificity was 1.00 (CI: 0.93-1.00), 0.88 (CI: 0.75-0.95), and 0.98 (CI: 0.89-1.00), respectively. Heterozygously G6PD-deficient females with a larger percentage of G6PD-sufficient RBCs are missed by routine methods measuring total G6PD activity. However, the majority of these females can be detected with both chromate inhibition and cytofluorometry.

Objective: Translations of the Diabetes Prevention Program (DPP) have proliferated in recent years, with increasing expansion to digital formats. Although these DPP translations have consistently shown favorable clinical outcomes, long-term data for digital formats are limited. This study's objective was to examine clinical outcomes up to 3 years post-baseline and the relationship between program engagement and clinical outcomes in a digital DPP., Research Design and Methods: In a single-arm, non-randomized trial, 220 patients previously diagnosed with prediabetes were enrolled in the Omada Health Program, a commercially available, 16-week DPP-based weight loss intervention followed by an ongoing weight maintenance intervention. Changes in body weight and A1c were assessed annually. Relationships between program engagement during the first year and clinical outcomes across 3 years were examined., Results: Participants were socioeconomically diverse (62% women, 50.2% non-Hispanic white, 51.7% college educated or higher). From baseline to 3 years, those participants who completed four or more lessons and nine or more lessons achieved significant sustained weight loss (-3.0% and -2.9%, respectively) and an absolute reduction in A1c (-0.31 and -0.33, respectively) with an average remission from the prediabetes range to the normal glycemic range. Factor analysis of engagement metrics during the first year revealed two underlying dimensions, one comprising lesson completion and health behavior tracking consistency, and the other comprising website logins and group participation. When these two factors were used to predict weight loss, only the logins and group participation factor was a significant predictor of weight loss at 16 weeks and 1 year., Conclusions: This study demonstrates significant long-term reductions in body weight and A1c in a digital DPP and identifies patterns of program engagement that predict weight loss., Competing Interests: Competing interests: The authors declare the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: SCS was employed by Omada Health and received salary and stock options. LJ was a statistical consultant of Omada Health and was paid a salary. RJE was employed by Omada Health and received salary and stock options. KM was employed by Omada Health and received salary and stock options. ALP was a scientific advisor for Omada Health and received stock options.

Aim: To determine the cross-sectional and longitudinal associations between diabetes distress and diabetes management., Methods: In a non-interventional study, 224 adults with Type 1 diabetes were assessed for diabetes distress, missed insulin boluses, hypoglycaemic episodes, and HbA 1c at baseline and 9 months., Results: At baseline, greater distress was associated with higher HbA 1c and a greater percentage of missed insulin boluses. Longitudinally, elevated baseline distress was related to increased missed insulin boluses, and decreases in distress were associated with decreases in HbA 1c . In supplementary analyses, neither depression symptoms nor a diagnosis of major depressive disorder was associated with missed insulin boluses, HbA 1c or hypoglycaemic episodes in cross-sectional or longitudinal analyses., Conclusions: Significant cross-sectional and longitudinal associations were found between diabetes distress and management; in contrast, no parallel associations were found for major depressive disorder or depression symptoms. Findings suggest that elevated distress may lead to more missed insulin boluses over time, suggesting a potential intervention target. The covarying association between distress and HbA 1c points to the complex and likely interactive associations between these constructs. Findings highlight the need to address distress as an integral part of diabetes management in routine care., (© 2017 Diabetes UK.)

Background: Transfusion-related immunomodulation (TRIM) encompasses immunosuppressive and proinflammatory effects induced by red blood cell (RBC) transfusion. Changes that occur during storage in the RBC product have been hypothesized to underlie TRIM, mediated by tolerance of toll-like receptors (TLR). We investigated whether transfusion of 35-day-stored autologous RBCs alters cytokine production in response to stimulation with lipopolysaccharide (LPS) or lipotheic acid (LTA), in a clinically relevant model of endotoxemia., Study Design and Methods: Eighteen volunteers received 2 ng/kg LPS intravenously, followed by normal saline or 2- or 35-day-stored autologous RBC transfusion. Before LPS, before transfusion, and 6 hours after transfusion blood was collected to measure cytokine gene expression. Whole blood was used for ex vivo stimulation with LPS and LTA, after which cytokine levels were measured with enzyme-linked immunosorbent assay., Results: In vivo LPS induced a biphasic response in cytokine mRNA with peak values 2 hours after LPS infusion. Storage time of RBC transfusion did not influence cytokine mRNA levels. In vivo infusion of LPS resulted in tolerance for ex vivo stimulation with LPS and LTA. However, transfusion of either fresh or stored RBCs did not further affect the capacity to produce cytokines after ex vivo stimulation., Conclusion: In a clinically relevant model of human endotoxemia, autologous transfusion of 35-day-stored RBCs does not influence cytokine mRNA levels nor does it change the capacity of white blood cells in whole blood to produce cytokines after ex vivo stimulation with LPS or LTA., (© 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Type 1 diabetes is a challenging condition to manage for various physiological and behavioural reasons. Regular exercise is important, but management of different forms of physical activity is particularly difficult for both the individual with type 1 diabetes and the health-care provider. People with type 1 diabetes tend to be at least as inactive as the general population, with a large percentage of individuals not maintaining a healthy body mass nor achieving the minimum amount of moderate to vigorous aerobic activity per week. Regular exercise can improve health and wellbeing, and can help individuals to achieve their target lipid profile, body composition, and fitness and glycaemic goals. However, several additional barriers to exercise can exist for a person with diabetes, including fear of hypoglycaemia, loss of glycaemic control, and inadequate knowledge around exercise management. This Review provides an up-to-date consensus on exercise management for individuals with type 1 diabetes who exercise regularly, including glucose targets for safe and effective exercise, and nutritional and insulin dose adjustments to protect against exercise-related glucose excursions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Correction of coagulopathy prior to central venous catheter (CVC) placement is advocated by guidelines, while retrospective studies support restrictive use of transfusion products., Study Design and Methods: We conducted a mixed vignette and questionnaire web survey to investigate current practice and preferences for CVC placement. Clinical vignettes were used to quantify the tendency to administer platelet concentrate. A positive ß-coefficient is in favour of administering platelet concentrate., Results: Ninety-seven physicians answered the survey questions (36 critical care physicians, 14 haematologists, 20 radiologists and 27 anaesthesiologist). Eighty-six physicians subsequently completed the clinical vignettes (response rate 71%). Preferences in favour of correcting thrombocytopenia prior CVC placement were platelet counts of 10 × 10 9 /L and 20 × 10 9 /L (ß = 3·9; ß = 3·2, respectively), the subclavian insertion site (ß = 0·8). An elevated INR (INR = 3; ß = 0·6) and an elevated aPTT (aPTT = 60 s; ß = 0·4) showed a positive trend towards platelet transfusion. Platelet transfusion was less likely in an emergency setting (ß = -0·4). Reported transfusion thresholds for CVC placement varied from <10 × 10 9 /L to 80 × 10 9 /L for platelet count, from 1·0 to 10·0 for INR and from 25 s to 150 s for aPTT. Implementation of ultrasound guidance as standard practice was limited., Conclusion: Current transfusion practice prior to CVC placement is highly variable. Physicians adjust the decision to correct coagulopathy prior CVC placement based on clinical parameters, insertion site and technique applied., (© 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Systemic inflammatory response syndrome (SIRS) is observed during critical illness in most patients. It is defined by a clinical definition. The composition of volatile organic compounds (VOCs) in exhaled breath may change during SIRS and may thus serve as a diagnostic tool. We investigated whether exhaled breath VOCs can serve as biomarker for SIRS in a human model of endotoxemia. Eighteen healthy volunteers received 2 ng Eschericia coli lipopolysaccharide (LPS) kg -1 body weight intravenously. Venous blood and exhaled breath were collected before infusion of LPS and every 2 h thereafter, up to 8 h after infusion. The interleukin (IL)-6 concentration was measured in plasma. VOCs in the exhaled breath were measured by gas chromatography and mass spectrometry. A mixed effects model was fitted to examine the relation between the measured compounds in exhaled breath and time after LPS infusion or IL-6 levels in plasma. Partially-least squares discriminant analysis (PLS-DA) was used to investigate whether we could discriminate between samples collected before and after LPS infusion. The exhaled concentrations of 3-methyl-pentane, 4-methyl-pentanol, 1-hexanol, 2,4-dimethyl-heptane, decane and one unknown compound changed after LPS infusion. However, the false-discovery rate was 43% for the total set of 52 compounds that were present in all samples. Of these VOCs only the unknown compound was associated with systemic levels of IL-6. The PLS-DA algorithm resulted in a moderate discriminatory accuracy. SIRS induced by endotoxemia in human volunteers resulted in minor changes in exhaled VOCs. We therefore conclude that LPS infusion in healthy volunteers does not induce metabolic effects that can be detected through VOC analysis of the exhaled breath. This trial is registered at the Dutch Trial Register: NTR4455.

Objectives: This study examined the relationship between medication adherence, cost sharing measured as out-of-pocket spending, and total annual spending in Medicare beneficiaries with type 2 diabetes (T2D) to evaluate whether pharmacy cost-sharing programs have the potential to decrease adherence. These programs may unintentionally increase the risk of medical complications and may result in higher spending overall., Study Design: This retrospective study used 2006 to 2009 Medicare claims data. The sample included patients 65 years or older with T2D (at least 1 claim with International Classification of Diseases, 9th Revision, Clinical Modification codes 250.x0 and 250.x2 and at least 1 antidiabetes drug claim)., Methods: Medication adherence was measured as proportion of days covered over the first 12 months of observation. Spending and adherence outcomes were defined in deciles., Results: The sample included 12,305 patient-year observations. Pharmacy spending for patients in the most adherent (10th) decile was 59% higher than that for patients in the least adherent (1st) decile ($4839 vs $3046). Yet, patients in the 10th decile had 49% lower total ($12,531 vs $24,468) and 64% lower medical spending ($7692 vs $21,421) than patients in the 1st decile. Greater out-of-pocket spending was correlated with lower adherence and higher total and medical spending., Conclusions: This study describes a widespread variation in medication adherence, pharmacy cost sharing, and medical spending in a sample of Medicare beneficiaries with T2D. We found that lower adherence was correlated with higher cost sharing in the Medicare population, perhaps because of unobserved confounding factors. However, the existing literature on patients with employer-sponsored insurance suggests some of this correlation may be indicative of causal relationships.

Objective: Despite the increased popularity of newer, fast-acting bolus insulin treatment options that allow for more flexibility in the timing of bolus insulin dosing in recent years, relatively little is known about people with diabetes who administer bolus insulin at differing times in relation to their meals. The purpose of this study was to investigate bolus insulin dose timing in relation to meals among people with type 1 (T1D) and type 2 (T2D) diabetes, as well as to better understand the characteristics and experiences of people who bolus dose at differing times., Methods: A web-based survey of adults with T1D and T2D treated with bolus insulin therapy in Germany, the UK, and USA was conducted., Results: A total of 906 respondents completed the survey (39% T1D; 61% T2D). A majority of respondents reported bolus dosing before meals in the previous week (57.0%), followed by after meals (18.9%), with meals (12.7%), and at varying times (11.5%). Compared to respondents who dosed with or after meals, those who dosed before meals were significantly less likely to experience hypoglycemia (before, 55.7%; with, 72.8%; after, 68.7%; p < .001) in the previous week. Respondents who bolus dosed before meals were significantly more likely to perceive bolus dose timing as flexible (45.5%) compared to those who dosed with (27.8%) or after (35.7%) meals (p < .001)., Conclusion: Results show that many people with T1D and T2D dose their bolus insulin with or after meals. Key limitations of all self-report surveys include potential bias in responses and generalizability of findings. However, the study was designed to help mitigate these limitations. The findings have implications for clinicians and suggest opportunities for improving diabetes education and care.

Objective: To determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D)., Research Design and Methods: A randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA 1c ≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% [53 ± 7.7 mmol/mol]); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only ( n = 149) or CGM+BGM ( n = 77) group. The primary outcome was time in range (70-180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%., Results: CGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively ( P < 0.001). Mean time in 70-180 mg/dL was 63 ± 13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group (adjusted difference 0%; one-sided 95% CI -2%). No severe hypoglycemic events occurred in the CGM-only group, and one occurred in the CGM+BGM group., Conclusions: Use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia., (© 2017 by the American Diabetes Association.)

Overview: This paper describes the study protocol used to evaluate the Resilient, Empowered, Active Living with Diabetes (REAL Diabetes) intervention and reports on baseline characteristics of recruited participants. REAL Diabetes is an activity-based intervention designed to address the needs of young adults diagnosed with type 1 (T1D) or type 2 diabetes (T2D) from low socioeconomic status or racial/ethnic minority backgrounds. The REAL intervention incorporates tailored delivery of seven content modules addressing various dimensions of health and well-being as they relate to diabetes, delivered by a licensed occupational therapist., Methods: In this pilot randomized controlled trial, participants are assigned to the REAL Diabetes intervention or an attention control condition. The study's primary recruitment strategies included in-person recruitment at diabetes clinics, mass mailings to clinic patients, and social media advertising. Data collection includes baseline and 6-month assessments of primary outcomes, secondary outcomes, and hypothesized mediators of intervention effects, as well as ongoing process evaluation assessment to ensure study protocol adherence and intervention fidelity., Results: At baseline, participants (n=81) were 51% female, 78% Latino, and on average 22.6years old with an average HbA1c of 10.8%. A majority of participants (61.7%) demonstrated clinically significant diabetes distress and 27.2% reported symptoms consistent with major depressive disorder. Compared to participants with T1D, participants with T2D had lower diabetes-related self-efficacy and problem-solving skills. Compared to participants recruited at clinics, participants recruited through other strategies had greater diabetes knowledge but weaker medication adherence., Discussion: Participants in the REAL study demonstrate clinically significant medical and psychosocial needs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Young adults with type 1 diabetes transitioning from pediatric to adult care are at risk for adverse outcomes. We developed a survey to evaluate transition experiences in two groups of young adults with type 1 diabetes, before (PEDS) and after (ADULT) transition to adult care., Research Design and Methods: We fielded an electronic survey to young adults (18 to <30 years) at 60 T1D Exchange Clinic Registry centers., Results: Surveys were completed by 602 young adults, 303 in the PEDS group (60% female, age 20 ± 2 years) and 299 in the ADULT group (62% female, age 24 ± 3 years). In the PEDS group, mean anticipated transition age was 22 ± 2 years; 64% remained in pediatric care because of emotional attachment to the provider. The ADULT group transitioned at age 19 ± 2 years, mainly after pediatric provider recommendation. More than 80% of respondents reported receiving counseling on type 1 diabetes self-management and screening tests from pediatric providers, but less than half (43% PEDS and 33% ADULT) reported discussing reproductive health. In the PEDS group, half had discussed transfer with pediatric providers. Of the ADULT participants, 63% received an adult provider referral, and 66% felt mostly/completely prepared to transition. ADULT participants with fewer pretransition pediatric visits or who felt unprepared for transition had increased odds of gaps >6 months between pediatric and adult care. Receipt of transition preparation counseling was not associated with self-reported hemoglobin A 1c <7.0% in either group., Conclusions: These results support the need for intensive efforts to integrate transition preparation counseling and care coordination into pediatric type 1 diabetes care., (© 2017 by the American Diabetes Association.)

Objective: To assess the effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic parameters and measures of glucose variability assessed by a 9-point self-monitoring blood glucose (SMBG) and continuous glucose monitoring (CGM) profiles, and patient-reported outcomes as an add-on to insulin among participants with type 1 diabetes., Research Design and Methods: In this randomized, double-blind study, 351 participants received canagliflozin 100 or 300 mg or placebo for 18 weeks. Change from baseline in daily mean glucose and SD was measured using a 9-point SMBG profile. In a subset of 89 participants who underwent CGM, the change from baseline in mean glucose, measures of glycemic variability (SD, coefficient of variation, and mean amplitude of glycemic excursions), and time spent in glycemic ranges were assessed. Change in treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire (n = 328)., Results: At week 18, reductions in daily mean glucose and SD measured using the 9-point SMBG profile were seen with canagliflozin 100 and 300 mg versus placebo. Reductions in mean glucose (-1.2, -0.7, and 0.6 mmol/L) and measures of glycemic variability assessed by CGM, such as changes in glucose SD (-0.3, -0.7, and 0.1 mmol/L), were also seen with canagliflozin 100 and 300 mg versus placebo, respectively. Canagliflozin 100 and 300 mg were associated with increases in time spent within target (glucose >3.9 to ≤10.0 mmol/L) compared with placebo (11.6%, 10.1%, and -3.5%, respectively) and commensurate reductions in time spent above the target level (glucose >10.0 mmol/L; -12.7%,-7.6%, and 5.7%, respectively). Participants showed greater improvement in treatment satisfaction with canagliflozin versus placebo; reductions in insulin dose, SD of glucose, and body weight contributed to the relationship between canagliflozin and satisfaction change., Conclusions: Canagliflozin improved indices of glycemic variability and was associated with improvement in treatment satisfaction versus placebo over 18 weeks among participants with type 1 diabetes. Although these data from this study demonstrate the potential benefits of canagliflozin in people with type 1 diabetes, canagliflozin is not approved for the treatment of type 1 diabetes and should not currently be used in people with type 1 diabetes., (© 2017 by the American Diabetes Association.)

Purpose: We identified and treated young adults with type 1 diabetes who had been lost to follow-up during their transfer from pediatric to adult care, comparing their clinical, psychosocial, and health care utilization outcomes to participants receiving continuous care (CC) throughout the transition to adult care., Methods: Individuals in their last year of pediatric care (CC group, n = 51) and individuals lost to follow-up in the transfer to adult care ("lapsed care" [LC] group, n = 24) were followed prospectively for 12 months. All participants were provided developmentally tailored diabetes education, case management, and clinical care through a structured transition program., Results: At baseline, LC participants reported lapses in care of 11.6 months. Compared with CC participants, they had higher hemoglobin A1C (A1C; p = .005), depressive symptoms (p = .05), incidence of severe hypoglycemia (p = .005), and emergency department visits (p = .004). At 12-month follow-up, CC and LC participants did not differ on the number of diabetes care visits (p = .23), severe hypoglycemia (no events), or emergency department visits (p = .22). Both groups' A1C improved during the study period (CC: p = .03; LC: p = .02). LC participants' depressive symptoms remained elevated (p = .10), and they reported a decline in life satisfaction (p = .007). There was greater loss to follow-up in the LC group (p = .04)., Conclusions: Our study suggests that, for young adults with a history of lapses in care, a structured transition program is effective in lowering A1C, reducing severe hypoglycemia and emergency department utilization, and improving uptake of routine diabetes care. Loss to follow-up and psychosocial concerns remain significant challenges in this population., Competing Interests: The authors do not disclose any conflicts of interest., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The accumulation of non-polar lipids arachidonic acid, 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE and 15-HETE during storage of transfusion products may play a role in the onset of transfusion-related acute lung injury (TRALI), a syndrome of respiratory distress after transfusion., Materials and Methods: We investigated non-polar lipid accumulation in red blood cells (RBCs) stored for 42 days, plasma stored for 7 days at either 4 or 20°C and platelet (PLT) transfusion products stored for 7 days. Furthermore, we investigated whether transfusion of RBCs with increased levels of non-polar lipids induces TRALI in a 'two-hit' human volunteer model. All products were produced following Dutch Blood Bank protocols and are according to European standards. Non-polar lipids were measured with high-performance liquid chromotography followed by mass spectrometry., Results: All non-polar lipids increased in RBCs after 21 days of storage compared to baseline. The non-polar lipid concentration in plasma increased significantly, and the increase was even more pronounced in products stored at 20°C. In platelets, baseline levels of 5-HETE and 15-HETE were higher than in RBCs or plasma. However, the non-polar lipids did not change significantly during storage of PLT products. Infusion of RBCs with increased levels of non-polar lipids did not induce TRALI in LPS-primed human volunteers., Conclusion: We conclude that non-polar lipids accumulate in RBC and plasma transfusion products and that accumulation is temperature dependent. Accumulation of non-polar lipids does not appear to explain the onset of TRALI (Dutch Trial Register - NTR4455)., (© 2016 International Society of Blood Transfusion.)

Cytochemistry is the discipline that is applied to visualize specific molecules in individual cells and has become an essential tool in life sciences. Immunocytochemistry was developed in the sixties of last century and is the most frequently used cytochemical application. However, metabolic mapping is the oldest cytochemical approach to localize activity of specific enzymes, but in the last decades of the previous century and the first decade of the present century it almost became obsolete. The popularity of this approach revived in the past few years. Metabolism gained interest as player in chronic and complex diseases such as cancer, diabetes, neurodegenerative diseases, and vascular diseases and both enzyme cytochemistry and metabolic mapping have become important tools in life sciences.In this chapter, we present glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most prevalent enzyme deficiency worldwide, to illustrate recent developments in enzyme cytochemistry or metabolic mapping. The first assays which were developed quantified enzyme activity but were unreliable for single cell evaluation. The field has expanded with the development of cytochemical single cell assays and DNA testing. Still, all assays-from the earliest developed tests up to the most recently developed tests-have their place in investigations on G6PD activity. Recently, nanoscopy has become available for light and fluorescence microscopy at the nanoscale. For nanoscopy, cytochemistry is an essential tool to visualize intracellular molecular processes. The ultimate goal in the coming years will be nanoscopy of living cells so that the molecular dynamics can be studied. Cytochemistry will undoubtedly play a critical role in these developments.

Background: Transfusion of a single unit of stored red blood cells (RBCs) has been hypothesized to induce supra-physiological levels of non-transferrin bound iron (NTBI), which may enhance inflammation and act as a nutrient for bacteria. We investigated the relation between RBC storage time and iron levels in a clinically relevant "two-hit" human transfusion model., Study Design and Methods: Eighteen healthy male volunteers (ages 18-35 years) were infused with 2 ng lipopolysaccharide (LPS)/kg to induce systemic inflammatory response syndrome. Two hours later, each participant received either 1 unit of 2-day stored (2D) autologous RBCs, 35-day stored (35D) autologous RBCs, or an equal volume of saline. Every 2 hours up to 8 hours after LPS infusion, hemoglobin, hemolysis parameters, and iron parameters, including NTBI, were measured., Results: Transfusion of both 2D and 35D RBCs caused increases in hemoglobin, plasma iron, and transferrin saturation; whereas levels remained stable in the saline group. Transfusion of 35D RBCs did not result in hemolysis nor did it lead to increased levels of NTBI compared with 2D RBCs or saline. LPS induced increases in ferritin, haptoglobin, bilirubin, and lactate dehydrogenase that were similar in all three groups., Conclusion: We conclude that 35D autologous RBCs do not cause hemolysis or increased levels of NTBI during human endotoxemia., (© 2016 AABB.)

Physical activity (PA) has numerous health benefits, particularly for those with diabetes. However, rates of long-term PA participation are often poor., Purpose: This study examined the effect of an intensive lifestyle intervention (ILI) on objectively assessed PA for a 4-yr period among older adults with type 2 diabetes., Methods: Data from 2400 participants (age = 59.3 ± 6.9 yr, body mass index = 36.1 ± 5.9 kg·m) with accelerometry data from the Look AHEAD trial were included in the analyses. Participants randomized to ILI were instructed to reduce caloric intake and progress to ≥175 min·wk of moderate-to-vigorous-intensity PA (MVPA), whereas those randomized to Diabetes Support and Education (DSE) served as the control group. PA was measured at baseline, year 1, and year 4 using an RT3 accelerometer, and bout-related MVPA (PA ≥3 METs, accumulated in bouts of ≥10 min in duration) was calculated., Results: Despite no differences at baseline (ILI = 93.4 ± 152.7 vs DSE = 88.4 ± 143.6 min·wk), bout-related MVPA was significantly greater in ILI compared with DSE at year 1 (151.0 ± 213.5 vs 87.5 ± 145.1 min·wk, P < 0.0001) and year 4 (102.9 ± 195.6 vs 73.9 ± 267.5 min·wk, P < 0.001), and more ILI participants achieved ≥175 min·wk at year 1 (29.1% vs 16.3%, P < 0.001) and year 4 (18.3% vs 10.0%, P < 0.001). Forty-one percent of ILI participants who achieved ≥175 min·wk at year 1 maintained this threshold of PA at year 4. However, the majority of ILI participants never achieved the ≥175 min·wk threshold., Conclusions: When measured objectively and compared with DSE, ILI engaged in significantly more bout-related MVPA for a 4-yr period. However, future intervention strategies should target the large percentage of individuals who fail to reach the MVPA goal as result of a lifestyle intervention., Competing Interests: The remaining authors have no conflicts of interest to report.

The German twin family study 'TwinLife' was designed to enhance our understanding of the development of social inequalities over the life course. The interdisciplinary project investigates mechanisms of social inequalities across the lifespan by taking into account psychological as well as social mechanisms, and their genetic origin as well as the interaction and covariation between these factors. Main characteristics of the study are: (1) a multidimensional perspective on social inequalities, (2) the assessment of developmental trajectories in childhood, adolescence, and young adulthood in a longitudinal design by using (3) a combination of a multi-cohort cross-sequential and an extended twin family design, while (4) capturing a large variation of behavioral and environmental factors in a representative sample of about 4,000 German twin families. In the present article, we first introduce the theoretical and empirical background of the TwinLife study, and second, describe the design, content, and implementation of TwinLife. Since the data will be made available as scientific use file, we also illustrate research possibilities provided by this project to the scientific community.