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.

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.

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.

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.

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.

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.

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.

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.

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.

Dog attack: the application of canine DNA profiling in forensic casework.

More than 100,000 dog attacks occur each year in Australia and many go unsolved. Dog attacks are not only a cause of human injury but may also involve injury and death to family pets, prized livestock and wildlife. Canine biological evidence can often be left behind on a victim or at the scene of an attack. Our laboratory provides canine DNA profiling for forensic investigations, utilising an in-house panel of 11 canine-specific autosomal short tandem repeat markers previously validated for use in casework. Case studies will be presented that outline methods for sampling of suspected canine biological evidence, profiling of canine DNA, statistical analysis, case outcomes and challenges for investigators.

Trunk strength and mobility changes in children with slow transit constipation.

BACKGROUND AND AIM: It appears that there are no published reports on childhood slow transit constipation (STC) that have considered the state of the musculoskeletal components of the trunk in these children. The present study aimed to determine whether children with STC have different trunk musculoskeletal characteristics that might be related to their defecation difficulties, compared to controls. METHODS: With the aid of computer-analyzed photographs and clinical testing, 41 children with STC and 41 age-matched controls were examined for Marfanoid features, sitting posture, spinal joint mobility and trunk muscle strength. The latter was assessed by measuring maximum voluntary abdominal bulging and retraction in sitting, and active trunk extension in prone-lying. Levels of general exercise and sedentary activities were evaluated by questionnaire. RESULTS: STC subjects were more slumped in relaxed sitting (P < or = 0.001), less able to bulge (P < or = 0.03) and less able to actively extend the trunk (P = 0.02) compared to controls. All subjects sat more erect during abdominal bulging (P < or = 0.03). CONCLUSION: The results show that STC children have reduced trunk control and posture, which indicates that clinicians should include training of trunk muscles and correction of sitting posture. There was no evidence that children with STC exercised less than the controls.

Colonic transit studies: normal values for adults and children with comparison of radiological and scintigraphic methods.

The sitz or plastic marker study for colonic transit has been around for many years. It is applicable where an X-ray machine exists, is widely used and is accepted as the gold standard for diagnosing constipation. Recently, radiopharmaceutical methods have been developed. The theme of this review is their possible roles in the assessment of paediatric bowel motility disorders in patients presenting to paediatric surgeons. This review presents data on total and segmental transit in normal adults and children and comparing the two techniques in adults. Reliability and reproducibility are presented. Normative data for colonic transit in adults and children are discussed and parameters for assessing abnormal transit are reviewed. Normal colonic transit takes 20-56 h. Plastic marker studies are more readily accessible, but the assessment may be misleading with current methods. Plastic markers show faster transit than scintigraphy. It is difficult to compare the two techniques because methods of reporting are different. Using scintigraphy, repeatability is good. Separation of normal from slow transit in the ascending colon is apparent at 24 and 48 h, but the determination of transit through the distal colon/rectum in adults may require studies of more than 7 days. In conclusion, plastic marker studies and scintigraphy show similar transit rates in young adults and children. However, scintigraphy has advantages of allowing transit through the stomach and small intestine to be measured and has proved useful in the diagnostic workup of children with intractable constipation.

Standard medical therapies do not alter colonic transit time in children with treatment-resistant slow-transit constipation.

BACKGROUND: Slow transit constipation (STC) is a form of chronic constipation characterised by prolonged passage of faecal matter through the colon. It is diagnosed by demonstrating delayed colonic transit on gastrointestinal transit studies. Traditionally, radio-opaque marker studies are performed. Recently, radioisotope nuclear transit studies (NTS) have been used in our centre to assess gastrointestinal transit time. This study aimed to evaluate if there are changes in colonic transit in STC children resistant to standard medical treatment over a prolonged period. METHODS: Children with STC resistant to standard medical therapy for > or =2 years who had undergone two separate NTS to assess their colonic transit (where the first study had identified slow colonic transit without anorectal retention) were identified after ethical approval. The geometric centre (GC) of radioisotope activity at 6, 24, 30 and 48 h was compared in the two transit studies to determine if changes occurred. RESULTS: Seven children (4 males) with proven STC resistant to standard medical therapy and two transit studies performed at different times were identified. Mean age was 7.0 years (5.4-10.8 years) at first study, and 11.4 years (9.7-14.2 years) at second study, with a mean of 4.4 years (1-8.5 years) between studies. There was no significant difference in colonic transit at any timepoint in the two tests (paired t test). CONCLUSIONS: We conclude that nuclear transit studies are reproducible in assessing slow colonic transit in children with treatment-resistant STC and demonstrate that conventional medical treatment over many years has no effect on underlying colonic motility.

Slow-transit constipation in children: our experience.

Constipation is a common problem in children, with childhood prevalence estimated at between 1 and 30%. It accounts for a significant percentage of referrals to paediatricians and paediatric gastroenterologists. It commonly runs in families, suggesting either an underlying genetic predisposition or common environmental factors, such as dietary exposure. The peak age for presentation of constipation is shortly after toilet training, when passage of hard stools can cause pain on defecation, which then triggers holding-on behaviour in the child. At the time of the next call to stool the toddler may try to prevent defecation by contraction of the pelvic floor muscles and anal sphincter. Unless the holding-on behaviour is quickly corrected by interventions to soften faeces and prevent further pain, the constipation can very rapidly become severe and chronic. Until recently, this mechanism was thought to be the only significant primary cause of constipation in childhood. In this review, we will summarise recent evidence to suggest that severe chronic constipation in children may also be due to slowed colonic transit.

Current management of the undescended testicle.

Cryptorchidism, where either one or both testes fails to migrate to the base of the scrotum, affects 4% to 5% of full-term and 9% to 30% of premature males at birth. The testis can be found in any position along its usual line of descent; however, approximately 80% will be located in the inguinal region, just outside the inguinal canal. Early correction, from 3 to 6 months of age, is currently advised. The preferred means of investigation and subsequent surgical intervention are dependent on the position of the cryptorchid testis. Risks associated with cryptorchidism include infertility and malignancy. The aim of appropriate management is to minimize these, and any other, associated complications.

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.

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'.

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.