Many paediatric patients with cancer experience significant chemotherapy side effects. Predisposition to drug reactions is governed by single nucleotide polymorphisms (SNPs). We performed a systematic review of the literature from 2006 through 2016. Outcomes of interest included patient characteristics, cancer type drug of interest, genes investigated, toxicity identified and genetic polymorphisms implicated. The primary toxicities studied were neurotoxicity cardiotoxicity, osteonecrosis, and thromboembolism and hypersensitivity reactions. The retrieved studies were grouped according to toxicity reported and SNP associations. This review highlights the discoveries to date in pharmacogenomics and paediatric oncology along with highlighting some of the important limitations in the area.

BACKGROUND: Previous studies have reached conflicting conclusions about the role of atopy as a risk factor for COPD. In part, this is attributable to variation in the definitions of airflow limitation and the treatment of people with asthma. OBJECTIVE: To establish whether there is any independent association between atopy and post-bronchodilator airflow limitation in the general population aged 40 years and over. METHODS: A cross-sectional survey was conducted in a general population sample of 2415 people aged 40 years and over in Australia. A history of ever being diagnosed with asthma was elicited by questionnaire. Atopy was defined as any skin prick test weal to common aeroallergens ≥4 mm. Airflow limitation was defined as post-bronchodilator spirometric (FEV1 /FVC) ratio <lower limit of normal. Analyses were adjusted for potential confounding due to age, sex, smoking, race and socio-economic status. RESULTS: The prevalence of atopy, ever diagnosed asthma and post-bronchodilator airflow obstruction was 44.8%, 19.3% and 7.5%, respectively. In the population as a whole, atopy was associated with lower FEV₁ (adjusted difference -0.068L, 95% confidence interval (CI) -0.104 to -0.032), FVC (adj. difference -0.043L, 95% CI -0.086 to -0.0009) and post-bronchodilator FEV₁/FVC ratio (adj. difference -0.011, 95% CI -0.017 to -0.0055). The effect of atopy on lung function was no longer apparent when participants who reported ever diagnosed asthma were excluded (FEV₁ -0.011L, [95% CI -0.05 to 0.028L], FVC -0.012L [95% CI -0.060 to 0.036] and FEV₁/FVC ratio -0.0012 [95% CI -0.0072 to 0.0047L]). CONCLUSION AND CLINICAL RELEVANCE: The apparent association between atopy and post-bronchodilator airflow limitation in the general population appears to be explained by the association between atopy and having ever diagnosed asthma and the effect of asthma on lung function.

BACKGROUND: Short-term IV sRLX (recombinant human relaxin-2) infusion enhances endothelium-dependent relaxation in mesenteric arteries. This is initially underpinned by increased NO followed by a transition to prostacyclin. The effects of short-term IV sRLX treatment on pressure-induced myogenic tone and vascular remodeling in these arteries are unknown. Therefore, we investigated the effects of sRLX infusion on pressure-induced myogenic tone and passive mechanical wall properties in mesenteric arteries. METHODS: Mesenteric artery myogenic tone and passive mechanics were examined after 48-hours and 10-days infusion of sRLX. Potential mechanisms of action were assessed by pressure myography, qPCR, and Western blot analysis. RESULTS: Neither 48-hours nor 10-days sRLX treatment had significant effects on myogenic tone, passive arterial wall stiffness, volume compliance, or axial lengthening. However, in 48-hours sRLX -treated rats, incubation with the NO synthase blocker L-NAME significantly increased myogenic tone (P<.05 vs placebo), demonstrating an increased contribution of NO to the regulation of myogenic tone. eNOS dimerization, but not phosphorylation, was significantly upregulated in the arteries of sRLX -treated rats. CONCLUSION: In mesenteric arteries, 48-hours sRLX treatment upregulates the role of NO in the regulation of myogenic tone by enhancing eNOS dimerization, without altering overall myogenic tone or vascular remodeling.

BACKGROUND: Dental practitioners agree that dietary counselling is essential for caries prevention; however, they provide advice infrequently due to a lack of confidence and competence. This study aimed to improve practises through an online training module exploring the use of a brief counselling method, and a diet assessment of caries risk form. METHODS: Dental practitioners (N = 41) completed a survey on current practises and confidence in providing dietary advice, followed by an online training module. Ten practitioners were involved in recruiting patients, eliciting a diet assessment of caries risk, and using brief counselling techniques with these patients. Patients were followed up at 6 months for a risk assessment review. Dental practitioners also completed a 6-month follow-up survey exploring changes in confidence and perceived barriers. RESULTS: Dental hygienists' confidence improved significantly following the intervention (P < 0.025). Patients showed a significant reduction in high-risk behaviour pertaining to quantity and timing of sugar intake, and significant trends in improvement of behaviours relating to frequency, exposure time and drinking style (P < 0.05). CONCLUSIONS: It appears that a simple online learning module can improve hygienists' confidence in dietary advice provision, and have a positive impact on patient behaviour change, within a relatively short time-frame.

OBJECTIVE: The natural history of nonfunctioning pituitary macroadenomas (NFPMA) after surgical resection is variable, with guidelines unable to define the duration of radiological follow-up. In this first Australian series, we identify risk factors for regrowth/recurrence of NFPMA to assist with guiding recommendations for long-term follow-up. DESIGN: Retrospective analysis of all radiotherapy-naïve cases with NFPMA resected between 1995 and 2013. PATIENTS: One hundred and twenty-three cases had both ≥2 postoperative scans and ≥12-month follow-up. MEASUREMENTS: Regrowth was defined as any sustained increase in diameter of residual adenoma or recurrence as any new adenoma occurring post complete resection on serial pituitary MRI. RESULTS: Median follow-up time was 48 months (interquartile range [IQR]: 31-86). Overall regrowth/recurrence occurred in 29% (36/123). Regrowth occurred in 40% (30/76) at a median time of 44.5 months (IQR 22-80) compared to recurrence of 12.5% (6/48; P=.003), occurring at a median time of 48 months (IQR 12-96; P=.7). Further treatment was required in 66.7% and 56.7%, respectively (=1.0). Risk factors for regrowth/recurrence by multivariate analysis were presence of residual disease and younger age at presentation. The longest time for regrowth was 168 months (14 years) and recurrence 156 months (13 years). CONCLUSIONS: Presence of postoperative residual adenoma and younger age at presentation are the main predictors of regrowth/recurrence in NFPMA. Long-term serial imaging is required to detect regrowth and recurrence in younger patients and those with residual disease. Most regrowth/recurrences will occur within 10 years of follow-up.

BACKGROUND: Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood. METHODS: A high-risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow-ups. RESULTS: Very early-onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7-6.1]), as was very early-onset remitting eczema (onset <6 months but not present from 2-5 years, OR = 2.7, 95% CI = 1.0-7.2) and early-onset persistent eczema (onset from 6-24 months, OR = 2.3, 95% CI = 1.2-4.7). Late-onset eczema (commenced from 2-5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1-8.2) but not at age 6 years. Only very early-onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4-4.1). CONCLUSION AND CLINICAL RELEVANCE: Eczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high-risk children. If these associations are causal, prevention of early-life eczema might reduce the risk of respiratory allergy.

Elevated COâ stimulates crop yields but leads to lower tissue and grain nitrogen concentrations [N], raising concerns about grain quality in cereals. To test whether N fertiliser application above optimum growth requirements can alleviate the decline in tissue [N], wheat was grown in a Free Air COâ Enrichment facility in a lowâ rainfall cropping system on high soil N. Crops were grown with and without addition of 50â 60 kg N/ha in 12 growing environments created by supplemental irrigation and two sowing dates over 3 years. Elevated COâ increased yield and biomass (on average by 25%) and decreased biomass [N] (3%â 9%) and grain [N] (5%). Nitrogen uptake was greater (20%) in crops grown under elevated COâ . Additional N supply had no effect on yield and biomass, confirming high soil N. Small increases in [N] with N addition were insufficient to offset declines in grain [N] under elevated COâ . Instead, N application increased the [N] in straw and decreased N harvest index. The results suggest that conventional addition of N does not mitigate grain [N] depression under elevated COâ , and lend support to hypotheses that link decreases in crop [N] with biochemical limitations rather than N supply.