The AST/ALT (De-Ritis) ratio: a novel marker for critical limb ischemia in peripheral arterial occlusive disease patients

The aspartat aminotransferase (AST)/alanin aminotransferase (ALT) (De-Ritis) ratio (AAR) is an easily applicable blood test. An elevated AAR on the one hand has been associated with an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD on the other hand is associated with an increase in cardiovascular disease, all-cause mortality, and diabetes. As the AAR is also elevated in case of muscular damage, we investigated AAR and its association with critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients. In our cross-sectional study, we included 1782 PAOD patients treated at our institution from 2005 to 2010. Patients with chronic alcohol consumption (>20 g/day) were excluded. AAR was calculated and the cohort was categorized into tertiles according to the AAR. An optimal cut-off value for the continuous AAR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI. In our cohort, occurrence of CLI significantly increased with an elevation in AAR. As an optimal cut-off value, an AAR of 1.67 (sensitivity 34.1%, specificity 81.0%) was identified. Two groups were categorized, 1st group containing 1385 patients (AAR < 1.67) and a 2nd group with 397 patients (AAR > 1.67). CLI was more frequent in AAR > 1.67 patients (166 [41.9%]) compared to AAR < 1.67 patients (329 [23.8%]) (P < 0.001), as was prior myocardial infarction (28 [7.1%] vs 54 [3.9%], P = 0.01). Regarding inflammatory parameters, C-reactive protein (median 8.1 mg/L [2.9–28.23] vs median 4.3 mg/L [2.0–11.5]) and fibrinogen (median 427.5 mg/dL [344.25–530.0] vs 388.0 mg/dL [327.0–493.0]) also significantly differed in the 2 patient groups (both P < 0.001). Finally, an AAR > 1.67 was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] 1.7–2.3) for CLI even after adjustment for other well-established vascular risk factors. An increased AAR is significantly associated with patients at high risk for CLI and other cardiovascular endpoints. The AAR is a broadly available and cheap marker, which might be useful to highlight patients at high risk for vascular endpoints

Highly Enantioselective Catalytic Asymmetric Synthesis of a (R)-Sibutramin Precursor

The first highly enantioselective, catalytic asymmetric synthesis of di-des-methylsibutramine 3 is described. Dienamide 10, prepared by acetic acid anhydride quenching of the condensation product of nitrile 4 with a methallyl magnesium chloride, proved to be an excellent substrate for ruthenium-catalyzed asymmetric hydrogenation with atropisomeric diphosphine ligands. Hydrogenation with a ruthenium/(R)- MeOBiPheP catalyst at S/C = 500, gave the chiral amide (R)-9 in 98.5% ee in almost quantitative yield. After acidic amide hydrolysis the desired amine (R)-3 was obtained without erosion of enantioselectivity. It is anticipated that the overall process will be amenable to large-scale production

Exoseal for puncture site closure after antegrade procedures in peripheral arterial disease patients

PURPOSEExoseal is a vascular clo­sure device consisting of a plug applier and a bio-absorbent polyglycolic acid plug available in sizes 5 F, 6 F, and 7 F. In this study, we aimed to evaluate the effectiveness and safety of the Exoseal vascular closure device (Cordis Corporation, Bridgewater, New Jersey, USA) for puncture site closure after antegrade endovascular procedures in peripheral arterial occlusive disease (PAOD) patients. MATERIALS AND METHODSIn this retrospective study, a total of 168 consecutive patients who underwent an interventional procedure due to PAOD, were included. In each case, an antegrade peripheral endovascular procedure was performed via the common femoral artery using the Seldinger technique, and Exoseal 5 F, 6 F, or 7 F was used for access site closure. The primary endpoint was a technically successful application of Exoseal. All complications at the access site within 24 hours were registered as a secondary endpoint.RESULTSIn a group of 168 patients (64.9% men, average age 71.9±11.9 years), the technical application of Exoseal was successful in 166 patients (98.8%). Within the first 24 hours after the procedure, 12 complications (7.2%) were recorded including, three pseudoaneurysms (1.8%) and nine hematomas (5.4%). None of the complications required surgical intervention.CONCLUSIONExoseal is a safe and effective device with high technical success and acceptable complication rates for access site closure after antegrade peripheral endovascular procedures

Dynamics of initial carbon allocation after drought release in mature Norway spruce—Increased belowground allocation of current photoassimilates covers only half of the carbon used for fine‐root growth

After drought events, tree recovery depends on sufficient carbon (C) allocation to the sink organs. The present study aimed to elucidate dynamics of tree-level C sink activity and allocation of recent photoassimilates (C$_{new}$) and stored C in c. 70-year-old Norway spruce (Picea abies) trees during a 4-week period after drought release. We conducted a continuous, whole-tree $^{13}$C labeling in parallel with controlled watering after 5 years of experimental summer drought. The fate of C$_{new}$ to growth and CO$_{2}$ efflux was tracked along branches, stems, coarse- and fine roots, ectomycorrhizae and root exudates to soil CO$_{2}$ efflux after drought release. Compared with control trees, drought recovering trees showed an overall 6% lower C sink activity and 19% less allocation of C$_{new}$ to aboveground sinks, indicating a low priority for aboveground sinks during recovery. In contrast, fine-root growth in recovering trees was seven times greater than that of controls. However, only half of the C used for new fine-root growth was comprised of C$_{new}$ while the other half was supplied by stored C. For drought recovery of mature spruce trees, in addition to C$_{new}$, stored C appears to be critical for the regeneration of the fine-root system and the associated water uptake capacity

ESVM guidelines:the diagnosis and management of Raynaud's phenomenon

Regarding the clinical diagnosis of Raynaud's phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud's phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud's phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment

Multi-scale characterisation of a ferroelectric polymer reveals the emergence of a morphological phase transition driven by temperature

[EN] Ferroelectric materials exhibit a phase transition to a paraelectric state driven by temperature - called the Curie transition. In conventional ferroelectrics, the Curie transition is caused by a change in crystal symmetry, while the material itself remains a continuous three-dimensional solid crystal. However, ferroelectric polymers behave differently. Polymeric materials are typically of semi-crystalline nature, meaning that they are an intermixture of crystalline and amorphous regions. Here, we demonstrate that the semi-crystalline morphology of the ferroelectric copolymer of vinylidene fluoride and trifluoroethylene (P(VDF-TrFE)) strongly affects its Curie transition, as not only a change in crystal symmetry but also in morphology occurs. We demonstrate, by high-resolution nanomechanical measurements, that the semicrystalline microstructure in the paraelectric state is formed by crystalline domains embedded into a softer amorphous phase. Using in situ X-ray diffraction measurements, we show that the local electromechanical response of the crystalline domains is counterbalanced by the amorphous phase, effectively masking its macroscopic effect. Our quantitative multiscale characterisations unite the nano- and macroscopic material properties of the ferroelectric polymer P(VDF-TrFE) through its semi-crystalline nature.European Union’s Horizon 2020 research and Innovation programme under the Marie Skłodowska-Curie grant agreement number 721874 (SPM2.0). RG acknowledges funding from the European Research Council ERC–AdG–340177 (3DNanoMech). This work was supported by the UK government’s Department for Business, Energy and Industrial Strategy. The dynamic mechanical analysis was supported by T. Koch from the Institute of Materials Science and Technology, TU Wien. We gratefully thank A. Muhamedagić for the contribution of artworks to the figures (armindesign.li).Peer reviewe

Association of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathic changes in limited systemic sclerosis

ObjectivesPathways contributing to endothelial dysfunction in patients with limited cutaneous systemic sclerosis (lcSSc) are largely unknown. The aim of this study was to investigate potential associations of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathy-related changes in patients with lcSSc and early-stage vasculopathy.MethodsAmino acids, calciotropic parameters, including 25-hydroxyvitamin D and parathyroid hormone (PTH), and bone turnover parameters, including osteocalcin and N-terminal peptide of procollagen-3 (P3NP), were measured in 38 lcSSc patients and 38 controls. Endothelial dysfunction was assessed by biochemical parameters, pulse-wave analysis, flow-mediated and nitroglycerine-mediated dilation. Additionally, vasculopathy-related and SSc-specific clinical changes including capillaroscopic, skin, renal, pulmonary, gastrointestinal and periodontal parameters were recorded.ResultsNo significant differences in amino acids, calciotropic and bone turnover parameters were observed between lcSSc patients and controls. In patients with lcSSc, several significant correlations were found between selected amino acids, parameters of endothelial dysfunction, vasculopathy-related and SSc-specific clinical changes (all with p &lt; 0.05). In addition, significant correlations were observed between PTH and 25-hydroxyvitamin D with homoarginine, and between osteocalcin, PTH and P3NP with modified Rodnan skin score and selected periodontal parameters (all with p &lt; 0.05). Vitamin D deficiency defined as 25-hydroxyvitamin D &lt; 20 ng/ml was associated with the presence of puffy finger (p = 0.046) and early pattern (p = 0.040).ConclusionSelected amino acids may affect endothelial function and may be associated to vasculopathy-related and clinical changes in lcSSc patients, while the association with parameters of bone metabolism seems to be minor

Confirmation of a non-synonymous SNP in PNPLA8 as a candidate causal mutation for Weaver syndrome in Brown Swiss cattle

Background: Bovine progressive degenerative myeloencephalopathy (Weaver syndrome) is a neurodegenerative disorder in Brown Swiss cattle that is characterized by progressive hind leg weakness and ataxia, while sensorium and spinal reflexes remain unaffected. Although the causal mutation has not been identified yet, an indirect genetic test based on six microsatellite markers and consequent exclusion of Weaver carriers from breeding have led to the complete absence of new cases for over two decades. Evaluation of disease status by imputation of 41 diagnostic single nucleotide polymorphisms (SNPs) and a common haplotype published in 2013 identified several suspected carriers in the current breeding population, which suggests a higher frequency of the Weaver allele than anticipated. In order to prevent the reemergence of the disease, this study aimed at mapping the gene that underlies Weaver syndrome and thus at providing the basis for direct genetic testing and monitoring of today's Braunvieh/Brown Swiss herds. Results: Combined linkage/linkage disequilibrium mapping on Bos taurus chromosome (BTA) 4 based on Illumina Bovine SNP50 genotypes of 43 Weaver-affected, 31 Weaver carrier and 86 Weaver-free animals resulted in a maximum likelihood ratio test statistic value at position 49,812,384 bp. The confidence interval (0.853 Mb) determined by the 2-LOD drop-off method was contained within a 1.72-Mb segment of extended homozygosity. Exploitation of whole-genome sequence data from two official Weaver carriers and 1145 other bulls that were sequenced in Run4 of the 1000 bull genomes project showed that only a non-synonymous SNP (rs800397662) within the PNPLA8 gene at position 49,878,773 bp was concordant with the Weaver carrier status. Targeted SNP genotyping confirmed this SNP as a candidate causal mutation for Weaver syndrome. Genotyping for the candidate causal mutation in a random sample of 2334 current Braunvieh animals suggested a frequency of the Weaver allele of 0.26 %. Conclusions: Through combined use of exhaustive sequencing data and SNP genotyping results, we were able to provide evidence that supports the non-synonymous mutation at position 49,878,773 bp as the most likely causal mutation for Weaver syndrome. Further studies are needed to uncover the exact mechanisms that underlie this syndrome

The Magnetoelectric Effect in Transition Metal Oxides: Insights and the Rational Design of New Materials from First Principles

The search for materials displaying a large magnetoelectric effect has occupied researchers for many decades. The rewards could include not only advanced electronics technologies, but also fundamental insights concerning the dielectric and magnetic properties of condensed matter. In this article, we focus on the magnetoelectric effect in transition metal oxides and review the manner in which first-principles calculations have helped guide the search for (and increasingly, predicted) new materials and shed light on the microscopic mechanisms responsible for magnetoelectric phenomena.Comment: 24 pages, 12 figure