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.