Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter.

Sustained exposure to pro-inflammatory cytokines in the leptomeninges is thought to play a major role in the pathogenetic mechanisms leading to cortical pathology in multiple sclerosis (MS). Although the molecular mechanisms underlying neurodegeneration in the grey matter remain unclear, several lines of evidence suggest a prominent role for tumour necrosis factor (TNF). Using cortical grey matter tissue blocks from post-mortem brains from 28 secondary progressive MS subjects and ten non-neurological controls, we describe an increase in expression of multiple steps in the TNF/TNF receptor 1 signaling pathway leading to necroptosis, including the key proteins TNFR1, FADD, RIPK1, RIPK3 and MLKL. Activation of this pathway was indicated by the phosphorylation of RIPK3 and MLKL and the formation of protein oligomers characteristic of necrosomes. In contrast, caspase-8 dependent apoptotic signaling was decreased. Upregulation of necroptotic signaling occurred predominantly in macroneurons in cortical layers II-III, with little expression in other cell types. The presence of activated necroptotic proteins in neurons was increased in MS cases with prominent meningeal inflammation, with a 30-fold increase in phosphoMLKL+ neurons in layers I-III. The density of phosphoMLKL+ neurons correlated inversely with age at death, age at progression and disease duration. In vivo induction of chronically elevated TNF and INFγ levels in the CSF in a rat model via lentiviral transduction in the meninges, triggered inflammation and neurodegeneration in the underlying cortical grey matter that was associated with increased neuronal expression of TNFR1 and activated necroptotic signaling proteins. Exposure of cultured primary rat cortical neurons to TNF induced necroptosis when apoptosis was inhibited. Our data suggest that neurons in the MS cortex are dying via TNF/TNFR1 stimulated necroptosis rather than apoptosis, possibly initiated in part by chronic meningeal inflammation. Neuronal necroptosis represents a pathogenetic mechanism that is amenable to therapeutic intervention at several points in the signaling pathway.

Reduced prevalence of impaired awareness of hypoglycemia in a population-based clinic sample of youth with type 1 diabetes.

BACKGROUND: Impaired awareness of hypoglycemia (IAH) is associated with an increased risk for severe hypoglycemia (SH). However, reduced rates of SH raise the question as to whether there has been a reduction in IAH. The aim of this study was to determine the change in prevalence of IAH in a population-based cohort of adolescents with Type 1 diabetes (T1D). METHODS: Children older than 12 years with T1D documented their responses to hypoglycemia based on the modified Clarke questionnaire. The prevalence of IAH was also analyzed in a similar population-based cohort using the same questionnaire in 2002. The clinical details of the participants and the number of SH events in the preceding year were determined from the Western Australian diabetes database. RESULTS: The questionnaire was administered to 413 children in 2002 and to 444 children in 2015 with similar baseline characteristics. The prevalence of IAH was 33% in 2002 and 21% in 2015 (P < .001). A lower HbA1c, younger age at diagnosis and longer duration of diabetes correlated with IAH in 2002 but not in 2015. There was a significant decline in the rates of SH in 2015 compared with 2002 (P < .001) despite a reduced HbA1c in 2015. IAH increased the risk of SH in both cohorts (52 vs 16 events/100 patient years in 2002 and 8 vs 2 events/100 patient years in 2015). CONCLUSIONS: Although IAH has reduced, IAH is still prevalent in a substantial minority of adolescents and continues to be associated with an increased risk of SH.

Prediction of congenital hypothyroidism based on initial screening thyroid-stimulating-hormone.

BACKGROUND: In thyroid-stimulating-hormone (TSH)-based newborn congenital hypothyroidism (CH) screening programs, the optimal screening-TSH cutoff level is critical to ensuring that true cases of CH are not missed. Screening-TSH results can also be used to predict the likelihood of CH and guide appropriate clinical management. The purpose of this study is to evaluate the predictive value of various screening-TSH levels in predicting a diagnosis of CH in the Ontario Newborn Screening Program (ONSP). METHODS: The initial screening and follow-up data of 444,744 full term infants born in Ontario, Canada from April 1, 2006 to March 31, 2010 were analyzed. Confirmed CH cases were based on local endocrinologists' report and initiation of thyroxine treatment. RESULTS: There were a total of 541 positive screening tests (~1/822 live births) of which 296 were true positives (~1:1,500 live births). Subjects were further subdivided based on screening-TSH and positive predictive values (PPV) were calculated. Twenty four percent in the 17-19.9 mIU/L range were true positives. In the 17-30 mIU/L range, 29 % were true positives with a significantly higher PPV for those sampled after (43 %) rather than before (25 %) 28 h of age (p < 0.02). Seventy three percent of neonates with an initial screening-TSH of ≥ 30 mIU/L and 97 % of those with ≥ 40 mIU/L were later confirmed to have CH. CONCLUSIONS: Infants with modestly elevated screening positive TSH levels between 17 and 19.9 mIU/L have a significant risk (24 %) of having CH. The very high frequency of true positives in term newborns with initial TSH values ≥ 30mIU/L suggests that this group should be referred directly to a pediatric endocrinologist in an effort to expedite further assessment and treatment. Screen positives with a modestly elevated TSH values (17-19.9 mIU/L) need to be examined in more detail with extended follow-up data to determine if they have transient or permanent CH.

Tissue reaction after intrastromal corneal ring implantation in an experimental animal model.

PURPOSE: To evaluate corneal wound healing in the hen animal model after additive surgery with an intracorneal ring segment (ICRS). METHODS: We implanted one ICRS in each eye of 76 hens. In control group 1 (n = 22 hens), the stromal channel was prepared but no ICRS was inserted. In control group 2 (n = 2 hens), no surgery was performed. Animals were randomly separated into groups and euthanized after clinical follow-up of 4 and 12 hours, 1, 2, 3, and 7 days, and 1, 2, 3, 4, and 6 months. Corneas were stained with hematoxylin-eosin. Apoptosis was measured by terminal uridine nick end-labeling assays. Cell proliferation and myofibroblast-like differentiation were assayed by BrdU and α-smooth muscle actin immunofluorescence microscopy. Stromal matrix changes were documented by electron microscopy. RESULTS: Epithelial and stromal cell apoptosis around the ICRS-implanted and control group 1 eyes peaked at 12 hours, but continued for 72 hours. In ICRS-implanted eyes, epithelial and stromal proliferation was present at 12 and 24 hours, respectively, and peaked at 7 days and 72 hours, respectively. Some proliferation in the ICRS-implanted group continued through the 6-month follow-up, and myofibroblast-like cells differentiated one to three months after ICRS implantation. The segments rotated within the stroma as the limbal inferior angle approached the epithelium. CONCLUSIONS: Wound healing after ICRS implantation in hen corneas was similar to that of other corneal surgical wounds in stages. However, there were some specific features related to the small size of the epithelial wound and the device permanently implanted inside the cornea.

A novel MC4R mutation associated with childhood-onset obesity: A case report.

The melanocortin-4-receptor gene (MC4R) is a key regulator of energy homeostasis, food intake and body weight. MC4R gene mutations are associated with early-onset severe obesity. Most patients are heterozygotes, with some reports of homozygotes and compound heterozygotes. The authors report a case involving an eight-year-old girl with progressive weight gain from infancy, body mass index 44 kg/m(2) (>97th percentile), hyperphagia, hyperinsulinemia and increased linear growth. There was no phenotype of morbid obesity in the parents or sibling. Coding regions and intron-exon boundaries of the genes encoding leptin, leptin receptor, pro-opiomelanocortin and MC4R were analyzed. Two heterozygous coding mutations in the MCR4 gene (S94N and C293R) were detected, of which the second has not been previously reported. The mutations were on opposite chromosomes, confirming compound heterozygosity. The molecular findings and clinical features associated with this novel MC4R mutation are described. The authors emphasize that rare mutations can be found in some patients with severe childhood-onset obesity.

Le gène récepteur de la mélanocortine 4 (MC4R) joue un rôle clé dans le maintien de l'homéostasie énergétique, de la prise alimentaire et du poids corporel. Les mutations du gène MC4R s'associent à une grave obésité à apparition précoce. La plupart des patients sont hétérozygotes, mais il y a certaines descriptions de patients homozygotes et d'hétérozygotes composés. Les auteurs présentent le cas d'une fillette de huit ans ayant une prise de poids progressive depuis la première enfance, un indice de masse corporel de 44 kg/m2 (>97e percentile), une hyperphagie, une hyperinsulinémie et une augmentation de la croissance linéaire. Les parents et la fratrie ne possédaient pas de phénotype d'obésité morbide. Les auteurs ont analysé les régions codantes et les limites intron-exon des gènes codant la leptine, son récepteur, la pro-opiomélanocortine et le MC4R. Ils ont décelé deux mutations en région codante du gène MCR4 (S94N et C293R), la deuxième n'ayant jamais été déclarée auparavant. Les mutations se situaient sur des chromosomes opposés, ce qui confirme leur hétérozygotie composée. Les auteurs décrivent les observations moléculaires et les caractéristiques cliniques associées à cette nouvelle mutation MC4R. Ils soulignent que certains patients ayant une importante obésité qui se manifeste pendant l'enfance peuvent présenter des mutations rares.

Multi-objective evolutionary design of adenosine receptor ligands.

A novel multiobjective evolutionary algorithm (MOEA) for de novo design was developed and applied to the discovery of new adenosine receptor antagonists. This method consists of several iterative cycles of structure generation, evaluation, and selection. We applied an evolutionary algorithm (the so-called Molecule Commander) to generate candidate A1 adenosine receptor antagonists, which were evaluated against multiple criteria and objectives consisting of high (predicted) affinity and selectivity for the receptor, together with good ADMET properties. A pharmacophore model for the human A1 adenosine receptor (hA1AR) was created to serve as an objective function for evolution. In addition, three support vector machine models based on molecular fingerprints were developed for the other adenosine receptor subtypes (hA2A, hA2B, and hA3) and applied as negative objective functions, to aim for selectivity. Structures with a higher evolutionary fitness with respect to ADMET and pharmacophore matching scores were selected as input for the next generation and thus developed toward overall fitter ("better") compounds. We finally obtained a collection of 3946 unique compounds from which we derived chemical scaffolds. As a proof-of-principle, six of these templates were selected for actual synthesis and subsequently tested for activity toward all adenosine receptors subtypes. Interestingly, scaffolds 2 and 3 displayed low micromolar affinity for many of the adenosine receptor subtypes. To further investigate our evolutionary design method, we performed systematic modifications on scaffold 3. These modifications were guided by the substitution patterns as observed in the set of generated compounds that contained scaffold 3. We found that an increased affinity with appreciable selectivity for hA1AR over the other adenosine receptor subtypes was achieved through substitution of the scaffold; compound 3a had a Ki value of 280 nM with approximately 10-fold selectivity with respect to hA2AR, while 3g had a 1.6 µM affinity for hA1AR with negligible affinity for the hA2A, hA2B, and hA3 receptor subtypes.

Scleral changes induced by atropine in chicks as an experimental model of myopia.

PURPOSE: To determine the effects of intravitreal atropine on scleral growth in the form-deprived chick as an experimental model of myopia. METHODS: Five groups of five chicks were studied from day 0-12 post-hatching. One group remained untreated (C), and four were form-deprived by monocular light diffusers to induce myopia. Two groups (RL and A) wore diffusers for 9 days, and the other two groups (D and D + A) wore diffusers throughout the study. Group D received no further treatment (myopia positive control). Groups A and D + A received intravitreal injections of atropine for days 9-12. Measurements of refractive error and axial length were performed on days 0, 9, and 12. Sclera changes were assessed in cartilaginous and fibrous layers by histological analysis. RESULTS: All form-deprived eyes had a myopic refractive error on day 9. All atropine-treated groups were hyperopic on day 12. The effect of atropine was most evident in Group D + A in which diffusers were maintained throughout treatment and changes in refractive error were statistically significant. The observed changes in axial length were in line with the changes in refractive error. The scleral fibrous layer thickness increased, and the sceral cartilaginous layer underwent a slight thinning compared to Group D, the myopia positive control. CONCLUSIONS: If the signals that induce growth remain during atropine treatment, morphological changes in sclera are produced: the scleral fibrous layer thickened, and the sceral cartilaginous layer thinned. These changes resulted in refractive error recovery, and the ocular growth was stopped. The data suggested the atropine was acting throughout the scleral fibrous layer.

Polarization-based colour tuning of mixed colloidal quantum-dot thin films using direct patterning.

Colloidal quantum-dots (cQDs) are finding increasingly widespread application in photonics and optoelectronics, providing high brightness and record-wide colour gamuts. However, the external quantum efficiencies in thin-film device architectures are still limited due to losses into waveguide modes and different strategies are being explored to promote the outcoupling of emission. Here we use a template-stripping-based direct-patterning strategy to fabricate linear gratings at the surface of cQD thin films. The linear gratings enhance optical outcoupling through Bragg scattering, yielding bright emission with a strong degree of linear polarization. By patterning linear gratings with different periodicities and orientations onto a film of mixed-colour cQDs, we demonstrate polarization-based active colour tuning of the thin-film emission.

Microvascular complications assessment in adolescents with 2- to 5-yr duration of type 1 diabetes from 1990 to 2006.

OBJECTIVE: Microvascular complications occur in adolescents with type 1 diabetes, although guidelines vary as to when screening should commence and prevalence data for those with ≤5-yr duration are limited. We therefore investigated trends in prevalence of early microvascular complications over 17 yr. RESEARCH DESIGN AND METHODS: 819 adolescents (54% female) aged 11-17 yr with 2- to 5-yr diabetes duration were assessed for complications at a tertiary pediatric diabetes clinic between 1990 and 2006. Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) by timed overnight urine collections and peripheral nerve function by thermal/vibration threshold at the foot. Results were analyzed by age, time period of assessment, and duration. RESULTS: Early retinopathy declined from 1990 to 2002 (16-7%, p < 0.01), then remained unchanged until 2006. Early elevation of AER (≥7.5 µg/min) and microalbuminuria (≥20 µg/min) did not change over time, whereas peripheral nerve abnormalities increased (14-28%, p < 0.01). Median hemoglobin A1c improved (8.7-8.2%, p < 0.01), in parallel with increased total daily insulin dose and injections per day (p < 0.01). Body mass index standard deviation score increased over time (0.55-0.79, p < 0.01). In multivariate logistic regression, early retinopathy was associated with earlier time period [odds ratio (OR) 0.68, confidence interval (CI) 0.55-0.85, p < 0.01] and older age (OR 1.19, CI 1.02-1.39, p = 0.03). AER ≥ 7.5 µg/min was associated with older age (1.19, 1.06-1.34, p < 0.01) and longer diabetes duration (OR 1.28, CI 1.02-1.62, p = 0.04) and height-adjusted peripheral nerve abnormalities with later time period (OR 1.26, CI 1.05-1.50, p = 0.01). CONCLUSIONS: Early complications are not uncommon in adolescents with 2- to 5-yr diabetes duration, despite more intensive management in recent years.

Adrenal Cushing Syndrome Diagnosed During Pregnancy: Successful Medical Management With Metyrapone.

Adrenal Cushing syndrome during pregnancy is rare, and there is limited information on the effect and safety of metyrapone treatment both for mother and fetus. We present a 24-year-old woman diagnosed with adrenal Cushing syndrome at the end of the second trimester. We elected treatment with metyrapone titrated to 250 mg 3 times daily, resulting in good clinical response and maternal serum and saliva cortisol levels in the upper half of the normal pregnancy range. A healthy male infant was born at 35 weeks' gestation, with no clinical signs of adrenal insufficiency, this despite a low cortisol of 5 nmol/L on the first day of life. We measured metyrapone in maternal and umbilical cord blood samples, demonstrating fetal venous metyrapone levels similar to maternal venous concentration, and a fetal arterial cord concentration at about 60% of the fetal venous cord concentration. This case demonstrates that salivary cortisol levels may be used to monitor the effect of metyrapone on adrenal Cushing syndrome during pregnancy. We show, for the first time in humans, that metyrapone does cross the placenta and may suppress fetal cortisol production without necessarily causing clinical signs of adrenal insufficiency.

Parathyroid Hormone in Pregnancy: Vitamin D and Other Determinants.

We aimed to assess the parathyroid hormone (PTH) concentration in pregnant women at the beginning of pregnancy (1st trimester) and within days before delivery (3rd trimester) and evaluate its determinants. From September 2014 through December 2015 in a cross-sectional study, 204 women in the 1st trimester of pregnancy and 203 women in the 3rd trimester of pregnancy were recruited. Blood samples were collected to measure PTH and circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Lifestyle and demographic data were collected using a questionnaire. Serum 25(OH)D and PTH were inversely correlated in both early and late pregnancy. Our analyses suggest that in the 3rd trimester of pregnancy, a 25(OH)D level of 18.9 ng/mL (47.3 nmol/L) could serve as an inflection point for the maximal suppression of PTH. Statistically significant determinants of PTH concentrations in multiple regression were 25(OH)D concentrations, season, multiparity and education of the partner (all p < 0.05) in early pregnancy. In late pregnancy, 25(OH)D concentrations and country of origin were statistically significant determinants of PTH concentrations (all p < 0.05). These factors and their effect on PTH appear to be vastly determined by 25(OH)D; however, they might also affect PTH through other mechanisms besides 25(OH)D.

Bladder Base Displacement during Abdominal Muscles Contraction and Functional Activities in Primiparous Women Assessed by Transabdominal Ultrasound: A Descriptive Study.

This study described the response of the bladder base (BB) by transabdominal ultrasound in primiparous women during movements that activate the abdominopelvic cavity musculature and cause variations in intra-abdominal pressure (IAP). A descriptive cross-sectional study was conducted in 64 primiparous women at eight weeks after uncomplicated delivery. BB displacement was measured using a 5-MHz convex transducer in a suprapubic position. Participants were asked to perform the isolated contraction of pelvic floor musculature (PFM) and transverse abdominis (TrA), cough at high lung volume and trunk flexion with and without maximal voluntary contraction of PFM. PFM contraction elevated the BB in all but one participant, whereas TrA contraction caused the BB to ascend in 56% of the women and descend in the rest; their combined contraction rose the BB in 65% of the women although the effect was greater with only PFM contraction (p < 0.01). The BB descended in all participants during coughing and trunk flexion although the descent was inferior with the joint maximal voluntary contraction of PFM (p < 0.01). In conclusion, TrA contraction must be assessed individually in puerperal women since its effect on the BB varies among subjects. During movements increasing IAP, such as coughing or curl-ups, the anticipatory contraction of PFM reduces bladder descent although not sufficiently to counteract bladder displacement.

Accurate non-invasive image-based cytotoxicity assays for cultured cells.

BACKGROUND: The CloneSelect Imager system is an image-based visualisation system for cell growth assessment. Traditionally cell proliferation is measured with the colorimetric MTT assay. RESULTS: Here we show that both the CloneSelect Imager and the MTT approach result in comparable EC50 values when assaying the cytotoxicity of cisplatin and oxaliplatin on various cell lines. However, the image-based technique was found non-invasive, considerably quicker and more accurate than the MTT assay. CONCLUSIONS: This new image-based technique has the potential to replace the cumbersome MTT assay when fast, unbiased and high-throughput cytotoxicity assays are requested.

Unprecedented water addition to the α,ß-unsaturated enone bond, mediated by the combination of carbonate and platinum(II).

The cytostatic compounds cis-[Pt(A9pyp)(dmso)Cl(2)] (1) and [Pt(A9pyp)(dmso)(cbdca)] (2) (A9pyp=(E)-[1-(9-anthryl)-3-(2-pyridyl)-2-propenone) as carrier ligand; cbdca=cyclobutane dicarboxylate) have been found to add water across the enone C==C bond of the ligand A9pyp. The water addition occurs in the presence of carbonate buffer, and has been followed in detail using NMR and ESI-MS spectroscopy. The spectroscopic data clearly indicate that the platinum(II) ion, the carbonate species, and the proximity of the enone C==C bond to the metal ion, are all required for this unusual hydration. A difference in kinetics is observed between chloride and cbdca, showing that the Pt-ligand dissociation plays an important role in the hydration kinetics.

Copper curcuminoids containing anthracene groups: fluorescent molecules with cytotoxic activity.

The coordination chemistry of the new curcuminoid ligand, 1,7-(di-9-anthracene-1,6-heptadiene-3,5-dione), abbreviated 9Accm has been studied, resulting in two new copper-9Accm compounds. Compound 1, [Cu(phen)Cl(9Accm)], was synthesized by reacting 9Accm with [Cu(phen)Cl(2)] in a 1:1 ratio (M:L) and compound 2, [Cu(9Accm)(2)], was prepared from Cu(OAc)(2) and 9Accm (1:2). UV-vis, electron paramagnetic resonance (EPR), and superconducting quantum interference device (SQUID) measurements were some of the techniques employed to portray these species; studies on single crystals of free 9Accm, [Cu(phen)Cl(9Accm)] and [Cu(9Accm)(2)(py)] provided detailed structural information about compounds 1 and 2·py, being the first two copper-curcuminoids crystallographically described. In addition the antitumor activity of the new compounds was studied and compared with free 9Accm for a number of human tumor cells. To provide more insight on the mode of action of these compounds under biological conditions, additional experiments were accomplished, including studies on the nature of their interactions with calf thymus DNA by UV-vis titration and Circular Dichroism. These experiments together with DNA-binding studies indicate electrostatic interactions between some of these species and the double helix, pointing out the weak nature of the interaction of the compounds with CT-DNA. The intrinsic fluorescence of the free ligand and both copper compounds provided valuable information over the cellular process and therefore, fluorescence microscopy studies were performed using a human osteosarcoma cell line. Studies in vitro using this technique suggest that the action of these molecules seems to occur outside the nuclei.

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Assessing the clinical utility of the diabetes eating problem survey-revised (DEPS-R) in adolescents with type 1 diabetes.

OBJECTIVE: Eating disorders are prevalent among adolescents with type 1 diabetes (T1D). We examined the clinical utility of the Diabetes Eating Problem Survey-Revised (DEPS-R), a brief self-report questionnaire developed for patients with T1D, to identify at-risk adolescents. We aimed to determine whether a positive DEPS-R screen was predictive of a formal diagnosis of an eating disorder as per the DSM-V. In addition, we assessed whether other variables including psychosocial characteristics and diabetes conflict were associated with an abnormal DEPS-R screen. METHODS: Cross-sectional study of 116 T1D adolescents aged 12-17 years. All participants completed the DEPS-R screening; both participants and parents completed a questionnaire addressing psychosocial characteristics/conflict around diabetes management. Clinical variables were obtained from participant charts. Differences were examined between positive and negative DEPS-R groups. Adolescents who screened positive were offered a referral to a specialized eating disorder team for further assessment. RESULTS: From 116 participants (mean age ± SD = 14.6 years ± 1.56), 21% (24/116) scored positive for DEPS-R More females than males had abnormal DEPS-R (75% vs 25%, P = 0.001). Those with positive DEPS-R score had higher HbA1c% (mean = 9.3 ± 1.3 vs 8.3 ± 1.2, P = 0.001). Positive DEPS-R group had higher conflict score for diabetes management in both parents' and children's assessments (both ps < 0.001). In regression analysis, being female (OR males = 0.07, 95%CI: 0.010-0.46, P = 0.006), older (OR = 2.01, 95%CI: 1.16-3.48, P = 0.040) and > child-reported conflict (OR = 1.78, 95%CI: 1.02-3.11, P = 0.044) were predictors of an abnormal DEPS-R score. CONCLUSION: The DEPS-R score is a useful clinical tool for identifying T1D adolescents at risk for disordered eating behaviour, but has a low positive predictive value (PPV) for identifying adolescents who meet diagnostic criteria for an eating disorder. Female gender, suboptimal diabetes control and increased conflict in diabetes management are associated with an abnormal DEPS-R score.

Closing the Gap: Results of the Multicenter Canadian Randomized Controlled Trial of Structured Transition in Young Adults With Type 1 Diabetes.

OBJECTIVE: To determine if a structured transition program for young adults with type 1 diabetes improves clinic attendance, glycemic control, diabetes-related distress, quality of life, and satisfaction with care. RESEARCH DESIGN AND METHODS: In this multicenter randomized controlled trial, young adults (17-20 years) with type 1 diabetes were randomly assigned to a transition program with a transition coordinator or to standard care. The intervention lasted 18 months (6 in pediatric and 12 in adult care). The primary outcome was the proportion of participants who failed to attend at least one adult diabetes clinic visit during the 12-month follow-up after completion of the intervention. RESULTS: We randomized 205 participants, 104 to the transition program and 101 to standard care. Clinic attendance was improved in the transition program (mean [SD] number of visits 4.1 [1.1] vs. 3.6 [1.2], P = 0.002), and there was greater satisfaction with care (mean [SD] score 29.0 [2.7] vs. 27.9 [3.4], P = 0.032) and less diabetes-related distress (mean [SD] score 1.9 [0.8] vs. 2.1 [0.8], P = 0.049) reported than in standard care. There was a trend toward improvement in mean HbA1c (8.33% [68 mmol/mol] vs. 8.80% [73 mmol/mol], P = 0.057). During the 12-month follow-up, there was no difference in those failing to attend at least one clinic visit (P = 0.846), and the mean change in HbA1c did not differ between the groups (P = 0.073). At completion of follow-up, the groups did not differ with respect to satisfaction with care or diabetes-related distress and quality of life. CONCLUSIONS: Transition support during this 18-month intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but these benefits were not sustained 12 months after completion of the intervention.

Defect-Tolerant Plasmonic Elliptical Resonators for Long-Range Energy Transfer.

Energy transfer allows energy to be moved from one quantum emitter to another. If this process follows the Förster mechanism, efficient transfer requires the emitters to be extremely close (<10 nm). To increase the transfer range, nanophotonic structures have been explored for photon- or plasmon-mediated energy transfer. Here, we fabricate high-quality silver plasmonic resonators to examine long-distance plasmon-mediated energy transfer. Specifically, we design elliptical resonators that allow energy transfer between the foci, which are separated by up to 10 µm. The geometry of the ellipse guarantees that all plasmons emitted from one focus are collected and channeled through different paths to the other focus. Thus, energy can be transferred even if a micrometer-sized defect obstructs the direct path between the focal points. We characterize the spectral and spatial profiles of the resonator modes and show that these can be used to transfer energy between green- and red-emitting colloidal quantum dots printed with subwavelength accuracy using electrohydrodynamic nanodripping. Rate-equation modeling of the time-resolved fluorescence from the quantum dots further confirms the long-distance energy transfer.