Multichannel magnetogastrogram: a clinical marker for pediatric chronic nausea.

Chronic nausea is a widespread functional disease in children with numerous comorbidities. High-resolution electrogastrogram (HR-EGG) has shown sufficient sensitivity as a noninvasive clinical marker to objectively detect distinct gastric slow wave properties in children with functional nausea. We hypothesized that the increased precision of magnetogastrogram (MGG) slow wave recordings could provide supplementary information not evident on HR-EGG. We evaluated simultaneous pre- and postprandial MGG and HR-EGG recordings in pediatric patients with chronic nausea and healthy asymptomatic subjects, while also measuring nausea intensity and nausea severity. We found significant reductions in postprandial dominant frequency and normogastric power, and higher levels of postprandial bradygastric power in patients with nausea in both MGG and HR-EGG. MGG also detected significantly lower preprandial normogastric power in patients. A significant difference in the mean preprandial gastric slow wave propagation direction was observed in patients as compared with controls in both MGG (control: 180 ± 61°, patient: 34 ±72°; P < 0.05) and HR-EGG (control: 240 ± 39°, patient: 180 ± 46°; P < 0.05). Patients also showed a significant change in the mean slow wave direction between pre- and postprandial periods in MGG (P < 0.05). No statistical differences were observed in propagation speed between healthy subjects and patients in either MGG or HR-EGG pre/postprandial periods. The use of MGG and/or HR-EGG represents an opportunity to assess noninvasively the effects of chronic nausea on gastric slow wave activity. MGG data may offer the opportunity for further refinement of the more portable and economical HR-EGG in future machine-learning approaches for functional nausea.NEW & NOTEWORTHY Pediatric chronic nausea is a difficult-to-measure subjective complaint that requires objective diagnosis, clinical assessment, and individualized treatment plans. Our study demonstrates that multichannel MGG used in conjunction with custom HR-EGG detects key pathological signatures of functional nausea in children. This quantifiable measure may allow more personalized diagnosis and treatment in addition to minimizing the cost and potential radiation associated with current diagnostic approaches.

Production of a Functional Factor, p40, by Lactobacillus rhamnosus GG Is Promoted by Intestinal Epithelial Cell-Secreted Extracellular Vesicles.

The symbiotic relationship between the gut microbiome and the host provides a nutrient-rich environment for gut microbes and has beneficial effects on host health. Although the composition of the gut microbiome is known to be influenced by both host genetics and environmental factors, host effects on the activities and functions of the gut microbial communities remain poorly understood. Intestinal epithelial cells exert front-line responses to gut microbes and contribute to maintaining a healthy intestinal homeostasis. Here, seeking to elucidate whether intestinal epithelial cells modulate Lactobacillus rhamnosus GG (LGG) functions, we examined the production of p40, an LGG-derived secretory protein that protects intestinal epithelial cells against inflammation. We found that growth medium conditioned with colonic epithelial cell-derived components promotes p40 protein synthesis and secretion by LGG and enhances LGG-stimulated protective responses in intestinal epithelial cells. Furthermore, when LGG was cultured with the colonic luminal contents from healthy mice, p40 production was upregulated but was attenuated with luminal contents from mice with intestinal inflammation. Importantly, the colonic epithelial cell-derived components potentiated LGG-produced p40 levels in a mouse model of colitis and enhanced LGG-mediated amelioration of intestinal inflammation in this model. Notably, we found that colonic epithelial cell-secreted extracellular vesicles participate in communicating with LGG and that heat shock protein 90 (HSP90) in these vesicles might mediate the promotion of p40 production. These results reveal a previously unrecognized mechanism by which the anti-inflammatory effect of LGG is reinforced by intestinal epithelial cells and thereby maintains intestinal health.

Activation of epidermal growth factor receptor mediates mucin production stimulated by p40, a Lactobacillus rhamnosus GG-derived protein.

The mucus layer coating the gastrointestinal tract serves as the first line of intestinal defense against infection and injury. Probiotics promote mucin production by goblet cells in the intestine. p40, a Lactobacillus rhamnosus GG-derived soluble protein, has been shown to transactivate the EGF receptor (EGFR) in intestinal epithelial cells, which is required for inhibition of apoptosis and preservation of barrier function in the colon, thereby ameliorating intestinal injury and colitis. Because activation of EGFR has been shown to up-regulate mucin production in goblet cells, the purpose of this study was to investigate the effects and mechanisms of p40 regulation of mucin production. p40 activated EGFR and its downstream target, Akt, in a concentration-dependent manner in LS174T cells. p40 stimulated Muc2 gene expression and mucin production in LS174T cells, which were abolished by inhibition of EGFR kinase activity, down-regulation of EGFR expression by EGFR siRNA transfection, or suppression of Akt activation. Treatment with p40 increased mucin production in the colonic epithelium, thus thickening the mucus layer in the colon of wild type, but not of Egfr(wa5) mice, which have a dominant negative mutation in the EGFR kinase domain. Furthermore, inhibition of mucin-type O-linked glycosylation suppressed the effect of p40 on increasing mucin production and protecting intestinal epithelial cells from TNF-induced apoptosis in colon organ culture. Thus, these results suggest that p40-stimulated activation of EGFR mediates up-regulation of mucin production, which may contribute to the mechanisms by which p40 protects the intestinal epithelium from injury.

Clostridium difficile infection in the pediatric transplant patient.

CDIs are on the rise in both hospital and community settings in adults and children. Children with cancer or a history of HSCT or SOT appear to be at higher risk for primary disease, recurrent disease, and severe outcomes when compared to children with other comorbidities. The reasons for this are not clear and no studies to date have analyzed risk factors for CDI in pediatric transplant patients. Colonization rates in children with cancer and a transplant history are also high. Determining which children are colonized with Clostridium difficile and symptomatic from another source vs. symptomatic from CDI is difficult and a clinical conundrum for the transplant physician. The use of fecal transplantation for severe or rCDI is likely safe and effective in the immunosuppressed pediatric cancer or transplant patient, but this will need to be more thoroughly studied in this patient population.

A human milk oligosaccharide prevents intestinal inflammation in adulthood via modulating gut microbial metabolism.

Observational evidence suggests that human milk oligosaccharides (HMOs) promote the growth of commensal bacteria in early life and adulthood. However, the mechanisms by which HMOs benefit health through modulation of gut microbial homeostasis remain largely unknown. 2'-fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk and contributes to the essential health benefits associated with human milk consumption. Here, we investigated how 2'-FL prevents colitis in adulthood through its effects on the gut microbial community. We found that the gut microbiota from adult mice that consumed 2'-FL exhibited an increase in abundance of several health-associated genera, including Bifidobacterium and Lactobacillus. The 2'-FL-modulated gut microbial community exerted preventive effects on colitis in adult mice. By using Bifidobacterium infantis as a 2'-FL-consuming bacterial model, exploratory metabolomics revealed novel 2'-FL-enriched secretory metabolites by Bifidobacterium infantis, including pantothenol. Importantly, pantothenate significantly protected the intestinal barrier against oxidative stress and mitigated colitis in adult mice. Furthermore, microbial metabolic pathway analysis identified 26 dysregulated metabolic pathways in fecal microbiota from patients with ulcerative colitis, which were significantly regulated by 2'-FL treatment in adult mice, indicating that 2'-FL has the potential to rectify dysregulated microbial metabolism in colitis. These findings support the contribution of the 2'-FL-shaped gut microbial community and bacterial metabolite production to the protection of intestinal integrity and prevention of intestinal inflammation in adulthood.IMPORTANCEAt present, neither basic research nor clinical studies have revealed the exact biological functions or mechanisms of action of individual oligosaccharides during development or in adulthood. Thus, it remains largely unknown whether human milk oligosaccharides could serve as effective therapeutics for gastrointestinal-related diseases. Results from the present study uncover 2'-FL-driven alterations in bacterial metabolism and identify novel B. infantis-secreted metabolites following the consumption of 2'-FL, including pantothenol. This work further demonstrates a previously unrecognized role of pantothenate in significantly protecting the intestinal barrier against oxidative stress and mitigating colitis in adult mice. Remarkably, 2'-FL-enhanced bacterial metabolic pathways are found to be dysregulated in the fecal microbiota of ulcerative colitis patients. These novel metabolic pathways underlying the bioactivities of 2'-FL may lay a foundation for applying individual oligosaccharides for prophylactic intervention for diseases associated with impaired intestinal homeostasis.

Impact of maternal depression on malnutrition treatment outcomes in older children with sickle cell anemia.

BACKGROUND: Malnutrition and sickle cell anemia (SCA) result in high childhood mortality rates. Although maternal depression is an established risk factor for malnutrition in younger children, little is known about its impact on treatment response in children with malnutrition. We aimed to determine the relationship, if any, between maternal depression scores and malnutrition treatment outcomes in older children with SCA. METHODS: We conducted a planned ancillary study to our randomized controlled feasibility trial for managing severe acute malnutrition in children aged 5-12 with SCA in northern Nigeria (NCT03634488). Mothers of participants completed a depression screen using the Patient Health Questionnaire (PHQ-9).We used a multivariable linear regression model to describe the relationship between the baseline maternal PHQ-9 score and the trial participant's final body mass index (BMI) z-score. RESULTS: Out of 108 mother-child dyads, 101 with maternal baseline PHQ-9 scores were eligible for inclusion in this analysis. At baseline, 25.7% of mothers (26 of 101) screened positive for at least mild depression (PHQ-9 score of 5 or above). The baseline maternal PHQ-9 score was negatively associated with the child's BMI z-score after 12 weeks of malnutrition treatment (ß=-0.045, p = 0.041). CONCLUSIONS: Maternal depressive symptoms has an impact on malnutrition treatment outcomes. Treatment of malnutrition in older children with sickle cell anemia should include screening for maternal depression and, if indicated, appropriate maternal referral for depression evaluation and treatment. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (#NCT03634488) on January 30, 2018, https://clinicaltrials.gov/study/NCT03634488 .

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

Several 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 ß-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.

Automated Machine Learning Pipeline Framework for Classification of Pediatric Functional Nausea Using High-Resolution Electrogastrogram.

OBJECTIVE: Pediatric functional nausea is challenging for patients to manage and for clinicians to treat since it lacks objective diagnosis and assessment. A data-driven non-invasive diagnostic screening tool that distinguishes the electro-pathophysiology of pediatric functional nausea from healthy controls would be an invaluable aid to support clinical decision-making in diagnosis and management of patient treatment methodology. The purpose of this paper is to present an innovative approach for objectively classifying pediatric functional nausea using cutaneous high-resolution electrogastrogram data. METHODS: We present an Automated Electrogastrogram Data Analytics Pipeline framework and demonstrate its use in a 3x8 factorial design to identify an optimal classification model according to a defined objective function. Low-fidelity synthetic high-resolution electrogastrogram data were generated to validate outputs and determine SOBI-ICA noise reduction effectiveness. RESULTS: A 10 parameter support vector machine binary classifier with a radial basis function kernel was selected as the overall top-performing model from a pool of over 1000 alternatives via maximization of an objective function. This resulted in a 91.6% test ROC AUC score. CONCLUSION: Using an automated machine learning pipeline approach to process high-resolution electrogastrogram data allows for clinically significant objective classification of pediatric functional nausea. SIGNIFICANCE: To our knowledge, this is the first study to demonstrate clinically significant performance in the objective classification of pediatric nausea patients from healthy control subjects using experimental high-resolution electrogastrogram data. These results indicate a promising potential for high-resolution electrogastrography to serve as a data-driven screening tool for the objective diagnosis of pediatric functional nausea.

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

BACKGROUND & AIMS: 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. METHODS: 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 1ß (Setd1ß), and mice in early life or in adulthood. Anti-transforming growth factor ß (TGFß)-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, TGFß 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. RESULTS: p40 up-regulated expression of Setd1b in YAMC cells. Accordingly, p40 enhanced H3K4me1/3 in YAMC cells in a Setd1ß-dependent manner. p40-regulated Setd1ß mediated programming the TGFß locus into a transcriptionally permissive chromatin state and promoting TGFß 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 TGFß function by neutralizing antibodies diminished the long-lasting effects of neonatal p40 supplementation on differentiation of Tregs and protection against colitis in adult mice. CONCLUSIONS: Exposure to p40 in early life enables an epigenetic imprint on TGFß, leading to long-lasting production of TGFß by intestinal epithelial cells to expand Tregs and protect the gut against inflammation.

The effect of chronic nausea on gastric slow wave spatiotemporal dynamics in children.

BACKGROUND: Chronic nausea in adolescents with functional gastrointestinal disorders is an increasingly reported but poorly understood symptom that negatively affects quality of life. Functional gastrointestinal disorders are known to correlate closely with slow wave rhythm disturbances. The ability to characterize gastric electrophysiologic perturbations in functional nausea patients could provide potential diagnostic and therapeutic tools for nausea patients. METHODS: We used high-resolution electrogastrograms (HR-EGG) to measure gastric slow wave parameters in pediatric chronic nausea patients and healthy subjects both pre- and postprandial. We computed the dominant frequency, percentage power distribution, gastric slow wave propagation direction, and speed from HR-EGG. KEY RESULTS: We observed significant differences in the dominant frequency and power distributed in normal and bradyarrhythmia frequency ranges when comparing patients and healthy subjects. Propagation patterns in healthy subjects were predominantly anterograde, while patients exhibited a variety of abnormalities including retrograde, anterograde, and disrupted patterns. There was a significant difference in the preprandial mean slow wave direction between healthy subjects (222° ± 22°) and patients (103° ± 66°; p Ë‚ 0.01), although the postprandial mean direction between healthy subjects and patients was similar (p = 0.73). No significant difference in slow wave propagation speed was found between patients and healthy subjects in either pre- (p = 0.21) or postprandial periods (p = 0.75). CONCLUSIONS AND INFERENCES: The spatiotemporal characterization of gastric slow wave activity using HR-EGG distinguishes symptomatic chronic nausea patients from healthy subjects. This characterization may in turn inform and direct clinical decision-making and lead to further insight into its pathophysiology.

CYP2C19 Phenotype and Risk of Proton Pump Inhibitor-Associated Infections.

OBJECTIVES: Proton pump inhibitors (PPIs) are often used in pediatrics to treat common gastrointestinal disorders, and there are growing concerns for infectious adverse events. Because CYP2C19 inactivates PPIs, genetic variants that increase CYP2C19 function may decrease PPI exposure and infections. We tested the hypothesis that CYP2C19 metabolizer phenotypes are associated with infection event rates in children exposed to PPIs. METHODS: This retrospective biorepository cohort study included individuals aged 0 to 36 months at the time of PPI exposure. Respiratory tract and gastrointestinal tract infection events were identified by using International Classification of Diseases codes in the year after the first PPI mention. Variants defining CYP2C19 *2, *3, *4, *8, *9, and *17 were genotyped, and all individuals were classified as CYP2C19 poor or intermediate, normal metabolizers (NMs), or rapid or ultrarapid metabolizers (RM/UMs). Infection rates were compared by using univariate and multivariate analyses. RESULTS: In all, 670 individuals were included (median age 7 months; 44% girls). CYP2C19 NMs (n = 267; 40%) had a higher infection rate than RM/UMs (n = 220; 33%; median 2 vs 1 infections per person per year; P = .03). There was no difference between poor or intermediate (n = 183; 27%) and NMs. In multivariable analysis of NMs and RM/UMs adjusting for age, sex, PPI dose, and comorbidities, CYP2C19 metabolizer status remained a significant risk factor for infection events (odds ratio 0.70 [95% confidence interval 0.50-0.97] for RM/UMs versus NMs). CONCLUSIONS: PPI therapy is associated with higher infection rates in children with normal CYP2C19 function than in those with increased CYP2C19 function, highlighting this adverse effect of PPI therapy and the relevance of CYP2C19 genotypes to PPI therapeutic decision-making.

Supplementation of p40, a Lactobacillus rhamnosus GG-derived protein, in early life promotes epidermal growth factor receptor-dependent intestinal development and long-term health outcomes.

The beneficial effects of the gut microbiota on growth in early life are well known. However, knowledge about the mechanisms underlying regulating intestinal development by the microbiota is limited. p40, a Lactobacillus rhamnosus GG-derived protein, transactivates epidermal growth factor receptor (EGFR) in intestinal epithelial cells for protecting the intestinal epithelium against injury and inflammation. Here, we developed p40-containing pectin/zein hydrogels for targeted delivery of p40 to the small intestine and the colon. Treatment with p40-containing hydrogels from postnatal day 2 to 21 significantly enhanced bodyweight gain prior to weaning and functional maturation of the intestine, including intestinal epithelial cell proliferation, differentiation, and tight junction formation, and IgA production in early life in wild-type mice. These p40-induced effects were abolished in mice with specific deletion of EGFR in intestinal epithelial cells, suggesting that transactivation of EGFR in intestinal epithelial cells may mediate p40-regulated intestinal development. Furthermore, neonatal p40 treatment reduced the susceptibility to intestinal injury and colitis and promoted protective immune responses, including IgA production and differentiation of regulatory T cells, in adult mice. These findings reveal novel roles of neonatal supplementation of probiotic-derived factors in promoting EGFR-mediated maturation of intestinal functions and innate immunity, which likely promote long-term beneficial outcomes.

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 < or = 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 < or = 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.

Predicting energy expenditure of physical activity using hip- and wrist-worn accelerometers.

To investigate the association between physical activity and health, we need accurate and detailed free-living physical activity measurements. The determination of energy expenditure of activity (EEACT) may also be useful in the treatment and maintenance of nutritional diseases such as diabetes mellitus. Minute-to-minute energy expenditure during a 24-h period was measured in 60 sedentary normal female volunteers (35.4 +/- 9.0 years, body mass index 30.0 +/- 5.9 kg/m2), using a state-of-the-art whole-room indirect calorimeter. The activities ranged from sedentary deskwork to walking and stepping at different intensities. Body movements were simultaneously measured using a hip-worn triaxial accelerometer (Tritrac-R3D, Hemokentics, Inc., Madison, Wisconsin) and a wrist-worn uniaxial accelerometer (ActiWatch AW64, MiniMitter Co., Sunriver, Oregon) on the dominant arm. Movement data from the accelerometers were used to develop nonlinear prediction models (separately and combined) to estimate EEACT and compared for accuracy. In a subgroup (n=12), a second 24-h study period was repeated for cross-validation of the combined model. The combined model, using Tritrac-R3D and ActiWatch, accurately estimated total EEACT (97.7 +/- 3.2% of the measured values, p=0.781), as compared with using ActiWatch (86.0 +/- 4.7%, p<0.001) or Tritrac-R3D (90.0 +/- 4.6%, p<0.001) alone. This model was also accurate for all intensity categories during various physical activities. The subgroup cross-validation also showed accurate and reproducible predictions by the combination model. In this study, we demonstrated that movement measured using accelerometers at the hip and wrist could be used to accurately predict EEACT of various types and intensity of activities. This concept can be extended to develop valid models for the accurate measurement of free-living energy metabolism in clinical populations.

Endoscopic diagnosis of duodenal stenosis in a 5-month-old male infant.

Duodenal stenosis and duodenal atresia are well-known gastrointestinal anomalies in patients with Down syndrome. Although duodenal atresia presents early and classically with vomiting in the immediate neonatal period, the presentation of duodenal stenosis can be significantly more subtle and the diagnosis delayed. Here, we describe the case of a 5-month-old male infant with Down syndrome and delayed presentation of high-grade duodenal stenosis diagnosed endoscopically. Pediatric gastroenterologists should include duodenal stenosis in the differential diagnosis of older infants and children with vomiting and should be familiar with the endoscopic appearance of this lesion.

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 (> or = 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.

Efficiency of walking and stepping: relationship to body fatness.

OBJECTIVE: To determine energetic efficiency of walking and stepping in a heterogeneous normal adult population and its association with body fatness and to assess within- and between-individual variations. RESEARCH METHODS AND PROCEDURES: Using a combination of a whole-room indirect calorimeter and a large precision force platform, we simultaneously measured minute-by-minute energy expenditure (EE) and mechanical work during walking and stepping in healthy adult men (n = 60) and women (n = 85). Efficiency was calculated as a ratio (percentage) of mechanical work and EE of activity. Efficiency of walking and stepping performed at various intensities was compared for reproducibility within the same day (morning and afternoon) and correlated with a subject's characteristics. RESULTS: The efficiency of walking was negatively correlated with body fatness in both men and women at 0.9 to 1.2 m/s but positively correlated with body fatness in men and not correlated in women at the slowest speed tested (0.6 m/s). Efficiency of walking and stepping of various intensities was reproducible during the same day. Compared at similar EE levels, walking was more efficient than stepping (26% to 27% vs. 18% to 22%, p < 0.01). Women were significantly (p < 0.01) more efficient than men during stepping. Age, sex, body mass, fat-free mass, fitness (maximal oxygen uptake), height, and speed variations contributed to the between-subject differences in efficiency. DISCUSSION: Obese individuals were less efficient than lean individuals during normal-speed walking. Significant interindividual variations in efficiency of walking and stepping may be attributed to habituation and physical characteristics such as age, sex, and fitness level.