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Early cognitive, motor, and language skills were evaluated in 165 children, 91 with Spina Bifida (SB) and 74 developing typically. Assessments were given at 5 time points (6, 12, 18, 24, and 36 months of age). Three latent growth curve models were conducted to evaluate the development of these early skills, with social economic status and etiology as predictors of growth. Lesion level and shunting effects were included for group comparison. Children with SB exhibited lower levels of functioning in all areas, with slower rates of growth in cognition and language, but more acceleration in growth of motor skills. The impact of lesion level and shunting significantly related to growth in cognition and motor skills but not in language. [ABSTRACT FROM AUTHOR]

In a sample of 415 predominantly minority women with physical disabilities recruited from private and public specialty outpatient clinics, we examined experiences of physical, sexual, and disability-related abuse within the past year and its associations with demographic, disability, and psychosocial characteristics. Logistic regression analyses identified 27% of the variance and indicated that women with disabilities who were younger, more educated, less mobile, more socially isolated, and who had higher levels of depression may have a higher likelihood of having experienced abuse in the past year. This model correctly identified 84% of the abused women with disabilities. Questions of directionality, the role of disability, and validity testing are discussed. [ABSTRACT FROM AUTHOR]

This study examines the sense of self of women with physical disabilities in terms of self-esteem, self-cognition (perceptions of how others see them), and social isolation. It was hypothesized that these variables mediate the relation of precursor variables (age, education, severity of disability, and childhood experiences, including overprotection, familial affection, and school environment) and outcomes (intimacy, employment, and health promoting behaviors). Data were gathered from a sample of 881 community-dwelling women in the USA, 475 with a variety of mild to severe physical disabilities, and 406 without disabilities. Correlation analyses indicated that the women with disabilities had significantly lower self-cognition and self-esteem, and greater social isolation than the women without disabilities, as well as significantly less education, more overprotection during childhood, poorer quality of intimate relationships, and lower rates of salaried employment. Path analysis indicated that each of the sense of self mediators was significantly related to the outcome of intimacy, that both social isolation and self-esteem were significantly related to health promoting behaviors, and that only self-esteem was significantly related to employment. Respondents who were older, less disabled, less educated, less over-protected, and had more affection shown in the home tended to feel that others saw them more positively. Women with positive school environments, less over-protection, and more affection in the home experienced less social isolation; age, education, and disability severity were not significantly related to social isolation. Older respondents with less disability, a more positive school environment, less over-protection, and more affection in the home tended to have greater self-esteem; education was not significantly related to self-esteem. Older respondents tended to report less intimacy. Younger, more educated, and less disabled respondents were significantly more likely to be employed. More highly educated respondents reported engaging in more health promoting behaviors. [ABSTRACT FROM AUTHOR]

Recent work in single-cell imaging has allowed unprecedented insight into single-cell interactions that control disease progression. However, approaches to understanding the combined extracellular and cellular microenvironment are limited. In the current protocol, we describe an approach that allows single-cell type imaging using matrix-assisted laser desorption/ionization immunohistochemistry (MALDI-IHC) of UV (ultraviolet) photocleavable mass tags combined with N-glycomic and ECM-targeted proteomic imaging from the same formalin-fixed paraffin-embedded tissue section. These approaches use the same imaging mass spectrometry platform to provide a comprehensive view of both the cellular and extracellular tissue microenvironment., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To conduct the first known comprehensive examination of loneliness and its correlates in a diverse sample of people with spinal cord injury (SCI)., Methods: A cross-sectional sample of 343 people with SCI provided responses to the 20-item UCLA Loneliness Scale-Version 3. We examined the relation of loneliness to measures of demographic, disability, physical health, and social characteristics., Results: The majority (56%) of respondents had scores indicating high levels of loneliness. At least a quarter of respondents indicated that they often felt alone, left out, isolated, and lacking in companionship. At least a quarter rarely or never felt there were people who really understood them, with whom they could talk, and with whom they had a lot in common. In univariate analyses, loneliness was associated with several demographic, disability, and health characteristics suggesting potential risk factors. In multiple regression analyses, social characteristics (social integration, social support, satisfaction with social roles) were the most strongly associated with loneliness., Conclusions: Our findings underscore the high prevalence of loneliness among people with SCI. Given the adverse health consequences of loneliness documented in the general literature, there is an urgent need for researchers, healthcare providers, and policy makers to address the loneliness crisis in this population.

Hepatocellular carcinoma (HCC) mortality rates continue to increase faster than those of other cancer types due to high heterogeneity, which limits diagnosis and treatment. Pathological and molecular subtyping have identified that HCC tumors with poor outcomes are characterized by intratumoral collagenous accumulation. However, the translational and post-translational regulation of tumor collagen, which is critical to the outcome, remains largely unknown. Here, we investigate the spatial extracellular proteome to understand the differences associated with HCC tumors defined by Hoshida transcriptomic subtypes of poor outcome (Subtype 1; S1; n = 12) and better outcome (Subtype 3; S3; n = 24) that show differential stroma-regulated pathways. Collagen-targeted mass spectrometry imaging (MSI) with the same-tissue reference libraries, built from untargeted and targeted LC-MS/MS was used to spatially define the extracellular microenvironment from clinically-characterized, formalin-fixed, paraffin-embedded tissue sections. Collagen α-1(I) chain domains for discoidin-domain receptor and integrin binding showed distinctive spatial distribution within the tumor microenvironment. Hydroxylated proline (HYP)-containing peptides from the triple helical regions of fibrillar collagens distinguished S1 from S3 tumors. Exploratory machine learning on multiple peptides extracted from the tumor regions could distinguish S1 and S3 tumors (with an area under the receiver operating curve of ≥0.98; 95% confidence intervals between 0.976 and 1.00; and accuracies above 94%). An overall finding was that the extracellular microenvironment has a high potential to predict clinically relevant outcomes in HCC.

Purpose/objective: This study aims to explore the perspectives of rehabilitation professionals regarding the barriers to spinal cord injury (SCI) rehabilitation services in Nepal., Research Method/design: A qualitative study involved 15 rehabilitation professionals working in the Spinal Injury Rehabilitation Center in Nepal. After obtaining informed consent, in-depth semistructured interviews were conducted using Zoom and phone calls between June and July 2023. Braun and Clarke's thematic analysis approach was utilized to analyze the interviews and generate themes from the participants' responses., Results: The participants represented nine different rehabilitation professions. Over half of them were female (53.33%), and 86.67% had one to 10 years of experience in SCI rehabilitation. From in-depth interviews, four themes depicting barriers to rehabilitation were identified: (a) resource constraints within the rehabilitation centers, (b) concerns related to finance, awareness, and support mechanisms, (c) systemic problems coupled with geographical and physical barriers, and (d) beliefs and practices influencing access and adherence to rehabilitation., Conclusions and Implications: Delivering effective rehabilitation services for people with SCI presents a range of barriers. Considering the critical importance of rehabilitation for this population, the findings underscore the necessity of engaging stakeholders at multiple levels, individuals, communities, and government agencies to address the identified barriers and improve rehabilitation services in Nepal. The implications of the findings are further discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Design: Cross-sectional survey., Objective: To evaluate the perceived helpfulness of pharmacological and non-pharmacological interventions and their combinations for neuropathic pain (NeuP) and subcategories of NeuP after spinal cord injury (SCI)., Setting: Six Spinal Cord Injury Model System Centers., Methods: Three hundred ninety one individuals at least one year post traumatic SCI were enrolled. A telephone survey was conducted to determine the pharmacologic and non-pharmacologic treatments used in the last 12 months for each participant's three worst pains, whether these treatments were "helpful", and if currently used, each treatments' effectiveness., Results: Two hundred twenty participants (56%) reported 354 distinct NeuPs. Pharmacological treatments rated helpful for NeuP were non-tramadol opioids (opioids were helpful for 86% of opioid treated NeuPs), cannabinoids (83%), and anti-epileptics (79%). Non-pharmacological treatments rated helpful for NeuP were massage (76%), body position adjustment (74%), and relaxation therapy (70%). Those who used both opioids and exercise reported greater NeuP treatment helpfulness compared to participants using opioids without exercise (P = 0.03)., Conclusions: Opioids, cannabinoids, and massage were reported more commonly as helpful than treatments recommended as first-line therapies by current clinical practice guidelines (CPGs) for NeuP after SCI (antiepileptics and antidepressants). Individuals with SCI likely value the modulating effects of pharmacological and non-pharmacological treatments on the affective components of pain in addition to the sensory components of pain when appraising treatment helpfulness.

Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames. Most HLA-II peptides colocalize with known CD4 + T cell epitopes in coronavirus disease 2019 patients, including 2 reported immunodominant regions in the SARS-CoV-2 membrane protein. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and nonstructural and noncanonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4 + and CD8 + T cell epitopes to maximize vaccine effectiveness., Competing Interests: Declaration of interests S.W.-G., D.-Y.C., S.S., K.R.C., N.H., S.A.C., J.G.A., M.S., and P.C.S. are named co-inventors on a patent application related to this work, filed by The Broad Institute, that is being made available in accordance with the COVID-19 technology licensing framework to maximize access to university innovations. N.H. is a founder of Neon Therapeutics (now BioNTech US), was a member of its scientific advisory board, and holds shares. N.H. is also an advisor for IFM Therapeutics. S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, Seer, and PrognomIQ. J.G.A. is a past employee of Neon Therapeutics (now BioNTech US). P.C.S. is a cofounder of and consultant to Sherlock Biosciences and Delve Biosciences and a board member of Danaher Corporation and holds equity in the companies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mounting empirical evidence suggests that, compared to women without disabilities, women with disabilities are more likely to experience interpersonal violence (IPV). However, there is extremely limited research attention on IPV against women with spinal cord injury (SCI), a particularly understudied and underserved population., Objectives: To conduct the first known examination of lifetime IPV experience in women with SCI, to explore demographic and disability-related correlates of IPV, and to examine the health impacts of IPV., Methods: The sample included 175 women with traumatic SCI from across the United States who enrolled in a randomized controlled trial of an online psychological health promotion intervention. The data, which included a brief measure of lifetime abuse, were collected as part of the baseline survey administered prior to randomization to the intervention or control conditions., Results: The majority (55%) of the women described experiencing some abuse in their lifetime, with 43% reporting physical abuse, 32% reporting sexual abuse, and 23% reporting disability-related abuse. Sixteen percent of the women indicated that they had experienced all three (physical, sexual, disability) types of abuse. Few demographic and disability characteristics were related to overall lifetime IPV experience; however, disability characteristics were associated with disability-related IPV victimization. In addition, those with a history of IPV had poorer self-reported health and greater depression., Conclusion: This study suggests that IPV is common among women with SCI. More research is needed to understand the prevalence, risk factors, and consequences of IPV against women with SCI to help inform policy and practice., Competing Interests: Conflicts of Interest The authors report no conflicts of interest., (©2023 American Spinal Injury Association.)

This study represents the first known research addressing the impact of the COVID-19 pandemic on women with spinal cord injury (SCI) in the United States. Women in this population face unique barriers that put them at elevated risk for compromised quality of life, risk that was magnified by physical and social restrictions imposed during the pandemic. This qualitative study examined the perceptions of women with SCI and the effect of the pandemic on their lives. The predominantly White and relatively well-educated sample of 105 women with traumatic SCI was diverse in age, injury characteristics, and geographic representation. Recruited across the USA, participants in an online psychological health intervention trial were asked to respond to the item, "Please tell us how COVID-19 has affected you and your life", administered May-October, 2020. An overall sentiment rating of impact was coded as well as the impact of COVID-19 on eight individual themes: Physical Health, Mental Health, Social Health, Activities of Daily Living, Exercise, Work, Activities Outside the Home, and Activities at Home. Sentiment responses were rated as positive, negative, a mixture of positive and negative impacts, or neutral impact. Participants described the overall impact of COVID-19 as negative (54%), positive (10%), mixed (21%) or neutral (15%). Sentiment ratings to individual themes were also described. Our findings highlight the importance of providing access to disability-sensitive and affordable support, resources, and interventions for women with SCI, especially during a public health crisis.

CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies., Competing Interests: Declaration of interests R.J.X. is a co-founder of Celsius Therapeutics and Jnana Therapeutics, a member of the Scientific Advisory Board at Nestle, and a member of the Board of Directors at Moonlake Immunotherapeutics. S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, Seer, and PrognomIQ., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Serial multi-omic analysis of proteome, phosphoproteome, and acetylome provides insights into changes in protein expression, cell signaling, cross-talk and epigenetic pathways involved in disease pathology and treatment. However, ubiquitylome and HLA peptidome data collection used to understand protein degradation and antigen presentation have not together been serialized, and instead require separate samples for parallel processing using distinct protocols. Here we present MONTE, a highly sensitive multi-omic native tissue enrichment workflow, that enables serial, deep-scale analysis of HLA-I and HLA-II immunopeptidome, ubiquitylome, proteome, phosphoproteome, and acetylome from the same tissue sample. We demonstrate that the depth of coverage and quantitative precision of each 'ome is not compromised by serialization, and the addition of HLA immunopeptidomics enables the identification of peptides derived from cancer/testis antigens and patient specific neoantigens. We evaluate the technical feasibility of the MONTE workflow using a small cohort of patient lung adenocarcinoma tumors., (© 2023. The Author(s).)

Purpose: Few studies have examined the impacts of the COVID-19 pandemic on the lives of people with spinal cord injury (SCI), a population uniquely vulnerable to pandemic-related stressors. This study examines the impact of the pandemic on three life domains (psychosocial health, health and health behavior, and social participation) and identifies risk factors for adverse psychosocial health impacts in a sample of people with SCI., Method: A diverse sample of 346 adults with SCI completed a survey assessing demographic, disability, health, and social characteristics, and perceived impacts of the pandemic., Results: Many respondents reported no change on items reflecting psychosocial health, health and health behavior, and social participation; however, among those reporting change, more reported negative than positive impacts. Negative impacts were most striking with regard to psychosocial health and social engagement, with approximately half reporting a worsening of stress, depression, anxiety, and loneliness and a reduction in face-to-face interactions and participation in life roles. Regression analyses revealed that those at greater risk of adverse psychosocial impacts were women, were non-Black, were in poorer health, had greater unmet care needs, and were less satisfied with their social roles and activities., Conclusions: Although not universal, negative impacts were reported by many respondents 9-15 months into the pandemic. Future research should examine the impacts of the pandemic over time and on a wider range of outcomes. Such research could generate substantial benefits in understanding, preventing, or minimizing the adverse effects of the evolving pandemic and future public health emergencies in people with SCI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort., Methods: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight support, overground training, and stationary robotic systems. The outcome measures included the calculation of quality adjusted life years (QALYs) using the EQ-5D and therapy costs. We estimate cost-effectiveness using the incremental cost utility ratio and present results on the cost-effectiveness plane and on cost-effectiveness acceptability curves., Results: Participants in the prospective, practice-based cohort with complete EQ-5D data (n = 99) qualified for the analysis. Both conventional training and overground robotic training experienced an improvement in QALYs. Only people with incomplete SCI improved with conventional locomotor training, 0.045 (SD 0.28), and only people with complete SCI improved with overground robotic training, 0.097 (SD 0.20). Costs were lower for conventional training, $1758 (SD $1697) versus overground robotic training $3952 (SD $3989), and lower for those with incomplete versus complete injury. Conventional overground training was more effective and cost less than robotic therapy for people with incomplete SCI. Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost utility ratio for overground robotic training for people with complete spinal cord injury was $12,353/QALY., Conclusions: The most cost-effective locomotor training strategy for people with SCI differed based on injury completeness. Conventional training was more cost-effective than overground robotic training for people with incomplete SCI. Overground robotic training was more cost-effective than conventional training for people with complete SCI. The effect estimates may be subject to limitations associated with small sample sizes and practice-based evidence methodology. These estimates provide a baseline for future research., (© 2023. The Author(s).)

Context/objective: Spinal cord injury (SCI) often results in a significant loss of mobility and independence coinciding with reports of decreased quality of life (QOL), community participation, and medical complications often requiring re-hospitalization. Locomotor training (LT), the repetition of stepping-like patterning has shown beneficial effects for improving walking ability after motor incomplete SCI, but the potential impact of LT on psychosocial outcomes has not been well-established. The purpose of this study was to evaluate one year QOL, community participation and re-hospitalization outcomes between individuals who participated in a standardized LT program and those who received usual care (UC)., Design/setting/participants: A retrospective (nested case/control) analysis was completed using SCI Model Systems (SCIMS) data comparing one year post-injury outcomes between individuals with traumatic motor incomplete SCI who participated in standardized LT to those who received UC., Outcome Measures: Outcomes compared include the following: Satisfaction with Life Scale (SWLS™), Craig Handicap Assessment and Reporting Technique-Short Form (CHART-SF™), and whether or not an individual was re-hospitalized during the first year of injury., Results: Statistically significant improvements for the LT group were found in the following outcomes: SWLS (P = 0.019); and CHART subscales [mobility (P = <0.001)]; occupation (P = 0.028); with small to medium effects sizes., Conclusion: Individuals who completed a standardized LT intervention reported greater improvements in satisfaction with life, community participation, and fewer re-hospitalizations at one year post-injury in comparison to those who received UC. Future randomized controlled trials are needed to verify these findings.

Immunopeptidome profiling of infected cells is a powerful technique for detecting viral peptides that are naturally processed and loaded onto class I human leukocyte antigens (HLAs-I). Here, we provide a protocol for preparing samples for immunopeptidome profiling that can inactivate enveloped viruses while still preserving the integrity of the HLA-I complex. We detail steps for lysate preparation of infected cells followed by HLA-I immunoprecipitation and virus inactivation. We further describe peptide purification for mass spectrometry outside a high-containment facility. For complete details on the use and execution of this protocol, please refer to Weingarten-Gabbay et al. (2021). 1 ., Competing Interests: Declaration of interests S.W.-G., S.K., S.A.C., J.G.A., M.S., and P.C.S. are named co-inventors on a patent application related to this manuscript filed by The Broad Institute that is being made available in accordance with the COVID-19 technology licensing framework to maximize access to university innovations. N.L.W. is a consultant for Carver Biosciences. D.B.K. own equity in Affimed N.V., Agenus, Armata Pharmaceuticals, Breakbio, BioMarin Pharmaceutical, Celldex Therapeutics, Clovis Oncology, Editas Medicine, Exelixis, Gilead Sciences, Immunitybio, ImmunoGen, IMV, Lexicon Pharmaceuticals, Moderna, Neoleukin Therapeutics, Regeneron Pharmaceuticals, and Sesen Bio. BeiGene, a Chinese biotech company, supported unrelated SARS COV-2 research at TIGL. S.A.C. is a member of the scientific advisory boards of Kymera, PrognomIQ, PTM BioLabs, and Seer and an ad hoc scientific advisor to Pfizer and Biogen. J.G.A. is a past employee and shareholder of Neon Therapeutics, Inc. (now BioNTech US). P.C.S. is a co-founder of and consultant to Sherlock Biosciences and Delve Biosciences and a board member of Danaher Corporation and holds equity in the companies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This systematic review aims to gain a comprehensive understanding of the feasibility, acceptability, and efficacy of mindfulness-based interventions (MBIs) on depression, anxiety, fatigue, and health-related quality of life among individuals with upper motor neuron disorders (UMNDs)., Data Sources: PubMed, PsycINFO, Excerpta Medica Database, and Cumulative Index to Nursing and Allied Health Literature were searched for relevant studies published between January 2001 and June 2021., Study Selection: Clinical trials published in English evaluating MBIs in adults with the 4 most common UMNDs (multiple sclerosis, brain injury including stroke, spinal cord injury, amyotrophic lateral sclerosis) were included., Data Extraction: Two reviewers independently performed the risk of bias assessment using standardized tools and extracted desired data electronically., Data Synthesis: A total of 44 studies were included: 26 randomized controlled trials, 10 nonrandomized controlled trials, and 8 pre-post intervention studies. The average ± SD duration of MBIs was 8±2 weeks. On average, 85%±14% of participants completed the MBI, and the retention rate at follow-up was 80%±16%. Only 14% of the studies delivered MBIs virtually, and feasibility metrics were similar to in-person studies. Among studies reporting acceptability data, most participants reported satisfaction with the MBI. Randomized controlled trials that evaluated the effects of MBI on depression, anxiety, fatigue, and quality of life revealed greater relative improvement in these outcomes among MBI participants compared with controls, with differences greater when compared with passive control than active control participants. None of the studies included in this review studied dose response., Conclusions: Based on current data, MBIs are feasible and offer a promising approach to address the biopsychosocial needs of individuals with UMNDs. MBIs are associated with a high acceptance rate among participants, with notable improvements in depression, anxiety, fatigue, and quality of life post intervention. Future studies are needed to evaluate alternate models of delivery of MBIs and the dose-response relationship., (Published by Elsevier Inc.)

Objective: To characterize individuals with spinal cord injuries (SCI) who use outpatient physical therapy or community wellness services for locomotor training and predict the duration of services, controlling for demographic, injury, quality of life, and service and financial characteristics. We explore how the duration of services is related to locomotor strategy., Design: Observational study of participants at 4 SCI Model Systems centers with survival. Weibull regression model to predict the duration of services., Setting: Rehabilitation and community wellness facilities at 4 SCI Model Systems centers., Participants: Eligibility criteria were SCI or dysfunction resulting in motor impairment and the use of physical therapy or community wellness programs for locomotor/gait training. We excluded those who did not complete training or who experienced a disruption in training greater than 45 days. Our sample included 62 participants in conventional therapy and 37 participants in robotic exoskeleton training., Interventions: Outpatient physical therapy or community wellness services for locomotor/gait training., Main Outcome Measures: SCI characteristics (level and completeness of injury) and the duration of services from medical records. Self-reported perceptions of SCI consequences using the SCI-Functional Index for basic mobility and SCI-Quality of Life measurement system for bowel difficulties, bladder difficulties, and pain interference., Results: After controlling for predictors, the duration of services for the conventional therapy group was an average of 63% longer than for the robotic exoskeleton group, however each visit was 50% shorter in total time. Men had an 11% longer duration of services than women had. Participants with complete injuries had a duration of services that was approximately 1.72 times longer than participants with incomplete injuries. Perceived improvement was larger in the conventional group., Conclusions: Locomotor/gait training strategies are distinctive for individuals with SCI using a robotic exoskeleton in a community wellness facility as episodes are shorter but individual sessions are longer. Participants' preferences and the ability to pay for ongoing services may be critical factors associated with the duration of outpatient services., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Complex dietary polysaccharides such as β-glucans are widely used for their anti-inflammatory properties. We reported before that oral administration of Yeast β-glucan (YBG) in adult mice can help delay type 1 diabetes (T1D) onset and suppress gut inflammation through modulation of the structure and function of gut microbiota. Since juvenile age is characterized by profoundly changing immature gut microbiota, we examined the impact of oral treatment with YBG in non-obese diabetic (NOD) mice at this age. Juvenile mice that received daily oral administration of YBG starting at 15 days of age for 7 or 30 days were examined for changes in gut microbiota, immune characteristics, and T1D incidence. Mice that received YBG for 30 days but not 7 days, showed considerable changes in the composition and diversity of fecal microbiota as compared to controls. Predictive functional analysis, based on 16S rDNA sequences, revealed overrepresentation of glycan biosynthesis and metabolism, energy metabolism, and fatty acid biosynthesis pathways in mice that received YBG for 30 days. Immune phenotype of the colon showed skewing toward immune regulatory and Th17 cytokines with increases in IL-10, IL-17, and IL-21 and a decrease in TNF-α, although increases in some pro-inflammatory cytokines (IL-1b, IFN-γ) were observed. Most importantly, mice that received YBG treatment for 30 days showed significantly suppressed insulitis and delayed onset of hyperglycemia compared to controls. Overall, this study suggests that oral consumption of YBG beginning at pre-diabetic juvenile ages could have positive maturational changes to gut microbiota and immune functions and could result in a delay in the disease onset in those who are pre-disposed to T1D., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Taylor and Vasu.)

T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development., Competing Interests: Declaration of interests S.W.-G., S.K., S.S., K.R.C, N.H., S.A.C., J.G.A., M.S., and P.C.S. are named co-inventors on a patent application related to immunogenic compositions of this manuscript filed by The Broad Institute that is being made available in accordance with the COVID-19 technology licensing framework to maximize access to university innovations. D.L.-E., C.T., Y.W., M.R.D., W.A.D., and D.C.P. are employees and stockholders of Repertoire Immune Medicines. N.B. is an extramural member of the Parker Institute for Cancer Immunotherapy; receives research funds from Regeneron, Harbor Biomedical, DC Prime, and Dragonfly Therapeutics; and is on the advisory boards of Neon Therapeutics, Novartis, Avidea, Boehringer Ingelheim, Rome Therapeutics, Roswell Park Comprehensive Cancer Center, BreakBio, Carisma Therapeutics, CureVac, Genotwin, BioNTech, Gilead Therapeutics, Tempest Therapeutics, and the Cancer Research Institute. A.S. is a consultant for Gritstone, Flow Pharma, CellCarta, OxfordImmunotech, Immunoscape, and Avalia. La Jolla Institute for Immunology has filed for patent protection for various aspects of T cell epitope and vaccine design work. D.B.K. has previously advised Neon Therapeutics and has received consulting fees from Neon Therapeutics. D.B.K. owns equity in AduroBiotech, Agenus Inc., Armata Pharmaceuticals, Breakbio Corp., Biomarin Pharmaceutical Inc., Bristol Myers Squibb Com., Celldex Therapeutics Inc., Editas Medicine Inc., Exelixis Inc., Gilead Sciences Inc., IMV Inc., Lexicon Pharmaceuticals Inc., Moderna Inc., and Regeneron Pharmaceuticals. D.B.K. receives SARS-CoV-2 research support from BeiGene for a project unrelated to this publication. N.H. is a founder of Neon Therapeutics, Inc. (now BioNTech US), was a member of its scientific advisory board, and holds shares. N.H. is also an advisor for IFM Therapeutics. S.A.C. is a member of the scientific advisory boards of Kymera, PTM BioLabs, and Seer and a scientific advisor to Pfizer and Biogen. J.G.A. is a past employee and shareholder of Neon Therapeutics, Inc. (now BioNTech US). P.C.S. is a co-founder and shareholder of Sherlock Biosciences and a non-executive board member and shareholder of Danaher Corporation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunotherapies have emerged to treat diseases by selectively modulating a patient's immune response. Although the roles of T and B cells in adaptive immunity have been well studied, it remains difficult to select targets for immunotherapeutic strategies. Because human leukocyte antigen class II (HLA-II) peptides activate CD4+ T cells and regulate B cell activation, proliferation, and differentiation, these peptide antigens represent a class of potential immunotherapy targets and biomarkers. To better understand the molecular basis of how HLA-II antigen presentation is involved in disease progression and treatment, systematic HLA-II peptidomics combined with multiomic analyses of diverse cell types in healthy and diseased states is required. For this reason, MS-based innovations that facilitate investigations into the interplay between disease pathologies and the presentation of HLA-II peptides to CD4+ T cells will aid in the development of patient-focused immunotherapies., Competing Interests: Conflict of interest S. A. C. is a member of the scientific advisory boards of Kymera, PTM Biolabs, and Seer and a scientific advisor to Pfizer and Biogen. J. G. A. is a past employee and shareholder of Neon Therapeutics, Inc (now BioNTech US). S. K., S. S., K. R. C., S. A. C., and J. G. A. are named co-inventors on patent application(s) related to HLA peptide motif technology that is related to topics in this article filed by The Broad Institute., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Biofilms are highly tolerant to antibiotics and underlie the recalcitrance of many chronic infections. We demonstrate that mature Staphylococcus aureus biofilms can be substantially sensitized to the treatment by pulse dosing of an antibiotic - in this case, oxacillin. Pulse (periodic) dosing was compared to continuous application of antibiotic and was studied in a novel in vitro flow system which allowed for robust biofilm growth and tractable pharmacokinetics of dosing regimens. Our results highlight that a subpopulation of the biofilm survives antibiotic without becoming resistant, a population we refer to as persister bacteria. When oxacillin was continuously present the persister level did not decline, but, importantly, providing correctly timed periodic breaks decreased the surviving population. We found that the length of the periodic break impacted efficacy, and there was an optimal length that sensitized the biofilm to repeat treatment without allowing resistance expansion. Periodic dosing provides a potential simple solution to a complicated problem., (Copyright © 2020 Meyer, Taylor, Seidel, Gates and Lewis.)

Previously, we have shown that oral administration of yeast derived β-1,3/1,6-d-glucan enhances immune regulation and alters the composition of the gut microbiota. However, it is not known if other structurally distinct β-glucans have similar properties. Here, using C57BL/6 mice, we show the potential of a microalgae derived β-1,3-d-glucan, paramylon (PM), in shaping the gut microbiota and modulating the susceptibility to colitis. The community structure within the gut microbiota showed progressive changes including selective enrichment of specific communities and lowered community richness and diversity during prolonged oral treatment with PM. Compared to control mice, the gut microbiota of PM-treated mice had significantly higher abundance of Verrucomicrobia and lower abundance of Firmicutes. Specific taxa that were significantly more abundant in PM-treated mice include Akkermansia muciniphila and several Bacteroides members. Predictive functional analysis revealed overrepresentation of carbohydrate metabolism function in the fecal microbiota of PM recipients compared to controls, and this function was linked to Bacteroides spp. Prolonged pretreatment with PM not only diminished susceptibility to dextran sulfate sodium induced colitis severity, but also caused enhanced immune regulation. Overall, this study demonstrates the prebiotic properties of PM and the potential benefits of its prolonged oral consumption to gut health.

Aerobic ammonia oxidation to nitrite has been established as an important ecosystem process in regulating the level of nitrogen in marine ecosystems. This process is carried out by ammonia-oxidizing bacteria (AOB) within the classes Betaproteobacteria and Gammaproteobacteria and ammonia-oxidizing Archaea (AOA) from the phylum Thaumarchaeota, and the latter of which has been established as more prevalent in marine systems. This study investigated the presence, abundance, and activity of these groups of microbes at a beach near Springmaid Pier in Myrtle Beach, South Carolina, through the implementation of next generation sequencing, quantitative PCR (qPCR), and microcosm experiments to monitor activity. Sequencing analysis revealed a diverse community of ammonia-oxidizing microbes dominated by AOA classified within the family Nitrosopumilaceae, and qPCR revealed the abundance of AOA amoA genes over AOB by at least an order of magnitude in most samples. Microcosm studies indicate that the rates of potential ammonia oxidation in these communities satisfy Michaelis-Menten substrate kinetics and this process is more active at temperatures corresponding to summer months than winter. Potential rates in AOA medium were higher than that of AOB medium, indicating a potentially greater contribution of AOA to this process in this environment. In conclusion, this study provides further evidence of the dominance of AOA in these environments compared with AOB and highlights the overall efficiency of this process at turning over excess ammonium that may be present in these environments., (© 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Background: There are no known interventions addressing self-esteem in women following spinal cord injury (SCI)., Objectives: To test the feasibility of an online self-esteem intervention for women with disabilities, as modified for women with SCI., Method: We conducted a randomized, controlled feasibility test of a self-esteem intervention (N = 21). Participants were randomly assigned to the intervention or control group that received intervention materials at the end of the study. Intervention participants met as avatars for 7 weekly real-time group sessions in Second Life (SL), a free online virtual world. Feasibility indicators were study engagement, acceptability of SL and the intervention, and improvements on measures of psychological health promoting behaviors, social support, self-efficacy, self-esteem, and depression., Results: Intervention participants (n = 10) were highly engaged, and most described the SL program as more enjoyable and more convenient than in-person programs. All rated the intervention as "good" (n = 4) or "very good" (n = 6), and all 10 rated themselves has having made positive life changes as a result of the program. Intervention participants experienced significantly greater change than controls on two measures of health-promoting behavior (Health Promoting Lifestyle Profile-II Spiritual Growth/Self-actualization; Interpersonal Relations). Examining change in the intervention group using regression analyses, we found medium-to-large effects of the intervention on these behaviors and measures of depression (CESD-10, PHQ-9). The intervention had small effects on remaining measures., Conclusion: We found preliminary support for the feasibility of this modified self-esteem intervention offered in SL. Such programming may help circumvent barriers to community-based psychological services and may improve psychological health., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective : To provide the results of a robotic exoskeleton user satisfaction questionnaire completed by participants utilizing two robotic exoskeletons. Method : Seven individuals with physical disabilities engaged in two exoskeleton-assisted training phases with the REX and the Ekso 1.1 (Ekso), after which they completed a user satisfaction questionnaire. The questionnaire consisted of structured items with a Likert scale, which were averaged and compared, as well as free response questions, which were interpreted thematically. Results : Participants reported some differences in user satisfaction between the two exoskeletons. They indicated higher satisfaction with transferring in and out of the REX and with its appearance and higher satisfaction with the transportability of the Ekso. Expectations for exoskeleton use were relatively similar for the two devices, with some exceptions. Whereas participants indicated that many changes should be made to both exoskeletons, they reported that some were more necessary for the REX and others were more necessary for the Ekso. Participants reported that they would be somewhat likely to use both exoskeletons at home and in the community if they were available. Conclusions : This brief report provides an initial comparison of user satisfaction with two exoskeletons, thereby contributing to the growing body of literature in this area.Implications for rehabiliationContributes to the literature on user satisfaction with robotic exoskeletons Implications for rehabilitationEmphasizes the role of user/participant/patient feedback in rehabilitation researchProvides user satisfaction questionnaire items that can be used in future studies.

Studies of microbial community structure in intertidal and supratidal beach sands along the California and Gulf of Mexico coasts have begun to reveal geographical patterns in microbial diversity through the use of next generation sequencing technology. Only a few studies have targeted communities along the Eastern seaboard, leaving a variety of microbial ecosystems uncharacterized. In this study, we examine the microbial community structure within three South Carolina beaches along the Grand Strand via sequencing of the V4 region of the 16S rRNA gene to discern relationships between diversity and temporal or regional factors. Gammaproteobacteria, Planctomycetes, Acidobacteria, and Actinobacteria dominated the composition of these beaches. Diversity analyses revealed that highly diverse communities were similar in overall composition and diversity but showed different levels of community structure stability over time. The community structure in Pawleys Island sands showed no significant change over time, while Garden City experienced significant shifts between each sampling date. Community structure also differed between beaches and, to a lesser degree, sampling date. These data provide evidence of the high microbial diversity within these beach sands and suggest that even though beaches of the same geographic region can show similarity in composition and diversity at a particular timepoint, the nature of their community structure and underlying diversity may differ comparatively and over time., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the association between insurance provider and reported assistive technology (AT) use to access computers and electronic devices 1 year after sustaining tetraplegia., Design: Multicenter cross-sectional study., Setting: Participants enrolled in the Spinal Cord Injury Model Systems (SCIMS) National Database., Interventions: Not applicable., Participants: Men and women with tetraplegia (N=498) enrolled in the SCIMS National Database were included in the analysis., Main Outcome Measures: The primary study outcome was the use of AT when operating a computer or other mobile electronic device. The primary predictor was the subject's principal health insurance provider, which was grouped into the 3 categories: government (Medicare, Medicaid, and other government), private (private insurance, private funds, and other), and workers' compensation., Results: Overall, 34.7% of participants reported using AT to access computers and electronic devices. Results of logistic regression analysis revealed sex, injury level, injury completeness, self-perceived health status, and 12-month history of pressure ulcer were all significantly associated with AT use. After adjusting for these factors, participants with workers' compensation were more likely to report AT use than individuals with either government or private insurance., Conclusions: Despite significant technological advances, AT is not readily available to the people who might benefit most from its use. Findings from the present study are the first to shed light on AT funding sources and reveal that individuals with workers' compensation are more likely use AT than individuals with either government or private insurance. Additional work focused on AT use and functional outcomes is needed to assess the effect of barriers to use. Collectively, this work may inform insurers of the importance of having AT available for this unique population to potentially improve quality of life and participation., (Copyright © 2019 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Refinement of robotic exoskeletons for overground walking is progressing rapidly. We describe clinicians' experiences, evaluations, and training strategies using robotic exoskeletons in spinal cord injury rehabilitation and wellness settings and describe clinicians' perceptions of exoskeleton benefits and risks and developments that would enhance utility., Methods: We convened focus groups at 4 spinal cord injury model system centers. A court reporter took verbatim notes and provided a transcript. Research staff used a thematic coding approach to summarize discussions., Results: Thirty clinicians participated in focus groups. They reported using exoskeletons primarily in outpatient and wellness settings; 1 center used exoskeletons during inpatient rehabilitation. A typical episode of outpatient exoskeleton therapy comprises 20 to 30 sessions and at least 2 staff members are involved in each session. Treatment focuses on standing, stepping, and gait training; therapists measure progress with standardized assessments. Beyond improved gait, participants attributed physiological, psychological, and social benefits to exoskeleton use. Potential risks included falls, skin irritation, and disappointed expectations. Participants identified enhancements that would be of value including greater durability and adjustability, lighter weight, 1-hand controls, ability to navigate stairs and uneven surfaces, and ability to balance without upper extremity support., Discussion and Conclusions: Each spinal cord injury model system center had shared and distinct practices in terms of how it integrates robotic exoskeletons into physical therapy services. There is currently little evidence to guide integration of exoskeletons into rehabilitation therapy services and a pressing need to generate evidence to guide practice and to inform patients' expectations as more devices enter the market.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A231).

Background: The Capabilities of Upper Extremity Test (CUE-T) is a spinal cord injury (SCI)-specific instrument based on the CUE Questionnaire (CUE-Q). Objective: To evaluate the psychometric properties of CUE-T in children with cervical SCI and determine the lowest age appropriate for test administration. Method: In this repeated measures multicenter study, 39 youths, mean age 12.3 years and mean time post injury 5.14 years, completed two administrations of the CUE-T. Test-retest reliability, internal consistency, and known groups validity were measured. Concurrent and discriminant validity were measured against previously validated measures: CUE-Q, Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP), Spinal Cord Independence Measure (SCIM) III, SCIM III-Self Care (SCIM-SC), and SCIM-Mobility. Results: The CUE-T scores demonstrated strong test-retest reliability (ICC ≥ 0.95), strong internal consistency (α ≥ 0.90), and acceptable individual item agreement (κ ≥ 0.49). The hand subscale had better scores ( p < .05) for the motor incomplete versus complete known groups, and the arm, hand, and side subscales had better scores ( p < .05) for higher versus lower strength groups. The CUE-T had strong concurrent validity with the CUE-Q ( r = 0.85-0.87), GRASSP ( r = 0.78-0.90), and SCIM-SC ( r = 0.70) and moderate-to-weak correlation with the total SCIM ( r = 0.65) and SCIM-Mobility ( r = 0.51). Children older than 6 years with mature grasp patterns were able to complete the CUE-T. Conclusion: The CUE-T scores are reliable and valid for use in children with cervical SCI older than 6 years of age., Competing Interests: This study was funded by the Craig H. Neilsen Foundation, Spinal Cord Injury Research on the Translation Spectrum, Senior Research Award #282592. Dr. Mulcahey reports grants from Shriners Hospitals for Children, National Institute for Neurological Diseases and Stroke, Craig H. Neilsen Foundation, and The Rick Hansen Institute during the conduct of the study; personal fees from Topics in Spinal Cord Injury Rehabilitation, from the textbook The Child and Young Adult with Spinal Cord Injury, from Department of Defense, and from Craig H. Neilsen Foundation outside the submitted work. Ms. Calhoun Thielen reports a portion of her salary was paid by grants issued to Thomas Jefferson University by Craig H. Neilsen Foundation. Mary Free Bed Rehabilitation Hospital was a subaward recipient of the Neilsen Foundation grant #282592 awarded to Principal Investigator MJ Mulcahey. Mary Free Bed Rehabilitation is also the current recipient of two other Neilsen Foundation grants that are not related to this study. The Department of Rehabilitation Medicine and Thomas Jefferson University receive payment for preparation and supply of CUE-T test kits if these are provided by the Department. Dr. Marino reports grants from Craig H. Neilsen Foundation during the conduct of the study. Ms. Dent reports grants and nonfinancial support from Thomas Jefferson University during the conduct of the study.

Study Design: Multi-center, repeated measures OBJECTIVES: Evaluate psychometric properties of the SCIM-III in children., Setting: Seven facilities in North America METHODS: One-hundred and twenty-seven youths, mean age of 10.8 years and chronic spinal cord injury/dysfunction completed two administrations of the Spinal Cord Independence Measure-III (SCIM-III). Mean, standard deviation, range values were calculated for SCIM-III total and subscales for the entire sample, four age groups and injury characteristics. Test-retest reliability, concurrent validity, and floor and ceiling effects were examined., Results: Total SCIM-III and self-care (SC) subscale scores for the youngest age group were lower than those for the three older age groups. There were statistically significant differences in SC subscale scores between neurological level (NL) C5-T1 and T2 -T12; C5-T1 and L1-S4/5; and T2-T12 and L1-S4/5 and in in-room, and indoor/outdoor mobility subscale scores between C1-C4 and T2-T12; C1-C4 and L1-S4/5; C5-T1 and T2-T12; C5-T1 and L1-S4/5; and T2-T12 and L1-S4/5. All scores between motor complete and motor incomplete differed. Test-retest reliability was good (ICC values = > 0.84) and there was moderate to strong correlation between SCIM-III and the FIM® Instrument (r = 0.77-0.92). Ceiling effects were present in the SC subscale for the oldest age group (24%) and for NL L1-S4/5 (35.5%) and in in-room mobility subscale for 6-12 (45.7%), 13-15 (30.43%) and 16-17 (60%) ages, paraplegia (42.4%), tetraplegia (37.1%), incomplete injuries (50%), and T2-T12 (38%) and L1-S4/5 (100%) NL., Conclusion: Despite limitations in content range, the SCIM-III is reproducible, and a valid indicator of physical functioning in youth with SCI/D 6 years of age and older., Sponsorship: The study was funded by the Craig H. Neilsen Foundation, Spinal Cord Injury Research on the Translation Spectrum, Senior Research Award Grant #282592 (Mulcahey, PI).

Eph receptor and ephrin signalling has a major role in cell segregation and border formation, and may act through regulation of cell adhesion, repulsion or tension. To elucidate roles of cell repulsion and adhesion, we combined experiments in cell culture assays with quantitations of cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing cells have strong heterotypic and weak homotypic repulsion. EphB2 cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2-ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of cell behaviour reveal that heterotypic repulsion can account for cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders., (© 2017 The Authors.)

Objectives: To (1) examine a measure of loneliness and its correlates in people with spinal cord injury (SCI) to enhance our understanding of loneliness, which has received limited scientific study in the context of SCI; and (2) conduct preliminary analyses of the reliability and validity of the measure, including an evaluation of the unique impact of loneliness on psychological health., Design: Cross-sectional., Setting: Spinal Cord Injury Model Systems., Participants: People with SCI (N=175) participating in Spinal Cord Injury Model Systems follow-up interviews at 1 study site between April 2014 and June 2015., Interventions: Not applicable., Main Outcome Measure: The 3-item Loneliness Scale., Results: Examination of individual items showed that approximately 40% of the sample reported that they felt they lacked companionship, felt left out, and felt isolated from others either some of the time or often. Mean scores in our sample were elevated compared with published data on middle-aged and older adults. Results provided evidence of internal consistency, comparable to that reported in the literature, and preliminary evidence of convergent and divergent validity. Loneliness was related to psychological health even after controlling for measures of demographics, disability, and social integration, suggesting that loneliness captures more than just social isolation or social integration in people with SCI., Conclusions: Loneliness, which may be more common among people with SCI, is related to poorer psychological health. Given the serious physical and psychological health consequences of loneliness documented in the general literature, it is imperative that the experience of loneliness among people with SCI be given serious and systematic attention in the literature as well as in clinical practice., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

This study examined longitudinal associations between specific parenting factors and delay inhibition in socioeconomically disadvantaged preschoolers. At Time 1, parents and 2- to 4-year-old children (mean age = 3.21 years; N = 247) participated in a videotaped parent-child free play session, and children completed delay inhibition tasks (gift delay-wrap, gift delay-bow, and snack delay tasks). Three months later, at Time 2, children completed the same set of tasks. Parental responsiveness was coded from the parent-child free play sessions, and parental directive language was coded from transcripts of a subset of 127 of these sessions. Structural equation modeling was used, and covariates included age, gender, language skills, parental education, and Time 1 delay inhibition. Results indicated that in separate models, Time 1 parental directive language was significantly negatively associated with Time 2 delay inhibition, and Time 1 parental responsiveness was significantly positively associated with Time 2 delay inhibition. When these parenting factors were entered simultaneously, Time 1 parental directive language significantly predicted Time 2 delay inhibition whereas Time 1 parental responsiveness was no longer significant. Findings suggest that parental language that modulates the amount of autonomy allotted the child may be an important predictor of early delay inhibition skills.

This article reports findings from a cluster-randomized study of an integrated literacy- and math-focused preschool curriculum, comparing versions with and without an explicit socioemotional lesson component to a business-as-usual condition. Participants included 110 classroom teachers from randomized classrooms and approximately eight students from each classroom (N = 760) who averaged 4.48 (SD = 0.44) years of age at the start of the school year. There were positive impacts of the two versions of the curriculum on language, phonological awareness, math, and socioemotional outcomes, but there were no added benefits to academic or socioemotional outcomes for the children receiving explicit socioemotional instruction. Results are discussed with relevance to early childhood theory, policy, and goals of closing the school readiness gap., (© 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.)

While the majority of cells in an organism are static and remain relatively immobile in their tissue, migrating cells occur commonly during developmental processes and are crucial for a functioning immune response. The mode of migration has been described in terms of various types of random walks. To understand the details of the migratory behaviour we rely on mathematical models and their calibration to experimental data. Here we propose an approximate Bayesian inference scheme to calibrate a class of random walk models characterized by a specific, parametric particle re-orientation mechanism to observed trajectory data. We elaborate the concept of transition matrices (TMs) to detect random walk patterns and determine a statistic to quantify these TM to make them applicable for inference schemes. We apply the developed pipeline to in vivo trajectory data of macrophages and neutrophils, extracted from zebrafish that had undergone tail transection. We find that macrophage and neutrophils exhibit very distinct biased persistent random walk patterns, where the strengths of the persistence and bias are spatio-temporally regulated. Furthermore, the movement of macrophages is far less persistent than that of neutrophils in response to wounding.

This study examined the concurrent and longitudinal associations of parental responsiveness and inferential language input with cognitive skills and emotion knowledge among socioeconomically disadvantaged preschoolers. Parents and 2- to 4-year-old children (mean age=3.21 years, N=284) participated in a parent-child free play session, and children completed cognitive (language, early literacy, early mathematics) and emotion knowledge assessments. Approximately 1 year later, children completed the same assessment battery. Parental responsiveness was coded from the videotaped parent-child free play sessions, and parental inferential language input was coded from transcripts of a subset of 127 of these sessions. All analyses controlled for child age, gender, and parental education, and longitudinal analyses controlled for initial skill level. Parental responsiveness significantly predicted all concurrent cognitive skills as well as literacy, math, and emotion knowledge 1 year later. Parental inferential language input was significantly positively associated with children's concurrent emotion knowledge. In longitudinal analyses, an interaction was found such that for children with stronger initial language skills, higher levels of parental inferential language input facilitated greater vocabulary development, whereas for children with weaker initial language skills, there was no association between parental inferential language input and change in children's vocabulary skills. These findings further our understanding of the roles of parental responsiveness and inferential language input in promoting children's school readiness skills., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Research has documented high rates of depression in people with spinal cord injury (SCI); however, most SCI research is conducted with predominantly male study participants. Additional research is needed on depression and depression treatment among women with SCI., Objective: Study objectives were to examine depression, correlates of depression, and depression treatment in a sample of women with SCI., Methods: The sample included 51 ethnically and racially diverse women with SCI who participated in a larger study on secondary conditions of women with diverse physical disabilities. Recruited through health clinics and community organizations in a large metropolitan area, participants completed structured interviews that included demographic and disability characteristics and measures of health and health care utilization., Results: Scores on the Beck Depression Inventory-II (BDI-II) indicated that 41% of the women had depressive symptomatology in the mild to severe range. BDI-II scores were significantly related to more severe secondary conditions, greater pain, and poorer health perceptions but not to demographic or disability variables. Nearly a third (n = 16) of the women had scores exceeding the standard cutoff for significant clinical depressive symptomatology, yet only 5 of those had received any treatment for depression in the past 3 months and only 1 had received counseling or psychotherapy. Lifelong depression treatment showed a similar pattern of predominantly pharmacologic treatment., Conclusion: Depression is a common problem for women with SCI, and many do not receive treatment, particularly psychological treatment. Disability-sensitive and affordable depression treatment must be made available to women with SCI.

This study used a longitudinal design to examine whether effortful control mediated the associations of parental education and home environment quality with preacademic knowledge in toddlers and young preschoolers. The sample consisted of 226 children (2 to 4 years of age at T1) from socioeconomically disadvantaged backgrounds. Parents provided data on parent education and home environment quality. Children completed effortful control, early literacy, and early math assessments. T2 effortful control partially mediated the associations of T1 parental education and T1 home environment quality with T3 emergent literacy after accounting for child age, gender, race/ethnicity, T1 effortful control, and T2 early literacy. T2 effortful control partially mediated the association between T1 parental education and T3 emergent math after accounting for child age, gender, race/ethnicity, T1 effortful control, and T2 early math. Prior to entry into preschool, parental education and home environment quality may shape effortful control which in turn influences preacademic knowledge.

Objectives: To determine whether demographic, injury, health, and functional factors similarly have the same predictive relation with both somatic and nonsomatic symptoms of depression, as well as whether somatic and nonsomatic symptoms of depression have the same association with quality of life (QOL)., Design: Secondary analysis of cross-sectional survey data., Setting: Community, Participants: Patients with traumatic spinal cord injury (N=4976) who completed an interview at 1 year postinjury between 2006 and 2011., Interventions: Not applicable., Main Outcome Measures: Somatic and nonsomatic symptoms of depression from the Patient Health Questionnaire-9 and QOL measured by the Satisfaction With Life Scale., Results: Structural equation modeling showed that the hypothesized model provided a good fit to the data, but modification of the model led to a significant improvement in model fit: Δχ(2)(1)=226.21, P<.001; comparative fit index=.976; χ(2)(199)=585.39, P<.001; root mean square error of approximation=.027 (90% confidence interval, .025-.030). The health-related factors including pain severity, pain interference, and health status were similarly associated with both somatic and nonsomatic symptoms of depression. QOL was negatively associated with nonsomatic symptoms of depression but was unrelated to somatic symptoms of depression., Conclusions: Assessment of depression after spinal cord injury should include a careful assessment of health concerns given the relation between health-related factors and both somatic and nonsomatic symptoms of depression. Treatments of depressive symptoms may be improved by targeting health concerns, such as pain, along with a specific focus on nonsomatic symptoms to improve the QOL., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

Objective: To examine correlates of depressive symptomatology in a sample of women with diverse physical disabilities to inform practice of modifiable risk factors that warrant attention and intervention., Design: Interview survey., Setting: Outpatient chronic care clinics., Participants: Racially and ethnically diverse women (N=415) aged 18 to 64 years living with physical disabilities., Interventions: Not applicable., Main Outcome Measure: Center for Epidemiologic Studies Depression Scale., Results: Depressive symptoms were high with more than half the women exceeding an established cutoff for clinically significant depressive symptomatology. In hierarchical multiple regression analyses, demographic, disability, and health variables explained significant variance in depressive symptoms; however, modifiable variables (pain interference, social support, abuse) contributed significantly to depression scores over and above demographic, disability, and health variables. Analyses examining predictors of depression classification revealed similar findings., Conclusions: Depression is a significant problem for many women with physical disabilities. Modifiable contributors to depressive symptoms may provide intervention opportunities for researchers and clinicians. Clinicians need to attend closely to pain, particularly perceptions of pain interference; social support and social isolation; and abuse among women with physical disabilities. It may be valuable to include pain self-management, social networking and social skill development, and safety and abuse prevention training when designing depression intervention programs for this population., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The current study examined the role of early executive functions (EF) and social language (SL) as well as responsive parenting as mediators of the effect of group on social problem-solving skills at 7 years of age for children with spina bifida and typically developing children., Method: A mediation analysis was used to determine if the effect of having spina bifida on school age social problem-solving skills was mediated through the effect of group on EF/SL at 3 years of age and responsive parenting at 12 and 18 months. As part of a larger longitudinal study, 103 infants (n = 49 with spina bifida; n = 54 typically developing) received measures of EF/SL at 3 years of age and mother-infant play interactions at 12 and 18 months of age were coded for a range of responsive parenting behaviors. Social problem-solving skills were measured with a game-like observational task at 7 years of age., Results: Group had a direct relation with later social problem-solving as well as an indirect relation through early EF/SL skills that, in turn, had a direct relation with later social problem solving. An indirect effect of responsive parenting on later social skills also was found through a direct effect on EF/SL skills., Conclusion: Early precursors of school age difficulties with social problem solving observed for children with spina bifida can be explained, in part, by difficulties in the first 3 years of life with EF/SL. Early responsive parenting appears to positively affect the development of these EF/SL skills. Implications for early intervention are an outcome of this study.

Sapropterin, a synthetic form of tetrahydrobiopterin (BH4), has been reported to improve symptoms in children with autism spectrum disorder (ASD). However, as BH4 is involved in multiple metabolic pathway that have been found to be dysregulated in ASD, including redox, pterin, monoamine neurotransmitter, nitric oxide (NO) and immune metabolism, the metabolic pathway by which sapropterin exerts its therapeutic effect in ASD effect remains unclear. This study investigated which metabolic pathways were associated with symptomatic improvement during sapropterin treatment. Ten participants (ages 2-6 years old) with current social and/or language delays, ASD and a central BH4 concentration 30 nM l(-1) were treated with a daily morning 20 mg kg(-1) dose of sapropterin for 16 weeks in an open-label fashion. At baseline, 8 weeks and 16 weeks after starting the treatment, measures of language, social function and behavior and biomarkers of redox, pterin, monoamine neurotransmitter, NO and immune metabolism were obtained. Two participants discontinued the study, one from mild adverse effects and another due to noncompliance. Overall, improvements in subscales of the Preschool Language Scale (PLS), Vineland Adaptive Behavior Scale (VABS), Aberrant Behavior Checklist (ABC) and autism symptoms questionnaire (ASQ) were seen. Significant changes in biomarkers of pterin, redox and NO were found. Improvement on several subscales of the PLS, VABS, ABC and ASQ were moderated by baseline and changes in biomarkers of NO and pterin metabolism, particularly baseline NO metabolism. These data suggest that behavioral improvement associated with daily 20 mg kg(-1) sapropterin treatment may involve NO metabolism, particularly the status of pretreatment NO metabolism.

Infants with Spina Bifida (SB) were compared to typically developing infants (TD) using a conjugate reinforcement paradigm at 6 months-of-age (n = 98) to evaluate learning, and retention of a sensory-motor contingency. Analyses evaluated infant arm-waving rates at baseline (wrist not tethered to mobile), during acquisition of the sensory-motor contingency (wrist tethered), and immediately after the acquisition phase and then after a delay (wrist not tethered), controlling for arm reaching ability, gestational age, and socioeconomic status. Although both groups responded to the contingency with increased arm-waving from baseline to acquisition, 15% to 29% fewer infants with SB than TD were found to learn the contingency depending on the criterion used to determine contingency learning. In addition, infants with SB who had learned the contingency had more difficulty retaining the contingency over time when sensory feedback was absent. The findings suggest that infants with SB do not learn motor contingencies as easily or at the same rate as TD infants, and are more likely to decrease motor responses when sensory feedback is absent. Results are discussed with reference to research on contingency learning in infants with and without neurodevelopmental disorders, and with reference to motor learning in school-age children with SB.