Structure and Functions of Pediatric Aerodigestive Programs: A Consensus Statement

Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients

Evaluation of guided imagery as treatment for recurrent abdominal pain in children: a randomized controlled trial

BACKGROUND: Because of the paucity of effective evidence-based therapies for children with recurrent abdominal pain, we evaluated the therapeutic effect of guided imagery, a well-studied self-regulation technique. METHODS: 22 children, aged 5 – 18 years, were randomized to learn either breathing exercises alone or guided imagery with progressive muscle relaxation. Both groups had 4-weekly sessions with a therapist. Children reported the numbers of days with pain, the pain intensity, and missed activities due to abdominal pain using a daily pain diary collected at baseline and during the intervention. Monthly phone calls to the children reported the number of days with pain and the number of days of missed activities experienced during the month of and month following the intervention. Children with ≤ 4 days of pain/month and no missed activities due to pain were defined as being healed. Depression, anxiety, and somatization were measured in both children and parents at baseline. RESULTS: At baseline the children who received guided imagery had more days of pain during the preceding month (23 vs. 14 days, P = 0.04). There were no differences in the intensity of painful episodes or any baseline psychological factors between the two groups. Children who learned guided imagery with progressive muscle relaxation had significantly greater decrease in the number of days with pain than those learning breathing exercises alone after one (67% vs. 21%, P = 0.05), and two (82% vs. 45%, P < 0.01) months and significantly greater decrease in days with missed activities at one (85% vs. 15%, P = 0.02) and two (95% vs. 77%. P = 0.05) months. During the two months of follow-up, more children who had learned guided imagery met the threshold of ≤ 4 day of pain each month and no missed activities (RR = 7.3, 95%CI [1.1,48.6]) than children who learned only the breathing exercises. CONCLUSION: The therapeutic efficacy of guided imagery with progressive muscle relaxation found in this study is consistent with our present understanding of the pathophysiology of recurrent abdominal pain in children. Although unfamiliar to many pediatricians, guided imagery is a simple, noninvasive therapy with potential benefit for treating children with RAP

Distributed lag and spline modeling for predicting energy expenditure from accelerometry in youth

Movement sensing using accelerometers is commonly used for the measurement of physical activity (PA) and estimating energy expenditure (EE) under free-living conditions. The major limitation of this approach is lack of accuracy and precision in estimating EE, especially in low-intensity activities. Thus the objective of this study was to investigate benefits of a distributed lag spline (DLS) modeling approach for the prediction of total daily EE (TEE) and EE in sedentary (1.0–1.5 metabolic equivalents; MET), light (1.5–3.0 MET), and moderate/vigorous (≥3.0 MET) intensity activities in 10- to 17-year-old youth (n = 76). We also explored feasibility of the DLS modeling approach to predict physical activity EE (PAEE) and METs. Movement was measured by Actigraph accelerometers placed on the hip, wrist, and ankle. With whole-room indirect calorimeter as the reference standard, prediction models (Hip, Wrist, Ankle, Hip+Wrist, Hip+Wrist+Ankle) for TEE, PAEE, and MET were developed and validated using the fivefold cross-validation method. The TEE predictions by these DLS models were not significantly different from the room calorimeter measurements (all P > 0.05). The Hip+Wrist+Ankle predicted TEE better than other models and reduced prediction errors in moderate/vigorous PA for TEE, MET, and PAEE (all P < 0.001). The Hip+Wrist reduced prediction errors for the PAEE and MET at sedentary PA (P = 0.020 and 0.021) compared with the Hip. Models that included Wrist correctly classified time spent at light PA better than other models. The means and standard deviations of the prediction errors for the Hip+Wrist+Ankle and Hip were 0.4 ± 144.0 and 1.5 ± 164.7 kcal for the TEE, 0.0 ± 84.2 and 1.3 ± 104.7 kcal for the PAEE, and −1.1 ± 97.6 and −0.1 ± 108.6 MET min for the MET models. We conclude that the DLS approach for accelerometer data improves detailed EE prediction in youth

Exposure to p40 in Early Life Prevents Intestinal Inflammation in Adulthood Through Inducing a Long-Lasting Epigenetic Imprint on TGFβ

Colonization by gut microbiota in early life confers beneficial effects on immunity throughout the host’s lifespan. We sought to elucidate the mechanisms whereby neonatal supplementation with p40, a probiotic functional factor, reprograms intestinal epithelial cells for protection against adult-onset intestinal inflammation. p40 was used to treat young adult mouse colonic (YAMC) epithelial cells with and without deletion of a methyltransferase, su(var)3-9, enhancer-of-zeste and trithorax domain–containing 1β (Setd1β), and mice in early life or in adulthood. Anti–transforming growth factor β (TGFβ)-neutralizing antibodies were administered to adult mice with and without colitis induced by 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium. We examined Setd1b and Tgfb gene expression, TGFβ production, monomethylation and trimethylation of histone H3 on the lysine 4 residue (H3K4me1/3), H3K4me3 enrichment in Tgfb promoter, differentiation of regulatory T cells (Tregs), and the inflammatory status. p40 up-regulated expression of Setd1b in YAMC cells. Accordingly, p40 enhanced H3K4me1/3 in YAMC cells in a Setd1β-dependent manner. p40-regulated Setd1β mediated programming the TGFβ locus into a transcriptionally permissive chromatin state and promoting TGFβ production in YAMC. Furthermore, transient exposure to p40 during the neonatal period and in adulthood resulted in the immediate increase in Tgfb gene expression. However, only neonatal p40 supplementation induced the sustained H3K4me1/3 and Tgfb gene expression that persisted into adulthood. Interfering with TGFβ function by neutralizing antibodies diminished the long-lasting effects of neonatal p40 supplementation on differentiation of Tregs and protection against colitis in adult mice. Exposure to p40 in early life enables an epigenetic imprint on TGFβ, leading to long-lasting production of TGFβ by intestinal epithelial cells to expand Tregs and protect the gut against inflammation. [Display omitted

Identification of a functional peptide of a probiotic bacterium-derived protein for the sustained effect on preventing colitis

ABSTRACTSeveral probiotic-derived factors have been identified as effectors of probiotics for exerting beneficial effects on the host. However, there is a paucity of studies to elucidate mechanisms of their functions. p40, a secretory protein, is originally isolated from a probiotic bacterium, Lactobacillus rhamnosus GG. Thus, this study aimed to apply structure-functional analysis to define the functional peptide of p40 that modulates the epigenetic program in intestinal epithelial cells for sustained prevention of colitis. In silico analysis revealed that p40 is composed of a signal peptide (1–28 residues) followed by a coiled-coil domain with uncharacterized function on the N-terminus, a linker region, and a β-sheet domain with high homology to CHAP on the C-terminus. Based on the p40 three-dimensional structure model, two recombinant p40 peptides were generated, p40N120 (28–120 residues) and p40N180 (28–180 residues) that contain first two and first three coiled coils, respectively. Compared to full-length p40 (p40F) and p40N180, p40N120 showed similar or higher effects on up-regulating expression of Setd1b (encoding a methyltransferase), promoting mono- and trimethylation of histone 3 on lysine 4 (H3K4me1/3), and enhancing Tgfb gene expression and protein production that leads to SMAD2 phosphorylation in human colonoids and a mouse colonic epithelial cell line. Furthermore, supplementation with p40F and p40N120 in early life increased H3K4me1, Tgfb expression and differentiation of regulatory T cells (Tregs) in the colon, and mitigated disruption of epithelial barrier and inflammation induced by DSS in adult mice. This study reveals the structural feature of p40 and identifies a functional peptide of p40 that could maintain intestinal homeostasis