Symptoms of Autism Spectrum Disorder (ASD) in individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): a systematic review

The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD in MPS III and quality assessed a total of 16 studies. Results indicated that difficulties within speech, language and communication consistent with ASD were present in MPS III, whilst repetitive and restricted behaviours and interests were less widely reported. The presence of ASD-like symptoms can result in late diagnosis or misdiagnosis of MPS III and prevent opportunities for genetic counselling and the provision of treatments

Investigating Non-invasive Measures of Stress in Ornamental Fish

The transport of ornamental marine fish may cause stress, which to date has been the subject of limited research. The present study aimed to characterise the behavioural and physiological responses to simulated transport stress in the common clownfish Amphiprion ocellaris (Cuvier, 1830) with the additional goal of validating non-invasive measures of water cortisol in a marine teleost for the first time. Behaviour and physiology of the animals was measured at different stages of transport (from initial capture and handling up to 72 hours transport time) and water quality measurements were taken from the transport water at key sampling points. In a second experiment biological filtration materials (“Bioballs” with denitrifying bacteria) were added to the transport bag to determine if stress was reduced when water quality was improved. The results of the study suggest that capture, handling and transport are stressful for clownfish, and the stress response appears to peak between 24 and 48 hours after the onset of the stressor. Water-borne cortisol was found to be a valid alternative to invasive methods of sampling, although only an average of 53% cortisol was recovered from sea water. Although handling and confinement appeared to be highly significant factors in eliciting the stress response water quality measurements revealed that fish are temporarily subjected to relatively high concentrations of ammonia as transport time increased, which may contribute to long-term effects on the health of the animals. This was reflected in an increased latency to feed and reduced social behaviours in fish transported for 24 hours or longer. Improving water quality did reduce the concentration of ammonia present; however, fish still exhibited elevated cortisol excretion suggesting that water quality is not the primary stressor associated with transport. Thus, the duration of transport should be restricted to a maximum of 24 hours to reduce the stress associated with this practice. A separate study investigated the potential for beauty treatment ‘fish spas’ to elicit stress in the freshwater cyprinid fish Garra rufa (Heckel, 1843). Water cortisol was measured non-invasively to determine if stress was reduced through the provision of environmental enrichment / furnishings, and whether stocking density influenced stress. Water quality was monitored to determine the effects of stocking density on environmental parameters (pH, ammonia, nitrite and nitrate). Finally, the effect of ii human hands being placed into the aquarium was investigated, to determine whether this influenced stress. Three hundred G. rufa were used in total, with groups being allocated randomly to one of four treatment groups: OP/B (optimum stocking density / barren tank – i.e. no enrichment); OP/E (optimum stocking density / enriched tank); OS/B (overstocked / barren tank); and OS/E (overstocked / enriched tank). Human hands were placed in each tank, and water samples were collected before and after for measurement of cortisol by ELISA, and to determine water quality parameters. The results revealed that overstocking tanks with G. rufa produced relatively higher baseline cortisol levels, suggesting that stocking density may have a significant effect on stress levels. The addition of furnishings into the aquarium did not reduce baseline cortisol levels in the fish prior to the introduction of human hands. However, fish maintained under enriched conditions exhibited a greater cortisol response when compared to individuals in barren tanks. It is hypothesised that the provision of enrichment reduces the available space for fish following the introduction of human hands, thereby increasing stress. Further studies are required to attempt to determine the effect of enrichment based upon the results of the present study. Feeding on human hands resulted in an elevated cortisol response from three out of the four treatment groups (with the exception of OP/B), with the results suggesting that either 1) the lower (i.e. optimal) stocking density and lack of enrichment in holding tanks is preferable for G. rufa fish welfare, or 2) the elevated cortisol reflected a response to a rewarding stimulus and is linked to increased foraging. Overall, the results of these studies have shown that water cortisol measurements are a valid means of assessing physiological stress in two species of fish in different contexts. This negates the need for invasive sampling and is an important refinement to existing protocols where fish are killed for plasma or whole body samples. The results also highlight the welfare impacts of transport and overstocking of ornamental fish providing valuable evidence that may be relevant to improving the husbandry and guidelines with respect to the ornamental fish industry

Validity of a self-report survey tool measuring the nutrition and physical activity environment of primary schools

Background: Valid tools measuring characteristics of the school environment associated with the physical activity and dietary behaviours of children are needed to accurately evaluate the impact of initiatives to improve school environments. The aim of this study was to assess the validity of Principal self-report of primary school healthy eating and physical activity environments. Methods: Primary school Principals (n = 42) in New South Wales, Australia were invited to complete a telephone survey of the school environment; the School Environment Assessment Tool – SEAT. Equivalent observational data were collected by pre-service teachers located within the school. The SEAT, involved 65 items that assessed food availability via canteens, vending machines and fundraisers and the presence of physical activity facilities, equipment and organised physical activities. Kappa statistics were used to assess agreement between the two measures. Results: Almost 70% of the survey demonstrated moderate to almost perfect agreement. Substantial agreement was found for 10 of 13 items assessing foods sold for fundraising, 3 of 6 items assessing physical activity facilities of the school, and both items assessing organised physical activities that occurred at recess and lunch and school sport. Limited agreement was found for items assessing foods sold through canteens and access to small screen recreation. Conclusions: The SEAT provides researchers and policy makers with a valid tool for assessing aspects of the school food and physical activity environment

Understanding implementation success: protocol for an in-depth, mixed-methods process evaluation of a cluster randomised controlled trial testing methods to improve detection of Lynch syndrome in Australian hospitals.

INTRODUCTION:In multisite intervention trials, implementation success often varies widely across settings. Process evaluations are crucial to interpreting trial outcomes and understanding contextual factors and causal chains necessary for successful implementation. Lynch syndrome is a hereditary cancer predisposition conferring an increased risk of colorectal, endometrial and other cancer types. Despite systematic screening protocols to identify Lynch syndrome, the condition remains largely underdiagnosed. The Hide and Seek Project ('HaSP') is a cluster randomised controlled trial determining the effectiveness of two approaches to improving Lynch syndrome detection at eight Australian hospital networks. To enhance widespread implementation of optimal Lynch syndrome identification, there is a need to understand not only what works, but also why, in what contexts, and at what costs. Here we describe an in-depth investigation of factors influencing successful implementation of procedures evaluated in the HaSP trial. METHODS AND ANALYSIS:A mixed-methods, theory-driven process evaluation will be undertaken in parallel to the HaSP trial. Data will include: interviews of Implementation Leads and Lynch syndrome stakeholders, pre-post implementation questionnaires, audio analysis of meetings and focus groups, observation of multidisciplinary team meetings, fidelity checklists and project log analysis. Results will be triangulated and coded, drawing on the Theoretical Domains Framework, Consolidated Framework for Implementation Research and Proctor's implementation outcomes. ETHICS AND DISSEMINATION:Use of a theory-based process evaluation will enhance interpretation and generalisability of HaSP trial findings, and contribute to the implementation research field by furthering understanding of the conditions necessary for implementation success. Ethical approval has been granted and results will be disseminated via publications in peer-reviewed journals and conference presentations. At trial completion, key findings will be fed back to sites to enable refinement of intervention strategies, both in the context of Lynch syndrome and for the possible generalisability of intervention components in other genetic and broader clinical specialties. HASP TRIAL REGISTRATION NUMBER:Australian New Zealand Clinical Trials Registry (Identifier: ACTRN12618001072202). Registered 27 June 2018. http://www.ANZCTR.org.au/ACTRN12618001072202.aspx

A persistent pesticide residue and the unusual catalytic proficiency of a dehalogenating enzyme

The soil of potato fields in The Netherlands harbors bacteria with the ability to metabolize 3-chloroacrylic acid, generated by the degradation of a pesticide (1,3-dichloropropene) that entered the environment in 1946. From examination of rate constants at elevated temperatures, we infer that the half-time at 25°C for spontaneous hydrolytic dechlorination of trans-3-chloroacrylic acid is 10,000 years, several orders of magnitude longer than half-times for spontaneous decomposition of other environmental pollutants such as 1,2-dichloroethane (72 years), paraoxon (13 months), atrazine (5 months), and aziridine (52 h). With thermodynamic parameters for activation similar to those for the spontaneous hydration of fumarate at pH 6.8, this slow reaction proceeds at a constant rate through the pH range between 2 and 12. However, at the active site of the enzyme 3-chloroacrylate dehalogenase (CaaD), isolated from a pseudomonad growing in these soils, hydrolytic dechlorination proceeds with a half-time of 0.18 s. Neither kcat nor kcat/Km is reduced by increasing solvent viscosity with trehalose, implying that the rate of enzymatic dechlorination is controlled by chemical events in catalysis rather than by diffusion-limited substrate binding or product release. CaaD achieves an ≈1012-fold rate enhancement, matching or surpassing the rate enhancements produced by many enzymes that act on more conventional biological substrates. One of those enzymes is 4-oxalocrotonate tautomerase, with which CaaD seems to share a common evolutionary origin

5-Year Follow-Up of a Telephone Intervention to Increase Fruit and Vegetable Consumption in Preschoolers: The ‘Healthy Habits’ Cluster Randomised Trial

Little is known about the long-term impact of telephone-based interventions to improve child diet. This trial aimed to assess the long-term effectiveness (after 5 years) of a telephone-based parent intervention in increasing children’s fruit and vegetable consumption. Parents of 3–5 year olds were recruited from 30 Australian preschools to participate in a cluster randomised controlled trial. Intervention parents received four, weekly, 30-min support calls aimed at modifying the home food environment. Control parents received printed materials. Consumption was assessed using the Fruit and Vegetable subscale of the Children’s Dietary Questionnaire (F&V-CDQ) (children) and daily servings of fruit and vegetables (children and parents) via parent telephone interview. Of the 394 parents who completed baseline, 57% (99 intervention, 127 control) completed follow-up. After 5-years, higher intervention F&V-CDQ scores, bordering on significance, were found in complete-case (+1.1, p = 0.06) and sensitivity analyses (+1.1, p = 0.06). There was no difference in parent or child consumption of daily fruit servings. Complete-case analysis indicated significantly higher consumption of child vegetable servings (+0.5 servings; p = 0.02), which was not significant in sensitivity analysis (+0.5 servings; p = 0.10). This telephone-based parent intervention targeting the family food environment may yield promising improvements in child fruit and vegetable consumption over a 5-year period

A cluster randomised controlled trial of a comprehensive accreditation intervention to reduce alcohol consumption at community sports clubs: study protocol

Introduction: Excessive alcohol consumption isresponsible for considerable harm from chronicdisease and injury. Within most developed countries,members of sporting clubs consume alcohol at levels above that of communities generally. Despite the potential benefits of interventions to address alcohol consumption in sporting clubs, there have been no randomised controlled trials to test the effectiveness of these interventions. The aim of this study is to examine the effectiveness of a comprehensive accreditation intervention with community football clubs (Rugby League, Rugby Union, soccer/association football and Australian Rules football) in reducing excessive alcohol consumption by club members.Methods and analysis: The study will be conducted in New South Wales, Australia, and employ a cluster randomised controlled trial design. Half of the football clubs recruited to the trial will be randomised to receive an intervention implemented over two and a half winter sporting seasons. The intervention is based on social ecology theory and is comprehensive in nature, containing multiple elements designed to decrease the supply of alcohol to intoxicated members, cease the provision of cheap and free alcohol, increase the availability and costattractiveness of non-alcoholic and low-alcoholic beverages, remove high alcohol drinks and cease drinking games. The intervention utilises a three-tiered accreditation framework designed to motivate intervention implementation. Football clubs in the control group will receive printed materials on topics unrelated to alcohol. Outcome data will be collected pre- and postintervention through cross-sectional telephone surveys of club members. The primary outcome measure will be alcohol consumption by club members at the club, assessed using a graduated frequency index and a seven day diary.Ethics and dissemination: The study was approved by The University of Newcastle Human Research Ethics Committee (reference: H-2008-0432). Study findings will be disseminated widely through peer-reviewed publications and conference presentations.<br /

Hydrolysis of N -Alkyl Sulfamates and the Catalytic Efficiency of an S–N Cleaving Sulfamidase

The final step in the degradation of heparin sulfate involves the enzymatic hydrolysis of its 2-sulfamido groups. To evaluate the power of the corresponding sulfamidases as catalysts, we examined the reaction of N-neopentyl sulfamate at elevated temperatures and found it to undergo specific acid catalyzed hydrolysis even at alkaline pH. A rate constant of 10−16 s−1 was calculated using the Eyring equation for water attack on the N-protonated species at pH 7, 25 °C. As a model for the pH neutral reaction, a rate constant for hydroxide attack on (CH3)3CCH2N+H2SO3− at pH 7, 25 °C was calculated to be 10−19 s−1. The corresponding rate enhancement (kcat/knon) produced by the N-sulfamidase of F. heparinum is approximately 1016-fold, which is somewhat larger than those generated by most hydrolytic enzymes but considerably smaller than those generated by S-O cleaving sulfatases

Ample evidence for fish sentience and pain

The majority of commentaries are supportive of our position on the scepticism that muddies the waters surrounding fish pain and sentience. There is substantial empirical evidence for pain in fish. Animals’ experience of pain cannot be compared to artificial intelligence (AI) because AI can only mimic responses to nociceptive input on the basis of human observations and programming. Accepting that fish are sentient would not be detrimental to the industries reliant on fish. A more proactive discussion between scientists and stakeholders is needed to improve fish welfare for the benefit of all