For proteins that traverse the secretory pathway, folding commences cotranslationally upon translocation into the endoplasmic reticulum. In this study, we have comprehensively analyzed the earliest maturation steps of the model glycoprotein influenza hemagglutinin (HA). These steps include cleavage of the signal sequence, glycosylation, binding by the chaperones calnexin and calreticulin, and the oxidoreductase ERp57, and oxidation. Our results show that the molecular choreography of the nascent HA chain is largely directed by multiple glycans that are strategically placed to elicit the binding of lectin chaperones. These chaperones are recruited to specific nascent chain locations to regulate and facilitate glycoprotein folding, thereby suggesting that the positioning of N-linked glycans in critical regions has evolved to optimize the folding process in the cell.

Objective To describe the methodology and report primary outcomes of an exploratory randomized clinical trial (RCT) of aerobic training for management of prolonged symptoms after mild traumatic brain injury (mTBI) in adolescents. Setting Outpatient research setting Participants Thirty adolescents between the ages of 12 and 17 years who sustained a mTBI and had between four and 16 weeks of persistent symptoms. Design Partially blinded, pilot RCT of sub-symptom exacerbation aerobic training compared to a full-body stretching program. Main Measures The primary outcome was post injury symptom improvement assessed by the adolescent’s self-reported Post Concussion Symptom Inventory (PCSI) repeated for at least six weeks of the intervention. Parent-reported PCSI and adherence are also described. Results Twenty-two percent of eligible participants enrolled in the trial. Repeated measures Analysis of Variance via mixed model analysis demonstrated a significant group by time interaction with self-reported PCSI ratings, indicating a greater rate of improvement in the sub-symptom exacerbation aerobic training compared to the full-body stretching group (F-value = 4.11, p-value = .044). Adherence to the home exercise programs was lower in the sub-symptom exacerbation aerobic training compared to the full-body stretching group (mean (SD) times per week = 4.42 (1.95) versus 5.85 (1.37), p < .0001) over the duration of the study. Conclusion Findings from this exploratory randomized clinical trial suggest sub-symptom exacerbation aerobic training is potentially beneficial for adolescents with persistent symptoms after mTBI. These findings and other recent research support the potential benefit of active rehabilitation programs for adolescents with persistent symptoms after mTBI. Larger replication studies are needed to verify findings and improve generalizability. Future work should focus on determining the optimal type, timing, and intensity of active rehabilitation programs and characteristics of individuals most likely to benefit.

.As the life expectancy of individuals with spina bifida increases, a lifelong need for management of many health issues in a rehabilitation setting has emerged in recent years. Physiatrists, in consultation with a variety of adult specialists, are particularly well suited to manage the common musculoskeletal, skin, bowel, bladder, renal, neurological, and other issues that arise in the adult population. This article reviews the last 20 yrs of literature pertinent to the rehabilitative care of this population, summarizes current evidence-based practice, and identifies key areas in which scientific evidence is lacking and future research is needed.

BACKGROUND Many organizations and health care providers support educating high school (HS) athletes about concussions to improve their attitudes and behaviors about reporting. The objectives of this study were to determine if previous education, sport played, and individual factors were associated with better knowledge about concussion and to determine if more knowledge was associated with improved self-reported attitudes toward reporting concussions among HS athletes. METHODS We conducted a survey of HS athletes aged 13 years to 18 years from two large, urban HSs. Players were recruited from selected seasonal (fall and winter) as well as men and women’s sports. During preseason, each participant was given a survey asking about his or her previous education, current knowledge, and self-reported attitudes and behaviors about reporting concussions. Bivariate and multivariate linear regression was used to evaluate the association of age, sex, sport, and previous concussion education with knowledge and self-reported attitudes and behaviors about reporting concussions. RESULTS Surveys were completed by 496 athletes. The median age was 15 years, and 384 (77.4%) were male. A total of 212 (42.7%) participated in football, 123 (24.8%) in soccer, 89 (17.9%) in basketball, and 72 (14.5%) in wrestling. One hundred sixteen (23.4%) reported a history of concussion. Improved knowledge regarding concussions was not associated with improved self-reported behaviors (p = 0.63) in bivariate regression models. The multivariate model demonstrated that older age (p = 0.01) and female sex (p = 0.03) were associated with better knowledge. Younger age (p = 0.01), female sex (p = 0.0002), and soccer participation (p = 0.02) were associated with better self-reported behaviors around reporting concussions. CONCLUSION Previous education on concussions was less predictive of knowledge about concussions when controlling for other factors such as sport and sex. Younger age, female sex, and soccer participation were more likely to be associated with better self-reported behaviors. Future studies need to focus on the development of interventions to improve concussion-specific knowledge and behaviors. LEVEL OF EVIDENCE Epidemiologic study, level III.

Background The benefit of preseason concussion education on athletes’ knowledge, attitudes, and behaviors is unclear. The purpose of the study was to determine the influence of preseason concussion education on knowledge and self-reported attitudes and reporting behaviors. We hypothesized that preseason education would lead to better knowledge and self-reported attitudes and better reporting of concussion symptoms during the season. Methods Prospective cohort comparing the benefits of a preseason lectured-based concussion education session at one high school with a control school. Participants included males and females age 13–18 years from two community high schools who were participating in higher concussion risk, fall or winter sports (football, soccer, wrestling, and basketball). The education school and control school included 234 and 262 participants, respectively. Outcomes were a pre- and post-season survey assessing knowledge and self-reported attitudes about concussions and an end of season questionnaire assessing concussion reporting behaviors during the season. Results Total scores on the combined (p<.0001), knowledge-based (p=.016), and behavioral-based (p<.0001) questions demonstrated statistically significant improvement in the education group. Scores peakedimmediately post education, but dissipated at the end of the season. There was a lower proportion in the education school (72%) compared to the control school (88%) that reported continued play despite having concussion symptoms during the season (p=.025). A similar proportion of athletes diagnosed with concussion during the season in the education (27%) and control schools (23%) reported returning to play before symptoms resolved (p=.81). Conclusion These findings suggest that a didactic-based preseason concussion education likely has minimal benefits. Other factors besides knowledge are likely influencing student-athlete concussion reporting behavior. Future research focused on changing the culture of concussion reporting is needed.

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WHAT'S KNOWN ON THIS SUBJECT:Cognitive and behavioral problems after pediatric traumatic brain injury lead to poor functioning across multiple settings and can persist long-term after injury. Executive dysfunction is particularly common; however, there is a paucity of evidence-based interventions to guide treatment. WHAT THIS STUDY ADDS:This study is among the largest randomized controlled trials performed in pediatric traumatic brain injury. It demonstrates the ability to use an online problemsolving-based intervention to improve caregiver ratings of executive dysfunction within 12 months after injury. abstract OBJECTIVE: Executive dysfunction after traumatic brain injury (TBI) in children is common and leads to significant problems in functioning across multiple settings. The objective of this study was to evaluate the efficacy of a web-based counselor-assisted problem solving (CAPS) intervention compared with an Internet resource comparison (IRC) for treatment of executive dysfunction within 12 months after complicated mild to severe TBI in adolescents. We hypothesized that CAPS would significantly improve parent ratings of executive dysfunction compared with an IRC. METHODS:Participants included 132 adolescents aged 12 to 17 years who sustained a complicated mild to severe TBI within 1 to 6 months before study enrollment. Study design was a multisite, assessorblinded, randomized controlled trial. Study sites included 3 tertiary pediatric hospitals and 2 tertiary general medical centers. The main outcome measure was primary caregiver Behavioral Rating Inventory of Executive Function Global Executive Composite at baseline and 6-month follow-up. Generalized linear models that controlled for baseline scores were used to compare the CAPS and IRC scores. RESULTS:In older teens, the CAPS group showed significant improvement in executive function behaviors at 6-month follow-up compared with the IRC group (F = 6.74, P = .01, Cohen' s d = 0.63). CONCLUSIONS:Findings indicate that web-based CAPS improves primary caregiver-rated executive functioning within the first 12 months after TBI in older adolescents. Future research needs to define the optimal timing after injury for delivery of CAPS and characteristics of individuals and families who are most likely to benefit from CAPS. Pediatrics 2013;132:e158-e166 AUTHORS:

Objective To provide a review of evidence and consensus-based description of healthcare and educational service delivery and related recommendations for children with traumatic brain injury. Methods Literature review and group discussion of best practices in management of children with traumatic brain injury (TBI) was performed to facilitate consensus-based recommendations from the American Congress on Rehabilitation Medicine’s Pediatric and Adolescent Task Force on Brain Injury. This group represented pediatric researchers in public health, medicine, psychology, rehabilitation, and education. Results Care for children with TBI in healthcare and educational systems is not well coordinated or integrated, resulting in increased risk for poor outcomes. Potential solutions include identifying at-risk children following TBI, evaluating their need for rehabilitation and transitional services, and improving utilization of educational services that support children across the lifespan. Conclusion Children with TBI are at risk for long-term consequences requiring management as well as monitoring following the injury. Current systems of care have challenges and inconsistencies leading to gaps in service delivery. Further efforts to improve knowledge of the long-term TBI effects in children, child and family needs, and identify best practices in pathways of care are essential for optimal care of children following TBI.