Decreased FXR Agonism in the Bile Acid Pool Is Associated with Impaired FXR Signaling in a Pig Model of Pediatric NAFLD.

The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected.

Ultrasound-Guided Infraclavicular Axillary Vein Versus Internal Jugular Vein Cannulation in Critically Ill Mechanically Ventilated Patients: A Randomized Trial.

Objectives: This clinical trial aimed to compare the ultrasound-guided in-plane infraclavicular cannulation of the axillary vein (AXV) and the ultrasound-guided out-of-plane cannulation of the internal jugular vein (IJV).

Design: A prospective, single-blinded, open label, parallel-group, randomized trial.

Setting: Two university-affiliated ICUs in Poland (Opole and Lublin).

Olive- and Coconut-Oil-Enriched Diets Decreased Secondary Bile Acids and Regulated Metabolic and Transcriptomic Markers of Brain Injury in the Frontal Cortexes of NAFLD Pigs.

The objective of this study was to investigate the effect of dietary fatty acid (FA) saturation and carbon chain length on brain bile acid (BA) metabolism and neuronal number in a pig model of pediatric NAFLD. Thirty 20-day-old Iberian pigs, pair-housed in pens, were randomly assigned to receive one of three hypercaloric diets for 10 weeks: (1) lard-enriched (LAR; = 5 pens), (2) olive-oil-enriched (OLI, = 5), and (3) coconut-oil-enriched (COC; = 5). Pig behavior and activity were analyzed throughout the study.

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: ) lard-enriched (LAR; = 5 pens), ) olive oil-enriched (OLI; = 5), and ) coconut oil-enriched (COC; = 5). Animals were euthanized on after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics.

Establishing a New ECMO Referral Center Using an ICU-Based Approach: A Feasibility and Safety Study.

Background: A high-volume center with a multidisciplinary team is regarded as the optimal place for providing extracorporeal membrane oxygenation (ECMO). We hypothesize that an ECMO center can also be successfully created and subsequently developed entirely by intensivists in a mid-size mixed intensive care unit (ICU).

Methods: A model was created for setting up a new ECMO referral center within the structure of an existing mixed ICU in a tertiary hospital.

Oral Administration of Coronavirus Spike Protein Provides Protection to Newborn Pigs When Challenged with PEDV.

To investigate whether oral administration of maize-produced S antigen can provide passive immunity to piglets against porcine epidemic diarrhea virus (PEDV), 16 pregnant sows were randomly assigned to one of four treatments: (1) injection of PEDV vaccine (INJ), (2) maize grain without S protein (CON), (3) maize grain containing low dose of S antigen (LOV) and (4) maize grain containing a high dose of S antigen (HOV). Vaccines were administered on days 57, 85 and 110 of gestation. Sows' serum and colostrum were collected at farrowing and milk on day 6 post-challenge to quantify neutralizing antibodies (NABs) and cytokines.

High-Fructose, High-Fat Diet Alters Muscle Composition and Fuel Utilization in a Juvenile Iberian Pig Model of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a serious metabolic condition affecting millions of people worldwide. A "Western-style diet" has been shown to induce pediatric NAFLD with the potential disruption of skeletal muscle composition and metabolism. To determine the in vivo effect of a "Western-style diet" on pediatric skeletal muscle fiber type and fuel utilization, 28 juvenile Iberian pigs were fed either a control diet (CON) or a high-fructose, high-fat diet (HFF), with or without probiotic supplementation, for 10 weeks.

Effect of Season and Parity on Reproduction Performance of Iberian Sows Bred with Duroc Semen.

The Iberian pig is an autochthonous breed from the Iberian Peninsula highly valued for its meat. The sows are often bred as Iberian × Duroc crossings for increased efficiency. Since sow parity and season affect the reproductive performance, we evaluated two-year records from a commercial farrow-to-finish farm (live, stillborn, and mummified piglets after artificial insemination, AI).

The Suinfort Semen Supplement Counters Seasonal Infertility in Iberian Sows.

Suinfort, a commercial semen supplement demonstrated to increase fertility and litter size in commercial sows, was tested to improve reproductive performance in Iberian sows. A total of 1430 Iberian sows were artificially inseminated (AI) with semen from Duroc boars and assigned by parity to receive the seminal additive Suinfort containing 2 IU oxytocin, 5 µg lecirelin, and 2 mM caffeine (SF; = 1713 AI), or to serve as non-supplemented controls (CON; = 2625 AI). CON showed a lower fertility comparing to winter for spring ( = 0.

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.

%polynova_2way: A SAS macro for implementation of mixed models for metabolomics data.

The generation of large metabolomic data sets has created a high demand for software that can fit statistical models to one-metabolite-at-a-time on hundreds of metabolites. We provide the %polynova_2way macro in SAS to identify metabolites differentially expressed in study designs with a two-way factorial treatment and hierarchical design structure. For each metabolite, the macro calculates the least squares means using a linear mixed model with fixed and random effects, runs a 2-way ANOVA, corrects the P-values for the number of metabolites using the false discovery rate or Bonferroni procedure, and calculate the P-value for the least squares mean differences for each metabolite.

Intermittent leucine pulses during continuous feeding alters novel components involved in skeletal muscle growth of neonatal pigs.

When neonatal pigs continuously fed formula are supplemented with leucine pulses, muscle protein synthesis and body weight gain are enhanced. To identify the responsible mechanisms, we combined plasma metabolomic analysis with transcriptome expression of the transcriptome and protein catabolic pathways in skeletal muscle. Piglets (n = 23, 7-day-old) were fed continuously a milk replacement formula via orogastric tube for 21 days with an additional parenteral infusion (800 μmol kg h) of either leucine (LEU) or alanine (CON) for 1 h every 4 h.

Neurodegeneration in juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease.

The objective of this study was to investigate whether juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease (NAFLD), cholestasis, and gut dysbiosis would develop histological and metabolic markers of neurodegeneration in the frontal cortex (FC) and whether supplementing probiotics would influence the response to the diet. Twenty-eight juvenile Iberian pigs were fed for 10 wk either a control (CON) or high-fructose high-fat (HFF) diet with or without a commercial probiotic mixture. Compared with CON, HFF-fed pigs had a decreased number of neurons and an increase in reactive astrocytes in FC tissue.

Ovulatory Response of Weaned Sows to an Altered Ratio of Exogenous Gonadotrophins.

At weaning, 33 mixed parity Hypor sows received either an injection of 400 IU equine chorionic gonadotrophin and 200 IU human chorionic gonadotrophin (hCG) (PG600; 13), PG600 with an additional 200 IU hCG 24 h later (Gn800; 11), or served as non-injected controls ( 9). All gonadotrophin treated sows received an injection of 750 IU hCG at 80 h after weaning to induce ovulation (designated as time 0 h). At 0, 24, 36, 40, 44, 48, and 60 h, all sows were subject to transrectal ultrasonography to determine numbers and sizes of large (>6 mm) follicles and time of ovulation.

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.

Rapid Postnatal Upregulation of Intestinal Farnesoid X Receptor-Fibroblast Growth Factor 19 Signaling in Premature Pigs.

Objectives: Bile acid (BA) homeostasis is regulated by intestinal cellular signaling involving the farnesoid X receptor (FXR) and fibroblast growth factor 19 (FGF19) secretion. Using preterm and term pigs as a model, we examined postnatal changes in expression of the FXR-FGF19 axis that is poorly characterized in human infants.

Methods: Pigs delivered by caesarean section at 10-day preterm and near full term (115-day gestation) were fitted with orogastric and umbilical arterial catheters.

20 Years of Secretagogin: Exocytosis and Beyond.

Calcium is one of the most important signaling factors in mammalian cells. Specific temporal and spatial calcium signals underlie fundamental processes such as cell growth, development, circadian rhythms, neurotransmission, hormonal actions and apoptosis. In order to translate calcium signals into cellular processes a vast number of proteins bind this ion with affinities from the nanomolar to millimolar range.

Analysis of the Paternally-Imprinted DLK1-MEG3 and IGF2-H19 Tandem Gene Loci in NT2 Embryonal Carcinoma Cells Identifies DLK1 as a Potential Therapeutic Target.

The paternally-imprinted genes insulin-like growth factor 2 (IGF2), H19, delta-like homologue 1 (DLK1), and maternally-expressed gene 3 (MEG3) are expressed from the tandem gene loci IGF2-H19 and DLK1-MEG3, which play crucial roles in initiating embryogenesis and development. The erasure of imprinting (EOI) at differentially methylated regions (DMRs) which regulate the expression of these genes maintains the developmental quiescence of primordial germ cells (PGCs) migrating through the embryo proper during embryogenesis and prevents them from forming teratomas. To address the potential involvement of the IGF2-H19 and DLK1-MEG3 loci in the pathogenesis of embryonal carcinoma (EC), we investigated their genomic imprinting at DMRs in the human PGC-derived EC cell line NTera-2 (NT2).

Sulodexide Slows Down the Senescence of Aortic Endothelial Cells Exposed to Serum from Patients with Peripheral Artery Diseases.

Background/aims: Aging of the arterial endothelial cells results in the appearance of their inflammatory phenotype, which may predispose patients to the acceleration of arteriosclerosis. We studied the effect of serum from patients with peripheral artery disease (PAD) on the senescence of human aortic endothelial cells (HAEC) and how that process is modulated by sulodexide.

Methods: HAEC replicative aging in vitro was studied in the presence of 10% PAD-serum (PAD Group) or10%PAD serum and Sulodexide 0.

Vitamin D kinetics in the acute phase of critical illness: A prospective observational study.

Purpose: The objective of this study was to assess the vitamin D kinetics in critically ill patients by performing periodic serum vitamin D measurements in short time intervals in the initial phase of a critical illness.

Materials And Methods: We performed vitamin D serum measurements: at admission and then in 12-hour time intervals. The minimum number of vitamin D measurements was 4, and the maximum was 8 per patient.

Inhibition of Mitochondrial p53 Accumulation by PFT-μ Prevents Cisplatin-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN), a debilitating major side effect of cancer treatment, is characterized by pain and sensory loss in hand and feet. Platinum-based chemotherapeutics like cisplatin frequently induce CIPN. The molecular mechanism underlying these neurotoxic symptoms is incompletely understood and there are no preventive or curative interventions.

Sulodexide Reduces the Proinflammatory Effect of Serum from Patients with Peripheral Artery Disease in Human Arterial Endothelial Cells.

Background/aims: Dysfunction of the arterial endothelial cells promotes the progression of atherosclerosis. We studied how exposure of human arterial endothelial cells to atherosclerotic serum from patients with peripheral artery disease changes the secretory activity of these cells, and whether that reaction is modified by sulodexide.

Methods: Endothelial cells in in vitro culture were exposed to standard culture medium ± 100pg/mL Interleukin-1(IL-1) or to medium supplemented with 20% atherosclerotic serum.

Pifithrin-μ Prevents Cisplatin-Induced Chemobrain by Preserving Neuronal Mitochondrial Function.

Cognitive impairment, termed chemobrain, is a common neurotoxicity associated with chemotherapy treatment, affecting an estimated 78% of patients. Prompted by the hypothesis that neuronal mitochondrial dysfunction underlies chemotherapy-induced cognitive impairment (CICI), we explored the efficacy of administering the small-molecule pifithrin (PFT)-μ, an inhibitor of mitochondrial p53 accumulation, in preventing CICI. Male C57BL/6J mice injected with cisplatin ± PFT-μ for two 5-day cycles were assessed for cognitive function using novel object/place recognition and alternation in a Y-maze.

The Microtubule-Associated Protein Tau and Its Relevance for Pancreatic Beta Cells.

Structural and biochemical alterations of the microtubule-associated protein tau (MAPT) are associated with degenerative disorders referred to as tauopathies. We have previously shown that MAPT is present in human islets of Langerhans, human insulinomas, and pancreatic beta-cell line models, with biophysical similarities to the pathological MAPT in the brain. Here, we further studied MAPT in pancreatic endocrine tissue to better understand the mechanisms that lead to functional dysregulation of pancreatic beta cells.

The cell cycle- and insulin-signaling-inhibiting miRNA expression pattern of very small embryonic-like stem cells contributes to their quiescent state.

Murine Oct4(+), very small embryonic-like stem cells (VSELs), are a quiescent stem cell population that requires a supportive co-culture layer to proliferate and/or to differentiate in vitro. Gene expression studies have revealed that the quiescence of these cells is due to changes in expression of parentally imprinted genes, including genes involved in cell cycle regulation and insulin and insulin-like growth factor signaling (IIS). To investigate the role of microRNAs (miRNAs) in VSEL quiescence, we performed miRNA studies in highly purified VSELs and observed a unique miRNA expression pattern in these cells.