Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards). 1st Edition.

These first Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards) have been developed to inform the healthcare requirements for CoHD services and enable all Australian patients, families and carers impacted by CoHD (paediatric CoHD and adult congenital heart disease [ACHD]) to live their best and healthiest lives. The CoHD Standards are designed to provide the clarity and certainty required for healthcare services to deliver excellent, comprehensive, inclusive, and equitable CoHD care across Australia for patients, families and carers, and offer an iterative roadmap to the future of these services. The CoHD Standards provide a framework for excellent CoHD care, encompassing key requirements and expectations for whole-of-life, holistic and connected healthcare service delivery. The CoHD Standards should be implemented in health services in conjunction with the National Safety and Quality Health Service Standards developed by the Australian Commission on Safety and Quality in Health Care. All healthcare services should comply with the CoHD Standards, as well as working to their organisation's or jurisdiction's agreed clinical governance framework, to guide the implementation of structures and processes that support safe care.

Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn.

Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input. Selectively targeting spinal dPVs, we reveal their widespread ipsilateral inhibition onto pre-motor and motor networks and demonstrate their role in gating sensory-evoked muscle activity using electromyography (EMG) recordings. dPV ablation altered limb kinematics and step-cycle timing during treadmill locomotion and reduced the transitions between sub-movements during spontaneous behavior. These findings reveal a circuit basis by which sensory convergence onto dorsal horn inhibitory neurons modulates motor output to facilitate smooth movement and context-appropriate transitions.

A new Hoxb8FlpO mouse line for intersectional approaches to dissect developmentally defined adult sensorimotor circuits.

Improvements in the speed and cost of expression profiling of neuronal tissues offer an unprecedented opportunity to define ever finer subgroups of neurons for functional studies. In the spinal cord, single cell RNA sequencing studies support decades of work on spinal cord lineage studies, offering a unique opportunity to probe adult function based on developmental lineage. While Cre/Flp recombinase intersectional strategies remain a powerful tool to manipulate spinal neurons, the field lacks genetic tools and strategies to restrict manipulations to the adult mouse spinal cord at the speed at which new tools develop. This study establishes a new workflow for intersectional mouse-viral strategies to dissect adult spinal function based on developmental lineages in a modular fashion. To restrict manipulations to the spinal cord, we generate a brain-sparing Hoxb8FlpO mouse line restricting Flp recombinase expression to caudal tissue. Recapitulating endogenous Hoxb8 gene expression, Flp-dependent reporter expression is present in the caudal embryo starting day 9.5. This expression restricts Flp activity in the adult to the caudal brainstem and below. Hoxb8FlpO heterozygous and homozygous mice do not develop any of the sensory or locomotor phenotypes evident in Hoxb8 heterozygous or mutant animals, suggesting normal developmental function of the Hoxb8 gene and protein in Hoxb8FlpO mice. Compared to the variability of brain recombination in available caudal Cre and Flp lines, Hoxb8FlpO activity is not present in the brain above the caudal brainstem, independent of mouse genetic background. Lastly, we combine the Hoxb8FlpO mouse line with dorsal horn developmental lineage Cre mouse lines to express GFP in developmentally determined dorsal horn populations. Using GFP-dependent Cre recombinase viruses and Cre recombinase-dependent inhibitory chemogenetics, we target developmentally defined lineages in the adult. We show how developmental knock-out versus transient adult silencing of the same ROR𝛃 lineage neurons affects adult sensorimotor behavior. In summary, this new mouse line and viral approach provides a blueprint to dissect adult somatosensory circuit function using Cre/Flp genetic tools to target spinal cord interneurons based on genetic lineage.

Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes.

The existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations, efforts to identify microbial biomarkers have been limited due to a lack of appropriately matched controls, stratification of participants within the autism spectrum, and sample size. To overcome these limitations, we crowdsourced the recruitment of families with age-matched sibling pairs between 2 and 7 years old (within 2 years of each other), where one child had a diagnosis of ASD and the other did not. Parents collected stool samples, provided a home video of their ASD child's natural social behavior, and responded online to diet and behavioral questionnaires. 16S rRNA V4 amplicon sequencing of 117 samples (60 ASD and 57 controls) identified 21 amplicon sequence variants (ASVs) that differed significantly between the two cohorts: 11 were found to be enriched in neurotypical children (six ASVs belonging to the Lachnospiraceae family), while 10 were enriched in children with ASD (including Ruminococcaceae and Bacteroidaceae families). Summarizing the expected KEGG orthologs of each predicted genome, the taxonomic biomarkers associated with children with ASD can use amino acids as precursors for butyragenic pathways, potentially altering the availability of neurotransmitters like glutamate and gamma aminobutyric acid (GABA).IMPORTANCE Autism spectrum disorder (ASD), which now affects 1 in 54 children in the United States, is known to have comorbidity with gut disorders of a variety of types; however, the link to the microbiome remains poorly characterized. Recent work has provided compelling evidence to link the gut microbiome to the autism phenotype in mouse models, but identification of specific taxa associated with autism has suffered replicability issues in humans. This has been due in part to sample size that sufficiently covers the spectrum of phenotypes known to autism (which range from subtle to severe) and a lack of appropriately matched controls. Our original study proposes to overcome these limitations by collecting stool-associated microbiome on 60 sibling pairs of children, one with autism and one neurotypically developing, both 2 to 7 years old and no more than 2 years apart in age. We use exact sequence variant analysis and both permutation and differential abundance procedures to identify 21 taxa with significant enrichment or depletion in the autism cohort compared to their matched sibling controls. Several of these 21 biomarkers have been identified in previous smaller studies; however, some are new to autism and known to be important in gut-brain interactions and/or are associated with specific fatty acid biosynthesis pathways.

Young Stroke Survivors' Preferred Methods of Meeting Their Unique Needs: Shaping Better Care.

OBJECTIVE: To determine how young stroke survivors want their unmet needs to be addressed, we undertook an international online survey of people living with stroke. METHODS: Participants self-selected to complete an online survey that included a questionnaire on demographics and stroke-related characteristics, the Young Stroke Needs Screening Tool, and a questionnaire on how they wanted their needs to be met. RESULTS: One hundred seventy-one responses were received (68% female respondents, mean age 45 years, interquartile range 36-51 years). Preferences for methods of meeting needs varied depending on the domain of need and participants' demographic and stroke-related characteristics. Face-to-face contact with a health care professional was a popular means of meeting needs, but methods outside of a traditional health care setting such as a succinct list of tips or peer support were widely acceptable and sometimes preferred. CONCLUSION: This work provides the impetus for developing alternative methods of meeting young stroke survivors' needs, many of which are not resource intensive or do not require an appointment with a health care professional.

Aging, working memory capacity and the proactive control of recollection: An event-related potential study.

The present study investigated the role of working memory capacity (WMC) in the control of recollection in young and older adults. We used electroencephalographic event-related potentials (ERPs) to examine the effects of age and of individual differences in WMC on the ability to prioritize recollection according to current goals. Targets in a recognition exclusion task were words encoded using two alternative decisions. The left parietal ERP old/new effect was used as an electrophysiological index of recollection, and the selectivity of recollection measured in terms of the difference in its magnitude according to whether recognized items were targets or non-targets. Young adults with higher WMC showed greater recollection selectivity than those with lower WMC, while older adults showed nonselective recollection which did not vary with WMC. The data suggest that aging impairs the ability to engage cognitive control effectively to prioritize what will be recollected.