Significance Control of immunologic tolerance and homeostasis rely on regulatory T lymphocytes that express the transcription factor FOXP3. To characterize the interindividual variation of human Treg cells, we performed a genome-wide expression and genotypic analysis of 168 human donors, healthy or affected by type-1 or type-2 diabetes (T1D, T2D). We identify cis -acting genetic variants that condition Treg effector but not specification genes, and gene clusters that suggest Treg-specific regulatory pathways for some key signature genes ( CTLA4 , DUSP4 ). We also identify factors that may control FOXP3 mRNA or protein expression, the specification of the Treg signature, and Treg suppressive efficacy. Although no single transcript correlates with diabetes, overall expression of the Treg signature is perturbed in T1D, but not T2D, patients.

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IntroductionProject ECHO (Extension for Community Healthcare Outcomes) is a tele-education outreach model that seeks to democratize specialty knowledge to reduce disparities and improve health outcomes. Limited utilization of endocrinologists forces many primary care providers (PCPs) to care for patients with type 1 diabetes (T1D) without specialty support. Accordingly, an ECHO T1D program was developed and piloted in Florida and California. Our goal was to demonstrate the feasibility of an ECHO program focused on T1D and improve PCPs’ abilities to manage patients with T1D.Research design and methodsHealth centers (ie, spokes) were recruited into the ECHO T1D pilot through an innovative approach, focusing on Federally Qualified Health Centers and through identification of high-need catchment areas using the Neighborhood Deprivation Index and provider geocoding. Participating spokes received weekly tele-education provided by the University of Florida and Stanford University hub specialty team through virtual ECHO clinics, real-time support with complex T1D medical decision-making, access to a diabetes support coach, and access to an online repository of diabetes care resources. Participating PCPs completed pre/post-tests assessing diabetes knowledge and confidence and an exit survey gleaning feedback about overall ECHO T1D program experiences.ResultsIn Florida, 12 spoke sites enrolled with 67 clinics serving >1000 patients with T1D. In California, 11 spoke sites enrolled with 37 clinics serving >900 patients with T1D. During the 6-month intervention, 27 tele-education clinics were offered and n=70 PCPs (22 from Florida, 48 from California) from participating spoke sites completed pre/post-test surveys assessing diabetes care knowledge and confidence in diabetes care. There was statistically significant improvement in diabetes knowledge (p≤0.01) as well as in diabetes confidence (p≤0.01).ConclusionsThe ECHO T1D pilot demonstrated proof of concept for a T1D-specific ECHO program and represents a viable model to reach medically underserved communities which do not use specialists.

A progressive, treadmill-based VO 2max is the gold standard of cardiorespiratory fitness determination but is rarely used in pediatric clinics due to time requirements and cost. Simpler and shorter fitness tests such as the Squat Test or Step Test may be feasible and clinically useful alternatives. However, performance comparisons of these tests to treadmill VO 2max tests are lacking. The primary aim of this cross-sectional study was to assess the correlation between Squat and Step Test scores and VO 2max in a pediatric population. As secondary outcomes, we calculated correlations between Rated Perceived Exertion Scale (RPE) scores, NIH PROMIS Physical Activity scores, and BMI z-score with VO 2max , and we also evaluated the ability of each fitness test to discriminate low and high-risk patients based on the FITNESSGram. Forty children aged 10-17 completed these simple cardiorespiratory fitness tests. Statistically significant correlations were observed between VO 2max and the Step Test (r =-0.549) and Squat Test (r =-0.429) scores, as well as participant BMI z-score (r =-0.458). RPE and PROMIS scores were not observed to be correlated with VO 2max. Area Under the Receiver Operator Curve was relatively high for BMI z-scores and the Step Test (AUC = 0.813, 0.713 respectively), and lower for the Squat Test (AUC = 0.610) in discriminating risk according to FITNESSGram Scores. In this sample, the Step Test performed best overall. These tests were safe, feasible, and may add great value in assessing cardiorespiratory fitness in a clinical setting.