Effects of Low-Calorie Sweetener Restriction on Glycemic Variability and Cardiometabolic Health in Children with Type 1 Diabetes: Findings of a Pilot and Feasibility Study.

Low-calorie sweeteners (LCS) are commonly consumed by children with type 1 diabetes (T1D), yet their role in cardiometabolic health is unclear. This study examined the feasibility, acceptability, and preliminary effects of 12 weeks of LCS restriction among children with T1D. Children (n = 31) with T1D completed a two-week run-in (n = 28) and were randomly assigned to avoid LCS (LCS restriction, n = 15) or continue their usual LCS intake (n = 13). Feasibility was assessed using recruitment, retention, and adherence rates percentages. Acceptability was assessed through parents completing a qualitative interview (subset, n = 15) and a satisfaction survey at follow-up. Preliminary outcomes were between-group differences in change in average daily time-in-range (TIR) over 12 weeks (primary), and other measures of glycemic variability, lipids, inflammatory biomarkers, visceral adiposity, and dietary intake (secondary). Linear regression, unadjusted and adjusted for age, sex, race, and change in BMI, was used to compare mean changes in all outcomes between groups. LCS restriction was feasible and acceptable. No between-group differences in change in TIR or other measures of glycemic variability were observed. However, significant decreases in TNF-alpha (-0.23 ± 0.08 pg/mL) and improvements in cholesterol (-0.31 ± 0.18 mmol/L) and LDL (-0.60 ± 0.39 mmol/L) were observed with usual LCS intake, compared with LCS restriction. Those randomized to LCS restriction did not report increases in total or added sugar intake, and lower energy intake was reported in both groups (-190.8 ± 106.40 kcal LCS restriction, -245.3 ± 112.90 kcal usual LCS intake group). Decreases in percent energy from carbohydrates (-8.5 ± 2.61) and increases in percent energy from protein (3.2 ± 1.16) and fat (5.2 ± 2.02) were reported with usual LCS intake compared with LCS restriction. Twelve weeks of LCS restriction did not compromise glycemic variability or cardiometabolic outcomes in this small sample of youth with T1D. Further examination of LCS restriction among children with T1D is warranted.

SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.

Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells. Mechanistically, SMYD3 binds to and regulates the transcription of UHRF1, encoding for a reader of H3K9me3, which binds to H3K9me3-enriched promoters of key immune-related genes, recruits DNMT1, and silences their expression. SMYD3 further maintains the repression of immune-related genes through intragenic deposition of H4K20me3. In vivo, Smyd3 depletion induces influx of CD8+ T cells and increases sensitivity to anti-programmed death 1 (PD-1) therapy. SMYD3 overexpression is associated with decreased CD8 T cell infiltration and poor response to neoadjuvant pembrolizumab. These data support combining SMYD3 depletion strategies with checkpoint blockade to overcome anti-PD-1 resistance in HPV-negative HNSCC.

Impacts of the COVID-19 Pandemic on Pediatric Type 1 Diabetes Management: A Qualitative Study.

PURPOSE: The purpose of this study was to understand impacts of the coronavirus (COVID-19) pandemic on pediatric type 1 diabetes management. METHODS: In-depth qualitative interviews were conducted with 15 parents of children (age 6-12 years) with type 1 diabetes. Parents responded to 8 open-ended questions about their experiences managing their children's type 1 diabetes during the COVID-19 pandemic. All interviews were transcribed, coded, and analyzed using qualitative thematic methods. RESULTS: Parents reported both positive and negative aspects of managing their children's type 1 diabetes during the COVID-19 pandemic. Facilitators of diabetes management included spending more time together at home and enhanced convenience of telehealth appointments and online supply ordering. Parents also described difficulties managing their children's type 1 diabetes during the COVID-19 pandemic, including a lack of structure in their child's daily routine, which led to increases in sedentary behavior. Furthermore, they reported psychosocial challenges of type 1 diabetes management, which were exacerbated by the pandemic. CONCLUSION: While the COVID-19 pandemic was described as having overall positive impacts on pediatric type 1 diabetes management, efforts to support parents in increasing children's physical activity and reducing screen time are needed, along with readily accessible mental health resources for both parents and their children with type 1 diabetes.

Fabrication of CoTiO3-TiO2 composite films from a heterobimetallic single source precursor for electrochemical sensing of dopamine.

Cobalt titanate-titania composite oxide films have been grown on FTO-coated glass substrates using a single-source heterometallic complex [Co2Ti4(µ-O)6(TFA)8(THF)6]·THF () which was obtained in quantitative yield from the reaction of diacetatocobalt(ii) tetrahydrate, tetraisopropoxytitanium(iv), and trifluoroacetic acid from a tetrahydrofuran solution. Physicochemical investigations of complex have been carried out by melting point, FT-IR, thermogravimetric and single-crystal X-ray diffraction analyses. CoTiO3-TiO2 films composed of spherical objects of various sizes have been grown from by aerosol-assisted chemical vapor deposition at different temperatures of 500, 550 and 600 °C. Thin films characterized by XRD, Raman and X-ray photoelectron spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis have been explored for electrochemical detection of dopamine (DA). The cyclic voltammetry with the CoTiO3-TiO2 electrode showed a DA oxidation peak at +0.215 V while linear sweep voltammetry displayed a detection limit (LoD) of 0.083 µM and a linear concentration range of 20-300 µM for DA. Thus, the CoTiO3-TiO2 electrode is a potential candidate for the sensitive and selective detection of DA.