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European Spine Journal - Depression, anxiety, catastrophising, and fear-avoidance beliefs are key "yellow flags" (YFs) that predict a poor outcome in back patients. Most surgeons...     

Die extraluminale Valvuloplastie der Vena saphena magna

Background

The great saphenous vein is still an indispensable replacement material for vessels in cardiac and vascular surgery. Therefore, treatment strategies in which insufficient veins can be preserved for a possible vascular reconstruction at a later date deserve attention. The procedure of external valvuloplasty (eVp) is the most widely used procedure for reparative therapy of an insufficiency of the great saphenous vein. In a systematic review the main question was whether long-term preservation is feasible.

Method

The electronic databases medline and web of science were systematically searched for articles in German and English in which the eVp was used for the treatment of varicose vein disease. In addition, the abstract collections from the annual meetings of vascular medical societies over the past 3 years and published in German journals were analyzed.

Results

Out of 62 screened abstracts 25 were considered relevant and included in the analysis. In the long-term most patients showed an improvement in venous hemodynamics and therefore also a reduction in the diameter of the veins. The recurrence rate of varicosis was 46.9?% in 10 years and 3.7–15.6?% of the initially reparative treated patients had to be treated again with an ablative procedure. Postoperative phlebitis affected the treatment results in 0–9.6?% of cases.

Conclusion

In selected patients with mobile valve cusps but enlarged diameter of valve bearing segments, preservation of the great saphenous vein is possible in the long-term. Organ-preserving treatment of varicosis should be provided for patients with a high risk profile of developing atherosclerotic vascular diseases whenever possible.     

Factorial Analysis of Fiber Laser Fusion Cutting of AISI 304 Stainless Steel: Evaluation of Effects on Process Performance,Kerf Geometry and Cut Edge Roughness

Factorial Design-of-Experiment analyses were applied for conventional and beam oscillation fiber laser cutting of 10 mm thick AISI 304 stainless steel. Considered factors in case of the conventional process with a static beam involve both laser and cutting gas parameters, in particular the laser power, the focal plane position, the cutting gas pressure, the nozzle stand-off distance as well as the nozzle diameter. The conducted trials were evaluated with respect to the achievable cutting speed, the cut kerf geometry and the cut edge roughness. Noticeable correlations between cut edge roughness and cut kerf geometry stimulated the development of a corresponding Computational Fluid Dynamics (CFD) model of the cutting gas flow through the kerf. A specific approach of data synchronization revealed that the experimentally determined roughness values do well correlate with numerically computed values of the backward directed component of the gas-induced shear stress and that the cut kerf geometry as internal process-inherent boundary condition influences relevant cutting characteristics more than controllable external cutting gas parameters. Finally, effects of circular beam oscillation were investigated by an additional factorial analysis considering the laser power, the focal plane position, the oscillation frequency and the oscillation amplitude as factors. The results demonstrate the potential of beam oscillation techniques for quality improvements in laser cutting.     

Dietary fat quality in regular fat diets has minor effects on biomarkers of inflammation in obese Zucker rats

Purpose

Adipose tissue-associated chronic inflammation is involved in the pathogenesis of obesity-related diseases. Dietary fatty acids are known to influence inflammatory processes. The aim of this study was to investigate, whether diets with regular fat contents but variable fat qualities affect adipose tissue-associated inflammation through the fatty acid composition of mesenteric adipose tissue (MAT).

Methods

Obese Zucker rats were fed diets containing 7 % wt:wt rapeseed oil, corn oil, or lard for 10 weeks. Fatty acid composition and endocrine function regarding adipokines and cytokines of MAT, number of total CD3⁺ T cells, and cytokine secretion of mesenteric lymph node (MLN)-derived lymphocytes were determined. Local effects in MAT and MLN were compared to systemic effects assessed in serum and peripheral blood mononuclear cells.

Results

Fatty acid composition of MAT reflected dietary fatty acid intake, without affecting endocrine function. Feeding the lard diet for 10 weeks increased the serum adiponectin and TNF-α secretion of blood lymphocytes, whereas CD3⁺ T cells in blood were decreased. No effects were seen for the secretion of adipokines and cytokines from MAT, the amount of T cells in MLN, and cytokine secretion of MLN lymphocytes.

Conclusions

In conclusion, feeding obese rats a diet with regular fat content but variable fat sources for 10 weeks, changed the fatty acid composition of MAT but not its secretory properties or MLN functions. Although the local immune system was not influenced, lard-feeding induced minor changes in systemic immune function.     

Self-testing for liver disease – response to an online liver test questionnaire

Abstract

Background: Elevated liver enzymes and chronic liver disease are associated with increased morbidity and mortality. Broad availability of internet questionnaires obtains representative insights into awareness of (chronic) liver disease in the general population. Also, these tools may be used to identify persons and populations at risk to prevent advanced liver disease.

Methods: An online questionnaire regarding awareness of liver disease, risk behavior and awareness of own liver tests was implemented online. During 43?months study period, 210,230 participants accessed the online questionnaire. Of these, 117,446 individuals completed the survey. All database access and input were registered and collected in a SQL based database for further evaluation.

Results: Awareness of own liver status was lower than expected. About 50.7% of all participants were uncertain about their liver enzyme status. In turn, risk behavior continues to be considerably high as 38.8% of participants stated high-risk behavior for alcohol consumption and 2.2% high-risk substance abuse such as cocaine or heroin. Our questionnaire was predominantly answered by participants under 65?years of age. Participants with high BMI may have been underrepresented.

Conclusion: Our study demonstrated the urgent need for improved liver screening, health education regarding risk behavior and improved awareness campaigns on liver disease. Interest of the general population may be presumed as more than 200,000 people accessed our test of their own accord.     

From the Cover: Trypanosomal TAC40 constitutes a novel subclass of mitochondrial β-barrel proteins specialized in mitochondrial genome inheritance

Mitochondria cannot form de novo but require mechanisms allowing their inheritance to daughter cells. In contrast to most other eukaryotes Trypanosoma brucei has a single mitochondrion whose single-unit genome is physically connected to the flagellum. Here we identify a β-barrel mitochondrial outer membrane protein, termed tripartite attachment complex 40 (TAC40), that localizes to this connection. TAC40 is essential for mitochondrial DNA inheritance and belongs to the mitochondrial porin protein family. However, it is not specifically related to any of the three subclasses of mitochondrial porins represented by the metabolite transporter voltage-dependent anion channel (VDAC), the protein translocator of the outer membrane 40 (TOM40), or the fungi-specific MDM10, a component of the endoplasmic reticulum–mitochondria encounter structure (ERMES). MDM10 and TAC40 mediate cellular architecture and participate in transmembrane complexes that are essential for mitochondrial DNA inheritance. In yeast MDM10, in the context of the ERMES, is postulated to connect the mitochondrial genomes to actin filaments, whereas in trypanosomes TAC40 mediates the linkage of the mitochondrial DNA to the basal body of the flagellum. However, TAC40 does not colocalize with trypanosomal orthologs of ERMES components and, unlike MDM10, it regulates neither mitochondrial morphology nor the assembly of the protein translocase. TAC40 therefore defines a novel subclass of mitochondrial porins that is distinct from VDAC, TOM40, and MDM10. However, whereas the architecture of the TAC40-containing complex in trypanosomes and the MDM10-containing ERMES in yeast is very different, both are organized around a β-barrel protein of the mitochondrial porin family that mediates a DNA–cytoskeleton linkage that is essential for mitochondrial DNA inheritance.Mitochondria are a hallmark of all eukaroytic cells. They derive from an endosymbiontic event between a free-living bacterium and a presumably prokaryotic host cell. More than 1.5 billion years of evolution resulted in a great diversification of mitochondria. As a consequence, the shape and number of organelles per cell as well as size, content, copy number, and organization of their genomes vary greatly between different taxons (1). However, all eukaryotes must be able to faithfully transmit mitochondria to their offspring (2, 3).Unlike most other eukaryotes, the parasitic protozoa Trypanosoma brucei has a single mitochondrion throughout its life and its cell cycle. Due to the single-unit nature of the mitochondrion, its duplication must be coordinated with the duplication of the nucleus (4). The mitochondrial genome of T. brucei, termed kinetoplast DNA (kDNA), is essential for growth of both the procyclic insect stage and the bloodstream form of the parasite (5). It consists of a disk-shaped single-unit kDNA network that localizes to a distinct region within the mitochondrial matrix (6). The kDNA is physically connected with the cytosolic basal body, the organizing center of the eukaryotic flagellum, via a high-order transmembrane structure termed tripartite attachment complex (TAC) (7) of which only few components have been identified (8–10). Replication of the kDNA network occurs at a defined stage of the cell cycle shortly before the onset of the nuclear S phase. After replication, the kDNA networks need to be correctly positioned so that during cell and mitochondrial division each daughter cell receives a single organelle with a single kDNA network. This process requires an intact TAC and is mediated by the movement of the basal body: one kDNA network remains connected to the basal body of the old flagellum whereas the other one segregates with the basal body of the new flagellum (7, 11).Unlike trypanosomes, Saccharomyces cerevisiae propagates by budding and contains highly dynamic mitochondria that constantly divide and fuse (12, 13). Mitochondrial inheritance in budding yeast therefore requires a mechanism to move mitochondria and their genomes from the mother cell into the growing bud. The protein-associated mitochondrial genomes of S. cerevisiae, termed nucleoids, localize to dozens of globular foci that are distributed all over the organelles. Most actively replicating nucleoids are associated with a protein complex that includes the outer membrane (OM) protein MDM10 as a central unit, as well as the proteins MDM12, MDM34, and MMM1 (14–16). The protein complex forms the endoplasmic reticulum (ER)–mitochondria encounter structure (ERMES) tethering the ER to the mitochondrion (17). The ERMES has also been suggested to connect to cytosolic actin fibers that mediate the movement of mitochondria to the bud of dividing yeast cells (14, 18, 19). Besides its role in mitochondrial inheritance, the ERMES has been implicated in maintenance of mitochondrial morphology and in phospholipid and calcium exchange as well as in the assembly of the protein translocase of the mitochondrial OM (TOM) (20, 21). Some of the proposed ERMES functions are controversial and there is evidence that some of them might be due to secondary effects caused by the drastically altered mitochondrial morphology (22).The central ERMES subunit, the β-barrel protein MDM10 belongs to the mitochondrial porin superfamily, which comprises the three members voltage-dependent anion channel (VDAC), Tom40, and MDM10. Whereas VDAC and Tom40 have so far been found in all eukaryotes, including T. brucei (23, 24), MDM10 is specific to the fungal clade.In this study we identify a mitochondrial OM protein of T. brucei as a novel component of the TAC. We show that the protein defines a novel subclass of the mitochondrial porin superfamily that is specialized in mitochondrial DNA inheritance.     

Joint Congress of European Neurology 31 May–3 June 2014 Istanbul,Turkey

Neuromyelitis optica (NMO, Devic’s syndrome), long considered a clinical variant of multiple sclerosis, is now regarded as a distinct disease entity. Major progress has been made in the diagnosis and treatment of NMO since aquaporin-4 antibodies (AQP4-Ab; also termed NMO-IgG) were first described in 2004. In this review, the Neuromyelitis Optica Study Group (NEMOS) summarizes recently obtained knowledge on NMO and highlights new developments in its diagnosis and treatment, based on current guidelines, the published literature and expert discussion at regular NEMOS meetings. Testing of AQP4-Ab is essential and is the most important test in the diagnostic work-up of suspected NMO, and helps to distinguish NMO from other autoimmune diseases. Furthermore, AQP4-Ab testing has expanded our knowledge of the clinical presentation of NMO spectrum disorders (NMOSD). In addition, imaging techniques, particularly magnetic resonance imaging of the brain and spinal cord, are obligatory in the diagnostic workup. It is important to note that brain lesions in NMO and NMOSD are not uncommon, do not rule out the diagnosis, and show characteristic patterns. Other imaging modalities such as optical coherence tomography are proposed as useful tools in the assessment of retinal damage. Therapy of NMO should be initiated early. Azathioprine and rituximab are suggested as first-line treatments, the latter being increasingly regarded as an established therapy with long-term efficacy and an acceptable safety profile in NMO patients. Other immunosuppressive drugs, such as methotrexate, mycophenolate mofetil and mitoxantrone, are recommended as second-line treatments. Promising new therapies are emerging in the form of anti-IL6 receptor, anti-complement or anti-AQP4-Ab biologicals.     

Discovery of Spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as Potent NOP and Opioid Receptor Agonists

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TNF promotes metastasis by impairing natural killer cell activity

Inflammatory mediators such as tumor necrosis factor (TNF) and interleukin-1 enhance tumor colony formation in different models of experimental and spontaneous metastasis. The involvement of the natural killer (NK) cell system in this process was investigated. Tumor necrosis factor does not appear to act directly on tumor cells by reducing their susceptibility to the cytotoxic action of NK cells but rather impairs NK activity in tumor-bearing mice. Such impairment of the natural killer system might be one means by which TNF supports tumor colony formation. Even though the metastasis-enhancing effect of TNF remained detectable in mice which have a greatly reduced NK cell cytotoxic activity due to a defect in the bg locus, normal mice which were depleted of NK cells by antibody treatment did not show enhanced metastasis after TNF injection. Therefore, the TNF-enhanced metastasis can only be seen as long as some NK cell function is operating in the animals. © 1996 Wiley-Liss, Inc.     

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21–23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.