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

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

Management of Acute Traumatic Central Cord Syndrome: A Narrative Review.

Study Design Narrative review. Objectives To provide an updated overview of the management of acute traumatic central cord syndrome (ATCCS). Methods A comprehensive narrative review of the literature was done to identify evidence-based treatment strategies for patients diagnosed with ATCCS. Results ATCCS is the most commonly encountered subtype of incomplete spinal cord injury and is characterized by worse sensory and motor function in the upper extremities compared with the lower extremities. It is most commonly seen in the setting of trauma such as motor vehicles or falls in elderly patients. The operative management of this injury has been historically variable as it can be seen in the setting of mechanical instability or preexisting cervical stenosis alone. While each patient should be evaluated on an individual basis, based on the current literature, the authors' preferred treatment is to perform early decompression and stabilization in patients that have any instability or significant neurologic deficit. Surgical intervention, in the appropriate patient, is associated with an earlier improvement in neurologic status, shorter hospital stay, and shorter intensive care unit stay. Conclusions While there is limited evidence regarding management of ATCCS, in the presence of mechanical instability or ongoing cord compression, surgical management is the treatment of choice. Further research needs to be conducted regarding treatment strategies and patient outcomes

The Influence of Regional Differences on the Reliability of the AO Spine Sacral Injury Classification System.

STUDY DESIGN Global cross-sectional survey. OBJECTIVE To explore the influence of geographic region on the AO Spine Sacral Classification System. METHODS A total of 158 AO Spine and AO Trauma members from 6 AO world regions (Africa, Asia, Europe, Latin and South America, Middle East, and North America) participated in a live webinar to assess the reliability, reproducibility, and accuracy of classifying sacral fractures using the AO Spine Sacral Classification System. This evaluation was performed with 26 cases presented in randomized order on 2 occasions 3 weeks apart. RESULTS A total of 8320 case assessments were performed. All regions demonstrated excellent intraobserver reproducibility for fracture morphology. Respondents from Europe (k = .80) and North America (k = .86) achieved excellent reproducibility for fracture subtype while respondents from all other regions displayed substantial reproducibility. All regions demonstrated at minimum substantial interobserver reliability for fracture morphology and subtype. Each region demonstrated >90% accuracy in classifying fracture morphology and >80% accuracy in fracture subtype compared to the gold standard. Type C morphology (p2 = .0000) and A3 (p1 = .0280), B2 (p1 = .0015), C0 (p1 = .0085), and C2 (p1 =.0016, p2 =.0000) subtypes showed significant regional disparity in classification accuracy (p1 = Assessment 1, p2 = Assessment 2). Respondents from Asia (except in A3) and the combined group of North, Latin, and South America had accuracy percentages below the combined mean, whereas respondents from Europe consistently scored above the mean. CONCLUSIONS In a global validation study of the AO Spine Sacral Classification System, substantial reliability of both fracture morphology and subtype classification was found across all geographic regions

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

The biodiversity hotspot as evolutionary hot-bed : spectacular radiation of Erica in the Cape Floristic Region

CITATION: Pirie, M. D., et al. 2016. The biodiversity hotspot as evolutionary hot-bed: spectacular radiation of Erica in the Cape Floristic Region.BMC Evolutionary Biology, 16:190, doi:10.1186/s12862-016-0764-3.The original publication is available at https://bmcevolbiol.biomedcentral.comBackground: The disproportionate species richness of the world’s biodiversity hotspots could be explained by low extinction (the evolutionary “museum”) and/or high speciation (the “hot-bed”) models. We test these models using the largest of the species rich plant groups that characterise the botanically diverse Cape Floristic Region (CFR): the genus Erica L. We generate a novel phylogenetic hypothesis informed by nuclear and plastid DNA sequences of c. 60 % of the c. 800 Erica species (of which 690 are endemic to the CFR), and use this to estimate clade ages (using RELTIME; BEAST), net diversification rates (GEIGER), and shifts in rates of diversification in different areas (BAMM; MuSSE). Results: The diversity of Erica species in the CFR is the result of a single radiation within the last c. 15 million years. Compared to ancestral lineages in the Palearctic, the rate of speciation accelerated across Africa and Madagascar, with a further burst of speciation within the CFR that also exceeds the net diversification rates of other Cape clades. Conclusions: Erica exemplifies the “hotbed” model of assemblage through recent speciation, implying that with the advent of the modern Cape a multitude of new niches opened and were successively occupied through local species diversification.https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-016-0764-3Publisher's versio

Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

Purpose The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon’s geographic location or years in practice infuences their preferred management of traumatic cervical facet dislocation injuries. Methods A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. Results A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a signifcant diference. Additionally, results also exhibited considerable management agreement between those with≤10 and>10 years of practice experience, with only 2 case exceptions noted. Conclusion More than half of responders, regardless of geographical location or practice experience, identifed MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe. Keywords Cervical spine · Trauma · Spinal injuries · Joint dislocations · Neck injuries · Spinal disease

Validation of the Hierarchical Nature of the AO Spine Sacral Classification and the Development of the Sacral AO Spine Injury Score

STUDY DESIGN: Global cross-sectional survey. OBJECTIVE: The objective of this study was to validate the hierarchical nature of the AO Spine Sacral Classification System and develop an injury scoring system. SUMMARY OF BACKGROUND DATA: Although substantial interobserver and intraobserver reliability of the AO Spine Sacral Classification System has been established, the hierarchical nature of the classification has yet to be validated. METHODS: Respondents numerically graded each variable within the classification system for severity. Based on the results, a Sacral AO Spine Injury Score (AOSIS) was developed. RESULTS: A total of 142 responses were received. The classification exhibited a hierarchical Injury Severity Score (ISS) progression (A1: 8 to C3: 95) with few exceptions. Subtypes B1 and B2 fractures showed no significant difference in ISS (B1 43.9 vs. B2 43.4, P =0.362). In addition, the transitions A3→B1 and B3→C0 represent significant decreases in ISS (A3 66.3 vs. B1 43.9, P CONCLUSIONS: The results of this study validate the hierarchical nature of the AO Spine Sacral Classification System. The Sacral AOSIS sets the foundation for further studies to develop a universally accepted treatment algorithm for the treatment of complex sacral injuries. LEVEL OF EVIDENCE: Level IV-Diagnostic

Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

PURPOSE: The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon\u27s geographic location or years in practice influences their preferred management of traumatic cervical facet dislocation injuries. METHODS: A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. RESULTS: A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a significant difference. Additionally, results also exhibited considerable management agreement between those with ≤ 10 and \u3e 10 years of practice experience, with only 2 case exceptions noted. CONCLUSION: More than half of responders, regardless of geographical location or practice experience, identified MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe

Development and reliability of the AOSpine CROST (Clinician Reported Outcome Spine Trauma): a tool to evaluate and predict outcomes from clinician’s perspective

Purpose: To report on the development of AOSpine CROST (Clinician Reported Outcome Spine Trauma) and results of an initial reliability study. Methods: The AOSpine CROST was developed using an iterative approach of multiple cycles of development, review, and revision including an expert clinician panel. Subsequently, a reliability study was performed among an expert panel who were provided with 20 spine trauma cases, administered twice with 4-week interval. The results of the developmental process were analyzed using descriptive statistics, the reliability per parameter using Kappa statistics, inter-rater rater agreement using intraclass correlation coefficient (ICC), and internal consistency using Cronbach’s α. Results: The AOSpine CROST was developed and consisted of 10 parameters, 2 of which are only applicable for surgically treated patents (‘Wound healing’ and ‘Implants’). A dichotomous scoring system (‘yes’ or ‘no’ response) was incorporated to express expected problems for the short term and long term. In the reliability study, 16 (84.2%) participated in the first round and 14 (73.7%) in the second. Intra-rater reliability was fair to good for both time points (κ = 0.40–0.80 and κ = 0.31–0.67). Results of inter-rater reliability were lower (κ = 0.18–0.60 and κ = 0.16–0.46). Inter-rater agreement for total scores showed moderate results (ICC = 0.52–0.60), and the internal consistency was acceptable (α = 0.76–0.82). Conclusions: The AOSpine CROST, an outcome tool for the surgeons, was developed using an iterative process. An initial reliability analysis showed fair to moderate results and acceptable internal consistency. Further clinical validation studies will be performed to further validate the tool