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The sustainable production of chemicals from renewable, nonedible biomass has emerged as an essential alternative to address pressing environmental issues arising from our heavy dependence on fossil resources. Microbial cell factories are engineered microorganisms harboring biosynthetic pathways streamlined to produce chemicals of interests from renewable carbon sources. The biosynthetic pathways for the production of chemicals can be defined into three categories with reference to the microbial host selected for engineering: native-existing pathways, nonnative-existing pathways, and nonnative-created pathways. Recent trends in leveraging native-existing pathways, discovering nonnative-existing pathways, and designing

Sustainable production of chemicals and materials from renewable non-food biomass using biorefineries has become increasingly important in an effort toward the vision of 'net zero carbon' that has recently been pledged by countries around the world. Systems metabolic engineering has allowed the efficient development of microbial strains overproducing an increasing number of chemicals and materials, some of which have been translated to industrial-scale production. Fermentation is one of the key processes determining the overall economics of bioprocesses, but has recently been attracting less research attention. In this Review, we revisit and discuss factors affecting the competitiveness of bacterial fermentation in connection to strain development by systems metabolic engineering. Future perspectives for developing efficient fermentation processes are also discussed.

Metabolic rewiring or reprogramming is the alteration of metabolism in living organisms, leading to disordered states aberrant from homeostasis. As large amounts of omics data become available, complex mechanisms leading to or driven by metabolic rewiring of cells can be better understood using reconstructed context-specific genome-scale metabolic models (GEMs). Here, we review recent advances in reconstructing context-specific GEMs for studying metabolic rewiring of human cells or tissues, from generic GEMs and omics databases to multiomics data integration methods. Also, we review recent studies that use context-specific GEMs to obtain insights such as identifying key regulators or therapeutic targets. Analyses of recent trends indicate the importance of integrating context-specific GEMs with multiscale networks for understanding metabolic diseases and advancing precision medicine.

Methyl anthranilate (MANT) is a widely used compound to give grape scent and flavor, but is currently produced by petroleum-based processes. Here, we report the direct fermentative production of MANT from glucose by metabolically engineered Escherichia coli and Corynebacterium glutamicum strains harboring a synthetic plant-derived metabolic pathway. Optimizing the key enzyme anthranilic acid (ANT) methyltransferase1 (AAMT1) expression, increasing the direct precursor ANT supply, and enhancing the intracellular availability and salvage of the cofactor S-adenosyl-l-methionine required by AAMT1, results in improved MANT production in both engineered microorganisms. Furthermore, in situ two-phase extractive fermentation using tributyrin as an extractant is developed to overcome MANT toxicity. Fed-batch cultures of the final engineered E. coli and C. glutamicum strains in two-phase cultivation mode led to the production of 4.47 and 5.74 g/L MANT, respectively, in minimal media containing glucose. The metabolic engineering strategies developed here will be useful for the production of volatile aromatic esters including MANT.

Inter-joint coordination and gait variability in knee osteoarthritis (KOA) has not been well investigated. Hip-knee cyclograms can visualize the relationship between the hip and knee joint simultaneously. The aim of this study was to elucidate differences in inter-joint coordination and gait variability with respect to KOA severity using hip-knee cyclograms. Fifty participants with KOA (early KOA, n = 20; advanced KOA, n = 30) and 26 participants (≥ 50 years) without KOA were recruited. We analyzed inter-joint coordination by hip-knee cyclogram parameters including range of motion (RoM), center of mass (CoM), perimeter, and area. Gait variability was assessed by the coefficient of variance (CV) of hip-knee cyclogram parameters. Knee RoM was significantly reduced and total perimeter tended to be decreased with KOA progression. KOA patients (both early and advanced) had reduced stance phase perimeter, swing phase area, and total area than controls. Reduced knee CoM and swing phase perimeter were observed only in advanced KOA. Both KOA groups had a greater CV for CoM, knee RoM, perimeter (stance phase, swing phase and total) and swing phase area than the controls. Increased CV of hip RoM was only observed in advanced KOA. These results demonstrate that hip-knee cyclograms can provide insights into KOA patient gait.

Production of industrial chemicals using renewable biomass feedstock is becoming increasingly important to address limited fossil resources, climate change and other environmental problems. To develop high-performance microbial cell factories, equivalent to chemical plants, microorganisms undergo systematic metabolic engineering to efficiently convert biomass-derived carbon sources into target chemicals. Over the past two decades, many engineered microorganisms capable of producing natural and non-natural chemicals have been developed. This Review details the current status of representative industrial chemicals that are produced through biological and/or chemical reactions. We present a comprehensive bio-based chemicals map that highlights the strategies and pathways of single or multiple biological reactions, chemical reactions and combinations thereof towards production of particular chemicals of interest. Future challenges are also discussed to enable production of even more diverse chemicals and more efficient production of chemicals from renewable feedstocks.

4-Amino-1-butanol (4AB) serves as an important intermediate compound for drugs and a precursor of biodegradable polymers used for gene delivery. Here, we report for the first time the fermentative production of 4AB from glucose by metabolically engineered Corynebacterium glutamicum harboring a newly designed pathway comprising a putrescine aminotransferase (encoded by ygjG) and an aldehyde dehydrogenase (encoded by yqhD) from Escherichia coli, which convert putrescine to 4AB. Application of several metabolic engineering strategies such as fine-tuning the expression levels of ygjG and yqhD, eliminating competing pathways, and optimizing culture condition further improved 4AB production. Fed-batch culture of the final metabolically engineered C. glutamicum strain produced 24.7 g/L of 4AB. The strategies reported here should be useful for the microbial production of primary amino alcohols from renewable resources. This article is protected by copyright. All rights reserved.

Objective To present new classification methods of knee osteoarthritis (KOA) using machine learning and compare its performance with conventional statistical methods as classification techniques using machine learning have recently been developed.Methods A total of 84 KOA patients and 97 normal participants were recruited. KOA patients were clustered into three groups according to the Kellgren-Lawrence (K-L) grading system. All subjects completed gait trials under the same experimental conditions. Machine learning-based classification using the support vector machine (SVM) classifier was performed to classify KOA patients and the severity of KOA. Logistic regression analysis was also performed to compare the results in classifying KOA patients with machine learning method.Results In the classification between KOA patients and normal subjects, the accuracy of classification was higher in machine learning method than in logistic regression analysis. In the classification of KOA severity, accuracy was enhanced through the feature selection process in the machine learning method. The most significant gait feature for classification was flexion and extension of the knee in the swing phase in the machine learning method.Conclusion The machine learning method is thought to be a new approach to complement conventional logistic regression analysis in the classification of KOA patients. It can be clinically used for diagnosis and gait correction of KOA patients.

Objective To replace camera-based three-dimensional motion analyzers which are widely used to analyze body movements and gait but are also costly and require a large dedicated space, this study evaluates the validity and reliability of inertial measurement unit (IMU)-based systems by analyzing their spatio-temporal and kinematic measurement parameters. Methods The investigation was conducted in three separate hospitals with three healthy participants. IMUs were attached to the abdomen as well as the thigh, shank, and foot of both legs of each participant. Each participant then completed a 10-m gait course 10 times. During each gait cycle, the hips, knees, and ankle joints were observed from the sagittal, frontal, and transverse planes. The experiments were conducted with both a camerabased system and an IMU-based system. The measured gait analysis data were evaluated for validity and reliability using root mean square error (RMSE) and intraclass correlation coefficient (ICC) analyses. Results The differences between the RMSE values of the two systems determined through kinematic parameters ranged from a minimum of 1.83 to a maximum of 3.98 with a tolerance close to 1%. The results of this study also confirmed the reliability of the IMU-based system, and all of the variables showed a statistically high ICC. Conclusion These results confirmed that IMU-based systems can reliably replace camera-based systems for clinical body motion and gait analyses.

This study discussed application of a machine learning approach (Support vector machine, SVM) for the automatic cognition of gait changes due to scoliosis using gait measures: kinematic based on gait phase segmentation. The gaits of 18 controls and 24 scoliosis patients were recorded and analyzed using inertial measurement unit (IMU)-based systems during normal walking. Altogether, 72 gait features were extracted for developing gait recognition models. Cross-validation test results indicated that the performance of SVM was 90.5% to recognize scoliosis patients and controls gait patterns. When features were optimally selected, a feature selection algorithm could effectively distinguish the age groups with 95.2% accuracy. Applying the method that the previous test used, the severity of scoliosis was classified after clinician labeled the severity based on the Cobb angle. Test results indicated an accuracy of 81.0% by the SVM to recognize scoliosis severity gait patterns. Optimal selected features could effectively distinguish the scoliosis severity with 85.7% accuracy. When the measured features are ranked in order of high contribution, the abduction and adduction of left hip joint in the single support phase is most important in gait of patients with scoliosis. These results demonstrate considerable potential in applying SVMs in gait classification for medical applications.

Summary With pressing issues arising in recent years, the United Nations proposed 17 Sustainable Development Goals (SDGs) as an agenda urging international cooperations for sustainable development. In this perspective, we examine the roles of systems metabolic engineering (SysME) and its contribution to improving the quality of life and protecting our environment, presenting how this field of study offers resolutions to the SDGs with relevant examples. We conclude with offering our opinion on the current state of SysME and the direction it should move forward in the generations to come, explicitly focusing on addressing the SDGs.

After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT.The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups.Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P .0001) and 6 months (8.8; P .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups.Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

Metabolic engineering allows development of microbial strains efficiently producing chemicals and materials, but it requires much time, effort, and cost to make the strains industrially competitive. Systems metabolic engineering, which integrates tools and strategies of systems biology, synthetic biology, and evolutionary engineering with traditional metabolic engineering, has recently been used to facilitate development of high-performance strains. The past decade has witnessed this interdisciplinary strategy continuously being improved toward the development of industrially competitive overproducer strains. In this article, current trends in systems metabolic engineering including tools and strategies are reviewed, focusing on recent developments in selection of host strains, metabolic pathway reconstruction, tolerance enhancement, and metabolic flux optimization. Also, future challenges and prospects are discussed.

Pseudomonas putida has gained much interest among metabolic engineers as a workhorse for producing valuable natural products. While a few gene knockout tools for P. putida have been reported, integration of heterologous genes into the chromosome of P. putida, an essential strategy to develop stable industrial strains producing heterologous bioproducts, requires development of a more efficient method. Current methods rely on time-consuming homologous recombination techniques and transposon-mediated random insertions. Here we report a RecET recombineering system for markerless integration of heterologous genes into the P. putida chromosome. The efficiency and capacity of the recombineering system were first demonstrated by knocking out various genetic loci on the P. putida chromosome with knockout lengths widely spanning 0.6-101.7 kb. The RecET recombineering system developed here allowed successful integration of biosynthetic gene clusters for four proof-of-concept bioproducts, including protein, polyketide, isoprenoid, and amino acid derivative, into the target genetic locus of P. putida chromosome. The markerless recombineering system was completed by combining Cre/lox system and developing efficient plasmid curing systems, generating final strains free of antibiotic markers and plasmids. This markerless recombineering system for efficient gene knockout and integration will expedite metabolic engineering of P. putida, a bacterial host strain of increasing academic and industrial interest.

Records of 490,767 cows collected from 1990 to 2012 by dairy herd milk test of National Agriculture Cooperative Federation The pedigree of dairy cattle were provided by Korea Animal Improvement Association. The data were used to analyze the longevity of dairy cows with the life traits such as days in milk, number of lactation, productive life, and life span. The data were also used to investigate genetic relationship of these longevity traits with profitability of dairy cows, including heritability and genetic correlation. The profitability was calculated with simulation of milk income and production costs for individual cows. Days in milk among the traits had -0.287, -0.572 and -0.536 of genetic correlation with number of lactations, productive life and lifespan, respectively. The heritabilities of life span, number of lactations, productive life, and days in milk were found to be 0.045, 0.047, 0.059 and 0.081, respectively. Genetic correlations of profit with productive life, number of lactations, and days in milk were identified as 0.072, 0.080, 0.098 and 0.101. These results suggested that days in milk was most desirable traits to represent longevity of Holstein dairy cattle. In general, since longevity and profitability were close genetic relationship each other, genetic improvement of longevity is necessary for better profitable cows.

OBJECTIVEThe application of pharmacological therapeutics in neurological disorders is limited by the ability of these agents to penetrate the blood-brain barrier (BBB). Focused ultrasound (FUS) has recently gained attention for its potential application as a method for locally opening the BBB and thereby facilitating drug delivery into the brain parenchyma. However, this method still requires optimization to maximize its safety and efficacy for clinical use. In the present study, the authors examined several sonication parameters of FUS influencing BBB opening in small animals.METHODSChanges in BBB permeability were observed during transcranial sonication using low-intensity FUS in 20 adult male Sprague-Dawley rats. The authors examined the effects of FUS sonication with different sonication parameters, varying acoustic pressure, center frequency, burst duration, microbubble (MB) type, MB dose, pulse repetition frequency (PRF), and total exposure time. The focal region of BBB opening was identified by Evans blue dye. Additionally, H & E staining was used to identify blood vessel damage.RESULTSAcoustic pressure amplitude and burst duration were closely associated with enhancement of BBB opening efficiency, but these parameters were also highly correlated with tissue damage in the sonicated region. In contrast, MB types, MB dose, total exposure time, and PRF had an influence on BBB opening without conspicuous tissue damage after FUS sonication.CONCLUSIONSThe study aimed to identify these influential conditions and provide safety and efficacy values for further studies. Future work based on the current results is anticipated to facilitate the implementation of FUS sonication for drug delivery in various CNS disease states in the near future.

Purpose Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as a therapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modality has not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells (pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed their mechanisms of therapeutic action. Materials and methods Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesion of cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injection of pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequent immunostaining analyses. Results Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesterase activity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferase did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglial cells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. Conclusion Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populations and cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than direct differentiation of injected pMSCs into cholinergic neurons.

Genome engineering of Corynebacterium glutamicum, an important industrial microorganism for amino acids production, currently relies on random mutagenesis and inefficient double crossover events. Here we report a rapid genome engineering strategy to scarlessly knock out one or more genes in C. glutamicum in sequential and iterative manner. Recombinase RecT is used to incorporate synthetic single-stranded oligodeoxyribonucleotides into the genome and CRISPR/Cas9 to counter-select negative mutants. We completed the system by engineering the respective plasmids harboring CRISPR/Cas9 and RecT for efficient curing such that multiple gene targets can be done iteratively and final strains will be free of plasmids. To demonstrate the system, seven different mutants were constructed within two weeks to study the combinatorial deletion effects of three different genes on the production of γ-aminobutyric acid, an industrially relevant chemical of much interest. This genome engineering strategy will expedite metabolic engineering of C. glutamicum.

It is well known that the insular cortex is involved in the processing of painful input. The aim of this study was to evaluate the pain modulation role of the insular cortex during motor cortex stimulation (MCS). After inducing neuropathic pain (NP) rat models by the spared nerve injury method, we made a lesion on the rostral agranular insular cortex (RAIC) unilaterally and compared behaviorally determined pain threshold and latency in 2 groups: Group A (NP + MCS;n=7) and Group B (NP + RAIC lesion + MCS;n=7). Also, we simultaneously recorded neuronal activity (NP;n=9) in the thalamus of the ventral posterolateral nucleus and RAIC to evaluate electrophysiological changes from MCS. The pain threshold and tolerance latency increased in Group A with “MCS on” and in Group B with or without “MCS on.” Moreover, its increase in Group B with “MCS on” was more than that of Group B without MCS or of Group A, suggesting that MCS and RAIC lesioning are involved in pain modulation. Compared with the “MCS off” condition, the “MCS on” induced significant threshold changes in an electrophysiological study. Our data suggest that the RAIC has its own pain modulation effect, which is influenced by MCS.

OBJECTIVE To evaluate the computed tomography (CT) findings compared with pathologic features and to determine whether CT findings are useful for diagnosis of appendiceal metastasis in patients with underlying malignancy. MATERIALS AND METHODS Preoperative CT examinations of 59 patients who had underlying malignancy and underwent appendectomy were evaluated. Appendiceal metastasis (n = 21) and nonmetastasis (n = 38) were pathologically confirmed. Computed tomography features (appendiceal morphology and diameter, presence of ascites, rectal shelf, omental cake, lymphadenopathy or organ metastasis) were retrospectively reviewed, and compared with histopathological findings. Fisher exact test and Wilcoxon rank sum test were performed for statistical analysis. RESULTS Mean diameter of appendiceal metastasis was significantly larger (9.1 mm) than that of nonmetastasis (5.2 mm), (P < 0.0001). The CT morphology of appendiceal metastasis showed broad spectrum, and 3 cases of nodular thickening was only detected in appendiceal metastasis. There was a significant difference between groups (P = 0.0102). Appendiceal metastasis was more frequently associated with peritoneal seeding (ascitis, rectal shelf, omental cake) than nonmetastasis (P < 0.0001). Histopathological invasion of appendiceal metastasis was more frequently seen in serosa-mesoappendix (n = 20, 100%) or muscularis propria (n = 17, 85%), than in submucosa (n = 10, 50%) or mucosa layer (n = 7, 35%). Acute appendicitis was more commonly detected in metastasis (n = 4) than in nonmetastasis (n = 1) (P = 0.0495). CONCLUSIONS Evaluation of CT features of appendix and peritoneum may be useful for prediction of appendiceal metastasis in patients with underlying malignancy.

Background 5-Aminovaleric acid (5AVA) is an important five-carbon platform chemical that can be used for the synthesis of polymers and other chemicals of industrial interest. Enzymatic conversion of l-lysine to 5AVA has been achieved by employing lysine 2-monooxygenase encoded by the davB gene and 5-aminovaleramidase encoded by the davA gene. Additionally, a recombinant Escherichia coli strain expressing the davB and davA genes has been developed for bioconversion of l-lysine to 5AVA. To use glucose and xylose derived from lignocellulosic biomass as substrates, rather than l-lysine as a substrate, we previously examined direct fermentative production of 5AVA from glucose by metabolically engineered E. coli strains. However, the yield and productivity of 5AVA achieved by recombinant E. coli strains remain very low. Thus, Corynebacterium glutamicum, a highly efficient l-lysine producing microorganism, should be useful in the development of direct fermentative production of 5AVA using l-lysine as a precursor for 5AVA. Here, we report the development of metabolically engineered C. glutamicum strains for enhanced fermentative production of 5AVA from glucose. Results Various expression vectors containing different promoters and origins of replication were examined for optimal expression of Pseudomonas putida davB and davA genes encoding lysine 2-monooxygenase and delta-aminovaleramidase, respectively. Among them, expression of the C. glutamicum codon-optimized davA gene fused with His6-Tag at its N-Terminal and the davB gene as an operon under a strong synthetic H36 promoter (plasmid p36davAB3) in C. glutamicum enabled the most efficient production of 5AVA. Flask culture and fed-batch culture of this strain produced 6.9 and 19.7 g/L (together with 11.9 g/L glutaric acid as major byproduct) of 5AVA, respectively. Homology modeling suggested that endogenous gamma-aminobutyrate aminotransferase encoded by the gabT gene might be responsible for the conversion of 5AVA to glutaric acid in recombinant C. glutamicum. Fed-batch culture of a C. glutamicum gabT mutant-harboring p36davAB3 produced 33.1 g/L 5AVA with much reduced (2.0 g/L) production of glutaric acid. Conclusions Corynebacterium glutamicum was successfully engineered to produce 5AVA from glucose by optimizing the expression of two key enzymes, lysine 2-monooxygenase and delta-aminovaleramidase. In addition, production of glutaric acid, a major byproduct, was significantly reduced by employing C. glutamicum gabT mutant as a host strain. The metabolically engineered C. glutamicum strains developed in this study should be useful for enhanced fermentative production of the novel C5 platform chemical 5AVA from renewable resources. Electronic supplementary material The online version of this article (doi:10.1186/s12934-016-0566-8) contains supplementary material, which is available to authorized users.

Systems metabolic engineering, which recently emerged as metabolic engineering integrated with systems biology, synthetic biology, and evolutionary engineering, allows engineering of microorganisms on a systemic level for the production of valuable chemicals far beyond its native capabilities. Here, we review the strategies for systems metabolic engineering and particularly its applications in Escherichia coli . First, we cover the various tools developed for genetic manipulation in E. coli to increase the production titers of desired chemicals. Next, we detail the strategies for systems metabolic engineering in E. coli , covering the engineering of the native metabolism, the expansion of metabolism with synthetic pathways, and the process engineering aspects undertaken to achieve higher production titers of desired chemicals. Finally, we examine a couple of notable products as case studies produced in E. coli strains developed by systems metabolic engineering. The large portfolio of chemical products successfully produced by engineered E. coli listed here demonstrates the sheer capacity of what can be envisioned and achieved with respect to microbial production of chemicals. Systems metabolic engineering is no longer in its infancy; it is now widely employed and is also positioned to further embrace next-generation interdisciplinary principles and innovation for its upgrade. Systems metabolic engineering will play increasingly important roles in developing industrial strains including E. coli that are capable of efficiently producing natural and nonnatural chemicals and materials from renewable nonfood biomass.

Objective Endovascular repair of ruptured abdominal aortic aneurysm (rAAA) is being increasingly performed despite lack of good evidence for its superiority. Other reported studies suffer from patient selection and publication bias with limited follow-up. This study is a single-center propensity score comparing early and midterm outcomes between open surgical repair (OSR) and endovascular repair of rAAA (REVAR). Methods A retrospective review from January 2001 to November 2010 identified 312 patients who underwent rAAA repairs. Thirty-one patients with antecedent AAA repair and three with incomplete records were excluded, leaving 37 REVARs and 241 OSRs. Propensity score-based matching for sex, age, preoperative hemodynamic status, surgeon's annual AAA volume, and preoperative cardiopulmonary resuscitation was performed in a 1:3 ratio to compare outcomes. Thirty-seven REVARs were matched with 111 OSRs. Late survival was estimated by Kaplan-Meier methods. Results Operative time and blood replacement were higher with OSR. Overall complication rates were similar (54% REVAR vs 66% OSR; P = .23), except for higher incidences of tracheostomies (21% vs 3%; P = .015), myocardial infarction (38% vs 18%; P = .036), and acute tubular necrosis (47% vs 21%; P = .009) with OSR. Operative mortality rates were similar (22% REVAR vs 32% OSR), with an odds ratio of 0.63 for REVAR (95% confidence interval=[0.24, 1.48]; P = .40). No differences in the incidences for secondary interventions for aneurysm- or graft-related complications were noted (22% REVAR vs 22% OSR; P = .99). Kaplan-Meier estimates of 1-, 2-, and 3-year survival rates were also similar (50%, 50%, 42% REVAR vs 54%, 52%, 47% OSR; P = .66). Conclusions REVAR for rAAA does not seem to conclusively confer either acute or late survival advantages. Routine use of REVAR should be deferred until prospective, randomized trial data become available.

Objective To review the evolution of traumatic thoracic aortic injury (TTAI) treatment at a single institution. Methods Retrospective analysis of all patients included in an institutional trauma registry and vascular surgery database who underwent treatment of TTAI between January 1999 and January 2011. Results Ninety-one patients (69 males) were treated for TTAI. The mean age was 38.5 years (range, 16-79 years). Forty-one patients underwent open repair (OR) and 50 thoracic endovascular repair (TEVAR), 37 with thoracic stent grafts (TSG) alone, 11 with infrarenal aortic extender cuffs (AEC), and two with a combination of TSG and AEC. OR was performed exclusively until 2004; the last one was performed in January 2007. All TTAIs have since been treated with TEVAR. The left subclavian artery (LSA) was fully covered in 10 patients (20%) and partially covered in eight patients, with revascularization in only two cases. The use of AEC and avoidance of LSA coverage increased after 2007. Baseline characteristics and injury severity scores were similar between groups. The mortality rate was higher in the OR group (19.5% vs 6.0%; P = .06), although it did not reach statistical significance. The overall incidence of morbidities was similar between the two groups (42% OR vs 50% TEVAR). Two patients developed paraplegia (4.4%) after OR compared with none after TEVAR. In the TEVAR group, a pseudoaneurysm, an iliac artery thrombosis, and a retroperitoneal hematoma developed in one patient each. Overall, eight patients (16%) developed stent graft-related complications (SRC), with two developing early (within 30 days) complications. All complications were related to poor apposition, requiring 10 reinterventions. Four patients underwent open conversions with no mortality. Nine out of 10 SRCs were associated with the use of thoracic stent graft malapposition. No patient treated with AEC had endoleaks or SRC. Conclusions TEVAR for TTAI has superior survival outcomes and has replaced OR. SRC requiring reintervention is associated with malapposition and the use of TSG. Until TTAI-specific endografts become available, use of AEC may minimize malapposition and reduce reinterventions. Routine overstenting of the LSA is not necessary and may increase SRC.

Introduction: Situs inversus totalis (SIT) is an uncommon condition, with an incidence of 1 in 10,000. Surgery for SIT patients is more difficult because of the uncommon anatomy. Experience in laparoscopic surgery for patients with SIT is very limited. Only a few cases of laparoscopic colorectal resections have been reported in the literature. We present the first robot-assisted low anterior resection for rectal cancer in a patient with SIT. Patient: A 70-year-old woman with SIT who presented with rectal bleeding underwent a colonoscopy and barium enema. This workup revealed a rectal cancer 10 cm from the anal verge. The magnetic resonance imaging scan revealed a T3/4 tumor in the rectum with perirectal lymph node involvement, whereas the computed tomography positron emission tomography scan did not reveal any distal metastasis. She underwent neoadjuvant chemoradiotherapy 6 weeks before surgery. Postoperatively, she made an uneventful recovery and was discharged on day 6. Surgical Technique: After laparoscopic examination and displacement of the small bowel, 4 robot trocars were inserted into 4 quadrants of the abdomen. A fifth port was inserted and used by the assistant. The robot cart was docked from the right side with arms 1, 2, and 3 in the right upper quadrant (Cadiere grasper), left lower quadrant (bipolar Maryland grasper), and left upper quadrant (monopolar scissors), respectively, for colonic mobilization without splenic flexure takedown. For pelvic dissection, arms 1 and 3 were moved to the right upper quadrant and right lower quadrant, respectively. After adequate pelvic dissection, the robot cart was undocked, and a laparoscopic articulating linear stapler was used to transect the rectum from the left lower quadrant port. Bowel continuity was restored with a circular stapler. A loop ileostomy was created through the extraction site in the right lower quadrant. Conclusions: Robot-assisted low anterior resection for SIT patients can be performed safely and confers the benefits of laparoscopic low anterior resection with additional advantages unique to the da Vinci system.

Background Incidental visualization of indeterminate pulmonary nodules is considered a clinical dilemma. Methods We identified patients for inclusion in this study by searching for the term “indeterminate nodules” in the radiology database of rectal cancer patients who underwent surgery. Patients with definite metastatic disease were excluded. Results In total, 224 patients underwent chest computerized tomography (CT) and 59 of these patients had indeterminate pulmonary nodules detected more than twice by CT scan. Six patients (10.2%) were confirmed to have metastatic lesions on follow-up evaluation. Pulmonary nodule size (P = 0.028), pathologic N status (P = 0.049), positive nodal status (P = 0.036) and the number of positive lymph nodes (P = 0.033) were significant risk factors for pulmonary metastasis. In the pulmonary metastasis group, the patients who had received adjuvant oxaliplatin-based (FOLFOX4) chemotherapy had longer intervals to developing metastasis compared to patients who had not received it. Conclusions It is not necessary to perform excessive surveillance routinely for all rectal cancer patients who have indeterminate pulmonary lesions. Intensive follow-up chest CT or other invasive diagnostic modalities should be considered only in patients with pulmonary nodules larger than 5.7 mm or positive nodal status. In addition, patients receiving adjuvant FOLFOX4 chemotherapy should be followed-up for longer periods. J. Surg. Oncol. 2012; 106:481–485. © 2012 Wiley Periodicals, Inc.

Intersphincteric resection (ISR) is the ultimate sphincter saving procedure for low rectal cancer. Hemorrhoids are a common benign condition. We present and discuss a case of ISR which developed painful edematous hemorrhoids after ISR. A 62-year-old female with low rectal cancer received neoadjuvant chemoradiotherapy with successful down staging of tumor before undergoing robot assisted ISR with coloanal hand-sewn anastomosis. She had pre-existing external hemorrhoids which were not excised. She developed painful and edematous external hemorrhoids 4 days after surgery. These were treated conservatively before discharge. Many colorectal surgeons performing ISR have experienced similar situations in their patients, but none have reported on this phenomenon. We discuss the possible factors that may contribute to this situation. A possible solution is prophylactic excision of the hemorrhoids during coloanal anastomosis. Painful hemorrhoids may occur after ISR and if managed conservatively, the outcome is skin tags.

Thoracic stent graft collapse is a rare complication of thoracic endovascular aortic repair that is mostly asymptomatic and occurs ≤ 3 months of the procedure. We describe the case of a 36-year-old man who presented with symptomatic endograft collapse 38 months after an initial thoracic endovascular aortic repair that was performed for traumatic aortic transection. He had sudden and complete loss of bilateral lower extremity motor and sensory functions (spinal cord ischemia) and anal sphincter tone. The patient was successfully treated with redo thoracic endovascular aortic repair, followed by open conversion and device explantation.

An electric active stabilizer suspension system has been developed as a technology for controlling vehicle roll. The system includes various sensors that detect the vehicle's running state, and active stabilizer actuators that use electric motors and reduction gears to control roll. The electric stabilizer suspension system was compared with hydraulic stabilizer systems, and an investigation demonstrated the superiority of the developed system, which offers outstanding vehicle behavior, improved responsiveness and reduced energy consumption (including energy regeneration).

Silica-based optical fibre sensors are widely used in structural health monitoring systems for strain and deflection measurement. One drawback of silica-based optical fibre sensors is their low strain toughness. In general, silica-based optical fibre sensors can only reliably measure strains up to 2%. Recently, polymer optical fibre sensors have been investigated for large strain measurement. Because of their high optical losses, the length of the polymer optical fibres is limited to 100 m. In this paper, we present a novel economical technique to fabricate hybrid silica/polymer optical fibre sensors that are capable of measuring large strain. First, stress analysis of a surface-mounted optical fibre sensor is performed to understand the effect of mechanical properties on the load distribution between the optical fibre and the host structure. Next, the procedure for fabricating a tapered polymer sensing element between two silica optical fibres is explained. The experimental set-up and the components used in the fabrication process are described in detail. Test results of the fabricated silica/polymer optical fibre strain sensor are presented.

ObjectiveThe purpose of this study is to evaluate contemporary results of ruptured aortoiliac aneurysms (RAAA) and identify the role of surgeons' annual aortic volume and other prognostic indicators for early outcome.MethodsA retrospective review identified 213 consecutive patients who presented with an atherosclerotic RAAA without thoracic extension over 6.5 years ending in June 2007. Excluded were 31 ruptures treated by endovascular repair (EVAR) or following previous EVAR, also excluded were two chronic asymptomatic hemodynamically stable ruptures. Ten patients were not treated due to either patient's refusal or prohibitive surgical risk. Demographic, preoperative, intraoperative, and postoperative variables were collected. Log rank test and Cox proportional hazard model analyses were utilized to identify factors contributing to mortality and morbidity in these patients. Survival rates were estimated by Kaplan-Meier method.ResultsOne hundred thirty-one males and 39 females with a mean age of 74.5 ± 8.1 years underwent consecutive RAAA repairs. The operative mortality rate was 38.2% (65/170), including 29 intraoperative deaths. Using multivariate analysis, surgeon's average annual AAA volume (20 average annual AAA cases/y) had a higher 30-day survival rates (78.4% vs 57.9%, P = .024). Octogenarians had a lower 30-day survival rate of 49.0% vs 70.5% (P = .012). Patients who developed postoperative intestinal ischemia had a lower 30-day survival rate compared with patients without (48.1% vs 15.3%, P = .002). Increased intraoperative fluid and blood product usage was associated with bowel ischemia (P < .05).ConclusionsRAAA remains a highly lethal problem. The improved early outcomes of surgeons with high-volume AAA have strong implications for training, emergency staffing needs and alternative treatment strategies.