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Risk attitudes have a significant impact on human decision making. In contrast to the conventional assumption of stable, universal risk attitudes, previous research has found domain-specific and age-related differences in risk attitudes. For this reason, a systematic review including 19 studies was conducted to evaluate the relationship between self-reported risk attitudes and aging in different domains of decision making. The results suggest a negative relationship between aging and self-reported risk attitudes. Age-related differences in risk attitudes also vary between different domains. Nine studies examined general risk attitudes, with eight finding a negative relationship with aging. Eight out of 11 studies found a negative relationship in the financial domain. All nine studies in the health domain identified a negative association as well. The seven studies included in the social domain showed mixed results. All six studies in the recreational domain identified a negative association. Four out of five studies in the ethical domain found a negative relationship. The three studies included in the driving and career domain also showed negative relationships between risk attitudes and aging. Potential policy implications are discussed.

Sugar-sweetened beverages (SSBs) are associated with increased body weight and obesity, which induce a wide array of health impairments such as diabetes or cardiovascular disorders. Excise taxes have been introduced to counteract SSB consumption. We investigated the effect of sugar taxes on SSB sales in Hungary and France using a synthetic control approach. For France, we found a slight decrease in SSB sales after tax implementation while overall soft drink sales increased. For Hungary, there was only a short-term decrease in SSB sales which disappeared after 2 years, leading to an overall increase in SSB sales. However, both effects are characterized by great uncertainty.

Das phanotypische und genetische Spektrum autoinflammatorischer Erkrankungen hat in den letzten Jahren stetig zugenommen. So sind mittlerweile mehrere monogen bedingte autoinflammatorische Erkrankungen bekannt, bei denen Fieberschube nicht im Vordergrund stehen und die neben Zeichen systemischer Entzundung auch Autoimmunphanomene oder eine pathologische Infektanfalligkeit aufweisen. Fur autoinflammatorische Erkrankungen, die mit einer unkontrollierten Aktivitat der Zytokine, IL-1β, TNF-α oder Typ-1-IFN einhergehen, stehen kausale Therapien zur Verfugung. Daher kommt der Sicherung der genetischen Diagnose eine grose Rolle zu. Die molekulargenetische Abklarung eines Patienten mit Autoinflammation sollte in Abhangigkeit von der Symptomkonstellation stufenweise erfolgen. Bei eindeutigen Symptomen kann als Erstes die Einzelgensequenzierung erfolgen. NGS-basierte Methoden wie die Panelsequenzierung und die Exomsequenzierung sowie die Array-CGH sind bei unklarer Symptomatik sinnvoll.

Objective The aim of this study was to get insights in mechanisms of coping and social support in multiple sclerosis (MS). Background Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. MS strains the patient through its unpredictable course and increasing disability. Material and Methods A cross-sectional study was conducted. Two hundred and forty-three patients with MS were consecutively examined at two neurological hospitals. Besides sociodemographic variables, the level of impairment, depression, social support, and coping behavior was assessed. Results Researched patients were on average 44.0 years old (SD=11.6), were diagnosed for 8.2 years (SD=7.1), and had a mean EDSS of 4.0 (SD=2.2). Patients with MS with an EDSS of 3.0–6.0 are using more intensively cognitive or behavioral coping techniques than less (EDSS≤2.5) or stronger impaired patients (EDSS≥6.5). The level of impairment was further correlated with the amount of reported social support. Conclusion Differences in coping behavior could be observed for different levels of impairment through MS. Patients tackle more intensively and more actively with their disease when trying to adapt to increasing disability with an EDSS range between 3.0 and 6.0. In addition, the coping behavior of patients with MS was connected to social support, especially support by family, friends, or other patients with MS. Results refer to the importance of special trainings to enhance coping abilities of patients with MS.

Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA., A central antiviral defence is immune recognition of cystolic DNA. Here the authors show that RPA and RAD51, in cooperation with TREX1, function to protect the cytosol from self-DNA.

89. Jahresversammlung der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie, Lübeck, Germany, 9 May 2018 - 12 May 2018; Laryngo-Rhino-Otologie 97(S 02), S27-S28 (2018). doi:10.1055/s-0038-1639811 special issue: "Abstract- und Posterband - 89. Jahresversammlung der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie e.V., Bonn - Forschung heute - Zukunft morgen / Deutsche Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie e.V., Bonn : Musik- und Kongresshalle (MuK) Lübeck, 09.-12.05.2018, Präsidentin: Prof. Dr. med. Barbara Wollenberg, Lübeck", Published by Thieme, Stuttgart [u.a.]

Background Loss-of-function CECR1 mutations cause polyarteritis nodosa (PAN) with childhood onset, an autoinflammatory disorder without significant signs of autoimmunity. Herein we describe the unusual presentation of an autoimmune phenotype with constitutive type I interferon activation in siblings with adenosine deaminase 2 (ADA2) deficiency. Case presentation We describe two siblings with early-onset recurrent strokes, arthritis, oral ulcers, discoid rash, peripheral vascular occlusive disease and high antinuclear antibody titers. Assessment of interferon signatures in blood revealed constitutive type I interferon activation. Aicardi-Goutières syndrome (AGS) was suspected, but no mutation in the known AGS genes were detected. Whole exome sequencing identified compound heterozygosity for a known and a novel mutation in the CECR1 gene. Functional consequences of the mutations were demonstrated by marked reduction in ADA2 catalytic activity. Conclusions Our findings demonstrate that ADA2 deficiency can cause an unusual autoimmune phenotype extending the phenotypic spectrum of PAN. Constitutive interferon I activation in patient blood suggests a possible role of type I interferon in disease pathogenesis which may have therapeutic implications.

Over the past years the phenotypic and genetic spectrum of autoinflammatory diseases has continuously increased. Moreover, several monogenic autoinflammatory disorders have now been identified where febrile episodes are not among the leading symptoms and which can be accompanied by autoimmune phenomena and susceptibility to infections. Autoinflammatory conditions that are characterized by uncontrolled activity of cytokines, such as interleukin-1 beta (IL1β), tumor necrosis factor alpha (TNF-α) and type 1 interferons (1-IFN), are amenable to specific therapeutic interventions. Thus, identification of the underlying genetic cause is important. During diagnostic work-up, genetic testing of a patient with autoinflammation should be carried out depending on the clinical presentation. If a distinct disorder is suspected, sequencing of the causative gene should be performed. Genetic tests using next generation sequencing (NGS), such as panel sequencing, exome sequencing and array comparative genomic hybridization (CGH) can be carried out if symptoms cannot be assigned to a specific disease entity.

Objectives Familial chilblain lupus is a monogenic form of cutaneous lupus erythematosus caused by loss-of-function mutations in the nucleases TREX1 or SAMHD1. In a family without TREX1 or SAMHD1 mutation, we sought to determine the causative gene and the underlying disease pathology. Methods Exome sequencing was used for disease gene identification. Structural analysis was performed by homology modelling and docking simulations. Type I interferon (IFN) activation was assessed in cells transfected with STING cDNA using an IFN-â reporter and Western blotting. IFN signatures in patient blood in response to tofacitinib treatment were measured by RT-PCR of IFN-stimulated genes. Results In a multigenerational family with five members affected with chilblain lupus, we identified a heterozygous mutation of STING, a signalling molecule in the cytosolic DNA sensing pathway. Structural and functional analyses indicate that mutant STING enhances homodimerisation in the absence of its ligand cGAMP resulting in constitutive type I IFN activation. Treatment of two affected family members with the Janus kinase ( JAK) inhibitor tofacitinib led to a marked suppression of the IFN signature. Conclusions A heterozygous gain-of-function mutation in STING can cause familial chilblain lupus. These findings expand the genetic spectrum of type I IFNdependent disorders and suggest that JAK inhibition may be of therapeutic value. Fil: König, Nadja. Technische Universität Dresden; Alemania Fil: Fiehn, Christoph. Acura Akutklinik Für Rheumatologie Baden-baden; Alemania Fil: Wolf, Christine. Technische Universität Dresden; Alemania Fil: Schuster, Max. Technische Universität Dresden; Alemania Fil: Cura Costa, Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina Fil: Tüngler, Victoria. Technische Universität Dresden; Alemania Fil: Alvarez, Hugo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina Fil: Chara, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina Fil: Engel, Kerstin. Technische Universität Dresden; Alemania Fil: Goldbach Mansky, Raphaela. Technische Universität Dresden; Alemania Fil: Günther, Claudia. National Institutes of Health; Estados Unidos Fil: Lee Kirsch, Min Ae. Technische Universität Dresden; Alemania

High-resolution submillimeter line and continuum observations are important in probing the morphology, column density, and dynamics of the molecular gas and dust around obscured active galactic nuclei (AGNs). With high-resolution (0.? 06 × 0.? 05 (6 × 5 pc)) ALMA 690 GHz observations we have found bright (TB > 80 K) and compact (full width half maximum size (FWHM) size of 10 × 7 pc) CO 6-5 line emission in the nuclear region of the extremely radio-quiet galaxy NGC 1377. The CO 6-5 intensity is partially aligned with the previously discovered jet/outflow of NGC 1377 and is tracing dense (n > 104cm-3) hot molecular gas at the base of the outflow. The velocity structure is complex and shifts across the jet/outflow are discussed in terms of separate overlapping kinematical components or rotation. High-velocity gas (Δv ± 145km s-1) is detected inside r < 2-3 pc and we suggest that it is emerging from an inclined rotating disk or torus of position angle PA = 140° ± 20° with a dynamical mass of 3 × 106M⊙. This mass is consistent with that of a supermassive black hole (SMBH), as inferred from the M-σ relation. The gas mass of the proposed disk/torus constitutes

Heteroleptic ate complexes of the type K[M{N(SiMe3)2}2{OSi(OtBu)3}] (M = Cr, Mn, Co) were synthesized by adding one equivalent of the potassium salt KOSi(OtBu)3 to the bis(trimethylsilyl)amide precursors [Cr{N(SiMe3)2}2(thf)2], [Mn{N(SiMe3)2}2(thf)] and [Co{N(SiMe3)2}2(thf)], respectively. Surprisingly, the reaction of CrCl3(thf)3 with only two equivalents of KOSi(OtBu)3 yielded the homoleptic ate complex K[Cr{OSi(OtBu)3}4]. The compounds were characterized by elemental analysis and DRIFT spectroscopy as well as X-ray crystallography.

Colloidal stability due to rejection between particles with identical charge is a severe problem in water treatment. Pretreatment of industrial effluents such as olive mill or cowshed dairy wastewater includes the addition of “coagulants” aimed at neutralizing the colloids and reducing their rejection. However, the amount and type of coagulant are usually determined by “trial-and-error” jar tests due to the lack of an efficient method to evaluate the effluents' charge. This study presents a method for direct evaluation of the efficiency of type and dose of coagulants based on particle charge detector (PCD) measurements of the colloidal effluents and the coagulant to be used as the neutralizing compound. This presumably trivial procedure is not common, apparently due to the fact that measuring colloidal charge with a PCD is less widely used than ζ potential measurements. A few examples of the effective use of this procedure are presented.

Dimetallic ate complexes were synthesized from the divalent transition metal silylamide complexes {Fe[N(SiMe3)2]2}2, Cr[N(SiMe3)2]2(thf), Co[N(SiMe3)2]2(thf)2, and {Mn[N(SiHMe2)2]2}2 (thf = tetrahydrofuran) by the addition of the corresponding lithium or sodium silylamide salt. Accordingly, donor-free LiFe[N(SiMe3)2]3 and NaMn[N(SiHMe2)2]3 as well as thf-coordinated (thf)NaCr[N(SiMe3)2]3 and (thf)NaCo[N(SiMe3)2]3 were obtained. The thf-containing mixed iron(II)/lithium bis(trimethylsilyl)amide complex (thf)LiFe[N(SiMe3)2]3 was synthesized by the simple addition of thf to the donor-free complex LiFe[N(SiMe3)2]3. All of the complexes were characterized by IR spectroscopy and elemental analysis, and the effective magnetic moments in solution were determined by the Evans method. The solid-state structures of these bis(trimethylsilyl)amido-derived complexes were additionally determined by X-ray crystallography.

Ab initio calculations on the octahedral dysprosium aluminate complex [Dy(AlMe4)3] (1) predict weak SMM properties. Dynamic magnetic susceptibility measurements on 1 confirm the theoretical predictions, revealing fast relaxation of the magnetization via quantum tunnelling.

Diagnosis and treatment of children with mild traumatic brain injury (mTBI) remain a challenge since initial signs and symptoms do not always indicate the severity of the trauma. Therefore, guidelines regarding the decision upon imaging methods and ambulatory or hospitalized treatment are needed. The goal of our study was to investigate if the standard that was allied from the PECARN rules and is applied in this study can ensure that patients with clinically important brain injury are recognized and leads to outcomes with a low complication rate, a high patient satisfaction and minimal post-concussion syndrome incidence. We enrolled 478 children with mTBI and contacted their families with a questionnaire. Out of these, 267 valid questionnaires were received. Patient records and questionnaires were analyzed yielding a number of 140 ambulatory and 127 hospitalized patients. Patients with mild TBI were admitted according to the above-mentioned guidelines or sent home for observation through their parents after thorough patient examination and information. Among ambulatory patients only 13 children (9%) underwent any imaging procedure; however, none of those showed any pathological findings. Next, in 41 of 127 hospitalized patients (32.2%) an imaging study was performed and of these only 3 according to 2.4% of hospitalized patients showed pathological findings, namely a skull fracture, two of them in combination with an intracranial hemorrhage. The duration of inpatient observation was 48 h in most cases (55.3%). Moreover, a majority of all patients (72.4%) did not seek any follow-up visit and did not need any further treatment. Of all patients in the study, only 10 patients according to 3.7% developed a post-concussion syndrome. Patient satisfaction was very high in both, the ambulatory and hospitalized patient group. This study confirms that PECARN rules as administered in this study can ensure safe decision-making regarding ambulatory or inpatient treatment.

Type I interferons mediate immune defense against viral infections. The induction of type I interferons has stimulating and modulating effects on the innate and adaptive immune systems thereby reducing tolerance against self-antigens. Genetic defects that result in an inadequate activation of the type I interferon system can cause a group of inflammatory disorders, which are collectively referred to as type I interferonopathies. While the clinical spectrum of type I interferonopathies is broad and heterogeneous, neurological and cutaneous symptoms are the most frequent manifestations. Some clinical and genetic features of type I interferonopathies are shared by multifactorial diseases, such as systemic lupus erythematosus and systemic vasculitis. Advances in understanding the disease mechanisms underlying type I interferonopathies have pinpointed novel targets for therapeutic interventions.

Use of conventional pretreatment for pickle industry brine wastewater (BWW) is not efficient due to its low pH, high salt content and high concentrations of suspended and organic matter. The goal of this work was to inspect different clay minerals and berberine-based organoclays as possible flocculants to reduce BWW turbidity, total and volatile suspended solids (TSS and VSS, respectively) and chemical oxygen demand (COD). Preliminary flocculation tests showed Volclay KWK (VO) and Pangel C150 (C150) to be the best candidates for a two-step sedimentation test, with the highest TSS, VSS, COD and turbidity reductions. Adsorption isotherms showed that VO and C150 adsorb different amounts of berberine, and therefore a common reference line for organoclay preparation was based on their point of zero charge. Two-step sedimentation tests showed that combining VO-berberine and VO (organoclay and raw clay, respectively) better reduces the inspected parameters than two steps with VO, whereas the opposite held true for C150-berberine and C150. Out of all treatments, two steps using C150 showed the best TSS, COD and turbidity reduction. C150 appears to be an excellent candidate for a future multistage flocculation and sedimentation processes for BWW treatment.

The alkaline earth metal alkyl complexes [Ba(AlEt(4))(2)](n) and Mg(AlMe(4))(2) were directly grafted onto periodic mesoporous silica MCM-41, which had been dehydroxylated at 270 °C (specific surface area a(s): 1023 m(2) g(-1); pore volume V(p): 1.08 cm(3) g(-1); main pore diameter 3.4 nm). Alternatively, barium alkyl surface species were generated by sequential grafting of MCM-41 with Ba[N(SiHMe(2))(2)](2)(thf)(4) and AlEt(3) to yield the hybrid material AlEt(3)@Ba[N(SiHMe(2))(2)](2)(thf)(4)@MCM-41. For a better understanding of the surface chemistry, AlEt(3)@MCM-41 was also accessed. All hybrid materials were analyzed by diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, elemental analysis, nitrogen physisorption, and solid-state NMR spectroscopy; this clearly revealed distinct surface chemistry for the alkylaluminate-treated materials [Ba(AlEt(4))(2)]@MCM-41 and Mg(AlMe(4))(2)@MCM-41. In an attempt to mimic the surface chemistry, the organometallic precursors were treated with HOSi(OtBu)(3). The reaction of equimolar amounts of {Ba[N(SiHMe(2))(2)](2)}(n) and HOSi(OtBu)(3) produced a mixed silylamido/siloxide cluster of Ba(3)[OSi(OtBu)(3)](3)[N(SiHMe(2))(2)](3) with bridging-only siloxide ligands as well as one bridging and two terminal silylamido ligands. The Schlenk equilibrium was found to govern the [Ba(AlEt(4))(2)](n)-HOSi(OtBu)(3) and Mg(AlMe(4))(2)-HOSi(OtBu)(3) reactions, leading to the isolation of complexes of [Ba(AlEt(4))(2) (toluene)](2) and Mg[OSi(OtBu)(3))](2)(AlMe(3))(2), respectively. Allowing for a donor-induced cleavage of Mg(AlMe(4))(2), the reaction of [MgMe(2)] with one or two equivalents of HOSi(OtBu)(3) was studied. While putative Mg[OSi(OtBu)(3)](Me) and Mg[OSi(OtBu)(3)](2) could not be crystallized from the reaction mixtures, cluster complexes Mg(5)(O)[OSi(OtBu)(3)](5)Me(3) and Mg(4)(OH)(2)[OSi(OtBu)(3)](6) could be unambiguously identified by X-ray crystallography.

In mares, repeated embryo collection in successive oestrous cycles is necessary if a greater number of foals should be produced. We investigated effects of repeated embryo collection in fertile donor mares on embryo recovery rates. In addition, an influence of the individual mare and season on embryo recovery rates was studied. In nine mares, a total of 153 embryo collections were performed during 30 months (17 ± 2.2 embryo collections per mare). The overall embryo recovery rate was 64% and did not differ among mares. Between successive embryo collection procedures, recovery rate varied significantly; however, no increase or decrease in the embryo recovery rate with increasing number of successive embryo collections was seen. In three mares, ovulation ceased from November to February. In the remaining six mares, embryo production was successfully continued throughout winter and no influence of the month on embryo recovery rates was detected.

There is interest in studying interactions between organic modifiers and raw commercial clays aiming the production of low-cost “organoclays”. In this study we report the interaction between berberine — a monovalent organic cation — and three commercial bentonites and a Turkish zeolite. The Turkish zeolite exhibited adsorption at values of 5–10% of the cation exchange capacity (CEC) with no neutralization of the particles. Adsorption of the organo-cation on Egyptian bentonite, Volclay KWK and Pure-Flo B80, was above the CEC of the bentonites, yielding neutral and even slightly positively charged particles. Electron microscopy and X-ray diffraction results showed expansion of the basal spacing of the smectite. Such low-cost organo-bentonites might be suitable for environmental applications as removal of pollutants, drug and pesticides delivery, or water treatment. Application in turbidity reduction of industrial effluents is demonstrated.

Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is limited by partially dose-dependent side-effects. Predictors of therapeutic response may result in individualized risk stratification and MX dosing. ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux. Here, we investigated the role of ABC-gene single nucleotide polymorphisms (SNPs) for clinical MX response, corroborated by experimental in vitro and in vivo data. Frequencies of ABCB1 2677G>T, 3435C>T and five ABCG2-SNPs were analysed in 832 multiple sclerosis patients (Germany, Spain) and 264 healthy donors. Using a flow-cytometry-based in vitro assay, MX efflux in leukocytes from individuals with variant alleles in both ABC-genes (designated genotype ABCB1/ABCG2-L(ow), 22.2% of patients) was 37.7% lower than from individuals homozygous for common alleles (ABCB1/ABCG2-H(igh), P < 0.05, 14.8% of patients), resulting in genotype-dependent MX accumulation and cell death. Addition of glucocorticosteroids (GCs) inhibited MX efflux in vitro. ABC-transporters were highly expressed in leukocyte subsets, glial and neuronal cells as well as myocardium, i.e. cells/tissues potentially affected by MX therapy. In vivo significance was further corroborated in experimental autoimmune encephalomyelitis in Abcg2(-/-) animals. Using a MX dose titrated to be ineffective in wild-type animals, disease course and histopathology in Abcg2(-/-) mice were strongly ameliorated. Retrospective clinical analysis in MX monotherapy patients (n = 155) used expanded disability status scale, relapse rate and multiple sclerosis functional composite as major outcome parameters. The clinical response rate [overall 121 of 155 patients (78.1%)] increased significantly with genotypes associated with decreasing ABCB1/ABCG2-function [ABCB1/ABCG2-H 15/24 (62.5%) responders, ABCB1/ABCG2-I(ntermediate) 78/98 (79.6%), ABCB1/ABCG2-L 28/33 (84.8%), exact Cochran-Armitage test P = 0.039]. The odds ratio for response was 1.9 (95% CI 1.0-3.5) with each increase in ABCB1/ABCG2 score (from ABCB1/ABCG2-H to -I-, and -I to -L). In 36 patients with severe cardiac or haematological side effects no statistically relevant difference in genotype frequency was observed. However, one patient with biopsy proven cardiomyopathy only after 24 mg/m2 MX exhibited a rare genotype with variant, partly homozygous alleles in 3 ABC-transporter genes. In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis. Combined MX/GC-treatment warrants further investigation.

In a controlled clinical trial, the efficacy of an intravenous combination of cimetidine and pirenzepine (group A: 62 patients) was compared with that of an intragastric administration of a magnesium-aluminium-hydroxide concentrate (group B: 58 patients) in preventing visible and occult upper gastrointestinal tract bleeding in intensive-care patients. It was found that both forms of therapy had the same favourable effect on the extent and incidence rate of visible and occult gastric bleeding. The antacid was more effective than the cimetidine-pirenzepine combination in raising the pH level to 4 or higher (P less than 0.05). Intensive-care patients should, therefore, be treated with the antacid whenever possible, since it is equally effective as the cimetidine-pirenzepine combination in preventing bleeding from the upper gastrointestinal tract, whereas it is superior in elevating the gastric pH. Besides, the use of the antacid is also less costly.

SummaryLymphatic complications are minor complications after varicose vein surgery. The frequency of lymphatic complications following an operation on varicose veins is very rarely discussed in literature. Patients, method: We investigated their frequency in a prospective study. Results: Between January 2004 and December 2005 in the cases of 3565 varicose vein operations we found 345 or 9.7% lymphatic complications, i.d. 123 cysts (3.4%), 24 fistulas (0.7%), 7 lymphorrhoe (0.2%) and 5 lymphoedema (0.14%). Conclusion: Lymphoedema is the only longlasting complication of the varicose vein surgery.

SummaryWe present two case reports concerning patients who had to undergone surgical treatment according tp the diagnosis of thrombophlebitis with insufficiency of the greater saphenous vein and putative encapsulated haematoma in the lower left leg area. During the operation we found tumours with urgent suspicion of malignancy. The histological examination revealed the diagnosis of mesenchymal chondrosarcoma and malignant peripheral nerve sheath tumour which are extremely malignant, but very rare neoplasmas with unfavourable prognosis. Conclusion: Since both types of tumours are often located below the knee, phlebotomists and vascular surgeons should take them into account as differential diagnosis.

Die Varikophlebitis ist die wichtigste akute Komplikation einer Stammvarikose der V. saphena magna oder parva. Infolge Aszension kann es zu einer Thrombusmigration uber die saphenofemorale bzw. parvopopliteale Mundung und uber insuffiziente Perforansvenen in das tiefe Venensystem kommen, was zu einer Lungenembolie fuhren kann. 116 Patienten wurden im Zeitraum von Januar 2003 bis Dezember 2005 wegen einer farbduplexsonographisch nachgewiesenen aszendierenden Varikophlebitis operiert. Alle Patienten wurden entsprechend der Klassifikation nach Steckmeier in 4 Gruppen eingeteilt. Typ I (35,3%): Der aszendierende Thrombus erreicht nicht die saphenofemorale oder parvopopliteale Mundung. Typ II (44,8%): Der proximale Thrombusanteil erreicht die Mundungsregion. Typ III (15,5%): Der Thrombus ragt uber die Mundung hinaus in das tiefe Venensystem. Typ IV (4,4%): Der Thrombus wachst transfaszial uber insuffiziente Perforansvenen in das tiefe venose System. Wir sehen fur die Typen I bis III eine dringliche Operationsindikation. Die Operation beinhaltet die Krossektomie mit Stammvenenexharese, evtl. uber zusatzliche Inzisionen, die Entfernung aller Varikosen und die Ligatur oder Dissektion der insuffizienten Perforansvenen. Intraoperative Komplikationen wurden nicht beobachtet. Die Quote der N.-saphenus-Irritationen betrug 6% und die im Bereich des N. suralis 4,3%. Flachenhamatome traten in 27,6% auf und in 7,7% konservativ beherrschbare Wundheilungsstorungen. Bei 58% der Kranken wurde mittels Thrombophiliescreenings eine Hamostasestorung festgestellt, wobei die APC-Resistenz (37,4%) und die Hyperhomozysteinamie (23,9%) die haufigsten Gendefekte darstellten. Unsere Resultate belegen, dass die dringliche, einzeitige Operation der aszendierenden Varikophlebitis ein bezuglich des Risikos thromboembolischer Komplikationen sicheres und die klinische Symptomatik der Patienten rasch linderndes Verfahren darstellt. Das Vorliegen einer Hamostasestorung sollte in Betracht gezogen werden.

Von Januar bis Dezember 2004 wurden alle 237 Patienten, die mit einer endoskopisch subfaszialen Perforantendissektion (ESDP) behandelt werden mussten, mit einem speziellen ESDP-Untersuchungsbogen erfasst und nach einem einheitlichen Bewertungsschema beurteilt. Durch die Insufflation von Gas erreichen wir die fur die Ausschaltung der insuffizienten Perforansvenen notwendige Vergroserung des subfaszialen Raums. Die Lokalisationsdiagnostik der Vv. perforantes geschieht ebenso wie die Beurteilung der tiefen Beinvenen und die Markierung der Insuffizienzpunkte des epifaszialen Venensystems ausschlieslich mittels uneingeschrankt reproduzierbarer Farbduplexsonographie. 201 Patienten oder 85% wurden nach 6 Wochen, 6 Monaten und 1 Jahr nachuntersucht. In 70% der Falle wurde synchron zur ESDP die epifasziale Sanierung der Varikose vorgenommen. Anhaltende diffuse Dysasthesien traten in 6% der Falle auf. Bei 1,5% war nach 1 Jahr ein sensibler Defizit des N. saphenus klinisch relevant und bei 1% beobachteten wir eine Lasion der Rr. calcanei medialis des N. tibialis posterior. 17 (8,5%) Flachenhamatomen standen einem operationspflichtigen subfaszialen Hamatom gegenuber. Die 1,5% Wundheilungsstorungen waren konservativ beherrschbar; nur in einem Fall musste eine epifasziale Abszedierung inzidiert werden. Bei einem Hochrisikopatienten (0,5%) entwickelte sich postoperativ eine tiefe Beinvenenthrombose. Bei 82% der nachuntersuchten Patienten war nach 12 Monaten die Stauungssymptomatik rucklaufig. 89% der Ulkusfalle wurden mit einem vollstandig eingeheilten Transplantat entlassen. Rezidivulzerationen nach 1 Jahr beobachteten wir bei 16%, dabei war das postthrombotische Syndrom doppelt so haufig betroffen wie die primare Varikose. Wir fanden nach 1 Jahr bei 13% der Patienten neue oder persistierende Vv. perforantes. War die Klappeninsuffizienz durch die postthrombotische Krankheit hervorgerufen, war dagegen die Perforantenrezidivhaufigkeit mit 26% nach 12 Monaten doppelt so hoch. Insgesamt fanden wir nach 1 Jahr bei etwa drei Viertel unserer Patienten den Trend zur Verbesserung der venosen Hamodynamik, wie auch des klinischen Befundes, bestatigt. Durch die guten Langzeitergebnisse bei geringen postoperativen Komplikationsraten unter einem standardisierten stationaren Behandlungsregime ist die ESDP als hochst effektives Verfahren im Therapiekonzept der fortgeschrittenen chronisch venosen Insuffizienz nicht mehr wegzudenken.

Mehrdimensionale Warmestromberechnung haben sich gegenuber den klassischen mestechnischen Untersuchungen mehr und mehr etabliert. Bislang wurde in mehreren, auch europaischen, Untersuchungen die Rechengenauigkeit der Berechnungsprogramme untersucht. Auch Vergleichsuntersuchungen zwischen Berechnung und Messung wurden bereits unternommen oder sind in Bearbeitung. Konnen aber auch die in der Praxis auftretende Probleme anhand der normativen Festlegungen ausreichend behandelt werden und ist der Kenntnisstand der Bearbeiter bei der physikalisch korrekten Modellierung verbleibender Interpretationsspielraume gros genug um ein Problem adaquat losen zu konnen? Um diese Frage zu untersuchen, haben sich sieben deutsche Institute einer Ringrechnung unterzogen. Die Ergebnisse zeigen trotz der offenen Fragestellung gute Ubereinstimmung. Typische Fehler lassen sich vermeiden, wenn die qualifizierten Anwender fur die auftretenden Probleme sensibilisiert sind. Dazu sollten die einzelnen Institute anhand eines definierten Schemas durch das DIBt gepruft und als Recheninstitut anerkannt werden.

Bis(dimethylsilyl)amide and bis(dimethylphenylsilyl)amide complexes of the divalent transition metals chromium, manganese, and cobalt were synthesized. Dimeric, donor-free {Mn[N(SiHMe2)2]2}2 could be obtained via two different pathways, a salt metathesis route (utilizing MnCl2(thf)1.5 and LiN(SiHMe2)2) and a transsilylamination protocol (utilizing Mn[N(SiMe3)2]2(thf) and HN(SiHMe2)2). Addition of 1,1,3,3-tetramethylethylendiamine (tmeda) to {Mn[N(SiHMe2)2]2}2 yielded the monomeric adduct Mn[N(SiHMe2)2]2(tmeda). The syntheses of Cr[N(SiHMe2)2]2(tmeda), Co[N(SiMe3)2][N(SiHMe2)2](tmeda), and Co[N(SiHMe2)2]2(tmeda) were achieved by transsilylamination from Cr[N(SiMe3)2]2(tmeda) and {Co[N(SiMe3)2]2}2(μ-tmeda), respectively. Bis(dimethylphenylsilyl)amide complexes Mn[N(SiMe2Ph)2]2, Cr[N(SiMe2Ph)2]2, and Co[N(SiMe2Ph)2]2(thf) were obtained via salt metathesis employing MCl2(thf)x (M = Cr, Mn, Co) with equimolar amounts of LiN(SiMe2Ph)2 in n-hexane. Treatment of CrCl2 with LiN(SiMe2Ph)2 in thf gave Cr[N(SiMe2Ph)2]2(thf)2, featuring an almost square planar trans-coordination. All complexes were examined by elemental analyses, DRIFT and UV-vis spectroscopy, as well as X-ray structure analysis, paying particular attention to secondary M---SiH β-agostic and M---π(arene) interactions. Magnetic moments were determined by Evans' method.

The enzymes 5-lipoxygenase (5-LO) and glycogen synthase kinase (GSK)-3 represent promising drug targets in inflammation. We made use of the bisindole core of indirubin, present in GSK-3 inhibitors, to innovatively target 5-LO at the ATP-binding site for the design of dual 5-LO/GSK-3 inhibitors. Evaluation of substituted indirubin derivatives led to the identification of (3Z)-6-bromo-3-[(3E)-3-hydroxyiminoindolin-2-ylidene]indolin-2-one (15) as a potent, direct, and reversible 5-LO inhibitor (IC50 = 1.5 μM), with comparable cellular effectiveness on 5-LO and GSK-3. Together, we present indirubins as novel chemotypes for the development of 5-LO inhibitors, the interference with the ATP-binding site as a novel strategy for 5-LO targeting, and dual 5-LO/GSK-3 inhibition as an unconventional and promising concept for anti-inflammatory intervention. © 2014 American Chemical Society.

Dacher aus Beton weisen gegenuber traditionellen Holzsparrendachern Vorteile bezuglich des Temperaturverhaltens im Sommer, der Luftdichtheit und des Schallschutzes auf. Zudem sind bei Betondachern weniger Gewerke beteiligt. Daher sind sie nicht so schadensanfallig wie Sparrendacher. Durch einen hohen Vorfertigungsgrad der Dachelemente im Werk kann die Montagezeit von Betondachern auf der Baustelle kurz gehalten werden, was sich kostengunstig auswirkt. In drei gleichartigen Dachgeschoswohnungen am gleichen Standort wurden je ein Beton-, Porenbeton- und ein Sparrendach eingebaut. Durch die grosformatige Ausfuhrung der Beton- und Porenbeton-Unterkonstruktion sowie der Dammelemente liesen sich die Betondacher innerhalb eines Tages problemlos errichten. Die montagetechnischen Vorgange wurden dokumentiert und die bauphysikalischen Eigenschaften wahrend der sommerlichen und winterlichen Mesperiode untersucht. Die erwarteten Vorteile der Betondacher konnten in diesem Pilotprojekt aufgezeigt werden. In Folgeprojekten lassen sich auch die Kosten der Betondacher weiter reduzieren.

Interleukin-6 (IL-6) has recently been implicated in multiple sclerosis (MS), since IL-6 deficient mice were resistant to a demyelinating form of experimental autoimmune encephalomyelitis and IL-6 expression was upregulated in MS. The cytokine IL-6 and its action mediating soluble receptors (sIL-6R and sgp130) were measured in cerebrospinal fluid (CSF) and serum of 61 MS patients and 39 controls. In the presence of unchanged IL-6 concentrations, sIL-6R and sgp130 serum levels were significantly increased in MS and correlated with disease severity. Furthermore, sgp130 CSF levels were decreased in MS, suggesting a possibly altered IL-6 regulation in the CSF.

Die gliedkinetische Ataxie der oberen Extremitaten ist eines der am meisten behindernden Symptome einer multiplen Sklerose (MS). Die symptomatische Therapie zielt v.a. auf die Behandlung des cerebellaren Tremors, wobei einige ausreichend auf ihre Effektivitat hin getestete medikamentose und operative Strategien zur Verfugung stehen. Dagegen sind insbesondere physio- und ergotherapeutische Behandlungsverfahren nur selten systematisch untersucht worden. Dies gilt auch fur die von MS-Patienten und Therapeuten berichtete gunstige Beeinflussung der zerebellaren Ataxie der Arme durch eine lokale Eisbehandlung. Wir untersuchten 21 MS-Patienten vor und in einigen Zeitintervallen 1 bis 45 min nach einer lokalen Kuhlungstherapie des Unterarmes mittels einer von uns zusammengestellten und validierten 6teiligen Testbatterie, die sowohl klinisch-neurologische Befunde als auch alltagsrelevante Funktionsablaufe enthalt. Zu jedem Untersuchungszeitpunkt erfolgten zusatzlich Messungen von Temperatur und Nervenleitgeschwindigkeit. Samtliche Versuchsdurchgange wurden zur spateren Analyse auf Video dokumentiert. Die standardisierte Auswertung erfolgte sowohl durch die Untersucher als auch durch ein nicht mit der Versuchsdurchfuhrung befastes zweites Team anhand numerischer Skalen fur die Bewegungsqualitat wahrend der Testung. Bei allen Patienten zeigte sich ein positiver Effekt nach Kuhlung v.a. auf die Auspragung des Intentionstremors, der meist 45 min anhielt, in einigen Fallen sogar langer. Als wahrscheinliche Ursache fur die Reduktion des Intentionstremors wird eine kuhlungsbedingte Minderung propriozeptiver Afferenzen diskutiert. Die Patienten konnen von einer Kuhlungsbehandlung im Rahmen einer Selbsttherapie profitieren, wenn eine zeitlich begrenzte Reduktion des Intentionstremors erforderlich ist, z.B. bei Arbeiten am PC, Leistung einer Unterschrift oder auch vor Durchfuhrung einer Selbstkatheterisierung.

OBJECTIVE—To assess the quality of life (QoL) of patients with multiple sclerosis in France, Germany, and the United Kingdom with a cross sectional study. METHODS—Patients were classified into three severity groups according to the expanded disability severity scale (EDSS); stage I, II, and III, corresponding to mild (EDSS 1.0-3.5), moderate (EDSS 4.0-6.0), or severe (EDSS 6.5-8.0) multiple sclerosis respectively. Ninety patients with multiple sclerosis and 30 control patients without multiple sclerosis were recruited in each country. Control patients were matched to the patients with multiple sclerosis according to age and sex. Quality of life was assessed using the functional status questionnaire (FSQ). RESULTS—The aspects of QoL that were mostly affected in the three countries under study were physical function and general wellbeing. Social role function decreased with increased severity of disease in France and in particular in Germany. Multiple sclerosis did not seem to have an impact on psychological function. The QoL of control patients was systematically higher than that of patients with multiple sclerosis. CONCLUSIONS—Use of such a generic scale showed that progression of multiple sclerosis is accompanied by a decrease in QoL and suggested that this could be a relevant measurement in assessing the effect of treatment and progression of disease. Variation between countries, however, may be important.