Biomechanical effect of pedicle screw distribution in AIS instrumentation using a segmental translation technique: computer modeling and simulation

BACKGROUND: Efforts to select the appropriate number of implants in adolescent idiopathic scoliosis (AIS) instrumentation are hampered by a lack of biomechanical studies. The objective was to biomechanically evaluate screw density at different regions in the curve for AIS correction to test the hypothesis that alternative screw patterns do not compromise anticipated correction in AIS when using a segmental translation technique. METHODS: Instrumentation simulations were computationally performed for 10 AIS cases. We simulated simultaneous concave and convex segmental translation for a reference screw pattern (bilateral polyaxial pedicle screws with dorsal height adjustability at every level fused) and four alternative patterns; screws were dropped respectively on convex or concave side at alternate levels or at the periapical levels (21 to 25% fewer screws). Predicted deformity correction and screw forces were compared. RESULTS: Final simulated Cobb angle differences with the alternative screw patterns varied between 1 degrees to 5 degrees (39 simulations) and 8 degrees (1 simulation) compared to the reference maximal density screw pattern. Thoracic kyphosis and apical vertebral rotation were within 2 degrees of the reference screw pattern. Screw forces were 76 +/- 43 N, 96 +/- 58 N, 90 +/- 54 N, 82 +/- 33 N, and 79 +/- 42 N, respectively, for the reference screw pattern and screw dropouts at convex alternate levels, concave alternate levels, convex periapical levels, and concave periapical levels. Bone-screw forces for the alternative patterns were higher than the reference pattern (p 0.28). Alternate dropout screw forces were higher than periapical dropouts (p < 0.05). CONCLUSIONS: Using a simultaneous segmental translation technique, deformity correction can be achieved with 23% fewer screws than maximal density screw pattern, but resulted in 25% higher bone-screw forces. Screw dropouts could be either on the convex side or on the concave side at alternate levels or at periapical levels. Periapical screw dropouts may more likely result in lower bone-screw force increase than alternate level screw dropouts

Reproductive Isolation and Ecological Niche Partition among Larvae of the Morphologically Cryptic Sister Species Chironomus riparius and C. piger

Background One of the central issues in ecology is the question what allows sympatric occurrence of closely related species in the same general area? The non-biting midges Chironomus riparius and C. piger, interbreeding in the laboratory, have been shown to coexist frequently despite of their close relatedness, similar ecology and high morphological similarity. Methodology/Principal Findings In order to investigate factors shaping niche partitioning of these cryptic sister species, we explored the actual degree of reproductive isolation in the field. Congruent results from nuclear microsatellite and mitochondrial haplotype analyses indicated complete absence of interspecific gene-flow. Autocorrelation analysis showed a non-random spatial distribution of the two species. Though not dispersal limited at the scale of the study area, the sister species occurred less often than expected at the same site, indicating past or present competition. Correlation and multiple regression analyses suggested the repartition of the available habitat along water chemistry gradients (nitrite, conductivity, CaCO3), ultimately governed by differences in summer precipitation regime. Conclusions We show that these morphologically cryptic sister species partition their niches due to a certain degree of ecological distinctness and total reproductive isolation in the field. The coexistence of these species provides a suitable model system for the investigation of factors shaping the distribution of closely related, cryptic species

Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-β

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-β and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-α, IL-6, IL-10 and IL-1β in monocytes than did lysates. Secreted IL-18, which, like IL-1β, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine production by TLR2-deficient murine macrophages was only moderately diminished in response to live Bb but was drastically impaired against lysates; TLR2 deficiency had no significant effect on uptake and degradation of spirochetes. As with PBMCs, live Bb was a much more potent inducer of IFN-β and ISGs in isolated monocytes than were lysates or a synthetic TLR2 agonist. Collectively, our results indicate that the enhanced innate immune responses of monocytes following phagocytosis of live Bb have both TLR2-dependent and -independent components and that the latter induce transcription of type I IFNs and ISGs

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352