In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor.

Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (Aß), Tau (τ), and α-Synuclein (αS) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer's Disease (AD) and Parkinson's Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1-10 pM, 10-100 fM for Aß, τ, and αS, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. The detection of each amyloid was specific to their aptamers; Aß, τ, and αS peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.

Characterization of quantitative susceptibility mapping in the left ventricular myocardium.

BACKGROUND: Myocardial quantitative susceptibility mapping (QSM) may offer better specificity to iron than conventional T2* imaging in the assessment of cardiac diseases, including intra-myocardial hemorrhage. However, the precision and repeatability of cardiac QSM have not yet been characterized. The aim of this study is to characterize these key metrics in a healthy volunteer cohort and show the feasibility of the method in patients. METHODS: Free breathing respiratory-navigated multi-echo 3D gradient echo images were acquired, from which QSM maps were reconstructed using the Morphology Enhanced Dipole Inversion toolbox. This technique was first evaluated in a susceptibility phantom containing tubes with known concentrations of gadolinium. In vivo characterization of myocardial QSM was then performed in a cohort of 10 healthy volunteers where each subject was scanned twice. Mean segment susceptibility, precision (standard deviation of voxel magnetic susceptibilities within one segment), and repeatability (absolute difference in segment mean susceptibility between repeats) of QSM were calculated for each American Heart Association (AHA) myocardial segment. Finally, the feasibility of the method was shown in 10 patients, including four with hemorrhagic infarcts. RESULTS: The phantom experiment showed a strong linear relationship between measured and predicted susceptibility shifts (R2 > 0.99). For the healthy volunteer cohort, AHA segment analysis showed the mean segment susceptibility was 0.00 ± 0.02 ppm, the mean precision was 0.05 ± 0.04 ppm, and the mean repeatability was 0.02 ± 0.02 ppm. Cardiac QSM was successfully performed in all patients. Focal iron deposits were successfully visualized in the patients with hemorrhagic myocardial infarctions. CONCLUSION: The precision and repeatability of cardiac QSM were successfully characterized in phantom and in vivo experiments. The feasibility of the technique was also successfully demonstrated in patients. While challenges still remain, further clinical evaluation of the technique is now warranted. TRIAL REGISTRATION: This work does not report on a health care intervention.

Compartment-based reconstruction of 3D acquisition-weighted 31 P cardiac magnetic resonance spectroscopic imaging at 7 T: A reproducibility study.

Even at 7 T, cardiac 31 P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment-based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment-based methods, applied to three different acquisition schemes at 7 T. Twelve healthy volunteers were scanned twice. Each scan session consisted of a 6.5-min 3D acquisition-weighted (AW) cardiac 31 P phase encode-based MRSI acquisition and two 6.5-min truncated k-space acquisitions with increased averaging (4 × 4 × 4 central k-space phase encodes and fractional SLAM [fSLAM] optimized k-space phase encodes). Spectra were reconstructed using (i) AW Fourier reconstruction; (ii) AW SLAM; (iii) AW SLIM; (iv) 4 × 4 × 4 SLAM; (v) 4 × 4 × 4 SLIM; and (vi) fSLAM acquisition-reconstruction combinations. The phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio, the PCr SNR, and spatial response functions were computed, in addition to coefficients of reproducibility and variability. Using the compartment-based reconstruction algorithms with the AW 31 P acquisition resulted in a significant increase in SNR compared with previously published Fourier-based MRSI reconstruction methods while maintaining the measured PCr/ATP ratio and improving interscan reproducibility. The alternative acquisition strategies with truncated k-space performed no better than the common AW approach. Compartment-based spectroscopy approaches provide an attractive reconstruction method for cardiac 31 P spectroscopy at 7 T, improving reproducibility and SNR without the need for a dedicated k-space sampling strategy.

Improved hyperspectral inversion of aquatic reflectance under non-uniform vertical mixing.

Estimating the concentration of water constituents by optical remote sensing assumes absorption and scattering processes to be uniform over the observation depth. Using hyperspectral reflectance, we present a method to direct the retrieval of the backscattering coefficient (bb(λ)) from reflectance (> 600 nm) towards wavebands where absorption by water dominates the reflectance curve. Two experiments demonstrate the impact of hyperspectral inversion in the selected band set. First, optical simulations show that the resulting distribution of bb(λ) is sensitive to particle mixing conditions, although a robust indicator of non-uniformity was not found for all scenarios of stratification. Second, in the absence of spectral backscattering profiles from in situ data sets, it is shown how substituting the median of bb(λ) into a near infra-red / red band ratio algorithm improved chlorophyll-a estimates (root mean square error 75.45 mg m-3 became 44.13 mg m-3). This approach also allows propagation of the uncertainty in bb estimates to water constituent concentrations.

The Role of the Fused Ring in Bicyclic Triazolium Organocatalysts: Kinetic, X-ray, and DFT Insights.

Bicyclic triazolium scaffolds are widely employed in N-heterocyclic carbene (NHC) organocatalysis. While the incorporation of a fused ring was initially for synthetic utility in accessing chiral, modular triazolyl scaffolds, recent results highlight the potential for impact upon reaction outcome with the underpinning origins unclear. The common first step to all triazolium-catalyzed transformations is C(3)-H deprotonation to form the triazolylidene NHC. Herein, we report an analysis of the impact of size of the fused (5-, 6-, and 7-membered, n = 1, 2, and 3, respectively) ring on the C(3) proton transfer reactions of a series of bicyclic triazolium salts. Rate constants for the deuteroxide-catalyzed C(3)-H/D-exchange of triazolium salts, kDO, were significantly influenced by the size of the adjacent fused ring, with the kinetic acidity trend, or protofugalities, following the order kDO (n = 1) > kDO (n = 2) ≈ kDO (n = 3). Detailed analyses of X-ray diffraction (XRD) data for 20 triazolium salts (including 16 new structures) and of computational data for the corresponding triazolylidene NHCs provide insight on structural effects of alteration of fused ring size. In particular, changes in internal triazolyl NCN angle and positioning of the most proximal CH2 with variation in fused ring size are proposed to influence the experimental protofugality order.

Quantitative susceptibility mapping (QSM) of the cardiovascular system: challenges and perspectives.

Quantitative susceptibility mapping (QSM) is a powerful, non-invasive, magnetic resonance imaging (MRI) technique that relies on measurement of magnetic susceptibility. So far, QSM has been employed mostly to study neurological disorders characterized by iron accumulation, such as Parkinson's and Alzheimer's diseases. Nonetheless, QSM allows mapping key indicators of cardiac disease such as blood oxygenation and myocardial iron content. For this reason, the application of QSM offers an unprecedented opportunity to gain a better understanding of the pathophysiological changes associated with cardiovascular disease and to monitor their evolution and response to treatment. Recent studies on cardiovascular QSM have shown the feasibility of a non-invasive assessment of blood oxygenation, myocardial iron content and myocardial fibre orientation, as well as carotid plaque composition. Significant technical challenges remain, the most evident of which are related to cardiac and respiratory motion, blood flow, chemical shift effects and susceptibility artefacts. Significant work is ongoing to overcome these challenges and integrate the QSM technique into clinical practice in the cardiovascular field.

Biocapacity and cost-effectiveness benefits of increased peatland restoration in Scotland.

Ecological Footprint and biocapacity accounting is a widely-used ecological accounting framework which tracks human demand against the biosphere's rate of regeneration. However, current national assessments do not yet include carbon-dense peatlands, hindering the evaluation of peatland biocapacity contributions. Also, the economic efficiency of peatland restoration is understudied and needed to inform land use decisions. We provide the first assessment of Scotland's biocapacity and add peatlands as a novel land type. We then project the biocapacity impacts in 2050 of current peatland restoration targets and various alternative management scenarios. Finally, we estimate the cost per tonne of greenhouse gas abated of various peatland restoration scenarios, and compare this with estimates of afforestation mitigation costs from the literature. Our results show that Scotland's per-person biocapacity exceeds the UK average by a factor of three. However, despite covering 25% of land area, peatland biocapacity increases Scotland's biocapacity total by only 2%, while the Carbon Footprint of degraded peatlands increases Scotland's ecological deficit by 40%. Current peatland restoration targets of the Scottish Government are estimated to reduce the national ecological deficit by only 9% in 2050. The cost-effectiveness of peatland restoration is context-dependent, and extremely cost-effective methods are applicable to peatland areas far exceeding current government restoration targets. Our findings provide land managers with evidence in favour of increased peatland restoration, both in terms of boosting biocapacity, and economic cost-effectiveness.

A 3D hybrid-shot spiral sequence for hyperpolarized 13C imaging.

PURPOSE: Hyperpolarized imaging experiments have conflicting requirements of high spatial, temporal, and spectral resolution. Spectral-spatial RF excitation has been shown to form an attractive magnetization-efficient method for hyperpolarized imaging, but the optimum readout strategy is not yet known. METHODS: In this work, we propose a novel 3D hybrid-shot spiral sequence which features two constant density regions that permit the retrospective reconstruction of either high spatial or high temporal resolution images post hoc, (adaptive spatiotemporal imaging) allowing greater flexibility in acquisition and reconstruction. RESULTS: We have implemented this sequence, both via simulation and on a preclinical scanner, to demonstrate its feasibility, in both a 1H phantom and with hyperpolarized 13C pyruvate in vivo. CONCLUSIONS: This sequence forms an attractive method for acquiring hyperpolarized imaging datasets, providing adaptive spatiotemporal imaging to ameliorate the conflict of spatial and temporal resolution, with significant potential for clinical translation.

Rapid, B1 -insensitive, dual-band quasi-adiabatic saturation transfer with optimal control for complete quantification of myocardial ATP flux.

PURPOSE: Phosphorus saturation-transfer experiments can quantify metabolic fluxes noninvasively. Typically, the forward flux through the creatine kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of γ-ATP. The quantification of total ATP utilization is currently underexplored, as it requires simultaneous saturation of inorganic phosphate ( Pi ) and PCr. This is challenging, as currently available saturation pulses reduce the already-low γ-ATP signal present. METHODS: Using a hybrid optimal-control and Shinnar-Le Roux method, a quasi-adiabatic RF pulse was designed for the dual saturation of PCr and Pi to enable determination of total ATP utilization. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before being applied to perfused rat hearts at 11.7 T. RESULTS: The quasi-adiabatic pulse was insensitive to a >2.5-fold variation in B1 , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective B1 . This enabled the complete quantification of the synthesis and degradation fluxes for ATP in 30-45 minutes in the perfused rat heart. While the net synthesis flux (4.24 ± 0.8 mM/s, SEM) was not significantly different from degradation flux (6.88 ± 2 mM/s, P = .06) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi -to-ATP measurement that may explain a trend suggesting a possible imbalance. CONCLUSIONS: This work demonstrates a novel quasi-adiabatic dual-saturation RF pulse with significantly improved performance that can be used to measure ATP turnover in the heart in vivo.

Integration of Radiometric Ground-Based Data and High-Resolution QuickBird Imagery with Multivariate Modeling to Estimate Maize Traits in the Nile Delta of Egypt.

In site-specific management, rapid and accurate identification of crop stress at a large scale is critical. Radiometric ground-based data and satellite imaging with advanced spatial and spectral resolution allow for a deeper understanding of crop stress and the level of stress in a given area. This research aimed to assess the potential of radiometric ground-based data and high-resolution QuickBird satellite imagery to determine the leaf area index (LAI), biomass fresh weight (BFW) and chlorophyll meter (Chlm) of maize across well-irrigated, water stress and salinity stress areas in the Nile Delta of Egypt. Partial least squares regression (PLSR) and multiple linear regression (MLR) were evaluated to estimate the three measured traits based on vegetation spectral indices (vegetation-SRIs) derived from these methods and their combination. Maize field visits were conducted during the summer seasons from 28 to 30 July 2007 to collect ground reference data concurrent with the acquisition of radiometric ground-based measurements and QuickBird satellite imagery. The results showed that the majority of vegetation-SRIs extracted from radiometric ground-based data and high-resolution satellite images were more effective in estimating LAI, BFW, and Chlm. In general, the vegetation-SRIs of radiometric ground-based data showed higher R2 with measured traits compared to the vegetation-SRIs extracted from high-resolution satellite imagery. The coefficient of determination (R2) of the significant relationships between vegetation-SRIs of both methods and three measured traits varied from 0.64 to 0.89. For example, with QuickBird high-resolution satellite images, the relationships of the green normalized difference vegetation index (GNDVI) with LAI and BFW showed the highest R2 of 0.80 and 0.84, respectively. Overall, the ground-based vegetation-SRIs and the satellite-based indices were found to be in good agreement to assess the measured traits of maize. Both the calibration (Cal.) and validation (Val.) models of PLSR and MLR showed the highest performance in predicting the three measured traits based on the combination of vegetation-SRIs from radiometric ground-based data and high-resolution QuickBird satellite imagery. For example, validation (Val.) models of PLSR and MLR showed the highest performance in predicting the measured traits based on the combination of vegetation-SRIs from radiometric ground-based data and high-resolution QuickBird satellite imagery with R2 (0.91) of both methods for LAI, R2 (0.91-0.93) for BFW respectively, and R2 (0.82) of both methods for Chlm. The models of PLSR and MLR showed approximately the same performance in predicting the three measured traits and no clear difference was found between them and their combinations. In conclusion, the results obtained from this study showed that radiometric ground-based measurements and high spectral resolution remote-sensing imagery have the potential to offer necessary crop monitoring information across well-irrigated, water stress and salinity stress in regions suffering lack of freshwater resources.

Structural Reassignment and Absolute Stereochemistry of Madurastatin C1 (MBJ-0034) and the Related Aziridine Siderophores: Madurastatins A1, B1, and MBJ-0035.

The madurastatins are pentapeptide siderophores originally described as containing an unusual salicylate-capped N-terminal aziridine ring. Isolation of madurastatin C1 (1) (also designated MBJ-0034), from Actinomadura sp. DEM31376 (itself isolated from a deep sea sediment), prompted structural reevaluation of the madurastatin siderophores, in line with the recent work of Thorson and Shaaban. NMR spectroscopy in combination with partial synthesis allowed confirmation of the structure of madurastatin C1 (1) as containing an N-terminal 2-(2-hydroxyphenyl)oxazoline in place of the originally postulated aziridine, while absolute stereochemistry was determined via Harada's advanced Marfey's method. Therefore, this work further supports Thorson and Shaaban's proposed structural revision of the madurastatin class of siderophores (madurastatins A1 (2), B1 (3), C1 (1), and MBJ-0036 (4)) as N-terminal 2-(2-hydroxyphenyl)oxazolines.

The disease-ameliorating function of autoregulatory CD8 T cells is mediated by targeting of encephalitogenic CD4 T cells in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS, and CD8 T cells are the predominant T cell population in MS lesions. Given that transfer of CNS-specific CD8 T cells results in an attenuated clinical demyelinating disease in C57BL/6 mice with immunization-induced experimental autoimmune encephalomyelitis (EAE), we investigated the cellular targets and mechanisms of autoreactive regulatory CD8 T cells. In this study we report that myelin oligodendrocyte glycoprotein peptide (MOG35-55)-induced CD8 T cells could also attenuate adoptively transferred, CD4 T cell-mediated EAE. Whereas CD8(-/-) mice exhibited more severe EAE associated with increased autoreactivity and inflammatory cytokine production by myelin-specific CD4 T cells, this was reversed by adoptive transfer of MOG-specific CD8 T cells. These autoregulatory CD8 T cells required in vivo MHC class Ia (K(b)D(b)) presentation. Interestingly, MOG-specific CD8 T cells could also suppress adoptively induced disease using wild-type MOG35-55-specific CD4 T cells transferred into K(b)D(b-/-) recipient mice, suggesting direct targeting of encephalitogenic CD4 T cells. In vivo trafficking analysis revealed that autoregulatory CD8 T cells are dependent on neuroinflammation for CNS infiltration, and their suppression/cytotoxicity of MOG-specific CD4 T cells is observed both in the periphery and in the CNS. These studies provide important insights into the mechanism of disease suppression mediated by autoreactive CD8 T cells in EAE.

Multi-factorial influences on sex ratio: a spatio-temporal investigation of endocrine disruptor pollution and neighborhood stress.

BACKGROUND: It is suggested the declining male birth proportion in some industrialized countries is linked to ubiquitous endocrine disruptor exposure. Stress and advanced parental age are determinants which frequently present positive findings. Multi-factorial influences on population sex ratio are rarely explored or tested in research. OBJECTIVES: To test the hypothesis that dual factors of pollution and population stress affects sex proportion at birth through geographical analysis of Central Scotland. METHODS: The study incorporates the use of Geographical Information Systems (GIS) tools to overlay modeled point source endocrine disruptor air emissions with "small-area" data on multiple deprivation (a proxy measurement of stress) and birth sex. Historical review of regional sex ratio trends presents additional data on sex ratio in Scotland to consider. RESULTS: There was no overall concentration in Central Scotland of low sex ratio neighborhoods with areas where endocrine disruptor air pollution and deprivation or economic stress were high. Historical regional trends in Scotland (from 1973), however, do show significantly lower sex ratio values for populations where industrial air pollution is highest (i.e. Eastern Central Scotland). CONCLUSIONS: Use of small area data sets and pollution inventories is a potential new method of inquiry for reproductive environmental and health protection monitoring and has produced interesting findings.

Compartment-based reconstruction of acquisition-weighted 31P cardiac MRSI reduces sensitivity to cardiac motion and scan planning.

Motivation: 31P magnetic resonance spectroscopic imaging (31P MRSI) is a powerful technique for investigating the metabolic effects of treatments for heart failure in vivo, allowing a better understanding of their mechanism of action in patient cohorts. Unfortunately, cardiac 31P MRSI is fundamentally limited by low SNR, which leads to compromises in acquisition, such as no cardiac or respiratory gating or low spatial resolution, in order to achieve reasonable scan times. Spectroscopy with linear algebra modeling (SLAM) reconstruction may be able to address these challenges and therefore improve repeatability by incorporating a segmented localizer into the reconstruction. Methods: Six healthy volunteers were scanned twice in a test-retest procedure to allow quantification of repeatability. Each scan consisted of anatomical localizers and two acquisition-weighted (AW) 31P MRSI acquisitions, which were acquired with and without cardiac gating. Five patients with heart failure with a preserved ejection fraction were then scanned with the same 31P MRSI sequence without cardiac gating. All 31P MRSI datasets were reconstructed with both conventional Fourier transform (FT)-based reconstruction and SLAM reconstruction, which were compared statistically. The effect of shifting the 31P MRSI acquisition field of view was also investigated. Results: In the healthy volunteer cohort, the spectral fit of the SLAM reconstructions had significantly improved Cramer-Rao lower bounds (CRLBs) compared to the FT-based reconstruction of non-cardiac gated data, as well as improved coefficients of variability and repeatability. The SLAM reconstruction found a significant difference in the PCr/ATP ratio between the healthy volunteer and patient cohorts, which the FT-based reconstruction did not find. Furthermore, the SLAM reconstruction was less influenced by the placement of the field of view (FOV) of the 31P MRSI acquisition in post hoc analysis. Discussion: The experimental benefits of the SLAM reconstruction for AW data were demonstrated by the improvements in fit confidence and repeatability seen in the healthy volunteer cohort and post hoc FOV analysis. The benefit of SLAM reconstruction of AW data for clinical studies was then illustrated by the patient cohort, which suggested improved sensitivity to clinically significant changes in the PCr/ATP ratio.

Hands-free Femoral Traction Using the Bookwalter Retractor System During Anterior Approaches to the Acetabulum.

SUMMARY: Displaced acetabular fractures with medial and cranial displacement of the femoral head commonly require an anterior approach for reduction and stabilization. Restoration of the femoral head to its native position under the reduced acetabular dome is a primary goal of surgery. We present a surgical technique for applying traction to the proximal femur using the Bookwalter retractor system during the repair of acetabular fractures when using an anterior approach. By placing traction in line with the femoral neck, the femoral head is moved to a more anatomical position allowing acetabular fracture fragments to be reduced unimpeded and the femoral head may be used as a reconstructive template. We review a case series of 116 patients treated using this technique and report the short- and long-term radiographic and clinical results of treatment.

Local Infiltrative Analgesia of Murine Femur Fractures In Vivo Does Not Inhibit Fracture Healing.

The opioid epidemic in the United States has forced care providers to seek out alternatives to narcotic analgesics. Physicians involved in trauma care, including orthopaedic trauma surgeons, often have patients requiring significant amounts of these medications, especially in the perioperative period, given the acuity and severity of their injuries. Modalities such as local infiltration of fractures with anesthetic agents during operative treatment may provide some benefit to this population by decreasing postoperative pain and narcotic usage. However, prior data suggest that these agents are chondrotoxic, which may impede secondary fracture healing. The purpose of this study was to investigate the hypothesis that local anesthetics decrease secondary bone healing and callus formation in stabilized murine femur fractures through chondrocyte apoptosis. Male C57BL/6 mice underwent intramedullary stabilization and fracture of bilateral femurs followed by immediate infiltration of the fracture site with local anesthetic agents. Femurs were dissected at 10- and 20-days post-fracture and evaluated by [Formula: see text]CT and histological analysis. No significant differences were seen in callus size or mineralization between controls and fractures treated with a local anesthetic. When the callus was analyzed histologically, local anesthetic agents appeared to increase cartilage density. Therefore, infiltration of local anesthetics during operative treatment of fracture as part of a multimodal approach to pain control does not appear to significantly affect callus formation in a preclinical model, although subclinical molecular effects may be present. Local infiltrative analgesia with local anesthetics may be used as an adjunct for perioperative pain control during femur fracture surgery without a significant effect on secondary bone healing.

Preoperative and Intraoperative Considerations Using Intramedullary Nails for the Treatment of Tibial Shaft Fractures Below Total Knee Arthroplasty.

SUMMARY: Periprosthetic tibial shaft fractures below total knee arthroplasty (TKA) are relatively rare, with an incidence of approximately 1%. However, as the rates of arthroplasty increase, orthopaedic surgeons are likely to see a corresponding increase in these types of fractures. Native tibial shaft fractures are routinely treated with either nails or plates, and the success of intramedullary nailing of tibial shaft fractures has been well described in the literature. In this article, we seek to describe a case series of tibial shaft fractures in patients with ipsilateral TKA treated with infrapatellar intramedullary nailing. We will focus on preoperative considerations including templating and measurement of the anterior cortical implant distance on the lateral radiograph to ensure space for safe nail passage. We will also discuss intraoperative technical tricks, including Kirschner wire insertion for sounding the start point, utilization of the curved awl, use of hand reamers, and rotation of the nail to bypass the implant. Using meticulous preoperative planning and technical intraoperative tricks, patients with tibial shaft fractures below TKA may be successfully treated with intramedullary nailing.

Extra-articular Unstable Iliac Fractures: Associated Injuries, Fixation Strategies, and Outcomes.

OBJECTIVE: To characterize the associated injuries, fixation constructs, and outcomes of extra-articular unstable iliac fractures. DESIGN: Retrospective cohort study. SETTING: Level I trauma center. PATIENTS: Thirty-three extra-articular unstable iliac fractures treated over a 20-year period. INTERVENTION: Percutaneous or open fixation of iliac fractures at the pelvic brim AND/OR iliac crest. MAIN OUTCOME MEASURES: Incidence of union, fixation failure, and angiography at the time of injury. RESULTS: Twenty-five patients were treated operatively with appropriate follow-up. Four patients had fixation failure with displacement, all in the group with only brim OR crest fixation (4/8 patients, 50% rate). In patients with both crest AND brim fixation (n = 17), there were no cases of implant failure or late displacement. In displaced fractures (n = 22), 4 patients (18%) required embolization by interventional radiology. In all 4 cases, the superior gluteal artery was embolized. In patients with both crest AND brim fixation, all went on to uneventful union with an average Visual Analog Scale (VAS) pain score of 0.9 (range, 0-5) at final follow-up. CONCLUSIONS: Extra-articular unstable iliac fractures are high-energy injuries that demonstrate a high rate of union when both pelvic brim AND iliac crest fixation is used. Approximately 1 in 5 patients with a displaced iliac fracture presented with a superior gluteal artery disruption requiring embolization. Pelvic brim OR iliac crest fixation used in isolation was associated with a fixation failure rate of 50%, supporting previous biomechanical work. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Mirubactin C rescues the lethal effect of cell wall biosynthesis mutations in Bacillus subtilis.

Growth of most rod-shaped bacteria is accompanied by the insertion of new peptidoglycan into the cylindrical cell wall. This insertion, which helps maintain and determine the shape of the cell, is guided by a protein machine called the rod complex or elongasome. Although most of the proteins in this complex are essential under normal growth conditions, cell viability can be rescued, for reasons that are not understood, by the presence of a high (mM) Mg2+ concentration. We screened for natural product compounds that could rescue the growth of mutants affected in rod-complex function. By screening > 2,000 extracts from a diverse collection of actinobacteria, we identified a compound, mirubactin C, related to the known iron siderophore mirubactin A, which rescued growth in the low micromolar range, and this activity was confirmed using synthetic mirubactin C. The compound also displayed toxicity at higher concentrations, and this effect appears related to iron homeostasis. However, several lines of evidence suggest that the mirubactin C rescuing activity is not due simply to iron sequestration. The results support an emerging view that the functions of bacterial siderophores extend well beyond simply iron binding and uptake.