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For the current aging population, protein is an important macronutrient to counteract the development of sarcopenia. Protein digestion is influenced by the capacity of the digestive system. The current evidence is reviewed about the impact of aging on the human digestive system and related to protein digestion in vivo . Aging changes the digestive organs which impacts protein digestion. Dentition decreases and mastication changes, potentially affecting particle size reduction. Stomach gastric acidity is unchanged, gastric emptying is delayed, while total transit time remains unchanged. Production of enzymes by the pancreas is decreased, but any changes in the small intestine remain unresolved. Animal studies showed decreased fecal protein digestion in older compared to young animals. Human studies showed decreased postprandial peripheral plasma appearance of ingested amino acids and increased splanchnic extraction. The findings suggest that the deteriorating digestive system with aging results in decreased protein digestion. Interpretation of the results should be taken with caution because of interindividual differences in the aging process, and because studies on protein digestion in aging humans are scarce. More information is needed on healthy aging and its relation to the digestive tract and protein digestion, several methods including in vitro experiments are valuable in this perspective.

Regulatory T cells (Tregs) suppress pro-inflammatory conventional T cell (Tconv) responses. As lipids impact cell signaling and function, we compare the lipid composition of CD4 + thymus-derived (t)Tregs and Tconvs. Lipidomics reveal constitutive enrichment of neutral lipids in Tconvs and phospholipids in tTregs. TNFR2-co-stimulated effector tTregs and Tconvs are both glycolytic, but only in tTregs are glycolysis and the tricarboxylic acid (TCA) cycle linked to a boost in fatty acid (FA) synthesis (FAS), supported by relevant gene expression. FA chains in tTregs are longer and more unsaturated than in Tconvs. In contrast to Tconvs, tTregs effectively use either lactate or glucose for FAS and rely on this process for proliferation. FASN and SCD1, enzymes responsible for FAS and FA desaturation, prove essential for the ability of tTregs to suppress Tconvs. These data illuminate how effector tTregs can thrive in inflamed or cancerous tissues with limiting glucose but abundant lactate levels., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Diabetes is a widespread metabolic disorder and results from insulin resistance and impaired insulin secretion. Modifiable factors like diet, physical activity, and body weight play crucial roles in diabetes prevention, with targeted interventions reducing diabetes risk by about 60%. High-protein consumption, above the recommended intake of 0.8 g/kg body weight per day, have often explored in relation to diabetes risk. However, the relationship between dietary protein and diabetes is multifaceted. Observational studies have linked high total and animal protein intake to an increased risk of type 2 diabetes, particularly in obese women. Elevated levels of branched-chain amino acids (BCAA), which can result from dietary intake, protein breakdown, as well as an impaired catabolism, are strong predictors of cardiometabolic risk and insulin resistance. With several mechanism linking BCAA to insulin resistance. On the other hand, intervention studies suggest that high-protein diets can support weight loss and improve cardiometabolic risk factors. However, the impact on insulin sensitivity and glucose homeostasis is not straightforward. Proteins and amino acids stimulate both insulin and glucagon secretion, influencing glucose levels, but chronic effects remain uncertain. This short narrative review aims to provide an update on the relationship between increased dietary protein intake, amino acids, insulin resistance and type 2 diabetes, and to describe protein recommendations for type 2 diabetes., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mensink.)

Tregs can facilitate transplant tolerance and attenuate autoimmune and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg expansion and function in vivo and to create therapeutic Treg products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naive, thymus-derived Tregs (tTregs) from human blood that promotes their differentiation into nonlymphoid tissue-resident (NLT-resident) effector Tregs, without Th-like polarization. In contrast, CD28 costimulation maintains a lymphoid tissue-resident (LT-resident) Treg phenotype. We base this conclusion on transcriptome and proteome analysis of TNFR2- and CD28-costimulated CD4+ tTregs and conventional T cells (Tconvs), followed by bioinformatic comparison with published transcriptomic Treg signatures from NLT and LT in health and disease, including autoimmunity and cancer. These analyses illuminate that TNFR2 costimulation promoted tTreg capacity for survival, migration, immunosuppression, and tissue regeneration. Functional studies confirmed improved migratory ability of TNFR2-costimulated tTregs. Flow cytometry validated the presence of the TNFR2-driven tTreg signature in effector/memory Tregs from the human placenta, as opposed to blood. Thus, TNFR2 can be exploited as a driver of NLT-resident tTreg differentiation for adoptive cell therapy or antibody-based immunomodulation in human disease.

To identify the potential anabolic properties of a dairy-plant protein blend as compared to single plant-based and single dairy protein, the postprandial amino acid (AA) response of pea protein, milk protein, micellar casein, and a casein-pea protein blend was investigated in healthy older adults (age 72.3 ± 3.4 years, BMI 25.3 ± 2.9 kg/m 2 ). Plasma AA levels were measured, before and up to 5 h after ingestion of each 20 g protein. Blending casein-pea in a 60/40 mixture resulted in improved plasma AA availability, i.e. area under the curve (AUC) and peak height, of total (essential) AA and of key AAs methionine and leucine compared to pea only, while preserving the higher availability of arginine. The casein/pea blend clearly showed an AA response that was in between that of its single constituents, indicating that blending could be a solution to improve a lower quality (plant) protein, which could be of relevance for older adults.

Introduction: Physical activity has been suggested to alleviate gastrointestinal (GI) symptoms in patients with irritable bowel syndrome (IBS); however, evidence is scarce. Running has become increasingly popular and may be beneficial for patients with IBS. To obtain more insight in the potential application of running as therapy, we aimed to explore the impact of running and its intensity on GI symptoms in patients with IBS., Methods: Data from a large observational study in runners were used for this nested case-control study, which included 153 runners with IBS and 153 controls. All participants had completed a questionnaire on personal characteristics, running characteristics and GI symptoms. Regarding GI symptoms, the severity of nine symptoms was asked, both at rest and during and/or shortly (up to 3 h) after running. Each symptom could be scored on a scale from 0 (not bothersome) to 100 (very bothersome), resulting in a maximum total score of 900 points., Key Results: The prevalence and total severity score of GI symptoms were higher in runners with IBS than in controls, both at rest and during running. Among runners with IBS, the median (25th-75th percentile) total severity score during/after running was significantly lower than at rest (118 [50-200] vs. 150 [90-217]), while in controls no significant difference between running and rest was observed. Analyses stratified for running intensity revealed that the beneficial effect in runners with IBS was present when their most intensive training session was moderately intensive or intensive but not very intensive., Conclusions & Inferences: Running, particularly on moderate intensity, could have a beneficial effect on GI symptoms in patients with IBS., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objective: Human energy expenditure and substrate oxidation are under circadian control and food intake is a time cue for the human biological clock, leading to 24h feeding-fasting cycles in energy and substrate metabolism. In recent years, (intermittent) fasting protocols have also become popular to improve metabolic health. Here, we aimed to investigate the impact of food intake on the 24h patterns of energy metabolism as well as to provide data on the timeline of changes in energy metabolism that occur upon an extended period of fasting., Research Design and Methods: In a randomized, cross-over design, twelve healthy males underwent a 60h fast which was compared to a 60h fed condition. In the fed condition meals were provided at energy balance throughout the study. Conditions were separated by a two week period of habitual diet. Volunteers resided in a respiration chamber for the entire 60h to measure energy expenditure and substrate oxidation hour by hour. Volunteers performed a standardized activity protocol while in the chamber. Blood samples were drawn after 12, 36 and 60h., Results: Immediately following the breakfast meal (in the fed condition), fat oxidation became higher in the fasted condition compared to the fed condition and remained elevated throughout the study period. The initial rapid increase in fat oxidation corresponded with a decline in the hepatokine activin A (r = -0.86, p = 0.001). The contribution of fat oxidation to total energy expenditure gradually increased with extended abstinence from food, peaking after 51h of fasting at 160 mg/min. Carbohydrate oxidation stabilized at a low level during the second day of fasting and averaged around 60 mg/min with only modest elevations in response to physical activity. Although 24h energy expenditure was significantly lower with prolonged fasting (11.0 ± 0.4 vs 9.8 ± 0.2 and 10.9 ± 0.3 vs 10.3 ± 0.3 MJ in fed vs fasting, day 2 and 3 respectively, p < 0.01), the 24h fluctuations in energy expenditure were comparable between the fasted and fed condition. The fluctuations in substrate oxidation were, however, significantly (p < 0.001 for both carbohydrate and fat oxidation) altered in the fasted state, favouring fat oxidation., Conclusions: Energy expenditure displays a day-night rhythm, which is independent of food intake. In contrast, the day-night rhythm of both carbohydrate and fat oxidation is mainly driven by food intake. Upon extended fasting, the absolute rate of fat oxidation rapidly increases and keeps increasing during a 60h fast, whereas carbohydrate oxidation becomes progressively diminished., Trial Registration: www.trialregister.nl NTR 2042., Competing Interests: Conflict of interest This clinical trial was granted by Top Institute Food and Nutrition. The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

NutriProfiel® is a tool to measure micronutrient status and to assess diet quality. It consists of measurement of micronutrient status in blood and a short food frequency questionnaire (FFQ) ('Eetscore-FFQ'). Based on the results, individuals receive a dietary advice. In this study, we evaluated the application of NutriProfiel in athletes ('NutriProfiel-Sport') by assessing the coverage of nutrient intake of the Eetscore-FFQ (part 1) and by evaluating athlete's dietary behaviour after using NutriProfiel-Sport and their satisfaction with this tool (part 2). For part 1, data of 419 athletes were used. We evaluated the coverage of nutrient intake of the Eetscore-FFQ using first and second MOMents (MOM1 and MOM2) sum scores of food items in the questionnaire. Forty-eight athletes were involved in part 2. They gave blood samples for micronutrient status measurement and were asked to complete the Eetscore-FFQ at baseline and after 3 months, as well as a questionnaire on their satisfaction with NutriProfiel-Sport. Results showed that for most nutrients, MOM1 and MOM2 scores were above 80 %, meaning that nutrient intake was sufficiently covered by the Eetscore-FFQ. No difference in diet quality was observed between baseline and after 3 months. Nevertheless, a majority of athletes reported the NutriProfiel-Sport results and advice as useful. On a scale from 0 to 10, NutriProfiel-Sport was graded with a mean (±sd) score of 7⋅6 (±0⋅8). In conclusion, NutriProfiel-Sport is a potential valuable and appreciated tool for athletes and the Eetscore-FFQ as part of this tool sufficiently covers nutrient intake in athletes., (© The Author(s) 2023.)

Objectives: Abdominal complaints (AC) during exercise are a common problem in runners. Nutrition is known to play a role in exercise-related AC, but information on the role of habitual dietary intake is limited. We assessed the prevalence of AC in a large cohort of runners, and investigated its association with potential risk factors, with a particular focus on nutritional factors in the habitual diet., Methods: A total of 1993 runners completed two online questionnaires: a general questionnaire on, among others, running habits and exercise-related AC and a Food Frequency Questionnaire. Runners with and without either upper AC (UAC) or lower AC (LAC) were compared regarding personal characteristics, running characteristics and habitual dietary intake., Results: 1139 runners (57%) reported AC during and/or up to 3 hours after running: 302 runners (15%) reported UAC, 1115 (56%) LAC and 278 (14%) both. In about one-third of runners with AC, these complaints negatively affected their running. Exercise-related AC were positively associated with female gender, younger age and more intense running. Most associations with nutritional factors were observed only for LAC in men, with a higher intake of energy, all macronutrients and grain products in men with LAC. In both men and women, a higher intake of tea and unhealthy choices were associated with AC., Conclusion: Exercise-related AC were quite prevalent, and in about one-third of the cases, AC impacted their running. Being female, having a younger age and running at higher intensity were positively associated with AC. Some aspects of the habitual diet were associated with AC. Most notable were positive associations for intake of fat, tea and unhealthy choices., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Lower limb tendinopathy (LLT) is highly prevalent in runners. Treatment can be challenging, and knowledge of risk factors may be valuable to develop preventive or treatment interventions for LLT. The aims of this study were (1) to assess the prevalence of three common LLTs (Achilles tendinopathy (AT), patellar tendinopathy and plantar fasciopathy) in a large cohort of Dutch and Belgian runners and (2) to investigate its association with potential risk factors, with a particular focus on nutritional factors in the habitual diet., Methods: A total of 1993 runners were included in the study. They completed two online questionnaires: a general questionnaire on running habits and injuries and a Food Frequency Questionnaire. Runners with and without LLT were compared regarding personal characteristics, running characteristics and nutritional factors., Results: The point prevalence for the three LLTs was 6%; 33% of the runners reported LLT in the past and 35% had either a current or past LLT. AT was the most prevalent type of LLT, and prevalence rates for all types of LLT were higher in men than women. Positive associations with LLT were observed for age and running years (men and women), running level and running distance (men). No associations between LLT and nutritional factors were observed., Conclusion: One-third of this population of runners had ever experienced an LLT. These tendinopathies were associated with gender, age and running load, but not with nutritional factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sugar beet leaves can be a viable and economically interesting source of high-quality protein for the food industry. We investigated how storage conditions and leaf wounding at harvest affect the content and quality of the soluble protein. After collection, leaves were either stored intact or shredded to mimic wounding induced by commercial leaf harvesters. Leaf material was stored in small volumes at different temperatures to assess leaf physiology or in larger volumes to assess temperature development at different locations in the bins. Protein degradation was more pronounced at higher storage temperatures. Wounding accelerated the degradation of soluble protein at all temperatures. Both wounding and storage at higher temperatures greatly stimulated respiration activity and heat production. At temperatures below 5°C, ribulose-1,5-biphosphate carboxylase oxygenase (RuBisCO) in intact leaves was preserved for up to 3 weeks. At temperatures of 30-40°C, RuBisCO degradation occurred within 48 h. Degradation was more pronounced in shredded leaves. In 0.8-m 3 storage bins at ambient temperature, core temperatures rapidly increased, up to 25°C in intact leaves and up to 45°C in shredded leaves within 2-3 days. Immediate storage at 5°C greatly suppressed the temperature increase in intact but not in shredded leaves. The indirect effect of excessive wounding, that is, heat production, is discussed as the pivotal factor responsible for increased degradation of protein. For optimal retention of soluble protein levels and quality in harvested sugar beet leaves, it is advised to minimize wounding and to store the material at temperatures around -5°C. PRACTICAL APPLICATION: To preserve the soluble protein content and quality for at least 3 weeks, sugar beet leaves should be harvested with minimal wounding and stored at temperatures between 1 and 5°C. When aiming to store minimally wounded leaves in larger volumes, it must be ensured that the product temperature in the core of the biomass meets the temperature criterium or the cooling strategy must be adjusted. The principles of minimal wounding and low temperature storage are transferable to other leafy crops that are harvested for food protein., (© 2023 Wageningen Food & Biobased Research. Journal of Food Science published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Background: Unabsorbed free amino acids (AAs) at the end of the small intestine result in a potential preventable nutritional loss., Objectives: This study aimed to quantify free AAs in terminal ileal digesta of both humans and pigs to investigate its relevance for the nutritional value of food proteins., Methods: Two studies with three diets were performed: a human study-ileal digesta from eight adult ileostomates were collected over 9 h after ingestion of a single meal unsupplemented or supplemented with 30 g zein or whey; pig study-12 cannulated pigs were fed for 7 d with a diet containing whey or zein or no-protein diet, and ileal digesta were collected on the last 2 d. Digesta were analyzed for total and 13 free AAs. True ileal digestibility (TID) of AAs was compared with and without free AAs., Results: All terminal ileal digesta samples contained free AAs. The TID of AAs in whey was 97% ± 2.4% (mean ± SD) in human ileostomates and 97% ± 1.9% in growing pigs. If the analyzed free AAs would have been absorbed, TID of whey would increase by 0.4%-units in humans and 0.1%-units in pigs. The TID of AAs in zein was 70% ± 16.4% in humans and 77% ± 20.6% in pigs and would increase by 2.3%-units and 3.5%-units, respectively, if the analyzed free AAs would have been fully absorbed. The largest difference was observed for threonine from zein: if free threonine was absorbed, the TID would increase by 6.6%-units in both species (P < 0.05)., Conclusions: Free AAs are present at the end of the small intestine and can potentially have a nutritionally relevant effect for poorly digestible protein sources, whereas the effect is negligible for highly digestible protein sources. This result provides insight into the room for improvement of a protein's nutritional value if all free AAs are to be absorbed. J Nutr 2023;xx:xx-xx. This trial was registered at clinicaltrials.gov as NCT04207372., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Exercise efficiency and economy are key determinants of endurance exercise performance. In this cross-over intervention trial, we investigated the effect of adherence to a low carbohydrate, high fat (LCHF) diet versus a high carbohydrate (HC) diet on gross efficiency (GE) and (OC) during exercise, both after 2 days and after 14 days of adherence., Methods: Fourteen recreational male athletes followed a two-week LCHF diet (<10 energy % carbohydrate) and a two-week HC diet (>50 energy % carbohydrate), in random order, with a wash-out period of three weeks in between. After 2 and 14 days on each diet, the athletes performed a 90-minutes submaximal exercise session on a bicycle ergometer. Indirect calorimetry measurements were done after 60 minutes of exercise to calculate GE and OC., Results: GE was significantly lower on the LCHF diet compared to the HC diet, after 2 days (17.6±1.9 vs. 18.8±1.2%, P=0.011, for the LCHF and HC diet respectively), not after 14 days. OC was significantly higher on the LCHF diet compared to the HC diet, after 2 days (1191±138 vs. 1087±72 mL O2/kCal, P=0.003, for the LCHF and HC diet respectively), and showed a strong tendency to remain higher after 14 days, P=0.018., Conclusions: Although LCHF diets are popular strategies to increase fat oxidation during exercise, adherence to a LCHF diet was associated with a lower exercise efficiency and economy compared to a HC diet.

Background: Patients discharged from the Intensive Care Unit (ICU) frequently suffer from ICU-acquired weakness because of immobilization and massive inflammation-induced muscle mass loss. Consequently, rehospitalization, reduced quality of life (QoL), increased disabilities, and higher post-ICU mortality is observed. Exercise rehabilitation and optimal nutrition, particularly protein intake, are pivotal to regaining muscle mass and function. Studies have shown that protein requirements in the post-ICU phase are often unmet. Furthermore, protein supplementation in other patient groups has shown beneficial effects. However, a study on protein supplementation during the post-ICU period is lacking. This study aims to investigate the effect of a six-week intervention of daily porcine protein supplementation versus an isocaloric control (maltodextrin) on functional outcomes in the post-ICU period in patients with moderately severe ICU-acquired weakness., Methods: 72 post-ICU patients with moderately severe ICU-acquired weakness of Hospital Gelderse Vallei will be randomly assigned to either the intervention or the control group (36 per arm). The intervention group receives a porcine protein supplement twice a day. The control group receives a maltodextrin supplement twice a day. The intervention starts on the first day in the general ward and lasts 42 days (6 weeks). The primary outcome is the between-group difference in physical function at hospital discharge (t;=2), the end of the intervention (t;=3, day 42), and the 3-month follow-up (t;=4) expressed as a composite score consisting of handgrip strength, muscle strength leg, muscle strength arm and exercise capacity. Secondary outcomes encompass physical function, QoL, Activity of daily living (ADL), and plasma amino acids concentrations. Lastly, ICU readmission after ICU discharge, hospital readmission after hospital discharge, and overall survival status will be considered. Linear mixed models will be used to test the treatment effect for the primary and secondary outcome measures., Discussion: This trial will be the first to investigate porcine protein supplementation compared with carbohydrate supplementation in the post-ICU period aiming to improve functional outcomes of ICU survivors with moderately severe ICU-acquired weakness., Trial Registration: The study has been registered at ClinicalTrials.gov. Number: NCT05405764., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent studies suggest that circulating fibroblast growth factor 21 (FGF21) may be a marker of metabolic health status. We performed a secondary analysis of a 12-week randomized controlled trial to investigate the effects of two energy restriction (ER) diets on fasting and postprandial plasma FGF21 levels, as well as to explore correlations of plasma FGF21 with metabolic health markers, (macro)nutrient intake and sweet-taste preference. Abdominally obese subjects aged 40-70 years ( n = 110) were randomized to one of two 25% ER diets (high-nutrient-quality diet or low-nutrient-quality diet) or a control group. Plasma FGF21 was measured in the fasting state and 120 min after a mixed meal. Both ER diets did not affect fasting or postprandial plasma FGF21 levels despite weight loss and accompanying health improvements. At baseline, the postprandial FGF21 response was inversely correlated to fasting plasma glucose ( ρ = -0.24, p = 0.020) and insulin ( ρ = -0.32, p = 0.001), HOMA-IR ( ρ = -0.34, p = 0.001), visceral adipose tissue ( ρ = -0.24, p = 0.046), and the liver enzyme aspartate aminotransferase ( ρ = -0.23, p = 0.021). Diet-induced changes in these markers did not correlate to changes in plasma FGF21 levels upon intervention. Baseline higher habitual polysaccharide intake, but not mono- and disaccharide intake or sweet-taste preference, was related to lower fasting plasma FGF21 ( p = 0.022). In conclusion, we found no clear evidence that fasting plasma FGF21 is a marker for metabolic health status. Circulating FGF21 dynamics in response to an acute nutritional challenge may reflect metabolic health status better than fasting levels.

The CD4 + regulatory T (Treg) cell lineage, defined by FOXP3 expression, comprises thymus-derived (t)Treg cells and peripherally induced (p)Treg cells. As a model for Treg cells, studies employ TGF-β-induced (i)Treg cells generated from CD4 + conventional T (Tconv) cells in vitro. Here, we describe how human iTreg cells relate to human blood-derived tTreg and Tconv cells according to proteomic analysis. Each of these cell populations had a unique protein expression pattern. iTreg cells had very limited overlap in protein expression with tTreg cells, regardless of cell activation status and instead shared signaling and metabolic proteins with Tconv cells. tTreg cells had a uniquely modest response to CD3/CD28-mediated stimulation. As a benchmark, we used a previously defined proteomic signature that discerns ex vivo naïve and effector Treg cells from Tconv cells and includes conserved Treg cell properties. iTreg cells largely lacked this Treg cell core signature and highly expressed e.g. STAT4 and NFATC2, which may contribute to inflammatory responses. We also used a proteomic signature that distinguishes ex vivo effector Treg cells from Tconv cells and naïve Treg cells. iTreg cells contained part of this effector Treg cell signature, suggesting acquisition of pTreg cell features. In conclusion, iTreg cells are distinct from tTreg cells and share limited features with ex vivo Treg cells at the proteomic level., (© 2022. The Author(s).)

Introduction: Nutrition plays an essential role in the recovery of critical illness. In the post-Intensive Care Unit (ICU) period, patients typically return to oral nutrition gradually. However, studies quantifying nutritional intake in the post-ICU hospitalization period are scarce and formal guidelines are lacking. This study aims to describe energy and protein intake in detail over the entire post-ICU hospitalization period and explore associations between protein intake and clinical outcomes., Methods: A prospective observational single-center cohort study was conducted amongst post-ICU patients in general wards after a minimum ICU-stay of 72 h and who received (par)enteral feeding for ≥24 h in the ICU. Oral intake was assessed daily using food order lines and digital photography of meal leftovers. Other data, including amounts of (par)enteral nutrition, were collected from electronic medical records. The primary outcome was to identify energy and protein intake, and reached targets, in the post-ICU period. In addition, length of hospital stay after ICU discharge, readmission and mortality rates were compared between patients meeting protein targets or not., Results: In total, 48 patients were included. Complete nutritional data of 34 patients were analyzed in the current study, adding up to a total number of 484 observational days, 1681 photos and 6634 food order lines. Inter-rater agreement was excellent (ICC 0.878). Overall mean energy and protein adequacy for all nutritional groups was 82.3% (SD 18.3) and 83.1% (SD 19.8). Only 51.2% of the study participants (n = 21) reached overall >90% of prescribed protein targets during their entire post-ICU ward stay. The lowest intake was seen in the patient group with exclusively oral intake (median protein adequacy 75.5%), whereas patients with (supplemental) enteral nutrition (EN) all met >90% of their protein targets. Prescribed targets were below recommendations, and prescribed calories and proteins were neither ordered nor consumed. Discontinuation of EN resulted in immediate marked drops in energy (44.1%) and protein intake (50.7%). Subsequently, patients needed up to six days to reach protein targets again. No differences in clinical outcomes were observed., Conclusion: Most patients did not meet energy and protein targets in the post-ICU hospitalization period. Nutrition performance was highly dependent on the route of nutrition and was lowest among patients with oral intake only (despite of food fortification strategies and/or oral nutritional supplements). The best intake was observed in patients receiving (supplemental) EN. However, cessation of EN posed an immediate nutritional risk. No differences in clinical outcomes were found in this study. Our findings stress the need for follow-up studies to close the gap with individualized nutritional support in the post-ICU period to reach protein and energy targets., Competing Interests: Conflict of interest Prof. Dr A.R.H. van Zanten reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Baxter, Braun, Cardinal Health, Danone-Nutricia, Dim-3, Fresenius Kabi, Mermaid, Lyric, and Nestle-Novartis. The other authors have nothing to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There is a growing demand for plant-based protein-rich products for human consumption. During the production of plant-based protein-rich products, ingredients such as soy generally undergo several processing methods. However, little is known on the effect of processing methods on protein nutritional quality. To gain a better understanding of the effect of processing on the protein quality of soy, we performed a quantitative review of in-vivo and in-vitro studies that assessed the indispensable amino acid (IAA) composition and digestibility of varying soy products, to obtain digestibility indispensable amino acids scores (DIAAS) and protein digestibility corrected amino acid scores (PDCAAS). For all soy products combined, mean DIAAS was 84.5 ± 11.4 and mean PDCAAS was 85.6 ± 18.2. Data analyses showed different protein quality scores between soy product groups. DIAAS increased from tofu, soy flakes, soy hulls, soy flour, soy protein isolate, soybean, soybean meal, soy protein concentrate to soymilk with the highest DIAAS. In addition, we observed broad variations in protein quality scores within soy product groups, indicating that differences and variations in protein quality scores may also be attributed to various forms of post-processing (such as additional heat-treatment or moisture conditions), as well as study conditions. After excluding post-processed data points, for all soy products combined, mean DIAAS was 86.0 ± 10.8 and mean PDCAAS was 92.4 ± 11.9. This study confirms that the majority of soy products have high protein quality scores and we demonstrated that processing and post-processing conditions can increase or decrease protein quality. Additional experimental studies are needed to quantify to which extent processing and post-processing impact protein quality of plant-based protein-rich products relevant for human consumption., Competing Interests: Author AW is an employee of Unilever. Author LvB was an internship student at Unilever for her Master in Nutrition and Health, Wageningen University, at the time of conducting the study. Unilever markets food products made from plant-based proteins. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van den Berg, Mes, Mensink and Wanders.)

Background: Tendinopathy is a painful condition that is prevalent in athletes as well as the general human population, and whose management is challenging., Objective: This systematic review aimed to evaluate the impact of nutrition on the prevention and treatment of tendinopathy., Methods: Searches were conducted in PubMed, EMBASE, Web of Science, and SPORTDiscus without restriction to year of publication. Studies examining the impact of exposure to nutrient intake in an adult human population on 1) prevalence/incidence of tendinopathy, 2) clinical outcomes of tendinopathy, 3) structural changes in the tendon by imaging modalities. Experimental and observational study designs written in English, Dutch, or German were eligible., Results: Nineteen studies met the inclusion criteria. The effects of the habitual diet were investigated in one study. Four studies examined the effects of exposure to alcohol. Alcohol consumption can be a potential risk factor associated with Achilles tendinopathy and rotator cuff tears, although findings were inconsistent. The use of dietary supplements was examined in fourteen studies. Among these, collagen-derived peptides were most often part of the supplements evaluated. Combining training and dietary supplements seems to induce better clinical and functional outcomes in tendinopathy., Conclusion: This review demonstrates the paucity of high-quality studies and a wide variety among studies regarding nutrients, tendon location, study population, and reported outcome measures. Individual studies showed promising clinical implications for the use of dietary supplements, particularly those containing collagen-derived peptides. However, giving any definitive dietary recommendations on the prevention and treatment of tendinopathy remains elusive., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate., Objectives: The aim of the study was to examine the additional effects of nutrient quality on top of ER., Methods: A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed., Results: The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet., Conclusions: A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: It is not feasible to determine the true ileal amino acid (AA) digestibility of protein sources in humans on a routine basis, and the growing pig has been recommended as an animal model for this purpose but requires further validation., Objectives: To determine and compare true ileal AA digestibility between adult human ileostomates and growing cannulated pigs for a range of food proteins., Methods: Seven protein sources (black beans, bread, collagen, pigeon peas, wheat bran, whey protein isolate, and zein) that spanned the range of digestibilities typically seen in foods were evaluated. Six female growing pigs received each of the protein sources, as well as a protein-free diet, and digesta were collected via ileal T-cannula. Adult human ileostomates consumed the same protein sources (5-8 ileostomates, depending on the protein source), as well as a protein-free diet, and digesta were collected. Titanium dioxide and celite were included in the diets as indigestible markers. True ileal AA digestibility coefficients were determined., Results: There was a significant effect of protein source (P ≤ 0.001) for all AAs. The effect of species was not significant (P > 0.05) except for total lysine (but not for available lysine). When analyzed within diets, the statistically significant species effect for true lysine digestibility was found for black beans only. Pig and human digestibility values were generally highly and significantly (P ≤ 0.05) correlated. A linear regression equation derived for true ileal AA digestibility (given as coefficients) determined in the human and pig for the overall mean of all AAs was (y = human, x = pig) y = 1.00x - 0.010, with the slope not statistically significant (P > 0.05) from unity and the intercept not different (P > 0.05) from zero., Conclusions: True ileal AA digestibility values determined in the growing pig can be directly used for predicting digestibility in adult humans., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

CD4 + conventional T cells (Tconvs) mediate adaptive immune responses, whereas regulatory T cells (Tregs) suppress those responses to safeguard the body from autoimmunity and inflammatory diseases. The opposing activities of Tconvs and Tregs depend on the stage of the immune response and their environment, with an orchestrating role for cytokine- and costimulatory receptors. Nutrient availability also impacts T-cell functionality via metabolic and biosynthetic processes that are largely unexplored. Many data argue that costimulation by Tumor Necrosis Factor Receptor 2 (TNFR2) favors support of Treg over Tconv responses and therefore TNFR2 is a key clinical target. Here, we review the pertinent literature on this topic and highlight the newly identified role of TNFR2 as a metabolic regulator for thymus-derived (t)Tregs. We present novel transcriptomic and metabolomic data that show the differential impact of TNFR2 on Tconv and tTreg gene expression and reveal distinct metabolic impact on both cell types., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mensink, Tran, Zaal, Schrama, Berkers, Borst and de Kivit.)

Introduction: Critically ill patients in the Intensive Care Unit (ICU) should receive nutritional support matched to their metabolic needs as both under- and overfeeding energy has been shown to increase mortality. Critical illness can significantly affect metabolism. Consequently, resting energy expenditure (REE) can vary markedly during critical illness. Therefore, indirect calorimetry to estimate REE is recommended to determine energy requirements in individual ICU patients and to guide optimal nutritional support. Currently, the Quark metabolic monitor is considered the gold standard in our ICU, but novel mechanical support devices are also equipped with indirect calorimetry functionalities. This study aimed to evaluate the performance of a currently unevaluated device., Methods: A cross-sectional analysis in mechanically ventilated patients was conducted in a mixed medical-surgical ICU. The primary outcome was a numerical and visual comparison of the performance of the Beacon indirect calorimeter to calculate REE compared to the Quark device using Bland Altman plots. Performance was evaluated using bias, precision, accuracy, and reliability. Secondary analysis included a comparison with REE estimated by predictive equations., Results: Seventy-one measurements were obtained in 27 mechanically ventilated subjects. An underestimation by the Beacon device in calculated REE of -96.2 kcal/day (4.5%) was found. There was a bias towards higher VCO 2 and lower VO 2 values with Beacon as compared to Quark. The reliability of the Beacon was good, with an absolute intraclass correlation coefficient of 0.897 (95%CI 0.751-0.955; p = 0.000). There was a poor correlation (<0.40) between the separate indirect calorimetry devices and most predictive equations. Only the Faisy predictive equations had good reliability (ICC 0.687, p = 0.002)., Conclusions: Beacon indirect calorimetry accurately determined REE in mechanically ventilated critically ill patients compared to the gold standard in our ICU (Quark indirect calorimeter), although confidence intervals were wide. There was low bias and good reliability. On the other hand, predictive equations performed poorly compared to both devices, underestimating the true metabolic needs of mechanically ventilated ICU patients., Competing Interests: Declaration of competing interest Prof. Dr A.R.H. van Zanten reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from AOP pharma, Braun, Cardinal Health, Danone-Nutricia, Dim-3, Fresenius Kabi, Mermaid, Lyric, and Nestle-Novartis. The other authors have nothing to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Since the emergence of the Goose/Guangdong H5 lineage in 1996 and spillover of highly pathogenic avian influenza (HPAI) from poultry to wild birds, outbreaks have become increasingly frequent in wild birds. The latest outbreak in the Netherlands occurred in the fall-winter of 2020-2021 and was linked to incursions of HPAI H5N8 virus. During the larger national outbreak, wild birds in rehabilitation center "Vogelklas Karel Schot (VKS)" in Rotterdam presented with clinical signs compatible with HPAI, including head shaking, torticollis, and abnormal gait. During an epidemiologic investigation at VKS, water samples from the pools in the enclosures and oropharyngeal and cloacal swabs from 128 birds of different species were analyzed for the presence of H5N8 virus. Forty-five birds and the pool water tested positive for the virus. The outbreak at VKS was likely introduced by one or more infected geese ( Anser anser , Anser anser domesticus , Branta leucopsis ), after which the virus spread via pool water and with the relocation of infected birds within the center. In principle, such outbreaks are preventable. Recent updates about HPAI to provide guidance to help avoid future incursions of HPAI into wildlife rescue centers are reported.

Purpose: This study assessed adherence to, feasibility of, and barriers and facilitators of implementation of an app developed to monitor and follow-up with pain in children with cancer at home., Methods: Children (8-18 years) receiving cancer treatment (all diagnoses) or their parents (of children aged 0-7 years) used the KLIK Pain Monitor app for 3 weeks. Pain was assessed twice daily using an 11-point numeric rating scale (NRS-11) (ranging from 0 to 10). Healthcare professionals (HCP's) from the hospital's Pediatric Pain Service were instructed to follow-up with clinically significant pain scores (≥ 4) within 120 min (scores 4-6) or 30 min (scores 7-10). Adherence, feasibility, and implementation outcomes were assessed using questionnaires, app log data, and interviews., Results: Twenty-seven children (M age = 7.3 years, 51.8% male) and six HCP's participated. Sixty-three percent (N = 17) of families used the app on a daily basis during three weeks, and 18.5% (N = 5) reported pain scores twice daily during that time (family adherence). Twelve out of 27 children (44.4%) reported a clinically significant pain score at least once. In 70% (14/20) of clinically significant pain scores, HCP's followed-up with families within the set timeframe (HCP adherence). Outcomes reveal feasibility for the majority of app functions (i.e., positive evaluation by ≥ 70% families/HCP's), and non-feasible aspects could be resolved. Identified barriers and facilitators were used to improve future implementation efforts., Conclusion: Use of the KLIK Pain Monitor app seems feasible. Future research will determine its effectiveness in reducing pain in children with cancer at home., (© 2021. The Author(s).)