Mutation in leads to early motor dysfunction and widespread aberrant axon terminals in a beta-propeller protein associated neurodegeneration (BPAN) patient-inspired mouse model.

Beta-propeller Protein Associated Neurodegeneration (BPAN) is a devastating neurodevelopmental and neurodegenerative disease linked to variants in . Currently, there is no cure or disease altering treatment for this disease. This is, in part, due to a lack of insight into early phenotypes of BPAN progression and 's role in establishing and maintaining neurological function.

New labor curves of dilation and station to improve the accuracy of predicting labor progress.

Background: The diagnosis of failure to progress, the most common indication for intrapartum cesarean delivery, is based on the assessment of cervical dilation and station over time. Labor curves serve as references for expected changes in dilation and fetal descent. The labor curves of Friedman, Zhang et al, and others are based on time alone and derived from mothers with spontaneous labor onset.

Sex differences in the effects of mild traumatic brain injury and progesterone treatment on anxiety-like behavior and fear conditioning in rats.

Mild traumatic brain injuries (mild TBIs) commonly occur in young adults of both sexes, oftentimes in high-stress environments. In humans, sex differences have been observed in the development of post-concussive anxiety and PTSD-like behaviors. Progesterone, a sex steroid that has neuroprotective properties, restores cognitive function in animal models following more severe TBI, but its effectiveness in preventing the psychological symptoms associated with mild TBI has not been evaluated.

GABA Receptor and Serotonin Transporter Expression Changes Dissociate Following Mild Traumatic Brain Injury: Influence of Sex and Estrus Cycle Phase in Rats.

Mild traumatic brain injuries (mild TBIs) can affect both males and females, but females are more likely to report long-term psychological complications, including changes in mood and generalized anxiety. Additionally, reproductive cycle phase has been shown to affect mild TBI symptom expression within females. These variances may result from sex differences in mild TBI-induced alterations to neurotransmission in brain regions that influence mood and emotion, possibly mediated by sex steroids.

Chronic administration of glucocorticoid receptor ligands increases anxiety-like behavior and selectively increase serotonin transporters in the ventral hippocampus.

Organic cation transporter-3 (OCT3) is widely distributed in the brain with high expression in portions of the stress axis. These high capacity, polyspecific transporters function in monoamine clearance and are sensitive to the stress hormone corticosterone. In rats, withdrawal from chronic amphetamine increases OCT3 expression in specific limbic brain regions involved anxiety and stress responses, including the ventral hippocampus, central nucleus of amygdala (CeA) and dorsomedial hypothalamus.

Transmembrane Batten Disease Proteins Interact With a Shared Network of Vesicle Sorting Proteins, Impacting Their Synaptic Enrichment.

Batten disease is unique among lysosomal storage disorders for the early and profound manifestation in the central nervous system, but little is known regarding potential neuron-specific roles for the disease-associated proteins. We demonstrate substantial overlap in the protein interactomes of three transmembrane Batten proteins (CLN3, CLN6, and CLN8), and that their absence leads to synaptic depletion of key partners (i.e.

Author Correction: Characterization of a recurrent missense mutation in the forkhead DNA-binding domain of FOXP1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A multimodal approach to identify clinically relevant biomarkers to comprehensively monitor disease progression in a mouse model of pediatric neurodegenerative disease.

While research has accelerated the development of new treatments for pediatric neurodegenerative disorders, the ability to demonstrate the long-term efficacy of these therapies has been hindered by the lack of convincing, noninvasive methods for tracking disease progression both in animal models and in human clinical trials. Here, we unveil a new translational platform for tracking disease progression in an animal model of a pediatric neurodegenerative disorder, CLN6-Batten disease. Instead of looking at a handful of parameters or a single "needle in a haystack", we embrace the idea that disease progression, in mice and patients alike, is a diverse phenomenon best characterized by a combination of relevant biomarkers.

Therapeutic landscape for Batten disease: current treatments and future prospects.

Batten disease (also known as neuronal ceroid lipofuscinoses) constitutes a family of devastating lysosomal storage disorders that collectively represent the most common inherited paediatric neurodegenerative disorders worldwide. Batten disease can result from mutations in 1 of 13 genes. These mutations lead to a group of diseases with loosely overlapping symptoms and pathology.

Characterization of a recurrent missense mutation in the forkhead DNA-binding domain of FOXP1.

Haploinsufficiency of Forkhead box protein P1 (FOXP1), a highly conserved transcription factor, leads to developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. Most of the reported FOXP1 mutations occur on the C-terminus of the protein and cluster around to the forkhead domain. All reported FOXP1 pathogenic variants result in abnormal cellular localization and loss of transcriptional repression activity of the protein product.

Cultural and Social Predictors of Substance Abuse Recovery among American Indian and Non-American Indian Pregnant and Parenting Women.

Substance abuse is especially undesirable among pregnant or parenting women (PPW). As such, there is a need to examine the factors impacting positive treatment outcomes, particularly among American Indian/Alaska Native (AI/AN) PPW, as they are seeking substance abuse treatment at rates considerably higher than the national average. This study aimed to identify the social and cultural mechanisms that support their recovery.

A porcine model of neurofibromatosis type 1 that mimics the human disease.

Loss of the NF1 tumor suppressor gene causes the autosomal dominant condition, neurofibromatosis type 1 (NF1). Children and adults with NF1 suffer from pathologies including benign and malignant tumors to cognitive deficits, seizures, growth abnormalities, and peripheral neuropathies. NF1 encodes neurofibromin, a Ras-GTPase activating protein, and NF1 mutations result in hyperactivated Ras signaling in patients.

Genetic ataxia telangiectasia porcine model phenocopies the multisystemic features of the human disease.

Ataxia telangiectasia (AT) is a progressive multisystem autosomal recessive disorder caused by mutations in the AT-mutated (ATM) gene. Early onset AT in children is characterized by cerebellar degeneration, leading to motor impairment. Lung disease and cancer are the two most common causes of death in AT patients.

A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies.

The Neuronal Ceroid Lipofuscinoses (NCLs), also known as Batten disease, result from mutations in over a dozen genes. Although, adults are susceptible, the NCLs are frequently classified as pediatric neurodegenerative diseases due to their greater pediatric prevalence. Initial clinical presentation usually consists of either seizures or retinopathy but develops to encompass both in conjunction with declining motor and cognitive function.

Nonsense pathogenic variants in exon 1 of PHOX2B lead to translational reinitiation in congenital central hypoventilation syndrome.

Pathogenic variants in PHOX2B lead to congenital central hypoventilation syndrome (CCHS), a rare disorder of the nervous system characterized by autonomic dysregulation and hypoventilation typically presenting in the neonatal period, although a milder late-onset (LO) presentation has been reported. More than 90% of cases are caused by polyalanine repeat mutations (PARMs) in the C-terminus of the protein; however non-polyalanine repeat mutations (NPARMs) have been reported. Most NPARMs are located in exon 3 of PHOX2B and result in a more severe clinical presentation including Hirschsprung disease (HSCR) and/or peripheral neuroblastic tumors (PNTs).

Emergency Department Utilization for Mental Health in American Indian Children.

Objectives: To examine emergency department (ED) visits for mental health concerns by American Indian children in a multicenter cohort. To analyze demographic and clinical factors, the types of mental health concerns, and repeat mental health visits.

Study Design: Cross-sectional study of children 5-18 years old who visited 1 of 6 EDs in the Upper Midwest from June 2011 to May 2012 and self-identified as white or American Indian.

Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.

The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset.

Associations among family socioeconomic status, EEG power at birth, and cognitive skills during infancy.

Past research has demonstrated links between cortical activity, measured via EEG power, and cognitive processes during infancy. In a separate line of research, family socioeconomic status (SES) has been strongly associated with children's early cognitive development, with socioeconomic disparities emerging during the second year of life for both language and declarative memory skills. The present study examined associations among resting EEG power at birth, SES, and language and memory skills at 15-months in a sample of full-term infants.

Molecular Mechanisms of Cannabis Signaling in the Brain.

Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system.

Ceftriaxone attenuates acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens of the rat.

Background And Purpose: Ceftriaxone is a β-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens.

Expedited Operative Care of Hip Fractures Results in Significantly Lower Cost of Treatment.

Background: There are an estimated 150,000 hip fractures per year in the United States, with estimated costs of care between $10.3 billion and $15.2 billion.

OnabotulinumtoxinA Injections for the Treatment of Cyclic Vomiting Syndrome.

Cyclic vomiting syndrome (CVS) is a disorder characterized by episodes of nausea and vomiting lasting 1 to 5 days, followed by asymptomatic periods. The etiology and pathophysiology of CVS are unknown, but CVS shares similar characteristics to those of migraine headaches. Tricyclic antidepressants have the most evidence and are generally effective for prophylaxis of further episodes in patients with CVS.

Effective treatment of dyssynergic defecation using sacral neuromodulation in a patient with cerebral palsy.

Background: Dyssynergic defecation is a complex bowel problem that leads to chronic constipation and abdominal pain. Management is often challenging owing to the incoordination of multiple pelvic floor muscles involved in normal defecation.

Case: We report a case of dyssynergic defecatory dysfunction in a patient with cerebral palsy treated with sacral neuromodulation.