Uncovering the origin of Z-configured double bonds in polyketides: intermediate E-double bond formation during borrelidin biosynthesis

Formation of Z-configured double bonds in reduced polyketides is uncommon and their origins have not been extensively studied. To investigate the origin of the Z-configured double bond in the macrolide borrelidin, the recombinant dehydratase domains BorDH2 and B0rDH3 were assayed with a synthetic analogue of the predicted tetraketide substrate. The configuration of the dehydrated products was determined to be E in both cases by comparison to synthetic standards. Detailed NMR spectroscopic analysis of the biosynthetic intermediate pre-borrelidin confirmed the E,E-configuration of the fulllength polyketide synthase product. In contrast to a previously-proposed hypothesis, our results show that in this case the Z-configured double bond is not formed via dehydration from a 3 L-configured precursor, but rather as the result of a later isomerization process.Marie Curie programme of the European UnionEmmy Noether programme of the Deutsche ForschungsgemeinschaftDAA

Sacral Fractures and Associated Injuries.

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to describe the injuries associated with sacral fractures and to analyze their impact on patient outcome. METHODS: A comprehensive narrative review of the literature was performed to identify the injuries associated with sacral fractures. RESULTS: Sacral fractures are uncommon injuries that result from high-energy trauma, and that, due to their rarity, are frequently underdiagnosed and mistreated. Only 5% of sacral fractures occur in isolation. Injuries most often associated with sacral fractures include neurologic injuries (present in up to 50% of sacral fractures), pelvic ring disruptions, hip and lumbar spine fractures, active pelvic/ abdominal bleeding and the presence of an open fracture or significant soft tissue injury. Diagnosis of pelvic ring fractures and fractures extending to the lumbar spine are key factors for the appropriate management of sacral fractures. Importantly, associated systemic (cranial, thoracic, and abdominopelvic) or musculoskeletal injuries should be promptly assessed and addressed. These associated injuries often dictate the management and eventual outcome of sacral fractures and, therefore, any treatment algorithm should take them into consideration. CONCLUSIONS: Sacral fractures are complex in nature and often associated with other often-missed injuries. This review summarizes the most relevant associated injuries in sacral fractures and discusses on their appropriate management

AOSpine—Spine Trauma Classification System: The Value of Modifiers: A Narrative Review With Commentary on Evolving Descriptive Principles

Study Design: Narrative review. Objectives: To describe the current AOSpine Trauma Classification system for spinal trauma and highlight the value of patient-specific modifiers for facilitating communication and nuances in treatment. Methods: The classification for spine trauma previously developed by The AOSpine Knowledge Forum is reviewed and the importance of case modifiers in this system is discussed. Results: A successful classification system facilitates communication and agreement between physicians while also determining injury severity and provides guidance on prognosis and treatment. As each injury may be unique among different patients, the importance of considering patient-specific characteristics is highlighted in this review. In the current AOSpine Trauma Classification, the spinal column is divided into 4 regions: the upper cervical spine (C0-C2), subaxial cervical spine (C3-C7), thoracolumbar spine (T1-L5), and the sacral spine (S1-S5, including coccyx). Each region is classified according to a hierarchical system with increasing levels of injury or instability and represents the morphology of the injury, neurologic status, and clinical modifiers. Specifically, these clinical modifiers are denoted starting with M followed by a number. They describe unique conditions that may change treatment approach such as the presence of significant soft tissue damage, uncertainty about posterior tension band injury, or the presence of a critical disc herniation in a cervical bilateral facet dislocation. These characteristics are described in detail for each spinal region. Conclusions: Patient-specific modifiers in the AOSpine Trauma Classification highlight unique clinical characteristics for each injury and facilitate communication and treatment between surgeons

Modulating Myeloid Immune Cell Migration Using Multivalently Presented Monosaccharide Ligands for Advanced Immunotherapy

Due to their importance for the outcome of the inflammatory response, the motile myeloid cells are a focus of novel treatment options. The interplay of selectins and their ligands with leukocytes and endothelial cells, which mediate endothelial attachment and transmigration of immune cells, can be modulated by selectin‐binding structures. Here, a library of selectin‐targeting ligands coupled to either gold, silver, iron oxide nanospheres, or quantum dots of 5–10 nm in size is used to systematically study their impact on immune cell motility. The multivalent presentation of the carbohydrate mimetics results in very low sub‐nanomolar binding to L ‐selectin. Using human primary monocytes, granulocytes, lymphocytes, and macrophages, it is shown that the ligands exhibit only minor effects on uptake, whereas the motility of leukocytes is critically affected as observed in migration assays evaluated by flow cytometry. The carbohydrate mimetic ring structure, sulfation, in particular, and the degree of ligand presentation, are constituents which cohere in this process. Specific carbohydrate ligands can thus selectively regulate leukocyte subsets. These data form the basis for advanced immunotherapy which inhibits the amplification of inflammation by restricting leukocyte influx to injured tissue sites. Furthermore, the targeting ligands may complement existing treatment options for inflammatory diseases

Variation in global treatment for subaxial cervical spine isolated unilateral facet fractures.

PURPOSE To determine the variation in the global treatment practices for subaxial unilateral cervical spine facet fractures based on surgeon experience, practice setting, and surgical subspecialty. METHODS A survey was sent to 272 members of the AO Spine Subaxial Injury Classification System Validation Group worldwide. Questions surveyed surgeon preferences with regard to diagnostic work-up and treatment of fracture types F1-F3, according to the AO Spine Subaxial Cervical Spine Injury Classification System, with various associated neurologic injuries. RESULTS A total of 161 responses were received. Academic surgeons use the facet portion of the AO Spine classification system less frequently (61.6%) compared to hospital-employed and private practice surgeons (81.1% and 81.8%, respectively) (p = 0.029). The overall consensus was in favor of operative treatment for any facet fracture with radicular symptoms (N2) and for any fractures categorized as F2N2 and above. For F3N0 fractures, significantly less surgeons from Africa/Asia/Middle East (49%) and Europe (59.2%) chose operative treatment than from North/Latin/South America (74.1%) (p = 0.025). For F3N1 fractures, significantly less surgeons from Africa/Asia/Middle East (52%) and Europe (63.3%) recommended operative treatment than from North/Latin/South America (84.5%) (p = 0.001). More than 95% of surgeons included CT in their work-up of facet fractures, regardless of the type. No statistically significant differences were seen in the need for MRI to decide treatment. CONCLUSION Considerable agreement exists between surgeon preferences with regard to unilateral facet fracture management with few exceptions. F2N2 fracture subtypes and subtypes with radiculopathy (N2) appear to be the threshold for operative treatment

Health professionals’ perspective on the applicability of AO Spine PROST (patient reported outcome Spine trauma) in people with a motor-complete traumatic or non-traumatic spinal cord injury

Purpose: The AO Spine PROST (Patient Reported Outcome Spine Trauma) was developed for people with spine trauma and minor or no neurological impairment. The purpose is to investigate health professionals’ perspective on the applicability of the AO Spine PROST for people with motor-complete traumatic or non-traumatic spinal cord injury (SCI), using a discussion meeting and international survey study. Methods: A discussion meeting with SCI rehabilitation physicians in the Netherlands was performed, followed by a worldwide online survey among the AO Spine International community, involved in the care of people with SCI. Participants rated the comprehensibility, relevance, acceptability, feasibility and completeness of the AO Spine PROST on a 1–5 point scale (5 most positive). Comments could be provided per question. Results: The discussion meeting was attended by 13 SCI rehabilitation physicians. The survey was completed by 196 participants. Comprehensibility (mean ± SD: 4.1 ± 0.8), acceptability (4.0 ± 0.8), relevance (3.9 ± 0.8), completeness (3.9 ± 0.8), and feasibility (4.1 ± 0.7) of the AO Spine PROST were rated positively for use in people with motor-complete traumatic or non-traumatic SCI. Only a few participants questioned the relevance of items on the lower extremities (e.g., walking) or missed items on pulmonary functioning and complications. Some recommendations were made for improvement in instructions, terminology and examples of the tool. Conclusion: Health professionals found the AO Spine PROST generally applicable for people with motor-complete traumatic or non-traumatic SCI. This study provides further evidence for the use of the AO Spine PROST in spine trauma care, rehabilitation and research, as well as suggestions for its further development.</p

Effect of local TGF-β1 and IGF-1 release on implant fixation: comparison with hydroxyapatite coating: A paired study in dogs

Background and purpose Hydroxyapatite (HA) coating stimulates the osseointegration of cementless orthopedic implants. Recently, locally released osteogenic growth factors have also been shown experimentally to stimulate osseointegration so that bone fills gaps around orthopedic implants. Here, we have compared the effect of local release of TGF-β 1 and IGF-1 with that of hydroxyapatite coating on implant fixation

Establishing the Injury Severity of Subaxial Cervical Spine Trauma: Validating the Hierarchical Nature of the AO Spine Subaxial Cervical Spine Injury Classification System.

STUDY DESIGN Global cross-sectional survey. OBJECTIVE To validate the AO Spine Subaxial Cervical Spine Injury Classification by examining the perceived injury severity by surgeon across AO geographical regions and practice experience. SUMMARY OF BACKGROUND DATA Previous subaxial cervical spine injury classifications have been limited by subpar interobserver reliability and clinical applicability. In an attempt to create a universally validated scheme with prognostic value, AO Spine established a subaxial cervical spine injury classification involving four elements: (1) injury morphology, (2) facet injury involvement, (3) neurologic status, and (4) case-specific modifiers. METHODS A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. Respondents graded the severity of each variable of the classification system on a scale from zero (low severity) to 100 (high severity). Primary outcome was to assess differences in perceived injury severity for each injury type over geographic regions and level of practice experience. RESULTS A total of 189 responses were received. Overall, the classification system exhibited a hierarchical progression in subtype injury severity scores. Only three subtypes showed a significant difference in injury severity score among geographic regions: F3 (floating lateral mass fracture, p:0.04), N3 (incomplete spinal cord injury, p:0.03), and M2 (critical disk herniation, p:0.04). When stratified by surgeon experience, pairwise comparison showed only 2 morphological subtypes, B1 (bony posterior tension band injury, p:0.02) and F2 (unstable facet fracture, p:0.03), and one neurologic subtype (N3, p:0.02) exhibited a significant difference in injury severity score. CONCLUSIONS The AO Spine Subaxial Cervical Spine Injury Classification System has shown to be reliable and suitable for proper patient management. The study shows this classification is substantially generalizable by geographic region and surgeon experience; and provides a consistent method of communication among physicians while covering the majority of subaxial cervical spine traumatic injuries.Level of Evidence: 4

C2 prosthesis: anterior upper cervical fixation device to reconstruct the second cervical vertebra

Destruction of the second cervical vertebra leads to a highly unstable situation. Reconstruction is difficult because the axis plays a central role in rotatory movements and has a unique function in redistributing axial loads. The axis transfers the axial load of the two lateral masses of the atlas to three surfaces on the third cervical vertebra: the two articular facets and the vertebral body. As reconstruction is difficult and the instability in this region is life threatening, pathological processes are often treated less radically compared to other areas of the cervical spine. However, this more moderate approach may result in worse outcomes and prognoses. This paper presents the development of a new implant (C2 prosthesis) and two illustrative cases describing the implementation of this new implant. The C2 prosthesis provides anterior support and therefore allows a more radical surgical approach