Early risk factors for lumbar discectomy: an 11-year follow-up of 57,408 adolescents

There is a lack of longitudinal studies on the risk factors of lumbar discectomy. Using combined population survey and hospital discharge register data in a prospective longitudinal design, we investigated the association between adolescent risk factors and lumbar discectomy until early middle age. A prospective cohort of health survey respondents (n = 57,408) aged 14–18 years was followed for 651,000 person-years (average follow-up, 11.3 years). Study endpoints were lumbar discectomy, death or end of follow-up. Participants’ mean age at the end of follow-up was 27 years. In multivariate Cox’s regression analysis, the significant risk factor for lumbar discectomy among male respondents was daily smoking, HR being 1.5 (95% CI 1.1–2.2). In females, frequent participation in sports clubs (HR 2.7, 95% CI 1.1–6.3) and overweight (HR 2.1; 95% CI 1.1–4.1) were significantly associated with an increased risk of lumbar discectomy. Daily smoking in males and frequent participation in sports clubs and overweight in females measured at adolescence were statistically associated with lumbar discectomy at an 11-year follow-up, although the hazard ratios were relatively small. Further study of these common risk factors and their modifications may lead to a better understanding of the causes of lumbar disc herniation

Selection of Specific Protein Binders for Pre-Defined Targets from an Optimized Library of Artificial Helicoidal Repeat Proteins (alphaRep)

We previously designed a new family of artificial proteins named αRep based on a subgroup of thermostable helicoidal HEAT-like repeats. We have now assembled a large optimized αRep library. In this library, the side chains at each variable position are not fully randomized but instead encoded by a distribution of codons based on the natural frequency of side chains of the natural repeats family. The library construction is based on a polymerization of micro-genes and therefore results in a distribution of proteins with a variable number of repeats. We improved the library construction process using a “filtration” procedure to retain only fully coding modules that were recombined to recreate sequence diversity. The final library named Lib2.1 contains 1.7×10(9) independent clones. Here, we used phage display to select, from the previously described library or from the new library, new specific αRep proteins binding to four different non-related predefined protein targets. Specific binders were selected in each case. The results show that binders with various sizes are selected including relatively long sequences, with up to 7 repeats. ITC-measured affinities vary with K(d) values ranging from micromolar to nanomolar ranges. The formation of complexes is associated with a significant thermal stabilization of the bound target protein. The crystal structures of two complexes between αRep and their cognate targets were solved and show that the new interfaces are established by the variable surfaces of the repeated modules, as well by the variable N-cap residues. These results suggest that αRep library is a new and versatile source of tight and specific binding proteins with favorable biophysical properties