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Phenytoin is a known human teratogen with unknown etiology. Several mechanisms have been proposed including disturbances in folate metabolism, induction of embryonic hypoxia following phenytoin-induced bradycardia, free radical formation following re-oxygenation and phenytoin-induced maternal hyperglycemia. Using high frequency ultrasound, we demonstrated that phenytoin induced a dramatic decrease in the heart rate of embryos. This coincided with a moderate transient decrease in maternal heart rate and blood glucose levels. Embryonic heart rate had not fully recovered 24 h later in some embryos despite normal maternal physiological parameters. In a separate study, extent of hypoxia was measured using the marker pimonidazole. Phenytoin-exposed embryos did not demonstrate increased hypoxia compared to control embryos at 2, 4, 8 or 24 h dosing. Together our results show that phenytoin induces malformations as a result of a combination of insults: embryonic bradycardia, maternal bradycardia and maternal hyperglycemia. However, this does not appear to result in measurable embryonic hypoxia in our animal model.

Due to its simplicity, time-limited eating (TLE) may represent a more feasible approach for treating adolescents with obesity compared to other caloric restriction regimens. This pilot study examines the feasibility and safety of TLE combined with continuous glucose monitoring (CGM) in adolescents. Fifty adolescents with BMI ≥95th percentile were recruited to complete a 12-week study. All received standard nutritional counseling, wore a CGM daily, and were randomized to: (1) Prolonged eating window: 12 h eating/12 h fasting + blinded CGM, (2) TLE (8 h eating/16 h fasting, 5 days per week) + blinded CGM, (3) TLE + real-time CGM feedback. Recruitment, retention, and adherence were recorded as indicators of feasibility. Weight loss, dietary intake, physical activity, eating behaviors, and quality of life over the course of the intervention were explored as secondary outcomes. Forty-five participants completed the study (16.4 ± 1.3 years, 64% female, 49% Hispanic, 75% public insurance). There was high adherence to prescribed eating windows (TLE 5.2 d/wk [SD 1.1], control 6.1 d/wk [SD 1.4]) and daily CGM wear (5.85 d/wk [SD 4.8]). Most of the adolescents (90%) assigned to TLE reported that limiting their eating window and wearing a CGM was feasible without negative impact on daily functioning or adverse events. There were no between-group difference in terms of weight loss, energy intake, quality of life, physical activity, or eating behaviors. TLE combined with CGM appears feasible and safe among adolescents with obesity. Further investigation in larger samples, with a longer intervention duration and follow-up assessments are needed.

Background This scoping review provides a timely synthesis of the use of continuous glucose monitoring in obesity research with considerations to adherence to continuous glucose monitor devices and metrics most frequently reported. Methods This scoping review was conducted adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Eligible studies (n = 31) evaluated continuous glucose monitor use in research on participants, of all ages, with overweight or obesity. Results Reviewed studies varied in duration from one to 84 days (mean: 8.74 d, SD 15.2, range 1–84 d) with 889 participants total (range: 11–118 participants). Across all studies, the mean percent continuous glucose monitor wear time (actual/intended wear time in days) was 92% (numerator – mean: 266.1 d, SD: 452, range: 9–1596 d/denominator – mean: 271.6 d, SD: 451.5, range: 9–1596 d). Continuous glucose monitoring was utilized to provide biofeedback (n = 2, 6%), monitor dietary adherence (n = 2, 6%), and assess glycemic variability (n = 29, 93%). The most common variability metrics reported were standard deviation (n = 19, 62%), area under the curve (n = 12, 39%), and glycemic range (n = 12, 39%). Conclusions Available evidence suggests that continuous glucose monitoring is a well-tolerated and versatile tool for obesity research in pediatric and adult patients. Future investigation is needed to substantiate the feasibility and utility of continuous glucose monitors in obesity research and maximize comparability across studies.

Purpose: This study examines how baseline demographics, psychosocial characteristics, and intervention delivery predict engagement among adolescents with overweight and obesity seeking treatment. Methods: Data originates from a multisite randomized control trial evaluating the efficacy of an app-based weight loss intervention, compared with standard in-clinic model in adolescents with overweight and obesity. Participants were randomized to one of the three arms: (1) AppCoach, (2) AppAlone, or (3) Control. Demographic, executive functioning (EF), and depression questionnaires were completed at baseline. Percent engagement was compared within and between groups defined by demographics and depressive symptoms. Quantile regression was used to evaluate the association between age and EF on percent engagement. Results: Baseline demographics were not associated with engagement within or between groups. Neither baseline self-reported depressive symptoms (p = 0.244) nor deficits in EF (p = 0.34) were predictors of engagement. Univariate analysis found that the control arm had the highest engagement (83%) compared with AppCoach (63.5%) and AppAlone (22.5%, p = 0.02). Hispanic ethnicity was predictive of higher engagement in the control arm (p = 0.02). On multivariate quartile regression no other baseline characteristics were significant predictors of engagement. Conclusion: Baseline demographics and individual psychosocial characteristics were not related to engagement in this cohort. The intervention arm that required parental involvement resulted in the greatest engagement suggesting that family involvement may overshadow individual behavioral phenotype and thus promote better engagement. Further investigation is needed to understand how program delivery can be leveraged to optimize treatment engagement and outcomes in adolescence. Clinical Trial Registration number: NCT03500835.

BACKGROUND: Time limited eating (TLE) has been shown to be effective for weight loss and improvement of glycemic control in adults with obesity and type 2 diabetes (T2D), but has not been well studied in adolescents. TLE may be a more feasible, flexible and effective dietary intervention for adolescents because it removes the need for intensive counting of calories or macronutrients, and emphasizes eating during a specified time period. OBJECTIVES: The aim of this study is to assess the feasibility of a TLE approach in adolescents with obesity using a continuous glucose monitor (CGM) to promote adherence to the intervention. METHODS: We propose a prospective, randomized controlled trial, in 60 adolescents (ages 14–18) with obesity (BMI% ≥ 95th percentile). Youth will be randomized to one of three treatment groups for a 12-week intervention: Group 1) Low sugar and carbohydrate education (LSC, 5% of total daily calories from sugar (< 35 g)/day; < 90 g carbohydrate (CHO)/day) + blinded CGM (used to monitor adherence and glycemic outcomes without real time feedback), Group 2) LSC + TLE (16-h fast/8-h feed for 5 days per week) + blinded CGM, and Group 3) LSC + TLE+ real time feedback via CGM (to evaluate effect of providing CGM data on intervention efficacy). Outcomes will include change in total body fat (TBF) percentage measured on DEXA scan, BMI status and fasting blood glucose at 12 weeks compared to baseline. CONCLUSIONS: TLE is a potentially powerful lifestyle intervention that could be readily integrated into pediatric weight management programs to optimize their impact and accelerate healthy changes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03954223

BACKGROUND There are a wide range of drugs including antidepressants, anticonvulsants and antipsychotics that cause embryonic bradycardia in vitro but it is unknown if they have a similar effect in vivo. One way to verify whether these in vitro findings are replicated in vivo is by the use of ultrasound examination of dosed pregnant rats. We tested this by examining the effect of dofetilide on embryonic heart rate (HR) in vivo using ultrasound. METHODS Rats were dosed with dofetilide (4 or 2.5 mg/kg) on GD11 or (5 or 2.5 mg/kg) on GD13 and embryonic HR assessed by ultrasound, 2 and 24 hr later. Fetuses were examined for malformations on GD20. RESULTS HR of control rat embryos showed a wide range at each gestational day. Dosing with dofetilide on GD11 caused severe bradycardia (∼60% reduction) 2 hours after dosing with recovery after 24 h of >60% of LD but death and slow HR among the HD embryos. At term, 32% of the LD surviving fetuses had hypoplastic upper lip while >90% of HD embryos had died. On GD13, embryonic HR was reduced in a dose-dependent manner with >85% of LD and HD recovered by 24 hr. At term, all LD fetuses were normal while 29% of HD fetuses had limb defects. CONCLUSIONS Ultrasound is a useful technique to investigate the effect of maternally administered drugs on the embryonic HR in the rat. The results may provide more information about the safety of these drugs in pregnancy leading to better risk assessment for the human