Identification of (PDZ-RhoGEF) as an in vivo regulator of synapses and cognition.

Given the influence of cognitive abilities on life outcomes, there is inherent value in identifying genes involved in controlling learning and memory. Further, cognitive dysfunction is a core feature of many neuropsychiatric disorders. Here, we use a combinatory in silico approach to identify human gene targets that will have an especially high likelihood of individually and directly impacting cognition.

Effects of interval treadmill training on spatiotemporal parameters in children with cerebral palsy: A machine learning approach.

Quantifying individualized rehabilitation responses and optimizing therapy for each person is challenging. For interventions like treadmill training, there are multiple parameters, such as speed or incline, that can be adjusted throughout sessions. This study evaluates if causal modeling and Bayesian Additive Regression Trees (BART) can be used to accurately track the direct effects of treadmill training on gait.

Development and validation of a stakeholder-driven, self-contained electronic informed consent platform for trio-based genomic research studies.

Increasingly long and complex informed consents have yielded studies demonstrating comparatively low participant and with traditional face-to-face approaches. In parallel, interest in electronic consents for clinical and research genomics has steadily increased, yet limited data are available for trio-based genomic discovery studies. We describe the design, development, implementation, and validation of an electronic iConsent application for trio-based genomic research deployed to support genomic studies of cerebral palsy.

Increased regional activity of a pro-autophagy pathway in schizophrenia as a contributor to sex differences in the disease pathology.

Based on recent genome-wide association studies, it is theorized that altered regulation of autophagy contributes to the pathophysiology of schizophrenia and bipolar disorder. As activity of autophagy-regulatory pathways is controlled by discrete phosphorylation sites on the relevant proteins, phospho-protein profiling is one of the few approaches available for enabling a quantitative assessment of autophagic activity in the brain. Despite this, a comprehensive phospho-protein assessment in the brains of schizophrenia and bipolar disorder subjects is currently lacking.

Assessing protein distribution and dendritic spine morphology relationships using structured illumination microscopy in cultured neurons.

Dendritic spines are protrusions on dendrites forming the postsynaptic aspect of excitatory connections within the brain. Spine morphology is associated with synaptic functional strength and the spatial regulation of protein nanodomains within dendritic spines is an important determinant of spine structure and function. Here, we present a protocol to resolve the nanoscale localization of proteins within dendritic spines using structured illumination microscopy.

A Mixed Methods Study of Practice Variation in Selective Dorsal Rhizotomy: A Study by the Cerebral Palsy Research Network.

Background: Selective dorsal rhizotomy (SDR) is an established procedure for the treatment of spasticity associated with cerebral palsy (CP). With the indications for the procedure expanding, we aimed to investigate provider perception about SDR candidates against the characteristics of those undergoing SDR in the CP Research Network (CPRN) registry.

Methods: This was a mixed methods study.

Stress-mediated dysregulation of the Rap1 small GTPase impairs hippocampal structure and function.

The effects of repeated stress on cognitive impairment are thought to be mediated, at least in part, by reductions in the stability of dendritic spines in brain regions critical for proper learning and memory, including the hippocampus. Small GTPases are particularly potent regulators of dendritic spine formation, stability, and morphology in hippocampal neurons. Through the use of small GTPase protein profiling in mice, we identify increased levels of synaptic Rap1 in the hippocampal CA3 region in response to escalating, intermittent stress.

Aberrant regulation of the Rap1 small GTPase in response to escalating, intermittent stress produces hippocampal synaptic and cognitive dysfunction.

The effects of repeated stress on cognitive impairment are thought to be mediated, at least in part, by reductions in the stability of dendritic spines in brain regions critical for proper learning and memory, including the hippocampus. Small GTPases are particularly potent regulators of dendritic spine formation, stability, and morphology in hippocampal neurons. Through the use of small GTPase protein profiling in mice, we identify increased levels of synaptic Rap1 in the hippocampal CA3 region in response to escalating, intermittent stress.

Supportive mobility devices across the lifespan in Cerebral Palsy: a modified Delphi study to establish stakeholder research priorities.

Purpose: The aim of this study was to co-develop research priorities and identify meaningful research questions with a diverse group of stakeholders representing the CP community for implementation in subsequent research activities. The overarching aim of this research was to 1) Understand the mobility experiences, supported mobility device (SMD) use, and desired participation outcomes of people with cerebral palsy (CP) across the lifespan; and 2) Describe how perspectives of rehabilitation care and professional resources may influence mobility decision-making processes and outcomes.

Materials And Methods: A three-round modified Delphi consensus study was conducted with a stakeholder advisory panel consisting of three adults with CP, two parents of children with CP, and four SMD providers.

Individualized orthotic alignment and footwear for balance and mobility in children with bilateral spastic cerebral palsy: A randomized trial.

Aim: To examine whether designed-to-be-rigid ankle-foot orthoses and footwear combinations with individualized alignment and footwear designs (AFO-FC/IAFD) would be more effective than designed-to-be-rigid AFO with non-individualized alignment and footwear designs (AFO-FC/NAFD) in children with cerebral palsy (CP).

Method: Nineteen children with bilateral spastic CP were randomized to AFO-FC/NAFD (n = 10) or AFO-FC/IAFD (n = 9) groups. Fifteen were male, average age 6 years 11 months (range 4 years 2 months-9 years 11 months), classified in Gross Motor Function Classification System levels II (n = 15) and III (n = 4).

"That's frustrating": Perceptions of ankle foot orthosis provision, use, and needs among people with cerebral palsy and caregivers.

Background: Cerebral palsy (CP) affects roughly 3 per 1000 births in the United States and is the most common pediatric developmental motor disability. Ankle foot orthoses (AFOs) are commonly prescribed to provide support and improve function for individuals with CP.

Objectives: The study objective was to evaluate the lived experiences of individuals with CP and their caregivers regarding AFO access, use, and priorities.

Supportive mobility device use across the life span by individuals with cerebral palsy: A qualitative study.

Aim: To understand the mobility experiences, supportive mobility device (SMD) use, and desired participation outcomes of individuals with cerebral palsy (CP) across the life span, and describe how perspectives of rehabilitation care and professional resources may influence mobility decision-making processes and outcomes.

Method: In the second phase of an overarching study, focus groups were conducted with 164 participants (68 individuals with CP; 32 females, 36 males; mean age 17y 8mo, SD 11y 11mo, range 3-68y), 74 caregivers (50 females, 24 males), and 22 healthcare providers (14 females, eight males) across four US cities. Sessions were audio-recorded, transcribed, and analysed using constant comparison.

Comparison of Sagittal Plane Stiffness of Nonarticulated Pediatric Ankle-Foot Orthoses Designed to be Rigid.

Introduction: When studying the effect of ankle-foot orthoses (AFOs) on gait, it is important to know their sagittal plane stiffness. However, there are no established thresholds for stiffness of non-articulated AFOs designed to be rigid. If wanting to implement published algorithms for ankle-foot orthosis-footwear combinations (AFO-FCs), the AFOs must be equally as stiff as those of the developer of the published AFO-FC algorithms.

Pseudopotentials for Electronic Structure Theory.

We present a general method of constructing pseodopotentials from first-principles, all-electron, and full-potential electronic structure calculations of a solid. The method is applied to bcc Na, at low-temperature equilibrium volume. The essential steps of the method involve (i) calculating an all-electron Kohn-Sham eigenstate, (ii) replacing the oscillating part of the wave function (inside the muffin-tin spheres) of this state, with a smooth function, (iii) representing the smooth wave function in a Fourier series, and (iv) inverting the Kohn-Sham equation, to extract the pseudopotential that produces the state generated in steps i-iii.

Effects of Orthoses on Standing Postural Control and Muscle Activity in Children With Cerebral Palsy.

Purpose: This exploratory study assessed postural control and muscle activity in children with cerebral palsy while standing barefoot (BF), in prescribed ankle-foot orthoses (AFOs) and in distal control orthoses (DCOs), which stabilized foot-ankle and deliberately aligned the shank.

Methods: This within-subject study evaluated 10 participants, Gross Motor Functional Classification System level III, across the 3 ankle-foot conditions in: (1) static standing duration and (2) modified Clinical Test of Sensory Interaction on Balance with electromyography (EMG) on 7 muscles.

Results: Participants had significantly decreased center of gravity (COG) velocity sway in DCO versus BF and AFO, decreased loss of balance (LOB), and increased standing for DCO versus BF.

Functional outcomes of pediatric patients in Short-term Pediatric Rehabilitation Intensive Therapy (SPRINT) while receiving acute oncologic and hematologic care.

Background: Pediatric patients with oncologic and hematologic diagnoses who experience newly acquired functional deficits during a hospitalization may benefit from intensive therapies. However, acute medical issues or disease treatment plans may prevent a safe transfer to the inpatient rehabilitation unit. Accordingly, Short-term Pediatric Rehabilitation Intensive Therapy (SPRINT), a 2-week inpatient intensive therapy program, was developed for pediatric patients on an acute care service.

Akt-mTOR hypoactivity in bipolar disorder gives rise to cognitive impairments associated with altered neuronal structure and function.

The Akt family of kinases exerts many of its cellular effects via the activation of the mammalian target of rapamycin (mTOR) kinase through a series of intermediary proteins. Multiple lines of evidence have identified Akt-family kinases as candidate schizophrenia and bipolar disorder genes. Although dysfunction of the prefrontal cortex (PFC) is a key feature of both schizophrenia and bipolar disorder, no studies have comprehensively assessed potential alterations in Akt-mTOR pathway activity in the PFC of either disorder.

Physical Activity Measurement in Children Who Use Mobility Assistive Devices: Accelerometry and Global Positioning System.

Purpose: To explore the usefulness of combining accelerometry, global positioning systems, and geographic information systems, to describe the time spent in different locations and physical activity (PA) duration/count levels by location for 4 children with cerebral palsy (CP) who use assistive devices (AD).

Methods: A descriptive multiple-case study.

Results: Combining the 3 instruments was useful in describing and differentiating duration by location, and amount and location of PA across differing functional levels and AD.

Evaluation of a passive pediatric leg exoskeleton during gait.

Background: Children with hemiparesis are commonly prescribed ankle foot orthoses to help improve gait; however, these orthoses often result in only small and variable changes in gait. Research with adult stroke survivors has suggested that orthoses that extend beyond the ankle using long, passive tendon-like structures (i.e.

Accelerometer Measurements Indicate That Arm Movements of Children With Cerebral Palsy Do Not Increase After Constraint-Induced Movement Therapy (CIMT).

Importance: Constraint-induced movement therapy (CIMT) is a common treatment for children with unilateral cerebral palsy (CP). Although clinic-based assessments have demonstrated improvements in arm function after CIMT, whether these changes are translated and sustained outside of a clinic setting remains unclear.

Objective: Accelerometers were used to quantify arm movement for children with CP 1 wk before, during, and 4 wk or more after CIMT; measurements were compared with those from typically developing (TD) peers.

[F]FEPPA PET imaging for monitoring CD68-positive microglia/macrophage neuroinflammation in nonhuman primates.

Purpose: The aim of this study was to examine whether the translocator protein 18-kDa (TSPO) PET ligand [F]FEPPA has the sensitivity for detecting changes in CD68-positive microglial/macrophage activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (iPSC-mDA).

Methods: In vivo positron emission tomography (PET) imaging with [F]FEPPA was used in conjunction with postmortem CD68 immunostaining to evaluate neuroinflammation in the brains of hemiparkinsonian rhesus macaques (n = 6) that received allogeneic iPSC-mDA grafts in the putamen ipsilateral to MPTP administration.

Results: Based on assessment of radiotracer uptake and confirmed by visual inspection of the imaging data, nonhuman primates with allogeneic grafts showed increased [F]FEPPA binding at the graft sites relative to the contralateral putamen.

The Rap1 small GTPase is a critical mediator of the effects of stress on prefrontal cortical dysfunction.

The neural molecular and biochemical response to stress is a distinct physiological process, and multiple lines of evidence indicate that the prefrontal cortex (PFC) is particularly sensitive to, and afflicted by, exposure to stress. Largely through this PFC dysfunction, stress has a characterized role in facilitating cognitive impairment, which is often dissociable from its effects on non-cognitive behaviors. The Rap1 small GTPase pathway has emerged as a commonly disrupted intracellular target in neuropsychiatric conditions, whether it be via alterations in Rap1 expression or through alterations in the expression of direct and specific upstream Rap1 activators and inhibitors.