Reduction In Systemic Inflammation Research Articles

Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats.

In this study, we present the potential application of deuterium-depleted water (DDW) for the prevention and adjuvant treatment of obesity in rats. We tested the hypothesis that DDW can alleviate diet-induced obesity (DIO) and its associated metabolic impairments. Rats fed a high-fat diet had an increased body weight index (BWI), glucose concentration, and level of certain proinflammatory cytokines; decreased levels of insulin in the serum; decreased tryptophan and serotonin in the brain, and a decreased concentration of some heavy metals in the liver. Drinking DDW at a concentration of 10 ppm deuterium/protium (D/H) ad libitum for 3 weeks restored the BWI, glucose (serum), tryptophan (brain), and serotonin (brain) levels and concentration of Zn in the liver in the DIO animals to those of the controls. The levels of proinflammatory cytokines (IL-1β, IL-6, IFNγ) and anti-inflammatory TNFα were decreased in DIO rats, while anti-inflammatory cytokine (IL-4, IL-10) levels remained at the control levels, which is indicative of a pathophysiological syndrome. In contrast, in groups of rats treated with DDW, a significant increase in anti-inflammatory (IL-4, IL-10) and proinflammatory cytokines (IFNγ) was observed. This finding indicates a reduction in systemic inflammation in obese animals treated with DDW. Similarly, the high-fat diet caused an increased level of oxidative stress products, which was accompanied by decreased activity of both superoxide dismutase and catalase, whereas the administration of DDW decreased the level of oxidative stress and enhanced antioxidant enzyme activities.

Dietary Bioactive Fatty Acids as Modulators of Immune Function: Implications on Human Health.

Diet is major modifiable risk factor for cardiovascular disease that can influence the immune status of the individual and contribute to persistent low-grade inflammation. In recent years, there has been an increased appreciation of the role of polyunsaturated fatty acids (PUFA) in improving immune function and reduction of systemic inflammation via the modulation of pattern recognition receptors (PRR) on immune cells. Extensive research on the use of bioactive lipids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their metabolites have illustrated the importance of these pro-resolving lipid mediators in modulating signaling through PRRs. While their mechanism of action, bioavailability in the blood, and their efficacy for clinical use forms an active area of research, they are found widely administered as marine animal-based supplements like fish oil and krill oil to promote health. The focus of this review will be to discuss the effect of these bioactive fatty acids and their metabolites on immune cells and the resulting inflammatory response, with a brief discussion about modern methods for their analysis using mass spectrometry-based methods.

689 Early Improvement After Intravenous Ustekinumab Induction in Patients With Ulcerative Colitis: Results From the UNIFI Induction Trial

INTRODUCTION: The UNIFI induction study evaluated the efficacy and safety of ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) after a single intravenous infusion. In this analysis, we evaluated the rapidity of the onset of the treatment effect. METHODS: Eligible patients were randomly assigned to placebo (PBO) or UST 130 mg or ∼6 mg/kg. Patients recorded stool frequency and categorized rectal bleeding daily for the 7 days before each visit. Partial Mayo scores were calculated at baseline and Week 2 using the average of the stool frequency and rectal bleeding scores from the most recent consecutive 3-day period before the visit and the physician's global assessment score recorded at the visit. C-reactive protein (CRP) and fecal biomarkers were measured at baseline and Day 14. RESULTS: At baseline, the mean 3-day average daily stool frequency was 7.0 in the PBO group, 6.9 in the UST 130-mg group, and 7.0 in the UST ∼6-mg/kg group. Patients receiving UST showed greater reductions in the daily number of stools compared with PBO as soon as the first assessment time point at Day 7. Mean changes from baseline in daily stool frequency were -0.7 for PBO, -1.0 for UST 130-mg (P = 0.098), and -1.2 for UST ∼6-mg/kg group (P = 0.018) by Day 7, respectively, and -0.9, -1.6 (P < 0.001), and -1.9 (P < 0.001) by Day 13, respectively (Figure 1). Rectal bleeding scores at baseline and Week 2 are summarized in Figure 2. Patients receiving UST showed significantly greater improvement from baseline to Day 14 in partial Mayo score and CRP (Table, P < 0.001 for all comparisons of UST vs PBO). Differences between the UST and PBO treatment groups in mean changes from baseline to Day 14 in fecal calprotectin did not reach significance (PBO -33.96 mg/kg, UST 130 mg 79.12 mg/kg [P = 0.875], UST ∼6 mg/kg -412.68 mg/kg [P = 0.152]). However, patients receiving UST showed significantly greater improvement in fecal calprotectin at Week 4 (mean changes from baseline: PBO -226.78 mg/kg, UST 130 mg -881.22 mg/kg [P = 0.013], UST ∼6 mg/kg -802.75 mg/kg [P < 0.001]). Similar results were observed for fecal lactoferrin. CONCLUSION: The effect of UST began rapidly after induction, with symptomatic improvement and reduction of systemic inflammation seen as early as the first assessments at Days 7 and 14, respectively.

Effects of cessation of cigarette smoking on eicosanoid biomarkers of inflammation and oxidative damage.

The urinary metabolites “prostaglandin E2 metabolite” (PGE-M) and (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α) are biomarkers of inflammation and oxidative damage, respectively, and are elevated in cigarette smokers. Relatively little is known about the effects of smoking cessation on these biomarkers. To investigate this, current cigarette smokers interested in quitting were recruited and invited to participate in a smoking cessation study where varenicline (Chantix) and brief supportive behavioral counseling were offered at each visit after baseline. Subjects returned to the clinic during the 12 week treatment phase for 9 visits post cessation on days 3, 7, 14, 21, 28, 42, 56, 70 and 84. Urine samples were collected at each visit and analyzed by liquid chromatography-tandem mass spectrometry for PGE-M, 8-iso-PGF2α, and cotinine. Cotinine values demonstrated that 15 of 38 subjects quit smoking for the entire 84 day period. Significant decreases in mean levels of PGE-M and 8-iso-PGF2α per milligram creatinine were observed in these subjects, by 44% (p = 0.0014) and 27% (p<0.001), respectively. The results of this study demonstrate that cessation of smoking for 84 days results in modest but significant declines in urinary PGE-M and 8-iso-PGF2α indicating reductions in systemic inflammation and oxidative damage. Given that levels were only modestly decreased, these markers are not specific to tobacco-smoke exposure. The modest declines in these biomarkers should be considered when planning studies with ex-smokers. There is a “hangover” from smoking that lasts at least 3 months.

Abstract # 3160 Effects of two-week smartphone-based mindfulness training on markers of inflammation: A randomized controlled trial

Mindfulness interventions, which train people to monitor present-moment experience with a lens of acceptance, are inconsistently associated with reductions in systemic inflammation. Here, we examine the impact of brief mindfulness training on circulating CRP and IL-6, explore treatment response in subgroups at risk for heightened inflammation, and test acceptance training as a mechanism of these effects. 153 stressed community adults were randomly assigned to one of three 14-lesson smartphone-based interventions: (1) training in both monitoring and acceptance (MA), (2) training in monitoring only (MO), or (3) active control training. Dried blood spots collected at pre- and post-intervention were assayed for CRP and IL-6. Contrary to predictions, there were no significant pre- to post-intervention changes in CRP or IL-6 across or between groups. In exploratory subgroup analyses, MA training reduced CRP among both midlife (40–65 years; N = 41) and overweight participants (BMI > = 25; N = 64). Specifically, among midlife participants, MA reduced CRP compared to control (p = .01, d = 0.47) but not MO (p = .57, d = 0.08). Among overweight participants, MA reduced CRP compared to both MO (p =.04, d = 0.24) and control (p = .01, d = 0.35). There were no condition differences in these subgroups on changes in IL-6. Overall, two-week mindfulness training did not reduce markers of inflammation in a stressed but otherwise healthy population. Exploratory analyses suggest that this brief mindfulness intervention may reduce CRP in high-risk subgroups, and that acceptance is key for these effects.

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency.

BackgroundInflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue.MethodsThe relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice.FindingsIL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression.InterpretationIL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function.FundSao Paulo Research Foundation grant 2013/07607-8.

Dietary therapy and non-surgical periodontal treatment in obese patients with chronic periodontitis.

The effect of dietary weight loss intervention on periodontal therapy is unknown. Therefore, we aimed to evaluate whether weight loss improves the response of obese subjects to non-surgical periodontal treatment. This interventional study in obese patients was conducted at the University Hospital Dr. Peset (Valencia, Spain). Patients were divided into two groups with and without dietary therapy. All participants received non-surgical periodontal treatment. Periodontal, anthropometric and biochemical parameters were assessed at baseline and 12weeks. A total of 78 patients were re-evaluated after intervention. All periodontal parameters improved in both groups after periodontal treatment, but the reductions in mean probing depth (PD) (0.23mm vs. 0.12mm) and in percentage of sites with PD 4-5mm (10.4% vs. 5.89%) were significantly higher in the dietary group. Additionally, complement component 3 (C3) and tumour necrosis factor alpha (TNFα) decreased in the dietary group after intervention. Percentage of change in mean PD correlated with change in C3 (r=0.233, p=0.043), and percentage of change in sites with PD 4-5mm correlated with change in TNFα (r=0.414, p=0.012). This study suggests that dietary weight loss intervention causes a greater reduction in systemic inflammation, which may enhance the response to periodontal treatment.

The Effect of Statins in Epilepsy: A Systematic Review.

Background and Objectives:Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, used for the management of hypercholesterolemia and related atherosclerotic diseases. Several studies have indicated the neuroprotective effects of statins on several neuropathological conditions. However, the role of these medications in epilepsy is still unclear. The purpose is to evaluate and summarize the level of evidence on the efficacy of statins in neuronal hyperexcitability and the neuroinflammatory processes of epilepsy.Methods:A systematic review was performed. Eligibility Criteria: This review involved studies conducted in humans and nonhuman experimental models, covering the use of an inhibitor of HMG-CoA reductase, alone or accompanied by another medication, in epilepsy. Information Sources: A systematic literature search was performed in PubMed, Embase, Ebsco Host, Scopus, Science Direct, Medline, and LILACS. Risk of Bias: It was evaluated with the Newcastle–Ottawa Scale and the experimental studies were evaluated using the GRADE tool.Results:Twenty articles of the 183 evaluated were included. Sixteen studies were conducted in animal models and four studies in humans. Most studies in mice reported a reduction in epileptiform activity and reduction in systemic inflammation with the treatment of statins, potentially influencing epilepsy control. Few studies in humans were performed in the geriatric population with variable results (neuroinflammation, seizure prevention, cell death, prevention of kindling, increase in convulsive threshold, increase in latency, decrease in frequency of crisis, and reduction in mortality) related to reduction in the rate of hospitalizations, mortality, and prevention of epilepsy. Studies in mice found a decrease in interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha and an increase in IL-10 and endothelial nitric oxide synthase.Conclusions:The possible antiepileptic mechanism of statins may be related to the reduction in neuroinflammation mediated by a decrease in pro-inflammatory cytokines and action in the nitrergic system. Further studies evaluating the impact of statins on seizure control are necessary.

Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis. A Randomized, Controlled, Multicenter Clinical Trial.

Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (β-carotene, coenzyme Q10, γ-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P < 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).

Dietary Supplementation with Galactooligosaccharide (GOS) Attenuates High-Fat, High-Cholesterol Containing Western Diet (WD)–Induced Glucose Intolerance

WD induces the development of type 2 diabetes (T2DM). In addition to the direct effects on gut dysbiosis, we have shown that WD also affect intestinal barrier function leading to increased release of LPS into circulation resulting in chronic inflammation that underlies the development of T2DM; oral supplementation with curcumin attenuate these WD-induced effects. Herein we examined the effects of GOS supplementation on WD induced changes. C57BL/6 mice were either fed a standard chow or WD or WD+GOS or WD+Curcumin (WD+C) for 16 weeks. Glucose tolerance tests were performed and while no significant differences were seen in female mice (Panels A and C), WD-induced glucose intolerance was significantly attenuated by GOS or curcumin supplementation in male mice (Panels B and D). Although plasma LPS levels were not significantly affected, a significant decrease in circulating macrophages (Panel E) as well as neutrophils (Panel F) was noted with GOS or Curcumin supplementation indicating a reduction in systemic inflammation. Gene expression and histological changes in the ileum and colon indicate GOS or curcumin-mediated increase in mucin production and maintenance of mucous layer integrity. Dietary supplementation with GOS or Curcumin, therefore, represents a simple strategy to ameliorate the metabolic/diabetogenic effects of WD. Disclosure H. He: None. S.S. Ghosh: None. P.J. Yannie: None. J. Wang: None. S. Ghosh: None.

Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy.

Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacerbate mucosal damage. Restoration of the microbiota through fecal-pellet gavage drives healing of cisplatin-induced intestinal damage. Bacterial translocation to the blood stream is correspondingly abrogated, resulting in a significant reduction in systemic inflammation, as evidenced by decreased serum IL-6 and reduced mobilization of granulocytes. Mechanistically, reversal of dysbiosis in response to fecal gavage results in the production of protective mucins and mobilization of CD11b+ myeloid cells to the intestinal mucosa, which promotes angiogenesis. Administration of Ruminococcus gnavus, a bacterial strain selectively depleted by cisplatin treatment, could only partially restore the integrity of the intestinal mucosa and reduce systemic inflammation, without measurable increases in the accumulation of mucin proteins. Together, our results indicate that reconstitution of the full repertoire of intestinal bacteria altered by cisplatin treatment accelerates healing of the intestinal epithelium and ameliorates systemic inflammation. Therefore, fecal microbiota transplant could paradoxically prevent life-threatening bacteremia in cancer patients treated with chemotherapy.

Heavy Cannabis Use Associated With Reduction in Activated and Inflammatory Immune Cell Frequencies in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Individuals.

Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)-infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined. The impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry. Individuals were categorized into heavy, medium, or occasional cannabis users or noncannabis users based on the amount of the cannabis metabolite 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) detected in plasma by mass spectrometry. Heavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR+CD38+CD4+ and CD8+ T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23- and tumor necrosis factor-α-producing antigen-presenting cells. While the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.

Reduction of systemic inflammation after cardiac resynchronization therapy: A new form of response?

Reduction of systemic inflammation after cardiac resynchronization therapy: A new form of response?

High-density lipoprotein-mimicking nanodiscs carrying peptide for enhanced therapeutic angiogenesis in diabetic hindlimb ischemia

Therapeutic strategies using endogenous stem cell mobilizer can provide effective cell-free therapy for addressing various ischemic diseases. In particular, substance P (SP) exhibited therapeutic regeneration by facilitating mobilization of endogenous stem cells from bone marrow to the injured sites. However, its therapeutic effect has been limited due to short half-life and rapid degradation of administered SP peptides in vivo. Here we sought to develop high-density lipoprotein (HDL)-mimicking nanodiscs conjugated with SP (HDL-SP) in order to increase the in vivo half-life, bone marrow targeting, and therapeutic efficacy of SP for the treatment of diabetic peripheral ischemia. Conjugation of SP onto HDL nanodisc led to remarkable ∼3215- and ∼1060-fold increase in the ex vivo and in vivo half-lives of SP, respectively. Accordingly, HDL-SP nanodiscs improved retention of SP in bone marrow after systemic administration, leading to efficient mobilization of stem cells from bone marrow into blood circulation and reduction of systemic inflammation. Consequently, nanodisc based SP peptide delivery promoted blood vessel formation, blood perfusion recovery and markedly improved limb salvage in diabetic hindlimb ischemia model relative to administration of free SP without nanodisc modification. Therefore, HDL-SP nanodisc can provide a novel strategy for the treatment of diabetic ischemia and HDL nanodisc modification could be potentially useful for the extension of plasma circulation of other labile peptides.

Alpha-Linolenic Acid Supplementation is Associated with Changes in Inflammatory Markers and Endoplasmic Reticulum Stress in Diabetic Rats

Background: The aim of this study was to evaluate the effects of α-linolenic acid (ALA) supplementation on inflammation and endoplasmic reticulum stress (ERS) in streptozotocin induced diabetic rats.Methods: We studied 40 Wistar rats divided into four groups: control, control+ALA, diabetes and diabetes+ALA. The +ALA groups received supplementation of 3 g of ALA from flaxseed, daily for a period of 8 weeks. Measurements of blood glucose levels, serum insulin, lipid profile, serum cytokines (TNF-α, IL-6 and INF-γ) and body weight were performed before and after the ALA supplementation. Protein expression of AKT, IRE1-α, XBP-1, BIP, HSP-70, HSP-90, TNF-α and CHOP were evaluated in liver tissue.Results: The diabetes+ALA group had lower liver and greater epidydimal adipose tissue weight in relation to the diabetes group, besides no difference in total body weight. Diabetes+ALA group showed lower glucose and triglyceride levels after the ALA supplementation compared to diabetes group, but no difference in total cholesterol. Insulin levels were significantly lower in the diabetic group compared to the control, but there was no difference between the control group and diabetes+ALA group. The ALA supplementation did not determine significant changes in TNF-α and IL-6 levels. However, the diabetic+ALA group showed a decrease in the serum INF-γ levels after the supplementation period. We also observed increased expression of HSP-90 and HSP-70 in hepatic tissue of the diabetes+ALA animals compared to the diabetes group, associated to lower BIP and XBP-1 protein expression. We also observed a decrease in AKT protein expression in the diabetes+ALA groupConclusion: In conclusion, supplementation of ALA reduced blood glucose and serum triglyceride levels associated to a reduction in systemic inflammation and it was also able to influence important pathways involved in the modulation of ERS.

Gut microbial diversity in HIV infection post combined antiretroviral therapy

Purpose of reviewAlthough the HIV-infected population is living longer and getting older under current treatment regimens, significant challenges arise for health management as the infection is associated with various premature aging phenotypes, particularly increased incidence of cardiovascular diseases (CVDs). Here we review the current understanding of HIV-related gut dysbiosis in association with CVD and advances in clinical trials aiming to restore gut microbial diversity.Recent findingIdentification of a unique signature for gut dysbiosis in HIV infection between different cohorts remains challenging. However, low diversity of microbiota combined with the outgrowth of pathogenic bacterial species together with dysregulated metabolic pathways have been linked to compromised gut immunity, bacterial translocation and systemic inflammation, hence higher CVD risk among different cohorts. Data from recent clinical trials aiming to evaluate the tolerability and efficacy of probiotics in treated HIV+ patients are promising and support a significant increase in microbiota diversity and reduction of systemic inflammation. However, the impact of these microbial and immunological corrections on the prevalence of CVD in HIV+ patients remains unclear.SummaryPositive immunological outcomes following enrichment of the gut microbial diversity have been documented, and further trials are in progress to evaluate the range of patients, with different immunological backgrounds, who might benefit from these treatments.

Favorable Cardio-Metabolic Outcomes Following High Carbohydrate Intake in Accordance with the Daniel Fast: A Review of Available Findings

The Daniel Fast is a biblically inspired dietary program rich in carbohydrate, most closely resembling a vegan diet but with additional restrictions, including the elimination of processed foods, white flour products, preservatives, additives, sweeteners, caffeine, and alcohol. While no specific requirements are placed on the ingestion of specific percentages of macronutrients, the mean daily carbohydrate intake is by default approximately 60%, while protein and fat intake are 15% and 25%, respectively. Despite a relatively high carbohydrate intake, multiple favorable cardio-metabolic effects are noted when following the plan, in as few as three weeks. This includes improvements in HOMA-IR, which may be at least in part due to the lower glycemic load and high dietary fiber content of the foods consumed. Other notable changes include reductions in systemic inflammation, total and LDL-cholesterol, oxidative stress, blood pressure, and body weight/body fat. Short and moderate-term compliance to the program is excellent-better than most dietary programs, perhaps due to the ad libitum nature of this plan. This paper presents an overview of the Daniel Fast, a carbohydrate-rich dietary program, including relevant findings from both human and animal investigations using this dietary model.

Exclusive enteral nutrition provides an effective bridge to safer interval elective surgery for adults with Crohn's disease.

Few studies have reported the systematic use of exclusive enteral nutrition in the perioperative setting. To test the hypothesis that exclusive enteral nutrition provides a safe and effective bridge to surgery and reduces post-operative complications, in adult patients with Crohn's disease requiring urgent surgery for stricturing or penetrating complications. Patients treated with exclusive enteral nutrition prior to surgery were each matched with two control patients for disease behaviour, type of surgery, age at diagnosis and disease duration. Data on disease phenotype, nutritional status, operative course and post-operative complications were obtained. Twenty-five per cent [13/51] patients treated with exclusive enteral nutrition avoided surgery. Exclusive enteral nutrition had no effect on pre-operative weight, but it significantly reduced serum CRP [median at baseline 36 (interquartile range, IQR: 13-91] vs. pre-operation 8 (4-31) mg/L, P=0.02]. The median (IQR) length of surgery was shorter in patients pre-optimised with exclusive enteral nutrition than controls [3.0 (2.5-3.5) vs. 3.5 (3.0-4.0) hours respectively, P<0.001]. Multivariable logistic regression analysis confirmed that going straight-to-surgery compared exclusive enteral nutrition pre-optimisation was associated with a ninefold increase in the incidence of post-operative abscess and/or anastomotic leak [OR 9.1; 95% CI (1.2-71.2), P=0.04]. Exclusive enteral nutrition frequently down-stages the need for surgery in patients presenting with stricturing or penetrating complications of Crohn's disease; it is associated with a reduction in systemic inflammation, operative times and the incidence of post-operative abscess or anastomotic leak. Further trials are needed to elucidate how exclusive enteral nutrition may improve operative outcomes.

Pediatric acute liver failure of undetermined cause

Experience gained through treatment trials of HLH and MAS in childhood may inform study design for therapy of PALF. Successful approaches to limiting neuroinflammation through reduction of systemic inflammation and standardized neuroprotection protocols that limit glial injury could significantly improve intact survival. Finally, given that PALF is a rare disease, investigative efforts must include broad multicenter collaboration and careful stewardship of biorepository specimens. (Hepatology 2017;65:1026-1037).

Sequestration of ubiquitous dietary derived pigments enables mitochondrial light sensing.

Animals alter their physiological states in response to their environment. We show that the introduction of a chlorophyll metabolite, a light-absorbing pigment widely consumed in human diets, to Caenorhabditis elegans results in animals whose fat mass can be modulated by exposure to light, despite the worm consuming the same amount of food. In the presence of the chlorophyll metabolite, exposing the worms to light increased adenosine triphosphate, reduced oxidative damage, and increased median life spans, without an effect on animal reproduction. Mice fed a dietary metabolite of chlorophyll and exposed to light, over several months, showed reductions in systemic inflammation as measured by plasma α-macroglobulin. We propose that dietary chlorophyll metabolites can enable mitochondria to use light as an environmental cue, by absorbing light and transferring the energy to mitochondrial coenzyme Q.