7 research outputs found
Canine RNF170 Single Base Deletion in a Naturally Occurring Model for Human Neuroaxonal Dystrophy.
BACKGROUND
Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology.
OBJECTIVES
To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause.
METHODS
Clinical and postmortem evaluations, together with a genome-wide association study and autozygosity mapping approach, followed by whole-genome sequencing.
RESULTS
Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1-bp (base pair) deletion in RNF170 encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)). The age of this canine RNF170 variant was estimated at ~30 years, before the reproductive isolation of the MAS breed.
CONCLUSIONS
RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia-85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
The motivations for the adoption of management innovation by local governments and its performance effects
This article analyses the economic, political and institutional antecedents and performance effects of the adoption of shared Senior Management Teams (SMTs) – a management innovation (MI) that occurs when a team of senior managers oversees two or more public organizations. Findings from statistical analysis of 201 English local governments and interviews with organizational leaders reveal that shared SMTs are adopted to develop organisational capacity in resource‐challenged, politically risk‐averse governments, and in response to coercive and mimetic institutional pressures. Importantly, sharing SMTs may reduce rather than enhance efficiency and effectiveness due to redundancy costs and the political transaction costs associated with diverting resources away from a high‐performing partner to support their lower‐performing counterpart
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Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm
To investigate associations in toddlers born extremely preterm (<28 weeks) between neonatal neuroimaging and 18- to 22-month developmental and behavioral outcomes.
Cohort analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely preterm. Subjects underwent cranial ultrasonography and near-term magnetic resonance imaging (MRI). At 18-22 months of corrected age, the assessment included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem and Competence Scale scores and the Bayley Scales of Infant Development, Third Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the Competence Scale assesses social-emotional competence. We examined associations of Problem and Competence scores and positive screen rates with cranial ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were compared using ANOVA and positive screen rates with the χ2 test. We computed correlations between BITSEA and Bayley-III scores.
Of the 397 children, positive BITSEA screens were found in 34% for the Problem score and 26% for the Competence score. Presence of lesions on near-term MRI that included cerebellar lesions were significantly associated with lower BITSEA Competence but not with Problem scores; Competence scores were inversely related to the presence/significance of lesions. Positive screens on Competence scores and on both Competence and Problem scores were significantly associated with Bayley-III cognitive and language scores <85 (P < .001).
Social–emotional competence contributes to deficits in cognitive and language development. Presence of injury on near-term MRI that includes cerebellar lesions is associated with later social–emotional competence and may be a useful predictor to guide early assessment and intervention.
ClinicalTrials.gov: NCT00063063 and NCT00233324
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Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.
Objective To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. Study design EPT infants (240/7-276/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. Results Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score Conclusions EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation