Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease.

Neuroinflammation is a key driver of neurodegenerative disease, however the tools available to model this disease biology at the systems level are lacking. We describe a translational drug discovery platform based on organotypic culture of murine cortical brain slices that recapitulate disease-relevant neuroinflammatory biology. After an acute injury response, the brain slices assume a chronic neuroinflammatory state marked by transcriptomic profiles indicative of activation of microglia and astrocytes and loss of neuronal function. Microglia are necessary for manifestation of this neuroinflammation, as depletion of microglia prior to isolation of the brain slices prevents both activation of astrocytes and robust loss of synaptic function genes. The transcriptomic pattern of neuroinflammation in the mouse platform is present in published datasets derived from patients with amyotrophic lateral sclerosis, Huntington's disease, and frontotemporal dementia. Pharmacological utility of the platform was validated by demonstrating reversal of microglial activation and the overall transcriptomic signature with transforming growth factor-ß. Additional anti-inflammatory targets were screened and inhibitors of glucocorticoid receptors, COX-2, dihydrofolate reductase, and NLRP3 inflammasome all failed to reverse the neuroinflammatory signature. Bioinformatics analysis of the neuroinflammatory signature identified protein tyrosine phosphatase non-receptor type 11 (PTPN11/SHP2) as a potential target. Three structurally distinct inhibitors of PTPN11 (RMC-4550, TN0155, IACS-13909) reversed the neuroinflammatory disease signature. Collectively, these results highlight the utility of this novel neuroinflammatory platform for facilitating identification and validation of targets for neuroinflammatory neurodegenerative disease drug discovery.

Development of the data registry for the Cardiac Neurodevelopmental Outcome Collaborative.

Children with congenital heart disease (CHD) can face neurodevelopmental, psychological, and behavioural difficulties beginning in infancy and continuing through adulthood. Despite overall improvements in medical care and a growing focus on neurodevelopmental screening and evaluation in recent years, neurodevelopmental disabilities, delays, and deficits remain a concern. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with the goal of improving neurodevelopmental outcomes for individuals with CHD and pediatric heart disease. This paper describes the establishment of a centralised clinical data registry to standardize data collection across member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. The goal of this registry is to foster collaboration for large, multi-centre research and quality improvement initiatives that will benefit individuals and families with CHD and improve their quality of life. We describe the components of the registry, initial research projects proposed using data from the registry, and lessons learned in the development of the registry.

Spasticity Management Teams, Evaluations, and Tools: A Canadian Cross-Sectional Survey.

OBJECTIVE: The objective of this study is to determine the physical evaluations and assessment tools used by a group of Canadian healthcare professionals treating adults with spasticity. METHODS: A cross-sectional web-based 19-question survey was developed to determine the types of physical evaluations, tone-related impairment measurements, and assessment tools used in the management of adults with spasticity. The survey was distributed to healthcare professionals from the Canadian Advances in Neuro-Orthopedics for Spasticity Congress database. RESULTS: Eighty study participants (61 physiatrists and 19 other healthcare professionals) completed the survey and were included. Nearly half (46.3%, 37/80) of the participants reported having an inter- or trans-disciplinary team managing individuals with spasticity. Visual observation of movement, available range of motion determination, tone during velocity-dependent passive range of motion looking for a spastic catch, spasticity, and clonus, and evaluation of gait were the most frequently used physical evaluations. The most frequently used spasticity tools were the Modified Ashworth Scale, goniometer, and Goal Attainment Scale. Results were similar in brain- and spinal cord-predominant etiologies. To evaluate goals, qualitative description was used most (37.5%). CONCLUSION: Our findings provide a better understanding of the spasticity management landscape in Canada with respect to staffing, physical evaluations, and outcome measurements used in clinical practice. For all etiologies of spasticity, visual observation of patient movement, Modified Ashworth Scale, and qualitative goal outcomes descriptions were most commonly used to guide treatment and optimize outcomes. Understanding the current practice of spasticity assessment will help provide guidance for clinical evaluation and management of spasticity.

Abnormal infant neurobehavior and later neurodevelopmental delays in children with critical CHD.

Infants with critical CHD have abnormal neurobehavior assessed by the Neonatal ICU Network Neurobehavioral Scales. This retrospective cohort study hypothesized associations between abnormal infant neurobehavior in the first month of life and later neurodevelopmental outcomes at 1-2 years of age. Associations between abnormal infant attention (orienting to and tracking stimuli) on the Neonatal ICU Network Neurobehavioral Scales and later motor, cognitive, and language neurodevelopmental outcomes on the Bayley Scales of Infant Development-III at follow-up were examined with descriptive statistics and univariable and multivariable regression. Multiple imputation was used to account for missing outcome data. 189 infants with critical CHD were included, and 69% had abnormal neurobehavioral attention scores. 58 (31%) returned as toddlers for neurodevelopmental follow-up, of which 23% had motor delay. Abnormal infant attention had high sensitivity (92%, 95% CI 60-100%) but low specificity (36%, 95% CI 23-52%) for later motor delay. Higher infant attention scores were associated with higher later motor scores in univariable analysis (coefficient 3.49, 95% CI 0.52,6.46, p = 0.025), but not in multivariable analyses. Neither cognitive nor language scores were associated with infant attention scores. Lower birth weight and male sex were significantly associated with lower motor scores in multivariable analysis (p = 0.048, 0.007). Although impaired infant attention is interdependent with other clinical and demographic risk factors, it may be a sensitive clinical marker of risk for later motor delay. In children with critical CHD, impaired infant attention may be capturing early signs of abnormal visual-motor neurodevelopment.

Telehealth services for cardiac neurodevelopmental care during the COVID-19 pandemic: a site survey from the Cardiac Neurodevelopmental Outcome Collaborative.

OBJECTIVE: COVID-19 has markedly impacted the provision of neurodevelopmental care. In response, the Cardiac Neurodevelopmental Outcome Collaborative established a Task Force to assess the telehealth practices of cardiac neurodevelopmental programmes during COVID-19, including adaptation of services, test protocols and interventions, and perceived obstacles, disparities, successes, and training needs. STUDY DESIGN: A 47-item online survey was sent to 42 Cardiac Neurodevelopmental Outcome Collaborative member sites across North America within a 3-week timeframe (22 July to 11 August 2020) to collect cross-sectional data on practices. RESULTS: Of the 30 participating sites (71.4% response rate), all were providing at least some clinical services at the time of the survey and 24 sites (80%) reported using telehealth. All but one of these sites were offering new telehealth services in response to COVID-19, with the most striking change being the capacity to offer new intervention services for children and their caregivers. Only a third of sites were able to carry out standardised, performance-based, neurodevelopmental testing with children and adolescents using telehealth, and none had completed comparable testing with infants and toddlers. Barriers associated with language, child ability, and access to technology were identified as contributing to disparities in telehealth access. CONCLUSIONS: Telehealth has enabled continuation of at least some cardiac neurodevelopmental services during COVID-19, despite the challenges experienced by providers, children, families, and health systems. The Cardiac Neurodevelopmental Outcome Collaborative provides a unique platform for sharing challenges and successes across sites, as we continue to shape an evidence-based, efficient, and consistent approach to the care of individuals with CHD.

Developmental care pathway for hospitalised infants with CHD: on behalf of the Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative.

Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, "Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease," includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.

The hand diagram: A novel outcome measure following supercharged end-to-side anterior interosseous nerve to ulnar nerve transfer in severe compressive ulnar neuropathy.

BACKGROUND: With advances in the surgical management for severe ulnar neuropathy with the introduction of the super charged-end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar nerve transfer, a simple and reliable outcome measure is required. There is currently not "one" standardized outcome measure used to represent and compare results. PURPOSE: To present the abduction hand diagram as a "novel", reproducible, and simple outcome measure for patients with severe ulnar neuropathy. STUDY DESIGN: Retrospective case series. METHODS: Nine patients with severe entrapment/compressive ulnar neuropathy at the elbow were reviewed. Clinical parameters included preoperative and postoperative abduction tracings, Medical Research Grade (MRC) muscle strength, key pinch strength, Disability of the Hand Arm and Shoulder (DASH) score, and crossed finger test. Electrodiagnostic data included change in compound muscle action potentials (CMAP) amplitude of the first dorsal interosseous (FDI), and abductor digiti minimi (ADM). Summary statistics were used for demographic and clinical data. RESULTS: Average follow-up was 22.8 ± 9.3 months. At 18-months of follow up, 44% had ADM MRC grade 3 strength or higher, mean key pinch strength improved to 72 ± 19.3%, and mean DASH was 33 ± 28.7. There was a mean increase of 16.7 ± 9.1 mm and 31.5 ± 12 mm in total and summed hand abduction tracing measurements respectively. CONCLUSIONS: Hand abduction tracings are a quantitative outcome measure to follow recovery over time for intrinsic hand function and can be used in patients with severe ulnar neuropathy following surgical intervention.

Traumatic peripheral nerve injuries: diagnosis and management.

PURPOSE OF REVIEW: To review advances in the diagnostic evaluation and management of traumatic peripheral nerve injuries. RECENT FINDINGS: Serial multimodal assessment of peripheral nerve injuries facilitates assessment of spontaneous axonal regeneration and selection of appropriate patients for early surgical intervention. Novel surgical and rehabilitative approaches have been developed to complement established strategies, particularly in the area of nerve grafting, targeted rehabilitation strategies and interventions to promote nerve regeneration. However, several management challenges remain, including incomplete reinnervation, traumatic neuroma development, maladaptive central remodeling and management of fatigue, which compromise functional recovery. SUMMARY: Innovative approaches to the assessment and treatment of peripheral nerve injuries hold promise in improving the degree of functional recovery; however, this remains a complex and evolving area.

The pediatric heart network's study on long-term outcomes of children with HLHS and the impact of Norwood Shunt type in the single ventricle reconstruction trial cohort (SVRIII): Design and adaptations.

BACKGROUND: The Single Ventricle Reconstruction (SVR) Trial was the first randomized clinical trial of a surgical approach for treatment of congenital heart disease. Infants with hypoplastic left heart syndrome (HLHS) and other single right ventricle (RV) anomalies were randomized to a modified Blalock Taussig Thomas shunt (mBTTS) or a right-ventricular-to-pulmonary-artery shunt (RVPAS) at the time of the Norwood procedure. The aim of the Long-term Outcomes of Children with HLHS and the Impact of Norwood Shunt Type (SVR III) study is to compare early adolescent outcomes including measures of cardiac function, transplant-free survival, and neurodevelopment, between those who received a mBTTS and those who received an RVPAS. METHODS: Transplant-free survivors of the SVR cohort were enrolled at 10 to 15 years of age for multifaceted in-person evaluation of cardiac function (cardiac magnetic resonance [CMR], echocardiogram and exercise test) and neurodevelopmental evaluation. Right ventricular ejection fraction measured by CMR served as the primary outcome. Development of arrhythmias, protein losing enteropathy, and other comorbidities were assessed through annual medical history interview. Through the course of SVR III, protocol modifications to engage SVR trial participants were designed to enhance recruitment and retention. CONCLUSIONS: Evaluation of long-term outcomes will provide important data to inform decisions about the shunt type placed at the Norwood operation and will improve the understanding of cardiovascular and neurodevelopmental outcomes for early adolescents with HLHS.

Integrating Telehealth Into Neurodevelopmental Assessment: A Model From the Cardiac Neurodevelopmental Outcome Collaborative.

OBJECTIVE: In the wake of the COVID-19 pandemic, psychologists were pushed to look beyond traditional in-person models of neurodevelopmental assessment to maintain continuity of care. A wealth of data demonstrates that telehealth is efficacious for pediatric behavioral intervention; however, best practices for incorporating telehealth into neurodevelopmental assessment are yet to be developed. In this topical review, we propose a conceptual model to demonstrate how telehealth can be incorporated into various components of neurodevelopmental assessment. METHODS: Harnessing existing literature and expertise from a multidisciplinary task force comprised of clinicians, researchers, and patient/parent representatives from the subspecialty of cardiac neurodevelopmental care, a conceptual framework for telehealth neurodevelopmental assessment was developed. Considerations for health equity and access to care are discussed, as well as general guidelines for clinical implementation and gaps in existing literature. RESULTS: There are opportunities to integrate telehealth within each stage of neurodevelopmental assessment, from intake to testing, through to follow-up care. Further research is needed to determine whether telehealth mitigates or exacerbates disparities in access to care for vulnerable populations as well as to provide evidence of validity for a wider range of neurodevelopmental measures to be administered via telehealth. CONCLUSIONS: While many practices are returning to traditional, face-to-face neurodevelopmental assessment services, psychologists have a unique opportunity to harness the momentum for telehealth care initiated during the pandemic to optimize the use of clinical resources, broaden service delivery, and increase access to care for pediatric neurodevelopmental assessment.

Developmental Care Practice and Documentation Variability in the Cardiac ICU.

OBJECTIVES: Describe variability in developmental care practices, as documented in the electronic health record, for infants undergoing congenital heart surgery. DESIGN: Multicenter, retrospective, cohort study. SETTING: Six pediatric cardiac centers. PATIENTS: One hundred eighty-two infants undergoing one of three index operations: Norwood palliation, aortic arch reconstruction with ventricular septal defect closure, or arterial switch. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Core domains of developmental care encompassing pain assessment, feeding, infant holding, caregiver involvement, therapy, and psychosocial services were reviewed. Practices varied across individuals, institutions, and the hospital stay. At five of six sites, greater than 90% of individuals had physical or occupational therapy services as part of their care, but the day of first evaluation ranged from day of admission to postoperative day 28. Similar patterns were seen in feeding team and social work involvement. Consistent documentation of developmental care was dependent on the domain and site. Of the total days reviewed (n = 1,192), pain scores were documented in 95%. In those same days, documentation of whether or not a patient was out of the crib to be held varied by site from 11% to 93%. Type of oral feeding, breast versus bottle, was documented on the day prior to discharge 48% of the time. CONCLUSIONS: There are significant, quantifiable variations in documented developmental care practices at both the individual and site level. More reliable documentation of developmental care practices is required to associate these variables with later outcomes and investigate disparities in individualized developmental care practices.

Feeding outcomes in post-discharge feeding clinic for infants following cardiac surgery.

INTRODUCTION: The aim of this study was to describe the development and assess the usefulness of a feeding clinic to help infants with CHD tolerate the highest level of oral feeding while achieving growth velocity and supporting neurodevelopment. MATERIALS AND METHODS: This retrospective, cohort study assessed feeding outcomes for infants who underwent cardiac surgery at <30 days of age with cardiopulmonary bypass between February 2016 and April 2020. Diagnoses, age at surgery, hospitalisation variables, and feeding outcomes were compared between two cohorts, pre- and post-implementation of a specialised feeding clinic using Exact Wilcoxon signed-rank test, chi-squared, or Fisher's exact test. The association between time to full oral feed and risk factors was assessed using univariable and multivariable Cox regression model. RESULTS: Post-clinic infants (n = 116) surgery was performed at a median of 6 days of life (interquartile range: 4, 8) with median hospital length of stay of 19 days (interquartile range: 16, 26). Infants' median age at first clinic visit was at 30 days old (interquartile range: 24, 40) and took median 10 days (interquartile range: 7, 12) after hospital discharge to first clinic visit. In the post-clinic cohort, the median time to 100% oral feeding was 47 days (interquartile range: 27, 96) compared to the 60 days (interquartile range: 20, 84) in the pre-clinic cohort (n = 22), but the difference was not statistically significant. DISCUSSION: The cardiac feeding clinic was utilised by our neonatal surgery population and feasible in coordination with cardiology follow-up visits. Future assessment of cardiac feeding clinic impact should include additional measures of feeding and neurodevelopmental success.

Postoperative management and rehabilitation after the supercharged end-to-side anterior interosseous nerve to ulnar motor nerve transfer: A report of 3 cases.

INTRODUCTION: Compressive ulnar neuropathy at the elbow is the second most common compressive neuropathy. Nerve transfers are used for severe ulnar neuropathies as a means of facilitating recovery. Hand therapy and rehabilitation after nerve transfers have not been extensively explored. PURPOSE OF THE STUDY: The aim of this repeated case study was to describe the responses, functional outcome, and neuromuscular health of three participants after the supercharged end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar motor nerve transfer do describe the hand therapy and recovery of 3 cases reflecting different recovery potential mediators, trajectories, and outcomes. STUDY DESIGN: Repeated case study. METHODS: Three participants of similar age (76-80 years) that had severe ulnar neuropathy who underwent surgical treatment including a SETS AIN to ulnar motor nerve surgery were purposively selected from an ongoing clinical trial, based on their response to the surgical and the rehabilitation intervention (large, moderate, and small improvements). Clinical evaluations included measuring range of motion, strength testing, and clinical tests (ie, Egawa's sign) and, subjective assessment of rehabilitation adherence., Quick Disability of Arm, Shoulder and Hand and decomposition-based quantitative electromyography were performed at >23 months to evaluate patients. RESULTS: All the three participants completed the surgical and hand therapy interventions, demonstrating a variable course of recovery and functional outcomes. The Quick Disability of Arm, Shoulder and Hand scores (>23 months) for participants A, B, and C were 68, 30, and 18, respectively. The person with the least improvement had idiopathic Parkinson's disease, dyslipidemia, history of depression, and gout. Comparison across cases suggested that the comorbidities, longer time from neuropathy to the surgical intervention, and psychosocial barriers to exercise and rehabilitation adherence influenced the recovery process. The participants with the best outcomes demonstrated improvements in his lower motor neurons or motor unit counts (109 and 18 motor units in the abductor digiti minimi (ADM) and first dorsal interosseous, respectively) and motor unit stability (39.5% and 37.6% near-fiber jiggle in the ADM and first dorsal interosseous, respectively). The participant with moderate response to the interventions had a motor unit count of 93 for the ADM muscle. We were unable to determine motor unit counts and measurements from the participant with the poorest outcomes due to his physical limitations. CONCLUSIONS: SETS AIN to ulnar motor nerve followed by multimodal hand therapy provides measurable improvements in neurophysiology and function, although engagement in hand therapy and outcomes appear to be mediated by comorbid physical and psychosocial health.

A Collaborative Learning Assessment of Developmental Care Practices for Infants in the Cardiac Intensive Care Unit.

OBJECTIVE: Assess differences in approaches to and provision of developmental care for infants undergoing surgery for congenital heart disease. STUDY DESIGN: A collaborative learning approach was used to stratify, assess, and compare individualized developmental care practices among multidisciplinary teams at 6 pediatric heart centers. Round robin site visits were completed with structured site visit goals and postvisit reporting. Practices of the hosting site were assessed by the visiting team and reviewed along with center self-assessments across specific domains including pain management, environment, cue-based care, and family based care coordination. RESULTS: Developmental care for infants in the cardiac intensive care unit (CICU) varies at both a center and individual level. Differences in care are primarily driven by variations in infrastructure and resources, composition of multidisciplinary teams, education of team members, and use of developmental care champions. Management of pain follows a protocol in most cardiac intensive care units, but the environment varies across centers, and the provision of cue-based infant care and family-based care coordination varies widely both within and across centers. The project led to proposed changes in clinical care and center infrastructure at each participating site. CONCLUSIONS: A collaborative learning design fostered rapid dissemination, comparison, and sharing of strategies to approach a complex multidisciplinary care paradigm. Our assessment of experiences revealed marked variability across and within centers. The collaborative findings were a first step toward strategies to quantify and measure developmental care practices in the cardiac intensive care unit to assess the association of complex inpatient practices with long-term neurodevelopmental outcomes.

The Benefits and Bias in Neurodevelopmental Evaluation for Children with Congenital Heart Disease.

Neurodevelopmental (ND) impairment is common in children with congenital heart disease (CHD). While routine ND surveillance and evaluation of high-risk patients has become the standard-of-care, capture rate, barriers to referral, and potential patient benefits remain incompletely understood. Electronic data warehouse records from a single center were reviewed to identify all eligible and evaluated patients between July 2015 and December 2017 based on current guidelines for ND screening in CHD. Diagnoses, referring provider, and payor were considered. Potential benefit of the evaluation was defined as receipt of new diagnosis, referral for additional evaluation, or referral for a new service. Contingencies were assessed with Fisher's exact test. In this retrospective, cohort study, of 3434 children identified as eligible for ND evaluation, 135 were evaluated (4%). Appropriate evaluation was affected by diagnostic bias against coarctation of the aorta (CoArc) and favoring hypoplastic left heart syndrome (HLHS) (1.8 vs. 11.9%, p<0.01). Referrals were disproportionally made by a select group of cardiologists, and the rate of ND appointment non-compliance was higher in self-pay compared to insured patients (78% vs 27%, p<0.01). Potential benefit rate was 70-80% amongst individuals with the three most common diagnoses requiring neonatal surgery (CoArc, transposition of the great arteries, and HLHS). Appropriate ND evaluation in CHD is impacted by diagnosis, provider, and insurance status. Potential benefit of ND evaluation is high regardless of diagnosis. Strategies to improve access to ND evaluations and provider understanding of the at-risk population will likely improve longitudinal ND surveillance and clinical benefit.

The origins and development of the cardiac neurodevelopment outcome collaborative: creating innovative clinical, quality improvement, and research opportunities.

Compared to the general population, individuals with complex congenital heart disease are at increased risk for deficits in cognitive, neurodevelopmental, psychosocial, and physical functioning, resulting in a diminished health-related quality of life. These deficits have been well described over the past 25 years, but significant gaps remain in our understanding of the best practices to improve neurodevelopmental and psychosocial outcomes and health-related quality of life for individuals with paediatric and congenital heart disease. Innovative clinical, quality improvement, and research opportunities with collaboration across multiple disciplines and institutions were needed to address these gaps. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with a described mission to determine and implement best practices of neurodevelopmental and psychosocial services for individuals and their families with paediatric and congenital heart disease through clinical, quality improvement, and research initiatives. The vision is to be a multi-centre, multi-national, multi-disciplinary group of healthcare professionals committed to working together and partnering with families to optimise neurodevelopmental outcomes for individuals with paediatric and congenital heart disease through clinical, quality, and research initiatives, intending to maximise quality of life for every individual across the lifespan. This manuscript describes the development and organisation of the Cardiac Neurodevelopmental Outcome Collaborative.

Variations in practice in cardiac neurodevelopmental follow-up programs.

Over the last two decades, heart centres have developed strategies to meet the neurodevelopmental needs of children with congenital heart disease. Since the publication of guidelines in 2012, cardiac neurodevelopmental follow-up programmes have become more widespread. Local neurodevelopmental programmes, however, have been developed independently in widely varying environments. We sought to characterise variation in structure and personnel in cardiac neurodevelopmental programmes. A 31-item survey was sent to all member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. Multidisciplinary teams at each centre completed the survey. Responses were compiled in a descriptive fashion. Of the 29 invited centres, 23 responded to the survey (79%). Centres reported more anticipated neurodevelopment visits between birth and 5 years of age (median 5, range 2-8) than 5-18 years (median 2, range 0-10) with 53% of centres lacking any standard for routine neurodevelopment evaluations after 5 years of age. Estimated annual neurodevelopment clinic volume ranged from 85 to 428 visits with a median of 16% of visits involving children >5 years of age. Among responding centres, the Bayley Scales of Infant and Toddler Development and Wechsler Preschool and Primary Scale of Intelligence were the most routinely used tests. Neonatal clinical assessment was more common (64%) than routine neonatal brain imaging (23%) during hospitalisation. In response to clinical need and published guidelines, centres have established formal cardiac neurodevelopment follow-up programmes. Centres vary considerably in their approaches to routine screening and objective testing, with many centres currently focussing their resources on evaluating younger patients.

Impact of diet on the persistence of early vascular remodeling and stiffening induced by intrauterine growth restriction and a maternal high-fat diet.

Intrauterine growth restriction (IUGR) and maternal high-fat diet (HFD) independently predispose offspring to hypertension. In a rat model, IUGR more so than maternal HFD increases arterial stiffness with vascular remodeling as early as postnatal day (PND) 21. The trajectory of such early vascular changes remains unknown. We hypothesized that IUGR would increase blood pressure (BP), arterial stiffness, and markers of ongoing detrimental vascular remodeling in adult rats exposed to a maternal HFD regardless of weaning diet. Adult female rats were fed either a regular diet (RD) or an HFD before mating through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either a RD or HFD through PND 60. For both control and IUGR rats, this design resulted in the following three diet groups: offspring from RD dams weaned to a RD and offspring from HFD dams weaned to a RD or to an HFD (IHH). In both males and females, only IHH increased systolic BP, but IUGR and HFD both alone and in combination increased arterial stiffness. Aortas contained fewer but thicker elastin bands in IHH rats and IUGR offspring from dams fed an HFD and weaned to a regular diet. IHH increased aortic lysl oxidase protein. In summary, the PND 21 rat mediators of vascular remodeling from IUGR and maternal HFD normalize by PND 60 while changes in elastin and arterial stiffness persist. We speculate that the longer-term risk of hypertension from dietary mediators is augmented by underlying IUGR-induced structural changes to the extracellular matrix.NEW & NOTEWORTHY We report that a combined insult of intrauterine growth restriction and maternal high-fat diet increases the risk of early cardiovascular pathology both independently and in conjunction with a continued high-fat diet in offspring.

The association between feeding protocol compliance and weight gain following high-risk neonatal cardiac surgery.

BACKGROUND: Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions' feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols. METHODS: Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals. RESULTS: Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates. CONCLUSIONS: High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.

A paratransgenic strategy to block transmission of Xylella fastidiosa from the glassy-winged sharpshooter Homalodisca vitripennis.

BACKGROUND: Arthropod-borne diseases remain a leading cause of human morbidity and mortality and exact an enormous toll on global agriculture. The practice of insecticide-based control is fraught with issues of excessive cost, human and environmental toxicity, unwanted impact on beneficial insects and selection of resistant insects. Efforts to modulate insects to eliminate pathogen transmission have gained some traction and remain future options for disease control. RESULTS: Here, we report a paratransgenic strategy that targets transmission of Xylella fastidiosa, a leading bacterial pathogen of agriculture, by the Glassy-Winged Sharpshooter (GWSS), Homalodisca vitripennis. Earlier, we identified Pantoea agglomerans, a bacterial symbiont of the GWSS as the paratransgenic control agent. We genetically engineered P. agglomerans to express two antimicrobial peptides (AMP)-melittin and scorpine-like molecule (SLM). Melittin and SLM were chosen as the effector molecules based on in vitro studies, which showed that both molecules have anti-Xylella activity at concentrations that did not kill P. agglomerans. Using these AMP-expressing strains of P. agglomerans, we demonstrated disruption of pathogen transmission from insects to grape plants below detectable levels. CONCLUSION: This is the first report of halting pathogen transmission from paratransgenically modified insects. It is also the first demonstration of paratransgenic control in an agriculturally important insect vector.