Estrogen receptor beta in the central amygdala regulates the deleterious behavioral and neuronal consequences of repeated social stress in female rats.

While over 95% of the population has reported experiencing extreme stress or trauma, females of reproductive age develop stress-induced neuropsychiatric disorders at twice the rate of males. This suggests that ovarian hormones may facilitate neural processes that increase stress susceptibility and underlie the heightened rates of these disorders, like depression and anxiety, that result from stress exposure in females. However, there is contradicting evidence in the literature regarding estrogen's role in stress-related behavioral outcomes. Estrogen signaling through estrogen receptor beta (ERß) has been traditionally thought of as anxiolytic, but recent studies suggest estrogen exhibits distinct effects in the context of stress. Furthermore, ERß is found abundantly in many stress-sensitive brain loci, including the central amygdala (CeA), in which transcription of the vital stress hormone, corticotropin releasing factor (CRF), can be regulated by an estrogen response element. Therefore, these experiments sought to identify the role of CeA ERß activity during stress on behavioral outcomes in naturally cycling, adult, female Sprague-Dawley rats. Rats were exposed to an ethological model of vicarious social stress, witness stress (WS), in which they experienced the sensory and psychological aspects of an aggressive social defeat encounter between two males. Following WS, rats exhibited stress-induced anxiety-like behaviors in the marble burying taskand brain analysis revealed increased ERß and CRF specifically within the CeA following exposure to stress cues. Subsequent experiments were designed to target this receptor in the CeA using microinjections of the ERß antagonist, PHTPP, prior to each stress session. During WS, estrogen signaling through ERß was responsible for the behavioral sensitization to repeated social stress. Sucrose preference, acoustic startle, and marble burying tasks determined that blocking ERß in the CeA during WS prevented the development of depressive-, anxiety-like, and hypervigilant behaviors. Additionally, brain analysis revealed a long-term decrease of intra-CeA CRF expression in PHTPP-treated rats. These experiments indicate that ERß signaling in the CeA, likely through its effects on CRF, contributes to the development of negative valence behaviors that result from exposure to repeated social stress in female rats.

Determination of Chemical Irritation Potential Using a Defined Gene Signature Set on Tissue-Engineered Human Skin Equivalents.

There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full-thickness human skin equivalent or human ex vivo skin and gene signatures determined for known irritants and nonirritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2, and matrix metalloproteinase gene MMP-3) that could distinguish potential irritants from nonirritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system.

The Long-term Effect of Different Exercise Intensities on High-Density Lipoprotein Cholesterol in Older Men and Women Using the Per Protocol Approach: The Generation 100 Study.

OBJECTIVE: To examine whether 5 years of high-intensity interval training (HIIT) increases high-density lipoprotein cholesterol (HDL-C) concentration more than moderate-intensity continuous training (MICT) and control (CON) in older men and women. METHODS: A total of 1567 older adults (790 [50.4%] women) were randomized (2:1:1) to either CON (n=780; asked to follow the national recommendations for physical activity) or 2 weekly sessions of HIIT (10-minute warm-up followed by 4×4-minute intervals at ∼90% of peak heart rate) or MICT (50 minutes of continuous work at ∼70% of peak heart rate). Serum HDL-C concentration was measured by standard procedures at baseline and at 1 year, 3 years, and 5 years. The study took place between August 21, 2012, and June 31, 2018. Linear mixed models were used to determine between-group differences during 5 years using the per protocol approach. RESULTS: Men in HIIT had a smaller reduction in HDL-C (-1.2%) than men in CON (-6.9%) and MICT (-7.8%) after 5 years (P=.01 and P=.03 for CON vs HIIT and MICT vs HIIT, respectively). No effect of exercise intensity on HDL-C was seen in women. Changes in peak oxygen uptake were associated with changes in HDL-C in both men and women, whereas changes in body weight and fat mass were not. CONCLUSION: In men, HIIT seems to be the best strategy to prevent a decline in HDL-C during a 5-year period. No effect of exercise intensity was seen for older women. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01666340.

The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals.

BACKGROUND: High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism. OBJECTIVE: To examine the effects of consumption of two to three extra serves of green leafy vegetables daily on bone metabolism. METHODS: Thirty individuals (mean age 61.8 ± 9.9 years, 67% male) completed three experimental phases in a randomised controlled crossover design, each lasting four weeks, with a washout period of four weeks between phases (clinical trial registration: ACTRN12615000194561). The three experimental phases were: (i) increased dietary vitamin K1 by consuming green leafy vegetables (H-K; ~200 g/d containing 164.3 [99.5-384.7] µg/d of vitamin K1); (ii) low vitamin K1 by consuming vitamin K1-poor vegetables (L-K; ~200 g/d containing 9.4 [7.7-11.6] µg/d of vitamin K1); and (iii) control (CON) where participants consumed an energy-matched non-vegetable control. OC forms, total OC (tOC), carboxylated OC (cOC) and undercarboxylated OC (ucOC), were measured in serum pre- and post-intervention for each experimental phase using a sandwich-electrochemiluminescence immunoassay. RESULTS: Pre-intervention tOC, ucOC and ucOC:tOC levels were similar between phases (P > .05). Following H-K, but not L-K, tOC, ucOC and ucOC:tOC levels were significantly lower compared to pre-intervention levels (P ≤ .001) and compared to CON (~14%, 31% and 19%, respectively, all P < .05), while cOC remained unchanged. CONCLUSIONS: In middle-aged healthy men and women, an easily achieved increase in dietary intake of vitamin K1-rich green leafy vegetables substantially reduces serum tOC and ucOC suggesting increased entry of OC into bone matrix, where it may improve the material property of bone. In conjunction with previous epidemiological and randomised controlled trial data, these findings suggest that interventions to increase vegetable intake over extended periods should include bone end points including fracture risk.

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF.

The effect of chronic oral vitamin D supplementation on adiposity and insulin secretion in hypothalamic obese rats.

Reduced plasma vitamin D (VD) levels may contribute to excessive white adipose tissue, insulin resistance (IR) and dyslipidaemia. We evaluated the effect of chronic oral VD supplementation on adiposity and insulin secretion in monosodium glutamate (MSG)-treated rats. During their first 5 d of life, male neonate rats received subcutaneous injections of MSG (4 g/kg), while the control (CON) group received saline solution. After weaning, groups were randomly distributed into VD supplemented (12 µg/kg; three times/week) and non-supplemented (NS) rats, forming four experimental groups (n 15 rats/group): CON-NS, CON-VD, MSG-NS and MSG-VD. At 76 d of life, rats were submitted to an oral glucose tolerance test (OGTT; 2 g/kg), and at 86 d, obesity, IR and plasma metabolic parameters were evaluated. Pancreatic islets were isolated for glucose-induced insulin secretion (GIIS), cholinergic insulinotropic response and muscarinic 3 receptor (M3R), protein kinase C (PKC) and protein kinase A (PKA) expressions. Pancreas was submitted to histological analyses. VD supplementation decreased hyperinsulinaemia (86 %), hypertriacylglycerolaemia (50 %) and restored insulin sensibility (89 %) in MSG-VD rats, without modifying adiposity, OGTT or GIIS, compared with the MSG-NS group. The cholinergic action was reduced (57 %) in islets from MSG-VD rats, without any change in M3R, PKA or PKC expression. In conclusion, chronic oral VD supplementation of MSG-obese rats was able to prevent hyperinsulinaemia and IR, improving triacylglycerolaemia without modifying adiposity. A reduced cholinergic pancreatic effect, in response to VD, could be involved in the normalisation of plasma insulin levels, an event that appears to be independent of M3R and its downstream pathways.

The feasibility and acceptability of morning versus evening exercise for overweight and obese adults: A randomized controlled trial.

BACKGROUND: The time of day that people exercise could have an influence on the efficacy of exercise for weight loss, via differences in adherence and/or physiological adaptations. However, there is currently no evidence to support an optimal time of day for exercise to maximise efficacy. PURPOSE: To examine the feasibility and acceptability of prescribed morning and evening exercise. METHODS: Twenty inactive, overweight adults aged 18-60 years were recruited for a 12-week intervention and randomized to one of three groups using a 2:2:1 random allocation ratio: i) morning exercise (AM; n = 9); ii) evening exercise (PM; n = 7); or iii) waitlist control (CON; n = 4). Exercise groups were prescribed self-paced walking or running on a treadmill to achieve a weekly total of 250 min. Feasibility and acceptability data were collected, and physiological and behavioural outcomes associated with energy balance were measured at baseline, mid- and post-intervention. RESULTS: Attrition was low (n = 2 dropped out), with high measurement completion rates (>80%). The intervention groups had high adherence rates to exercise sessions (94% and 87% for the AM and PM groups, respectively). No adverse events resulting from the intervention were reported. Both intervention groups displayed improvements to their cardiometabolic risk profile; cardiorespiratory fitness improved by 5.2 ±â€¯4.7, and 4.6 ±â€¯4.5 mL kg-1.min-1 and body fat percentage reduced by 1.2 ±â€¯1.4, and -0.6 ±â€¯1.2% for AM and PM groups, respectively. CONCLUSION: This feasibility study provides evidence that morning and evening exercise interventions are feasible, and also provides justification for a large-scale randomized controlled trial. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000457448p, 7/4/2016).

Prediction of massive bleeding in a prehospital setting: validation of six scoring systems. / Predicción de hemorragia masiva a nivel extrahospitalario: validación de seis escalas.

OBJECTIVE: To validate the diagnostic ability of six different scores to predict massive bleeding in a prehospital setting. DESIGN: Retrospective cohort. SETTING: Prehospital attention of patients with severe trauma. SUBJECTS: Subjects with more than 15 years, a history of severe trauma (defined by code 15 criteria), that were initially assisted in a prehospital setting by the emergency services between January 2010 and December 2015 and were then transferred to a level one trauma center in Madrid. VARIABLES: To validate: 1. Trauma Associated Severe Haemorrhage Score. 2. Assessment of Blood Consumption Score. 3. Emergency Transfusión Score. 4. Índice de Shock. 5. Prince of Wales Hospital/Rainer Score. 6. Larson Score. RESULTS: 548 subjects were studied, 76,8% (420) were male, median age was 38 (interquartile range [IQR]: 27-50). Injury Severity Score was 18 (IQR: 9-29). Blunt trauma represented 82,5% (452) of the cases. Overall, frequency of MB was 9,2% (48), median intensive care unit admission days was 2,1 (IQR: 0,8 - 6,2) and hospital mortality rate was 11,2% (59). Emergency Transfusión Score had the highest precisions (AUC 0,85), followed by Trauma Associated Severe Haemorrhage score and Prince of Wales Hospital/Rainer Score (AUC 0,82); Assessment of Blood Consumption Score was the less precise (AUC 0,68). CONCLUSION: In the prehospital setting the application of any the six scoring systems predicts the presence of massive hemorrhage and allows the activation of massive transfusion protocols while the patient is transferred to a hospital.

Timing of post-resistance exercise nutrient ingestion: effects on gastric emptying and glucose and amino acid responses in humans.

This study examined the effects of post-resistance exercise protein ingestion timing on the rate of gastric emptying (GE) and blood glucose (BG) and plasma branched-chain amino acid (BCAA) responses. In all, eleven healthy participants randomly ingested 400 ml of a nutrient-rich drink containing 12 g carbohydrates and 20 g protein at rest (Con), at 5 min (post-exercise (PE)-5) or at 30 min (PE-30) after a single bout of strenuous resistance exercises. The first and second sets comprised ten repetitions at 50 % of each participant's one-repetition maximum (1RM). The third, fourth and fifth sets comprised ten repetitions at 75 % of 1RM, and the sixth set involved repeated repetitions until exhaustion. Following ingestion of the nutrient-rich drink, we assessed the GE rate using 13C-sodium acetate breath test and evaluated two parameters according to the T max-calc (time when the recovery per hour is maximised), which is a standard analytical method, and T 1/2 (time when the total cumulative dose of [13CO2] reaches one-half). T max-calc and T 1/2 were slower for the PE-5 condition than for either the PE-30 or Con condition (T max-calc; Con: 53 (sd 7) min, PE-5: 83 (sd 16) min, PE-30: 62 (sd 9) min, T 1/2; Con: 91 (sd 7) min, PE-5: 113 (sd 21) min, PE-30: 91 (sd 11) min, P<0·05). BG and BCAA responses were also slower for the PE-5 condition than for either the PE-30 or Con condition. Ingesting nutrients immediately after strenuous resistance exercise acutely delayed GE, which affected BG and plasma BCAA levels in blood circulation.

Energy depletion by 24-h fast leads to compensatory appetite responses compared with matched energy depletion by exercise in healthy young males.

Although there is a growing interest for the effects of intermittent fasting on energy balance, this study aimed to compare appetite, energy intake and food reward responses with an energy depletion induced either by 24-h food restriction or an equivalent deficit with exercise in healthy males. In all, twelve healthy lean males (21·5 (sd 0·5) years old; BMI: 22·5 (sd 1·7) kg/m2) participated in this study. Body composition, aerobic capacity, food preferences and energy intake were assessed. They randomly completed three conditions: (i) no depletion (CON); (ii) full 24-h energy restrictions (Def-EI); and (iii) exercise condition (Def-EX). Ad libitum energy intake and food reward were assessed at the end of each session. Appetite feelings were assessed regularly. Ad libitum energy intake was higher on Def-EI (7330 (sd 2975) kJ (1752 (sd 711) kcal) compared with that on CON (5301 (sd 1205) kJ (1267 (sd 288) kcal)) (P<0·05), with no difference between CON and Def-EX (6238 (sd 1741) kJ (1491 (sd 416) kcal) (P=0·38) and between Def-EX and Def-EI (P=0·22). There was no difference in the percent energy ingested from macronutrients. Hunger was lower on CON and Def-EX compared with Def-EI (P<0·001). Satiety was higher on CON and Def-EI compared with that on Def-EX (P<0·001). There was a significant interaction condition × time for food choice fat bias (P=0·04), showing a greater preference for high-fat v. low-fat food during Def-EI and Def-EX. Although 24-h fasting leads to increased energy intake at the following test meal (without total daily energy intake difference), increased hunger profile and decreased post-meal food choice fat bias, such nutritional responses are not observed after a similar deficit induced by exercise.

Soy protein improves tibial whole-bone and tissue-level biomechanical properties in ovariectomized and ovary-intact, low-fit female rats.

BACKGROUND: Osteoporosis and related fractures, decreased physical activity, and metabolic dysfunction are serious health concerns for postmenopausal women. Soy protein might counter the negative effects of menopause on bone and metabolic health due to the additive or synergistic effects of its bioactive components. OBJECTIVE: To evaluate the effects of ovariectomy (OVX) and a soy-protein diet (SOY) on bone outcomes in female, low-capacity running (LCR) rats selectively bred for low aerobic fitness as a model of menopause. METHODS: At 27 weeks of age, LCR rats (N = 40) underwent OVX or sham (SHAM) surgery and were randomized to one of two isocaloric and isonitrogenous plant-protein-based dietary treatments: 1) soy-protein (SOY; soybean meal); or, 2) control (CON, corn-gluten meal), resulting in four treatment groups. During the 30-week dietary intervention, animals were provided ad libitum access to food and water; body weight and food intake were measured weekly. At completion of the 30-week intervention, body composition was measured using EchoMRI; animals were fasted overnight, euthanized, and blood and hindlimbs collected. Plasma markers of bone formation (osteocalcin, OC; N-terminal propeptide of type I procollagen, P1NP) and resorption (tartrate-resistant acid phosphatase, TRAP5b; C-terminal telopeptide of type I collagen, CTx) were measured using ELISA. Tibial trabecular microarchitecture and cortical geometry were evaluated using µCT; and torsional loading to failure was used to assess cortical biomechanical properties. Advanced glycation end-product (AGE) content of the femur was measured using a fluorimetric assay, and was expressed relative to collagen content measured by a colorimetric OH-proline assay. Two-factor ANOVA or ANOVCA was used to test for significant main and interactive effects of ovarian status (OV STAT: OVX vs. SHAM) and DIET (SOY vs. CON); final body weight was included as a covariate for body-weight-dependent cortical geometry and biomechanical properties. RESULTS: OVX had significantly greater CTx than SHAM; SOY did not affect bone turnover markers. OVX adversely affected trabecular microarchitecture as evidenced by reduced BV/TV, trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity density (Conn.D), and by increased trabecular separation (Tb.Sp) and structural model index (SMI). SOY increased BV/TV only in ovary-intact animals. There was no effect of OVX or SOY on tibial cortical geometry. In SHAM and OVX rats, SOY significantly improved whole-bone strength and stiffness; SOY also increased tissue-level stiffness and tended to increase tissue-level strength (p = 0.067). There was no effect of OVX or SOY on AGE content. CONCLUSION: Soy protein improved cortical bone biomechanical properties in female low-fit rats, regardless of ovarian hormone status.

Consumption of transglycosylated starch down-regulates expression of mucosal innate immune response genes in the large intestine using a pig model.

Benefits of resistant starch (RS) consumption on host physiology encompass microbial activity-derived attenuation of intestinal inflammation. However, little is known about anti-inflammatory properties of RS of type 4. This study compared the effects of transglycosylated starch (TGS) consumption on the jejunal barrier function and expression of genes related to inflammation, barrier function and the mucosal defence in jejunum, ileum, caecum and colon of pigs. Moreover, interactions of TGS-induced alterations in bacterial metabolites and composition with host mucosal responses were assessed using sparse partial least squares regression and relevance network analysis. Intestinal samples were collected after pigs (n 8/diet; 4 months of age) were fed the experimental diets for 10 d. Consumption of TGS did not modify jejunal barrier function and gene expression. By contrast, TGS down-regulated the caecal expression of zonula occludens-1 and mucin 2 and of genes within the toll-like receptor 4 and NF-κB pro-inflammatory signalling cascade. Relevance networks revealed a microbiome signature on ileal, caecal and colonic mucosal signalling as TGS-derived changes in bacterial genera and fermentation acids, such as propionic acid, correlated with the differently expressed genes in ileum, caecum and colon of pigs. In conclusion, the present findings suggest certain anti-inflammatory capabilities of TGS by down-regulating the expression of pro-inflammatory pathways in the caecal mucosa, which seems to be mediated, at least in part, by TGS-induced changes in microbial action in the large intestine.

Comparison of Thermal Manikin Modeling and Human Subjects' Response During Use of Cooling Devices Under Personal Protective Ensembles in the Heat.

IntroductionPersonal protective equipment (PPE) recommended for use in West Africa during the Ebola outbreak increased risk for heat illness, and countermeasures addressing this issue would be valuable.Hypothesis/ProblemThe purpose of this study was to examine the physiological impact and heat perception of four different personal cooling devices (PCDs) under impermeable PPE during low-intensity exercise in a hot and humid environment using thermal manikin modeling and human testing. METHODS: Six healthy male subjects walked on a treadmill in a hot/humid environment (32°C/92% relative humidity [RH]) at three metabolic equivalents (METs) for 60 minutes wearing PPE recommended for use in West Africa and one of four different personal cooling devices (PCDs; PCD1, PCD2, PCD3, and PCD4) or no PCD for control (CON). The same ensembles were tested with thermal manikin modeling software in the same conditions to compare the results. RESULTS: All PCDs seemed to reduce physiological heat stress characteristics when worn under PPE compared to CON. Both the manikin and human testing provided similar results in core temperature (Tc) and heat sensation (HS) in both magnitude and relationship. While the manikin and human data provided similar skin temperature (Tsk) characterization, Tsk estimation by the manikin seemed to be slightly over-estimated. Weight loss, as estimated by the manikin, was under-estimated compared to the human measurement. CONCLUSION: Personal cooling device use in conjunction with impermeable PPE may be advantageous in mitigating physiological and perceptual burdens of heat stress. Evaluation of PCDs worn under PPE can be done effectively via human or manikin testing; however, Tsk may be over-estimated and weight loss may be under-estimated. Thermal manikin testing of PCDs may provide fast and accurate information to persons recommending or using PCDs with PPE. QuinnT, KimJH, SeoY, CocaA. Comparison of thermal manikin modeling and human subjects' response during use of cooling devices under personal protective ensembles in the heat. Prehosp Disaster Med. 2018;33(3):279-287.

Reanimación con control de daños en el trauma grave pediátrico / Damage control resuscitation in pediatric severe trauma

INTRODUCCIÓN: El trauma es una importante causa de morbimortalidad en la población pediátrica, alcanzando el primer lugar en mortalidad en nuestro país, sin considerar las patologías perinatales y las malformaciones congénitas. Un porcentaje importante de las muertes precoces y tardías secundarias a esta causa, así como sus secuelas, podrían prevenirse con una óptima y oportuna reanimación. OBJETIVOS: Revisar -a la luz de la evidencia existente- la atingencia de la reanimación con control de daños (RCD) en el trauma pediátrico grave, con énfasis en el manejo médico. MATERIAL Y MÉTODOS: Se usó la base de datos PubMed, Cochrane Library y Google académico, empleando como términos de búsqueda (MeSH): trauma, politrauma, reanimación, control de daños, líquidos de reanimación, hipotensión permisiva, coagulopatía, transfusión masiva y niños. RESULTADOS: El concepto de RCD puede ser aplicado en el trauma grave en niños, teniendo en cuenta sus particularidades anatomo-fisiológicas. El principio se basa en el manejo de la tríada letal (coagulopatía, acidosis e hipotermia) asociado a una cirugía con control de daños. En este contexto se analiza la limitación de cristaloides, la hipotensión permisiva y la reanimación hemostática en el manejo inicial del trauma pediátrico gra ve. CONCLUSIONES: Estudios futuros deberán establecer el verdadero rol de la hipotensión permisiva, la relación óptima de hemoderivados a transfundir y la mejor estrategia para predecir la activación de protocolos de transfusión masiva y su impacto en niños con trauma grave.

INTRODUCTION: Trauma is an important cause of morbidity and mortality in the pediatric population. It has the first place in mortality in our country without considering perinatal pathologies and congenital malformations. An important percentage of early and late deaths secondary to this cau se, as well as its sequelae, could be prevented with optimal and timely resuscitation. OBJECTIVE: To review the applicability of damage control resuscitation (DCR) in severe pediatric trauma, with emphasis on medical management. Material and Methods: The PubMed, the Cochrane Library and the Google academic database were used. Search terms (MeSH) were: trauma, polytrauma, resuscitation, damage-control, fluids, permissive hypotension, coagulopathy, massive transfusion and children. RESULTS: The concept of DCR can be applied to severe pediatric trauma, taking into account their anatomical and physiological characteristics. The principle is based on the management of the lethal triad (coagulopathy, acidosis and hypothermia) associated with damage control surgery. Limitation of crystalloids, permissive hypotension and hemostatic resuscitation are reviewed in the initial treatment of severe pediatric trauma. CONCLUSION: Future studies should establish the true role of permissive hypotension, the optimal relationship between blood products and the best strategy to predict the activation of massive transfusion protocols and their impact on children with severe trauma.

Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice.

n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3-)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3- male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3- offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3- animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes.

Effects of dietary live yeast supplementation on growth performance, diarrhoea severity, intestinal permeability and immunological parameters of weaned piglets challenged with enterotoxigenic Escherichia coli K88.

This study aimed to investigate the effects of dietary live yeast (LY) supplementation on growth, intestinal permeability and immunological parameters of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Piglets weaned at 21 d were allocated into three treatments with six pens and six piglets per pen, receiving the control diet (CON), diets supplemented with antibiotics plus zinc oxide (ANT-ZnO) and LY (Saccharomyces cerevisiae strain CNCM I-4407), respectively, for a period of 2 weeks. On day 8, thirty-six piglets were selected as control without ETEC (CON), CON-ETEC, ANT-ZnO-ETEC and LY-ETEC groups challenged with ETEC until day 10 for sample collections. Piglets fed ANT-ZnO diet had the highest average daily gain and average daily feed intake (P<0·05) during the 1st week, but ADG of piglets fed the ANT-ZnO diet was similar as piglets fed LY diet during the second week. Piglets with LY-ETEC or ANT-ZnO-ETEC had markedly lower diarrhoea score (P<0·05) than piglets with CON-ETEC during the 24 h after ETEC challenge. Relative to piglets with CON, the counts of E. coli, urinary ratio of lactulose to mannitol, plasma IL-6 concentration, mRNA abundances of innate immunity-related genes in ileum and mesenteric lymph node tissues were increased (P<0·05), whereas the villous height of jejunum and relative protein expression of ileum claudin-1 were decreased (P<0·05) in piglets with CON-ETEC; however, these parameters did not markedly change in piglets with LY-ETEC or ANT-ZnO-ETEC. In summary, dietary LY supplementation could alleviate the severity of diarrhoea in piglets with ETEC, which may be associated with the improved permeability, innate immunity and bacterial profile.

A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.

A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (P<0·05) of genes coding for v-Akt murine thymoma viral oncogene homolog 2, resistin and v-Raf-1 murine leukaemia viral oncogene homolog 1 (Raf1) in offspring skeletal muscle and acetyl-CoA carboxylase (Acaca), fatty acid synthase and phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit ß in offspring liver. Skeletal muscle neuropeptide Y and hepatic Kruppel-like factor 10 were up-regulated in HFS v. CON offspring (P<0·05). Compared with CON, Acaca and Raf1 protein expression levels were significantly lower in HFS offspring. Maternal HFS induced higher homoeostasis model of assessment index of insulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

Blood fatty acid changes in healthy young Americans in response to a 10-week diet that increased n-3 and reduced n-6 fatty acid consumption: a randomised controlled trial.

Military personnel generally under-consume n-3 fatty acids and overconsume n-6 fatty acids. In a placebo-controlled, double-blinded study, we investigated whether a diet suitable for implementation in military dining facilities and civilian cafeterias could benefit n-3/n-6 fatty acid status of consumers. Three volunteer groups were provided different diets for 10 weeks. Control (CON) participants consumed meals from the US Military's Standard Garrison Dining Facility Menu. Experimental, moderate (EXP-Mod) and experimental-high (EXP-High) participants consumed the same meals, but high n-6 fatty acid and low n-3 fatty acid containing chicken, egg, oils and food ingredients were replaced with products having less n-6 fatty acids and more n-3 fatty acids. The EXP-High participants also consumed smoothies containing 1000 mg n-3 fatty acids per serving, whereas other participants received placebo smoothies. Plasma and erythrocyte EPA and DHA in CON group remained unchanged throughout, whereas EPA, DHA and Omega-3 Index increased in EXP-Mod and EXP-High groups, and were higher than in CON group after 5 weeks. After 10 weeks, Omega-3 Index in EXP-High group had increased further. No participants exhibited changes in fasting plasma TAG, total cholesterol, LDL, HDL, mood or emotional reactivity. Replacing high linoleic acid (LA) containing foods in dining facility menus with similar high oleic acid/low LA and high n-3 fatty acid foods can improve n-6/n-3 blood fatty acid status after 5 weeks. The diets were well accepted and suitable for implementation in group feeding settings like military dining facilities and civilian cafeterias.

Effects of subacute ingestion of chlorogenic acids on sleep architecture and energy metabolism through activity of the autonomic nervous system: a randomised, placebo-controlled, double-blinded cross-over trial.

Chlorogenic acids (CGA) are the most abundant polyphenols in coffee. Continuous consumption of CGA reduces body fat and body weight. Since energy metabolism and sleep are controlled by common regulatory factors, consumption of CGA might modulate sleep. Lack of sleep has been identified as a risk factor for obesity, hypertension and type 2 diabetes. The aim of this study was to determine the effects of ingesting CGA over 5 d on energy metabolism and sleep quality in humans. A total of nine healthy subjects (four male and five female) completed a placebo-controlled, double-blinded, cross-over intervention study. Subjects consumed a test beverage containing 0 or 600 mg of CGA for 5 d. On the fifth night, subjects stayed in a whole-room metabolic chamber to measure energy metabolism; sleep was evaluated using polysomnographic recording. It was found that CGA shortened sleep latency (9 (sem 2) v. 16 (sem 4) min, P<0·05) compared with the control, whereas no effect on sleep architecture, such as slow-wave sleep, rapid eye movement or waking after sleep onset, was observed. Indirect calorimetry revealed that consumption of CGA increased fat oxidation (510 (sem 84) kJ/8 h (122 (sem 20) kcal/8 h) v. 331 (sem 79) kJ/8 h (81 (sem 19) kcal/8 h), P<0·05) but did not affect energy expenditure during sleep. Consumption of CGA enhanced parasympathetic activity assessed from heart-rate variability during sleep (999 (sem 77) v. 919 (sem 54), P<0·05). A period of 5-d CGA consumption significantly increased fat oxidation during sleep, suggesting that beverages containing CGA may be beneficial to reduce body fat and prevent obesity. Consumption of CGA shortened sleep latency and did not adversely affect sleep quality.

Ginsenoside Rg1 suppresses early stage of adipocyte development via activation of C/EBP homologous protein-10 in 3T3-L1 and attenuates fat accumulation in high fat diet-induced obese zebrafish.

BACKGROUND: Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. METHODS: 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. RESULTS: Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the C/EBPß transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase 3ß, which are also essential for stimulating the expression of CEBPß. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. CONCLUSION: We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.