Cardiac cycle: an observational/interventional study protocol to characterise cardiopulmonary function and evaluate a home-based cycling program in children and adolescents born extremely preterm.

INTRODUCTION: Extremely preterm (EP)/extremely low birthweight (ELBW) individuals may have an increased risk for adverse cardiovascular outcomes. Compared with term-born controls, these individuals have poorer lung function and reduced exercise capacity. Exercise interventions play an important role in reducing cardiopulmonary risk, however their use in EP/ELBW cohorts is unknown. This study, cardiac cycle, aims to characterise the cardiopulmonary system of children and adolescents who were born EP compared with those born at term, following acute and chronic exercise bouts. METHODS AND ANALYSIS: The single-centre study comprises a home-based exercise intervention, with physiological characterisation at baseline and after completion of the intervention. Fifty-eight children and adolescents aged 10-18 years who were born EP and/or with ELBW will be recruited. Cardiopulmonary function assessed via measures of blood pressure, arterial stiffness, capillary density, peak oxygen consumption, lung clearance indexes and ventricular structure/function, will be compared with 58 age-matched and sex-matched term-born controls at baseline and post intervention. The intervention will consist of a 10-week stationary cycling programme, utilising Zwift technology. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committee of the Royal Children's Hospital Melbourne under HREC2019.053. Results will be disseminated via peer-reviewed journal regardless of outcome. TRIAL REGISTRATION NUMBER: 12619000539134, ANZCTR.

Inter-arm differences in regional arterial stiffness and geometry lead to inter-arm systolic blood pressure differences: A modelling study.

An inter-arm systolic blood pressure difference (ISBPD), if substantial in magnitude (typically defined as ≥10 mmHg), is a potential cardiovascular risk factor in adults, due to its association with cardiovascular events/mortality. A substantial ISBPD occurs in approximately 10% of the adult population, and, although associations with vascular disease and elevated stiffness have been reported, the mechanisms underlying ISBPD remain unknown. The aim of this study was to investigate whether inter-arm differences in segmental pulse wave velocity, cross-sectional area, or vascular bed compliance/resistance could give rise to substantial differences in brachial pressures between arms; for example, due to differences in pulse wave transmission and reflection. Using an established one-dimensional model of the major systemic arteries, pulse wave velocity (PWV) was uniformly increased or decreased in arteries of 1) the supra-aortic region leading up to the arm, 2) the brachial region, 3) the forearm, and 4) all of these (entire arm pathway); for the left arm, right arm, and both arms. Cross-sectional area and vascular bed compliance and resistance of the arms were similarly varied. Inter-arm differences in segmental PWV and cross-sectional area (but not bilateral changes) led to associated substantial inter-arm SBP differences, which were observed with changes to brachial, forearm and/or entire arm pathways and were related to altered transmission of forward waves and amplitude/timing of reflected waves. Vascular bed compliance and resistance had minimal influence. We conclude that inter-arm differences in arterial stiffness and geometry may contribute to inter-arm systolic blood pressure differences, warranting further investigation.

Normative blood pressure response to exercise stress testing in children and adolescents.

OBJECTIVE: To describe normative values for blood pressure (BP) response to maximal exercise in children/adolescents undergoing a treadmill stress test. METHODS: From a retrospective analysis of medical records, patients who had undergone a Bruce protocol exercise stress test, with (1) normal cardiovascular system and (2) a body mass index percentile rank below 95% were included for analysis. Sex, age, height, weight, resting and peak heart rate, resting and peak systolic blood pressure (SBP), test duration, stage of Bruce protocol at termination, reason for undergoing the test and reason for termination of test were collected. Percentiles for exercise-induced changes in SBP were constructed by age and height for each sex with the use of quantile regression models. RESULTS: 648 patients with a median age of 12.4 years (range 6-18 years) were included. Typical indications for stress testing were investigation of potential rhythm abnormalities, syncope/dizziness and chest pain and were deemed healthy by an overseeing cardiologist. Mean test duration was 12.6±2.2 min. Reference percentiles for change in SBP by sex, age and height are presented. CONCLUSION: The presented reference percentiles for the change in SBP for normal children and adolescents will have utility for detecting abnormally high or low BP responses to exercise in these age groups.

Assessment of diastolic blood pressure with the auscultatory method in children and adolescents under exercise conditions.

Controversy surrounds whether to define resting diastolic blood pressure (DBP) as the onset of the fourth or fifth Korotkoff phase (K4, sound muffling, or K5, sound disappearance) in children and adolescents. Although undetectable in some children (due to sounds continuing to zero cuff pressure), K5 is currently recommended for consistency with adult practice and because K4 can be difficult to discern or undetectable. However, to our knowledge, no studies have specifically assessed the reliability of measuring DBP with K4 and K5 in children and adolescents under exercise conditions. We therefore measured DBP before and immediately after a Bruce protocol stress test in 90 children and adolescents aged 12.3 ± 3.5 years (mean ± SD) in a cardiology clinic setting. When detected, K4 and K5 were 63.5 ± 9.2 and 60.2 ± 12.6 mmHg, respectively, at rest and 59.2 ± 14.6 mmHg (p = 0.028 vs rest) and 52.9 ± 18.3 mmHg (p < 0.001), respectively, immediately post-exercise. K4 and K5 were not detected in 41% and 4% of participants at rest or in 29% and 37% post-exercise, respectively, while K5 resulted in unrealistic DBP values (<30 mmHg) in an additional 11%. Better exercise performance was associated with a more frequent absence of K5 post-exercise, and after excluding participants performing at <10th percentile for age, post-exercise K4 was absent in 23%, and plausible K5 values were not obtained in 59% (p < 0.001). Although neither K4 nor K5 alone were reliable measures of DBP immediately post-exercise, a novel hybrid approach using K4, if detected, or K5, if not, produced reasonable DBP measurements in 97% of participants.

Magnitude and significance of interarm blood pressure differences in children and adolescents.

BACKGROUND: An interarm difference (IAD) in blood pressure (BP) of 10 mmHg or more is a potential cardiovascular risk factor in adults, given its association with cardiovascular events/mortality. In children and adolescents, accurate BP assessment is critical for identifying risk of end organ damage. However, IAD has not been systematically studied in paediatric patients; if present and of significant magnitude, measuring BP in only one arm could lead to misclassification of hypertensive status. METHOD: In 95 children/adolescents with a normal aorta (including 15 with a history of tetralogy of Fallot) aged 7-18 years attending the Royal Children's Hospital, Melbourne, we aimed to determine the magnitude of IAD, frequency of IAD of at least 10 mmHg, difference in BP classification between arms, and influence of repeat measures on IAD in a single visit. After 5 min rest, simultaneous bilateral BP was measured in triplicate with an automated device. RESULTS: Absolute systolic IAD was 5.0 mmHg (median, interquartile range 2-8 mmHg) and was 10 mmHg or more in 14%, with no change on repeat measures. In patients with a history of aortic surgery, IAD of 10 mmHg or more occurred in 27% (transposition of the great arteries, n = 15) and 75% (aortic coarctation, n = 8). Differences in BP classification, based on initial left vs. right arm measures, occurred in 25% (normal aorta) and 40%/63% (aortic surgery), or 17% and 33%/50%, respectively if second and third measurements were averaged. CONCLUSION: Substantial interarm BP differences were common, even in apparently healthy children and adolescents: evaluation of IAD may, therefore, be important for BP classification in the paediatric setting.

Improving undergraduate education in surgical paediatrics using near-peer assisted learning tutorials.

INTRODUCTION: Near-peer assisted learning (NPAL) has been welcomed in recent years as a favourable method for teaching medical students. It has proven advantages for both the educator and the learner. As such it was identified as an ideal approach for delivering the local curriculum within a paediatric surgical setting. Short duration of placements further suggests that structured tutorials would best guarantee coverage of the student curriculum. Our hypothesis was that the introduction of a structured programme such as this could lead to reduced dependence on senior staff for teaching, increased exposure of junior staff as educators, and increased coverage of the curriculum. METHODS: Curriculum outcomes were identified, and a series of tutorials developed for delivery by juniors within the department. Pre and post intervention questionnaires were given to students rotating through the department. RESULTS: 70 responses were analysed (23 pre; 47 post intervention). Reliance on Consultant teaching dropped 29% and engagement of surgical, GP and foundation trainees in teaching increased by 29%, 43% and 9% respectively. Overall curriculum coverage increased by 12%. CONCLUSION: A near-peer assisted tutorial programme is an effective way of increasing coverage of the medical curriculum with benefits for tutors and learners, whilst increasing junior engagement in teaching and reducing burden on Consultants.

Ketamine modulates hippocampal neurogenesis and pro-inflammatory cytokines but not stressor induced neurochemical changes.

Considerable recent attention has focused on the rapid antidepressant effects observed in treatment resistant patients produced by the NMDA receptor antagonist, ketamine. Surprisingly, the effects of ketamine in the context of stressor exposure, as well as the consequences of its chronic use are unclear. Thus, we assessed the impact of acute and repeated ketamine treatment together with acute [restraint or lipopolysaccharide (LPS)] or chronic (unpredictable different psychogenic challenges) stressor exposure. Importantly, acute ketamine treatment did provoke an antidepressant-like effect in a forced swim test (FST) and this effect lasted for 8 days following repeated exposure to the drug. Although acute restraint and LPS individually provoked the expected elevation of plasma corticosterone and brain-region specific monoamine variations, ketamine had no influence on corticosterone and had, at best, sparse effects on the monoamine changes. Similarly, ketamine did not appreciably influence the stressor induced neurochemical and sucrose preference alterations, it did however, dose-dependently reverse the LPS induced elevation of the pro-inflammatory cytokines, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Likewise, repeated ketamine administration increased adult hippocampal neurogenesis. These data indicate that repeated ketamine administration had greater behavioral consequences than acute treatment and that the drug might be imparting antidepressant effects through its effects on neuroplasticity and inflammatory processes rather than the typical neurochemical/hormonal factors affected by stressors. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

An acute bout of aerobic exercise alters interarm systolic blood pressure difference.

BACKGROUND: Clinically, when a difference of at least 10 mmHg in systolic blood pressure (SBP) between arms exists, it is identified as an interarm systolic blood pressure difference (ISBPD). At rest, ISBPD is linked with hypertension, peripheral vascular disease, and increased premature mortality. Exercise may reveal underlying cardiovascular pathologies otherwise absent at rest. However, there have been no investigations to examine the effect of exercise on ISBPD. AIM: The aim of this investigation was to determine whether exercise may alter ISBPD when detected at rest or reveal ISBPD when it was not observed in the resting condition. METHODS: An experienced investigator sequentially measured SBP using standard auscultation in each arm (alternating order) in 85 normotensive individuals (22±6 years, 39 male, 46 female). ISBPD was quantified before exercise (PRE). Participants then completed a three-stage protocol on a cycle ergometer. A cadence of 50 rpm was maintained at a workload of 3 (EX-3; light) and 6 (EX-6; moderate) METS and during an active recovery (REC). At each stage, SBP was measured upon achieving steady-state heart rate. A logistic regression analysis was used to determine the change in odds ratio of ISBPD when exposed to exercise. RESULTS: Thirteen percent (n=11) of patients presented with ISBPD during PRE and the degree of ISBPD was lower (3.81 mmHg; P<0.05) in REC than PRE. In individuals who did not present with ISBPD during PRE (n=74), progression from EX-3 to EX-6 significantly increased the odds of developing ISBPD (4.31; P<0.05). CONCLUSION: In individuals with ISBPD at PRE, active recovery from exercise attenuated the difference between interarm SBP. Moderate-intensity exercise resulted in ISBPD not otherwise present at rest.

Validation of a Chromosomal Microarray for Prenatal Diagnosis Using a Prospective Cohort of Pregnancies with Increased Risk for Chromosome Abnormalities.

AIM: Validation of a chromosomal microarray for improved prenatal diagnosis for chromosomal abnormalities among high-risk pregnancies. METHODS: A cohort of 213 pregnancies was investigated by chromosomal microarray and the results were compared with quantitative fluorescent polymerase chain reaction (QF-PCR), karyotype, and 850K single-nucleotide polymorphism microarray results. The detection limit of mosaicism was determined by assaying different trisomy mosaic constructs down to ∼12%. Imprecision estimates from replicates of mean log2 ratio values for a 200 kb deletion and 400 kb duplication were determined by evaluating the coefficient of variation (CV%). RESULTS: Excluding pregnancies with aneuploidy, the chromosomal microarray detected 19/213 (8.9%) pregnancies with copy number abnormalities. These were classified as pathogenic in 11/213 (5.2%) cases, as variants of uncertain significance in 4/213 (1.9%) cases, and as likely benign in 4/213 (1.9%) cases. In 15/213 (7.0%) pregnancies, these abnormalities were not detectable by karyotype. Importantly, 8/11 (72.7%) of the pathogenic abnormalities detected by chromosomal microarray were only detectable by this modality. There were no false-positive results and only eight false-negative results. The chromosomal microarray showed excellent sensitivity (96.2%) and specificity (100.0%). The lower detection limit for mosaicism was ∼12%. Imprecision for the 0.2 Mb deletion (11.6 CV%) and 0.4 Mb duplication (5.9 CV%) was very low. CONCLUSION: This chromosomal microarray showed excellent diagnostic performance with improved detection rates compared to karyotyping for prenatal diagnosis of clinically relevant fetal chromosomal abnormalities.

The interactive effects of ketamine and magnesium upon depressive-like pathology.

Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment-resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration. However, it is also a drug with an abusive potential and can have marked side effects. Hence, this study aimed at enhancing the antidepressant-like effects of ketamine (allowing for lower dosing regimens) by coadministering magnesium hydroaspartate (Mg(2+) normally affects the same receptors as ketamine) and also assessed whether an Mg(2+)-deficient diet would modify the impact of ketamine. It was found that a single 15 mg/kg dose of ketamine did indeed induce rapid antidepressant-like effects in the forced swim test but did not affect brain levels of the brain-derived neurotrophic factor. Contrary to our hypothesis, magnesium administration or deficiency did not influence the impact of ketamine on these outcomes. Thus, these data do not support the use of magnesium as an adjunct agent and instead suggest that further research involving other antidepressant and animal models is required to confirm the present findings.

Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

Endogenous ghrelin's role in hippocampal neuroprotection after global cerebral ischemia: does endogenous ghrelin protect against global stroke?

Ghrelin is a gastrointestinal hormone with a well-characterized role in feeding and metabolism. Recent evidence suggests that ghrelin may also be neuroprotective after injury in animal models of cerebral ischemia. Thus exogenous ghrelin treatment can improve cell survival, reduce infarct size, and rescue memory deficits in focal ischemia models, doing so by suppressing inflammation and apoptosis. Endogenous ghrelin plays a key a role in a number of physiological processes, including feeding, metabolism, stress, and anxiety. However, no study has examined whether endogenous ghrelin also contributes to neuroprotection after cerebral ischemia. Here, we aimed to determine whether endogenous ghrelin normally protects against neuronal cell death and cognitive impairments after global cerebral ischemia and whether such changes are linked with inflammation or apoptosis. We used a two-vessel occlusion (2VO) model of global cerebral ischemia in wild-type (wt) and ghrelin knockout (ghr-/-) C57/Bl6J mice. ghr-/- mice had improved cell survival in the Cornu Ammonis(CA)-2/3 region of the hippocampus-a region of significant growth hormone secretagogue receptor expression. They also displayed less cellular degeneration than wt mice after the 2VO (Fluoro-Jade) and had less cognitive impairment in the novel object-recognition test. These outcomes were despite evidence of more neuroinflammation and apoptosis in the ghr-/- and less of a postsurgery hypothermia. Finally, we found that mortality in the week following the 2VO was reduced more in ghr-/- mice than in wt. Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic.

Transabdominal electrical stimulation increases colonic propagating pressure waves in paediatric slow transit constipation.

BACKGROUND AND AIMS: In slow-transit constipation (STC) pancolonic manometry shows significantly reduced antegrade propagating sequences (PS) and no response to physiological stimuli. This study aimed to determine whether transcutaneous electrical stimulation using interferential current (IFC) applied to the abdomen increased colonic PS in STC children. METHODS: Eight children (8-18 years) with confirmed STC had 24-h colonic manometry using a water-perfused, 8-channel catheter with 7.5 cm sidehole distance introduced via appendix stomas. They then received 12 sessions (20 min/3× per week) of IFC stimulation (2 paraspinal and 2 abdominal electrodes), applied at a comfortable intensity (<40 mA, carrier frequency 4 kHz, varying beat frequency 80-150 Hz). Colonic manometry was repeated 2 (n=6) and 7 (n=2) months after IFC. RESULTS: IFC significantly increased frequency of total PS/24h (mean ± SEM, pre 78 ± 34 vs post 210 ± 62, p=0.008, n=7), antegrade PS/24h (43 ± 16 vs 112 ± 20, p=0.01) and high amplitude PS (HAPS/24h, 5 ± 2:10 ± 3, p=0.04), with amplitude, velocity, or propagating distance unchanged. There was increased activity on waking and 4/8 ceased using antegrade continence enemas. CONCLUSIONS AND INFERENCES: Transcutaneous IFC increased colonic PS frequency in STC children with effects lasting 2-7 months. IFC may provide a treatment for children with treatment-resistant STC.

Stressor-like effects of c-Jun N-terminal kinase (JNK) inhibition.

There is an urgent need for novel treatment strategies for stressor related disorders, particularly depression and anxiety disorders. Indeed, existing drug treatments are only clinically successful in a subset of patients and relapse is common. This likely stems from the fact that stressor disorders are heterogeneous with multiple biological pathways being affected. To this end, the present investigation sought to assess in mice the contribution of the c-Jun N terminal kinase (JNK) pathway to the behavioral, hormonal and neurochemical effects of an acute stressor. Indeed, although JNK has been shown to modulate glucocorticoid receptors in vitro, virtually nothing is known of the role for JNK in affecting stressor induced pathology. We presently found that the JNK antagonist, SP600125, (but not the p38 antagonist, SB203580) increased plasma corticosterone levels under resting conditions and in the context of an acute stressor (wet bedding + restraint). SP600125 also reduced exploration in an open field arena, but prevented the stressor induced increase in open arm exploration in an elevated plus maze. Finally, SP600125 affected noradrenergic activity in the central amygdala and locus coruleus under resting condition, but prevented the noradrenergic effects within the paraventricular nucleus of the hypothalamus that were induced by the acute stressor exposure. These data suggest inhibiting endogenous JNK can have stressor-like corticoid, behavioral and central monoamine effects under basal conditions, but can actually reverse some behavioral and neurochemical effects of an acute stressor. Thus, endogenous JNK appears to affect stress relevant processes in a context-dependent manner.

Viral-toxin interactions and Parkinson's disease: poly I:C priming enhanced the neurodegenerative effects of paraquat.

BACKGROUND: Parkinson's disease (PD) has been linked with exposure to a variety of environmental and immunological insults (for example, infectious pathogens) in which inflammatory and oxidative processes seem to be involved. In particular, epidemiological studies have found that pesticide exposure and infections may be linked with the incidence of PD. The present study sought to determine whether exposure to a viral mimic prior to exposure to pesticides would exacerbate PD-like pathology. METHODS: Mice received a supra-nigral infusion of 5 µg of the double-stranded RNA viral analog, polyinosinic: polycytidylic acid (poly(I:C)), followed 2, 7 or 14 days later by administration of the pesticide, paraquat (nine 10 mg/kg injections over three weeks). RESULTS: As hypothesized, poly(I:C) pre-treatment enhanced dopamine (DA) neuron loss in the substantia nigra pars compacta elicited by subsequent paraquat treatment. The augmented neuronal loss was accompanied by robust signs of microglial activation, and by increased expression of the catalytic subunit (gp91) of the NADPH oxidase oxidative stress enzyme. However, the paraquat and poly(I:C) treatments did not appreciably affect home-cage activity, striatal DA terminals, or subventricular neurogenesis. CONCLUSIONS: These findings suggest that viral agents can sensitize microglial-dependent inflammatory responses, thereby rendering nigral DA neurons vulnerable to further environmental toxin exposure.

Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress.

BACKGROUND: Ghrelin plays important roles in glucose metabolism, appetite, and body weight regulation, and recent evidence suggests ghrelin prevents excessive anxiety under conditions of chronic stress. METHODS: We used ghrelin knockout (ghr-/-) mice to examine the role of endogenous ghrelin in anxious behavior and hypothalamic-pituitary-adrenal axis (HPA) responses to acute stress. RESULTS: Ghr-/- mice are more anxious after acute restraint stress, compared with wild-type (WT) mice, with three independent behavioral tests. Acute restraint stress exacerbated neuronal activation in the hypothalamic paraventricular nucleus and medial nucleus of the amygdala in ghr-/- mice compared with WT, and exogenous ghrelin reversed this effect. Acute stress increased neuronal activation in the centrally projecting Edinger-Westphal nucleus in WT but not ghr-/- mice. Ghr-/- mice exhibited a lower corticosterone response after stress, suggesting dysfunctional glucocorticoid negative feedback in the absence of ghrelin. We found no differences in dexamethasone-induced Fos expression between ghr-/- and WT mice, suggesting central feedback was not impaired. Adrenocorticotropic hormone replacement elevated plasma corticosterone in ghr-/-, compared with WT mice, indicating increased adrenal sensitivity. The adrenocorticotropic hormone response to acute stress was significantly reduced in ghr-/- mice, compared with control subjects. Pro-opiomelanocortin anterior pituitary cells express significant growth hormone secretagogue receptor. CONCLUSIONS: Ghrelin reduces anxiety after acute stress by stimulating the HPA axis at the level of the anterior pituitary. A novel neuronal growth hormone secretagogue receptor circuit involving urocortin 1 neurons in the centrally projecting Edinger-Westphal nucleus promotes an appropriate stress response. Thus, ghrelin regulates acute stress and offers potential therapeutic efficacy in human mood and stress disorders.

Slow-transit constipation with concurrent upper gastrointestinal dysmotility and its response to transcutaneous electrical stimulation.

PURPOSE: Transcutaneous electrical stimulation (TES) speeds up colonic transit in children with slow-transit constipation (STC). This study examined if concurrent upper gastrointestinal dysmotility (UGD) affected response to TES. METHODS: Radio-nuclear transit studies (NTS) were performed before and after TES treatment of STC as part of a larger randomised controlled trial. UGD was defined as delayed gastric emptying and/or slow small bowel transit. Improvement was defined as increase of ≥1 Geometric Centre (median radiotracer position at each time [small bowel = 1, toilet = 6]). RESULTS: Forty-six subjects completed the trial, 34 had NTS after stimulation (21 M, 8-17 years, mean 11.3 years; symptoms >9 years). Active stimulation increased transit in >50% versus only 25% with sham (p = 0.04). Seventeen children also had UGD. In children with STC and either normal upper GI motility (NUGM) and UGD, NTS improved slightly after 1 month (57 vs. 60%; p = 0.9) and more after 2 months (88 vs. 40%; p = 0.07). However, mean transit rate significantly increased with NUGM, but not UGD (5.0 ± 0.2: 3.6 ± 0.6, p < 0.01). CONCLUSION: Transcutaneous electrical stimulation was beneficial for STC, with response weakly associated with UGD. As measured by NTS, STC children with NUGM responded slightly more, but with significantly greater increased transit compared to those with UGD. Higher numbers are needed to determine if the difference is important.