Clinching of inductively heated aluminum die casting

The aim of the investigations described in this article is to improve the clinching of aluminum die casting. The focus is on clinching an aluminum die casting alloy by local heat treatment and hence to join them in a process-safe manner. For this purpose, a heating strategy is used to warm up the die casting alloys to reduce temporarily and reversibly the elongation and the yield strength in the material. In preliminary investigations, three different heating strategies (heating plate, resistance heating and inductive heating) have been investigated. Induction heating has been selected as the most suitable method due to the short heating time and the production of crack-free clinch points. In this paper, two clinching tool systems (one with a flexible die, one with a rigid die) were used. For these tools, two inductors with different diameter were manufactured. The effects of each inductor and clinching tool on an aluminum die casting alloy, such as heating time and crack behavior, were investigated. Surface images of the clinch points in regard to the heat treatment temperature were analyzed. Furthermore, the characteristic parameters of the joints such as interlock, bottom thickness and neck thickness were examined. In addition, the strength of the joined parts was investigated by head tension tests. The results of the developed method showed that it is possible to produce crack-free clinching joints below 6 s. Furthermore, the local heating led to an increasing interlock resulting in a 26% increase of the head tensile strength

Measurement of exhaled volatile organic compounds from patients with chronic obstructive pulmonary disease (COPD) using closed gas loop GC-IMS and GC-APCI-MS

Due to its high sensitivity, compact size and low cost Ion Mobility Spectrometry (IMS) has the potential to become a point-of-care breath analyzer. Therefore, we developed a prototype of a compact, closed gas loop IMS with gas chromatographic (GC) pre-separation and high resolving power of R = 90. In this study, we evaluated the performance of this GC-IMS under clinical conditions in a COPD study to find correlations between VOCs (10 ppbv to 1 ppmv) and COPD. Furthermore, in order to investigate possible correlations between ultra-low concentrated breath VOCs (0.1 pptv to 1 ppbv) and COPD, a modified mass spectrometer (MS) with atmospheric pressure chemical ionization (APCI) and GC pre-separation (GC-APCI-MS) was used. The GC-IMS has been used in 58 subjects (21 smokers with moderate COPD, 12 ex-smokers with COPD, 16 healthy smokers and 9 non-smokers). GC-APCI-MS data were available for 94 subjects (21 smokers with moderate COPD, 25 ex-smokers with COPD, 25 healthy smokers and 23 non-smokers). For 44 subjects, a comparison between GC-IMS and GC-APCI-MS data could be performed. Due to service intervals, subject availability and corrupt data, patient numbers were different for GC-APCI-MS and GC-IMS measurements. Using GC-IMS, three VOCs have been found showing a significant difference between healthy controls and patients with COPD. In the GC-APCI-MS data, we only observed one distinctive VOC, which has been identified as 2-pentanone. This proof-of-principle study shows the potential of our high-resolution GC-IMS in the clinical environment. Due to different linear dynamic response ranges, the data of GC-IMS and GC-APCI-MS were only comparable to a limited extent

Characterization, dietary habits and nutritional intake of omnivorous, lacto-ovo vegetarian and vegan runners – a pilot study

Background The number of people preferring plant-based nutrition is growing continuously in the western world. Vegetarianism and veganism are also becoming increasingly popular among individuals participating in sport. However, whether recreationally active vegetarian and vegan populations can meet their nutritional needs is not clear. Methods The purpose of this cross-sectional study was to compare the nutrient intake of omnivorous (OMN, n = 27), lacto-ovo vegetarian (LOV, n = 25) and vegan (VEG, n = 27) recreational runners (two to five training sessions per week) with intake recommendations of the German, Austrian and Swiss Nutrition Societies (Deutsche, Österreichische und Schweizerische Gesellschaften für Ernährung, D-A-CH) for the general population. Lifestyle factors and supplement intake were examined via questionnaires; dietary habits and nutrient intake were determined based on 3-day dietary records. Results More than half of each group did not reach the recommended energy intake (OMN: 10.4, 8.70–12.1; LOV: 9.67, 8.55–10.8; VEG: 10.2, 9.12–11.3 MJ). Carbohydrate intake was slightly below the recommendations of > 50 EN% in OMN (46.7, 43.6–49.8 EN%), while LOV (49.4, 45.5–53.3 EN%) and VEG (55.2, 51.4–59.0 EN%) consumed adequate amounts (p = 0.003). The recommended protein intake of 0.8 g/kg body weight (D-A-CH) was exceeded in all three groups (OMN: 1.50, 1.27–1.66; LOV: 1.34, 1.09–1.56; VEG: 1.25; 1.07–1.42 g/kg BW; p = 0.047). Only VEG (26.3, 22.7–29.8 EN%) did not achieve the recommended fat intake of 30 EN%. The supply of micronutrients, such as vitamin D and cobalamin, was dependent on supplement intake. Additionally, female OMN and LOV achieved the recommended daily intake of 15 mg iron only after supplementation, while VEG consumed adequate amounts solely via food. Conclusion All three groups were sufficiently supplied with most nutrients despite the exceptions mentioned above. The VEG group even showed advantages in nutrient intake (e.g. carbohydrates, fiber and iron) in comparison to the other groups. However, the demand for energy and several macro- and micronutrients might be higher for athletes. Thus, it is also necessary to analyze the endogenous status of nutrients to evaluate the influence of a vegetarian and vegan diet on the nutrient supply of athletes

Changes in serum metabolomics in idiopathic pulmonary fibrosis and effect of approved antifibrotic medication

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality and morbidity. Approval of antifibrotic therapy has ameliorated disease progression, but therapy response is heterogeneous and to date, adequate biomarkers predicting therapy response are lacking. In recent years metabolomic technology has improved and is broadly applied in cancer research thus enabling its use in other fields. Recently both aberrant metabolic and lipidomic pathways have been described to influence profibrotic responses. We thus aimed to characterize the metabolomic and lipidomic changes between IPF and healthy volunteers (HV) and analyze metabolomic changes following treatment with nintedanib and pirfenidone. We collected serial serum samples from two IPF cohorts from Germany (n = 122) and Spain (n = 21) and additionally age-matched healthy volunteers (n = 16). Metabolomic analysis of 630 metabolites covering 14 small molecule and 12 different lipid classes was carried out using flow injection analysis tandem mass spectrometry for lipids and liquid chromatography tandem mass spectrometry for small molecules. Levels were correlated with survival and disease severity. We identified 109 deregulated analytes in IPF compared to HV in cohort 1 and 112 deregulated analytes in cohort 2. Metabolites which were up-regulated in both cohorts were mainly triglycerides while the main class of down-regulated metabolites were phosphatidylcholines. Only a minority of de-regulated analytes were small molecules. Triglyceride subclasses were inversely correlated with baseline disease severity (GAP-score) and a clinical compound endpoint of lung function decline or death. No changes in the metabolic profiles were observed following treatment with pirfenidone. Nintedanib treatment induced up-regulation of triglycerides and phosphatidylcholines. Patients in whom an increase in these metabolites was observed showed a trend towards better survival using the 2-years composite endpoint (HR 2.46, p = 0.06). In conclusion, we report major changes in metabolites in two independent cohorts testing a large number of patients. Specific lipidic metabolite signatures may serve as biomarkers for disease progression or favorable treatment response to nintedanib

Impact of the Gut Microbiota on Atorvastatin Mediated Effects on Blood Lipids

Background and aims: The mechanisms of interindividual variation of lipid regulation by statins, such as the low-density lipoprotein cholesterol (LDL) lowering effects, are not fully understood yet. Here, we used a gut microbiota depleted mouse model to investigate the relation between the gut microbiota and the regulatory property of atorvastatin on blood lipids. Methods: Mice (C57BL/6) with intact gut microbiota or antibiotic induced abiotic mice (ABS) were put on standard chow diet (SCD) or high fat diet (HFD) for six weeks. Atorvastatin (10 mg/kg body weight/day) or a control vehicle were applied per gavage for the last four weeks of dietary treatment. Blood lipids including total cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and sphingolipids were measured to probe microbiota-dependent effects of atorvastatin. The expression of genes involved in hepatic and intestinal cholesterol metabolism was analyzed with qRT-PCR. The alteration of the microbiota profile was examined using 16S rRNA qPCR in mice with intact gut microbiota. Results: HFD feeding significantly increased total blood cholesterol and LDL levels, as compared to SCD in both mice with intact and depleted gut microbiota. The cholesterol lowering effect of atorvastatin was significantly attenuated in mice with depleted gut microbiota. Moreover, we observed a global shift in the abundance of several sphingolipids upon atorvastatin treatment which was absent in gut microbiota depleted mice. The regulatory effect of atorvastatin on the expression of distinct hepatic and intestinal cholesterol-regulating genes, including Ldlr, Srebp2 and Npc1l1 was altered upon depletion of gut microbiota. In response to HFD feeding, the relative abundance of the bacterial phyla Bacteroidetes decreased, while the abundance of Firmicutes increased. The altered ratio between Firmicutes to Bacteroidetes was partly reversed in HFD fed mice treated with atorvastatin. Conclusions: Our findings support a regulatory impact of atorvastatin on the gut microbial profile and, in turn, demonstrate a crucial role of the gut microbiome for atorvastatin-related effects on blood lipids. These results provide novel insights into potential microbiota-dependent mechanisms of lipid regulation by statins, which may account for variable response to statin treatment

Metabolic Signatures of Type 2 Diabetes Mellitus and Hypertension in COVID-19 Patients With Different Disease Severity.

Increased COVID-19 disease severity is higher among patients with type 2 diabetes mellitus and hypertension. However, the metabolic pathways underlying this association are not fully characterized. This study aims to identify the metabolic signature associated with increased COVID-19 severity in patients with diabetes mellitus and hypertension. One hundred and fifteen COVID-19 patients were divided based on disease severity, diabetes status, and hypertension status. Targeted metabolomics of serum samples from all patients was performed using tandem mass spectrometry followed by multivariate and univariate models. Reduced levels of various triacylglycerols were observed with increased disease severity in the diabetic patients, including those containing palmitic (C16:0), docosapentaenoic (C22:5, DPA), and docosahexaenoic (C22:6, DHA) acids (FDR < 0.01). Functional enrichment analysis revealed triacylglycerols as the pathway exhibiting the most significant changes in severe COVID-19 in diabetic patients (FDR = 7.1 × 10). Similarly, reduced levels of various triacylglycerols were also observed in hypertensive patients corresponding with increased disease severity, including those containing palmitic, oleic (C18:1), and docosahexaenoic acids. Functional enrichment analysis revealed long-chain polyunsaturated fatty acids (n-3 and n-6) as the pathway exhibiting the most significant changes with increased disease severity in hypertensive patients (FDR = 0.07). Reduced levels of triacylglycerols containing specific long-chain unsaturated, monounsaturated, and polyunsaturated fatty acids are associated with increased COVID-19 severity in diabetic and hypertensive patients, offering potential novel diagnostic and therapeutic targets.This research was funded by the Qatar National Research Fund, Grant Number NPRP11S-1212-170092

Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE).

Background&#xD;Exhaled breath contains numerous volatile organic compounds (VOCs) known to be related to lung disease like asthma. Its collection is non-invasive, simple to perform and therefore an attractive method for the use even in young children. We analysed breath in children of the multicenter All Age Asthma Cohort (ALLIANCE) to evaluate if "breathomics" have the potential to phenotype patients with asthma and wheeze, and to identify extrinsic risk factors for underlying disease mechanisms.&#xD;Methods&#xD;A breath sample was collected from 142 children (asthma: 51, pre-school wheezers: 55, healthy controls: 36) and analysed using gas chromatography-mass spectrometry (GC/MS). Children were diagnosed according to GINA guidelines and comprehensively examined each year over up to seven years. Forty children repeated the breath collection after 24 or 48 months. &#xD;Results&#xD;Most breath VOCs differing between groups reflect the exposome of the children. We observed lower levels of lifestyle-related VOCs and higher levels of the environmental pollutants, especially naphthalene, in children with asthma or wheeze. Naphthalene was also higher in symptomatic patients and in wheezers with recent inhaled corticosteroid use. No relationships with lung function or TH2 inflammation were detected.&#xD;Conclusion&#xD;Increased levels of naphthalene in asthmatics and wheezers and the relationship to disease severity could indicate a role of environmental or indoor air pollution for the development or progress of asthma. Breath VOCs might help to elucidate the role of the exposome for the development of asthma.&#xD;The study was registered at ClinicalTrials.gov (NCT02496468).&#xD;&#xD

Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR <= 0.05) in comparison to mild and asymptomatic cases. Indeed, we identified betaine and BCAAs as potential prognostic metabolic biomarkers of severity and mortality, respectively, in COVID-19 patients who have been exposed to TB. Moreover, we identified serum alanine as an important metabolite at the interface of severity and mortality. Hence, our data associated COVID-19 mortality and morbidity with a long-term metabolically driven consequence of TB infection. In summary, our study provides evidence for a higher mortality rate among COVID-19 infection patients who have history of prior TB infection diagnosis, which mandates validation in larger population cohorts

Limited Impact of Pivalate-Induced Secondary Carnitine Deficiency on Hepatic Transcriptome and Hepatic and Plasma Metabolome in Nursery Pigs

Administration of pivalate has been demonstrated to be suitable for the induction of secondary carnitine deficiency (CD) in pigs, as model objects for humans. In order to comprehensively characterize the metabolic effects of secondary CD in the liver of pigs, the present study aimed to carry out comparative analysis of the hepatic transcriptome and hepatic and plasma metabolome of a total of 12 male 5-week-old pigs administered either pivalate (group PIV, n = 6) or vehicle (group CON, n = 6) for 28 days. Pigs of group PIV had approximately 40–60% lower concentrations of free carnitine and acetylcarnitine in plasma, liver and different skeletal muscles than pigs of group CON (p &lt; 0.05). Transcript profiling of the liver revealed 140 differentially expressed genes (DEGs) between group PIV and group CON (fold change &gt; 1.2 or &lt;−1.2, p-value &lt; 0.05). Biological process terms dealing with the innate immune response were found to be enriched with the DEGs (p &lt; 0.05). Using a targeted metabolomics approach for the simultaneous quantification of 630 metabolites, 9 liver metabolites and 18 plasma metabolites were identified to be different between group PIV and group CON (p &lt; 0.05). Considering the limited alterations of the hepatic transcriptome and of the liver and plasma metabolome, it can be concluded that pivalate-induced secondary CD is not associated with significant hepatic metabolism changes in pigs

Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML