Dietary fat composition shapes bile acid metabolism and severity of liver injury in a pig model of pediatric NAFLD.

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD.NEW & NOTEWORTHY Bile acid homeostasis and signaling is disrupted in NAFLD and may play a central role in the development of the disease. However, there are no studies addressing the impact of diet on bile acid metabolism in patients with NAFLD. In juvenile Iberian pigs, we show that fatty acid composition in high-fat high-fructose diets affects BA levels in liver, plasma, and colon but these changes were not associated with the severity of the disease.

Ni-Doped Ordered Nanoporous Carbon Prepared from Chestnut Wood Tannins for the Removal and Photocatalytic Degradation of Methylene Blue.

In this work, Ni-doped ordered nanoporous carbon was prepared by a simple and green one-pot solvent evaporation induced self-assembly process, where chestnut wood tannins were used as a precursor, Pluronic® F-127 as a soft template, and Ni2+ as a crosslinking agent and catalytic component. The prepared carbon exhibited a 2D hexagonally ordered nanorod array mesoporous structure with an average pore diameter of ~5 nm. Nickel was found to be present on the surface of nanoporous carbon in the form of nickel oxide, nickel hydroxide, and metallic nickel. Nickel nanoparticles, with an average size of 13.1 nm, were well dispersed on the carbon surface. The synthesized carbon was then tested for the removal of methylene blue under different conditions. It was found that the amount of methylene blue removed increased with increasing pH and concentration of carbon but decreased with increasing concentration of methylene blue. Furthermore, photocatalytic tests carried out under visible light illumination showed that purple light had the greatest effect on the methylene blue adsorption/degradation, with the maximum percent degradation achieved at ~4 h illumination time, and that the percent degradation at lower concentrations of methylene blue was much higher than that at higher concentrations. The adsorption/degradation process exhibited pseudo second-order kinetics and strong initial adsorption, and the prepared carbon showed high magnetic properties and good recyclability.

Consumption of High-Fructose Corn Syrup Compared with Sucrose Promotes Adiposity and Increased Triglyceridemia but Comparable NAFLD Severity in Juvenile Iberian Pigs.

BACKGROUND: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated. OBJECTIVES: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity. METHODS: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = 3 pens; 281.6-486.8 g/kg diet) or HFCS (n = 4; 444.3-724.8 g/kg diet) during 16 wk. Diets exceeded the animal's energy requirements by providing sugars in excess, but met the requirements for all other nutrients. Animals were killed at 165 d of age after blood sampling, and liver, muscle, and gut were collected for histology, metabolome, and microbiome analyses. Data were analyzed by multivariate and univariate statistics. RESULTS: Compared with SUC, HFCS increased subcutaneous fat, triacylglycerides in plasma, and butyrate in colon (P ≤ 0.05). In addition, HFCS decreased UMP and short-chain acyl carnitines in liver, and urea nitrogen and creatinine in serum (P ≤ 0.05). Microbiome analysis showed a 24.8% average dissimilarity between HFCS and SUC associated with changes in SCFA-producing bacteria. Body weight gain, intramuscular fat, histological and serum markers of liver injury, and circulating hormones, glucose, and proinflammatory cytokines did not differ between diets. CONCLUSIONS: Fructose consumption derived from HFCS promoted butyrate synthesis, triglyceridemia, and subcutaneous lipid deposition in juvenile Iberian pigs, but did not increase serum and histological markers of NAFLD compared with a sucrose-enriched diet. Longer studies could be needed to observe differences in liver injury among sugar types.

Dysregulated FXR-FGF19 signaling and choline metabolism are associated with gut dysbiosis and hyperplasia in a novel pig model of pediatric NASH.

To investigate the role of bile acids (BAs) in the pathogenesis of diet-induced nonalcoholic steatohepatitis (NASH), we fed a "Western-style diet" [high fructose, high fat (HFF)] enriched with fructose, cholesterol, and saturated fat for 10 wk to juvenile Iberian pigs. We also supplemented probiotics with in vitro BA deconjugating activity to evaluate their potential therapeutic effect in NASH. Liver lipid and function, cytokines, and hormones were analyzed using commercially available kits. Metabolites, BAs, and fatty acids were measured by liquid chromatography-mass spectrometry. Histology and gene and protein expression analyses were performed using standard protocols. HFF-fed pigs developed NASH, cholestasis, and impaired enterohepatic Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in the absence of obesity and insulin resistance. Choline depletion in HFF livers was associated with decreased lipoprotein and cholesterol in serum and an increase of choline-containing phospholipids in colon contents and trimethylamine-N-oxide in the liver. Additionally, gut dysbiosis and hyperplasia increased with the severity of NASH, and were correlated with increased colonic levels of choline metabolites and secondary BAs. Supplementation of probiotics in the HFF diet enhanced NASH, inhibited hepatic autophagy, increased excretion of taurine and choline, and decreased gut microbial diversity. In conclusion, dysregulation of BA homeostasis was associated with injury and choline depletion in the liver, as well as increased biliary secretion, gut metabolism and excretion of choline-based phospholipids. Choline depletion limited lipoprotein synthesis, resulting in hepatic steatosis, whereas secondary BAs and choline-containing phospholipids in colon may have promoted dysbiosis, hyperplasia, and trimethylamine synthesis, causing further damage to the liver.NEW & NOTEWORTHY Impaired Farnesoid-X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling and cholestasis has been described in nonalcoholic fatty liver disease (NAFLD) patients. However, therapeutic interventions with FXR agonists have produced contradictory results. In a swine model of pediatric nonalcoholic steatohepatitis (NASH), we show that the uncoupling of intestinal FXR-FGF19 signaling and a decrease in FGF19 levels are associated with a choline-deficient phenotype of NASH and increased choline excretion in the gut, with the subsequent dysbiosis, colonic hyperplasia, and accumulation of trimethylamine-N-oxide in the liver.

Prematurity reduces citrulline-arginine-nitric oxide production and precedes the onset of necrotizing enterocolitis in piglets.

Necrotizing enterocolitis (NEC) is associated with low plasma arginine and vascular dysfunction. It is not clear whether low intestinal citrulline production, the precursor for arginine synthesis, occurs before and thus predisposes to NEC or if it results from tissue damage. This study was designed to test the hypothesis that whole body rates of citrulline, arginine, and nitric oxide synthesis are low in premature pigs and that they precede NEC. Piglets delivered by cesarean section at 103 days [preterm (PT)], 110 days [near-term (NT)], or 114 days [full-term (FT)] of gestation were given total parenteral nutrition and after 2 days orogastrically fed infant formula for 42 h to induce NEC. Citrulline and arginine fluxes were determined before and during the feeding protocol. Gross macroscopic and histological NEC scores and plasma fatty acid binding protein (iFABP) concentration were determined as indicators of NEC. Intestinal gene expression for enzymes of the arginine pathway were quantitated. A lower ( P < 0.05) survival rate was observed for PT (8/27) than for NT (9/9) and FT pigs (11/11). PT pigs had higher macroscopic gross ( P < 0.05) and histological NEC ( P < 0.05) scores and iFABP concentration ( P < 0.05) than pigs of more advanced gestational age. PT pigs had lower citrulline production and arginine fluxes ( P < 0.05) throughout and a reduced gene expression in genes of the citrulline-arginine pathway. In summary, intestinal enzyme expression and whole body citrulline and arginine fluxes were reduced in PT pigs compared with animals of more advance gestational age and preceded the development of NEC. NEW & NOTEWORTHY Arginine supplementation prevents necrotizing enterocolitis (NEC), the most common gastrointestinal emergency of prematurity. Citrulline (precursor for arginine) production is reduced during NEC, and this is believed to be a consequence of intestinal damage. In a swine model of NEC, we show that intestinal gene expression of the enzymes for citrulline production and whole body citrulline and arginine fluxes are reduced and precede the onset of NEC in premature pigs. Reduced citrulline production during prematurity may be a predisposition to NEC.

Basins of attraction in human balance.

Falls are a recognized risk factor for unintentional injuries among older adults, accounting for a large proportion of fractures, emergency department visits, and urgent hospitalizations. Human balance and gait research traditionally uses linear or qualitative tests to assess and describe human motion; however, human motion is neither a simple nor a linear process. The objective of this research is to identify and to learn more about what factors affect balance using nonlinear dynamical techniques, such as basin boundaries. Human balance data was collected using dual force plates for leans using only ankle movements as well as for unrestricted leans. Algorithms to describe the basin boundary were created and compared based on how well each method encloses the experimental data points as well as captures the differences between the two leaning conditions.

Comparison of axillary, tympanic membrane and rectal temperature measurement in cats.

OBJECTIVES: Rectal temperature (RT) is routinely used to assess body temperature in cats but has limitations and can be poorly tolerated. Axillary temperature (AT) and tympanic membrane temperature (TMT) are reported alternatives. This study aimed to determine the differences between RT and AT, and between RT and TMT in cats. Additional aims were to examine the effect of environmental and patient factors on these differences and to assess patient tolerance to each technique. METHODS: AT, TMT and RT were measured in immediate succession. Measurement order was randomised, as was the choice of left or right axilla and tympanic membrane. A digital thermometer and a veterinary infrared ear thermometer were used. The subjective tolerance of each procedure was recorded. RESULTS: One hundred and fifty cats were included. Significantly more conscious cats were tolerant of AT (90.6%) than TMT (81.2%) and RT (53.0%). The rectal-axillary temperature difference ranged from -1.2°C to 1.4°C (median 0.1°C) and was within ± 0.5°C in 78.0% of cats. On multivariable analysis the difference was larger in overweight cats, neutered cats, cats in which the right axilla was used and as the RT increased. The rectal-tympanic membrane temperature difference ranged from -1.6°C to 3°C (median -0.3°C) and was within ± 0.5°C in 51.3% of cats, significantly fewer than for AT (P <0.001). The rectal-tympanic membrane temperature difference increased as the RT increased. CONCLUSIONS AND RELEVANCE: TMT and AT should not be used interchangeably with RT in cats. When RT measurement is not possible, AT is recommended over TMT as it is better tolerated and significantly fewer cats had clinically unacceptable differences (>0.5°C). AT may more closely reflect RT in normal or underweight cats than it does in overweight cats.

The use of an alternate light source for detecting bones underwater.

When searching underwater crime scenes or disaster scenes for fragmentary human remains, it may be advantageous for forensic divers to be able to detect the presence of bones and teeth among other marine materials (such as shells and rocks). In terrestrial environments, this can typically be accomplished by visual and instrumental methods, but underwater conditions make it difficult to employ detection and sorting techniques in these environments. This study investigates fluorescence of bones and teeth and other marine materials using a submersible alternate light source (ALS) and concludes that an ALS can be a useful tool for detecting bones and teeth in underwater searches as well in terrestrial searches and laboratory environments. The results could impact the methods and equipment used by forensic divers and forensic anthropologists when searching for skeletal remains, potentially increasing the quantity and efficiency of forensic evidence recovered.

Rib butterfly fractures as a possible indicator of blast trauma.

Forensic anthropologists have become increasingly involved in the interpretation of skeletal trauma caused by exploding ordnance. This study examines the cause and significance of butterfly fractures observed in a recent study investigating skeletal blast trauma by Christensen et al. Fractured ribs resulting from blast events carried out in the original study were re-examined revealing that rib butterfly fractures with the tensile indicator on the visceral surface were present in 100% of viable pig specimens. Additionally, manual fracture testing was performed on 46 pig ribs to simulate the bending force believed to have been sustained in the original blast events. Fracture testing resulted in 93% of specimens presenting butterfly fractures with the tensile indicator on the visceral surface. This fracture pattern differs significantly from that normally observed in association with other types of trauma events and may aid forensic anthropologists and other investigators in the identification and interpretation of blast events.

Primary and secondary skeletal blast trauma.

This study examines primary (resulting from blast wave) and secondary (resulting from disintegrated, penetrating fragments) blast trauma to the skeleton. Eleven pigs were exposed to semi-controlled blast events of varying explosive type, charge size, and distance, including some cases with shrapnel. Skeletal trauma was found to be extensive, presenting as complex, comminuted fractures with numerous small, displaced bone splinters and fragments. Traumatic amputation of the limbs and cranium was also observed. Fractures were concentrated in areas nearer the blast, but there was generally no identifiable point of impact. Fractures were more random in appearance and widespread than those typically associated with gunshot or blunt force injury events. These patterns appear to be uniquely associated with blast trauma and may therefore assist forensic anthropologists and other forensic examiners in the interpretation of skeletal trauma by enabling them to differentiate between blast trauma and trauma resulting from some other cause.

The reliability of visually comparing small frontal sinuses.

Several studies have investigated frontal sinus comparison for personal identification. One study addressed the statistical reliability of correct identification using automated digital methods and resulted in a 96% accuracy rate. Missed matches with the digital methods generally involved small, less featured sinuses. This study investigates the hypothesis that human examiners may be able to more accurately identify correct matches than digital methods, even when the comparisons involve small frontal sinuses. Participants were provided two sets of 28 radiographs and were instructed to identify matching radiographs and list the radiographs that did not have a corresponding match. Overall, error rates were low, with correct associations identified at a rate of 0.983. No incorrect associations ("false positives") were made. Correct association rates were highest among participants "experienced" examining radiographs. Results support previous assertions that frontal sinus radiographs are a reliable means of personal identification even when the frontal sinuses are small.