Normative Values for the Head Shake Sensory Organization Test in an Active Duty Military Cohort.

INTRODUCTION: The Head Shake Sensory Organization Test (HS-SOT) assesses postural stability while the head is moving and may also identify deficits in attention associated with the dual task conditions of moving the head at a specified speed while maintaining balance. Normative values for the HS-SOT have not been established in a healthy military population or other highly trained populations such as athletes. Establishing normative values in a military population will enable clinicians to compare the scores of patients with medical conditions that affect postural stability and sensory integration such as concussion or traumatic brain injury, vestibular dysfunction, or migraine to those of a healthy population to determine a need for intervention and for return to duty considerations. The purposes of this cross-sectional study were to establish normative values for the HS-SOT within the military population, to determine whether HS-SOT scores differed between men and women or among age groups, and to determine whether HS-SOT scores differed from scores on similar conditions of the Sensory Organization Test (SOT). MATERIALS AND METHODS: Active duty service members (n = 237, 54 female) at Joint Base Lewis-McChord, Washington, Fort Campbell, Kentucky, and the National Capitol Region (Washington, D.C, Maryland, and Virginia) completed the SOT and HS-SOT on the NeuroCom® Balance Master™. Parametric and non-parametric comparisons were analyzed for the equilibrium scores for the SOT and HS-SOT conditions 2 (SOT-2, HS-SOT-2, respectively) and 5 (SOT-5, HS-SOT-5, respectively) and the equilibrium score ratios (ESRs) for HS-SOT-2 and HS-SOT-5 for the total sample, men and women, and age group categories (18-26 years, 27-35 years, and 36-45 years). RESULTS: There were no differences in HS-SOT-2 or HS-SOT-5 equilibrium ratio scores between men (0.99 ±.029 and 0.83 ±0.25, respectively) and women (1.00 ±0.03 and 0.81 ±0.21, respectively). There were no differences in the SOT-2 equilibrium scores (F = 2.29, P = 0.10) or SOT-5 equilibrium scores (Kruskal-Wallis H = 3.26, P = 0.20) among the different age groups. SOT-2 equilibrium scores were higher than the HS-SOT-2 equilibrium scores (Z = -4.10, P < 0.001). SOT-5 equilibrium scores were also higher than HS-SOT-5 equilibrium scores (Z = -12.22, P < 0.001), and the HS-SOT-2 and HS-SOT-5 equilibrium scores differed from each other (Z = -13.26, P < 0.001). CONCLUSIONS: This study established normative values for the HS-SOT in a military population. Equilibrium scores did not differ between men and women or among age groups, suggesting that these values can be used as reference points for most service members. Postural stability was found to be significantly challenged during head motion, indicating the HS-SOT is a valuable tool for identifying subtle impairments in postural stability. These findings have important implications for early detection and intervention in individuals with medical conditions affecting balance, particularly concussions or vestibular disorders.

Gold Nanotapes and Nanopinecones in a Quantitative Lateral Flow Assay for the Cancer Biomarker Carcinoembryonic Antigen.

Colorectal cancer is the third most common malignancy and the second leading cause of cancer death globally. Multiple studies have linked levels of carcinoembryonic antigen in patient serum to poor disease prognosis. Hence, the ability to detect low levels of carcinoembryonic antigen has applications in earlier disease diagnosis, assessment, and recurrence monitoring. Existing carcinoembryonic antigen detection methods often require multiple reagents, trained operators, or complex procedures. A method alleviating these issues is the lateral flow assay, a paper-based platform that allows the detection and quantification of target analytes in complex mixtures. The tests are rapid, are point-of-care, possess a long shelf life, and can be stored at ambient conditions, making them ideal for use in a range of settings. Although lateral flow assays typically use spherical gold nanoparticles to generate the classic red signal, recent literature has shown that alternate morphologies to spheres can improve the limit of detection. In this work, we report the application of alternative gold nanoparticle morphologies, gold nanotapes (∼35 nm in length) and gold nanopinecones (∼90 nm in diameter), in a lateral flow assay for carcinoembryonic antigen. In a comparative assay, gold nanopinecones exhibited a ∼2× improvement in the limit of detection compared to commercially available spherical gold nanoparticles for the same antibody loading and total gold content, whereas the number of gold nanopinecones in each test was ∼3.2× less. In the fully optimized test, a limit of detection of 14.4 pg/mL was obtained using the gold nanopinecones, representing a 24-fold improvement over the previously reported gold-nanoparticle-based carcinoembryonic antigen lateral flow assay.

State of the Evidence for Use of Psychotropic Medications in School-Age Youth.

Psychotropic medications are commonly prescribed to school-aged youth for the management of mental health concerns. This paper describes the current state of evidence for psychotropic medications in school-aged youth. More specifically, the following sections summarize relevant medication research trials and practice parameters pertaining to psychotropic medication prescribing as well as the specific medications indicated for a range of commonly presenting disorders and symptom clusters in school-aged youth. For each of these disorders and symptom clusters, key findings pertaining to the current state of science and practice are highlighted for the purpose of offering patients, clinicians, researchers, and policymakers with nuanced considerations for the role of psychopharmacology within the context of a larger "whole-child" approach to care that relies on the collaboration of providers and services across systems of care to promote optimal child and family health and wellness. The paper concludes with a discussion about supporting the use of medication treatments in schools, including considerations for ensuring effective family-school-health system collaboration to best meet youth mental health needs.

Genetic Covariation Between the Vertically Transmitted Endophyte Epichloë canadensis and Its Host Canada Wildrye.

Symbiotic mutualisms are thought to be stabilized by correlations between the interacting genotypes which may be strengthened via vertical transmission and/or reduced genetic variability within each species. Vertical transmission, however, may weaken interactions over time as the endosymbionts would acquire mutations that could not be purged. Additionally, temporal variation in a conditional mutualism could create genetic variation and increased variation in the interaction outcome. In this study, we assessed genetic variation in both members of a symbiosis, the endosymbiotic fungal endophyte Epichloë canadensis and its grass host Canada wildrye (Elymus canadensis). Both species exhibited comparable levels of diversity, mostly within populations rather than between. There were significant differences between populations, although not in the same pattern for the two species, and the differences were not correlated with geographic distance for either species. Interindividual genetic distance matrices for the two species were significantly correlated, although all combinations of discriminant analysis of principle components (DAPC) defined multilocus genotype groups were found suggesting that strict genotype matching is not necessary. Variation in interaction outcome is common in grass/endophyte interactions, and our results suggest that the accumulation of mutations overtime combined with temporal variation in selection pressures increasing genetic variation in the symbiosis may be the cause.

Tomato receptor-like cytoplasmic kinase Fir1 is involved in flagellin signaling and preinvasion immunity.

Detection of bacterial flagellin by the tomato (Solanum lycopersicum) receptors Flagellin sensing 2 (Fls2) and Fls3 triggers activation of pattern-triggered immunity (PTI). We identified the tomato Fls2/Fls3-interacting receptor-like cytoplasmic kinase 1 (Fir1) protein that is involved in PTI triggered by flagellin perception. Fir1 localized to the plasma membrane and interacted with Fls2 and Fls3 in yeast (Saccharomyces cerevisiae) and in planta. CRISPR/Cas9-generated tomato fir1 mutants were impaired in several immune responses induced by the flagellin-derived peptides flg22 and flgII-28, including resistance to Pseudomonas syringae pv. tomato (Pst) DC3000, production of reactive oxygen species, and enhanced PATHOGENESIS-RELATED 1b (PR1b) gene expression, but not MAP kinase phosphorylation. Remarkably, fir1 mutants developed larger Pst DC3000 populations than wild-type plants, whereas no differences were observed in wild-type and fir1 mutant plants infected with the flagellin deficient Pst DC3000ΔfliC. fir1 mutants failed to close stomata when infected with Pst DC3000 and Pseudomonas fluorescens and were more susceptible to Pst DC3000 than wild-type plants when inoculated by dipping, but not by vacuum-infiltration, indicating involvement of Fir1 in preinvasion immunity. RNA-seq analysis detected fewer differentially expressed genes in fir1 mutants and altered expression of jasmonic acid (JA)-related genes. In support of JA response deregulation in fir1 mutants, these plants were similarly susceptible to Pst DC3000 and to the coronatine-deficient Pst DC3118 strain, and more resistant to the necrotrophic fungus Botrytis cinerea following PTI activation. These results indicate that tomato Fir1 is required for a subset of flagellin-triggered PTI responses and support a model in which Fir1 negatively regulates JA signaling during PTI activation.

The impact of clinical trial enrollment on specialty palliative care utilization in pediatric patients with high-grade gliomas.

BACKGROUND: Palliative care (PC) provides numerous benefits for children with cancer. Pediatric patients with high-grade glioma (HGG) are particularly well suited for early PC involvement given their high symptom burden and poor prognosis. However, studies continue to reveal that children with cancer, including HGG, have delayed PC involvement. We hypothesized that clinical trial enrollment may lead to a lack of or delay in PC involvement in this population. PROCEDURE: For each patient in our cohort of 43 pediatric patients with HGG, demographic, diagnostic, therapeutic, clinical trial enrollment, and PC information were collected. Statistical analysis was performed comparing PC characteristics between patients who did and did not enroll in a clinical trial. RESULTS: Seventy-two percent of patients had at least one visit with a PC provider. Fifty-six percent of patients enrolled in a clinical trial with HGG-directed therapy. Seventy-one percent of patients who enrolled in a clinical trial received specialty PC compared to 74% of non-trial participants (p = 1.000). Patients who enrolled in clinical trials received PC earlier in their disease course measured in days before death (mean = 177 days) compared to those who did not enroll (mean = 113 days, p = .180), though not statistically significant. CONCLUSIONS: The prevalence of clinical trial enrollment is high in patients with HGG and will likely increase as the genomic/epigenomic landscape of these tumors is better understood. As such, our data reassuringly suggest that trial participation does not interfere with the receipt of specialty PC in this population.

Balance Confidence and Balance Performance, But Not Fall History Are Associated With Quality of Life in Community-Dwelling Older Adults: A Cross Sectional Study.

BACKGROUND AND PURPOSE: Fear of falling (FoF) is highly prevalent in community-dwelling older adults and is associated with low health-related quality of life (QoL). Low QoL is associated with increased health care utilization and is a predictor of future falls, but few studies have examined the relationship between high-level balance and dynamic gait performance and QoL in community-dwelling older adults. The purpose of this cross-sectional study was to determine whether there is a relationship between FoF avoidance behaviors, balance confidence, performance on measures of high-level mobility, and QoL in community-dwelling older adults. The secondary purpose was to determine whether older adults who fall have a different QoL than older adults who have not fallen in the past year. METHODS: Eighty-nine community-dwelling older adults (76.33 ± 6.84 years, 54 female, 34 fallers) completed the World Health Organization Quality of Life-BREF (WHOQOL-BREF), Activities-specific Balance Confidence Scale (ABC), Fear of Falling Avoidance Behavior Questionnaire (FFABQ), Functional Gait Assessment (FGA), and Community Balance and Mobility Scale (CB&M). Correlation and multiple regression analyses were calculated to determine the relationship between the outcome measures and domains on the WHOQOL-BREF. RESULTS AND DISCUSSION: Significant correlations were observed between the WHOQOL-BREF physical health domain and the ABC, FFABQ, FGA, and CB&M (ρ= 0.524, -0.509, 0.348, and r = 0.423, respectively), the WHOQOL-BREF psychological domain and the ABC (ρ= 0.284) and FFABQ (ρ=-0.384), and the WHOQOL-BREF environment domain and the ABC (ρ= 0.343) and FFABQ (ρ=-0.406). No correlations were found between WHOQOL-BREF domain scores and a history of falls. CONCLUSIONS: Performance-based outcome measures that measure high-level mobility such as the CB&M and FGA, and patient-reported outcome measures for balance confidence and FoF avoidance behavior such as the ABC and FFABQ, are correlated with the physical health QoL domain on the WHOQOL-BREF. The ABC and FFABQ are correlated with psychological and environment QoL. Fall history was not correlated with QoL. Interventions to decrease FoF or improve high-level mobility may improve QoL in community-dwelling older adults.

Screening for pediatric behavioral health in primary care in rural and urban clinics.

INTRODUCTION: The prevalence of behavioral health disorders in children is approximately 15%-20%, yet less than half of the children ever receive treatment for these conditions. The lack of access to behavioral health care is common in urban areas but even more difficult to access in rural areas. Screening for behavioral health in a primary care setting is one of the first strategies to reduce this problem and improve access to care. The primary goal of this study was to examine behavioral health screening practices of pediatric primary care providers in a rural midwestern state. METHOD: A survey that queried family practice/internal medicine and pediatric providers who provide care to pediatric patients was delivered to over 300 primary care providers across the state. The number of surveys returned was 112. RESULTS: The Modified Checklist for Autism tool was administered by 80% of pediatric providers and 30% of family practice primary care providers. The Patient Health Questionnaire for depression was administered by 72% of pediatric and 80% of family practice providers. Most of the primary care providers had a behavioral health provider present in the clinic, which likely resulted in higher screening rates compared to the national average. DISCUSSION: The screening practices of the family practice and pediatric subspecialities reflect their respective current professional organization recommendations. Although most providers believe it is important to screen for developmental and behavioral disorders, further system changes are needed to support screening for development and broader behavioral problems along with depression among family practice providers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Examining early intervention referral patterns in neonatal intensive care unit follow up clinics using telemedicine during COVID-19.

BACKGROUND: Neonatal intensive care unit (NICU) follow up programs are in place to ensure infant health and development are monitored after discharge. The COVID-19 Public Health Epidemic (PHE) negatively impacted the ability to conduct in-person NICU follow up visits. AIMS: This study examines using telemedicine in NICU follow up clinics and compares the rates of referral for further medical and/or educational developmental evaluation. A second objective of the study examines if telemedicine can be implemented in the future to ensure access to families while maintaining high levels of caregiver satisfaction. METHOD: Data were obtained retrospectively from clinical records from one state's NICU follow-up program. Patterns of referral for further developmental evaluation and caregiver satisfaction prior to the COVID-19 PHE and during the first year of the COVID-19 PHE were examined. A total of 658 NICU follow up visits (384 in-person and 274 telemedicine) were included. RESULTS: Chi Square analyses revealed significantly more medically related referrals were made during telemedicine visits compared to in-person visits, χ2 (1) = 5.55, p .05. There were no significant differences between the clinic types in the number of educationally based referrals made, χ2 (1) = 0.028, p > .05. CONCLUSION: The rates of referral for further evaluation made from in-person and telemedicine clinics were comparable, and caregivers were highly satisfied with telemedicine clinic visits. NICU follow up via a virtual platform saves time, money and is equally effective or better in identifying the need for referral for further evaluation.

Expanding Access to CNS-TAP: Design, Development, and Initial Use of a Complex Precision Health Specialty Web App for Neuro-Oncology.

This paper offers a case study to demonstrate how a complex scoring model tool called CNS-TAP, originally created by a neuro-oncology team at one institution, was upgraded and made accessible to a wider audience. In the Results and Discussion, many issues of web app design, development, and sustainability are covered. Overall, we chart a path to expand access to many unique software tools created and needed by today's medical specialists.

The Relationship Between Neonatal Surgery, Postpartum Depression, and Infant Clinical Course.

OBJECTIVE: Postpartum depression (PPD) affects 10-15% of mothers in the general population, and studies show increased incidence for mothers of infants with serious health conditions. This study investigates incidence of PPD in mothers of surgical patients in the neonatal intensive care unit (NICU) and characterizes these patients' clinical and neurodevelopmental outcomes. METHODS: This retrospective cohort study analyzed Nebraska's Tracking Infant Progress Statewide (TIPS) database and referring hospital medical records from February 2013 to June 2018. Upon NICU discharge, children were referred to the TIPS program, with scheduled follow-up appointments at approximately 6 months corrected age. All patients seen in NICU follow-up clinic with recorded scores for maternal Edinburgh postnatal depression screen (EPDS) were eligible except infants with congenital heart disease as this cohort was previously studied. Patients were stratified into groups based on presence or absence of a general surgical procedure within the first 6 months of life and positive (≥ 10) or negative (< 10) EPDS score. Statistical analyses assessed for significant differences between groups regarding gestational age, birth weight, maternal age, length of NICU stay (LOS), number of days on a ventilator, payment method, ethnicity, developmental testing, and rate of referral for early intervention services. RESULTS: Of 436 patients, 83 were surgical patients (16 with positive EPDS; 19.3% incidence), and 353 were non-surgical patients (44 with positive EPDS; 12.5% incidence). Statistical analysis showed no significant relationship between neonatal surgery and positive EPDS (χ2 = 2.6, p = 0.1). While the surgical cohort had longer LOS and days on ventilator, maternal EPDS did not predict these factors. In the surgical cohort, mothers of children not independent on oral feeding at discharge were more likely to screen positive for depression (7/14, 50% vs. 7/61, 11%; p < 0.05). CONCLUSION: Mothers of surgical patients are not significantly more likely to screen positive for post-partum depression compared to other NICU mothers. This underscores the importance of routine screening for PPD in mothers of both surgical and non-surgical NICU patients in order to identify parents and children at risk.

Panobinostat penetrates the blood-brain barrier and achieves effective brain concentrations in a murine model.

PURPOSE: Panobinostat, an orally bioavailable pan-HDAC inhibitor, has demonstrated potent activity in multiple malignancies, including pediatric brain tumors such as DIPG, with increased activity against H3K27M mutant cell lines. Given limited evidence regarding the CNS penetration of panobinostat, we sought to characterize its BBB penetration in a murine model. METHODS: Panobinostat 15 mg/kg was administered IV to 12 CD-1 female mice. At specified time points, mice were euthanized, blood samples were collected, and brains were removed. LC-MS was performed to quantify panobinostat concentrations. Cmax and AUC were estimated and correlated with previously published pharmacokinetic analyses and reports of IC-50 values in DIPG cell lines. RESULTS: Mean panobinostat plasma concentrations (ng/mL) were 27.3 ± 2.5 at 1 h, 7.56 ± 1.8 at 2 h, 1.48 ± 0.56 at 4 h, and 2.33 ± 1.18 at 7 h. Mean panobinostat brain concentrations (ng/g) were 60.5 ± 6.1 at 1 h, 42.9 ± 5.4 at 2 h, 33.2 ± 6.1 at 4 h, and 28.1 ± 4.3 at 7 h. Brain-to-plasma ratio at 1 h was 2.22 and the brain to plasma AUC ratio was 2.63. Based on the published human pharmacokinetic data, the anticipated Cmax in humans is expected to be significantly higher than the IC-50 identified in DIPG models. CONCLUSION: It is expected that panobinostat would be effective in CNS tumors where the IC-50 is in the low nanomolar range. Thus, our data demonstrate panobinostat crosses the BBB and achieves concentrations above the IC-50 for DIPG and other brain tumors and should be explored further for clinical efficacy.

Normative values for the Sensory Organization Test in an active duty military cohort.

BACKGROUND: Computerized dynamic posturography is commonly used to assess balance in service members, but normative values for the military population have not been established. RESEARCH QUESTION: What are the normative values for the Motor Control Test (MCT), Sensory Organization Test (SOT) and the enhanced SOT (eSOT) within the military population and at which point do they differ? METHODS: Cross-sectional study. 237 active duty service members (78 % male) completed the MCT, SOT and the eSOT with the sway manipulated at a gain of 1.2, 1.4, 1.6, 1.8, or 2.0. A Mann-Whitney U test was used to compare the means of men and women for the SOT and MCT composite scores. A Kruskal-Wallis H test was used to compare the means of age groups for the SOT composite score. An independent t-test was used to compare the SOT composite scores from our military population to the manufacturer's normative (civilian) data. The means and standard deviations for the eSOT scores were reported for each gain. Paired-samples t-tests were performed to compare the SOT composite score with the eSOT composite score for each level of gain. RESULTS: There was no difference between SOT composite scores for men and women (Mann-Whitney U = 4363.50, p = 0.19) or among age groups (Kruskal-Wallis = 2.77, p = 0.25). The mean SOT composite scores were not different from the manufacturer's normative values (p = 0.155). SOT composite scores were significantly higher than eSOT composite scores for gains of 1.4 (t = 3.16, p = 0.003), 1.6 (t = 5.73, p < 0.001), 1.8 (t = 5.26, p < 0.001) and 2.0 (t = 5.89, p < 0.001). MCT composite scores were lower in the 18-26 year old than the 36-45 year old age group (p = 0.013). SIGNIFICANCE: This study establishes normative values for the MCT, SOT and eSOT in active duty military service members. The results suggest that the manufacturer's normal values are appropriate for making judgments about the postural stability of service members.

Off-label prescribing of targeted anticancer therapy at a large pediatric cancer center.

BACKGROUND: Off-label drug prescribing is common in pediatric clinical medicine, though the extent and impact of this practice in pediatric oncology has not yet been characterized. METHODS: We completed a retrospective single-institution cohort study evaluating prevalence, characteristics, and clinical outcomes of off-label prescribing of 108 FDA-approved targeted anticancer drugs in patients < 30 years old treated for cancer from 2007 to 2017. Dosing strategies were adjusted for body size and compared to FDA-approved adult dosing regimen. A composite toxicity endpoint was defined as a patient having unplanned clinic visits, emergency department visits, or unplanned hospital admissions that were at least possibly related to the off-label treatment. RESULTS: The overall prevalence of off-label use of targeted therapies was 9.2% (n = 374 patients). The prevalence increased significantly over the study period (P < .0001). Patients treated off-label were more likely to have neuro-oncology diagnoses compared to patients not treated off-label (46% vs 29%; P < .0001). Of the 108 potential agents, 38 (35%) were used by at least one patient. The median starting dose was below the FDA-approved normalized dose for 44.4% of agents. Fifteen percent of patients had a complete response while receiving off-label therapy, 38% experienced toxicity as defined, and 13% discontinued off-label therapy due to toxicity. CONCLUSIONS: In this real-world evaluation of prescribing at a large pediatric cancer center, off-label prescribing of FDA-approved targeted therapies was common, increasing in prevalence, encompassed a broad sample of targeted agents, and was tolerable. Clinicians commonly start dosing below the equivalent FDA-approved dose.

A double-blind, randomized, controlled study of two dose strengths of dalfampridine extended release on walking deficits in ischemic stroke.

BACKGROUND: Stroke-induced ischemia affects both cortex and underlying white matter. Dalfampridine extended release tablets (D-ER) enhance action potential conduction in demyelinated axons, which may positively affect post-stroke recovery. OBJECTIVE: Based on promising preliminary data, we compared efficacy of D-ER administered at 7.5 mg or 10 mg with placebo on post-stroke ambulation. Primary study outcome (response) was a ≥20% increase on the 2-minute walk test (2 MinWT) at 12 weeks after first drug administration. METHODS: This was a multicenter, randomized, placebo-controlled, 3-arm, parallel-group, safety and efficacy trial. After obtaining baseline measures of 2 MinWT, Walk-12, and Timed Up and Go, subjects entered a 2-week, single-blind placebo run-in period and were randomized 1:1:1 to receive 7.5 mg D-ER, 10 mg D-ER, or placebo, dosed twice-daily for 12 weeks. Follow-up evaluations occurred at weeks 14 and 16 when subjects were off study drug. RESULTS: The study was terminated early with 377 of planned 540 patients enrolled, due to no treatment effect. At week 12, mean increase in distances walked in 2 minutes were similar among the 3 study groups (14.9±40.0 feet; 19.4±39.6 feet; and 20.4±38.3 feet for placebo, 7.5 mg D-ER, and 10 mg D-ER, respectively). The proportion of subjects who showed ≥20% improvement on 2 MinWT at week 12 was 13.5%, 14.0%, and 19.0%, for placebo, 7.5 mg D-ER, and 10 mg D-ER, respectively; these were nonsignificant changes from baseline for all groups. CONCLUSIONS: D-ER at either a 7.5-mg or 10-mg dose did not significantly increase performance on the 2 MinWT in stroke survivors with gait impairment, although this study was terminated early before full enrollment. (Clinical Trial # NCT02271217).

Generation and Molecular Characterization of CRISPR/Cas9-Induced Mutations in 63 Immunity-Associated Genes in Tomato Reveals Specificity and a Range of Gene Modifications.

The CRISPR/Cas9 system is a powerful tool for targeted gene editing in many organisms including plants. However, most of the reported uses of CRISPR/Cas9 in plants have focused on modifying one or a few genes, and thus the overall specificity, types of mutations, and heritability of gene alterations remain unclear. Here, we describe the molecular characterization of 361 T0 transgenic tomato plants that were generated using CRISPR/Cas9 to induce mutations in 63 immunity-associated genes. Among the T0 transformed plants, 245 carried mutations (68%), with 20% of those plants being homozygous for the mutation, 30% being heterozygous, 32% having two different mutations (biallelic), and 18% having multiple mutations (chimeric). The mutations were predominantly short insertions or deletions, with 87% of the affected sequences being smaller than 10 bp. The majority of 1 bp insertions were A (50%) or T (29%). The mutations from the T0 generation were stably transmitted to later generations, although new mutations were detected in some T1 plants. No mutations were detected in 18 potential off-target sites among 144 plants. Our study provides a broad and detailed view into the effectiveness of CRISPR/Cas9 for genome editing in an economically important plant species.

Objective Dual-Task Turning Measures for Return-to-Duty Assessment After Mild Traumatic Brain Injury: The ReTURN Study Protocol.

Determining readiness for duty after mild traumatic brain injury (mTBI) is essential for the safety of service members and their unit. Currently, these decisions are primarily based on self-reported symptoms, objective measures that assess a single system, or standardized physical or cognitive tests that may be insensitive or lack ecological validity for warrior tasks. While significant technological advancements have been made in a variety of assessments of these individual systems, assessments of isolated tasks are neither diagnostically accurate nor representative of the demands imposed by daily life and military activities. Emerging evidence suggests that complex tasks, such as dual-task paradigms or turning, have utility in probing functional deficits after mTBI. Objective measures from turning tasks in single- or dual-task conditions, therefore, may be highly valuable for clinical assessments and return-to-duty decisions after mTBI. The goals of this study are to assess the diagnostic accuracy, predictive capacity, and responsiveness to rehabilitation of objective, dual-task turning measures within an mTBI population. These goals will be accomplished over two phases. Phase 1 will enroll civilians at three sites and active-duty service members at one site to examine the diagnostic accuracy and predictive capacity of dual-task turning outcomes. Phase 1 participants will complete a series of turning tasks while wearing inertial sensors and a battery of clinical questionnaires, neurocognitive testing, and standard clinical assessments of function. Phase 2 will enroll active-duty service members referred for rehabilitation from two military medical treatment facilities to investigate the responsiveness to rehabilitation of objective dual-task turning measures. Phase 2 participants will complete two assessments of turning while wearing inertial sensors: a baseline assessment prior to the first rehabilitation session and a post-rehabilitation assessment after the physical therapist determines the participant has completed his/her rehabilitation course. A variable selection procedure will then be implemented to determine the best task and outcome measure for return-to-duty decisions based on diagnostic accuracy, predictive capacity, and responsiveness to rehabilitation. Overall, the results of this study will provide guidance and potential new tools for clinical decisions in individuals with mTBI. Clinical Trial Registration: clinicaltrials.gov, Identifier NCT03892291.

Sitting Matters! Differences Between Sitters and Nonsitters at 6 Months' Adjusted Age in Infants At-Risk and Born Preterm.

PURPOSE: Sitting delays in infants born preterm compound cognitive and language deficits. This retrospective study examines differences in prematurity-related risk and compares developmental outcomes between sitters and nonsitters at 6 months' adjusted age. METHODS: A total of 105 graduates of the neonatal intensive care unit met inclusion criteria. Infant demographic and medical risk profiles and 6-month Bayley Scales of Infant Development-3rd edition (BSID-III) cognitive and language scores were retrieved. Infants who sat with hands free greater than 60 seconds were classified as "sitters." RESULTS: Sixty-nine percent of the sample were nonsitters and were born earlier, had lower birth weights, were chronologically older at follow-up, and spent more days with respiratory support. BSID-III scores were significantly higher in sitters but did not differ by gender, multiple birth, head ultrasound results, payment type, or race/ethnicity. CONCLUSION: Sitting abilities at 6 months' adjusted age are associated with prematurity risk factors. Cognitive and language scores differ significantly between sitters and nonsitters.