Functional outcome 5 years after non-operative treatment of type A spinal fractures

This study was conducted to study the functional outcome after non-operative treatment of type A thoracolumbar spinal fractures without neurological deficit. Functional outcome was determined following the International Classification of Functioning, Disability and Health, measuring restrictions in body function and structure, restrictions in activities, and restrictions in participation/quality of life. All patients were treated non-operatively for a type A thoracolumbar (Th11-L4) spinal fracture at the University Hospital Groningen, The Netherlands. Thirty-three of the eighty-one selected patients agreed to participate in the study (response-rate 41%). Respondents were older than non-respondents (mean 50.5 years vs. 39.2 years), but did not differ from each other concerning injury-related variables. Patients with a neurological deficit were excluded. Treatment consisted either of mobilisation without brace, or of bedrest followed by wearing a brace. Restrictions in body function and structure were measured by physical tests (dynamic lifting test and bicycle ergometry test); restrictions in activities were measured by means of questionnaires, the Roland Morris Disability Questionnaire (RMDQ) and Visual Analogue Scale Spine Score (VAS). Restrictions in participation/quality of life were assessed with the Short Form 36 (SF-36) and by means of return to work status. Thirty-seven per cent of the patients were not able to perform the dynamic lifting test within normal range. In the ergometry test, 40.9% of the patients performed below the lowest normal value, 36.4% of the patients achieved a high VO2-max. Mean RMDQ-score was 5.2, the mean VAS-score was 79. No significant differences between patients and healthy subjects were found in SF-36 scores, neither were differences found between braced and unbraced patients in any of the outcome measures. Concerning the return to work status, 10% of the subjects had stopped working and received social security benefits, 24% had arranged changes in their work and 14% had changed their job. We conclude that patients do reasonably well 5 years after non-operative treatment of a thoracolumbar fracture, although outcome is diverse in the different categories and physical functioning seems restricted in a considerable number of patients.</p

Long-term outcome of sports injuries:results after inpatient treatment

OBJECTIVE: To investigate whether sports injuries result in long-term disabilities and handicaps and to establish variables with a prognostic value for the occurrence of these long-term consequences. MATERIALS AND METHODS: All patients older than 17 years of age and admitted to the University Hospital Groningen because of a sports injury were entered in the study. By filling in a questionnaire 1-4 years after the injury an inventory was made of the long-term consequences. MAIN OUTCOME MEASURES: Absenteeism from work and sports, experienced disabilities or handicaps and the Sickness Impact Profile 68 (SIP68). RESULTS: Out of 306 patients 229 (75%) returned a completed questionnaire. Sixty-seven per cent of the working population had been unfit for work up to one year, whereas 4% still had not resumed work. Absenteeism from sports was also considerable; nearly half of the population did not participate in sports for more than a year. Furthermore, 32% of the patients still experienced disability or handicap following the injury. This finding is in agreement with the results of the SIP68 (odds ratio 6.8; confidence interval (95% CI): 3.51-13.08). Two prognostic variables could be distinguished: 'gender' and 'type of sport'. Long-term consequences occur more often in women (p < 0.03) and with playing outdoor soccer, horse riding or skiing (p < 0.01). CONCLUSIONS: Sports injuries can lead to long-term disabilities and handicaps. The variables 'gender' and 'type of sport' were of prognostic significance. Record 2 of 12 - SilverPlatter MEDLINE(R)

Body-composition reference data for simple and reference techniques and a 4-component model: A new UK reference child

Background: A routine pediatric clinical assessment of body composition is increasingly recommended but has long been hampered by the following 2 factors: a lack of appropriate techniques and a lack of reference data with which to interpret individual measurements. Several techniques have become available, but reference data are needed. Objective: We aimed to provide body-composition reference data for use in clinical practice and research. Design: Body composition was measured by using a gold standard 4-component model, along with various widely used reference and bedside methods, in a large, representative sample of British children aged from 4 to ≥20 y. Measurements were made of anthropometric variables (weight, height, 4 skinfold thicknesses, and waist girth), dual-energy X-ray absorptiometry, body density, bioelectrical impedance, and total body water, and 4-component fat and fat-free masses were calculated. Reference charts and SD scores (SDSs) were constructed for each outcome by using the lambda-mu-sigma method. The same outcomes were generated for the fat-free mass index and fat mass index. Results: Body-composition growth charts and SDSs for 5-20 y were based on a final sample of 533 individuals. Correlations between SDSs by using different techniques were ≥0.68 for adiposity outcomes and ≥0.80 for fat-free mass outcomes. Conclusions: These comprehensive reference data for pediatric body composition can be used across a variety of techniques. Together with advances in measurement technologies, the data should greatly enhance the ability of clinicians to assess and monitor body composition in routine clinical practice and should facilitate the use of body-composition measurements in research studies. © 2012 American Society for Nutrition

Six years beyond pediatric trauma: child and parental ratings of children’s health-related quality of life in relation to parental mental health

Purpose: To examine the relationship between child self-report and parent proxy report of health-related quality of life (HRQL) and how parents’ mental health status relates to the HRQL ratings 6 years after minor to severe injury of the child. Materials and methods: This cross-sectional cohort study was performed at a regional pediatric trauma center in Stockholm, Sweden. The PedsQL 4.0 versions for ages 5–7, 8–12, and 13–18 years were completed by 177 child–parent dyads 6 years after injury to the child. The parents also rated their own mental health through the mental health domain (MH) in the SF-36 Health Survey. Results: The children’s median age was 13 years (IQR 10–16 years), 54 % were males, and the median ISS was 5 (IQR 2–9). Most of the parents were female (77 %), born in Sweden (79 %), and half had university degrees. There was no statistically significant difference between child self-report and parent proxy report in any of the PedsQL 4.0 scales or summary scales. The levels of agreement between child self-report and parent proxy reports were excellent (ICC ≥ 0.80) for all scales with the exception of emotional functioning (ICC 0.53) which also was the scale with the lowest internal consistency in child self-report (α 0.60). Multiple regression analyses showed that worse parental mental health status correlated with worse child self-report and parent proxy report of children’s HRQL. Conclusions: Children and their parents’ reports on child’s HRQL were in agreement. Decreased mental health in parents was associated with lower scores on parent proxy reports and child self-reports of HRQL after injury. The current investigation highlights the possible relationship between parent’s mental health status and children’s HRQL long after an injury, which should be considered in future investigations and in clinical care

An intestinal epithelial defect conferring ER stress results in inflammation involving both innate and adaptive immunity

We recently characterized Winnie mice carrying a missense mutation in Muc2, leading to severe endoplasmic reticulum stress in intestinal goblet cells and spontaneous colitis. In this study, we characterized the immune responses due to this intestinal epithelial dysfunction. In Winnie, there was a fourfold increase in activated dendritic cells (DCs; CD11c+ major histocompatibility complex (MHC) class IIhi) in the colonic lamina propria accompanied by decreased colonic secretion of an inhibitor of DC activation, thymic stromal lymphopoietin (TSLP). Winnie also displayed a significant increase in mRNA expression of the mucosal TH17 signature genes Il17a, IL17f, Tgfb, and Ccr6, particularly in the distal colon. Winnie mesenteric lymph node leukocytes secreted multiple TH1, TH2, and TH17 cytokines on activation, with a large increase in interleukin-17A (IL-17A) progressively with age. A major source of mucosal IL-17A in Winnie was CD4+ T lymphocytes. Loss of T and B lymphocytes in Rag1-/- × Winnie (RaW) crosses did not prevent spontaneous inflammation but did prevent progression with age in the colon but not the cecum. Adoptive transfer of naive T cells into RaW mice caused more rapid and severe colitis than in Rag1-/-, indicating that the epithelial defect results in an intestinal microenvironment conducive to T-cell activation. Thus, the Winnie primary epithelial defect results in complex multicytokine-mediated colitis involving both innate and adaptive immune components with a prominent IL-23/TH17 response, similar to that of human ulcerative colitis

SecA, a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data

Cloning, annotation and developmental expression of the chicken intestinal MUC2 gene

Intestinal mucin 2 (MUC2) encodes a heavily glycosylated, gel-forming mucin, which creates an important protective mucosal layer along the gastrointestinal tract in humans and other species. This first line of defense guards against attacks from microorganisms and is integral to the innate immune system. As a first step towards characterizing the innate immune response of MUC2 in different species, we report the cloning of a full-length, 11,359 bp chicken MUC2cDNA, and describe the genomic organization and functional annotation of this complex, 74.5 kb locus. MUC2 contains 64 exons and demonstrates distinct spatiotemporal expression profiles throughout development in the gastrointestinal tract; expression increases with gestational age and from anterior to posterior along the gut. The chicken protein has a similar domain organization as the human orthologue, with a signal peptide and several von Willebrand domains in the N-terminus and the characteristic cystine knot at the C-terminus. The PTS domain of the chicken MUC2 protein spans ~1600 amino acids and is interspersed with four CysD motifs. However, the PTS domain in the chicken diverges significantly from the human orthologue; although the chicken domain is shorter, the repetitive unit is 69 amino acids in length, which is three times longer than the human. The amino acid composition shows very little similarity to the human motif, which potentially contributes to differences in the innate immune response between species, as glycosylation across this rapidly evolving domain provides much of the musical barrier. Future studies of the function of MUC2 in the innate immune response system in chicken could provide an important model organism to increase our understanding of the biological significance of MUC2 in host defense and highlight the potential of the chicken for creating new immune-based therapies

Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium