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Microbe-produced molecules (xenometabolites) found in foods or produced by gut microbiota are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-oxidation of one or more odd-chain long-chain cyclopropane fatty acids (CpFAs). We deduced two possible candidates, cis-11,12-methylene-pentadecanoic acid (cis-11,12-MPD) and cis-13,14-methylene-heptadecanoic acid (cis-13,14-MHD). Authentic standards were synthesized: cis-11-pentadecenoic acid and cis-13-heptadecenoic acid were generated (using Jones reagent) from cis-11-pentadecene-1-ol and cis-13-heptadecene-1-ol, respectively, and these were converted to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, we determined the presence/absence of cis-11,12-MPD and cis-13,14-MHD in archived piglet biospecimens. Both CpFAs were detected in rectal contents of sow and soy-fed piglets. Archived mass spectra were analyzed post hoc from a second independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs. This confirmed the presence of both CpFAs in plasma and revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids cis-11,12-MPD and cis-13,14-MHD can be components of the mammalian lipidome and are viable candidate precursors of cis-3,4-methylene-heptanoylcarnitine produced from partial β-oxidation in liver or other tissues.

Abstract Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates. In 13 pigs, acute sepsis was induced by IV infusion of Pseudomonas aeruginosa, while in 9 pigs saline (control) was given for 18 h. Blood samples were collected between 12 and 18 h and analyzed with HPLC and LCMS. In sepsis, glucose plasma concentration was reduced (p = 0.0028). A concordant increase in splanchnic area net release of glucose (p = 0.0049), due to reduced uptake in the portal drained viscera (PDV) (p = 0.0032) with an unchanged liver production (p = 0.7861). The hindquarter showed a higher release of alanine (p = 0.0002), glutamine (p = 0.003), and lactate (p = 0.0007), but not for glycerol (p = 0.5718). Diminished PDV uptake of gluconeogenic amino acids, increased liver uptake of these substrates (p

Microbe-produced molecules (xenometabolites) found in foods or produced by gut microbiota are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-oxidation of one or more “odd-chain” long-chain cyclopropane fatty acids (CpFAs). We deduced two possible candidates, cis-11,12-methylene-pentadecanoic acid (cis-11,12-MPD) and cis-13,14-methylene-heptadecanoic acid (cis-13,14-MHD). Authentic standards were synthesized: cis-11-pentadecenoic acid and cis-13-heptadecenoic acid were generated (using Jones reagent) from cis-11-pentadecene-1-ol and cis-13-heptadecene-1-ol, respectively, and these were converted to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, we determined the presence/absence of cis-11,12-MPD and cis-13,14-MHD in archived piglet biospecimens. Both CpFAs were detected in rectal contents of sow and soy-fed piglets. Archived mass spectra were analyzed post hoc from a second independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs. This confirmed the presence of both CpFAs in plasma and revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids cis-11,12-MPD and cis-13,14-MHD can be components of the mammalian lipidome and are viable candidate precursors of cis-3,4-methylene-heptanoylcarnitine produced from partial β-oxidation in liver or other tissues.

ObjectivesDespite the success of cochlear implant (CI) surgery for hearing restoration, reducing CI electrode insertion forces is an ongoing challenge with the goal to further reduce post-implantation hearing loss. While research in this field shows that both friction and quasistatic pressure forces occur during CI insertion, there is a lack of studies distinguishing between these origins. The present study was conducted to analyze the contribution of both force phenomena during automated CI insertion.MethodsFive MED-EL FLEX28 CI electrode arrays were inserted into both a regular and uncoiled version of the same average scala tympani (ST). Both ST models had a pressure release hole at the apical end, which was kept open or closed to quantify pressure forces. ST models were filled with different sodium dodecyl sulfate (SDS) lubricants (1, 5, and 10% SDS, water). The viscosity of lubricants was determined using a rheometer. Insertions were conducted with velocities ranging from v= 0.125 mm/s to 2.0 mm/s.ResultsViscosity of SDS lubricants at 20°C was 1.28, 1.96, and 2.51 mPas for 1, 5, and 10% SDS, respectively, which lies within the values reported for human perilymph. In the uncoiled ST model, forces remained within the noise floor (maximum: 0.049 × 10−3 N ± 1.5 × 10−3 N), indicating minimal contribution from quasistatic pressure. Conversely, forces using the regular, coiled ST model were at least an order of magnitude larger (minimum: Fmax = 28.95 × 10−3 N, v = 1 mm/s, 10% SDS), confirming that friction forces are the main contributor to total insertion forces. An N-way ANOVA revealed that both lubricant viscosity and insertion speed significantly reduce insertion forces (p

Purpose of reviewThis study aimed to discuss the use of the pulse stable isotope tracer approach to study changes in metabolism in healthy individuals and critically ill patients.Recent findings and conclusionWe found that in the postabsorptive state and healthy condition, intracellular protein breakdown and net intracellular protein breakdown, when calculated using the pulse tracer approach, are about double what has previously been reported using the more traditional primed-constant and continuous stable isotope approaches (600 versus 300 grams of protein/day). In critically ill patients, protein breakdown is even higher and calculated to be approximately 900 grams of protein/day, using the pulse tracer approach. Based on these data, we hypothesize that reducing protein breakdown in the postabsorptive state is key when trying to improve the condition of critically ill patients. Moreover, we also used the pulse tracer approach during feeding to better estimate the intracellular metabolic response to feeding. Our first observation is that endogenous protein breakdown does not seem to be reduced during feeding. We also have shown that when consuming a meal with a certain amount of protein, the biological value of that protein meal can be calculated with the pulse tracer approach. In conclusion, using the pulse stable isotope tracer approach to study protein kinetics in the postabsorptive state and during feeding expands our understanding of how dietary proteins can affect human protein metabolism. The intracellular protein synthesis stimulatory effect of a meal is an important factor to consider when calculating the exact protein requirements and needs, particularly in critical illness.

Abstract The mass production of plastic waste has caused an urgent worldwide public health crisis. Although government policies and industrial innovation are the driving forces to meet this challenge, trying to understand public attitudes may improve the efficiency of this process. Social media has become the main ways for the public to obtain information and express opinions and feelings. This motivated us to mine the perceptions and behavioral responses towards plastic usage using social media data. In this paper, we proposed a framework for data collection and analysis based on mainstream media in the UK to obtain public opinions on plastics. An unsupervised machine learning model based on Latent Dirichlet Allocation (LDA) has been employed to analyse and cluster the topics to deal with the lack of annotation of the data contents. An additional dictionary method was then proposed to evaluate the sentiment of the comments. The framework also provides tools to visualise the model and results to stimulate insightful understandings. We validated the framework's effectiveness by applying it to analyse three mainstream social media, where 6 first-level topic categories and 13 second-level topic categories from the comment texts related to plastics have been identified. The results show that public sentiment towards plastic products is generally stable. The spatiotemporal distribution of each topic's sentiment is highly correlated with the number of occurrences.

Sarcoptic mange, caused by Sarcoptes scabiei, is a disease that affects many species of mammals, including several wild ungulate species in the region of the European Alps, especially the Alpine chamois and the Alpine ibex, which act as parasite reservoirs. Here records of mange in alpine wild ungulates and its spread over time across the eastern parts of the European Alps are reviewed. First cases were recorded from Austria in 1824, and epizootic outbreaks have been described since then from the mountainous regions of Austria (mostly Tyrol, Carinthia, and Styria), Germany (Bavaria), Italy (Udine and Trentino) and Slovenia. Switzerland, by contrast, has so far been free of mange except for cases in wild boar, indicating that this species is not a reservoir host of sarcoptic mites for other ungulate species in the European Alps, and that, so far, the disease in ruminant ungulates is restricted to the eastern and central parts of the Alps. Mutual transmission among wild and domestic ruminants is possible and, together with the protection of vulnerable wildlife, is also a reason for monitoring and, if necessary, intervention to contain mange outbreaks.