Deciphering the Association of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice.

The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146-157 peptide to the neuropathologies.

Gut-brain axis interplay via STAT3 pathway: Implications of Helicobacter pylori derived secretome on inflammation and Alzheimer's disease.

Helicobacter pylori is a pathogenic bacterium that causes gastritis and gastric carcinoma. Besides gastric complications its potential link with gut-brain axis disruption and neurological disorders has also been reported. The current study investigated the plausible role and its associated molecular mechanism underlying H. pylori mediated gut-brain axis disruption and neuroinflammation leading to neurological modalities like Alzheimer's disease (AD). We have chosen the antimicrobial resistant and susceptible H. pylori strains on the basis of broth dilution method. We have observed the increased inflammatory response exerted by H. pylori strains in the gastric as well as in the neuronal compartment after treatment with Helicobacter pylori derived condition media (HPCM). Further, elevated expression of STAT1, STAT3, and AD-associated proteins- APP and APOE4 was monitored in HPCM-treated neuronal and neuron-astrocyte co-cultured cells. Excessive ROS generation has been found in these cells. The HPCM treatment to LN229 causes astrogliosis, evidenced by increased glial fibrillary acidic protein. Our results indicate the association of STAT3 as an important regulator in the H. pylori-mediated pathogenesis in neuronal cells. Notably, the inhibition of STAT3 by its specific inhibitor, BP-1-102, reduced the expression of pSTAT3 and AD markers in neuronal compartment induced by HPCM. Thus, our study demonstrates that H. pylori infection exacerbates inflammation in AGS cells and modulates the activity of STAT3 regulatory molecules. H. pylori secretome could affect neurological compartments by promoting STAT3 activation and inducing the expression of AD-associated signature markers. Further, pSTAT-3 inhibition mitigates the H. pylori associated neuroinflammation and amyloid pathology.

Nutrition assessment and MASH severity in children using the Healthy Eating Index.

BACKGROUND: Pediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD. METHODS: Diet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components. RESULTS: In all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index Z-score of 2.2 ± 0.5. Diet was classified as low HEI < 47.94 (n = 39), mid HEI ≥ 47.94 and < 58.89 (n = 41), or high HEI ≥ 58.89 (n=39). Children with high HEI (healthier diet) had lower body weight (p = 0.005) and more favorable lipids. Mean serum triglycerides for low, mid, and high HEI were 163, 148, and 120 mg/dL, respectively; p = 0.04 mid versus high, p = 0.01 low versus high. Mean HDL was 38, 41 and 43 mg/dL; p = 0.02 low vs high. Less severe steatosis was noted with added sugar ≤ 10% of calories (p = 0.03). Higher lobular inflammation is associated with a higher percentage of calories from fat (OR (95% CI) = 0.95 (0.91-1.00), p = 0.04). CONCLUSIONS: In children with MAFLD, high HEI is associated with lower body weight and more favorable lipids, while added sugar and fat intake has individual histologic features. Differential consumption of major dietary components may modify both metabolic risk factors and histologic liver injury, highlighting the importance of objective diet assessments in children with MAFLD.

Comprehensive insight into altered host cell-signaling cascades upon Helicobacter pylori and Epstein-Barr virus infections in cancer.

Cancer is characterized by mutagenic events that lead to disrupted cell signaling and cellular functions. It is one of the leading causes of death worldwide. Literature suggests that pathogens, mainly Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with the etiology of human cancer. Notably, their co-infection may lead to gastric cancer. Pathogen-mediated DNA damage could be the first and crucial step in the carcinogenesis process that modulates numerous cellular signaling pathways. Altogether, it dysregulates the metabolic pathways linked with cell growth, apoptosis, and DNA repair. Modulation in these pathways leads to abnormal growth and proliferation. Several signaling pathways such RTK, RAS/MAPK, PI3K/Akt, NFκB, JAK/STAT, HIF1α, and Wnt/ß-catenin are known to be altered in cancer. Therefore, this review focuses on the oncogenic roles of H. pylori, EBV, and its associated signaling cascades in various cancers. Scrutinizing these signaling pathways is crucial and may provide new insights and targets for preventing and treating H. pylori and EBV-associated cancers.

Redefining Lobe-Wise Ground-Glass Opacity in COVID-19 Through Deep Learning and its Correlation With Biochemical Parameters.

During COVID-19 pandemic qRT-PCR, CT scans and biochemical parameters were studied to understand the patients' physiological changes and disease progression. There is a lack of clear understanding of the correlation of lung inflammation with biochemical parameters available. Among the 1136 patients studied, C-reactive-protein (CRP) is the most critical parameter for classifying symptomatic and asymptomatic groups. Elevated CRP is corroborated with increased D-dimer, Gamma-glutamyl-transferase (GGT), and urea levels in COVID-19 patients. To overcome the limitations of manual chest CT scoring system, we segmented the lungs and detected ground-glass-opacity (GGO) in specific lobes from 2D CT images by 2D U-Net-based deep learning (DL) approach. Our method shows accuracy, compared to the manual method (  âˆ¼ 80%), which is subjected to the radiologist's experience. We determined a positive correlation of GGO in the right upper-middle (0.34) and lower (0.26) lobe with D-dimer. However, a modest correlation was observed with CRP, ferritin and other studied parameters. The final Dice Coefficient (or the F1 score) and Intersection-Over-Union for testing accuracy are 95.44% and 91.95%, respectively. This study can help reduce the burden and manual bias besides increasing the accuracy of GGO scoring. Further study on geographically diverse large populations may help to understand the association of the biochemical parameters and pattern of GGO in lung lobes with different SARS-CoV-2 Variants of Concern's disease pathogenesis in these populations.

Data on differential pathogenic ability of Helicobacter pylori isolated from distinct gastric niches.

Helicobacter pylori infection is associated with various gastrointestinal diseases and gastric cancer. Our data shows the H. pylori isolates and their associated pathology, isolated from two different stomach niches: gastric epithelium and gastric juice. Gastric adenocarcinoma (AGS) cells were infected with H. pylori juice (HJ1, HJ10 and HJ14) and biopsy (HB1, HB10 and HB14) isolates for 6, 12 and 24 hrs. To determine the cell migration ability of the infected cells, scratch wound assay was performed. The decrease in the wound area was measured by Image J software. Status of cell proliferation accessed by counting the cell number through trypan blue exclusion method. Further assessment of pathogenic potential and carcinogenic ability of the isolates was done by determining the genomic instability in the cell post infection. Cells were stained with DAPI and number of micro and macro nuclei was counted in the acquired images. The data will be helpful in understanding the difference in the carcinogenic ability of H. pylori with respect to their physiological niche.

Endoscopic Ultrasound-Guided Pancreatic Pseudocyst Drainage in Children: A Case Series.

Over the last one-decade, endoscopic ultrasound (EUS)-guided drainage has evolved as a preferred modality for treating pseudocyst over conventional surgical or radiological procedures among adults using plastic stents or lumen opposing stents; however, studies on EUS-guided pancreatic of pseudocyst among children are mainly in the form of case reports or small case series. Therefore, we aimed to describe four pediatric cases of the pseudo-pancreatic cyst treated successfully with EUS-guided cysto-gastrostomy using plastic stents. In all four cases, EUS-guided drainage was successful using plastic stent with no major complications, and none of them required any follow-up endoscopic or surgical intervention. EUS-guided cysto-gastrostomy offers an excellent and safe alternative to surgery for treating pancreatic pseudocysts in children.

Lower systemic inflammation is associated with gut firmicutes dominance and reduced liver injury in a novel ambulatory model of parenteral nutrition.

BACKGROUND: Total Parenteral Nutrition (TPN) provides lifesaving nutritional support to patients unable to maintain regular enteral nutrition (EN). Unfortunately, cholestasis is a significant side effect affecting 20-40% of paediatric patients. While the aetiology of TPN-associated injury remains ill-defined, an altered enterohepatic circulation in the absence of gut luminal nutrient content during TPN results in major gut microbial clonal shifts, resulting in metabolic endotoxemia and systemic inflammation driving liver injury and cholestasis. HYPOTHESIS: To interrogate the role of gut microbiota, using our novel ambulatory TPN piglet model, we hypothesized that clonal reduction of bacteria in Firmicutes phylum (predominant in EN) and an increase in pathogenic Gram-negative bacteria during TPN correlates with an increase in serum lipopolysaccharide and systemic inflammatory cytokines, driving liver injury. METHODS: Upon institutional approval, 16 animals were allocated to receive either TPN (n = 7) or EN only (n = 9). The TPN group was subdivided into a low systemic inflammation (TPN-LSI) and high systemic inflammation (TPN-HSI) based on the level of serum lipopolysaccharide. Culture-independent identification of faecal bacterial populations was determined by 16S rRNA. RESULTS: Piglets on TPN, in the TPN-HSI group, noted a loss of enterocyte protective Firmicutes bacteria and clonal proliferation of potent inflammatory and lipopolysaccharide containing pathogens: Fusobacterium, Bacteroidetes and Campylobacter compared to EN animals. Within the TPN group, the proportion of Firmicutes phylum correlated with lower portal lipopolysaccharide levels (r = -0.89). The TPN-LSI had a significantly lower level of serum bile acids compared to the TPN-HSI group (7.3 vs. 60.4 mg/dL; p = .018), increased day 14 weight (5.67 vs. 5.07 kg; p = .017) as well as a 13.7-fold decrease in serum conjugated bilirubin. CONCLUSION: We demonstrate a novel relationship between the gut microbiota and systemic inflammation in a TPN animal model. Pertinently, the degree of gut dysbiosis correlated with the severity of systemic inflammation. This study underscores the role of gut microbiota in driving liver injury mechanisms during TPN and supports a paradigm change in therapeutic targeting of the gut microbiota to mitigate TPN-related injury. KEY MESSAGESThis study identified a differential link between gut microbiota and inflammation-the higher the dysbiosis, the worse the systemic inflammatory markers.Higher levels of Firmicutes species correlated with reduced inflammation.

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy.

BACKGROUND: Almost 9%of deceased donor livers are discarded as marginal donor livers (MDL) due to concern of severe ischemia reperfusion injury (IRI). Emerging data supports ferroptosis (iron regulated hepatocellular death) as an IRI driver, however lack of robust preclinical model limits therapeutic testing. In this manuscript we describe the development of a novel rigorous internal control system utilizing normothermic perfusion of split livers to test ferroptosis regulators modulating IRI. METHODS: Upon institutional approval, split human MDLs were placed on our normothermic perfusion machine, Perfusion Regulated Organ Therapeutics with Enhanced Controlled Testing (PROTECT), pumping arterial and portal blood. Experiment 1 compared right (UR) and left (UL) lobes to validate PROTECT. Experiment 2 assessed ferroptosis regulator Deferoxamine in Deferoxamine Agent Treated (DMAT) vs. No Agent Internal Control (NAIC) lobes. Liver serology, histology, and ferroptosis genes were assessed. RESULTS: Successful MDL perfusion validated PROTECT with no ALT or AST difference between UR and UL (∆ALT UR: 235, ∆ALT UL: 212; ∆AST UR: 576, ∆AST UL: 389). Liver injury markers increased in NAIC vs. DMAT (∆ALT NAIC: 586, ∆ALT DMAT: -405; ∆AST NAIC: 617, ∆AST DMAT: -380). UR and UL had similar expression of ferroptosis regulators RPL8,HO-1 and HIFα. Significantly decreased intrahepatic iron (p = .038), HO-1 and HIFα in DMAT (HO-1 NAIC: 6.93, HO-1 DMAT: 2.74; HIFαNAIC: 8.67, HIFαDMAT: 2.60)and no hepatocellular necrosis or immunohistochemical staining (Ki67/Cytokeratin-7) differences were noted. CONCLUSION: PROTECT demonstrates the therapeutic utility of a novel normothermic perfusion split liver system for drug discovery and rapid translatability of therapeutics, driving a paradigm change in organ recovery and transplant medicine. Our study using human livers, provides preliminary proof of concept for the novel role of ferroptosis regulators in driving IRI.

Status of kinases in Epstein-Barr virus and Helicobacter pylori Coinfection in gastric Cancer cells.

BACKGROUND: Helicobacter pylori (H. pylori) and Epstein - Barr virus (EBV) plays a significant role in aggressive gastric cancer (GC). The investigation of genes associated with these pathogens and host kinases may be essential to understand the early and dynamic progression of GC. AIM: The study aimed to demonstrate the coinfection of EBV and H. pylori in the AGS cells through morphological changes, expression of the kinase and the probable apoptotic pathways. METHODS: Genomic DNA isolation of H. pylori and its characterization from clinical samples were performed. RT-qPCR of kinases was applied to scrutinize the gene expression of kinases in co-infected GC in a direct and indirect (separated through insert size 0.45 µm) H. pylori infection set up. Morphological changes in co-infected GC were quantified by measuring the tapering ends of gastric epithelial cells. Gene expression profiling of apoptotic genes was assessed through RT-qPCR. RESULTS: An interleukin-2-inducible T-cell kinase (ITK) showed significant upregulation with indirect H. pylori infection. Moreover, Ephrin type-B receptor six precursors (EPHB6) and Tyrosine-protein kinase Fyn (FYN) showed significant upregulation with direct coinfection. The tapering ends in AGS cells were found to be extended after 12 h. A total of 24 kinase genes were selected, out of which EPHB6, ITK, FYN, and TYK2 showed high expression as early as 12 h. These kinases may lead to rapid morphological changes in co-infected gastric cells. Likewise, apoptotic gene expression such as APAF-1 and Bcl2 family genes such as BAD, BID, BIK, BIM, BAX, AND BAK were significantly down-regulated in co-infected AGS cells. CONCLUSION: All the experiments were performed with novel isolates of H. pylori isolated from central India, for the functional assessment of GC. The effect of coinfection with EBV was more profoundly observed on morphological changes in AGS cells at 12 h as quantified by measuring the tapering of ends. This study also identifies the kinase and apoptotic genes modulated in co-infected cells, through direct and indirect approaches. We report that ITK, EPHB6, TYK2, FYN kinase are enhanced, whereas apoptotic genes such as APAF-1, BIK, FASL, BAX are significantly down-regulated in AGS cells coinfected with EBV and H. pylori.

Impaired Gut-Systemic Signaling Drives Total Parenteral Nutrition-Associated Injury.

BACKGROUND: Total parenteral nutrition (TPN) provides all nutritional needs intravenously. Although lifesaving, enthusiasm is significantly tempered due to side effects of liver and gut injury, as well as lack of mechanistic understanding into drivers of TPN injury. We hypothesized that the state of luminal nutritional deprivation with TPN drives alterations in gut-systemic signaling, contributing to injury, and tested this hypothesis using our ambulatory TPN model. METHODS: A total of 16 one-week-old piglets were allocated randomly to TPN (n = 8) or enteral nutrition (EN, n = 8) for 3 weeks. Liver, gut, and serum were analyzed. All tests were two-sided, with a significance level of 0.05. RESULTS: TPN resulted in significant hyperbilirubinemia and cholestatic liver injury, p = 0.034. Hepatic inflammation (cluster of differentiation 3 (CD3) immunohistochemistry) was higher with TPN (p = 0.021). No significant differences in alanine aminotransferase (ALT) or bile ductular proliferation were noted. TPN resulted in reduction of muscularis mucosa thickness and marked gut atrophy. Median and interquartile range for gut mass was 0.46 (0.30-0.58) g/cm in EN, and 0.19 (0.11-0.29) g/cm in TPN (p = 0.024). Key gut-systemic signaling regulators, liver farnesoid X receptor (FXR; p = 0.021), liver constitutive androstane receptor (CAR; p = 0.014), gut FXR (p = 0.028), G-coupled bile acid receptor (TGR5) (p = 0.003), epidermal growth factor (EGF; p = 0.016), organic anion transporter (OAT; p = 0.028), Mitogen-activated protein kinases-1 (MAPK1) (p = 0.037), and sodium uptake transporter sodium glucose-linked transporter (SGLT-1; p = 0.010) were significantly downregulated in TPN animals, whereas liver cholesterol 7 alpha-hydroxylase (CyP7A1) was substantially higher with TPN (p = 0.011). CONCLUSION: We report significant alterations in key hepatobiliary receptors driving gut-systemic signaling in a TPN piglet model. This presents a major advancement to our understanding of TPN-associated injury and suggests opportunities for strategic targeting of the gut-systemic axis, specifically, FXR, TGR5, and EGF in developing ameliorative strategies.

Behavioural and neuro-electrical correlates of cognitive performance in young mobile gamers of endless runner and match three genres.

Video game players have been shown to significantly out-perform non-video game players on a wide range of cognitive tasks. Exposure to specific genres of video games may also have a significant bearing in impacting certain task-specific domains of cognition. However, there is limited availability of scientific literature exploring the role of mobile game sub-genres on the cognitive abilities of an individual. The present study was therefore conducted to assess and compare the impact of playing either endless running video games (ERGs) or match three video games (MTGs) on behavioral and neuro-electrical correlates of cognitive performance in young adults, by using reaction time (RT) and P300, respectively. The ERG group included 45 male:female (M:F) ratio = 38:7 and the MTG group included 39 (M:F = 21:18) subjects who played ≥5 h/week of each respective video game genre in past 6 months. The ERG group had better behavioral performance in comparison to the MTG group, as indexed by their significantly faster visual reaction time (VRT). The ERG subjects also had significantly lower P300 amplitudes as compared to MTG subjects. However, no difference in either auditory reaction time (ART) or P300 latency could be ascertained between the two groups. These results suggest that not only were ERG players able to make faster decisions and performed better in visuo-motor tasks but, also had better optimization of neural resources in them as compared to the MTG players. The current data supports the notion that not only exposure to video games but also the nature (i.e. genre) of mobile game play determines the extent to which neural processes concerned with attentional orientation, information processing and cognitive control are influenced.

Oral rinses in growth inhibition and treatment of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) is well-known for its role in chronic gastritis and gastric cancer. Eradication of these carcinogenic bacteria from the gut is one of the challenges for clinicians. The complexity of treatment mainly owes to antibiotic resistance and relapse due to an additional reservoir in the oral cavity. Our study emphases the isolation of H. pylori from distinct habitats of the gut microenvironment (gastric biopsy and gastric juice) and its subsequent characterization. We have also evaluated the effect of various oral rinses on isolated H. pylori from different anatomical locations of included subjects. RESULTS: The possible strains isolated from two different habitats of the same subject shows a striking difference in their growth pattern. Promisingly, some of the included oral rinses are efficient in growth inhibition as per recommended 30 s treatment. The subsequent evaluation shows that oral rinse B (among A-E) is most effective and down-regulates the expression of one of the potent H. pylori gene, CagA, in the infected gastric adenocarcinoma (AGS) cells. CONCLUSION: Our study, for the first time, revealed that H. pylori, isolated from the different habitat of the same subject, show a different growth pattern. The expression of H. pylori pathogenic gene (CagA) was down-regulated by the use of oral rinses. Hence, oral rinses will reduce the H. pylori in the oral cavity and help to control its migration from oral to the gastric compartment and may be used as an adjuvant treatment option for its re-infection.

Developing a Novel Ambulatory Total Parenteral Nutrition-Dependent Short Bowel Syndrome Animal Model.

BACKGROUND: Short bowel syndrome (SBS) results from extensive bowel resection. Patients with SBS require total parenteral nutrition (TPN) for survival. Understanding mechanisms contributing to TPN-associated liver injury and gut atrophy are critical in developing SBS therapies. Existing SBS models using tethered animals have significant limitations and are unlike ambulatory human SBS patients. We hypothesized that we could induce SBS in piglets and develop an ambulatory TPN-SBS model. MATERIAL AND METHODS: Eighteen neonatal pigs received duodenal and jugular catheters. They were fitted with a jacket holding TPN and a miniaturized pump. Six piglets had 90% small bowel resection and catheter placement (SBS group). Non-SBS piglets were randomized into enteral nutrition (EN) or TPN. RESULTS: Bowel resection was successfully accomplished in SBS animals. Weight gain was similar in all groups. SBS animals had increased serum bilirubin compared to EN. Mean conjugated bilirubin ± SD was 0.045 ± 0.01 for EN, (P = 0.03 EN versus TPN and P = 0.03 SBS versus EN) and 1.09 ± 1.25 for TPN, (P = 0.62 TPN versus SBS). Gut density was reduced in the TPN group compared to EN and SBS groups. Mean gut density ± SD was 0.11 ± 0.04 for TPN (P = 0.0004 TPN versus SBS and P = 0.00007 TPN versus EN) and not statistically different for EN versus SBS (P = 0.32). CONCLUSIONS: We created a novel, ambulatory TPN-SBS model using piglets, mimicking long-term TPN delivery in human SBS patients. Our model demonstrated TPN-related conjugated hyperbilirubinemia and compensatory gut hypertrophy, as noted in humans with SBS. This model holds great potential for future research.

Role of the Gut⁻Liver Axis in Driving Parenteral Nutrition-Associated Injury.

For decades, parenteral nutrition (PN) has been a successful method for intravenous delivery of nutrition and remains an essential therapy for individuals with intolerance of enteral feedings or impaired gut function. Although the benefits of PN are evident, its use does not come without a significant risk of complications. For instance, parenteral nutrition-associated liver disease (PNALD)-a well-described cholestatic liver injury-and atrophic changes in the gut have both been described in patients receiving PN. Although several mechanisms for these changes have been postulated, data have revealed that the introduction of enteral nutrition may mitigate this injury. This observation has led to the hypothesis that gut-derived signals, originating in response to the presence of luminal contents, may contribute to a decrease in damage to the liver and gut. This review seeks to present the current knowledge regarding the modulation of what is known as the "gut⁻liver axis" and the gut-derived signals which play a role in PN-associated injury.

Effect of 6 Months of Meditation on Blood Sugar, Glycosylated Hemoglobin, and Insulin Levels in Patients of Coronary Artery Disease.

BACKGROUND AND OBJECTIVES: Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. It has been recognized that stress, diabetes, and hypertension are important in etiology and progression of CAD. This study is to evaluate the role of meditation in improving biochemical parameters such as blood glucose, glycosylated hemoglobin, and serum insulin levels in known CAD patients. MATERIAL AND METHODS: Sixty CAD patients are divided into two groups of which one group did meditation and other did not. Blood glucose, glycosylated hemoglobin, and fasting serum insulin levels were measured before and at the end of 6 months of study in both the groups. RESULTS: At the end of the study, significant decrease was seen in patients who practiced meditation as compared to other group. CONCLUSION: Meditation may modulate the physiological response to stress through neurohumoral activation, which may be a novel therapeutic target for the treatment of CAD.

Proceedings of the 2017 ASPEN Research Workshop-Gastric Bypass: Role of the Gut.

The goal of the National Institutes of Health-funded American Society for Parenteral and Enteral Nutrition 2017 research workshop (RW) "Gastric Bypass: Role of the Gut" was to focus on the exciting research evaluating gut-derived signals in modulating outcomes after bariatric surgery. Although gastric bypass surgery has undoubted positive effects, the mechanistic basis of improved outcomes cannot be solely explained by caloric restriction. Emerging data suggest that bile acid metabolic pathways, luminal contents, energy balance, gut mucosal integrity, as well as the gut microbiota are significantly modulated after bariatric surgery and may be responsible for the variable outcomes, each of which was rigorously evaluated. The RW served as a timely and novel academic meeting that brought together clinicians and researchers across the scientific spectrum, fostering a unique venue for interdisciplinary collaboration among investigators. It promoted engaging discussion and evolution of new research hypotheses and ideas, driving the development of novel ameliorative, therapeutic, and nonsurgical interventions targeting obesity and its comorbidities. Importantly, a critical evaluation of the current knowledge regarding gut-modulated signaling after bariatric surgery, potential pitfalls, and lacunae were thoroughly addressed.

Preserved Gut Microbial Diversity Accompanies Upregulation of TGR5 and Hepatobiliary Transporters in Bile Acid-Treated Animals Receiving Parenteral Nutrition.

BACKGROUND: Parenteral nutrition (PN) is a lifesaving therapy but is associated with gut atrophy and cholestasis. While bile acids (BAs) can modulate intestinal growth via gut receptors, the gut microbiome likely influences gut proliferation and inflammation. BAs also regulate the bile salt export pump (BSEP) involved in cholestasis. We hypothesized that the BA receptor agonist oleanolic acid (OA) regulates gut TGR5 receptor and modulates gut microbiota to prevent PN-associated injury. MATERIALS AND METHODS: Neonatal piglets were randomized to approximately 2 weeks of isocaloric enteral nutrition (EN), PN, or PN + enteral OA. Serum alanine aminotransferase, bilirubin, BAs, hepatic BSEP, gut TGR5, gut, liver morphology, and fecal microbiome utilizing 16S rRNA sequencing were evaluated. Kruskal-Wallis test, pairwise Mann-Whitney U test, and multilevel logistic regression analysis were performed. RESULTS: PN support resulted in gut atrophy substantially prevented by OA. The median (interquartile range) for villous/crypt ratio was as follows: EN, 3.37 (2.82-3.80); PN, 1.73 (1.54-2.27); and OA, 2.89 (2.17-3.34; P = .006). Pairwise comparisons yielded P = .002 (EN vs PN), P = .180 (EN vs OA), P = .026 (PN vs OA). OA upregulated TGR5 and BSEP without significant improvement in serum bilirubin ( P = .095). A decreased microbial diversity and shift toward proinflammatory phylum Bacteroidetes were seen with PN, which was prevented by OA. CONCLUSIONS: OA prevented PN-associated gut mucosal injury, Bacterioides expansion, and the decreased microbial diversity noted with PN. This study demonstrates a novel relationship among PN-associated gut dysfunction, BA treatment, and gut microbial changes.

Measuring distributed leadership agency in a hospital context.

Purpose The purpose of this paper is to develop and validate an instrument that can measure distributed leadership (DL) as employees' active participation in DL tasks. The authors designate this as the distributed leadership agency (DLA). Design/methodology/approach Data were collected throughout all departments and occupational groups at a merged centralized hospital setting in Denmark. A total of 1,774 employees from 24 hospital departments and 16 occupational groups completed our survey. Structural equation model and confirmatory factor analyses were applied to identify appropriate items and a test for measurement invariance, predictive, discriminant and convergent validity, and ANOVAs were applied to analyse group differences in DLA. Findings The identified unidimensional questionnaire consists of seven items, as it is different from, but associated with, empowering leadership, organizational influence, attitude to participation and trust in management. As theoretically predicted, DLA is positively related to self-efficacy, job satisfaction and innovative behaviour. Chief physicians, permanent employees and employee representatives scored higher on the scale than the rest of their respective counterparts. Practical implications The survey offers a method to assess a distribution of leadership agency in hospital organizations. Such assessment may provide a basis for organizational and leadership development. Originality/value The present study provides a reliable and valid quantitative instrument that measures how much employees at all hierarchical levels are involved in concrete leadership activities in the hospital context. Taking a normative perspective the authors could show that DL - measured with the DLA-questionnaire - has positive effects on employees' behaviour.

Oleanolic Acid Improves Gut Atrophy Induced by Parenteral Nutrition.

BACKGROUND: Nutrition support with parenteral nutrition (PN) is associated with gut atrophy. Prior studies have shown improvement with enteral chenodeoxycholic acid, a dual agonist for the farnesoid X receptor (FXR) and bile acid receptor TGR5. We hypothesized that gut growth is induced by TGR5 activation, and gut atrophy during PN administration could be prevented with the TGR5-specific agonist oleanolic acid (OA). METHODS: Neonatal pigs were implanted with duodenal and jugular vein catheters. Animals were provided equi-nutritious PN or enteral swine milk. A PN subgroup received enteral OA at 50 mg/kg/d. RESULTS: PN caused marked gut atrophy compared with enterally fed (EN) control animals. OA treatment led to preservation of gut mass demonstrated grossly and histologically. The mean ± SD gut weight as a percentage of body weight was 4.30 ± 0.26 for EN, 1.92 ± 0.06 for PN (P < .05, EN vs PN), and 3.39 ± 0.79 for PN+OA (P < .05, PN+OA vs PN). Mean ± SD gut density (g/cm) was 0.31 ± 0.03 for EN, 0.18 ± 0.03 for PN (P < .05 EN vs PN), and 0.27 ± 0.01 for PN+OA (P < .05 PN+OA vs PN). Histologically, a markedly decreased villous to crypt ratio was noted with PN, and OA significantly prevented this decrease. The mean ± SD v/c ratio was 3.51 ± 0.59 for EN, 1.69 ± 0.10 for PN (P < .05, EN vs PN), and 2.90 ± 0.23 for PN+OA (P < .05, PN+OA vs PN). Gut TGR5 messenger RNA expression was significantly elevated with OA treatment compared with both PN and EN. CONCLUSION: The bile acid-activated G protein-coupled receptor TGR5 agonist OA prevented gut atrophy associated with PN.