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Despite its name, signalling induced by the tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is versatile. Besides eliciting cell death by both apoptosis and necroptosis, TRAIL can also induce migration, proliferation, and cytokine production in cancerous and non-cancerous cells. Unravelling the mechanisms regulating the intricate balance between these different outputs could therefore facilitate our understanding of the role of TRAIL in tissue homeostasis, immunity, and cancer. Ubiquitination and its reversal, deubiquitination, are crucial modulators of immune receptor signalling. This review discusses recent progress on the orchestration of TRAIL signalling outcomes by ubiquitination of various components of the signalling complexes, our understanding of the molecular switches that decide between cell death and gene activation, and what remains to be discovered., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The internet is a valuable tool, but concerns exist regarding the quality and accuracy of medical information available online., Purpose: To evaluate the source and quality of information on the internet relating to anterolateral ligament reconstruction (ALLR) compared with anterior cruciate ligament reconstruction (ACLR)., Study Design: Cross-sectional study., Methods: A questionnaire was administered to 50 ACLR patients in Australia to determine their use of the internet to research their operation and their familiarity with the anterolateral ligament (ALL) of the knee. The most common search terms were determined, and the first 70 websites returned by the 5 most popular search engines were used to assess the quality of information about ACLR and ALLR. Each site was categorized by type and was assessed for quality and validity using the DISCERN score, the Journal of the American Medical Association (JAMA) benchmark criteria, and a novel specific content score for each procedure. The presence of the Health on the Net Code (HONcode) seal was also recorded., Results: The majority (84%) of ACLR patients used the internet to research their operation. The quality of information available for ALLR was significantly inferior to that for ACLR according to the DISCERN score (37.3 ± 3.4 vs 54.4 ± 4.6; P < .0001) and specific content score (5.3 ± 1.3 vs 11.0 ± 1.5; P < .0001). ACLR websites were predominantly physician produced, while the majority of ALLR websites were academic. In contrast to ACLR websites, the majority of ALLR websites did not provide information on the indication for treatment or potential complications. ALLR websites scored better on the JAMA benchmark criteria due to the predominance of academic websites. A greater proportion of ACLR websites (14.6%) versus ALLR websites (2.5%) provided an HONcode seal. Correlation was demonstrated between the DISCERN score and specific content scores for both ACLR and ALLR but not with JAMA benchmark criteria. The specific content score had high reliability for both ACLR and ALLR., Conclusion: The majority of patients undergoing ACLR in Australia used the internet to research the procedure. The quality of information on the internet relating to ALLR was significantly inferior to information about ACLR. Most ALLR websites failed to include crucial information about the indication or options for treatment, prognosis, and potential complications. Surgeons should be aware of the information to which their patients are exposed through the internet and should be proactive in directing patients to appropriate websites., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.

Introduction: The stabilization of an atlantoaxial (C1-C2) instability is demanding due to a complex atlantoaxial anatomy with proximity to the spinal cord, a variable run of the vertebral artery (VA) and narrow C2 pedicles. We perfomed the Goel & Harms fusion in combination with an intraoperative 3D imaging to ensure correct screw placement in the C2 pedicle. We hypothesized, that narrow C2 pedicles lead to a higher malposition rate of screws by perforation of the pedicle wall. The purpose of this study was to describe a certain pedicle size, under which the perforation rate rises., Patients and Methods: In this retrospective study, all patients (n=30) were operated in the Goel & Harms technique. The isthmus height and pedicle diameter of C2 were measured. The achieved screw position in C2 was evaluated according to Gertzbein & Robbin classification (GRGr)., Results: A statistically significant correlation was found between the pedicles size (isthmus height/pedicle diameter) and the achieved GRGr for the right (p=0.002/p=0.03) and left side (p=0.018/p=0.008). The ROC analysis yielded a Cut Off value for the pedicle size to distinguish between an intact or perforated pedicle wall (GRGr 1 or ≥2). The Cut-Off value was identified for the isthmus height (right 6.1mm, left 5.4mm) and for the pedicle diameter (6.6mm both sides)., Conclusion: The hypothesis, that narrow pedicles lead to a higher perforation rate of the pedicle wall, can be accepted. Pedicles of <6.6mm turned out to be a risk factor for a perforation of the pedicle wall (GRGr 2 or higher). Intraoperative 3D imaging is a feasible tool to confirm optimal screw position, which becomes even more important in cases with thin pedicles. The rising risk of VA injury in these cases support the additional use of navigation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The role of lateral extra-articular tenodesis (LEAT) to augment primary anterior cruciate ligament reconstruction (ACLR) remains controversial., Purpose: To determine whether the addition of LEAT to primary ACLR provides greater control of rotational laxity and improves clinical outcomes compared with ACLR alone and to assess the impact of early versus delayed ACLR., Study Design: Systematic review; Level of evidence, 3., Methods: Two reviewers independently searched 7 databases for randomized and nonrandomized clinical studies comparing ACLR plus LEAT versus ACLR alone. Animal, cadaveric, and biomechanical studies; revision or repair procedures; and studies using synthetic ligaments and multiligamentous-injured knees were excluded. Risk of bias was assessed with a modified Downs and Black checklist. The primary outcome was postoperative pivot shift. These data were pooled by use of a fixed-effects meta-analysis model. The studies were divided into delayed (>12 months) and early (≤12 months) reconstruction groups for meta-analysis. A best-evidence synthesis was performed on the remaining outcome measures., Results: Of 387 titles identified, 11 articles were included (5 of high quality). Meta-analysis of postoperative pivot shift in 3 studies of delayed primary ACLR showed a statistically significant difference for the pivot-shift test in favor of ACLR with LEAT (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.24-0.81; P = .008; I 2 = 0). Meta-analysis of 5 studies of early primary ACLR found no statistically significant difference with the addition of LEAT (OR, 0.60; 95% CI, 0.33-1.09; P = .10; I 2 = 33%). Insufficient evidence was available to determine whether the addition of LEAT had any effect on clinical, objective, subjective, and functional outcomes., Conclusion: In primary ACLR, no evidence is available showing additional benefit of LEAT in reducing the postoperative pivot shift in early reconstructions (≤12 months); however, LEAT may have a role in delayed ACLR. Strong evidence exists that a combined ACLR and LEAT reduces lateral femoral translation, but there is insufficient evidence to identify any benefit for other clinical outcomes., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages de novo LUBAC is a crucial component of various immune receptor signalling pathways. Here, we show that LUBAC forms part of the TRAIL-R-associated complex I as well as of the cytoplasmic TRAIL-induced complex II In both of these complexes, HOIP limits caspase-8 activity and, consequently, apoptosis whilst being itself cleaved in a caspase-8-dependent manner. Yet, by limiting the formation of a RIPK1/RIPK3/MLKL-containing complex, LUBAC also restricts TRAIL-induced necroptosis. We identify RIPK1 and caspase-8 as linearly ubiquitinated targets of LUBAC following TRAIL stimulation. Contrary to its role in preventing TRAIL-induced RIPK1-independent apoptosis, HOIP presence, but not its activity, is required for preventing necroptosis. By promoting recruitment of the IKK complex to complex I, LUBAC also promotes TRAIL-induced activation of NF-κB and, consequently, the production of cytokines, downstream of FADD, caspase-8 and cIAP1/2. Hence, LUBAC controls the TRAIL signalling outcome from complex I and II, two platforms which both trigger cell death and gene activation., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages. TRAIL-R suppression in tumor cells impaired CCL2 production and diminished both lung MDSC presence and tumor growth. In accordance, the receptor of CCL2, CCR2, is required to facilitate increased MDSC presence and tumor growth. Finally, TRAIL and CCL2 are co-regulated with MDSC/M2 markers in lung adenocarcinoma patients. Collectively, endogenous TRAIL/TRAIL-R-mediated CCL2 secretion promotes accumulation of tumor-supportive immune cells in the cancer microenvironment, thereby revealing a tumor-supportive immune-modulatory role of the TRAIL/TRAIL-R system in cancer biology., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of the present study was to histologically compare chondrotoxicity in surgically harvested intervertebral discs (IVDs) of patients following discoblock, discography, or no preoperative intervention., Methods: Thirty patients (IVD degeneration Modic ≥ 2°, Pfirrmann 3° or 4°) at L4/5 or L5/S1 who were planned for anterior lumbar interbody fusion were randomly assigned to three groups (open MRI: group DG - discography with gadobutrol; group DB - discoblock with bupivacaine at 4 weeks prior to surgery; group C - no intervention). The intervertebral discs were histologically evaluated and compared using ANOVA and Bonferroni tests for cell count, apoptosis, and proliferation., Results: A reduced cell count (groups DG vs. DB vs. C: 14.9 ± 7.1, 9.2 ± 3.8, and 16.6 ± 5.2 cells/mm 2 , respectively; p ANOVA  = 0.016), increased apoptosis (groups DG vs. DB vs. C: 34.9 ± 10.2, 47.4 ± 16.3, 32.6 ± 12.2 %, respectively; p ANOVA  = 0.039) and increased cell proliferation (post hoc pDB vs. DG or C p < 0.001; for 3-7 cell monoclonal cell nests: groups DG vs. DB vs. C: 2.4 ± 1, 3.9 ± 1, 2.2 ± 1.1, respectively; p intervention x nest size  = 0.006) were found in the IVDs of patients in group DB., Conclusions: This in vivo study suggests that chondrotoxic effects occur in IVD cells after the intradiscal injection of bupivacaine but not after gadobutrol administration., Key Points: • Local bupivacaine administration to intervertebral discs leads to cell toxicity and proliferation. • Gadobutrol demonstrated no significant effect on cell count, apoptosis, or cell proliferation. • In vivo cytotoxicity was demonstrated histologically in humans for the first time. • Addition/administration of bupivacaine during discographies must be judged critically.

The linear ubiquitin chain assembly complex (LUBAC), consisting of SHANK-associated RH-domain-interacting protein (SHARPIN), heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1), and HOIL-1-interacting protein (HOIP), is a critical regulator of inflammation and immunity. This is highlighted by the fact that patients with perturbed linear ubiquitination caused by mutations in the Hoip or Hoil-1 genes, resulting in knockouts of these proteins, may simultaneously suffer from immunodeficiency and autoinflammation. TLR3 plays a crucial, albeit controversial, role in viral infection and tissue damage. We identify a pivotal role of LUBAC in TLR3 signaling and discover a functional interaction between LUBAC components and TLR3 as crucial for immunity to influenza A virus infection. On the biochemical level, we identify LUBAC components as interacting with the TLR3-signaling complex (SC), thereby enabling TLR3-mediated gene activation. Absence of LUBAC components increases formation of a previously unrecognized TLR3-induced death-inducing SC, leading to enhanced cell death. Intriguingly, excessive TLR3-mediated cell death, induced by double-stranded RNA present in the skin of SHARPIN-deficient chronic proliferative dermatitis mice (cpdm), is a major contributor to their autoinflammatory skin phenotype, as genetic coablation of Tlr3 substantially ameliorated cpdm dermatitis. Thus, LUBAC components control TLR3-mediated innate immunity, thereby preventing development of immunodeficiency and autoinflammation., (© 2016 Zinngrebe et al.)

Priority effects, in which the order of species arrival dictates community assembly, can have a major influence on species diversity, but the genetic basis of priority effects remains unknown. Here, we suggest that nitrogen scavenging genes previously considered responsible for starvation avoidance may drive priority effects by causing rapid resource depletion. Using single-molecule sequencing, we de novo assembled the genome of the nectar-colonizing yeast, Metschnikowia reukaufii, across eight scaffolds and complete mitochondrion, with gap-free coverage over gene spaces. We found a high rate of tandem gene duplication in this genome, enriched for nitrogen metabolism and transport. Both high-capacity amino acid importers, GAP1 and PUT4, present as tandem gene arrays, were highly expressed in synthetic nectar and regulated by the availability and quality of amino acids. In experiments with competitive nectar yeast, Candida rancensis, amino acid addition alleviated suppression of C. rancensis by early arrival of M. reukaufii, corroborating that amino acid scavenging may contribute to priority effects. Because niche pre-emption via rapid resource depletion may underlie priority effects in a broad range of microbial, plant and animal communities, nutrient scavenging genes like the ones we considered here may be broadly relevant to understanding priority effects., (© 2016 The Author(s).)

Background: Despite the health benefits of regular physical activity, most children are insufficiently active. Schools are ideally placed to promote physical activity; however, many do not provide children with sufficient in-school activity or ensure they have the skills and motivation to be active beyond the school setting. The aim of this project is to modify, scale up and evaluate the effectiveness of an intervention previously shown to be efficacious in improving children's physical activity, fundamental movement skills and cardiorespiratory fitness. The 'Internet-based Professional Learning to help teachers support Activity in Youth' (iPLAY) study will focus largely on online delivery to enhance translational capacity., Methods/design: The intervention will be implemented at school and teacher levels, and will include six components: (i) quality physical education and school sport, (ii) classroom movement breaks, (iii) physically active homework, (iv) active playgrounds, (v) community physical activity links and (vi) parent/caregiver engagement. Experienced physical education teachers will deliver professional learning workshops and follow-up, individualized mentoring to primary teachers (i.e., Kindergarten - Year 6). These activities will be supported by online learning and resources. Teachers will then deliver the iPLAY intervention components in their schools. We will evaluate iPLAY in two complementary studies in primary schools across New South Wales (NSW), Australia. A cluster randomized controlled trial (RCT), involving a representative sample of 20 schools within NSW (1:1 allocation at the school level to intervention and attention control conditions), will assess effectiveness and cost-effectiveness at 12 and 24 months. Students' cardiorespiratory fitness will be the primary outcome in this trial. Key secondary outcomes will include students' moderate-to-vigorous physical activity (via accelerometers), fundamental movement skill proficiency, enjoyment of physical education and sport, cognitive control, performance on standardized tests of numeracy and literacy, and cost-effectiveness. A scale-up implementation study guided by the RE-AIM framework will evaluate the reach, effectiveness, adoption, implementation, and maintenance of the intervention when delivered in 160 primary schools in urban and regional areas of NSW., Discussion: This project will provide the evidence and a framework for government to guide physical activity promotion throughout NSW primary schools and a potential model for adoption in other states and countries., Trial Registration: Australia and New Zealand Clinical Trials Registry ( ACTRN12616000731493 ). Date of registration: June 3, 2016.

A small number of phytohormones dictate the pattern of plant form affecting fitness via reproductive architecture and the plant's ability to forage for light, water, and nutrients. Individual phytohormone contributions to plant architecture have been studied extensively, often following a single component of plant architecture, such as plant height or branching. Both brassinosteroid (BR) and gibberellin (GA) affect plant height, branching, and sexual organ development in maize (Zea mays). We identified the molecular basis of the nana plant2 (na2) phenotype as a loss-of-function mutation in one of the two maize paralogs of the Arabidopsis (Arabidopsis thaliana) BR biosynthetic gene DWARF1 (DWF1). These mutants accumulate the DWF1 substrate 24-methylenecholesterol and exhibit decreased levels of downstream BR metabolites. We utilized this mutant and known GA biosynthetic mutants to investigate the genetic interactions between BR and GA. Double mutants exhibited additivity for some phenotypes and epistasis for others with no unifying pattern, indicating that BR and GA interact to affect development but in a context-dependent manner. Similar results were observed in double mutant analyses using additional BR and GA biosynthetic mutant loci. Thus, the BR and GA interactions were neither locus nor allele specific. Exogenous application of GA3 to na2 and d5, a GA biosynthetic mutant, also resulted in a diverse pattern of growth responses, including BR-dependent GA responses. These findings demonstrate that BR and GA do not interact via a single inclusive pathway in maize but rather suggest that differential signal transduction and downstream responses are affected dependent upon the developmental context., (© 2016 American Society of Plant Biologists. All Rights Reserved.)

Background Context: An overload of the paravertebral muscles after surgical intervention is suggested to be the major cause of postoperative pain. In cross-sectional area analyses, increased atrophy of the multifidus muscle (MF) after conventional open versus minimally invasive posterior lumbar interbody fusion (PLIF) has been described. The three-dimensional characteristics of the paravertebral muscles and separate evaluation of the longissimus muscle (LS) have not been addressed in analyses thus far., Purpose: The purpose of the present study was to compare the MF and LS volume atrophy and fatty degeneration between single-level minimally invasive transforaminal lumbar interbody fusion (miTLIF) and conventional midline approach-based PLIF (coPLIF) of L4/L5 or L5/S1 at the index and superior adjacent segments., Design: This was a prospective, randomized, controlled, non-blinded study., Patient Sample: Fifty patients with single-level segment degeneration (Pfirrmann ≥III and Modic ≥3) of L4/L5 or L5/S1 not requiring decompression were randomly assigned to two groups., Outcome Measures: Paraspinal lumbar residual muscle tissue volume, change in the relative fat content of MF and LS at the index and superior adjacent segments, and clinical parameters, including a visual analogue scale (VAS) for low back pain and the Oswestry Disability Questionnaire (ODI) were the outcome measures in this study., Methods: Twenty-five patients were treated with miTLIF, and the remaining patients were treated with coPLIF (both with transpedicular fixation). Clinical scoring was performed preoperatively and at 1 week and 12 months postoperatively, and computed tomography was performed at the latter two follow-ups., Results: The LS damage at the index segment was similar in both groups (3% greater fat content increase in the coPLIF vs. the miTLIF group, p=.032), whereas MF atrophy and degeneration were increased (p<.001) in the coPLIF group. At the adjacent segment, muscle atrophy and increased fatty infiltration (p<.05) were minimal in both muscles but were similar in both groups. Visual analogue scale and ODI scores improved (p<.001), without differences between the groups., Conclusions: The muscle damage after miTLIF was inferior to that after coPLIF; spatially, however, the muscle sparing was predominantly attributed to the MF and, surprisingly, not to the LS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To date, it remains unclear whether the preservation of segmental motion by total disc replacement (TDR) or motion restriction by stand-alone anterior lumbar interbody fusion (ALIF) have an influence on postoperative degeneration of the posterior paraspinal muscles or the associated clinical results. Therefore, the purpose of the present prospective randomized study was to evaluate the clinical parameters and 3D quantitative radiological changes in the paraspinal muscles of the lumbar spine in surgically treated segments and superior adjacent segments after ALIF and TDR., Methods: A total of 50 patients with chronic low-back pain caused by single-level intervertebral disc degeneration (Pfirrmann Grade ≥ III) and/or osteochondrosis (Modic Type ≤ 2) without symptomatic facet joint degeneration (Fujiwara Grade ≤ 2, infiltration test) of the segments L4-5 or L5-S1 were randomly assigned to 2 treatment groups. Twenty-five patients were treated with a stand-alone ALIF and the remaining 25 patients underwent TDR. For ALIF and TDR, a retroperitoneal approach was used. At 1 week and at 12 months after surgery, CT was used to analyze paraspinal lumbar muscle tissue volume and relative fat content. Residual muscle tissue volume at 12 months and change in the relative fat content were compared between the groups. In addition, clinical parameters (visual analog scale [VAS] for low-back pain and Oswestry Disability Index [ODI] Questionnaire Version 2 for function) were compared., Results: Compared with 1 week after surgery, the radiological analysis at 12 months revealed a small decrease in the posterior muscle volume (the mean decrease was < 2.5%), along with a small increase in the relative fat content (the mean increase was < 1.9%), in both groups at the index and superior adjacent segments. At the adjacent segment, the ALIF group presented significantly less muscle tissue volume atrophy and a smaller increase in fat content compared with the TDR group. At final follow-up, the clinical parameters related to pain and function were significantly improved in both groups compared with 1 week postsurgery, but there were no differences between the groups., Conclusions: Motion restriction via stand-alone ALIF and motion preservation via TDR both present small changes in the posterior lumbar paraspinal muscles with regard to volume atrophy or fatty degeneration at the index and superior adjacent segments. Therefore, although the clinical outcome was not affected by the observed muscular changes, the authors concluded that the expected negative influence of motion restriction on the posterior muscles compared with motion preservation does not occur on a clinically relevant level.

Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1) ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-SC), at which they cooperate to limit gene activation. Whereas CYLD recruitment depends on its interaction with LUBAC, but not on LUBAC's M1-chain-forming capacity, A20 recruitment requires this activity. Intriguingly, CYLD and A20 exert opposing effects on M1 chain stability in the TNF-RSC and NOD2-SC. While CYLD cleaves M1 chains, and thereby sensitizes cells to TNF-induced death, A20 binding to them prevents their removal and, consequently, inhibits cell death. Thus, CYLD and A20 cooperatively restrict gene activation and regulate cell death via their respective activities on M1 chains. Hence, the interplay between LUBAC, M1-ubiquitin, CYLD, and A20 is central for physiological signaling through innate immune receptors., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Conventional αβ T cells have the ability to form a long-lasting resident memory T-cell (TRM ) population in nonlymphoid tissues after encountering foreign antigen. Conversely, the concept of 'innate memory', where the ability of nonadaptive branches of the immune system to deliver a rapid, strengthened immune response upon reinfection or rechallenge, is just emerging. Using the αβ T-cell-independent Aldara psoriasis mouse model in combination with genetic fate-mapping and reporter systems, we identified a subset of γδ T cells in mice that is capable of establishing a long-lived memory population in the skin. IL-17A/F-producing Vγ4(+) Vδ4(+) T cells populate and persist in the dermis for long periods of time after initial stimulation with Aldara. Experienced Vγ4(+) Vδ4(+) cells show enhanced effector functions and mediate an exacerbated secondary inflammatory response. In addition to identifying a unique feature of γδ T cells during inflammation, our results have direct relevance to the human disease as this quasi-innate memory provides a mechanistic insight into relapses and chronification of psoriasis., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although the importance of reactive astrocytes during CNS pathology is well established, the function of astroglia in adult CNS homeostasis is less well understood. With the use of conditional, astrocyte-restricted protein synthesis termination, we found that selective paralysis of GFAP(+) astrocytes in vivo led to rapid neuronal cell loss and severe motor deficits. This occurred while structural astroglial support still persisted and in the absence of any major microvascular damage. Whereas loss of astrocyte function did lead to microglial activation, this had no impact on the neuronal loss and clinical decline. Neuronal injury was caused by oxidative stress resulting from the reduced redox scavenging capability of dysfunctional astrocytes and could be prevented by the in vivo treatment with scavengers of reactive oxygen and nitrogen species (ROS/RNS). Our results suggest that the subpopulation of GFAP(+) astrocytes maintain neuronal health by controlling redox homeostasis in the adult CNS., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: With adolescent sport increasingly challenged by mismatches in size, new strategies are important to maximize participation. The objectives were to (1) improve the understanding of mismatches in physical size, speed and power in adolescent rugby union players, (2) explore associations between size and performance with demographic, playing-history, and injury profiles, and (3) explore the applicability of existing criteria for age/body mass-based dispensation (playing-down) strategies., Design: Cross-sectional study., Methods: Four hundred and eighty-five male community rugby union players were recruited from three Australian states selected to represent community-based U12, U13, U14 and U15 players. Body mass, stature, speed (10, 30, and 40 m sprints) and lower-leg power (relative peak power and relative peak force) were measured. Independent student t-tests, linear regressions and Chi square analyses were undertaken., Results: Mean values in age groups for size, speed and power masked considerable overlap in the ranges within specific age groups of adolescent rugby players. Only a small proportion of players (approximately 5%) shared the highest and lowest tertiles for speed, relative peak power and body mass. Physical size was not related to injury. The mean body mass of current community rugby union players was above the 75th percentile on normative growth-charts., Conclusion: The notion that bigger, faster, and more powerful characteristics occur simultaneously in adolescent rugby players was not supported in the present study. Current practices in body mass-based criteria for playing down an age group lack a sufficient evidence for decision-making. Dispensation solely based on body mass may not address mismatch in junior rugby union., (Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Many cancers harbor oncogenic mutations of KRAS. Effectors mediating cancer progression, invasion, and metastasis in KRAS-mutated cancers are only incompletely understood. Here we identify cancer cell-expressed murine TRAIL-R, whose main function ascribed so far has been the induction of apoptosis as a crucial mediator of KRAS-driven cancer progression, invasion, and metastasis and in vivo Rac-1 activation. Cancer cell-restricted genetic ablation of murine TRAIL-R in autochthonous KRAS-driven models of non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) reduces tumor growth, blunts metastasis, and prolongs survival by inhibiting cancer cell-autonomous migration, proliferation, and invasion. Consistent with this, high TRAIL-R2 expression correlates with invasion of human PDAC into lymph vessels and with shortened metastasis-free survival of KRAS-mutated colorectal cancer patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Steroid hormones are key regulators of growth and physiology in both plants and animals. The plant steroid hormones known as brassinosteroids (BRs) are essential for a wide range of developmental processes throughout the life cycle. In contrast with animal steroid hormones, which act mostly through nuclear receptors, BRs act through a cell-surface receptor kinase. The BR signal transduction pathway from the cell-surface receptor to nuclear gene expression has been elucidated in great molecular detail, and thus serves as a paradigm for receptor kinase signalling in plants. Furthermore, several mechanisms of signal integration have been identified that explain how BRs and other hormonal and environmental signals co-regulate specific developmental outputs in a synergistic or antagonistic manner., (© 2015 Authors; published by Portland Press Limited.)

Plant growth regulators, such as hormones and their respective biosynthesis inhibitors, are effective tools to elucidate the physiological function of phytohormones in plants. A problem of chemical treatments, however, is the potential for interaction of the active compound with the growth media substrate. We studied the interaction and efficacy of propiconazole, a potent and specific inhibitor of brassinosteroid biosynthesis, with common soilless greenhouse growth media for rice, sorghum, and maize. Many of the tested growth media interacted with propiconazole reducing its efficacy up to a hundred fold. To determine the molecular interaction of inhibitors with media substrates, Fourier Transform Infrared Spectroscopy and sorption isotherm analysis was applied. While mica clay substrates absorbed up to 1.3 mg of propiconazole per g substrate, calcined clays bound up to 12 mg of propiconazole per g substrate. The efficacy of the gibberellic acid biosynthesis inhibitor, uniconazole, and the most active brassinosteroid, brassinolide, was impacted similarly by the respective substrates. Conversely, gibberellic acid showed no distinct growth response in different media. Our results suggest that the reduction in efficacy of propiconazole, uniconazole, and brassinolide in bioassays when grown in calcined clay is caused by hydrophobic interactions between the plant growth regulators and the growth media. This was further confirmed by experiments using methanol-water solvent mixes with higher hydrophobicity values, which reduce the interaction of propiconazole and calcined clay.

Purpose: To evaluate and compare the costs of MRI-guided and CT-guided cervical nerve root infiltration for the minimally invasive treatment of radicular neck pain., Materials and Methods: Between September 2009 and April 2012, 22 patients (9 men, 13 women; mean age: 48.2 years) underwent MRI-guided (1.0 Tesla, Panorama HFO, Philips) single-site periradicular cervical nerve root infiltration with 40 mg triamcinolone acetonide. A further 64 patients (34 men, 30 women; mean age: 50.3 years) were treated under CT fluoroscopic guidance (Somatom Definition 64, Siemens). The mean overall costs were calculated as the sum of the prorated costs of equipment use (purchase, depreciation, maintenance, and energy costs), personnel costs and expenditure for disposables that were identified for MRI- and CT-guided procedures. Additionally, the cost of ultrasound guidance was calculated., Results: The mean intervention time was 24.9 min. (range: 12 - 36 min.) for MRI-guided infiltration and 19.7 min. (range: 5 - 54 min.) for CT-guided infiltration. The average total costs per patient were EUR 240 for MRI-guided interventions and EUR 124 for CT-guided interventions. These were (MRI/CT guidance) EUR 150/60 for equipment use, EUR 46/40 for personnel, and EUR 44/25 for disposables. The mean overall cost of ultrasound guidance was EUR 76., Conclusion: Cervical nerve root infiltration using MRI guidance is still about twice as expensive as infiltration using CT guidance. However, since it does not involve radiation exposure for patients and personnel, MRI-guided nerve root infiltration may become a promising alternative to the CT-guided procedure, especially since a further price decrease is expected for MRI devices and MR-compatible disposables. In contrast, ultrasound remains the less expensive method for nerve root infiltration guidance., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To evaluate the accuracy, safety, and efficacy of cervical nerve root injection therapy using magnetic resonance guidance in an open 1.0 T MRI system., Methods: Between September 2009 and April 2012, a total of 21 patients (9 men, 12 women; mean age 47.1 ± 11.1 years) underwent MR-guided cervical periradicular injection for cervical radicular pain in an open 1.0 T system. An interactive proton density-weighted turbo spin echo (PDw TSE) sequence was used for real-time guidance of the MR-compatible 20-gauge injection needle. Clinical outcome was evaluated on a verbal numeric rating scale (VNRS) before injection therapy (baseline) and at 1 week and 1, 3, and 6 months during follow-up., Results: All procedures were technically successful and there were no major complications. The mean preinterventional VNRS score was 7.42 and exhibited a statistically significant decrease (P < 0.001) at all follow-up time points: 3.86 ± 1.53 at 1 week, 3.21 ± 2.19 at 1 month, 2.58 ± 2.54 at 3 months, and 2.76 ± 2.63 at 6 months. At 6 months, 14.3 % of the patients reported complete resolution of radicular pain and 38.1 % each had either significant (4-8 VNRS score points) or mild (1-3 VNRS score points) relief of pain; 9.5 % experienced no pain relief., Conclusion: Magnetic resonance fluoroscopy-guided periradicular cervical spine injection is an accurate, safe, and efficacious treatment option for patients with cervical radicular pain. The technique may be a promising alternative to fluoroscopy- or CT-guided injections of the cervical spine, especially in young patients and in patients requiring repeat injections.

The general approach to the initial resuscitation of non-trauma patients does not differ from the ABCDE approach used to evaluate severely injured patients. After initial stabilization of vital functions patients are evaluated based on the symptoms and critical care interventions are initiated as and when necessary. Adequate structural logistics and personnel organization are crucial for the treatment of non-trauma critically ill patients although there is currently a lack of clearly defined requirements. For severely injured patients there are recommendations in the S3 guidelines on treatment of multiple trauma and severely injured patients and these can be modeled according to the white paper of the German Society of Trauma Surgery (DGU). However, structured training programs similar to the advanced trauma life support (ATLS®)/European resuscitation course (ETC®) that go beyond the current scope of advanced cardiac life support training are needed. The development of an advanced critically ill life support (ACILS®) concept for non-trauma critically ill patients in the resuscitation room should be supported.

Objectives: To evaluate the accuracy, safety and efficacy of magnetic resonance imaging (MRI)-guided facet joint injection therapy using a 1.0-T open MRI., Methods: One hundred and sixty-six facet joint blocks in 45 patients with lower back pain were performed under MR fluoroscopic guidance using a proton-density-weighted turbo-spin-echo sequence. An in-room monitor, wireless MR-mouse for operator-controlled multiplanar navigation, a flexible surface coil and MR-compatible 20-G needle were used. Clinical outcome was evaluated by questionnaire before intervention and after 1 week, 3, 6 and 12 months using a numerical visual analogue scale (VAS)., Results: All facet joint blocks were considered technically successful with distribution of the injectant within and/or around the targeted facet joint. No major complications occurred. The final outcome analysis included 38 patients. An immediate effect was reported by 63 % of the patients. A positive mid-/long-term effect was seen in 13 patients (34 %) after 6 months and in 9 patients (24 %) after 12 months. Mean VAS was reduced from 7.1 ± 1.7 (baseline) to 3.5 ± 2.2, 4.1 ± 3.0, 3.8 ± 2.9 and 4.6 ± 2.9 at 1 week, 3, 6 and 12 months (P < 0.01)., Conclusions: MR-guided facet joint injection therapy of the lumbosacral spine is accurate, safe and efficient in the symptomatic treatment of lower back pain.

We report the case of symptomatic extra-articular subspinal impingement in the hip joint caused by a pathological contact between the anterior inferior iliac spine (AIIS) and the femoral neck. A 28-year-old patient presented with activity-related inguinal pain on the right side and a positive anterior impingement test in the clinical examination. Radiological examinations revealed a hypertrophic AIIS with caudal extension below the acetabulum. After a positive injection test confirmed the AIIS as the origin of the pain, arthroscopic correction with partial resection of the AIIS was performed resulting in significant pain relief and improved range of motion.

Objectives: To assess the feasibility, safety and efficacy of real-time MR guidance and thermometry of percutaneous laser disc decompression (PLDD)., Methods: Twenty-four discs in 22 patients with chronic low-back and radicular pain were treated by PLDD using open 1.0-T magnetic-resonance imaging (MRI). A fluoroscopic proton-density-weighted turbo spin-echo (PDw TSE) sequence was used to position the laser fibre. Non-spoiled gradient-echo (GRE) sequences were employed for real-time thermal monitoring based on proton resonance frequency (PRF). Radicular pain was assessed over 6 months with a numerical rating scale (NRS)., Results: PLDD was technically successful in all cases, with adequate image quality for laser positioning. The PRF-based real-time temperature monitoring was found to be feasible in practice. After 6 months, 21 % reported complete remission of radicular pain, 63 % at least great pain relief and 74 % at least mild relief. We found a significant decrease in the NRS score between the pre-intervention and the 6-month follow-up assessment (P < 0.001). No major complications occurred; the single adverse event recorded, moderate motor impairment, resolved., Conclusions: Real-time MR guidance and PRF-based thermometry of PLDD in the lumbar spine under open 1.0-T MRI appears feasible, safe and effective and may pave the way to more precise operating procedures., Key Points: • Percutaneous laser disc decompression (PLDD) is increasingly used instead of conventional surgery. • Open 1.0-T MRI with temperature mapping seems technically successful in monitoring PLDD. • Pain relief was at least 'great' in 64 % of patients. • No major complications occurred. • Open 1.0-T MRI appears a safe and effective option for patient-tailored PLDD.

Objectives: The aim of the present study was to intra-individually compare provocative discography and discoblock (disc analgesia) of idiopathic degenerated discs (IDD) results to each other, to clinical parameters, and to MRI findings. By this the value of both diagnostic features should be critically reevaluated., Methods: 31 intervertebral IDD (Pfirrmann III°-IV°) of 26 patients were analyzed for surgery decision making by combined discoblock/discography procedure in an open MRI at 1T. A correlation analysis was performed between the Dallas Discogram Scale, pain discrimination score (PDS: concordant/discordant/no pain), positive discoblock (Numerical Rating Scale [NRS] reduction by ≥ 3, 60 min after intervention), presence of Modic changes or high intensity zones (HIZ), patient sex and age, intervention level, injection pressure and discography endpoint analysis (pain/pressure/anatomic/volume)., Results: Concordant pain could be evoked in 35% of the IDDs whereas discoblock was positive in 64%. Patients' age, sex, Dallas I, Dallas II, and Pfirrmann scores, as well as the presence of HIZ did not correlate to PDS or discoblock results. Discoblock correlated positively to concordant pain. Further positive correlation was found between PDS and intervention level/pressure, between discoblock and Modic changes/discography endpoint as well as between HIZ and discography endpoint., Conclusions: We suggest discoblock to be an additional tool for surgery decision making in patients with IDD because it correlates to concordant pain evoked by provocative discography as well as to presence of Modic changes. Additionally, assessment of a release instead of provocation of pain can be of advantage., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To compare the costs of CT- and MR-guided lumbosacral nerve root infiltration for minimally invasive treatment of low back pain and radicular pain., Methods: Ninety patients (54 men, 36 women; mean age, 45.5 ± 12.8 years) underwent MR-guided single-site periradicular lumbosacral nerve root infiltration with 40 mg of triamcinolone acetonide. A further 91 patients (48 men, 43 women; mean age, 59.1 ± 13.8 years) were treated under CT fluoroscopy guidance. Prorated costs of equipment use (purchase, depreciation and maintenance), staff costs based on involvement times and expenditure for disposables were identified for MR- and CT-guided procedures., Results: Mean intervention time was 20.6 min (14-30 min) for MR-guided and 14.3 min (7-32 min) for CT-guided treatment. The average total costs per patient were €177 for MR-guided and €88 for CT-guided interventions. These consisted of (MR/CT guidance) €93/29 for equipment use, €43/35 for staff and €41/24 for disposables., Conclusions: Lumbosacral nerve root infiltration using MRI guidance is still about twice as expensive as infiltration using CT guidance. Given the advantages of no radiation exposure and possible future decrease in prices for MRI devices and MR-compatible injection needles, MR-guided nerve root infiltration may become a promising alternative to the CT-guided procedure., Key Points: • MR-guided nerve root infiltration therapy is now technically and clinically established. • Costs using MRI guidance are still about double those for CT guidance. • MR guidance involves no radiation exposure to patients and personnel. • MR-guided nerve root infiltration may become a promising alternative to CT.

Objectives: The objective of this study was to evaluate the accuracy, safety, and efficacy of magnetic resonance (MR)-guided periradicular nerve root injection therapy using an open 1.0-T magnetic resonance imaging (MRI) system with fast dynamic imaging., Materials and Methods: Between April 2008 and November 2011, a total of 249 MR-guided periradicular nerve root injections were performed in 141 patients experiencing lumbosacral radicular pain. All interventions were performed in an open 1.0-T MRI system. An interactive proton-density-weighted fast spin-echo sequence was used for real-time guidance. An in-room monitor, a wireless MR mouse for operator-controlled multiplanar imaging, a flexible surface coil, and an MR-compatible 20-G needle were used. Informed consent was obtained from all patients. Clinical outcome was evaluated through clinical follow-up and a questionnaire before injection therapy (baseline) and 6 months after using a numeric visual analog scale., Results: All procedures were technically successful. No major complications occurred. At 6 months, of the 103 patients (197 injections; 57 men, 46 women; mean age, 49.5 years; range, 20-80) who enrolled in the outcome analysis, 14.6% reported complete remission of radicular pain; 53.4%, significant relief of pain; 22.3%, mild relief; and 9.7%, no relief of pain. We found a significant decrease of the visual analog scale score from the preintervention compared with the follow-up after 6 months (P < 0.001). No significant difference in the outcome was observed between the patients with degenerative foraminal stenoses and the patients with herniated disks., Conclusions: Magnetic resonance fluoroscopy-guided periradicular injection therapy for the lumbosacral spine under open 1.0-T MRI guidance is accurate, safe, and efficient in the symptomatic treatment of radicular pain. This technique may be a promising alternative to fluoroscopy- or computed tomography-guided spinal injections in the lumbosacral region, especially for young patients and patients undergoing serial therapeutic regimens.

There is growing evidence that adaptive immunity contributes to endogenous regeneration processes: For example, endogenous bone fracture repair is modulated by T cells even in the absence of infection. Because delayed or incomplete fracture healing is associated with poor long-term outcomes and high socioeconomic costs, we investigated the relationship between an individual's immune reactivity and healing outcome. Our study revealed that delayed fracture healing significantly correlated with enhanced levels of terminally differentiated CD8(+) effector memory T (TEMRA) cells (CD3(+)CD8(+)CD11a(++)CD28(-)CD57(+) T cells) in peripheral blood. This difference was long lasting, reflecting rather the individual's immune profile in response to lifelong antigen exposure than a post-fracture reaction. Moreover, CD8(+) TEMRA cells were enriched in fracture hematoma; these cells were the major producers of interferon-γ/tumor necrosis factor-α, which inhibit osteogenic differentiation and survival of human mesenchymal stromal cells. Accordingly, depletion of CD8(+) T cells in a mouse osteotomy model resulted in enhanced endogenous fracture regeneration, whereas a transfer of CD8(+) T cells impaired the healing process. Our data demonstrate the high impact of the individual adaptive immune profile on endogenous bone regeneration. Quantification of CD8(+) TEMRA cells represents a potential marker for the prognosis of the healing outcome and opens new opportunities for early and targeted intervention strategies.

Study Design: Prospective cohort study comparing evaluations of single-level anterior lumbar interbody fusion (ALIF) versus anteroposterior lumbar fusion (APLF)., Objective: To clinically and radiologically compare the outcome after angle-stable, locked, stand-alone ALIF with that obtained after APLF, in cases with degenerative disc disease (DDD)., Summary of Background Data: Fusion rates have been reported to be highest after interbody fusion with transpedicular fixation. However, transpedicular fixation is linked to significant damage of the paravertebral muscles, to screw displacement-related neurological and vascular complications, and to an increased rate of adjacent segment degeneration. When performed as a stand-alone procedure, the disadvantages of transpedicular fixation can be completely avoided by ALIF., Methods: Eighty patients with chronic low-back pain due to a single-level DDD (Modic ≥2) and facet joint arthritis (Fujiwara ≥3) were enrolled in this study. Forty patients received an anteroposterior fusion (ALIF with transpedicular fixation: APLF group) and 40 patients (ALIF group) were treated with a stand-alone ALIF using the Synfix-LR device. At 7 days, 3, 6, 12, and 24 months, and at a mean follow-up of 41 months, patients were clinically (visual analog scale, Oswestry Low Back Pain Disability Index, satisfaction) and radiologically (x-ray, and at 12 months, thin-slice computed tomography) compared., Results: Blood loss and duration of surgery were significantly lower in the ALIF group (P<0.001). Visual analog scale and Oswestry Low Back Pain Disability Index improved significantly over time (analysis of variance, P<0.001) in both groups, but both scores were significantly better in ALIF group (analysis of variance, P<0.001). Patients' satisfaction consistently ranked higher in the ALIF group (P=0.042 at 12 mo). No significant difference was found in the fusion rate throughout the study., Conclusions: Stand-alone ALIF leads to better clinical results than APLF, without differences in fusion rates after 41 months. Therefore, when a posterior approach is not needed for decompression or reposition, we suggest performing a stand-alone ALIF in cases with single-level DDD.

Purpose: Rapamycin, an immunosuppressive in transplant surgery, has an additional antiproliferative effect. The aim of this study was to investigate the potential protective effects of rapamycin on postoperative adhesion development., Methods: Ten rats per group underwent midline incision laparotomy and adhesion induction including bowel sutures. Therapy groups received daily intraperitoneal rapamycin injections (1.5 mg/kg body weight) for 3 weeks postoperatively. Controls were rats without any postoperative treatment, rats receiving the rapamycin solvent or a hyaluronic acid-carboxymethylcellulose membrane (Seprafilm(™))., Results: Postoperative rapamycin application led to enhanced adhesion development and there was a higher rate of wound infections. In addition, Seprafilm(™) did not reduce adhesions, in subgroups there were even more., Conclusions: Rapamycin is not recommendable for perioperative immunosuppression, it enhances adhesion development and leads to a higher rate of wound infections. Surprisingly, the established Seprafilm(™) membrane led to more adhesions in our experimental setting.

Brassinosteroids (BRs) are steroidal hormones that play pivotal roles during plant development. In addition to the characterization of BR deficient mutants, specific BR biosynthesis inhibitors played an essential role in the elucidation of BR function in plants. However, high costs and limited availability of common BR biosynthetic inhibitors constrain their key advantage as a species-independent tool to investigate BR function. We studied propiconazole (Pcz) as an alternative to the BR inhibitor brassinazole (Brz). Arabidopsis seedlings treated with Pcz phenocopied BR biosynthetic mutants. The steady state mRNA levels of BR, but not gibberellic acid (GA), regulated genes increased proportional to the concentrations of Pcz. Moreover, root inhibition and Pcz-induced expression of BR biosynthetic genes were rescued by 24epi-brassinolide, but not by GA(3) co-applications. Maize seedlings treated with Pcz showed impaired mesocotyl, coleoptile, and true leaf elongation. Interestingly, the genetic background strongly impacted the tissue specific sensitivity towards Pcz. Based on these findings we conclude that Pcz is a potent and specific inhibitor of BR biosynthesis and an alternative to Brz. The reduced cost and increased availability of Pcz, compared to Brz, opens new possibilities to study BR function in larger crop species.

Brassinosteroids (BRs) are plant hormones that regulate growth and development. They share structural similarities with animal steroids, which are decisive factors of sex determination. BRs are known to regulate morphogenesis and environmental stress responses, but their involvement in sex determination in plants has been only speculative. We show that BRs control sex determination in maize revealed through characterization of the classical dwarf mutant nana plant1 (na1), which also feminizes male flowers. na1 plants carry a loss-of-function mutation in a DET2 homolog--a gene in the BR biosynthetic pathway. The mutant accumulates the DET2-specific substrate (24R)-24-methylcholest-4-en-3-one with a concomitant decrease of downstream BR metabolites. Treatment of wild-type maize plants with BR biosynthesis inhibitors completely mimicked both dwarf and tasselseed phenotypes of na1 mutants. Tissue-specific na1 expression in anthers throughout their development supports the hypothesis that BRs promote masculinity of the male inflorescence. These findings suggest that, in the monoecious plant maize, BRs have been coopted to perform a sex determination function not found in plants with bisexual flowers.

Study Design: A retrospective controlled cohort study was performed for postoperative 3-dimensional muscle evaluation., Objective: Our aim was to establish a method for spatially continuous 3-dimensional analysis of the lumbar paravertebral muscles after instrumented circumferential single-level fusion., Summary of Background Data: Paravertebral muscle degeneration is thought to contribute to postoperative low back pain. Previous analysis methods did not regard on implant associated artifacts and on the multisegmental 3-dimensional character of the paravertebral muscles., Methods: At 1 week and 12 months postoperatively, thin slice computed tomography scans of the lumbar paravertebral muscles were digitally analyzed and compared for 20 patients with chronic low back pain owing to monosegmental degenerative disc disease ≥ Modic II° and high intensity zones at L4/5. Tissue-specific regions of all slices were determined for automated calculation of fat and muscle volume, and localization of fatty degenerated areas in a 3-dimensional computer reconstruction model., Results: All computed tomography scans were successfully digitally reconstructed and evaluated. A significant decrease of paravertebral muscle volume and an increase in volume fraction of fatty degeneration was observed at 12 months (Vmuscle 127.4±28.5 cm, V%fat 48.67±3.63%) compared with 1 week postoperatively (Vmuscle 217.4±34.2 cm, V%fat 12.57±2.28%). Fat tissue areas were most often located close to the spinal processes and anterolateral, close to the transverse processes., Conclusion: We established a 3-dimensional image analysis method for evaluating postoperative changes in the lumbar paravertebral muscles of patients, after circumferential single-level fusion, consistently accounting for implant-associated artifacts. We were able to demonstrate volume atrophy and an increase of fatty degeneration after 12 months compared with 1 week postoperatively.

Objective: To evaluate the feasibility of MR-guided discography using an open 1 Tesla MRI system., Methods: 48 disc segments of 41 patients scheduled for intradiscal thermal treatment, total disc replacement or spondylodesis were examined. A 1.0-T open MRI was used for instrument guidance and imaging. After primary disc puncture under guidance of interactive PDw TSE imaging, 1-2 ml of gadolinium contrast saline mixture was injected into the disc. The occurrence of memory pain during injection was recorded. Axial and sagittal T1w TSE images with and without fat saturation were obtained. All MRI discograms were analysed by two readers, who were blinded to the clinical findings., Results: Overall, the placement of the puncture needle in the targeted disc was accurate under real-time MR guidance. Injections were technically successful in all cases. No major complications occurred. The mean procedure time was 17 min (range 13-34 min). Image quality of contrast-enhanced MR discograms was excellent when using an optimized gadolinium contrast saline mixture of 1:600. Memory pain was detected in 16 out of 48 affected segments., Conclusion: MR-guided discography is accurate and safe. Multiplanar dynamic imaging facilitates the puncture of discs and provides high-quality MR discograms.

Background: With anterior lumbar interbody fusion (ALIF) alone, the morbidity associated with a posterior approach can be avoided. In this study we evaluated the use of a PEEK cage with an integrated angle-stable locking plate (SynFix-LR™)., Material and Methods: Thirty-two patients with osteochondrosis at L4/5 or L5/S1 were treated with the SynFix-LR™. Follow-up at 0, 3, 6, 9, 12, and 24 months included the Oswestry Disability Index (ODI), visual analog scale (VAS), and questions regarding satisfaction and use of pain medication. The fusion rate was assessed by X-ray and computed tomography (CT) examination., Results: A significant reduction of the ODI and VAS was achieved (p<0.05) with a high rate of patient satisfaction. After 2 years, 79% of the patients were able to dispense with long-term use of analgesics. We observed a fusion rate of 93% (X-ray) and 70% (CT) at final follow-up., Conclusion: The SynFix-LR™ device is a suitable option for the treatment of monosegmental osteochondrosis at L4/5 and L5/S1 with comparable or superior results in comparison to posterior or combined fusion techniques.

Voltage-gated potassium Kv1 channels have three extracellular linkers, the S1-S2, the S3-S4, and the S5-P. The S1-S2 is the only linker that has an N-glycan and it is at a conserved position on this linker on Kv1.1-Kv1.5 and Kv1.7 channels. We hypothesize that an N-glycan is found at only this position due to its effect on folding, trafficking, and/or function of these channels. To investigate this hypothesis, N-glycosylation sites were engineered at different positions on the extracellular linkers of Kv1.2 to determine the effects of N-glycans on channel surface protein expression and function. Our data suggest that for Kv1 channels, (1) placing an N-glycan at non-native positions on the S1-S2 linker decreased cell surface protein expression but the N-glycan still affected function similarly as if it were at its native position, (2) placing a non-native N-glycan on the S3-S4 linker significantly altered function, and (3) placing a non-native N-glycan on the S5-P linker disrupted both trafficking and function. We suggest that Kv1 channels have an N-glycan at a conserved position on only the S1-S2 linker to overcome the constraints for proper folding, trafficking, and function that appear to occur if the N-glycan is moved from this position.

Background and Aims: A contaminated or infected surgical site is considered a contraindication for the use of the nonabsorbable alloplastic materials employed to repair abdominal wall defects. Therefore, the biocompatibility of new prosthetic materials was investigated., Materials and Methods: Meshes measuring 1.5x1.5 cm made of conventional and titanium-coated polypropylene, polyglycol, or porcine dermal collagen were implanted under the abdominal wall of 96 rats (eight groups of 12 animals each) employing the inlay technique. Implantation of all four materials was performed both under semisterile conditions and bacterial contamination of the mesh. The meshes were explanted after 28 days., Results: All the materials implanted under semisterile conditions were incorporated into the abdominal wall with only few intraabdominal adhesions (mean adhesion scores: 1.0, 1.2, 1.0, 0.8 points, respectively, not significant). With the porcine dermal collagen, proliferation rate and the proportion of inflammatory cells were statistically lower (p<0.01). In the bacterial contamination group, all meshes were associated with a suppurating infection and strong adhesions between the bowel and mesh, which were most prominent in the case of dermal collagen (mean adhesion scores: 1.6, 1.7, 1.7, and 1.9 points, respectively, not significant). In this group, two animals died of peritonitis. In comparison with the other materials, the proliferation rate was significantly elevated (p=0.03). No significant differences were seen between the other materials employed., Conclusion: Irrespective of the material employed, implantation of alloplastic meshes in an abdominal wall contaminated with bacteria, is associated with suppurating infections, in particular in the case of the membrane-like porcine dermal collagen. Nonabsorbable alloplastic meshes and dermal skin grafts should therefore not be used to repair infected abdominal wall defects.

Clinical liver transplantation became an established therapy of end-stage liver disease since the first at least medium-term successful liver transplantation in 1967. Clinical studies have played a major part in improving peri- and postoperative therapy in liver transplantation. In this article clinical studies of major impact are presented. Main topics are studies dealing with immunosuppressants, improvements in surgical techniques, viral infections and tumor diseases. Controlled randomized multicentric studies are rare; most of the studies are unicentric. Further studies in the fields of reducing side effects of immunosuppression, the introduction of monoclonal antibodies and improvement of the therapy of viral hepatitis would be helpful. These studies should be controlled, randomized and multicentric.

The occurrence of a sustained vasodilation and hypotension after acute, dynamic exercise suggests that exercise may alter arterial baroreflex mechanisms. Therefore, we assessed systemic hemodynamics, baroreflex regulation of heart rate, and cardiac vagal tone after 60 min of cycling at 60% peak oxygen consumption in 12 healthy, untrained men and women (ages 21-28 yr). We derived sigmoidal carotid-cardiac baroreflex relations by measurement of R-R interval changes induced by ramped, stepwise, R-wave-triggered changes in external neck pressure from 40 to -65 mmHg. We estimated tonic cardiac vagal control with power spectral analysis of R-R interval variability in the respiratory frequency band (0.2-0.3 Hz) during frequency- and tidal volume-controlled breathing. Both mean arterial pressure and total peripheral resistance were reduced postexercise [pressure: from 86 +/- 2 (mean +/- SE) to 81 +/- 2 mmHg; resistance: from 23 +/- 2 to 16 +/- 1 units; both P < 0.05]. Cardiac output was increased postexercise (from 3.9 +/- 0.3 to 5.5 +/- 0.5 l/min, P < 0.05). Both slope and range of the carotid-cardiac baroreflex relation were increased postexercise (slope: from 4.7 +/- 0.7 to 6.1 +/- 0.9 ms/mmHg; range: from 186 +/- 23 to 238 +/- 30 ms, P < 0.05). Respiratory R-R interval variability (cardiac vagal tone) was not changed at any time after exercise, whereas heart rate and plasma norepinephrine levels were elevated. Thus moderate-intensity, dynamic exercise increases heart rate and cardiac output, reduces peripheral vascular resistance, and augments baroreflex responsiveness. Our data suggest that augmented baroreflex heart rate gain restrains rather than contributes to postexercise hypotension, which appears to be mediated predominately by vasodilation.

In a prospective study, 44 patients (11 women, 33 men) who had received orthotopic liver transplants underwent a total of 196 consecutive duplex Doppler ultrasound examinations. The aim of the study was to evaluate the correlation between the pulsatile flow index (PFI) and the damping index (DI) as far as complications as rejection or cholangitis were concerned. The patients were examined five times each on average. The PFI and DI were measured in the hepatic artery, the portal vein and the hepatic veins. The findings were compared with the clinical course (cholangitis, rejection) and the histomorphological diagnosis as determined in biopsy specimens. In biopsy-proven rejection episodes, the sensitivity of the PFI in the hepatic artery was 69.4%, the specificity 72.2%. The sensitivity of the DI in the hepatic vein was 89.4%, the specificity 89.1%. Combining the two, specificity was more than 90%. PFI and DI in the portal vein bore no apparent relation to clinical course or histomorphological diagnosis. We found duplex Doppler ultrasound extremely beneficial in determining the timing and indication for liver biopsy. In addition, this simple examination, which can be performed as often as desired, accurately shows the transplanted liver's response to measures taken to counter rejection.

100 patients of our kidney transplantation program and uneventful as regards their liver history were indexed by the pulsatile flow (PFI) of the hepatic artery and the damp curve (DI) of the hepatic veins. The average age of the patients was 36 years (20-50y). The pulsatile flow index (PFI) was calculated as 0.4 to 0.7. The damp index (DI) as 0.3 to 0.54. In 10 of these volunteers the measurement was performed 3 times per day for 5 days: there was no difference to be found in comparison to the values of the total group. The presented values of the PFI and DI give the normal range and will be the basis for further investigations in patients after liver transplantation or suffering from liver diseases.