Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital.

INTRODUCTION: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the 'Evaluating the Alimentary and Respiratory Tracts in Health and disease' (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions. METHODS AND ANALYSIS: The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor. ETHICS AND DISSEMINATION: Ethics approval: Sydney Children's Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04071314.

Nonoperative management in children with early acute appendicitis: A systematic review.

PURPOSE: Appendectomy has remained the gold standard treatment of acute appendicitis for more than 100years. Nonoperative management (NOM) has been shown to be a valid treatment alternative for acute uncomplicated appendicitis in adults. A systematic review of available evidence comparing operative management (OM) and NOM in children with acute uncomplicated appendicitis was performed. METHODS: Systematic searches of MedLine, Embase, and a clinical trial register (https://clinicaltrials.gov/) were performed in March 2016. Only articles that studied NOM for uncomplicated appendicitis in children were included. Data generation was performed independently by two authors, and quality was assessed using the rating schema by the Oxford Centre for Evidence-Based Medicine. RESULTS: 15 articles were selected: four retrospective analyses, four prospective cohort studies, four prospective nonrandomized comparative trials and one randomized controlled trial (RCT). Initial success of the NOM groups (a cure within two weeks of intervention) ranged from 58 to 100%, with 0.1-31.8% recurrence at one year. CONCLUSION: Although present literature is scarce, publications support the feasibility of further studies investigating NOM of acute uncomplicated appendicitis in children. Higher quality prospective RCTs with larger sample sizes and robust randomization methods, studying the noninferiority of NOM with antibiotics compared with OM are required to establish its utility. LEVEL OF EVIDENCE: This manuscript is a systematic review and thus assigned the lowest evidence used from the manuscripts analyzed which is a Level IV.

Practice makes imperfect: Working memory training can harm recognition memory performance.

There is a great deal of debate concerning the benefits of working memory (WM) training and whether that training can transfer to other tasks. Although a consistent finding is that WM training programs elicit a short-term near-transfer effect (i.e., improvement in WM skills), results are inconsistent when considering persistence of such improvement and far transfer effects. In this study, we compared three groups of participants: a group that received WM training, a group that received training on how to use a mental imagery memory strategy, and a control group that received no training. Although the WM training group improved on the trained task, their posttraining performance on nontrained WM tasks did not differ from that of the other two groups. In addition, although the imagery training group's performance on a recognition memory task increased after training, the WM training group's performance on the task decreased after training. Participants' descriptions of the strategies they used to remember the studied items indicated that WM training may lead people to adopt memory strategies that are less effective for other types of memory tasks. These results indicate that WM training may have unintended consequences for other types of memory performance.

Are children on jejunal feeds at risk of iron deficiency?

Children on exclusive jejunal feeding may be at risk of iron deficiency due to the feeds bypassing the duodenum, which is the primary site for iron absorption. We describe the biochemical and hematological features of six children on exclusive jejunal feeding who did not receive iron supplementation. At a mean (standard deviation) period of 11 (6.5) mo after commencing jejunal feeds, there was a significant reduction in both serum iron (18.5 g/L vs 9.8 g/L, P = 0.01) and transferrin saturation levels (23.1% vs 13.7%, P = 0.02), suggesting iron deficiency. However, there was no significant change in ferritin, hemoglobin and mean corpuscular volume levels post-commencement of jejunal feeds. This may be the result of small bowel adaptation in response to early iron deficiency. Larger and longer term prospective studies are required to investigate if children on jejunal feeds are at risk of developing iron deficiency.

Basic characterization of 64Cu-ATSM as a radiotherapy agent.

64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) is a promising radiotherapy agent for the treatment of hypoxic tumors. In an attempt to elucidate the radiobiological basis of 64Cu-ATSM radiotherapy, we have investigated the cellular response patterns in vitro cell line models. Cells were incubated with 64Cu-ATSM, and the dose-response curves were obtained by performing a clonogenic survival assay. Radiation-induced damage in DNA was evaluated using the alkali comet assay and apoptotic cells were detected using Annexin V-FITC and propidium iodide staining methods. Washout rate and subcellular distribution of 64Cu in cells were investigated to further assess the effectiveness of 64Cu-ATSM therapy on a molecular basis. A direct comparison of subcellular localization of Cu-ATSM was made with the flow tracer analog Cu-pyruvladehyde-bis(N4-methylthiosemicarbazone). In this study, 64Cu-ATSM was shown to reduce the clonogenic survival rate of tumor cells in a dose-dependent manner. Under hypoxic conditions, cells took up 64Cu-ATSM and radioactive 64Cu was highly accumulated in the cells. In the 64Cu-ATSM-treated cells, DNA damage by the radiation emitted from 64Cu was detected, and inhibition of cell proliferation and induction of apoptosis was observed at 24 and 36 h after the treatment. The typical features of postmitotic apoptosis induced by radiation were observed following 64Cu-ATSM treatment. The majority of the 64Cu taken up into the cells remained in the postmitochondrial supernatant (the cellular residue after removal of the nuclei and mitochondria), which indicates that the beta- particle emitted from 64Cu may be as effective as the Auger electrons in 64Cu-ATSM therapy. These data allow us to postulate that 64Cu-ATSM will be able to attack the hypoxic tumor cells directly, as well as potentially affecting the peripheral nonhypoxic regions indirectly by the beta- particle decay of 64Cu.