Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Thermoneutral Temperature Exposure Enhances Slow Wave Sleep with a Correlated Improvement in Amyloid Pathology in a Triple-Transgenic Mouse Model of Alzheimer's Disease.

Accumulation of amyloid-ß (Aß) plays an important role in Alzheimer's disease (AD) pathology. There is growing evidence that disordered sleep may accelerate AD pathology by impeding the physiological clearance of Aß from the brain that occurs in normal sleep. Therapeutic strategies for improving sleep quality may therefore help slow disease progression. It is well documented that the composition and dynamics of sleep are sensitive to ambient temperature. We therefore compared Aß pathology and sleep metrics derived from polysomnography in 12-month-old female 3xTg-AD mice (n = 8) exposed to thermoneutral temperatures during the light period over four weeks to those of age- and sex-matched controls (n = 8) that remained at normal housing temperature (22°C) during the same period. The treated group experienced greater proportions of slow wave sleep (SWS)-i.e., epochs of elevated 0.5-2 Hz slow wave activity during non-rapid eye movement (NREM) sleep-compared to controls. Assays performed on mouse brain tissue harvested at the end of the experiment showed that exposure to thermoneutral temperatures significantly reduced levels of DEA-soluble (but not RIPA- or FA-soluble) Aß40 and Aß42 in the hippocampus, though not in the cortex. With both groups pooled together and without regard to treatment condition, NREM sleep continuity and any measure of SWS within NREM at the end of the treatment period were inversely correlated with DEA-soluble Aß40 and Aß42 levels, again in the hippocampus but not in the cortex. These findings suggest that experimental manipulation of SWS could offer useful clues into the mechanisms and treatment of AD.

A stochastic model for topographically influenced cell migration.

Migrating cells traverse a range of topographic configurations presented by the native extracellular environment to conduct their physiologic functions. It is well documented cells can modulate their behaviour in response to different topographic features, finding promising applications in biomaterial and bioimplant design. It is useful, in these areas of research, to be able to predict which topographic arrangements could be used to promote certain patterns of migration prior to laboratory experimentation. Despite a profusion of study and interest shown in these fields by experimentalists, the related modelling literature is as yet relatively sparse and tend to focus more on either cell-matrix interaction or morphological responses of cells. We propose a mathematical model for individual cell migration based on an Ornstein-Uhlenbeck process, and set out to see if the model can be used to predict migration patterns on 2-d isotropic and anisotropic topographies, whose characteristics can be broadly described as either uniform flat, uniform linear with variable ridge density or non-uniform disordered with variable feature density. Results suggest the model is capable of producing realistic patterns of migration for flat and linear topographic patterns, with calibrated output closely approximating NIH3T3 fibroblast migration behaviour derived from an experimental dataset, in which migration linearity increased with ridge density and average speed was highest at intermediate ridge densities. Exploratory results for non-uniform disordered topographies suggest cell migration patterns may adopt disorderedness present in the topography and that 'distortion' introduced to linear topographic patterns may not impede linear guidance of migration, given its magnitude is bounded within certain limits. We conclude that an Ornstein-Uhlenbeck based model for topographically influenced migration may be useful to predict patterns of migration behaviour for certain isotropic (flat) and anisotropic (linear) topographies in the NIH3T3 fibroblast cell line, but additional investigation is required to predict with confidence migration patterns for non-uniform disordered topographic arrangements.

Mitochondrial reverse electron transport in myeloid cells perpetuates neuroinflammation.

Sustained smouldering, or low grade, activation of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis (MS) 1 . Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells 2 . However, how these metabolic features act to perpetuate neuroinflammation is currently unknown. Using a multiomics approach, we identified a new molecular signature that perpetuates the activation of myeloid cells through mitochondrial complex II (CII) and I (CI) activity driving reverse electron transport (RET) and the production of reactive oxygen species (ROS). Blocking RET in pro-inflammatory myeloid cells protected the central nervous system (CNS) against neurotoxic damage and improved functional outcomes in animal disease models in vivo . Our data show that RET in myeloid cells is a potential new therapeutic target to foster neuroprotection in smouldering inflammatory CNS disorders 3 .

Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

Sex and Sleep Disruption as Contributing Factors in Alzheimer's Disease.

Alzheimer's disease (AD) affects more women than men, with women throughout the menopausal transition potentially being the most under researched and at-risk group. Sleep disruptions, which are an established risk factor for AD, increase in prevalence with normal aging and are exacerbated in women during menopause. Sex differences showing more disrupted sleep patterns and increased AD pathology in women and female animal models have been established in literature, with much emphasis placed on loss of circulating gonadal hormones with age. Interestingly, increases in gonadotropins such as follicle stimulating hormone are emerging to be a major contributor to AD pathogenesis and may also play a role in sleep disruption, perhaps in combination with other lesser studied hormones. Several sleep influencing regions of the brain appear to be affected early in AD progression and some may exhibit sexual dimorphisms that may contribute to increased sleep disruptions in women with age. Additionally, some of the most common sleep disorders, as well as multiple health conditions that impair sleep quality, are more prevalent and more severe in women. These conditions are often comorbid with AD and have bi-directional relationships that contribute synergistically to cognitive decline and neuropathology. The association during aging of increased sleep disruption and sleep disorders, dramatic hormonal changes during and after menopause, and increased AD pathology may be interacting and contributing factors that lead to the increased number of women living with AD.

The amyloid-ß peptide: Guilty as charged?

Recent years have seen both considerable progress and controversy in the Alzheimer's disease (AD) field. After decades of slow to negligible movement towards the development of disease modifying therapies, promising outcomes in recent clinical trials with several monoclonal antibodies targeting various forms of the amyloid-ß (Aß) peptide have at last opened a possible way forward. In fact, at this point multiple anti-Aß therapeutics are close to receiving (or have already received) regulatory approval. Although these outcomes are not without some degree of divisiveness, the fact remains that targeting amyloid for removal has finally shown at least modest efficacy in slowing the otherwise relentless progression of the disease. Although the validation of the long standing amyloid cascade hypothesis would seem to be at hand, what remains is the puzzling issue of why - if Aß indeed causes AD - does removing it from the brain not stop the disease entirely.

Adaptive behaviour deficits in individuals with 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behaviour. However, the full profile of adaptive function in 3q29del has not been described nor has it been compared with other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes. METHODS: Individuals with 3q29del (n = 32, 62.5% male) were evaluated using the Vineland Adaptive Behaviour Scales, Third Edition, Comprehensive Parent/Caregiver Form (Vineland-3). We explored the relationship between adaptive behaviour and cognitive function, executive function, and neurodevelopmental and neuropsychiatric comorbidities in our 3q29del study sample, and we compared subjects with 3q29del with published data on fragile X syndrome, 22q11.2 deletion syndrome and 16p11.2 deletion and duplication syndromes. RESULTS: Individuals with 3q29del had global deficits in adaptive behaviour that were not driven by specific weaknesses in any given domain. Individual neurodevelopmental and neuropsychiatric diagnoses had a small effect on adaptive behaviour, and the cumulative number of comorbid diagnoses was significantly negatively associated with Vineland-3 performance. Both cognitive ability and executive function were significantly associated with adaptive behaviour, and executive function was a better predictor of Vineland-3 performance than cognitive ability. Finally, the severity of adaptive behaviour deficits in 3q29del was distinct from previously published data on comparable genomic disorders. CONCLUSIONS: Individuals with 3q29del have significant deficits in adaptive behaviour, affecting all domains assessed by the Vineland-3. Executive function is a better predictor of adaptive behaviour than cognitive ability in this population and suggests that interventions targeting executive function may be an effective therapeutic strategy.

Technical Factors Contributing to Nonunion in Supracondylar Distal Femur Fractures Treated With Lateral Locked Plating: A Risk-Stratified Analysis.

OBJECTIVE: To identify technical factors associated with nonunion after operative treatment with lateral locked plating. DESIGN: Retrospective cohort study. SETTING: Ten Level I trauma centers. PATIENT SELECTION CRITERIA: Adult patients with supracondylar distal femur fractures (OTA/AO type 33A or C) treated with lateral locked plating from 2010 through 2019. OUTCOME MEASURES AND COMPARISONS: Surgery for nonunion stratified by risk for nonunion. RESULTS: The cohort included 615 patients with supracondylar distal femur fractures. The median patient age was 61 years old (interquartile range: 46 -72years) and 375 (61%) were female. Observed were nonunion rates of 2% in a low risk of nonunion group (n = 129), 4% in a medium-risk group (n = 333), and 14% in a high-risk group (n = 153). Varus malreduction with an anatomic lateral distal femoral angle greater than 84 degrees, was associated with double the odds of nonunion compared to those without such varus [odds ratio, 2.1; 95% confidence interval (CI), 1.1-4.2; P = 0.03]. Malreduction by medial translation of the articular block increased the odds of nonunion, with 30% increased odds per 4 mm of medial translation (95% CI, 1.0-1.6; P = 0.03). Working length increased the odds of nonunion in the medium risk group, with an 18% increase in nonunion per 10-mm increase in working length (95% CI, 1.0-1.4; P = 0.01). Increased proximal screw density was protective against nonunion (odds ratio, 0.71; 95% CI, 0.53-0.92; P = 0.02) but yielded lower mRUST scores with each 0.1 increase in screw density associated with a 0.4-point lower mRUST (95% CI, -0.55 to -0.15; P < 0.001). Lateral plate length and type of plate material were not associated with nonunion. ( P > 0.05). CONCLUSIONS: Malreduction is a surgeon-controlled variable associated with nonunion after lateral locked plating of supracondylar distal femur fractures. Longer working lengths were associated with nonunion, suggesting that bridge plating may be less likely to succeed for longer fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Pouring cold water on fake news - a qualitative review of misinformation related to burns first aid.

Health misinformation is pervasive on the internet and social media, and can have wide-ranging and devastating repercussions. Burn injuries are highly prevalent, especially in resource-poor countries with less rigorous health and safety regulations and reduced access to quality healthcare, and especially among the pediatric population who rely on caregivers to tend to their injuries. Correct first aid is crucial to improving burn outcomes and avoiding further complications. The aim of this study was to qualitatively assess the content of misinformation related to burns online. A literature search was conducted on PubMed using search terms 'burns' OR 'burn injury' OR 'burns trauma' OR 'major burns' AND 'first aid' AND 'conspiracy' OR 'disinformation' OR 'misinformation' OR 'fake news'. Combinations of these terms were searched via Google, YouTube, Facebook, Instagram, TikTok and PubMed. Key areas of misinformation included unfounded use of 'natural' remedies, injudicious use of antibiotics, omission of key steps of first aid, and errors in specific details of first aid. Clinicians should be aware of misinformation available online related to first aid for burns, be aware that patients presenting with burns may have caused further injury with insufficient first aid or inappropriate home remedies, and lead public health campaigns to educate on the initial emergency management of burns.

Factors affecting energy efficiency in herringbone and rotary milking parlours.

The United Nations Sustainable Development Goals aim to double the productivity of small-medium food producers (2015-2030), while food demand is estimated to increase by 60 % by 2050. The objectives of this paper were to identify and quantify the relationship between energy efficiency and milking efficiency, identify the main energy consuming processes associated with milking, and investigate whether milking efficiency, energy efficiency or the relationship between them varies depending on parlour type. Energy and milking efficiency data from 26 pasture-based dairy farms in the Republic of Ireland were analysed (17 herringbone, nine rotary). Energy consumption was monitored continuously on the herringbone farms and for two distinct, seven-day periods (observation periods 1 and 2) for the rotary farms. Milking performance was monitored for all 26 farms during these periods. During the observation periods, the rotary farms achieved superior energy efficiency (29.85 Wh kgMilk-1) and milking efficiency (152 cows/hour) than the herringbone farms (32.83 Wh kgMilk-1, 97 cows/hour). Moderate correlations existed between milking efficiency (cows/hour) and energy efficiency (Wh kgMilk-1) for rotary (r = -0.58, R2 = 0.34) and herringbone (r = -0.44, R2 = 0.19). These results indicated that higher levels of milking efficiency were moderately correlated with improved energy efficiency.

Electrochemical treatment of textile wastewater using copper electrodes.

The conventional electrode aluminum used in electrocoagulation (EC) for the textile wastewater undergoes pitting type of corrosion, so dissolution of the same is very high during electrolysis. This research focuses on the treatment of real-time textile effluent with copper electrodes that corrode uniformly during electrolysis, with optimizing operating parameters for high color removal efficiency (CRE%). The sludge acquired was analyzed by XPS and XRD to study the mechanism of dye removal. The treated effluent was subjected to phytotoxicity analysis using Vigna radiata to study the toxicity effect of the intermediary products. 98.6% of CRE was attained in treating the effluent with copper electrodes. XPS and XRD results showed that both Cu(OH)2 and CuO served as coagulants in the dye removal. The phytotoxicity results showed that the percentage of germination, shoot and root lengths of Vigna radiata in the treated effluent were similar to the results obtained for the control.

Assessment of the current performance of grazing infrastructure across Irish dairy farms.

The increased average Irish dairy herd size in a post-quota environment has put heightened pressure on grazing infrastructure. In a rotational grazing system, grazing infrastructure consists of the paddock system, which delineates the grazing areas into appropriately sized grazing parcels, and the roadway network, which connects these paddocks to the milking parlor. Where herd size has increased without corresponding adaptations to the infrastructure, farm management and roadway network performance has been affected. The links between suboptimal grazing infrastructure and roadway network efficiency are poorly understood and not widely documented. The aims of this study were to (1) analyze the effect of herd expansion and paddock size on pasture allocations per paddock, (2) identify the factors that affect the total distance walked per year, and (3) create a metric to compare the efficiency of roadway networks across farms of varying grazing platforms. A sample population of 135 Irish dairy farms with a median herd size of 150 cows was used for this analysis. Herds were split into the following 5 categories: <100 cows, 100 to 149 cows, 150 to 199 cows, 200 to 249 cows, and ≥250 cows. Herds with ≥250 cows had a greater number of paddocks per farm and rotated around the grazing paddocks more frequently, with 46% of paddocks only suitable for 12 h allocations relative to herd size, compared with just 10% to 27% of paddocks for herds with <100 cows to herds with 200-249 cows. When predicting the total distance walked per year on each study farm, the mean distance from a paddock to the milking parlor was the strongest indicator (R2 = 0.8247). Other metrics, such as herd size, have failed to account for the location of the milking parlor relative to the grazing platform. The creation of the relative mean distance from a paddock to milking parlor (RMDMP) metric allowed the calculation of a farm's roadway network efficiency for moving the herd between paddocks and the milking parlor. The analyzed farms increased their efficiency in terms of RMDMP (0.34-40.74%) as they increased herd size post quota. However, the position of new additional paddocks relative to the milking parlor substantially affected their RMDMP.

Post-ischemic reorganization of sensory responses in cerebral cortex.

Introduction: Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response. Methods: We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats' forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation. Results: Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation in RFA modulated and disrupted the sensory response in sensory cortex. Discussion: The presence of a sensory response in RFA and the sensitivity of S1 to modulation by intracortical stimulation provides additional evidence for functional connectivity between premotor and somatosensory cortex. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.

The prevalence of anxiety disorders in dermatology outpatients: A systematic review and meta-analysis.

Anxiety is common in those with medical conditions and has significant impacts on mental well-being as well as physical health outcomes. While several systematic reviews have examined the prevalence of anxiety in specific dermatological conditions, no reviews have examined the prevalence across the entire dermatology outpatient setting. This systematic review aims to provide an overview to dermatologists of the prevalence of, and trends in, anxiety in their outpatient clinics. As such, prevalence of anxiety in dermatology outpatient clinics was examined, and variations across type of anxiety and dermatological conditions were assessed. A search of PubMed, Embase, Cochrane and PsycINFO was conducted for studies that assessed anxiety prevalence in dermatology outpatients, with the last search conducted on 7 September 2022. Results underwent title/abstract and full-text screening, followed by data extraction. Studies of patients 16 years and older and representative of dermatology clinics were included. Risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis was conducted using CMA software, and subgroup analysis was conducted on relevant variables. 5423 studies were identified, and 32 included, with a total n = 12,812 participants. Under the random effects model, prevalence was estimated at 26.7% (95%CI 22.4-31.4; 95%PI 9.7-55.4). Subgroup analysis revealed a higher prevalence among studies of psoriasis patients than general dermatology studies. Estimates of prevalence were higher when assessed via self-report screening than diagnostic interview. Anxiety occurred frequently among dermatology outpatients, especially psoriasis outpatients, at a higher rate than common estimates of prevalence in the general population. Given the effect of anxiety on patient outcomes and well-being, dermatologists are encouraged to consider how anxiety may impact patients in their clinic, and how they can best identify patients with anxiety and subsequently support them.

Outcomes of Total Knee Arthroplasty Revisions in Obese and Morbidly Obese Patient Populations.

BACKGROUND: The obese population is at higher risk for complications following primary total knee arthroplasty (TKA), but little data is available regarding revision outcomes. This study aimed to investigate the role of body mass index (BMI) in the cause for revision TKA and whether BMI classification is predictive of outcomes. METHODS: A multi-institutional database was generated, including revision TKAs from 2012 to 2019. Data collection included demographics, comorbidities, surgery types (primary revision, repeat revision), reasons for revision, lengths of hospital stay, and surgical times. Patients were compared using 3 BMI categories: nonobese (18.5 to 29.9), obese (30 to 39.9), and morbidly obese (≥40). Categorical and continuous variables were analyzed using chi-square and 1-way analysis of variance tests, respectively. Regression analyses were used to compare reasons for revision among weight classes. RESULTS: Obese and morbidly obese patients showed significant risk for repeat revision surgery in comparison to normal weight patients. Obese patients were at higher risk for primary revision due to stiffness/fibrosis and repeat revision due to malposition. In comparison to the obese population, morbidly obese patients were more likely to require primary revision for dislocation and implant loosening. CONCLUSION: Significant differences in primary and repeat revision etiologies exist among weight classes. Furthermore, obese and morbidly obese patients have a greater risk of requiring repeat revision surgery. These patients should be informed of their risk for multiple operations, and surgeons should be aware of the differences in revision etiologies when anticipating complications following primary TKA.

Epigenetic effects of folate and related B vitamins on brain health throughout life: Scientific substantiation and translation of the evidence for health improvement strategies.

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.

Implementation evaluation of an evidence-based emergency nursing framework (HIRAID): study protocol for a step-wedge randomised control trial.

INTRODUCTION: Poor patient assessment results in undetected clinical deterioration. Yet, there is no standardised assessment framework for >29 000 Australian emergency nurses. To reduce clinical variation and increase safety and quality of initial emergency nursing care, the evidence-based emergency nursing framework HIRAID (History, Identify Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) was developed and piloted. This paper presents the rationale and protocol for a multicentre clinical trial of HIRAID. METHODS AND ANALYSIS: Using an effectiveness-implementation hybrid design, the study incorporates a stepped-wedge cluster randomised controlled trial of HIRAID at 31 emergency departments (EDs) in New South Wales, Victoria and Queensland. The primary outcomes are incidence of inpatient deterioration related to ED care, time to analgesia, patient satisfaction and medical satisfaction with nursing clinical handover (effectiveness). Strategies that optimise HIRAID uptake (implementation) and implementation fidelity will be determined to assess if HIRAID was implemented as intended at all sites. ETHICS AND DISSEMINATION: Ethics has been approved for NSW sites through Greater Western Human Research Ethics Committee (2020/ETH02164), and for Victoria and Queensland sites through Royal Brisbane & Woman's Hospital Human Research Ethics Committee (2021/QRBW/80026). The final phase of the study will integrate the findings in a toolkit for national rollout. A dissemination, communications (variety of platforms) and upscaling strategy will be designed and actioned with the organisations that influence state and national level health policy and emergency nurse education, including the Australian Commission for Quality and Safety in Health Care. Scaling up of findings could be achieved by embedding HIRAID into national transition to nursing programmes, 'business as usual' ED training schedules and university curricula. TRIAL REGISTRATION NUMBER: ACTRN12621001456842.

Post-Ischemic Reorganization of Sensory Responses in Cerebral Cortex.

Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response. We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats' forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation. Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation evoked activity in RFA modulated and disrupted the sensory response in sensory cortex, providing additional evidence for the transmission of premotor activity to sensory cortex and the sensitivity of sensory cortex to premotor cortex's influence. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.

A distinct cognitive profile in individuals with 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome is associated with mild to moderate intellectual disability as well as comorbid psychopathology such as ADHD, anxiety, ASD and schizophrenia. A greater understanding of specific profiles that could increase risk for psychopathology is necessary in order to best understand and support individuals with 3q29 deletion syndrome. The goal of this study was to thus carefully outline the strengths and weaknesses of these individuals. A second goal was to ask whether the cognitive impact of the deletion predicted psychopathology in other domains. METHODS: We systematically evaluated cognitive ability, adaptive behaviour and psychopathology in 32 individuals with the canonical 3q29 deletion using gold-standard instruments and a standardised phenotyping protocol. RESULTS: Mean full scale IQ was 73 (range 40-99). Verbal subtest score (mean 80, range 31-106) was slightly higher and had a greater range than non-verbal subtest score (mean 75, range 53-98). Spatial ability was evaluated in a subset (n = 24) and was lower than verbal and non-verbal ability (mean 71, range 34-108). There was an average 14-point difference between verbal and non-verbal subset scores; 60% of the time the verbal subset score was higher than the non-verbal subset score. Study subjects with a verbal ability subtest score lower than the non-verbal subtest score were four times more likely to have a diagnosis of intellectual disability (suggestive, P value 0.07). The age at which a child first spoke two-word phrases was strongly associated with measures of verbal ability (P value 2.56e-07). Cognitive ability was correlated with adaptive behaviour measures (correlation 0.42, P value 0.02). However, although group means found equivalent scores, there was, on average, a 10-point gap between these skills (range -33 to 33), in either direction, in about 50% of the sample, suggesting that cognitive measures only partially inform adaptive ability. Cognitive ability scores did not have any significant relationship to cumulative burden of psychopathology nor to individual neurodevelopmental or psychiatric diagnoses. CONCLUSIONS: Individuals with 3q29 deletion syndrome have a complex pattern of cognitive disability. Two-thirds of individuals with the deletion will exhibit significant strength in verbal ability; this may mask deficits in non-verbal reasoning, leading to an overestimation of overall ability. Deficits in verbal ability may be the driver of intellectual disability diagnosis. Cognitive ability is not a strong indicator of other neurodevelopmental or psychiatric impairment; thus, individuals with 3q29 deletion syndrome who exhibit IQ scores within the normal range should receive all recommended behavioural evaluations.