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Transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed as a potential new tool in the treatment of major depressive disorder. Prior studies have demonstrated that taVNS enhances cognitive control and is able to modulate brain activity in key regions involved in cognitive emotion regulation, such as the anterior cingulate and medial prefrontal cortex, which is known to be impaired in depressed patients. Preclinical studies are lacking but may provide important insights into the working mechanisms of taVNS on cognitive emotion regulatory processes. In this between-subject study, 83 healthy subjects underwent a single-session of active taVNS or sham stimulation, after which cognitive reappraisal was examined using a computer-based cognitive emotion regulation task. Our results indicate that participants receiving active taVNS, compared to sham, were better at using cognitive reappraisal and rated their response to emotion-eliciting pictures as less intense. Yet, even though we found significant differences in behavioral measures of cognitive emotion regulation, no differences between groups were found in terms of physiological responses to the emotional stimuli. Overall, these findings suggest a positive effect of taVNS on the cognitive reappraisal of emotions, but future studies assessing objective measures of neural activity during cognitive emotion regulation following taVNS are warranted., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Transcranial Direct Current Stimulation (tDCS) is an effective treatment during the acute phase of a major depressive episode (MDE), although the evidence for its follow-up efficacy is mixed. A systematic review and meta-analysis were performed. MEDLINE/PubMed, Scopus (EMBASE), Web of Science, Cochrane Library and additional sources were searched from inception to April 29, 2021. Studies that followed up adults treated with tDCS during an MDE - using (interventional) and/or not using (observational) tDCS in the follow-up period were included. The primary outcome was the Hedges' g for the follow-up depression scores. Small study effects and sources of heterogeneity were explored. 427 studies were retrieved and 11 trials (13 datasets, n = 311) were included, most presenting moderate bias. Results showed a follow-up depression improvement (k = 13, g = -0.81, 95% confidence interval [CI]: -1.28; -0.34, I² = 84.0%), which was probably driven by the interventional studies (k = 7, g= -1.12, 95% CI: -1.84; -0.40, I² = 87.1%). No predictor of response was associated with the outcome. No risk of publication bias was found. Significant between-study heterogeneity may have influenced the overall results. Our findings suggest that tDCS produces effects beyond the intervention period during MDEs. Maintenance sessions are advised in future research., (Copyright © 2021. Published by Elsevier B.V.)

Background: Randomised clinical trials (RCTs) investigating transcranial direct current stimulation (tDCS) efficacy for depression show significant heterogeneity in outcomes., Objective: To investigate the magnitude of the sham tDCS response and its potential moderators in the treatment of depression., Methodology: A systematic review and aggregate meta-analysis (PROSPERO ID CRD42020161254). The systematic review was conducted in the PubMed, Scopus (EMBASE) and Cochrane Library databases. Only RCTs enrolling adult subjects with an acute depressive episode with a sham tDCS group were included., Results: Twenty-three studies (twenty-five datasets, 501 participants) were included. Sham tDCS response was large (Hedges' g = 1.09; 95% CI: 0.8;1.38). Secondary and subgroup analyses showed that sham protocols employing a ramp-up/ramp-down at the beginning and end of stimulation presented a significantly lower sham response compared to other protocols. Univariate meta-regression analyses found that sham response was associated with higher risk of blinding bias, and with thetreatment effect size of the active tDCS group. Subgroup analyses also showed that placement of the cathode over the lateral right frontal area (F8) presented a significantly lower sham response. Other moderators, including treatment resistance, baseline severity of depressive symptoms, and total charge delivered were not associated with the magnitude of the sham response., Conclusion: The sham tDCS response was large. Our findings demonstrate the need for standardization of sham tDCS protocols and bring attention to important considerations that can guide future RCTs employing tDCS for the treatment of MDD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the interaction of zinc source (ZnSO 4 vs. zinc amino acid complex) and vitamin E level (50 IU vs. 100 IU) on performance and intestinal health of broilers exposed to a temperature challenge in the finisher period. A total of 1224 day old male Ross 308 broilers were randomly distributed among 4 dietary treatments (9 replicates per treatment). Dietary treatments were organized in a 2 × 2 factorial arrangement: two sources of zinc, 60 mg/kg of Zn as ZnSO 4 .7H 2 O or 60 mg/kg of Zn as zinc amino acid complexes (ZnAA) combined with two levels of vitamin E (50 or 100 IU/kg). Zinc and vitamin E were added to a wheat/rye-based diet that was designed to create a mild nutritional challenge. From day 28 until day 36 (finisher period), all birds were subjected to chronic cyclic high temperatures (32°C ± 2°C and RH 55-65% for 6 h daily). The combination of ZnAA and 50 IU/kg of vitamin E improved weight gain in the starter (day 0-10), finisher (day 28-36) and overall period (day 0-36) and feed conversion ratio in the starter (day 0-10) and finisher phase (day 28-36). Providing Zn as ZnAA significantly improved villus length and villus/crypt ratio in the starter, grower and finisher period and decreased infiltration of T-lymphocytes and ovotransferrin leakage in the finisher period. In conclusion, providing broilers with a diet supplemented with ZnAA and a vitamin E level of 50 IU/kg, resulted in better growth performance as compared to all other dietary treatments. Interestingly, under the conditions of this study, positive effects of ZnAA on performance did not occur when vitamin E was supplemented at 100 IU/kg in feed. Moreover, providing zinc as zinc amino acid complex improved intestinal health., (© 2020 Wiley-VCH GmbH.)

Classic in vitro experiments (Severin's phenomenon) demonstrated that acute carnosine supplementation may potentiate muscle contractility. However, upon oral ingestion, carnosine is readily degraded in human plasma by the highly active serum carnosinase-1 (CN1). We developed a novel strategy to circumvent CN1 by preexercise ingestion of combined carnosine (CARN) and anserine (ANS), the methylated analog with similar biochemical properties but more resistant to CN1. First, in vitro hydrolysis was tested by adding carnosine and anserine to human plasma, alone or in combination. Second, five subjects were supplemented with 25 mg/kg anserine or 25 mg/kg of each anserine and carnosine to test in vivo bioavailability. Third, two double-blind, placebo-controlled, crossover studies investigated the effect of preexercise ANS + CARN (20 mg/kg body wt of each) supplementation on performance during a single all-out Wingate test following 6-min high-intensity cycling ( study A ) or three repeated Wingate tests ( study B ). In vitro experiments demonstrated slower degradation of anserine versus carnosine, which was further slowed by simultaneously adding carnosine. In vivo bioavailability of plasma anserine was more prominent [2.5-fold increased area under the curve (AUC)] when ANS + CARN versus ANS was ingested. Study A showed significantly higher (+6% ± 11%; P = 0.04) power in the first 5 s of the Wingate test following ANS + CARN (12.8 ± 2.4 W/kg) versus placebo (12.1 ± 2.2 W/kg). Study B demonstrated increased peak power (+3%) throughout three consecutive Wingate tests (ANS + CARN 10.5 ± 0.6 W/kg vs. placebo 10.2 ± 9.9 W/kg). These experiments reveal a novel acute nutritional method to effectively raise plasma anserine and carnosine by high-dose combined supplementation. This approach led to improved initial cycling power, revealing a new nutritional strategy to increase exercise performance. NEW & NOTEWORTHY Current results reveal that carnosine and anserine competitively bind to the highly active carnosinase enzyme in human plasma. Acute combined carnosine and anserine supplementation is therefore described as novel strategy to raise plasma anserine and carnosine. We report that indices of maximal exercise/muscle power during the initial stage of a Wingate test were significantly improved by preexercise 20-25mg/kg body wt anserine and carnosine supplementation, pointing toward a novel acute nutritional strategy to improve high-intensity exercise performance.

Objective: Research suggests that the combination of different non-invasive brain stimulation techniques, such as intermittent theta-burst stimulation (iTBS) and transcranial direct current stimulation (tDCS), could enhance the effects of stimulation. Studies investigating the combination of tDCS and iTBS over the dorsolateral prefrontal cortex (DLPFC) are lacking. In this within-subjects study, we evaluated the additive effects of iTBS with tDCS on psychophysiological measures of stress., Method: Sixty-eight healthy individuals were submitted to a bifrontal tDCS + iTBS and sham tDCS + iTBS protocol targeting the DLPFC with a one-week interval. The Maastricht Acute Stress Test was used to activate the stress system after stimulation. Stress reactivity and recovery were assessed using physiological and self-report measures., Results: The stressor evoked significant psychophysiological changes in both stimulation conditions. However, no evidence was found for differences between them in stress reactivity and recovery. Participants reported more pain and feelings of discomfort to the bifrontal tDCS + iTBS protocol., Conclusion: In this study set-up, iTBS plus tDCS was not superior to iTBS in downregulating stress in healthy subjects., Significance: There is no evidence for an effect of combined tDCS-iTBS of the DLPFC on stress according to the parameters employed in our study. Future studies should explore other stimulation parameters, additive approaches and/or neurobiological markers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Performance (from 10 weeks until slaughter), carcass and meat quality, and effectiveness of immunocastration was compared in crossbred offspring of stress positive (BP+) and negative (BP-) Belgian Piétrain and Canadian Duroc (CD) given the second vaccination of Improvac® at different times (4, 6, 8 weeks before slaughter). CD offspring had a significantly higher daily gain (DG) and feed intake (DFI), and lower predicted lean meat percentage (LMP) and dressing yield compared to BP+ and BP-, while feed conversion ratio (FCR) did not differ. CD offspring had significantly lower drip loss and higher pH i, intramuscular fat content than BP+ and BP- (except for pH i ). No significant effect of vaccination time on DG nor FCR was observed. Predicted LMP tended to increase as time-post injection decreased, while meat quality was minor affected. Earlier vaccination had no effect on the effectiveness of immunocastration based on testosterone and GnRH-binding., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Scope: The consumption of red and processed meat, and not white meat, associates with the development of various Western diseases such as colorectal cancer and type 2 diabetes. This work aims at unraveling novel meat-associated mechanisms that are involved in disease development., Methods and Results: A non-hypothesis driven strategy of untargeted metabolomics is applied to assess colon tissue from rats (fed a high dose of beef vs. white meat) and from pigs (fed red/processed meat vs. white meat), receiving a realistic human background diet. An increased carnitine metabolism is observed, which is reflected by higher levels of acylcarnitines and 3-dehydroxycarnitine (rats and pigs) and trimethylamine-N-oxide (rats). While 3-dehydroxycarnitine is higher in HT29 cells, incubated with colonic beef digests, acylcarnitine levels are reduced. This suggests an altered response from colon cancer cell line towards meat-induced oxidative stress. Moreover, metabolic differences between rat and pigs are observed in N-glycolylneuraminic acid incorporation, prostaglandin, and fatty acid synthesis., Conclusion: This study demonstrates elevated (acyl)carnitine metabolism in colon tissue of animals that follow a red meat-based diet, providing mechanistic insights that may aid in explaining the nutritional-physiological correlation between red/processed meat and Western diseases., (© 2021 Wiley-VCH GmbH.)

Mechanisms explaining epidemiological associations between red (processed) meat consumption and chronic disease risk are not yet elucidated, but may involve oxidative reactions, microbial composition alterations, inflammation and/or the formation of toxic bacterial metabolites. First, in vitro gastrointestinal digestion of 23 cooked beef-lard minces, to which varying doses of nitrite salt (range 0-40 g/kg) and sodium ascorbate (range 0-2 g/kg) were added, showed that nitrite salt decreased protein carbonylation up to 3-fold, and inhibited lipid oxidation, demonstrated by up to 4-fold lower levels of 'thiobarbituric acid reactive substances', 32-fold lower 4-hydroxynonenal, and 21-fold lower hexanal values. The use of ascorbate increased the antioxidant effect of low nitrite salt levels, whereas it slightly increased protein carbonylation at higher doses of nitrite salt. The addition of a low dose of ascorbate without nitrite salt slightly promoted oxidation during digestion, whereas higher doses had varying antioxidant effects. Second, 40 rats were fed a diet of cooked chicken- or beef-lard minces, either or not cured, for three weeks. Beef, compared to chicken, consumption increased lipid oxidation (2- to 4-fold) during digestion, and gut protein fermentation (cecal iso-butyrate, (iso-)valerate, and fecal indole, cresol), but oxidative stress and inflammation were generally not affected. Cured, compared to fresh, meat consumption significantly increased stomach protein carbonylation (+16%), colonic Ruminococcaceae (2.1-fold) and cecal propionate (+18%), whereas it decreased cecal butyrate (-25%), fecal phenol (-69%) and dimethyl disulfide (-61%) levels. Fecal acetaldehyde and diacetyl levels were increased in beef-fed rats by 2.8-fold and 5.9-fold respectively, and fecal carbon disulfide was 4-fold higher in rats consuming cured beef vs. fresh chicken. Given their known toxicity, the role of acetaldehyde and carbon disulfide in the relation between meat consumption and health should be investigated in future studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare no funding or conflicts of interest.

Background: chicken meat extract is a popular functional food in Asia. It is rich in the bioactive compounds carnosine and anserine, two histidine-containing dipeptides (HCD). Studies suggest that acute pre-exercise ingestion of chicken extracts has important applications towards exercise performance and fatigue control, but the evidence is equivocal. This study aimed to evaluate the ergogenic potential of the pre-exercise ingestion of a homemade chicken broth (CB) vs a placebo soup on a short-lasting, high-intensity cycling exercise., Methods: fourteen men participated in this double-blind, placebo-controlled, crossover intervention study. Subjects ingested either CB, thereby receiving 46.4 mg/kg body weight of HCD, or a placebo soup (similar in taste without HCD) 40 min before an 8 min cycling time trial (TT) was performed. Venous blood samples were collected at arrival (fasted), before exercise and at 5 min recovery. Plasma HCD were measured with UPLC-MS/MS and glutathione (in red blood cells) was measured through HPLC. Capillary blood samples were collected at different timepoints before and after exercise., Results: a significant improvement (p = 0.033; 5.2%) of the 8 min TT mean power was observed after CB supplementation compared to placebo. Post-exercise plasma carnosine (p <  0.05) and anserine (p <  0.001) was significantly increased after CB supplementation and not following placebo. No significant effect of CB supplementation was observed either on blood glutathione levels, nor on capillary blood analysis., Conclusions: oral CB supplementation improved the 8 min TT performance albeit it did not affect the acid-base balance or oxidative status parameters. Further research should unravel the potential role and mechanisms of HCD, present in CB, in this ergogenic approach.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Next to the risk of allograft failure, major obstacles for disease-free survival after kidney transplantation include a higher incidence of cancer, infection and cardiovascular events. Risk factors for adverse clinical outcomes include pre-existent comorbidities, the introduction of an immunodeficient status and (lack of) lifestyle changes after transplantation. Indeed, physical inactivity and poor physical fitness are important targets to address in order to improve clinical outcomes after kidney transplantation. This review summarizes the current evidence on exercise training after kidney transplantation, derived from randomized controlled trials. As much as possible, results are discussed in the perspective of the Standardized Outcomes in Nephrology-Transplantation core outcomes, which were recently described as critically important outcome domains for trials in kidney transplant recipients., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

This study was performed to investigate meat quality traits of loin and ham of commercial pigs as affected by genetic differences in carcass and growth traits of the parent lines. Three hybrid sow lines were crossbred with two types of Belgian Piétrain with different breeding goals (BP growth and BP carcass emphasizing daily growth and carcass conformation, respectively). Pig live performance and carcass quality of 270 offspring were measured, and meat quality of the loin and (cooked) ham was evaluated on 216 animals. Despite the differences in pig live performance and carcass quality for sow line, little effect on meat quality was observed. Only a lower (p < 0.05) intramuscular fat content of ham and a tendency (p < 0.1) toward lower cooking yield was observed in offspring of the sow line with the highest versus the lowest carcass lean content. Loin traits were only weakly associated with fresh and cooked ham quality traits., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The assessment of the actual contribution of red or processed meat to increasing the risk of suffering cardiovascular diseases (CVD) requires identification of specific harmful components and their underlying pathological mechanisms. In regards to CVD, meat lipids and their oxidation products have been recurrently studied due to their implications on lipid metabolism, hypercholesterolemia, obesity, and risk of suffering vascular events such as stroke. The impact of excess NaCl intake on increasing blood pressure is well-established and processed meat products have been recognized as a major contributor to dietary sodium in developed countries. Recent evidence has also suggested carnitine from red meat, as a precursor for trimethylamine-N-oxide, which has been shown to cause atherosclerosis, may increase the risk of suffering CVD in experimental animals. The present review aims to provide an updated overview, including evidence, controversies and unresolved questions on both the epidemiology and mechanisms relating red and processed meat consumption to CVD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Because of the need to abolish the castration of piglets without anaesthesia/analgesia, the pig industry is searching for a mode of action for the valorisation of meat with boar taint, an off-odour in entire male pigs. Carcasses with boar taint were selected by means of sensory and chemical analysis, after which patties with different levels of tainted boar meat were produced, as well as cooked ham and Frankfurter sausages using different smoke condensates and cooking temperatures. For these products orthonasal and retronasal boar taint odour were assessed by a trained expert panel. The results offer guidance regarding dilution of tainted meat (with <400 µg/kg androstenone if skatole is low or <200 µg/kg androstenone in concurrence with ≥37 µg/kg skatole) and the potential application of smoke condensates (e.g., Rudinsmoke C for sausages and Smokez LFBN for ham) as promising boar taint masking strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Because of the large diversity in processed meat products and the potential involvement of oxidation processes in the association between red and processed meat consumption and chronic diseases, the concentration of oxidation products after gastrointestinal digestion of commercial luncheon meat products was investigated. A broad spectrum of meat products (n = 24), displaying large variation in macro- and micronutrient composition and processing procedures, was digested in vitro by simulating digestion fluids of the human gastrointestinal tract. Lipid and protein oxidation was assessed in the meat products before digestion and in the corresponding digests by measurement of free malondialdehyde, 4-hydroxy-2-nonenal, hexanal and protein carbonyl compounds. Compared to an unprocessed cooked pork mince, that was included as a reference in the digestion experiment, levels of lipid oxidation products were low in the digests of most meat products. Only the digests of Parma ham had slightly higher or comparable levels as the reference pork. In contrast, protein carbonyl compounds were comparable or up to 6 times higher in the processed meat products compared to the reference pork. Particularly raw-cooked and precooked-cooked meat products and corresponding digests had higher protein carbonyl levels, but also lower protein contents and higher fat to protein ratios. In conclusion, most luncheon meat products and corresponding digests contained lower amounts of free lipid oxidation products, but more protein carbonyl compounds compared to the reference pork., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

It was hypothesized that dietary guanidinoacetic acid (GAA), the precursor of creatine (Cr), would be beneficial to heat-stressed finisher broilers owing to improved cellular energy status and arginine sparing effects. A total of 720 one-day-old male Ross 308 broilers were allocated to 3 treatments, 0 (control), 0.6, or 1.2 g/kg of GAA added to complete corn-soybean meal diets, and were fed for 39 D, with 12 replicates (20 birds each) per treatment. A chronic cyclic heat stress model (at a temperature of 34°C and 50 to 60% relative humidity for 7 h daily) was applied in the finisher phase (day 25-39). Samples were taken on day 26 and 39 to determine thrombocyte, white blood cell, corticosterone, protein and amino acid levels in blood and Cr, phosphocreatine (PCr), and adenosine triphosphate levels in the breast muscle. Meat quality was assessed on day 40 after overnight fasting. Guanidinoacetic acid at a dose of 1.2 g/kg decreased feed-to-gain ratio compared with the control in the grower phase (1.32 vs. 1.35, respectively; P <0.05). In the finisher period, the supplementation of 1.2 g/kg of GAA reduced feed intake compared with the control (-3.3%, P <0.05), whereas both GAA supplementation levels improved feed efficiency markedly (1.76, 1.66, and 1.67 for 0 [control], 0.6, and 1.2 g/kg of GAA, respectively, P <0.05). Mortality outcomes highlight that GAA feeding improved survival during heat stress, supported by lower panting frequency (linear effect, P <0.05). Plasma arginine was higher with increase in dietary GAA concentration on day 26 (+18.3 and + 30.8% for 0.6 and 1.2 g/kg of GAA, respectively; P <0.05). This suggests enhanced availability of arginine for other metabolic purposes than de novo GAA formation. In the breast muscle, PCr (day 39, P <0.05), free Cr (day 39, P <0.05), total Cr (both days, P <0.05), and PCr-to-adenosine triphosphate ratio (day 39, P <0.05) levels were increased with higher GAA content in diet. Guanidinoacetic acid supplementation improved feed conversion and survival during chronic cyclic heat stress, which may be associated with enhanced breast muscle energy status and arginine sparing effect., (Copyright © 2020. Published by Elsevier Inc.)

Phenolic compounds in pig diets, originating either from feed ingredients or additives, may occur as glycosides, that is conjugated to sugar moieties. Upon ingestion, their bioavailability and functionality depend on hydrolysis of the glycosidic bond by endogenous or microbial glycosidases. Hence, it is essential to map the glycosidase activities towards phenolic glycosides present along gut. Therefore, the activity of three key glycosidases, that is α-glucosidase (αGLU), β-glucosidase (βGLU) and β-galactosidase (βGAL), was quantified in small intestinal mucosa and digesta of piglets at different gastrointestinal sites (stomach, three parts of small intestine, caecum and colon) and at different ages around weaning (10 days before and 0, 2, 5, 14 and 28 days after weaning). Activity assays were performed with p-nitrophenyl glycosides at neutral pH. The αGLU activities in mucosa and digesta were low (overall means 1.4 and 60 U respectively) as compared to βGLU (15.2 and 199 U) and βGAL (23.4 and 298 U; p < .001). Moreover, αGLU activity in mucosa was unaffected by age. Conversely, βGLU and βGAL activities dropped significantly after weaning. Minimal levels, ranging between 18% and 54% of the pre-weaning values, were reached at 5 days post-weaning. Similarly, in small intestinal digesta, reductions from 60% up to 90% were observed for the three enzyme activities on day five post-weaning as compared to pre-weaning levels. In caecal contents, activities were lowest at 14 days post-weaning, while in stomach and colon no clear weaning-induced effects were observed. Our data suggest that weaning affects the glycosidase activity in mucosa (mainly endogenous origin) and digesta (primarily bacterial origin) with the most pronounced effects occurring 5 days post-weaning. Moreover, differences in activities exist between different glycosidases and between gut locations. These insights can facilitate the prediction of the fate of existing and newly synthetized glycosides after oral ingestion in piglets., (© 2020 Blackwell Verlag GmbH.)

This study was designed to compare performance, carcass and meat quality of crossbred of a hybrid sow x three sire lines, i.e. stress positive Belgian Piétrain (BP), stress negative French Piétrain (FP) and Canadian Duroc (CD). BP offspring had a significantly higher carcass yield (p < .001) and lean meat content (p < .001) in comparison with FP, which was higher than CD. BP offspring had significantly lower pH (p < .05), water-holding capacity (WHC) (p < .001) and intramuscular fat (IMF) (p < .001) content in the loin compared to FP and CD, but these meat quality parameters, with the exception of pH, were superior for CD as compared to FP. In accordance with loin quality, pH i , pH u , WHC and IMF of BP were significantly lower (p < .05) compared to CD in the fresh and cooked ham. Most often, FP offspring could not be differentiated from the other offspring, with the exception of cooking loss of the cooked ham. Trained and consumer taste panels resulted in no significant differences (p > .1) in sensory attributes, however, consumers preffered CD based on ranking., Competing Interests: Declaration of Competing Interest None of the authors has a personal or financial conflict of interest with this experiment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This pre-registered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M = 21.05, SD = 2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In institutional ethical and deontological guidelines, there is a prevailing, static understanding of the research partnership, with a clear boundary between researcher and participant. In this article, we argue that such a static understanding may run the risk of impeding the development of an enhanced contextual and dynamic intersubjective understanding of the research partnership and its impact on the growing importance of role boundaries in qualitative research. Drawing from a refugee health study on trauma and forced migration, we explore the different ways in which participants and the researcher engaged with the researcher's multiple positions and role boundaries. In doing so, we aim to contribute to a reflective research practice by providing tools to recognize signs of potential harm and offer potential vehicles of reconstruction and agency within the intersubjective space of a dynamic research relationship, within a continuous, shared renegotiation process of role boundaries.

Scope: To improve understanding of the epidemiological link between red and processed meat consumption and chronic diseases, more insight into the formation of metabolites during meat digestion is warranted., Methods and Results: Untargeted mass-spectrometry-based metabolomics is applied to explore the impact of red and processed meat consumption (compared to chicken), combined with a prudent or Western dietary pattern. A pig feeding study (n = 32), as a sentinel for humans, is conducted in a 2 × 2 factorial design for 4 weeks. The luminal content of the small intestine and colon are collected to determine their metabolic fingerprints. Seventy-six metabolites (38 in the small intestine, 32 in the colon, and 6 in both intestinal compartments) contributing to the distinct gut metabolic profiles of pigs fed either chicken or red and processed meat are (tentatively) identified. Consumption of red and processed meat results in higher levels of short- and medium-chain acylcarnitines and 3-dehydroxycarnitine, irrespective of dietary context, whereas long-chain acylcarnitines and monoacylglycerols are associated with the red and processed Western diet., Conclusion: The identification of red and processed meat-associated gut metabolites in this study contributes to the understanding of meat digestion in a complex but controlled dietary context and its potential health effects., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione (GSH) redox system. Therefore, these parameters were simultaneously measured throughout the weaning phase, in piglets differing in birth weight category and weaning age, as these pre-weaning factors are important determinants for the weaning transition. Low birth weight (LBW) and normal birth weight (NBW) littermates were assigned to one of three weaning treatments; i.e. weaning at 3 weeks of age (3w), weaning at 4 weeks of age (4w) and removal from the sow at 3 d of age and fed a milk replacer until weaning at 3 weeks of age (3d3w). For each of these treatments, six LBW and six NBW piglets were euthanized at 0, 2, 5, 12 or 28 d post-weaning piglets, adding up 180 piglets., Results: Weaning increased the glutathione peroxidase activity on d 5 post-weaning in plasma, and duodenal and jejunal mucosa. Small intestinal glutathione-S-transferase activity gradually increased until d 12 post-weaning, and this was combined with a progressive rise of mucosal GSH up till d 12 post-weaning. Oxidation of the GSH redox status (GSH/GSSG E h ) was only observed in the small intestinal mucosa of 3d3w weaned piglets at d 5 post-weaning. These piglets also demonstrated increased fluorescein isothiocyanate dextran (FD4) and horseradish peroxidase fluxes in the duodenum and distal jejunum during the experiment, and specifically demonstrated increased FD4 fluxes at d 2 to d 5 post-weaning. On the other hand, profound villus atrophy was observed during the weaning transition for all weaning treatments. Finally, LBW and NBW piglets did not demonstrate notable differences in GSH redox status, small intestinal barrier function and histo-morphology throughout the experiment., Conclusion: Although moderate changes in the GSH redox system were observed upon weaning, the GSH redox status remained at a steady state level in 3w and 4w weaned piglets and was therefore not associated with weaning induced villus atrophy. Conversely, 3d3w weaned piglets demonstrated GSH redox imbalance in the small intestinal mucosa, and this co-occurred with a temporal malfunction of their intestinal barrier function., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

The monoterpene thymol has been proposed as a valuable alternative to in-feed antibiotics in animal production. However, the effectiveness of the antimicrobial is comprised by its fast absorption in the upper gastrointestinal tract. In this work, two glucoconjugates, thymol α-d-glucopyranoside (TαG) and thymol β-d-glucopyranoside (TβG), were compared with free thymol for their potential to deliver higher concentrations of the active compound to the distal small intestine of supplemented piglets. Additionally, an analytical method was developed and validated for the simultaneous quantification of thymol and its glucoconjugates in different matrices. In stomach contents of pigs fed with 3333 μmol kg -1 thymol, TαG, or TβG, total thymol concentrations amounted to 3048, 2357, and 1820 μmol kg -1 dry matter, respectively. In glucoconjugate-fed pigs, over 30% of this concentration was present in the unconjugated form, suggesting partial hydrolysis in the stomach. No quantifiable levels of thymol or glucoconjugates were detected in the small intestine or cecum for any treatment, indicating that conjugation with one glucose unit did not sufficiently protect thymol from early absorption., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Pigs were fed either red and processed meat or chicken meat within either a prudent or a Western dietary pattern for four weeks (2 × 2 full factorial design). The colon microbial community and volatile organic compounds were assessed (either quantified or based on their presence). Results show that Lactobacilli were characteristic for the chicken × prudent dietary pattern treatment and Paraprevotella for the red and processed meat × prudent dietary pattern treatment. Enterobacteriaceae and Desulfovibrio were characteristic for the chicken × Western dietary pattern treatment and Butyrivibrio for the red and processed meat × Western dietary pattern treatment. Campylobacter was characteristic for chicken consumption and Clostridium XIVa for red and processed meat, irrespective of the dietary pattern. Ethyl valerate and 1-methylthio-propane were observed more frequently in pigs fed red and processed meat compared to chicken meat. The prevalence of 3-methylbutanal was >80% for pigs receiving a Western dietary pattern, whereas for pigs fed a prudent dietary pattern the prevalence was <35%. The concentration of butanoic acid was significantly higher when the prudent dietary pattern was given, compared to the Western dietary pattern, but no differences for other short chain fatty acids or protein fermentation products were observed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The present study evaluated gluco-conjugation as a measure to delay thymol absorption and enhance its antimicrobial activity in the gut of weaned piglets. The three dietary treatments consisted of a basal diet without additives (T CON ), supplemented with thymol at 3.7 mmol/kg dry matter (T THY ), or with an equimolar amount of thymol α-D-glucopyranoside (T TαG ). Each dietary treatment was replicated in 6 pens with 2 piglets per pen ( n = 12 for analytical parameters) and was supplemented for 14 days. The total (free plus gluco-conjugated) thymol concentrations in the stomach contents were 14% lower in T TαG as compared to T THY piglets. Neither of the additives could be detected further down the gut. E.coli counts in the proximal small intestine were significantly lower in T THY than in T TαG pigs (3.35 vs. 4.29 log 10 CFU/g); however, other bacterial counts and their metabolites were unaffected by treatment. A metagenomic bacterial analysis revealed a great relative abundance of Lactobacillus spp. in the distal small intestine (range 88.4%-99.9%), irrespective of treatment. The intestinal barrier function was improved by T THY , but not T TαG , compared to T CON. In conclusion, gluco-conjugation did not result in higher thymol concentrations in the gut, but conversely, it seemed to diminish the biological effects of thymol in vivo., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Red meat has been associated with an increased cardiovascular disease (CVD) risk, possibly through gut microbial-derived trimethylamine-N-oxide (TMAO). However, previous reports are conflicting, and influences from the background diet may modulate the impact of meat consumption. This study investigated the effect of red and white meat intake combined with two different background diets on urinary TMAO concentration and its association with the colon microbiome in addition to apparent hepatic TMAO-related activity. For 4 weeks, 32 pigs were fed chicken or red and processed meat combined with a prudent or western background diet. 1 H NMR-based metabolomics analysis was conducted on urine samples and hepatic mRNA expression of TMAO-related genes determined. Lower urinary TMAO concentrations were observed after intake of red and processed meat when consumed with a prudent compared to a western background diet. In addition, correlation analyses between urinary TMAO concentrations and relative abundance of colon bacterial groups suggested an association between TMAO and specific bacterial taxa. Diet did not affect the hepatic mRNA expression of genes related to TMAO formation. The results suggest that meat-induced TMAO formation is regulated by mechanisms other than alterations at the hepatic gene expression level, possibly involving modulations of the gut microbiota., Competing Interests: The authors declare no conflict of interest.

This case report highlights for the first time a possible link between the presence of alfa-1-antitrypsin deficiency (AATD) and the susceptibility to invasive infections. The current patient, with known AATD, initially presented with nausea, vomiting and headache secondary to Listeria monocytogenes rhombencephalitis. Further on, he developed respiratory insufficiency due to probable invasive pulmonary aspergillosis. Diagnostic work-up could not show any arguments for an underlying immunodeficiency or malignancy. The consecutive course of two rare invasive infections in a healthy individual posed the hypothesis if the underlying AATD could be considered a possible trigger for infections. Indirect clinical observations in literature indeed support this link and in addition, two possible pathophysiological pathways might explain the higher susceptibility for infections in AATD patients. First, alveolar macrophages are dysfunctional in AATD patients leading to a lower apoptotic clearance of bacteria and other (mostly intracellular) pathogens. Secondly, a lower release and lower function of tumour necrosis factor α (TNFα) is seen in alfa-1-antitrypsin depletion, priming the path to more frequent infections, a mechanism that is similar in anti-TNFα treated patients. This case is the first to report on severe or invasive infections related to AATD in humans.

The aim of the present study was to assess the effect of sex and to estimate genetic parameters for several traits related to plasma oxidative status in slaughter pigs, i.e., ferric reducing ability of plasma (FRAP), concentrations of α-tocopherol and malondialdehyde (MDA), and glutathione peroxidase (GPx) activity. Blood samples were collected at slaughter from 477 Piétrain × (Landrace × Large White intercross) pigs of 2 performance test stations. Heritabilities (±SE) of plasma oxidative status traits as well as their phenotypic and additive genetic correlations with animal performance traits were estimated with multiple-trait REML animal models using VCE software. Results displayed no significant difference between barrows and gilts for FRAP and α-tocopherol in plasma. However, gilts had a significantly higher concentration of MDA and lower GPx activity compared with barrows. Heritability estimates were high for GPx (0.55 ± 0.05), and medium to low for α-tocopherol (0.30 ± 0.06), FRAP (0.22 ± 0.05), and MDA (0.15 ± 0.04). Estimated additive genetic and phenotypic correlations between these four traits were generally low, except for a negative additive genetic correlation between FRAP and GPx of -0.45 (±0.23). Additive genetic correlations between plasma oxidative status traits and animal performance traits were also generally absent or low with maximum values of ~0.3. Parameter estimates in this study have to be interpreted with caution because of the small size of the dataset. Nevertheless, it may be concluded that there is considerable additive genetic variance for plasma oxidative status traits in slaughter pigs. More research is warranted on the genetic determination of oxidative stress in farm animals and its relevance in breeding programs., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Zinc is an essential nutritional trace element for all forms of life as it plays an important role in numerous biological processes. In poultry, zinc is provided by in-feed supplementation, mainly as zinc oxide or zinc sulfate. Alternatively zinc can be supplemented as organic sources, which are characterized by using an organic ligand that may be an amino acid, peptide, or protein to bind zinc and have a higher bioavailability than inorganic zinc sources. There are limited number of studies directly comparing the effects of inorganic vs. organic zinc sources on performance and intestinal health in broilers. Therefore, a digestibility and a performance study were conducted to evaluate and compare the effect of an amino acid-complexed zinc source vs. an inorganic zinc source on intestinal health. The experiment consisted of 2 treatments: either a zinc amino acid complex or zinc sulfate was added to a wheat-rye based diet at 60 ppm Zn, with 10 replicates (34 broilers per pen) per treatment. Effects on performance, intestinal morphology, microbiota composition, and oxidative stress were measured. Supplementing zinc amino acid complexes improved the zinc digestibility coefficient as compared to supplementation with zinc sulfate. Broilers supplemented with zinc amino acid complexes had a significantly lower feed conversion ratio in the starter phase compared to birds supplemented with zinc sulfate . A significantly higher villus length was observed in broilers supplemented with zinc amino acid complexes at days 10 and 28. Supplementation with zinc amino acid complexes resulted in a decreased abundance of several genera belonging to the phylum of Proteobacteria. Plasma malondialdehyde levels and glutathione peroxidase activity showed an improved oxidative status in broilers supplemented with zinc amino acid complexes. In conclusion, zinc supplied in feed as amino acid complex is more readily absorbed, potentially conferring a protective effect on villus epithelial cells in the starter phase., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Intake of red and processed meat has been suspected to increase colorectal cancer risk potentially via endogenous formation of carcinogenic N-nitroso compounds or increased lipid and protein oxidation. Here we investigated the effect of inulin fortification of a pork sausage on these parameters. For four weeks, healthy Sprague-Dawley rats (n = 30) were fed one of three diets: inulin-fortified pork sausage, control pork sausage or a standard chow diet. Fecal content of apparent total N-nitroso compounds (ATNC), nitrosothiols and nitrosyl iron compounds (FeNO) were analyzed in addition to liver metabolism and oxidation products formed in liver, plasma and diets. Intriguingly, inulin fortification reduced fecal ATNC (p = 0.03) and FeNO (p = 0.04) concentrations. The study revealed that inulin fortification of processed meat could be a strategy to reduce nitroso compounds formed endogenously after consumption., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Scope: Muscle food characteristics (fatty acid profile, heme-Fe, intrinsic antioxidants) that relate to the formation of (patho)physiological oxidation products during gastrointestinal digestion are investigated., Methods and Results: Muscles (n = 33) from 18 mammal, poultry, and fish species, of which some are mixed with lard to standardize their fatty acid profile, are digested in vitro. Lipid oxidation is assessed by thiobarbituric reactive substances (TBARS), n-3 PUFA derivative 4-hydroxy-2-hexenal and propanal, n-6 PUFA derivative 4-hydroxy-2-nonenal and hexanal, and protein oxidation by carbonylation. Digests of n-3 PUFA-rich fish demonstrated the highest n-3 PUFA oxidation, whereas digests of various poultry and rabbit muscles showed highest n-6 PUFA oxidation, which correlated significantly with the n-6/n-3 PUFA ratio. Without lard addition, lipid oxidation is significantly higher in chicken and pork loin digests versus beef and deer digests, whereas the opposite occurred when these muscles are mixed with lard. Protein carbonylation correlates significantly with levels of TBARS and the sum of hydroxy-alkenals in digests. The n-6/n-3 PUFA ratio correlates well with the 4-hydroxy-2-nonenal/4-hydroxy-2-hexenal ratio in digests., Conclusions: Muscular fatty acid profiles largely explain type and extent of lipid and protein oxidation during gastrointestinal digestion. Red meat only stimulates oxidation when digested with specific fat sources., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Poultry meat has high levels of histidine-containing dipeptides (HCD) and consumption of meat rich in HCD may elicit certain health benefits. The aim of this work was to compare the HCD content (anserine and carnosine) in the breast and thigh muscles of two broiler strains differing in growth rate, feeding regime, and age at slaughter. A 3 (production system) × 2 (sex) × 2 (age at slaughter) full factorial arrangement was applied with fast-growing Ross 308 chicks fed ad libitum (ROSS-AL), slow-growing Sasso T451 chicks fed ad libitum (SASSO-AL), and Ross 308 chicks given limited feeding (ROSS-LIM). At the age of 40 and 62 days, eight birds per production system × sex combination were randomly selected for sampling of the breast and thigh muscle. Muscle HCD content was determined by high-performance liquid chromatography (HPLC)., Results: Across treatments, levels of anserine were 2.5- and 1.9-fold higher than carnosine in breast and thigh muscle respectively (P < 0.001), and levels of anserine and carnosine were 2.2- and 2.8-fold higher respectively in breast versus thigh muscle (P < 0.001). In breast muscle, SASSO-AL had higher levels of HCD than ROSS-AL and ROSS-LIM (P < 0.001). Considering different market meat types, breast muscle of 62-day-old SASSO-AL birds had more than threefold higher content of HCD compared to thigh muscle of 40-day-old ROSS-AL birds (P < 0.001)., Conclusion: Large differences in muscle HCD content were found, varying according to type of muscle and broiler. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

1. Guanidinoacetic acid (GAA) is the single endogenous precursor of creatine, which plays a critical role in energy homeostasis of cells. Since GAA is endogenously converted to creatine by methylation, it was hypothesised that the effects of dietary GAA supplementation might determine the methionine (Met) availability in corn-soybean based diets. 2. A total of 540, one-day-old male Ross 308 broilers were allocated to nine dietary treatments with six replicates (10 birds each) in a 3 × 3 factorial arrangement with three graded levels of supplementary Met (+0.4 g/kg per level), whilst cystine was equal across groups, resulting in a low, medium and high level of total sulphur amino acids, and with three levels of GAA (0, 0.6 and 1.2 g/kg). Birds were fed for 42 days. 3. Increasing levels of supplemental Met enhanced performance indices in all rearing periods, although there was no effect on feed conversion ratio in the grower or feed intake in the finisher periods. Final body weight was 8.8% and 14.6% higher in the birds fed medium and high Met diets, respectively, compared to the low Met level. Relative breast weight and protein content in muscle on d 25 linearly increased with higher levels of Met. At low and high Met levels, growth in the finisher phase was negatively affected by supplementing GAA at 1.2 g/kg. It was suggested that disturbances in methylation homeostasis and/or changes in Arg metabolism might explain these findings. At the end of the grower phase, muscle creatine content was higher when feeding GAA at 0.6 and 1.2 g/kg (4464 and 4472, respectively, vs . 4054 mg/kg fresh muscle in the control group). 4. The effects of dietary GAA supplementation were influenced by the dietary Met level only in the finisher period, which indicates the need for proper sulphur amino acid formulation in diets when feeding GAA.

The purpose of this study was to evaluate whether NaHCO 3 , administered via a 9-h stacked loading protocol (i.e. repeated supplementation with small doses in order to obtain a gradual increase in blood [HCO 3 - ]), has an ergogenic effect on repeated all-out exercise. Twelve physically active males were randomly assigned to receive either NaHCO 3 (BIC) or placebo (PL) in a double-blind cross-over design. NaHCO 3 supplementation was divided in three identical 3-h cycles: a 6.3 g bolus at the start, followed by 2.1 g doses at +1-h and +2-h, yielding a total NaHCO 3 intake of 0.4 g·kg -1 BM over 9-h. At the end of each cycle, participants performed 2-min all-out cycling. Capillary blood samples were analyzed for [HCO 3 - ], pH and [La - ]. Pre-exercise blood [HCO 3 - ] in PL decreased from 25.6±0.2 mmol·L -1 in bout 1 to 23.6±0.2 mmol·L -1 in bout 4, while increasing from 25.5±0.2 to 31.2±0.4 mmol·L -1 in BIC (P<0.05). Concomitantly, pre-exercise pH values gradually decreased in PL (from 7.41±0.00 to 7.39±0.01) and increased in BIC (from 7.41±0.01 to 7.47±0.01; P<0.05). Mean power output of the four bouts was higher in BIC (428±20 W) than in PL (420±20 W; P<0.05). The ergogenic effect on repeated all-out exercise occurred in the absence of gastrointestinal distress., Competing Interests: Authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Quercetin has been shown to alleviate mucosal damage and modulate the glutathione (GSH) redox system in the colon of rodents. In the current study, we assessed whether quercetin was able to mitigate small intestinal dysfunction in weaned pigs. Here, 224 weaned piglets were fed a diet containing quercetin at either 0, 100, 300, or 900 mg/kg diet until d14 post-weaning, followed by a common basal diet until d42. Eight animals per treatment were sampled at d5 and d14 post-weaning. In these animals, the small intestinal histomorphology, barrier function, and protein abundance of occludin, caspase-3, and proliferating cell nuclear antigen were assessed. None of these parameters were affected, and neither did quercetin improve performance up to d42 post-weaning. The GSH redox system was evaluated in blood, small intestinal mucosa, and liver. Quercetin did not affect the glutathione peroxidase, glutathione reductase, and glutamate-cysteine ligase activity in these tissues. In contrast, the hepatic glutathione transferase (GST) activity was significantly increased by quercetin supplementation at d5 post-weaning of 100, 300, and 900 mg/kg. Importantly, d5 was characterized by a more oxidized GSH redox status. To conclude, dietary quercetin had little effect on the small intestine, but did upregulate hepatic GST in the occurrence of redox disturbance.

Glutathione (GSH) is considered to play an important role in maintaining the integrity of the small intestine. In piglets, altered mucosal GSH levels might therefore be involved in weaning-induced changes of the small intestinal morphology and barrier function. To test this hypothesis, we aimed to challenge the mucosal GSH redox status during the first 28 days after weaning, by feeding diets containing 5% fresh linseed oil (CON), or 2.5% (OF1) or 5% (OF2) peroxidized linseed oil (peroxide value 225 mEq O2/kg oil) and exploring the effects on gut integrity. Piglets were pair-fed and had a total daily feed allowance of 32 g/kg BW. A fourth treatment included animals that were fed the control diet ad libitum (ACON). Animals were sampled at days 5 and 28 post-weaning. The malondialdehyde (MDA) concentration and GSH redox status (GSH/GSSG Eh) were determined in blood, liver and small intestinal mucosa. Histomorphology of the duodenal and jejunal mucosa was determined, and Ussing chambers were used to assess fluorescein isothiocyanate dextran (FD4) and horseradish peroxidase (HRP) fluxes across the mucosa. Results show that peroxidized linseed oil imposed an oxidative challenge at day 28, but not at day 5 post-weaning. At day 28, increasing levels of dietary peroxides to pair-fed pigs linearly increased MDA levels in duodenal and jejunal mucosa. Moreover, FD4 fluxes were significantly increased in OF1 (+75%) and OF2 (+64%) in the duodenum, and HRP fluxes tended (P=0.099) to show similar differences, as compared to CON. This co-occurred with a significant 11 mV increase of the hepatic GSH/GSSG Eh, potentiated by a significantly increased GSH peroxidase activity for treatments OF1 (+47%) and OF2 (+63%) in liver as compared to CON. Furthermore; duodenal HRP flux significantly correlated with the hepatic glutathione disulphide (GSSG) level (r=0.650), as also observed in the jejunum for hepatic GSSG (r=0.627) and GSH/GSSG Eh (r=0.547). The jejunal permeability was not affected, but FD4 and HRP fluxes significantly correlated with the local GSH (r=0.619; r=0.733) and GSSG (r=0.635; r=0586) levels. Small intestinal histomorphology was not affected by dietary lipid peroxides, nor were there any correlations found with the GSH redox system. To conclude, under oxidative stress conditions, jejunal barrier function is related to the local and hepatic GSH redox system. It is suggested that the hepatic GSH system participates in the elimination of luminal peroxides, and thereby impacts on duodenal barrier function.

Human diets contain a complex mixture of antioxidants and pro-oxidants that contribute to the body's oxidative status. In this study, 32 pigs were fed chicken versus red and processed meat in the context of a prudent or Western dietary pattern for 4 weeks, to investigate their oxidative status. Lipid oxidation products (malondialdehyde, 4-hydroxy-2-nonenal, and hexanal) were higher in the chicken versus red and processed meat diets (1.7- to 8.3-fold) and subsequent in vitro (1.3- to 1.9-fold) and in vivo (1.4 to 3-fold) digests ( P < 0.001), which was presumably related to the higher polyunsaturated fatty acid content in chicken meat and/or the added antioxidants in processed meat. However, diet had only a marginal or no effect on the systemic oxidative status, as determined by plasma oxygen radical absorbance capacity, malondialdehyde, glutathione, and glutathione peroxidase activity in blood and organs, except for α-tocopherol, which was higher after the consumption of the chicken-Western diet. In conclusion, in contrast to the hypothesis, the consumption of chicken in comparison to that of the red and processed meat resulted in higher concentrations of lipid oxidation products in the pig intestinal contents; however, this was not reflected in the body's oxidative status.

Objectives: Recently, the Velopharyngeal Insufficiency (VPI) Effects on Life Outcomes (VELO) questionnaire, which evaluates the impact of speech and swallowing difficulties on health-related quality of life (HRQoL) in patients with VPI (Skirko et al., 2012), was translated to Dutch (Bruneel et al., 2017). The purpose of this study was to evaluate the reproducibility, responsiveness and construct validity of this Dutch version of the questionnaire., Methods: To evaluate the reproducibility, 50 parents and 14 children with cleft palate re-completed the questionnaire after two weeks. Thirty-five parents and 8 children with cleft palate completed the VELO questionnaire after one year for the evaluation of the responsiveness. The correlation between age and the VELO questionnaire (construct validity), and the internal consistency (Cronbach's α) were re-determined based on the responses of 73 parents and 24 children., Results: Based on descriptive statistics, results of the Wilcoxon signed rank-test, and the absolute (SEM) and relative (ICC) consistency, the questionnaire showed good reproducibility. VELO scores did not significantly differ after one year, neither when performing separate analyses for the intervention (speech therapy) and the non-intervention group. Correlations indicated higher HRQoL, as perceived by the parents, with increasing age. The reverse was the case for the youth report. Cronbach's α showed excellent internal consistency for both reports., Conclusions: The VELO questionnaire showed good reproducibility and internal consistency. Moreover, results reconfirmed the age effect on VELO scores. To understand the implications of the results regarding the questionnaire's responsiveness, future research should focus on the identification of factors influencing the patient's evolution in HRQoL., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study investigated the effect of N -acetyl-cysteine (NAC) supplementation through drinking water on animal performance and the glutathione (GSH) redox system in weaned piglets, particularly in relation to the immediate post-weaning feed intake. To this end, 168 piglets were weaned and either fed ad libitum or fasted the first two days, and either or not administered 200 mg/L NAC via the drinking water until d14 post-weaning. Next to animal performance until day 42 (d42), the GSH redox system was measured in erythrocytes, small intestinal mucosa, liver, lung, and kidney tissue at d0, d2, and d14 post-weaning. Animal performance and GSH levels were not affected by NAC, nor by fasting. Irrespective of treatment, a significant drop in GSH at d2 post-weaning was found as compared to d0, in particular in liver (-69%), distal jejunal mucosa (-72%), and lung tissue (-80%). Post-weaning changes of the GSH redox status were strongly tissue-dependent. To conclude, this research indicates that GSH redox homeostasis was largely affected in multiple organs during the weaning transition. NAC supplementation did not increase GSH levels in any tissue, not even in fasted animals, questioning the fact if cysteine is the first or only limiting factor determining the rate of GSH synthesis in the early post-weaning phase.

Scope: High red meat and sucrose consumption increases the epidemiological risk for chronic diseases. Mechanistic hypotheses include alterations in oxidative status, gut microbiome, fat deposition, and low-grade inflammation., Methods and Results: For 2 weeks, 40 rats consumed a diet high in white or red meat (chicken-based or beef-based cooked mince, respectively), and containing corn starch or sucrose in a 2 × 2 factorial design. Lard was mixed with lean chicken or beef to obtain comparable dietary fatty acid profiles. Beef (vs chicken)-fed rats had higher lipid oxidation products (malondialdehyde, 4-hydroxy-2-nonenal, and hexanal) in stomach content and blood, and lower blood glutathione. Sucrose (vs corn starch)-fed rats showed increased blood lipid oxidation products and glutathione peroxidase activity, higher liver weight and malondialdehyde concentrations, and mesenterial and retroperitoneal fat accumulation. Beef-sucrose-fed rats had increased cardiac weight, suggesting pathophysiological effects on the cardiovascular system. The colonic microbiome of beef-sucrose-fed rats showed an outgrowth of the sulfate-reducing family of the Desulfovibrionaceae, and lower abundance of the Lactobacillus genus, indicating intestinal dysbiosis. Blood C-reactive protein, a marker for inflammation, was not different among groups., Conclusions: Consumption of a cooked beef-based meat product with sucrose increased oxidative stress parameters and promoted cardiac hypertrophy and intestinal dysbiosis., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Helicobacter pylori gastritis affects gastric pH and concentrations of ascorbic acid, hydrogen peroxide, hypochlorite, ammonia and urea, pepsin, and mucin. First, the separate effects of each of these altered factors on oxidation of pork were investigated during in vitro gastrointestinal digestion. Lipid and protein oxidation increased (range 23-48%) in duodenal digests of pork previously exposed to elevated (6.1) versus normal acidic stomach pH (2.3 to 3.5) conditions. Salivary nitrite reduced the formation of lipid and protein oxidation products (range 14-20%) under normal acidic but not elevated stomach pH conditions. Higher amounts of hydrogen peroxide and lower amounts of ascorbic acid decreased concentrations of lipid oxidation products in duodenal pork digests, whereas ammonia slightly stimulated protein oxidation during digestion. Second, two H. pylori gastritis-duodenal digestion models were installed using a set of altered compound concentrations at normal acidic or elevated stomach pH. The elevated pH-gastritis-duodenal digestion model increased pork protein oxidation compared with the normal pH-gastritis and the normal digestion model (14.3 ± 2.1 vs 8.2 ± 1.0 nmol DNPH/mg protein, P < 0.001). Compared with the other models, protein oxidation was also increased when nitrite-cured pork was exposed to the elevated pH-gastritis-duodenal digestion model (10.8 ± 1.4 vs 5.9 ± 0.8 nmol DNPH/mg protein, P < 0.001), but no significant effect of the model was observed when the pork was seasoned with herbs. Lipid oxidation was not or was marginally affected by the installed model.

Coagulase-negative staphylococci (CNS) contribute to the product quality of fermented meats. In spontaneously fermented meats, CNS communities are variable and difficult to predict, as their compositions depend on a superposed combination of different processing factors. To partially disentangle this superposition, a meat model system was used to study the influence of temperature and pH on the CNS community dynamics. Therefore, cured pork mince was prepared that was divided into three batches of different initial acidity levels, namely pH 5.7, pH 5.5, and pH 5.3. These three batches were incubated at three different temperatures, namely 23 °C, 30 °C, and 37 °C. Hence, the experimental set-up resulted in nine combinations of different temperature and initial pH values. Samples were analysed after 3 and 14 days to monitor pH, colony counts, and species diversity of the CNS communities, based on mannitol-salt-phenol-red agar (MSA) medium. At conditions of mild acidity (pH 5.7) and low temperature (23 °C), as often encountered during artisan-type meat fermentations, a co-prevalence of Staphylococcus xylosus, Staphylococcus equorum, and Staphylococcus saprophyticus occurred. At the same initial pH but higher incubation temperatures (30 °C and 37 °C), Staphylococcus lugdunensis became the prevailing CNS species, besides S. saprophyticus (30 °C) and the coagulase-positive species Staphylococcus aureus (37 °C). When the initial pH was set at 5.5, S. saprophyticus was the prevailing CNS species at both 23 °C and 30 °C, but it was replaced by Staphylococcus epidermidis and Staphylococcus simulans at 37 °C after 3 and 14 days, respectively. At the most acidic conditions (pH 5.3), CNS counts declined and many of the MSA isolates were of non-staphylococcal nature. Among others, Staphylococcus carnosus (23 °C), Staphylococcus warneri (30 °C), and S. epidermidis (37 °C) were found. Overall, the results of the present study indicated that the processing factors temperature and pH had a clear impact on the shaping of staphylococcal communities during meat fermentation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

During spontaneous meat fermentations, Staphylococcus equorum , Staphylococcus saprophyticus , and Staphylococcus xylosus are generally the most prevailing species within the communities of coagulase-negative staphylococci (CNS). There is an interest to introduce CNS isolates from artisan-style spontaneous meat fermentations as starter cultures in more industrialized processes, as to confer additional quality benefits. However, staphylococcal competitiveness within the meat matrix is affected by the processing conditions, which vary considerably among product types. A major factor of variability relates to the intensity of acidification, driven by the concentration of added carbohydrates. The effect of pH on CNS prevalence was studied in both a mince-based meat fermentation model and in fermented sausages produced on pilot scale. Roughly, from all experiments combined, it appeared that a pH of 5.3 corresponded with a breakpoint for CNS selection. Above this value, a general prevalence by S. xylosus was found, even overruling the addition of starter cultures consisting of S. equorum and S. saprophyticus strains. At pH values below 5.3, S. xylosus was also accompanied by S. equorum (following a mild pH drop) and S. saprophyticus (following a stronger pH drop). Still, addition of starter cultures affected the volatile profile compared to the control batch, even if those starter cultures were not able to dominate during the ripening process. This study nonetheless provides a warning for an overly confident use of specific CNS species as starter cultures, especially when in a given processing context the prevailing conditions do not allow superior growth compared to the CNS from the background microbiota.

Background: Many efforts have been devoted to improve the performance of dendritic cell (DC)-based cancer vaccines. Ideally, a DC vaccine should induce robust type 1-polarized T-cell responses and efficiently expand antigen (Ag)-specific cytotoxic T-cells, while being applicable regardless of patient human leukocyte antigen (HLA) type. Production time should be short, while maximally being good manufacturing practice (GMP)-compliant. We developed a method that caters to all of these demands and demonstrated the superiority of the resulting product compared with DCs generated using a well-established "classical" protocol., Methods: Immunomagnetically purified monocytes were cultured in a closed system for 3 days in GMP-compliant serum-free medium and cytokines, and matured for 24 h using monophosphoryl lipid A (MPLA)+ interferon-gamma (IFN-γ). Mature DCs were electroporated with messenger RNA (mRNA) encoding full-length antigen and cryopreserved. "Classical" DCs were cultured for 8 days in flasks, with one round of medium and cytokine supplementation, and matured with tumor necrosis factor alpha (TNF-α) + prostaglandin E2 (PGE2) during the last 2 days., Results: Four-day MPLA/IFN-γ-matured DCs were superior to 8-day TNF-α/PGE2-matured DCs in terms of yield, co-stimulatory/co-inhibitory molecule expression, resilience to electroporation and cryopreservation and type 1-polarizing cytokine and chemokine release after cell thawing. Electroporated and cryopreserved DCs according to our protocol efficiently present epitopes from tumor antigen-encoding mRNA, inducing a strong expansion of antigen-specific CD8+ T-cells with full cytolytic capacity., Conclusion: We demonstrate using a GMP-compliant culture protocol the feasibility of generating high yields of mature DCs in a short time, with a superior immunogenic profile compared with 8-day TNF-α/PGE2-matured DCs, and capable of inducing vigorous cytotoxic T-cell responses to antigen from electroporated mRNA. This method is now being applied in our clinical trial program., (Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

(1) Guanidinoacetic acid (GAA) is the single immediate endogenous precursor of creatine (Cr). It was hypothesised that dietary GAA would have different effects on performance and energy metabolites in breast muscle depending on the nutrient density (ND) of corn-soybean-based diets. (2) A total of 540 one-day-old male Ross 308 broilers were allocated to 9 dietary treatments with 6 replicates (10 birds each) in a 3 × 3 factorial arrangement with three levels of ND (low, 2800; medium, 2950 and high, 3100 kcal metabolizable energy (ME)/kg; and with the other nutrients being constant relative to ME) and supplemented with three levels of GAA (0, 0.6 and 1.2 g/kg) in a 42-d feeding trial. (3) In the starter and grower periods, increasing levels of ND improved body weight (BW), average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR), with the exception of ADFI in the starter period. GAA supplementation did not affect performance characteristics. All performance indicators responded markedly to increasing ND in the finisher period, whereas the highest GAA level reduced ADFI compared to the unsupplemented control (156 vs. 162 g/d) and concomitantly FCR (1.81 vs. 1.93). No interactive effects were noted for any performance trait. The high ND diet resulted in more breast meat yield on d42, associated with higher fat content and darker colour compared to the other ND levels. The GAA supplementation did not affect carcass and breast traits. At the end of the experiment, Cr was elevated when feeding GAA at 1.2 g/kg (5455 vs. 4338 mg/kg fresh muscle). (4) To conclude, ND had a substantial effect on performance and carcass traits, whereas any effect of GAA was limited to FCR in the finisher period and independent of diet ND level.

Coagulase-negative staphylococci (CNS) are involved in colour and flavour formation of fermented meats. Their communities are established either spontaneously, as in some artisan-type products, or using a starter culture. The latter usually consists of Staphylococcus carnosus and/or Staphylococcus xylosus strains, although strains from other CNS species also have potential for application. However, it is not entirely clear how the fitness of alternative starter cultures within a fermented meat matrix compares to conventional ones and how this may be affected by processing conditions. Therefore, the aim of this study was to assess the influence of two key processing conditions, namely temperature and acidity, on the competitiveness of a cocktail of five different strains of CNS belonging to species that are potentially important for meat fermentation (Staphylococcus xylosus 2S7-2, S. carnosus 833, Staphylococcus epidermidis ATCC 12228, Staphylococcus equorum DFL-S19, and Staphylococcus saprophyticus FPS1). To this end, fermented meat models consisting of cured meat batters with initial pH values of 5.3, 5.5, or 5.7 were inoculated with these strains, stuffed in containers, and incubated at 23, 30, or 37 °C. Both the pH level and the temperature influenced the composition of the CNS communities, giving a competitive advantage to the best adapted species. Staphylococcus xylosus preferred low temperature and mild acidity, whereas an elevated temperature selected for S. epidermidis and a low pH for S. carnosus. Under the conditions tested, S. saprophyticus and S. equorum were outcompeted by the three other CNS species. Hence, CNS communities in fermented meats are not only established based on the initial presence of specific species in the meat batter but also by their subsequent adaptation to the processing conditions during fermentation, potentially overruling the use of starter cultures., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Staphylococcus carnosus and Staphylococcus xylosus are commonly used, individually or in combination, within conventional starter cultures for the purposes of colour and flavour development during meat fermentation. Yet, little is known about the relative importance of both species under different processing conditions. The present study aimed at investigating the competitiveness of S. carnosus within a meat starter culture under different acidification profiles. The experimental set-up involved a gradient of decreasing experimental control but increasing realism, ranging from liquid meat fermentation models in a meat simulation medium, over solid mince-based meat fermentation models, to fermented sausage production on pilot-scale level. In general, S. carnosus gained a fitness advantage over S. xylosus in the most acidified variants of each set-up. In contrast, increasing persistence of S. xylosus was seen at the mildest acidification profiles, especially when approximating actual meat fermentation practices. Under such conditions, S. carnosus was reduced to co-prevalence in the mince-based meat fermentation models and was fully outcompeted on pilot-scale level. The latter was even the case when no S. xylosus starter culture was added, whereby S. carnosus was overpowered by staphylococci that originated from the meat background (mostly S. xylosus strains). The results of the present study suggested that conventional starter cultures behave differently when applied in different technological set-ups or using different recipes, with possible repercussions on fermented meat product quality., (Copyright © 2018 Elsevier B.V. All rights reserved.)