Major Impacts of Widespread Structural Variation on Gene Expression and Crop Improvement in Tomato.

Structural variants (SVs) underlie important crop improvement and domestication traits. However, resolving the extent, diversity, and quantitative impact of SVs has been challenging. We used long-read nanopore sequencing to capture 238,490 SVs in 100 diverse tomato lines. This panSV genome, along with 14 new reference assemblies, revealed large-scale intermixing of diverse genotypes, as well as thousands of SVs intersecting genes and cis-regulatory regions. Hundreds of SV-gene pairs exhibit subtle and significant expression changes, which could broadly influence quantitative trait variation. By combining quantitative genetics with genome editing, we show how multiple SVs that changed gene dosage and expression levels modified fruit flavor, size, and production. In the last example, higher order epistasis among four SVs affecting three related transcription factors allowed introduction of an important harvesting trait in modern tomato. Our findings highlight the underexplored role of SVs in genotype-to-phenotype relationships and their widespread importance and utility in crop improvement.

Dynamic Organization of Neuronal Extracellular Matrix Revealed by HaloTag-HAPLN1.

The brain's extracellular matrix (ECM) regulates neuronal plasticity and animal behavior. ECM staining shows a net-like structure around a subset of neurons, a ring-like structure at the nodes of Ranvier, and diffuse staining in the interstitial matrix. However, understanding the structural features of ECM deposition across various neuronal types and subcellular compartments remains limited. To visualize the organization pattern and assembly process of the hyaluronan-scaffolded ECM in the brain, we fused a HaloTag to hyaluronan proteoglycan link protein 1, which links hyaluronan and proteoglycans. Expression or application of the probe in primary rat neuronal cultures enables us to identify spatial and temporal regulation of ECM deposition and heterogeneity in ECM aggregation among neuronal populations. Dual-color birthdating shows the ECM assembly process in culture and in vivo. Sparse expression in mouse brains of either sex reveals detailed ECM architectures around excitatory neurons and developmentally regulated dendritic ECM. Our study uncovers extensive structural features of the brain's ECM, suggesting diverse roles in regulating neuronal plasticity.

Repeated LPS induces training and tolerance of microglial responses across brain regions.

BACKGROUND: Neuroinflammation is involved in the pathogenesis of almost every central nervous system disorder. As the brain's innate immune cells, microglia fine tune their activity to a dynamic brain environment. Previous studies have shown that repeated bouts of peripheral inflammation can trigger long-term changes in microglial gene expression and function, a form of innate immune memory. METHODS AND RESULTS: In this study, we used multiple low-dose lipopolysaccharide (LPS) injections in adult mice to study the acute cytokine, transcriptomic, and microglia morphological changes that contribute to the formation of immune memory in the frontal cortex, hippocampus, and striatum, as well as the long-term effects of these changes on behavior. Training and tolerance of gene expression was shared across regions, and we identified 3 unique clusters of DEGs (2xLPS-sensitive, 4xLPS-sensitive, LPS-decreased) enriched for different biological functions. 2xLPS-sensitive DEG promoters were enriched for binding sites for IRF and NFkB family transcription factors, two key regulators of innate immune memory. We quantified shifts in microglia morphological populations and found that while the proportion of ramified and rod-like microglia mostly remained consistent within brain regions and sexes with LPS treatment, there was a shift from ameboid towards hypertrophic morphological states across immune memory states and a dynamic emergence and resolution of events of microglia aligning end-to-end with repeated LPS. CONCLUSIONS: Together, findings support the dynamic regulation of microglia during the formation of immune memories in the brain and support future work to exploit this model in brain disease contexts.

Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.

Commentary on stimulus-induced arousal with transient electroencephalographic improvement distinguishes nonictal from ictal generalized periodic discharges.

Here we critique recent arguments proposing to distinguish ictal from non-ictal generalized periodic discharges (GPDs) based on etiology and stimulation response, arguing that these are unreliable. We advocate for an empirical approach to GPDs: describe objectively, interpret through medication trials, and base further treatment on response. We call for evidence-based approaches considering meaningful clinical outcomes.

Prognostic Implications of Early Prediction in Posttraumatic Epilepsy.

Posttraumatic epilepsy (PTE) is a complication of traumatic brain injury that can increase morbidity, but predicting which patients may develop PTE remains a challenge. Much work has been done to identify a variety of risk factors and biomarkers, or a combination thereof, for patients at highest risk of PTE. However, several issues have hampered progress toward fully adapted PTE models. Such issues include the need for models that are well-validated, cost-effective, and account for competing outcomes like death. Additionally, while an accurate PTE prediction model can provide quantitative prognostic information, how such information is communicated to inform shared decision-making and treatment strategies requires consideration of an individual patient's clinical trajectory and unique values, especially given the current absence of direct anti-epileptogenic treatments. Future work exploring approaches integrating individualized communication of prediction model results are needed.

Immune checkpoint inhibitor-induced lichenoid drug eruption-sparing scar burns.

The authors present a striking case of a patient experiencing a lichenoid drug eruption secondary to immunotherapy, curiously sparing scarred skin from past burns. We observed vastly higher amounts of inflammatory lymphoid cells staining for PD-1; 70% in skin with a lichenoid drug reaction and 50% in scarred skin. The lack of a lichenoid reaction at sites of scarred skin may indicate that a basement membrane component may be causative for a lichenoid drug eruption.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

BACKGROUND: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. METHODS: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. RESULTS: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). CONCLUSIONS: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Impact of a Cancer Survivorship Continuing Medical Education Course on Learners' Attitudes and Intention to Change Practice.

An innovative, case-based continuing medical education course, Health After Cancer: Cancer Survivorship for Primary Care, was developed to engage clinicians in cancer survivorship care. A post-course survey measured the educational impact of the course on learners' intentions to change practice and changes in attitudes related to interprofessional collaborative practice. Qualitative analysis of free text responses was performed using the immersion-crystallization method. Learners earning continuing education credit (N = 1202) completed the post-course evaluation survey: 17.4% physicians, 8.0% advanced practice providers, 56.7% nurses, 2.2% pharmacists, 15.7% other health professionals. Learners' intended practice changes included improving communication (N = 438), incorporating knowledge into practice (N = 282), prioritizing survivorship clinical care (N = 167), and increasing oncology-primary care collaboration for patients (N = 53). Responses frequently involved more than one theme. Specific actions or knowledge that learners intended to incorporate into practice included improving their assessment of cancer survivor's risk and concerns (N = 128), incorporating knowledge of late effects of cancer treatment into practice (N = 122), educating patients about survivorship topics (N = 117), increasing empathy and understanding of survivors' experiences (N = 94), improving listening skills (N = 70), and dedicating more time to survivorship care (N = 63). Learners' changes in attitudes reflected an increased appreciation for collaboration, especially between oncology and primary care clinicians. A continuing medical education course designed to drive interest in engaging with cancer survivorship topics was effective at shaping learners' attitudes and intent to change practice, and has the potential to improve communication, care coordination, and healthcare experiences of cancer survivors.

Deep Learning Applications for Acute Stroke Management.

Brain imaging is essential to the clinical care of patients with stroke, a leading cause of disability and death worldwide. Whereas advanced neuroimaging techniques offer opportunities for aiding acute stroke management, several factors, including time delays, inter-clinician variability, and lack of systemic conglomeration of clinical information, hinder their maximal utility. Recent advances in deep machine learning (DL) offer new strategies for harnessing computational medical image analysis to inform decision making in acute stroke. We examine the current state of the field for DL models in stroke triage. First, we provide a brief, clinical practice-focused primer on DL. Next, we examine real-world examples of DL applications in pixel-wise labeling, volumetric lesion segmentation, stroke detection, and prediction of tissue fate postintervention. We evaluate recent deployments of deep neural networks and their ability to automatically select relevant clinical features for acute decision making, reduce inter-rater variability, and boost reliability in rapid neuroimaging assessments, and integrate neuroimaging with electronic medical record (EMR) data in order to support clinicians in routine and triage stroke management. Ultimately, we aim to provide a framework for critically evaluating existing automated approaches, thus equipping clinicians with the ability to understand and potentially apply DL approaches in order to address challenges in clinical practice. ANN NEUROL 2022;92:574-587.

Proteomic profiling of cutaneous melanoma explains the aggressiveness of distant organ metastasis.

Despite recent developments in managing metastatic melanomas, patients' overall survival remains low. Therefore, the current study aims to understand better the proteome-wide changes associated with melanoma metastasis that will assist with identifying targeted therapies. The latest development in mass spectrometry-based proteomics, together with extensive bioinformatics analysis, was used to investigate the molecular changes in 60 formalin-fixed and paraffin-embedded samples of primary and lymph nodes (LN) and distant organ metastatic melanomas. A total of 4631 proteins were identified, of which 72 and 453 were significantly changed between the LN and distant organ metastatic melanomas compared to the primary lesions (adj. p-value <0.05). An increase in proteins such as SLC9A3R1, CD20 and GRB2 and a decrease in CST6, SERPINB5 and ARG1 were associated with regional LN metastasis. By contrast, increased metastatic activities in distant organ metastatic melanomas were related to higher levels of CEACAM1, MC1R, AKT1 and MMP3-9 and decreased levels of CDKN2A, SDC1 and SDC4 proteins. Furthermore, machine learning analysis classified the lesions with up to 92% accuracy based on their metastatic status. The findings from this study provide up to date proteome-level information about the progression of melanomas to regional LN and distant organs, leading to the identification of protein signatures with potential for clinical translation.

Quantitative epileptiform burden and electroencephalography background features predict post-traumatic epilepsy.

BACKGROUND: Post-traumatic epilepsy (PTE) is a severe complication of traumatic brain injury (TBI). Electroencephalography aids early post-traumatic seizure diagnosis, but its optimal utility for PTE prediction remains unknown. We aim to evaluate the contribution of quantitative electroencephalograms to predict first-year PTE (PTE1). METHODS: We performed a multicentre, retrospective case-control study of patients with TBI. 63 PTE1 patients were matched with 63 non-PTE1 patients by admission Glasgow Coma Scale score, age and sex. We evaluated the association of quantitative electroencephalography features with PTE1 using logistic regressions and examined their predictive value relative to TBI mechanism and CT abnormalities. RESULTS: In the matched cohort (n=126), greater epileptiform burden, suppression burden and beta variability were associated with 4.6 times higher PTE1 risk based on multivariable logistic regression analysis (area under the receiver operating characteristic curve, AUC (95% CI) 0.69 (0.60 to 0.78)). Among 116 (92%) patients with available CT reports, adding quantitative electroencephalography features to a combined mechanism and CT model improved performance (AUC (95% CI), 0.71 (0.61 to 0.80) vs 0.61 (0.51 to 0.72)). CONCLUSIONS: Epileptiform and spectral characteristics enhance covariates identified on TBI admission and CT abnormalities in PTE1 prediction. Future trials should incorporate quantitative electroencephalography features to validate this enhancement of PTE risk stratification models.

Trends in Light and Temperature Sensitivity Recommendations among Licensed Biotechnology Drug Products.

PURPOSE: Inherent structural and functional properties of biotechnology-derived therapeutic biologics make them susceptible to light- and temperature-induced degradation and consequently can influence their quality. Photosensitivity of therapeutic proteins continues to be examined, but the commonalities and trends of storage conditions and information about light and temperature sensitivity among currently licensed therapeutic proteins has not been previously surveyed. METHODS: Using a comprehensive and relational database approach, we conducted a scientific survey of all licensed biotechnology-derived drug products with the goal of providing evidence-based information about recommended storage conditions of formulations sorted by light- and temperature-related attributes as described for each product at licensure. RESULTS: We report the prevalence of indications for light and temperature sensitivity in formulations categorized by their presentation type, number of doses, container type, dosage form and active molecule type. We also report the storage temperature range across formulations and diluents for reconstitution and dilution. Formulations with excipients that potentially facilitate light-induced and thermal degradation were also noted. CONCLUSIONS: The result of our analysis indicates that light and temperature sensitivity are prevalent across therapeutic protein formulations. However, when a formulation is reconstituted or diluted, both light and temperature sensitivity are less clear. In addition, light and temperature sensitivity are more well defined in liquid formulations than lyophilized powder formulations, and more well defined in products manufactured in autoinjectors, prefilled-syringes, and pens than products in vials. Overall, our report provides a data-driven summary of storage conditions among therapeutic protein formulations to support the development of future biologic drug products.

Same-day versus staged revascularization of bilateral moyamoya arteriopathy in pediatric patients.

PURPOSE: To compare the outcomes of conducting left and right hemisphere surgical revascularization on the same day versus different days for bilateral pediatric moyamoya arteriopathy patients. METHODS: We retrospectively analyzed mortality, stroke, and transient neurologic event (TNE) rates in North American bilateral pediatric moyamoya arteriopathy patients who underwent bilateral cerebral revascularization. RESULTS: A total of 38 pediatric (≤ 18 years old) patients at our institution underwent bilateral cerebral revascularization for moyamoya arteriopathy. Of these patients, 24 (63.2%) had both operations on the same day and 14 (36.8%) had the two operations on different days. The average length of stay for patients who underwent same-day bilateral revascularization was 6.9 ± 2.0 days and the average length of stay for each operation for patients who underwent staged bilateral revascularization was 4.5 ± 1.4 days, p = 0.001. While there were 7 (14.6%) postoperative strokes in patients who had both hemispheres revascularized on the same day, 0 (0%) strokes occurred in hemispheres after they had been operated on in the staged cohort, p = 0.042. Additionally, the postoperative stroke-free survival time in the ipsilateral hemisphere and TNE-free survival time were significantly longer in patients in the staged revascularization cohort. CONCLUSION: Same-day bilateral revascularization was associated with longer length of stay per operation, higher rate of ipsilateral stroke, and shorter postoperative TNE-free and stroke-free survival time in the revascularized hemisphere.

Impact of Race/Ethnicity and Insurance Status on Obstetric Outcomes: Secondary Analysis of the NuMoM2b Study.

OBJECTIVE: This study aimed to investigate the impact of race/ethnicity and insurance status on obstetric outcomes in nulliparous women. STUDY DESIGN: Secondary analysis of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-To-Be. Obstetric outcomes included the development of a hypertensive event during pregnancy, need for a cesarean section, delivery of a preterm neonate, and postpartum hemorrhage. RESULTS: Of 7,887 nulliparous women, 64.7% were non-Hispanic White (White), 13.4% non-Hispanic Black (Black), 17.8% Hispanic, and 4.1% were Asian. Black women had the highest rates of developing new-onset hypertension (32%) and delivering preterm (11%). Cesarean deliveries were the highest in Asian (32%) and Black women (32%). Individuals with government insurance were more likely to deliver preterm (11%) and/or experience hemorrhage after delivery. In multivariable analyses, race/ethnicity was associated with hypertension and cesarean delivery. More important, the adjusted odds ratios for preventable risk factors, such as obesity, diabetes, and severe anemia were greater than the adjusted odds ratios for race/ethnicity in terms of poor maternal outcome. CONCLUSION: Although disparities were observed between race/ethnicity and obstetric outcomes, other modifiable risk factors played a larger role in clinical differences. KEY POINTS: · Race or insurance alone had mixed associations with maternal morbidities.. · Race and insurance had low associations with maternal morbidities.. · Other, modifiable risk factors may be more important.. · Both social and biological factors impact health disparities..

Changes in Telehealth Experienced by Advanced Practice RNs During COVID-19: US Survey Results.

The sudden, expanded need for telehealth during the COVID-19 pandemic added to the challenges advanced practice RNs face in the United States. The purposes of this article are to summarize advanced practice RNs' responses about the use of telehealth before and during the pandemic and to analyze free-text comments about how the use of telehealth changed during the pandemic. A 20-item survey was distributed using convenience sampling to advanced practice RNs from June 1 to September 23, 2020. Analyses of descriptive and open text responses related to telehealth were conducted. Most of the respondents did not use telehealth prior to the pandemic (n = 5441 [73%]), but during the pandemic, half used telehealth at least daily (n = 3682 [49%]). The most common barriers related to telehealth were about the difficulty some populations had in accessing the necessary technology. The most common favorable comments cited by respondents were related to some patients' improved access to care. Telehealth use is unlikely to return to prepandemic levels. As a result, considerations of telehealth-related recommendations provided for advanced practice RN education, policy, and practice are encouraged for the purpose of increasing healthcare access.

Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes.

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.

A Quantitative Evaluation of Functional Recovery after Traumatic Lower Extremity Salvage.

INTRODUCTION: Soft tissue reconstruction is a routine component of lower extremity trauma care and focus is increasingly being directed towards understanding functional outcomes. This study aims to quantify functional recovery and identify variables associated with functional outcomes of patients who undergo traumatic limb salvage. METHODS: A retrospective review was performed of patients with lower extremity traumatic injuries requiring vascularized soft tissue reconstruction at a Level 1 trauma center between July 2007-December 2015. Postoperatively, patients were administered the 36-Item Short Form Health Survey Version 2 (SF-36v2) and the Lower Extremity Functional Scale (LEFS) questionnaires by telephone. Demographics, perioperative variables, and postoperative outcomes were analyzed by univariate and bivariate analysis. RESULTS: Forty-two patients with 42 flaps and a mean of 12.7 months follow up were included in the study. Limb salvage was successful in 38 patients (90.5%). Patients ≥ 40 years old had significantly worse SF-36v2 scores in physical functioning (P ≤0.01) and mental health (P ≤0.05) than their younger counterparts. Patients who had pre-existing hypertension demonstrated significantly lower physical functioning (P ≤0.01). Role limitation due to emotional health was significantly lower in patients who were female (P ≤0.01) or required revision surgery (P ≤0.01). The mean LEFS score was 37.7 ± 18.5. CONCLUSIONS: Patients exhibited poor functional outcomes following major limb trauma with attempted limb salvage based on two validated patient reported outcomes measures (PROMs). Patient characteristics should be considered in evaluating candidates for reconstruction to optimize outcomes and to effectively counsel patients on their functional prognosis.

Efficient Nicotinamide Adenine Dinucleotide Regeneration with a Rhodium-Carbene Catalyst and Isolation of a Hydride Intermediate.

Regeneration of nicotinamide adenine dinucleotide (NADH) has been the primary interest in the field of enzymatic transformation, especially associating oxidoreductases given the stoichiometric consumption. The synthesized carbene-ligated rhodium complex [(η5-Cp*)Rh(MDI)Cl]+ [Cp* = pentamethylcyclopentadienyl; MDI = 1,1'-methylenebis(3,3'-dimethylimidazolium)] acts as an exceptional catalyst in the reduction of NAD+ to NADH with a turnover frequency of 1730 h-1, which is over twice that of the higher catalytic activity of the commercially available catalyst [Cp*Rh(bpy)Cl]+ (bpy = 2,2'-bipyridine). Offsetting the contentious atmosphere currently taking place over the specific intermediate of the NADH regeneration, this study presents pivotal evidence of a metal hydride intermediate with a bis(carbene) ligand: a stable form of the rhodium hydride intermediate, [(η5-Cp*)Rh(MDI)H]+, was isolated and fully characterized. This enables thorough insight into the possible mechanism and exact intermediate structure in the NAD+ reduction process.

Corticomuscular coherence is reduced in relation to dorsiflexion fatigability to the same extent in adults with cerebral palsy as in neurologically intact adults.

PURPOSE: Fatigue is frequent in adults with cerebral palsy (CP) and it is unclear whether this is due to altered corticospinal drive. We aimed to compare changes in corticospinal drive following sustained muscle contractions in adults with CP and neurologically intact (NI) adults. METHODS: Fourteen adults with CP [age 37.6 (10.1), seven females, GMFCS levels I-II] and ten NI adults [age 35.4 (10.3), 6 females] performed 1-min static dorsiflexion at 30% of maximal voluntary contraction (MVC) before and after a submaximal contraction at 60% MVC. Electroencephalography (EEG) and electromyography (EMG) from the anterior tibial muscle were analyzed to quantify the coupling, expressed by corticomuscular coherence (CMC). RESULTS: Adults with CP had lower MVCs but similar time to exhaustion during the relative load of the fatigability trial. Both groups exhibited fatigability-related changes in EMG median frequency and EMG amplitude. The CP group showed lower beta band (16-35 Hz) CMC before fatigability, but both groups decreased beta band CMC following fatigability. There was a linear correlation between decrease of beta band CMC and fatigability-related increase in EMG. CONCLUSION: Fatigability following static contraction until failure was related to decreased beta band CMC in both NI adults and adults with CP. Our findings indicate that compensatory mechanisms to fatigability are present in both groups, and that fatigability affects the corticospinal drive in the same way. We suggest that the perceived physical fatigue in CP is related to the high relative load of activities of daily living rather than any particular physiological mechanism.