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Buruli ulcer (BU) is a neglected tropical disease of skin and subcutaneous tissues caused by Mycobacterium ulcerans. BU-endemic areas are highly focal, and M. ulcerans transmission dynamics vary by setting. In Victoria, Australia, BU is an endemic vector-borne zoonosis, with mosquitoes and native possums implicated in transmission, and humans incidental hosts. Despite the importance of possums as wildlife reservoirs of M. ulcerans, knowledge of BU in these animals is limited. Opportunistic necropsy-based and active trap-and-release surveillance studies were conducted across Melbourne and Geelong, Victoria, to investigate BU in possums. Demographic data and biological samples were collected, and cutaneous lesions suggestive of BU were mapped. Samples were tested for the presence of M. ulcerans DNA by IS2404 qPCR. The final dataset included 26 possums: 20 necropsied; 6 trapped and released. Most possums (77%) were common ringtails from inner Melbourne. Nine had ulcers, ranging from single and mild, to multiple and severe, exposing bones and tendons in three cases. M. ulcerans was confirmed in 73% (19/26) of examined possums: 8 with lesions and 11 without. Oral swabs were most frequently indicative of M. ulcerans infection status. Severely ulcerated possums had widespread systemic internal bacterial dissemination and were shedding M. ulcerans in faeces. The anatomical distribution of ulcers and PCR positivity of biological samples suggests possums may contract BU from bites of M. ulcerans-harbouring mosquitoes, traumatic skin wounds, ingestion of an unknown environmental source, and/or during early development in the pouch. Ringtail possums appear highly susceptible to infection with M. ulcerans and are important bacterial reservoirs in Victoria. Oral swabs should be considered for diagnosis or surveillance of infected possums. A One Health approach is needed to design and implement integrated interventions that reduce M. ulcerans transmission in Victoria, thereby protecting wildlife and humans from this emerging zoonotic disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hobbs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Australia, native possums are a major wildlife reservoir for Mycobacterium ulcerans , the causative agent of the neglected tropical skin disease Buruli ulcer (BU). Large-scale possum excreta surveys that use PCR to detect M. ulcerans in 100-1,000 s of excreta specimens are an important tool that can inform geospatial modeling and predict locations of future human BU risk. However, the significant expense of commercial kits used to extract DNA from specimens is a major barrier to routine implementation. Here, we developed a low-cost method for DNA extraction from possum excreta, possum tissue, and pure mycobacterial cultures, using a guanidinium isothiocyanate lysis solution and paramagnetic beads. In a 96-well plate format for high-throughput processing, the paramagnetic bead DNA extraction method was threefold less sensitive but only 1/6 the cost of a commonly used commercial kit. Applied to tissue swabs, the method was fourfold more sensitive and 1/5 the cost of a commercial kit. When used for preparing DNA from pure mycobacterial cultures, the method yielded purified genomic DNA with quality metrics comparable to more lengthy techniques. Our paramagnetic bead method is an economical means to undertake large-scale M. ulcerans environmental surveillance that will directly inform efforts to halt the spread of BU in Victoria, Australia, with potential for applicability in other endemic countries., Importance: Buruli ulcer (BU) is a neglected tropical skin disease, with an incidence that has dramatically increased in temperate southeastern Australia over the last decade. In southeastern Australia, BU is a zoonosis with native possums the major wildlife reservoir of the causative pathogen, Mycobacterium ulcerans . Infected possums shed M. ulcerans in their excreta, and excreta surveys using PCR to screen for the presence of pathogen DNA are a powerful means to predict future areas of Buruli ulcer risk for humans. However, excreta surveys across large geographic areas require testing of many thousands of samples. The cost of commercial DNA extraction reagents used for preparing samples for PCR testing can thus become prohibitive to effective surveillance. Here, we describe a simple, low-cost method for extracting DNA from possum excreta using paramagnetic beads. The method is versatile and adaptable to a variety of other sample types including swabs collected from possum tissues and pure cultures of mycobacteria., Competing Interests: The authors declare no conflict of interest.

In February 2023, a report of morbidity and mortality in waterbirds triggered a collaborative regional wildlife disease outbreak investigation and response, led by Parks Victoria. Triage, rehabilitation and diagnosis of sick and dead birds were undertaken by Zoos Victoria (ZV), Agriculture Victoria, Vets for Compassion, Wildlife Victoria and Melbourne Veterinary School (MVS). The field response focused on collection of sick and dead birds for wildlife welfare, for diagnosis, and to reduce environmental contamination. Botulism was suspected, based on clinical signs and lack of significant gross pathology, and this diagnosis was confirmed by PCR testing. Low pathogenicity avian influenza (LPAI) viruses non H5 or H7 were detected in two birds and ruled out in all in others tested. These incidental, non-clinical LPAI detections are considered part of the natural wild bird virus community in Australia. A number of elements contributed to the collaborative effort. Regional individuals had the necessary connections for reporting, collecting and transporting birds. There was rapid determination by the Victorian Department of Energy, Environment and Climate Action (DEECA) that Parks Victoria, as the land managers, should lead the response. Zoos Victoria provided capacity and expertise in wildlife triage and rehabilitation, and Agriculture Victoria, ZV and MVS were responsible for veterinary management of the response and diagnosis. Field investigation and response were conducted by Parks Victoria, Agriculture Victoria, MVS and veterinary teams from Vets for Compassion and Wildlife Victoria. Wildlife Health Australia (WHA) provided guidance and information, approved National Significant Disease Investigation Program funding and captured the event in the national wildlife health information database. Communication and media were important for community understanding of the event., (© 2024 The Author(s). Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Buruli ulcer is a chronic ulcerative disease of the skin and subcutaneous tissues caused by infection with Mycobacterium ulcerans. Although Australian possums are known to be susceptible to Buruli ulcer, many aspects of the disease in possums, including welfare impacts, remain largely unreported. Severe clinical Buruli ulcer was identified in four common ringtail possums (Pseudocheirus peregrinus) from Melbourne, Victoria. All four possums were euthanased due to the presence of deep ulcerative lesions on paws, with extensive tissue necrosis that exposed bones and tendons in three cases. Histologically, there was severe ulcerative necrotising pyogranulomatous dermatitis, panniculitis and myositis, with intralesional acid-fast bacteria. M. ulcerans was detected by real-time PCR in all swabs, tissues and faeces collected from all four cases. Buruli ulcer may be an important and under-recognised cause of poor possum welfare in endemic areas. The physical impacts of the severe cutaneous lesions, especially those extending to underlying bones and joints, would have directly impaired the mobility of these possums, affecting navigation of their natural environments and expression of natural behaviours including foraging and socialising. Systemic distribution of M. ulcerans throughout all major internal organs, as observed here, may further impact the health and fitness of infected possums. Faecal shedding of M. ulcerans in all four cases supports the role of possums as zoonotic reservoirs. Further research is needed to investigate the epidemiology, pathogenesis and welfare impacts of Buruli ulcer in possums and to inform the design of interventions that may protect their health and welfare., (© 2024 The Author(s). Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Chronic phalaris toxicity (CPT) is a neurological disease caused by animals ingesting toxins produced by early growth stages of Phalaris aquatica, a pasture plant introduced to the southeastern regions of Australia post colonization. Little is known about the clinical progression of CPT in wildlife, as incidents are sporadic and predominantly reported when animals are in the end stages of disease and in a poor welfare state. We studied a cohort of 35 eastern gray kangaroos (Macropus giganteus) affected by CPT to clarify clinical prognosis and survival rates. Kangaroos were captured in May, June, and July of 2022 at Plenty Gorge Parklands, Victoria, Australia. Each animal was radiotracked for 180 d, clinical progression and disease outcomes monitored twice a week. By the conclusion of the study, 24 animals had died (19 by euthanasia due to deterioration, five found dead). Ten animals survived, with two demonstrating a reduction in clinical signs and eight showing full resolution of clinical signs. One animal was disqualified from the study. The overall survival rate was 29.4% (95% confidence interval 17.5-49.5%). The survival duration of animals that died ranged from 5 to 133 d. There was no difference in survival rate based on sex (P=0.2), age class (P=0.49) or the month of capture (P=0.49). These results suggest that CPT is an important health and welfare concern for at-risk macropod populations, with high case-fatality rates and prolonged clinical durations. Further research to manage the disease via methods such as reducing Phalaris aquatica plant coverage and preventative treatments for animals is warranted to reduce disease incidences and improve disease outcomes in wildlife populations., (© Wildlife Disease Association 2024.)

Phalaris aquatica is pasture species introduced into Australia during early European settlement. Consumption of the plant can cause the neurological condition chronic phalaris toxicity (CPT) in sheep and cattle. In recent years, there has been an increase in reports of CPT in macropods, which has raised concerns regarding its impacts on their welfare. Currently, little is known about the distribution or seasonal patterns of this disease in wildlife, information pivotal in assessing its potential risks. Between 2021 and 2022, we conducted a survey targeting government bodies, veterinary businesses and wildlife organisations to investigate the locations and time of occurrence of CPT in macropods in the state of Victoria, Australia. We received 13 survey responses, 12 verbal reports, a full record of investigated cases from a university veterinary school and cases from a wildlife rescue organisation. Over the period of 11 years, Victoria had 918 cases of CPT recorded in macropods from 36 local government areas, with cases concentrated centrally just north of the state capital of Melbourne and July (midwinter) being the month with the highest case count (n = 220). There was a significant positive correlation between case count and both the abundance of kangaroos (Macropus giganteus and Macropus fuliginosus) (P < 0.01) and the abundance of P. aquatica (P = 0.009), and a significant negative correlation between annual case count and average rainfall of March (P = 0.016) and April (P = 0.02). Understanding these relationships will assist land and wildlife managers in predicting the risk and magnitude of disease outbreaks of CPT each in Victoria., (© 2024 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

The bacterial agent that causes fowl cholera, Pasteurella multocida, was isolated from two deceased wild waterbirds in Victoria, Australia, in 2013. Whole genome sequence analysis placed the isolates into ST20, a subtype described in farmed chickens from Queensland, Australia and more recently in feedlot cattle and in pigs across a broader area of the continent. This study also found ST20 between 2009 and 2022 on three chicken farms and two turkey farms located in four Australian states. The sequences of 25 of these ST20 isolates were compared to 280 P. multocida genomes from 23 countries and to 94 ST20 Illumina datasets from Queensland that have been deposited in public databases. The ST20 isolates formed a single phylogenetic clade and were clustered into four sub-groups with highly similar genomes, possessing either LPS type 1 or type 3 loci. Various repertoires of mobile genetic elements were present in isolates from farmed, but not wild birds, suggesting complex histories of spill-over between avian populations and gene acquisition within farm environments. No major antimicrobial resistance was predicted in any of the ST20 isolates by the genomic analysis. The closest relative of these isolates was a ST394 bovine respiratory tract isolate from Queensland, which differed from ST20 by only one allele and carried beta-lactam and tetracycline resistance genes. These findings underline the importance of understanding the role of wild and commercial birds in the maintenance of fowl cholera, and of implementing regular epidemiological surveillance and biosecurity management programmes in wildlife, as well as free-range poultry farms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Anticoagulant rodenticides (ARs) influence predator populations and threaten the stability of ecosystems. Understanding the prevalence and impact of rodenticides in predators is crucial to inform conservation planning and policy. We collected dead birds of four nocturnal predatory species across differing landscapes: forests, agricultural, urban. Liver samples were analysed for eight ARs: three First Generation ARs (FGARs) and five SGARs (Second Generation ARs). We investigated interspecific differences in liver concentrations and whether landscape composition influenced this. FGARs were rarely detected, except pindone at low concentrations in powerful owls Ninox strenua. SGARs, however, were detected in every species and 92 % of birds analysed. Concentrations of SGARs were at levels where potential toxicological or lethal impacts would have occurred in 33 % of powerful owls, 68 % of tawny frogmouths Podargus strigoides, 42 % of southern boobooks N. bookbook and 80 % of barn owls Tyto javanica. When multiple SGARs were detected, the likelihood of potentially lethal concentrations of rodenticides increased. There was no association between landscape composition and SGAR exposure, or the presence of multiple SGARs, suggesting rodenticide poisoning is ubiquitous across all landscapes sampled. This widespread human-driven contamination in wildlife is a major threat to wildlife health. Given the high prevalence and concentrations of SGARs in these birds across all landscape types, we support the formal consideration of SGARs as a threatening process. Furthermore, given species that do not primarily eat rodents (tawny frogmouths, powerful owls) have comparable liver rodenticide concentrations to rodent predators (southern boobook, eastern barn owl), it appears there is broader contamination of the food-web than anticipated. We provide evidence that SGARs have the potential to pose a threat to the survival of avian predator populations. Given the functional importance of predators in ecosystems, combined with the animal welfare impacts of these chemicals, we propose governments should regulate the use of SGARs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Health surveillance of wildlife populations is essential for conservation and reduction of the impacts of disease. Population declines and areas of overabundance of koalas (Phascolarctos cinereus) can disrupt the overall survival of the species as well as its habitat. This retrospective study was conducted to describe population distributions, identify areas which need increased surveillance and improve koala health surveillance methodology by Wildlife Health Victoria: Surveillance (WHV:S) at the Veterinary School of The University of Melbourne. Twelve years of Victorian koala observation data from the Atlas of Living Australia combined with surveillance data from WHV:S were used to create choropleth maps, using Quantum Geographic Information Systems of populations and surveillance events, visually representing hot spots. This data was further used to calculate health surveillance efforts between 2008 to the beginning of 2020. Analysis ranked postcodes throughout Victoria from low surveillance efforts to high, using standardised surveillance ratio's 95% confidence interval upper limits which were mapped using a colour gradient. This identified postcodes which need increased surveillance effort, corresponding to areas with high koala observations and low surveillance submissions. This analysis can guide surveillance for postcodes with koalas that were under-represented and inform improved methodology of future surveillance by WHV:S. The specific advice for improvements to WHV:S includes utilisation of citizen science and syndromic surveillance, website improvement, increasing community awareness and more. The limitations of this study were discussed., (© 2022 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

A molecular survey of herpesviruses in Australian native mammals was conducted, spanning 260 individuals from 27 species. Among the herpesviruses detected, a putative new gammaherpesvirus species was detected in the yellow-bellied glider (Petaurus australis), and another in the critically endangered Leadbeater's possum (Gymnobelideus leadbeateri). In addition, the known host range of the putative species macropodid gammaherpesvirus 3 (MaHV-3) is herein extended to the western grey kangaroo (Macropus fuliginosus). These findings expand our understanding of herpesviruses in Australian mammals and may inform biosecurity protocols for captive and translocated populations., (© 2022 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

Background: Vitamin and mineral supplements are widely used by children and adults diagnosed with autism spectrum disorder (ASD). Several studies have reported benefits of such supplements in resolving nutritional deficiencies, treating various metabolic problems and improving symptoms and overall quality of life., Methods: This research survey collected evaluations from 161 people about the effectiveness of ANRC-Essentials Plus (ANRC-EP), a vitamin/mineral/micronutrient supplement designed for children and adults with autism. Although this was an open-label survey, results were compared with a three-month randomized double-blind placebo-controlled study of an earlier version of the supplement. Evaluations included the Parent Global Impressions of Autism (PGIA) and the Overall Benefit/Adverse Effect scale of the National Survey on Treatment Effectiveness for Autism (NSTEA)., Results: The participants reported substantially higher Average PGIA Scores than the placebo group in a similar previous study, with an estimated effect size of 0.66. Based on the NSTEA questionnaire, 73% of participants rated the Overall Benefit as Moderate, Good, or Great, with scores that were substantially higher than the NSTEA study found for multi-vitamins, the average of 58 nutraceuticals, and the average of 28 psychiatric and seizure medications. The Overall Adverse Effect score was low (0.25/3.0), similar or slightly higher than other nutraceuticals, and much lower than the average of 28 psychiatric and seizure medications (0.9/3.0). Sub-analysis found that the Overall Benefit of ANRC-EP was not significantly affected by gender, age, autism severity, diet quality, self-limited diet, use of psychiatric or seizure medications, dosage, developmental history, intellectual disability, or seizures. This indicates that ANRC-EP may be beneficial for a wide range of children and adults with ASD. A limitation of this study is the retrospective nature of the survey, and that participants who had good benefits were more likely to respond., Conclusions: This study found that ANRC-EP had significant benefits for a wide range of symptoms, and low adverse effects., (© 2022. The Author(s).)

The powerful owl (Ninox strenua) is a threatened apex predator that consumes mainly arboreal marsupial prey. Low density populations reside in urban landscapes where their viability is tenuous. The catalyst for this research was the reported death of eight powerful owls around Melbourne, Australia, in less than one year (2020/2021). Eighteen deceased owls were toxicologically screened. We assessed toxic metals (Mercury Hg, Lead Pb, Cadmium Cd and Arsenic As) and anticoagulant rodenticides (ARs) in liver (n = 18 owls) and an extensive range of agricultural chemicals in muscle (n = 14). Almost all agricultural chemicals were below detection limits except for p,p-DDE, which was detected in 71% of birds at relatively low levels. Toxic metals detected in some individuals were generally at low levels. However, ARs were detected in 83.3% of powerful owls. The most common second-generation anticoagulant rodenticide (SGAR) detected was brodifacoum, which was present in every bird in which a rodenticide was detected. Brodifacoum was often present at toxic levels and in some instances at potentially lethal levels. Presence of brodifacoum was detected across the complete urban-forest/agriculture gradient, suggesting widespread exposure. Powerful owls do not scavenge but prey upon arboreal marsupials, and generally not rodents, suggesting that brodifacoum is entering the powerful owl food web via accidental or deliberate poisoning of non-target species (possums). We highlight a critical need to investigate SGARs in food webs globally, and not just in species directly targeted for poisoning or their predators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The concept of "acquired autism" refers to the hypothesis that amongst the massive heterogeneity that encompasses autism spectrum disorder (ASD) there may be several phenotypes that are neither syndromic nor innate. Strong and consistent evidence has linked exposure to various pharmacological and infective agents with an elevated risk of a diagnosis of ASD including maternal valproate use, rubella and herpes encephalitis. Autoimmune encephalitis (AE) describes a group of conditions characterised by the body's immune system mounting an attack on healthy brain cells causing brain inflammation. The resultant cognitive, psychiatric and neurological symptoms that follow AE have also included ASD or autism-like traits and states. We review the current literature on AE and ASD. Drawing also on associated literature on autoimmune psychosis (AP) and preliminary evidence of a psychosis-linked subtype of ASD, we conclude that AE may either act as a potentially causative agent for ASD, and/or produce symptoms that could easily be mistaken for or misdiagnosed as autism. Further studies are required to discern the connection between AE and autism. Where autism is accompanied by regression and atypical onset patterns, it may be prudent to investigate whether a differential diagnosis of AE would be more appropriate., Competing Interests: RS has been an advisor to and has received honoraria from Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Whiteley, Marlow, Kapoor, Blagojevic-Stokic and Sala.)

The concept of autism continues to evolve. Not only have the central diagnostic criteria that define autism evolved but understanding of the label and how autism is viewed in research, clinical and sociological terms has also changed. Several key issues have emerged in relation to research, clinical and sociological aspects of autism. Shifts in research focus to encompass the massive heterogeneity covered under the label and appreciation that autism rarely exists in a diagnostic vacuum have brought about new questions and challenges. Diagnostic changes, increasing moves towards early diagnosis and intervention, and a greater appreciation of autism in girls and women and into adulthood and old age have similarly impacted on autism in the clinic. Discussions about autism in socio-political terms have also increased, as exemplified by the rise of ideas such as neurodiversity and an increasingly vocal dialogue with those diagnosed on the autism spectrum. Such changes are to be welcomed, but at the same time bring with them new challenges. Those changes also offer an insight into what might be further to come for the label of autism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Whiteley, Carr and Shattock.)

Autism spectrum disorder (ASD) is a highly complex and heterogeneous developmental disorder that affects how individuals communicate with other people and relate to the world around them. Research and clinical focus on the behavioural and cognitive manifestations of ASD, whilst important, have obscured the recognition that ASD is also commonly associated with a range of physical and mental health conditions. Many physical conditions appear with greater frequency in individuals with ASD compared to non-ASD populations. These can contribute to a worsening of social communication and behaviour, lower quality of life, higher morbidity and premature mortality. We highlight some of the key physical comorbidities affecting the immune and the gastrointestinal systems, metabolism and brain function in ASD. We discuss how healthcare professionals working with individuals with ASD and parents/carers have a duty to recognise their needs in order to improve their overall health and wellbeing, deliver equality in their healthcare experiences and reduce the likelihood of morbidity and early mortality associated with the condition., Competing Interests: Dr Sala has been an advisor to or has received honoraria from Takeda. Dr Paul Whiteley reports grants from The Robert Luff Foundation, during the preparation of this paper. The authors report no other conflicts of interest in this work., (© 2020 Sala et al.)

The pathogenesis of synucleinopathies, common neuropathological lesions normally associated with some human neurodegenerative disorders such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, remains poorly understood. In animals, ingestion of the tryptamine-alkaloid-rich phalaris pastures plants causes a disorder called Phalaris staggers, a neurological syndrome reported in kangaroos. The aim of the study was to characterise the clinical and neuropathological changes associated with spontaneous cases of Phalaris staggers in kangaroos. Gross, histological, ultrastructural and Immunohistochemical studies were performed to demonstrate neuronal accumulation of neuromelanin and aggregated α-synuclein. ELISA and mass spectrometry were used to detect serum-borne α-synuclein and tryptamine alkaloids respectively. We report that neurons in the central and enteric nervous systems of affected kangaroos display extensive accumulation of neuromelanin in the perikaryon without affecting neuronal morphology. Ultrastructural studies confirmed the typical structure of neuromelanin. While we demonstrated strong staining of α-synuclein, restricted to neurons, intracytoplasmic Lewy bodies inclusions were not observed. α-synuclein aggregates levels were shown to be lower in sera of the affected kangaroos compared to unaffected herd mate kangaroos. Finally, mass spectrometry failed to detect the alkaloid toxins in the sera derived from the affected kangaroos. Our preliminary findings warrant further investigation of Phalaris staggers in kangaroos, potentially a valuable large animal model for environmentally-acquired toxic synucleinopathy.

Autism or autism spectrum disorder (ASD) is described as a lifelong condition with core behavioural symptoms appearing during infancy or early childhood. Genetic and other effects occurring during the earliest times of life are thought to play a significant contributory role to the presentation of autism, denoting that autism is typically seen as an innate or inborn condition. Such descriptions have, and continue to, define autism research and clinical practice. Inspection of the existing research literature, however, suggests that within the vast heterogeneity of autism, not everyone experiences autism in such a prescribed way. Various reports have observed the presentation of "acquired autism" following a period of typical development. Other findings have documented an abatement of clinically relevant autistic features and related comorbid pathology for some. Such reports offer important insights into the heterogeneity and complexity of autism., Competing Interests: Paul Whiteley and Kevin Carr report grants from the Robert Luff Foundation during the the writing of this paper. The authors report no other conflicts of interest in this work., (© 2019 Whiteley et al.)

Objectives: Autism spectrum disorder (ASD) refers to a group of conditions variably affecting communicative and social interactive abilities presenting alongside behaviors with various restricted and repetitive patterns. In addition to genetic factors that influence the onset of the symptoms, there is growing interest in the potential involvement of non-genetic environmental factors. Some aspects of breastfeeding practices, including rates, timing, or optimality, have been put forward as environmental risk factors for autism. However, previous studies showed a controversial relationship between ASD and breastfeeding., Methods: A meta-analysis on the association between maternal breastfeeding and ASD in children was conducted. We also explored potential moderating factors which might influence this association. Articles reporting the association between breastfeeding and a diagnosis of ASD were included., Results: Seven articles were included in the meta-analysis. Cumulatively, children with ASD (n = 1463), either in the form of clinical diagnosis or self-report, were significantly less likely to have been breastfed than children without ASD (n = 1180) (OR = 0.61, 95% CI = 0.45-0.83, P = 0.002). Subgroup analyses revealed that results remained significant for children who were breastfed with additional supplementation., Discussion: This meta-analysis provides evidence that breastfeeding (exclusively or including additional supplements) may protect against ASD. Prospective longitudinal research is required to disentangle the complex relationships and to explore potential pathophysiological mechanisms.

Previous studies have suggested environmental factors may contribute to the risk of attention-deficit/hyperactivity disorder (ADHD). The current meta-analysis examined (1) the difference in the duration of maternal breastfeeding between children with and without ADHD, and (2) the association between maternal breastfeeding and ADHD in children. The data of individual studies were synthesized with a random-effects model. Eleven articles were included in this meta-analysis. Children with ADHD had significantly less breastfeeding duration than controls (Hedges' g = - 0.36, 95% confidence intervals (CIs) = - 0.61 to - 0.11, p = 0.005; difference in means: - 2.44 months, 95% CIs = - 3.17 to - 1.71, p < 0.001). In addition, the rates of non-exclusive breastfeeding in children with ADHD is significantly higher in "under 3 months" (odds ratio (OR) = 1.90, 95% CIs = 1.45 to 2.48, p < 0.001) but lower in "6 to 12 months" (OR = 0.69, 95% CIs = 0.49 to 0.98, p = 0.039) and "over 12 months" (OR = 0.58, 95% CIs = 0.35 to 0.97, p = 0.038) than controls. Children with ADHD received significantly higher rate of exclusive breastfeeding duration "under 3 months" (OR = 1.51, 95% CIs = 1.20 to 1.89, p < 0.001) but lower in "over 3 months" (OR = 0.52, 95% CIs = 0.29 to 0.95, p = 0.033) than controls. Furthermore, an association was found between non-breastfeeding and ADHD children (adjusted OR = 3.71, 95% CI = 1.94 to 7.11, p < 0.001). Our results suggest maternal breastfeeding is associated with a lower risk of ADHD in children. Future longitudinal research is required to confirm/refute these findings and to explore possible mechanisms underlying this association.

The invasive ectoparasite Sarcoptes scabiei affects the welfare and conservation of Australian marsupials. Molecular data suggest that spillover from other hosts may be responsible for the emergence of this infectious disease, but the scale of such studies is limited. We performed expanded molecular typing of the S. scabiei mitochondrial cox1 gene from 81 skin scrapings from infested wombats ( Vombatus ursinus), koalas ( Phascolarctos cinereus), red foxes ( Vulpes vulpes), and dogs ( Canis lupus familiaris) across Australia. Combined with existing S. scabiei sequences, our analysis revealed 16 haplotypes among Australian animals, sharing between 93.3% and 99.7% sequence similarity. While some sequences were unique to specific hosts or to Australia, key haplotypes could be detected across several marsupial hosts as well as to wild or domestic canids in Australia. We identified 43 cox1 haplotypes with many Australian haplotypes identical to S. scabiei mites from inside and outside Europe. We concluded that multiple introduction events were plausible explanations to the origin and emergence of this parasite into Australian marsupials and that disease spillover from canids was likely. Together, our greatly expanded S. scabiei sequence dataset provided a more nuanced picture of both spillover and sustained intraspecific transmission for this important parasite.

Hundreds of scarlet macaw ( Ara macao cyanoptera ) skeletons have been recovered from archaeological contexts in the southwestern United States and northwestern Mexico (SW/NW). The location of these skeletons, >1,000 km outside their Neotropical endemic range, has suggested a far-reaching pre-Hispanic acquisition network. Clear evidence for scarlet macaw breeding within this network is only known from the settlement of Paquimé in NW dating between 1250 and 1450 CE. Although some scholars have speculated on the probable existence of earlier breeding centers in the SW/NW region, there has been no supporting evidence. In this study, we performed an ancient DNA analysis of scarlet macaws recovered from archaeological sites in Chaco Canyon and the contemporaneous Mimbres area of New Mexico. All samples were directly radiocarbon dated between 900 and 1200 CE. We reconstructed complete or near-complete mitochondrial genome sequences of 14 scarlet macaws from five different sites. We observed remarkably low genetic diversity in this sample, consistent with breeding of a small founder population translocated outside their natural range. Phylogeographic comparisons of our ancient DNA mitogenomes with mitochondrial sequences from macaws collected during the last 200 years from their endemic Neotropical range identified genetic affinity between the ancient macaws and a single rare haplogroup (Haplo6) observed only among wild macaws in Mexico and northern Guatemala. Our results suggest that people at an undiscovered pre-Hispanic settlement dating between 900 and 1200 CE managed a macaw breeding colony outside their endemic range and distributed these symbolically important birds through the SW., Competing Interests: The authors declare no conflict of interest.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, and nutritional deficiency may play a role in the development of ASD. A relationship between ASD and iron levels/iron deficiency (ID) has been reported; however, the results have been inconsistent. Therefore, we conducted this meta-analysis to examine the relationship between ASD and ID following the Meta-Analysis of Observational Studies in Epidemiology guidelines. We performed a systematic search of PubMed, ScienceDirect, Embase, ProQuest, ClinicalTrials.gov, and Cochrane CENTRAL databases up to September 22, 2017. Studies providing data on peripheral iron levels and/or the prevalence of ID in children with ASD vs those without ASD (non-ASD) were included. Primary outcomes included the difference in peripheral iron levels in children with ASD compared with those without ASD, and the odds ratio of ASD in children with ID compared with those without ID. Twenty-five articles met the inclusion criteria. We found that peripheral iron levels were not significantly different between the ASD and non-ASD groups, including serum ferritin (k = 4, Hedges g = 0.016, 95% confidence interval [CI] = -0.482 to 0.515, P = .949) or hair iron (k = 12; Hedges g = -0.219, 95% CI = -0.551 to 0.113, P = .196). There was no significant difference in the amount of iron in food content between the ASD and non-ASD groups (k = 6; Hedges g = -0.458, 95% CI = -1.246 to 0.330, P = .254). However, the reciprocal comorbidity of ASD and ID was significantly higher than in the children without these disorders. Our analysis showed that the available evidence is inconsistent with regard to whether children with ASD have lower iron levels. Future longitudinal studies are required to confirm or refute these associations and elucidate potential mechanisms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There is growing recognition that the risk of attention-deficit hyperactivity disorder (ADHD) in children may be influenced by micronutrient deficiencies, including iron. We conducted this meta-analysis to examine the association between ADHD and iron levels/iron deficiency (ID). We searched for the databases of the PubMed, ScienceDirect, Cochrane CENTRAL, and ClinicalTrials.gov up to August 9 th , 2017. Primary outcomes were differences in peripheral iron levels in children with ADHD versus healthy controls (HCs) and the severity of ADHD symptoms in children with/without ID (Hedges' g) and the pooled adjusted odds ratio (OR) of the association between ADHD and ID. Overall, seventeen articles met the inclusion criteria. Peripheral serum ferritin levels were significantly lower in ADHD children (children with ADHD = 1560, HCs = 4691, Hedges' g = -0.246, p = 0.013), but no significant difference in serum iron or transferrin levels. In addition, the severity of ADHD was significantly higher in the children with ID than those without ID (with ID = 79, without ID = 76, Hedges' g = 0.888, p = 0.002), and there was a significant association between ADHD and ID (OR = 1.636, p = 0.031). Our results suggest that ADHD is associated with lower serum ferritin levels and ID. Future longitudinal studies are required to confirm these associations and to elucidate potential mechanisms.

Background: Debilitating skin infestations caused by the mite, Sarcoptes scabiei, have a profound impact on human and animal health globally. In Australia, this impact is evident across different segments of Australian society, with a growing recognition that it can contribute to rapid declines of native Australian marsupials. Cross-host transmission has been suggested to play a significant role in the epidemiology and origin of mite infestations in different species but a chronic lack of genetic resources has made further inferences difficult. To investigate the origins and molecular epidemiology of S. scabiei in Australian wildlife, we sequenced the mitochondrial genomes of S. scabiei from diseased wombats (Vombatus ursinus) and koalas (Phascolarctos cinereus) spanning New South Wales, Victoria and Tasmania, and compared them with the recently sequenced mitochondrial genome sequences of S. scabiei from humans., Results: We found unique S. scabiei haplotypes among individual wombat and koala hosts with high sequence similarity (99.1% - 100%). Phylogenetic analysis of near full-length mitochondrial genomes revealed three clades of S. scabiei (one human and two marsupial), with no apparent geographic or host species pattern, suggestive of multiple introductions. The availability of additional mitochondrial gene sequences also enabled a re-evaluation of a range of putative molecular markers of S. scabiei, revealing that cox1 is the most informative gene for molecular epidemiological investigations. Utilising this gene target, we provide additional evidence to support cross-host transmission between different animal hosts., Conclusions: Our results suggest a history of parasite invasion through colonisation of Australia from hosts across the globe and the potential for cross-host transmission being a common feature of the epidemiology of this neglected pathogen. If this is the case, comparable patterns may exist elsewhere in the 'New World'. This work provides a basis for expanded molecular studies into mange epidemiology in humans and animals in Australia and other geographic regions.

Complex, diverse and rarely appearing without comorbidity, the autism spectrum disorders continue to be a source of research interest. With core symptoms variably impacting on social communication skills, the traditional focus of many research efforts has centred on the brain and how genetic and environmental processes impact on brain structure, function and/or connectivity to account for various behavioural presentations. Alongside emerging ideas on autistic traits being present in various clinical states, the autisms, and the overrepresentation of several comorbid conditions impacting on quality of life, other research avenues have opened up. The central role of the brain in relation to autism may be at least partially influenced by the functions of other organs. The gastrointestinal (GI) tract represents an important biological system pertinent to at least some autism. The notion of a gut-brain-behaviour axis has garnered support from various findings: an overrepresentation of functional and pathological bowel states, bowel and behavioural findings showing bidirectional associations, a possible relationship between diet, GI function and autism and recently, greater focus on aspects of the GI tract such as the collected gut microbiota in relation to autism. Gaps remain in our knowledge of the functions of the GI tract linked to autism, specifically regarding mechanisms of action onward to behavioural presentation. Set however within the context of diversity in the presentation of autism, science appears to be moving towards defining important GI-related autism phenotypes with the possibility of promising dietary and other related intervention options onward to improving quality of life.

Purpose: Koala retrovirus (KoRV) is undergoing endogenization into the genome of koalas in Australia, providing an opportunity to assess the effect of retrovirus infection on the health of a population. The prevalence of KoRV in north-eastern Australia (Queensland and New South Wales) is 100 %, whereas previous preliminary investigations in south-eastern Australia (Victoria) suggested KoRV is present at a lower prevalence, although the values have varied widely. Here, we describe a large study of free-ranging koalas in Victoria to estimate the prevalence of KoRV and assess the clinical significance of KoRV infection in wild koalas., Methodology: Blood or spleen samples from 648 koalas where tested for KoRV provirus, and subsequently genotyped, using PCRs to detect the pol and env genes respectively. Clinical data was also recorded where possible and analysed in comparison to infection status., Results: The prevalence of KoRV was 24.7 % (160/648). KoRV-A was detected in 141/160 cases, but KoRV-B, a genotype associated with neoplasia in captive koalas, was not detected. The genotype in 19 cases could not be determined. Genomic differences between KoRV in Victoria and type strains may have impacted genotyping. Factors associated with KoRV infection, based on multivariable analysis, were low body condition score, region sampled, and 'wet bottom' (a staining of the fur around the rump associated with chronic urinary incontinence). Koalas with wet bottom were nearly twice as likely to have KoRV provirus detected than those without wet bottom (odds ratio=1.90, 95 % confidence interval 1.21, 2.98)., Conclusion: Our findings have important implications for the conservation of this iconic species, particularly regarding translocation potential of Victorian koalas.

Autism spectrum disorders represent a diverse and heterogeneous array of conditions unified by the variable presence of specific behaviours impacting social and communicative functions (social affect) alongside other presentation. Common overt characteristics may come about as a consequence of several different genetic and biological processes differentially manifesting across different people or groups. The concept of plural 'autisms' is evolving, strengthened by an increasingly important evidence base detailing different developmental trajectories across the autism spectrum and the appearance of comorbidity variably interacting with core symptoms and onwards influencing quality of life. Reports that dietary intervention, specifically the removal of foods containing gluten and/or casein from the diet, may impact on the presentation of autism for some, complement this plural view of autism. Evidence suggestive of differing responses to the use of a gluten- and casein-free diet, defined as best- and non-response, has combined with some progress on determining the underlying genetic and biological correlates potentially related to such dietary elements. The preliminary suggestion of a possible diet-related autism phenotype is the result. This review will highlight several pertinent aspects onwards to an effect of food in some cases of autism including research on the pharmacological activity of food metabolites, immune response, issues with gut barrier function and some contribution from the gut microbiota. These represent promising areas in need of far greater research inspection in order to potentially define such a diet-related subgroup on the autism spectrum.

Herpesviruses have been reported in several marsupial species, but molecular classification has been limited to four herpesviruses in macropodids, a gammaherpesvirus in two antechinus species (Antechinus flavipes and Antechinus agilis), a gammaherpesvirus in a potoroid, the eastern bettong (Bettongia gaimardi) and two gammaherpesviruses in koalas (Phascolarctos cinereus). In this study we examined a range of Australian marsupials for the presence of herpesviruses using molecular and serological techniques, and also assessed risk factors associated with herpesvirus infection. Our study population included 99 koalas (Phascolarctos cinereus), 96 eastern grey kangaroos (Macropus giganteus), 50 Tasmanian devils (Sarcophilus harrisii) and 33 common wombats (Vombatus ursinius). In total, six novel herpesviruses (one alphaherpesvirus and five gammaherpesviruses) were identified in various host species. The overall prevalence of detection of herpesvirus DNA in our study population was 27.2% (95% confidence interval (CI) of 22.6-32.2%), but this varied between species and reached as high as 45.4% (95% CI 28.1-63.7%) in common wombats. Serum antibodies to two closely related macropodid herpesviruses (macropodid herpesvirus 1 and 2) were detected in 44.3% (95% CI 33.1-55.9%) of animals tested. This also varied between species and was as high as 92% (95% CI 74.0-99.0%) in eastern grey kangaroos. A number of epidemiological variables were identified as positive predictors for the presence of herpesvirus DNA in the marsupial samples evaluated. The most striking association was observed in koalas, where the presence of Chlamydia pecorum DNA was strongly associated with the presence of herpesvirus DNA (Odds Ratio = 60, 95% CI 12.1-297.8). Our results demonstrate the common presence of herpesviruses in Australian marsupials and provide directions for future research.

Naltrexone (NTX) is a long-acting opiate antagonist. Low-dose naltrexone (LDN) therapy has shown promising results in the treatment of several autoimmune disorders. Our aim was to formulate NTX into a cream for the delivery of LDN and develop an analytical technique for the quantification of NTX and its active metabolite 6-β-naltrexol (NTXol) during transdermal diffusion cell permeation studies. A 1% w/w NTX cream was formulated and drug permeation was examined over 24 h using static Franz diffusion cells mounted with pig skin. A Liquid Chromatography Quadrupole-Time of Flight Mass Spectrometry (LC-MS Q-ToF) method was developed for the detection of NTX and NTXol in the receptor solution, skin membrane and residual cream on the donor chamber after completion of the diffusion studies. The cream formulation exhibited steady state release of NTX over 24 h after an initial lag time of 2.74 h. The bioconversion of NTX to NTXol in the skin membrane was 1.1%. It was concluded that the cream may be an effective formulation for the sustained transdermal delivery of LDN. The novel LC Q-ToF MS method allowed the accurate measurement of NTX and NTXol levels across the diffusion cell assemblies and the quantification of NTX metabolism in the skin.

Case Report: Seven eastern grey kangaroos (Macropus giganteus) grazing pastures including Phalaris spp. in Victoria showed neurological deficits characterised by ataxia, head tremors and collapse. Gross examination of the brains and spinal cords of affected kangaroos showed a greenish discolouration in several regions of the grey matter. Histologically, intracytoplasmic accumulation of pigment granules was detected in the neurons, most prominently in the thalamus, brainstem and ventral horns of the spinal cord. Pigment granules were positive to stains used for identification of melanin, including Fontana-Masson stain and Schmorl's reaction., Conclusion: The combination of clinical signs and obvious neuronal pigmentation is consistent with chronic Phalaris spp. toxicity, a condition well documented in domestic ruminants., (© 2014 Australian Veterinary Association.)

We previously reported results based on the examination of a gluten- and casein-free diet as an intervention for children diagnosed with an autism spectrum disorder as part of the ScanBrit collaboration. Analysis based on grouped results indicated several significant differences between dietary and non-dietary participants across various core and peripheral areas of functioning. Results also indicated some disparity in individual responses to dietary modification potentially indicative of responder and non-responder differences. Further examination of the behavioural and psychometric data garnered from participants was undertaken, with a view to determining potential factors pertinent to response to dietary intervention. Participants with clinically significant scores indicative of inattention and hyperactivity behaviours and who had a significant positive changes to said scores were defined as responders to the dietary intervention. Analyses indicated several factors to be potentially pertinent to a positive response to dietary intervention in terms of symptom presentation. Chronological age was found to be the strongest predictor of response, where those participants aged between 7 and 9 years seemed to derive most benefit from dietary intervention. Further analysis based on the criteria for original study inclusion on the presence of the urine compound, trans-indolyl-3-acryloylglycine may also merit further investigation. These preliminary observations on potential best responder characteristics to a gluten- and casein-free diet for children with autism require independent replication.

We detected herpesvirus infection in a male yellow-footed antechinus (Antechinus flavipes) and male agile antechinus (Antechinus agilis) during the period of postmating male antechinus immunosuppression and mortality. Histopathologic examination of tissues revealed lesions consistent with herpesvirus infection in the prostate of both animals. Herpesvirus virions were observed by transmission electron microscopy in the prostate tissue collected from the male yellow-footed antechinus. Herpesvirus DNA was detected in prostate, liver, lung, kidney, spleen, and ocular/nasal tissues using a pan-herpesvirus PCR targeting the viral DNA polymerase. Nucleotide sequencing identified a novel herpesvirus from the Gammaherpesvirinae subfamily that we have tentatively designated dasyurid herpesvirus 1 (DaHV-1).

Context: With regard to biological effects, the increasing number of early failure of metal-on-metal (MoM) hip arthroplasties and possible parenteral exposure to orthopedic metal alloys have caused concern for patients and providers alike., Objective: We sought to characterize our outpatient clinical experience of patients with MoM and other forms of hip implants and associated serum/blood chromium and cobalt levels, with a focus on possible systemic sequelae., Methods: This was an observational and retrospective chart review of consecutive patients presenting to two outpatient medical toxicology clinics from January 1, 2010-June 1, 2012 with history of hip implants. Presenting signs, symptoms, and interventions were reviewed. Available cobalt and chromium levels were summarized as median concentration with interquartile range., Results: A total of 39 patients were analyzed; of the 39 patients, 26 had MoM hip implants while 13 did not. Twelve patients exhibited no symptoms and nine sought evaluation for fatigue while two other patients had been previously diagnosed with fibromyalgia. Tinnitus/hearing loss was also a frequent complaint noted in 12 patients (one presenting complaint), however there was no difference between the incidence of this symptom between the MoM and non-MoM groups. Three patients were provisionally diagnosed with demyelinating neuropathy with one patient demonstrating marked (subjective and objective) improvement after revision. Patients with MoM arthroplasties generally exhibit an approximately tenfold increase in metal ion levels than traditional arthroplasties. Finally, 20 (51.2%) patients had replacement or revision of their hip implant with subsequent decreases in metal ion levels., Discussion: A majority of our patients had minor symptoms (fatigue and muscle aches) or no symptoms (n = 23 or 59%). Documented peripheral neurotoxicity is uncommon. The decision for hip revision solely for toxicologic reasons is rare and usually involves a multidisciplinary approach., Conclusion: Most patients seeking toxicologic referral may be minimally symptomatic and seek guidance regarding elevated blood or serum metal ions; however, solely toxicologic-based interventions are unusual. Revision was associated with a decrease in metal ion levels; however, subjective complaints did not correlate with metal ion levels.

Dietary intervention as a tool for maintaining and improving physical health and wellbeing is a widely researched and discussed topic. Speculation that diet may similarly affect mental health and wellbeing particularly in cases of psychiatric and behavioral symptomatology opens up various avenues for potentially improving quality of life. We examine evidence suggestive that a gluten-free (GF), casein-free (CF), or gluten- and casein-free diet (GFCF) can ameliorate core and peripheral symptoms and improve developmental outcome in some cases of autism spectrum conditions. Although not wholly affirmative, the majority of published studies indicate statistically significant positive changes to symptom presentation following dietary intervention. In particular, changes to areas of communication, attention, and hyperactivity are detailed, despite the presence of various methodological shortcomings. Specific characteristics of best- and non-responders to intervention have not been fully elucidated; neither has the precise mode of action for any universal effect outside of known individual cases of food-related co-morbidity. With the publication of controlled medium- and long-term group studies of a gluten- and casein-free diet alongside more consolidated biological findings potentially linked to intervention, the appearance of a possible diet-related autism phenotype seems to be emerging supportive of a positive dietary effect in some cases. Further debate on whether such dietary intervention should form part of best practice guidelines for autism spectrum conditions (ASCs) and onward representative of an autism dietary-sensitive enteropathy is warranted.

A gammaherpesvirus was detected by polymerase chain reaction (PCR) in ocular, nasal and oropharyngeal swab samples collected from an adult free-ranging male eastern grey kangaroo (Macropus giganteus) with clinical signs of severe respiratory disease. This is the first time a gammaherpesvirus has been detected in a free-ranging macropod in Australia. The nucleotide sequence of a conserved region of the DNA polymerase gene of the detected virus showed a high degree of identity to a gammaherpesvirus recently detected in a zoological collection of eastern grey kangaroos in North America. The detection of this gammaherpesvirus in a free-ranging, native eastern grey kangaroo provides evidence that this species is a natural host., (© 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.)

There is now, for the first time, an integrated approach to complaints so that, where issues cross health and social care, the authorities must work together to produce one response that addresses the problem. This article looks at the approach that should be taken when considering complaints, and highlights tools and techniques that may help professionals avoid common delays and mistakes when responding to complainants.

On the basis of the connectionist model of leadership, we examined perceptions of leadership as a function of the contextual factors of race (Asian American, Caucasian American) and occupation (engineering, sales) in 3 experiments (1 student sample and 2 industry samples). Race and occupation exhibited differential effects for within- and between-race comparisons. With regard to within-race comparisons, leadership perceptions of Asian Americans were higher when race-occupation was a good fit (engineer position) than when race-occupation was a poor fit (sales position) for the two industry samples. With regard to between-race comparisons, leadership perceptions of Asian Americans were low relative to those of Caucasian Americans. Additionally, when race-occupation was a good fit for Asian Americans, such individuals were evaluated higher on perceptions of technical competence than were Caucasian Americans, whereas they were evaluated lower when race-occupation was a poor fit. Furthermore, our results demonstrated that race affects leadership perceptions through the activation of prototypic leadership attributes (i.e., implicit leadership theories). Implications for the findings are discussed in terms of the connectionist model of leadership and leadership opportunities for Asian Americans., (Copyright 2010 APA, all rights reserved)

There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders (ASDs). We report results from a two-stage, 24-month, randomised, controlled trial incorporating an adaptive 'catch-up' design and interim analysis. Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) assigned to diet (A) or non-diet (B) groups by stratified randomisation. Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) were used to assess core autism behaviours, Vineland Adaptive Behaviour Scales (VABS) to ascertain developmental level, and Attention-Deficit Hyperactivity Disorder - IV scale (ADHD-IV) to determine inattention and hyperactivity. Participants were tested at baseline, 8, and 12 months. Based on per protocol repeated measures analysis, data for 26 diet children and 29 controls were available at 12 months. At this point, there was a significant improvement to mean diet group scores (time*treatment interaction) on sub-domains of ADOS, GARS and ADHD-IV measures. Surpassing of predefined statistical thresholds as evidence of improvement in group A at 12 months sanctioned the re-assignment of group B participants to active dietary treatment. Stage 2 data for 18 group A and 17 group B participants were available at 24 months. Multiple scenario analysis based on inter- and intra-group comparisons showed some evidence of sustained clinical group improvements although possibly indicative of a plateau effect for intervention. Our results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD. In the absence of a placebo condition to the current investigation, we are, however, unable to disqualify potential effects derived from intervention outside of dietary changes. Further studies are required to ascertain potential best- and non-responders to intervention. The study was registered with ClincialTrials.gov, number NCT00614198.

Elevated levels of trans-indolyl-3-acryloylglycine (IAcrGly) have been reported in the urine of people with various conditions including pervasive developmental disorders (PDDs) such as autism and Asperger syndrome. Reversed-phase high-performance liquid chromatography with ultra-violet detection using traditional particle silica-based columns subsequent to solid-phase extraction (SPE) has been the preferred assay method; requiring long analytical run times, high flow rates and high solvent usage. Recent developments in monolithic HPLC column technology facilitated the development of a novel analytical method, for the detection and quantification of urinary IAcrGly. The revised method eliminates the requirement for SPE pre-treatment, reduces sample run-time and decreases solvent volumes. Five urine samples from people diagnosed with PDD were run in quadruplicate to test the intra- and inter-day reliability of the new method based on retention time, peak area and peak height for IAcrGly. Detection was by UV with IAcrGly confirmation by MS/MS-MS. Relative standard deviations showed significant improvement with the new method for all parameters. The new method represents a major advancement in the detection and quantification of IAcrGly by reducing time and cost of analysis whilst improving detection limits and reproducibility., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Background: Excretion of creatinine in urine represents the end-point of endogenous energy transfer from stored adenosine triphosphate in skeletal and cardiac muscle. Measurement of urinary creatinine is commonly used to correct for total urine concentration. Various quantitative measures of compounds suspected to be either pathological to, or indicative of, possible therapeutic interventions for Pervasive Developmental Disorders (PDD) have relied extensively on spot creatinine as a ratio quantity, although this important metabolite has not been exclusively studied within this population., Methods: Levels of urinary creatinine in spot urine samples were analyzed for a group of children diagnosed with PDD (n=24; median age, 75 months; range, 39-137 months) and a control group (n=50; median age, 109 months; range, 59-140 months). Diagnosis of PDD was confirmed using the Autism Diagnostic Interview-Revised. Samples were collected and analyzed blind for creatinine content using an improved Jaffe's reaction method., Results: Controlling for sample pH and body mass index, a significant decrease in urinary creatinine concentration was found in the PDD group compared to controls using a Mann-Whitney two-tailed ranks test (P=0.001)., Conclusion: Further studies of protein catabolism and renal function in autism are required to ascertain the relevance of decreased spot urinary creatinine excretion identified in this preliminary study. Issues regarding the use of single urine creatinine measurements and associated confounding variables are discussed in light of the findings, together with recommendations to use other internal or external standards for the quantification of urinary compounds in PDD research.

For years we have recognized that using genetics to target the right medicines to the right patients at the right time could improve health care; however, technical and financial constraints have prevented researchers from conducting the comprehensive, whole-genome association studies required to make such advances. Now, Perlegen and its collaborators are making personalized medicine and high density whole-genome association studies a reality. Perlegen quickly and cost-effectively analyzes millions of unique genetic variations in thousands of patients to identify the genetic differences associated with efficacy and side effects. This enables the pharmaceutical drug response to be predicted, and the therapeutic window of a treatment to be expanded. Perlegen licenses compounds that may benefit from this approach, and collaborates with pharmaceutical companies to rescue and better position medicines in their portfolios. Furthermore, the company collaborates with researchers in the public sector to discover the genetic variations associated with common diseases, paving the way for new therapeutics and diagnostics.

Background: The aim of the present study was to ascertain the Body Mass Index (BMI) (kg m(-2)) derived from parental reports of height (metres) and weight (kilograms) of a pilot sample of boys born and resident in the UK diagnosed with pervasive developmental disorders (PDD)., Method: Analysis of parental reporting of height and weight measurements in boys (n=50) diagnosed with PDD and comparison with age and sex-matched reference populations., Results: The majority of patients were above the 50th percentile for height (70%), weight (74%) and BMI (80%) with 21% exceeding cut-off points for overweight and 10% for clinical obesity. There were no significant differences (P < 0.05) found between PDD subgroups for any of the measures., Conclusion: Further studies are required to validate findings of skewed height, weight and BMI data in PDD.

Objectives: To ascertain the frequency of parental reporting of selected variables related to development, behaviour and physiology in subgroups diagnosed with pervasive developmental disorders (PDDs) and identify any significant intragroup differences., Design: Retrospective cross-sectional analysis of records of patients (n = 512) held on a computerized database with a chronological age between 3 and 11 years resident in the UK/Republic of Ireland and with a formal diagnosis of autism, Asperger syndrome (AS) or autism spectrum disorder (ASD)., Methods: Non-parametric analysis (P > 0.01) of the frequency of specific variables for PDD subgroups reported by parents/primary caregiver. VARIABLES INCLUDED: timing of symptom onset, presence of skills acquired prior to symptom onset, indications of regression and regression events, current language, history of viral infections, history of ear problems, achievement of continence, current skin complaints, current bowel habits and adverse events at parturition., Results: Preliminary results showed general agreement with the principle diagnostic differences between the PDD subgroups with patients diagnosed with AS showing an increased frequency of skills acquired before symptom onset (two- to three-word phrase speech, toileting skills) and a decreased frequency of regression in acquired skills when compared with other PDD subgroups. Developmental milestones such as the achievement of bowel and bladder continence were also more frequently reported for the AS group. Infantile feeding problems defined as vomiting, reflux, colic and failure to feed were more frequently reported for the AS group as was a reported history of the bacterial skin infection impetigo. Results are discussed with reference to relationships between behavioural and somatic factors in PDD.

Background: Autism is a heterogeneous pervasive developmental disorder with a poorly defined aetiology and pathophysiology. There are indications that the incidence of the disease is rising but still no definitive diagnostic biochemical markers have been isolated. Here we have addressed the hypothesis that urinary levels of trans -indolyl-3-acryloylglycine (IAG) are abnormal in patients diagnosed with autism spectrum disorders (ASD) compared to age-matched controls., Material/methods: Urine samples were collected on an opportunistic basis and analysed for IAG concentration (normalised against creatinine content to account for changes in urinary volume) using reversed phase HPLC with UV detection., Results: Statistical analysis (Mann-Whitney tests) showed highly significant increases (p=0.0002) in the levels of urinary IAG in the ASD group (median 942 microV per mmol/L of creatinine [interquartile range 521-1729], n=22) compared to asymptomatic controls (331 [163-456], n=18). Detailed retrospective analysis showed that gender (boys 625 microV per mmol/L of creatinine [294-1133], n=29; girls 460 [282-1193], n=11: P=0.79) and age (control donor median 10 years [8-14], n=15; ASD median 9 years [7-11] n=22: P=0.54) were not significantly correlated with IAG levels in this non-blinded volunteer study., Conclusions: Our results strongly suggest that urinary titres of IAG may constitute an objective diagnostic indicator for ASD. Mechanisms for the involvement of IAG in ASD are discussed together with future strategies to address its specificity.

Autism is a lifelong condition usually described as affecting social, cognitive and imaginative abilities. For many years, parents and some professionals have observed that in concordance with the behavioural and psychological symptoms of the condition, there are a number of physiological and biochemical correlates which may also be of relevance to the syndrome. One area of interest that encompasses many of these observations is the opioid-excess theory of autism. The main premise of this theory is that autism is the result of a metabolic disorder. Peptides with opioid activity derived from dietary sources, in particular foods that contain gluten and casein, pass through an abnormally permeable intestinal membrane and enter the central nervous system (CNS) to exert an effect on neurotransmission, as well as producing other physiologically-based symptoms. Numerous parents and professionals worldwide have found that removal of these exogenously derived compounds through exclusion diets can produce some amelioration in autistic and related behaviours. There is a surprisingly long history of research accompanying these ideas. The aim of this paper is to review the accompanying evidence in support of this theory and present new directions of intervention as a result of it.

Aging is associated with increased glial responsiveness that may enhance the brain's susceptibility to injury and disease. To determine whether unique age-related molecular responses occur in brain injury, we assessed mRNA levels of representative central nervous system (CNS) inflammation-related molecules in young (3 months) and aged (36 months) Fisher 344/Brown Norwegian F1 hybrid rats following cortical stab. Enhanced glial activation in older animals was accompanied by increased expression of a subset of inflammation-related mRNAs, including IL-1beta, TNFalpha, IL-6, ICAM-1, inducible nitric oxide synthase (iNOS), metalloproteinase-9 (MMP-9), and complement 3alpha-chain 1 (C3alpha1). Recognition of these age-specific differences may guide development of novel treatment regimes for older individuals.

Injection of adjuvant (Mycobacterium butyricum suspended in mineral oil) into rats produces an immune reaction that characteristically involves inflammatory destruction of cartilage and bone of the distal joints with concomitant swelling of surrounding tissues. Adjuvant-induced arthritis in rats is commonly used to evaluate compounds that might be of potential use as drugs for treatment of rheumatoid arthritis and other chronic inflammatory conditions. This unit describes a method for inducing arthritis by injecting adjuvant into the tail and evaluating a test compound for the ability to inhibit the inflammatory response.