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Summary Background There is increasing evidence from randomized-controlled trials demonstrating that nutritional support improves clinical outcomes in the population of malnourished medical inpatients. We investigated associations of trial characteristics including clinical setting, duration of intervention, individualization of nutritional support and amount of energy and protein, and effects on clinical outcomes in an updated meta-analysis. Methods We searched Cochrane Library, MEDLINE and EMBASE, from inception to December 15, 2020. Randomized-controlled trials investigating the effect of oral and enteral nutritional support interventions, when compared to usual care, on clinical outcomes of malnourished non-critically ill medical inpatients were included. Two reviewers independently extracted data and assessed risk of bias. The primary endpoint was all cause-mortality within 12-months. Results We included 29 randomized-controlled trials with a total of 7,166 patients. Heterogeneity across RCTs was high, with overall moderate study quality and mostly moderate or unclear risk of bias. Overall, there was an almost 30%-reduction in mortality in patients receiving nutritional support compared to patients not receiving nutritional support (253/2960 [8.5%] vs. 336/2976 [11.3%]) with an odds ratio of 0.72 (95% CI 0.57 to 0.91, p = 0.006). The most important predictors for the effect of nutritional trials on mortality were high protein strategies (odds ratio 0.57 vs. 0.93, I2 = 86.3%, p for heterogenity = 0.007) and long-term nutritional interventions (odds ratio 0.53 vs. 0.85, I2 = 76.2%, p for heterogenity = 0.040). Nutritional support also reduced unplanned hospital readmissions and length of hospital stay. Conclusions There is increasing evidence from randomized trials showing that nutritional support significantly reduces mortality, unplanned hospital readmissions and length of stay in medical inpatients at nutritional risk, despite heterogeneity and varying methodological quality among trials. Trials with high-protein strategies and long-lasting nutritional support interventions were most effective.

BACKGROUND The amount of the macronutrients protein and carbohydrate (CHO) in a mixed meal is known to affect each other's digestion, absorption, and subsequent metabolism. While the effect of the amount of dietary protein and fat on the glycemic response is well studied, the ability of postprandial plasma amino acid patterns to predict the meal composition is unknown. OBJECTIVE To study the postprandial plasma amino acid patterns in relation to the protein, CHO, and fat content of different mixed meals and to investigate if these patterns can predict the macronutrient meal composition. DESIGN Ten older adults were given 9 meals with 3 different levels (low, medium, and high) of protein, CHO, and fat in different combinations, taking the medium content as that of a standardized western meal. We monitored the postprandial plasma response for amino acids, glucose, insulin, and triglycerides for 8 h and the areas under the curve (AUC) were subsequently calculated. Multiple regression analysis was performed to determine if amino acid patterns could predict the meal composition. RESULTS Increasing meal CHO content reduced the postprandial plasma response of several amino acids including all branched chain amino acids (BCAA) (leucine; q

BACKGROUND Small- and large-intestinal perturbations have been described as prevalent extracardiac systemic manifestations in congestive heart failure (CHF), but alterations in protein digestion and absorption and plasma short-chain fatty acid (SCFA) concentrations and the potential link with other systemic effects (muscle and cognitive health) have not been investigated in CHF. METHODS We analyzed protein digestion and absorption with dual stable tracer method in 14 clinically stable, noncachectic CHF outpatients (mean left ventricular ejection fraction: 35.5% [95% CI, 30.9%-40.1%]) and 15 controls. Small-intestinal non-carrier-mediated permeability and active carrier-mediated glucose transport were quantified by sugar permeability test. Plasma SCFA (acetate, propionate, butyrate, isovalerate, valerate) concentrations were measured as intestinal microbial metabolites. Muscle function was assessed by isokinetic dynamometry, cognition by a battery of tests, and well-being by questionnaire. RESULTS Protein digestion and absorption were impaired by 29.2% (P = .001) and active glucose transport by 38.4% (P = .010) in CHF. Non-carrier-mediated permeability was not altered. Whereas plasma propionate, butyrate, and isovalerate concentrations were lower in CHF (P < .05), acetate and valerate concentrations did not differ. Overall, intestinal dysfunction was associated with impaired leg muscle quality, emotional distress, and cognitive dysfunction (P < .05). CONCLUSIONS We identified impaired protein digestion and absorption and altered SCFA concentrations as additional intestinal dysfunctions in CHF that are linked to reduced muscle and cognitive health and well-being. More research is needed to implement strategies to improve intestinal function in CHF and to investigate the mechanisms underlying its link with other systemic manifestations.

Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision on the type of protein or AA nutrition to deliver in ICU patients, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patients and matched control subjects using a novel pulse isotope method to obtain in-depth metabolic analysis. In 51 critically ill ICU patients (SOFA~6.6) and 49 healthy controls, we measured REE and body composition/phase-angle using BIA. In the postabsorptive state, we collected arterial (ized) blood for CRP and AA. Then, we administered an 8 mL solution containing 18 stable AA tracers as a pulse and calculated WBP. Enrichments: LC-MS/MS and statistics: t-test, ANCOVA. Compared to healthy, critically ill ICU patients had lower phase-angle (p 0.00001), and higher CRP (p 0.0001). Most AA concentrations were lower in ICU patients (p 0.0001), except tau-methylhistidine and phenylalanine. WBP of most AA were significantly (p 0.0001) higher with increases in glutamate (160%), glutamine (46%), and essential AA. Remarkably, net protein breakdown was lower. There were only weak relationships between AA concentrations and WBP. Critically ill ICU patients (SOFA 8-16) had lower values for phase angle (p = 0.0005) and small reductions of most plasma AA concentrations, but higher tau-methylhistidine (p = 0.0223) and hydroxyproline (p = 0.0028). Remarkably, the WBP of glutamate and glutamine were lower (p 0.05), as was their clearance, but WBP of tau-methylhistidine (p = 0.0215) and hydroxyproline (p = 0.0028) were higher. Our study in critically ill ICU patients shows that comprehensive metabolic phenotyping was able to reveal severe disturbances in specific AA pathways, in a disease severity dependent way. This information may guide improving nutritional compositions to improve the health of the critically ill patient. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).

Hospitalized, malnourished older adults with chronic obstructive pulmonary disease (COPD) have an elevated risk of readmission and mortality.Post-hoc, sub-group analysis from the NOURISH study cohort examined the effect of a high-protein oral nutritional supplement (ONS) containing HMB (HP-HMB) in malnourished, hospitalized older adults with COPD and to identify predictors of outcomes.The NOURISH study (n = 652) was a multicenter, randomized, placebo-controlled, double-blind trial. The COPD subgroup (n = 214) included hospitalized, malnourished (based on Subjective Global Assessment), older adults (≥65 y), with admission diagnosis of COPD who received either standard-of-care plus HP-HMB (n = 109) or standard-of-care and a placebo supplement (n = 105) prescribed 2 servings/day from within 3 days of hospital admission (baseline) and up to 90 days after discharge. The primary study outcome was a composite endpoint of incidence of death or non-elective readmission up to 90-day post-discharge, while secondary endpoints included changes in hand-grip strength, body weight, and nutritional biomarkers over time. Categorical outcomes were analyzed using Cochran-Mantel-Haenszel tests, longitudinal data by repeated measures analysis of covariance; and changes from baseline by analysis of covariance. p-values ≤ 0.05 were considered statistically significant. Multivariate logistic regression was used to model predictors of the primary outcome and components.In patients with COPD, 30, 60, and 90-day hospital readmission rate did not differ, but in contrast, 30, 60, and 90-day mortality risk was approximately 71% lower with HP-HMB supplementation relative to placebo (1.83%, 2.75%, 2.75% vs. 6.67%, 9.52% and 10.48%, p = 0.0395, 0.0193, 0.0113, resp.). In patients with COPD, compared to placebo, intake of HP-HMB resulted in a significant increase in handgrip strength (+1.56 kg vs. -0.34 kg, p = 0.0413) from discharge to day 30; increased body weight from baseline to hospital discharge (0.66 kg vs. -0.01 kg, p 0.05) and, improvements in blood nutritional biomarker concentrations. The multivariate logistic regression predictors of the death, readmission or composite endpoints in these COPD patients showed that participants who were severely malnourished (p = 0.0191) and had a Glasgow prognostic score (GPS) Score of 1 or 2 had statistically significant odds of readmission or death (p = 0.0227).Among malnourished, hospitalized patients with COPD, supplementation with HP-HMB was associated with a markedly decreased mortality risk, and improved handgrip strength, body weight, and nutritional biomarkers within a 90-day period after hospital discharge. This post-hoc, subgroup analysis highlights the importance of early identification of nutritional risk and administration of high-protein ONS in older, malnourished patients with COPD after hospital admission and continuing after hospital discharge.

Summary Background Severe muscle mass (MM) loss is a defining feature of cancer observed across all types and stages of disease and is an independent predictor of poor clinical outcomes including higher incidences of chemotherapy toxicity and decreased survival. Protein is essential to build MM, yet the optimal amount for preventing or treating muscle loss in patients with cancer remains undefined. Methods The Protein Recommendation to Increase Muscle (PRIMe) study is a single-center, two-armed, parallel, randomized, controlled pilot trial that assesses the feasibility of utilizing a high protein (HP) diet to positively impact clinical outcomes in people undergoing chemotherapy to treat colorectal cancer. Forty patients with newly diagnosed stage II-IV colorectal cancer who are scheduled to receive chemotherapy will be included. Participants are randomly assigned to a HP or normal protein (NP) diet for twelve weeks. The HP and NP groups receive nutrition recommendations to achieve 2.0 g of protein per kilogram of body weight per day (g∙kg−1∙d−1) and 1.0 g⋅kg−1⋅d−1, respectively. These values refer to the upper and lower recommended range of protein intake for people with cancer. Energy recommendations are based on measured energy expenditure. Assessments are completed within two weeks of starting chemotherapy (baseline), at week 6, and at week 12. Changes to skeletal MM, physical function, anthropometrics, body composition, muscle strength, physical activity, energy metabolism, metabolic markers, nutritional status, quality of life, readiness to change and psychosocial determinants of behavioural change are assessed between the HP and NP groups. Feasibility of the nutritional intervention is assessed by change in MM as a surrogate marker. Conclusions This evidence-based study investigates the feasibility of increasing protein intake following a diagnosis of cancer on clinical outcomes during treatment for colorectal cancer. This study will inform larger trials assessing the impact of increasing protein intake in cancer to determine their importance and integration into standard clinical care for people with cancer.

Gut-related symptoms and an increase in markers of gut dysfunction have been observed in patients with chronic obstructive pulmonary disease (COPD). It remains unclear whether exercise, in relation to inducing hypoxia, plays a role in disturbances in protein digestion and amino acid absorption and whole body protein kinetics. Sixteen clinically stable patients with moderate-to-very severe COPD and 12 matched healthy subjects completed the study. Protein digestion and amino acid absorption, whole body protein kinetics were measured in the postabsorptive state via a continuous infusion of stable tracers in combination with orally administered stable tracer sips during 20 min of walking exercise and up to 4 h post exercise. In addition, concentrations of short-chain fatty acid (SCFA) and amino acids were measured. Patients with COPD completed one study day, walking at maximal speed, whereas healthy subjects completed two, one matched to the speed of a patient with COPD and one at maximal speed. The patients with COPD tolerated 20 min of vigorous intensity walking with an elevated heart rate (P < 0.0001) and substantial desaturation (P = 0.006). During exercise, we observed lower protein digestion (P = 0.04) and higher SCFA acetate (P = 0.04) and propionate (P = 0.02) concentrations on max speed study days, lower amino acid absorption (P = 0.004) in subjects with oxygen desaturation, and lower net protein breakdown (P = 0.03) and propionate concentrations (P = 0.04) in patients with COPD. During late recovery from exercise, amino acid absorption (P = 0.02) and net protein breakdown (P = 0.02) were lower in patients with COPD. Our data suggest that 20 min of walking exercise is sufficient to cause perturbations in gut function and whole body protein metabolism during and up to 4 h post exercise in older adults and in patients with COPD with exercise-induced hypoxia. NEW & NOTEWORTHY Gut function is disturbed in older adults with COPD. As exercise is the cornerstone of pulmonary rehabilitation in COPD, knowledge of the response of the gut to aerobic exercise is of importance.

Sustained high levels of blood glucose in type 2 diabetes (T2DM) can have disastrous long-term health consequences. An essential component of clinical interventions for T2DM is monitoring dietary intake to keep plasma glucose levels within an acceptable range. Yet, current techniques to monitor food intake are time intensive and error prone. To address this issue, we are developing techniques to automatically monitor food intake and the composition of those foods using continuous glucose monitors (CGMs). This article presents the results of a clinical study in which participants consumed nine standardized meals with known macronutrients amounts (carbohydrate, protein, and fat) while wearing a CGM. We built a multitask neural network to estimate the macronutrient composition from the CGM signal, and compared it against a baseline linear regression. The best prediction result comes from our proposed neural network, trained with subject-dependent data, as measured by root mean squared relative error and correlation coefficient. These findings suggest that it is possible to estimate macronutrient composition from CGM signals, opening the possibility to develop automatic techniques to track food intake.

Synthetic dimethoxymethane (DMM) is a promising fuel or blend component as it offers outstanding combustion characteristics. DMM production from hydrogen (H2) and carbon dioxide (CO2) is technically feasible with established technology but results in a low overall process efficiency. Recent research in catalyst development has increased DMM yield significantly and new reaction pathways have been proposed. Yet, it remains unknown how the achievements in catalyst development affect process performance. To close this gap, we analyze processes based on five reaction pathways regarding exergy efficiency, production cost, and climate impact. As the pathways have different technology readiness levels, we develop a methodology that ensures consistent boundary conditions and model detail between pathways. The methodology enables a hierarchical optimization-based process design and evaluation. The results show that the non-oxidative (i.e., reductive, dehydrogenative, and transfer-hydrogenative) pathways consume stoichiometrically less H2 not only than the established and oxidative pathway, but also less than most other electricity-based fuels (e-fuels). The higher resource efficiency of these pathways increases process exergy efficiency from 75% to 84%; production cost (2.1$ Ldiesel-eq.−1) becomes competitive to other e-fuels; and the impact on climate change reduces by up to 92% compared to fossil diesel, if renewable electricity is utilized. Whereas the reductive pathway may already enable a sustainable production of DMM with only little catalyst improvements, the dehydrogenative and transfer-hydrogenative pathways still require a higher DMM selectivity and methanol conversion, respectively. With considerable catalyst improvements, a maximum exergy efficiency of 92% and minimum production cost of 2.0$ Ldiesel-eq.−1 are achievable. Our analyses show: With the non-oxidative pathways, the high potential of DMM is no longer restricted to its outstanding combustion characteristics but extended to its production., Energy & Environmental Science, 14 (7), ISSN:1754-5692, ISSN:1754-5706

Background Gastrointestinal symptoms are common during chemotherapy, but underlying disturbances in gut function and their impact on daily life are unclear. This study investigates gut function in a heterogenous group of cancer patients with gastrointestinal symptoms during chemotherapy and its relation to anabolic response, muscle health, and daily functioning. Methods In 16 patients with solid tumors (mostly stage III+IV) undergoing chemotherapy (T) and 16 healthy (H) matched controls, small-intestinal membrane integrity was measured by urine sugar tests. Protein digestion, absorption, and anabolic response to a conventional protein supplement were analyzed by stable-tracer methods. Muscle mass and strength and daily functioning were assessed. Results Eighty-one percent of T patients reported gastrointestinal symptoms. Small-intestinal membrane permeability was similar, but active glucose transport was lower in the T group (T, 35.5% +/- 3.4% vs H, 48.4% +/- 4.7%; P = .03). Protein digestion and absorption tended to be lower in the T group (0.67 +/- 0.02 vs 0.80 +/- 0.04; P = .08). Net protein anabolic response to feeding was comparable, although lower in cancer patients with recent weight loss. Gut permeability negatively correlated to hand grip strength, global health, and physical functioning, and active-transport capacity positively correlated to global health in the T group. Conclusion Advanced cancer patients with gastrointestinal symptoms during chemotherapy, particularly those with recent weight loss, show signs of impaired gut function negatively affecting muscle health, daily functioning, and anabolic response to feeding.

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of Met may result in hyperhomocysteinemia (HHcy), which is a risk factor for cardiovascular disease. This review discusses the evidence generated in preclinical and clinical studies on the importance and potentially harmful effects of Met supplementation and elaborates on potential clinical applications of supplemental Met with reference to clinical studies performed over the past 20 y. Recently acquired knowledge about the NOAEL (no observed adverse effect level) of 46.3 mg · kg-1 · d-1 and the LOAEL (lowest observed adverse effect level) of 91 mg · kg-1 · d-1 of supplemented Met will guide the design of future studies to further establish the role of Met as a potential (safe) candidate for nutritional supplementation in clinical applications.

In recent years, point-of-care (POC) devices, especially smart wearables, have been introduced to provide a cost-effective, comfortable, and accessible alternative to polysomnography (PSG)—the current gold standard—for the monitoring, screening, and diagnosis of obstructive sleep apnea (OSA). Thorough validation and human subject testing are essential steps in the translation of these device technologies to the market. However, every device development group tests their device in their own way. No standard guidelines exist for assessing the performance of these POC devices. The purpose of this paper is to critically distill the key aspects of the various protocols reported in the literature and present a protocol that unifies the best practices for testing wearable and other POC devices for OSA. A limited review and graphical descriptive analytics of literature—including journal articles, web sources, and clinical manuscripts by authoritative agencies in sleep medicine—are performed to glean the testing and validation methods employed for POC devices, specifically for OSA. The analysis suggests that the extent of heterogeneity of the demographics, the performance metrics, subject survey, hypotheses, and statistical analyses need to be carefully considered in a systematic protocol for testing POC devices for OSA. We provide a systematic method and list specific recommendations to extensively assess various performance criteria for human subject testing of POC devices. A rating scale of 1–3 is provided to encourage studies to put a focus on addressing the key elements of a testing protocol.

Precision agriculture technologies (PATs) are promoted as part of both economically efficient and environmentally sustainable agriculture practices. Available PATs are generally classified into two groups; namely, embodied-knowledge and information-intensive PATs. Adoption levels of embodied-knowledge PATs are high relative to information-intensive PATs. Previous studies on the adoption of PATs do not differentiate between embodied-knowledge and information-intensive PATs. Additionally, most studies focus on the adoption of one or two of the available PATs rather than on adoption intensity—defined as the total number of individual PATs adopted. This study fills this gap in the literature by focusing on PAT adoption in general, and adoption intensity of embodied-knowledge and information-intensive PATs in particular. The study uses data from 198 farm-operator respondents in eastern South Dakota from a 2017 survey and employs descriptive statistics and probit and Poisson regression models for the analyses. As per the study, GPS guidance, yield monitor, and automatic section control systems are the most popular PATs, each with adoption rates of over 50%. Overall, findings from the study show that the effect of cropland size, producers’ perceptions of profitability, and operator off-farm income are similar for both adoption and adoption intensity of embodied-knowledge and information-intensive PATs. However, there are differences in the effect of land productivity and familiarity with computer use between adoption and adoption intensity and between embodied-knowledge and information-intensive PATs. The effect of producers’ perception of the environmental benefits of PATs is inconclusive and needs to be investigated in future research. The results indicate that analyzing PATs as a group of technologies masks differences in determinants between embodied-knowledge and information-intensive PATs. The study provides insights for developing programs, policies, and outreach efforts that encourage the adoption and adoption intensity of both embodied-knowledge and information-intensive PATs. Findings from the study will also be of interest to precision agriculture researchers, extension personnel, agribusinesses, and policymakers who may consider PATs as tools for improving agricultural sustainability and food security.

BACKGROUND & AIMS: Sepsis is hypothesized as an arginine deficient state, with lack of nitric oxide (NO) for adequate microcirculation and local perfusion. This study aimed to investigate if prolonged (72-h) intravenous l-arginine administration in sepsis patients improves microcirculation. Secondly, effects on arginine and protein metabolism, and organ function were studied.METHODS: Critically ill patients with a diagnosis of septic shock participated in a long-term (72 h) randomized double-blind placebo-controlled parallel-group study. l-arginine-HCl (1.2 μmol kg-1 min-1; n = 9) or l-alanine (isocaloric control: 2.4 μmol kg-1 min-1; n = 9) was continuously infused. Primary study outcome was microcirculation, assessed as gastric mucosal perfusion by gastric tonometry (Pr-aCO2 gap) and skin perfusion by Laser Doppler flowmetry. Secondary endpoints were whole body (WB) arginine and protein metabolism, organ function and clinical outcomes. We measured global hemodynamics continuously for safety monitoring. Statistical analyses were performed by mixed model for repeated measures with treatment by time interaction as estimate for between-group difference.RESULTS: Pr-aCO2 increased only in the l-arginine group (p = 0.006), without a significant between-group difference (p = 0.17). We found no significant differences in skin perfusion parameters. l-arginine infusion resulted in a larger increase of plasma arginine and ornithine concentrations (p < 0.01), WB (endogenous) arginine appearance (p < 0.001), WB NO synthesis (p = 0.027) and WB arginine to urea conversion (p < 0.001) than infusion of l-alanine. We found no effect on global hemodynamics, and protein metabolism by l-arginine infusion. Organ function parameters were unaffected, except for a significant difference between groups in intra-abdominal pressure over time (p = 0.029).CONCLUSIONS: Prolonged intravenous l-arginine administration does not improve local perfusion and organ function despite an increase in WB NO synthesis. Administration is safe with regard to global hemodynamics, but the observed increase in Pr-aCO2 and intra-abdominal pressure warrants careful application of l-arginine infusion and further research, especially in the early stage of septic shock.

For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy as a disease modifying agent. NTBC-induced hypertyrosinaemia has been associated with cognitive impairment and potentially sight-threatening keratopathy. In the context of a non-lethal condition (ie, AKU), these serious risks call for an evaluation of the wider impact of NTBC on the tyrosine pathway. We hypothesised that NTBC increases the tyrosine pool size and concentrations in tissues. In AKU mice tyrosine concentrations of tissue homogenates were measured before and after treatment with NTBC. In humans, pulse injection with l-[13 C9 ]tyrosine and l-[d8 ]phenylalanine was used along with compartmental modelling to estimate the size of tyrosine pools before and after treatment with NTBC. We found that NTBC increased tyrosine concentrations in murine tissues by five to nine folds. It also significantly increased the tyrosine pool size in humans (P

Background Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping has never been conducted in those with COPD. We examined whether depressed COPD patients have certain clinical/functional features and exhibit a specific amino acid phenotype which may guide the development of targeted (nutritional) therapies. Methods Seventy-eight outpatients with moderate to severe COPD (GOLD II–IV) were stratified based on presence of depression using a validated questionnaire. Lung function, disease history, habitual physical activity and protein intake, body composition, cognitive and physical performance, and quality of life were measured. Comprehensive metabolic flux analysis was conducted by pulse stable amino acid isotope administration. We obtained blood samples to measure postabsorptive kinetics (production and clearance rates) and plasma concentrations of amino acids by LC–MS/MS. Data are expressed as mean [95% CI]. Stats were done by graphpad Prism 9.1.0. ɑ Results The COPD depressed (CD, n = 27) patients on average had mild depression, were obese (BMI: 31.7 [28.4, 34.9] kg/m2), and were characterized by shorter 6-min walk distance (P = 0.055), physical inactivity (P = 0.03), and poor quality of life (P = 0.01) compared to the non-depressed COPD (CN, n = 51) group. Lung function, disease history, body composition, cognitive performance, and daily protein intake were not different between the groups. In the CD group, plasma branched chain amino acid concentration (BCAA) was lower (P = 0.02), whereas leucine (P = 0.01) and phenylalanine (P = 0.003) clearance rates were higher. Reduced values were found for tyrosine plasma concentration (P = 0.005) even after adjustment for the large neutral amino acid concentration (= sum BCAA, tyrosine, phenylalanine and tryptophan) as a marker of dopamine synthesis (P = 0.048). Conclusion Mild depression in COPD is associated with poor daily performance and quality of life, and a set of metabolic changes in depressed COPD that include perturbation of large neutral amino acids, specifically the BCAAs. Trial registration clinicaltrials.gov: NCT01787682, 11 February 2013—Retrospectively registered; NCT02770092, 12 May 2016—Retrospectively registered; NCT02780219, 23 May 2016—Retrospectively registered; NCT03796455, 8 January 2019—Retrospectively registered.

BACKGROUND & AIMS: Malnutrition has been recognized as a major risk factor for adverse postoperative outcomes. The ESPEN Symposium on perioperative nutrition was held in Nottingham, UK, on 14-15 October 2018 and the aims of this document were to highlight the scientific basis for the nutritional and metabolic management of surgical patients.METHODS: This paper represents the opinion of experts in this multidisciplinary field and those of a patient and caregiver, based on current evidence. It highlights the current state of the art.RESULTS: Surgical patients may present with varying degrees of malnutrition, sarcopenia, cachexia, obesity and myosteatosis. Preoperative optimization can help improve outcomes. Perioperative fluid therapy should aim at keeping the patient in as near zero fluid and electrolyte balance as possible. Similarly, glycemic control is especially important in those patients with poorly controlled diabetes, with a stepwise increase in the risk of infectious complications and mortality per increasing HbA1c. Immobilization can induce a decline in basal energy expenditure, reduced insulin sensitivity, anabolic resistance to protein nutrition and muscle strength, all of which impair clinical outcomes. There is a role for pharmaconutrition, pre-, pro- and syn-biotics, with the evidence being stronger in those undergoing surgery for gastrointestinal cancer.CONCLUSIONS: Nutritional assessment of the surgical patient together with the appropriate interventions to restore the energy deficit, avoid weight loss, preserve the gut microbiome and improve functional performance are all necessary components of the nutritional, metabolic and functional conditioning of the surgical patient.

In complex, expensive optimization domains we often narrowly focus on finding high performing solutions, instead of expanding our understanding of the domain itself. But what if we could quickly understand the complex behaviors that can emerge in said domains instead? We introduce surrogate-assisted phenotypic niching, a quality diversity algorithm which allows to discover a large, diverse set of behaviors by using computationally expensive phenotypic features. In this work we discover the types of air flow in a 2D fluid dynamics optimization problem. A fast GPU-based fluid dynamics solver is used in conjunction with surrogate models to accurately predict fluid characteristics from the shapes that produce the air flow. We show that these features can be modeled in a data-driven way while sampling to improve performance, rather than explicitly sampling to improve feature models. Our method can reduce the need to run an infeasibly large set of simulations while still being able to design a large diversity of air flows and the shapes that cause them. Discovering diversity of behaviors helps engineers to better understand expensive domains and their solutions.

Hypothyroidism is an endocrine disorder whose management raises many challenges in clinical practice. Its standard treatment is levothyroxine (LT4). The goal of the treatment is to normalize signs and symptoms, as well as to achieve thyroid-stimulating hormone (TSH) concentrations within the reference range, on an individual basis. It is known that 5–10 % of hypothyroid patients remain to be symptomatic, despite achieving the target TSH levels, which, in turn, affects their quality of life. After ruling out other causes of non-thyroid origin for this persistence, it is suggested that these patients could benefit from the use of liothyronine (LT3), added to LT4, especially if polymorphism of the deiodinase 2 (D2) genes is documented. There exist a variety of LT3 preparations, whose concentrations vary from 5 to 50 ug, with the recommended LT4/LT3 ratio of 13:1–20:1. The goals of combination therapy should be to achieve a physiological ratio of free triiodothyronine/free thyroxine (FT3/FT4) and non-suppression of TSH. Since there is currently no guide that makes evidence-based recommendations on the use of LT3 in primary hypothyroidism, more clinical studies are needed to be able to identify hypothyroid patients who may benefit from the use of LT3, by identifying new biomarkers.

Background: 90-day mortality and rehospitalizations are important hospital quality metrics. Biomarkers that predict these outcomes among malnourished hospitalized patients could identify those at risk and help direct care plans. Objectives: To identify biomarkers that predict 90-day (primary) and 30-day (secondary) mortality or nonelective rehospitalization. Design and Participants: An analysis of the ability of biomarkers to predict 90- and 30-day mortality and rehospitalization among malnourished hospitalized patients. Setting: 52 blood biomarkers were measured in 193 participants in NOURISH, a randomized trial that determined the effects of a nutritional supplement on 90-day readmission and death in patients >65 years. Composite outcomes were defined as readmission or death over 90-days or 30-days. Univariate Cox Proportional Hazards models were used to select best predictors of outcomes. Markers with the strongest association were included in multivariate stepwise regression. Final model of hospital readmission or death was derived using stepwise selection. Measurements: Nutritional, inflammatory, hormonal and muscle biomarkers. Results: Mean age was 76 years, 51% were men. In univariate models, 10 biomarkers were significantly associated with 90-day outcomes and 4 biomarkers with 30-day outcomes. In multivariate stepwise selection, glutamate, hydroxyproline, tau-methylhistidine levels, and sex were associated with death and readmission within 90-days. In stepwise selection, age-adjusted model that included sex and these 3 amino-acids demonstrated moderate discriminating ability over 90-days (C-statistic 0.68 (95%CI 0.61, 0.75); age-adjusted model that included sex, hydroxyproline and Charlson Comorbidity Index was predictive of 30-day outcomes (C-statistic 0.76 (95%CI 0.68, 0.85). Conclusions: Baseline glutamate, hydroxyproline, and tau-methylhistidine levels, along with sex and age, predict risk of 90-day mortality and nonelective readmission in malnourished hospitalized older patients. This biomarker set should be further validated in prospective studies and could be useful in prognostication of malnourished hospitalized patients and guiding in-hospital care.

Summary Background & aims Muscle wasting in cancer negatively affects physical function and quality of life. This study investigates amino acid metabolism and the association with muscle mass and function in patients with cancer. Methods In 16 patients with advanced cancer undergoing chemotherapy and 16 healthy controls, we administered an intravenous pulse and prime of stable amino acid tracers. We took blood samples to measure the Rate of appearance (Ra), whole body production (WBP), clearance (Cl), and post absorptive whole body net protein breakdown (WBnetPB). Plasma amino acid concentrations and enrichments were analysed by LC-MS/MS. We assessed muscle mass, handgrip/leg/respiratory muscle strength and reported physical activity, quality of life, and physical function. Results Muscle strength was lower in cancer patients than in healthy controls. Total and limb muscle mass, reported physical activity and WBnetPB were comparable. WBP and Cl of tau-methylhistidine, leucine, glutamine and taurine were higher in cancer patients as well as glycine Cl. Amino acid metabolism was correlated with low muscle mass, strength, physical function and quality of life. Conclusions Myofibrillar protein breakdown and production of amino acids involved in muscle contractility are up regulated in patients with cancer undergoing chemotherapy and related to muscle weakness and reduced physical outcomes.

Background & aims: Carbohydrates (CHO) and leucine (LEU) both have insulinotropic properties, and could therefore enhance the protein anabolic capacity of dietary proteins, which are important nutrients in preventing muscle loss in patients with Chronic Obstructive Pulmonary Disease (COPD). LEU is also known to activate protein anabolic signaling pathways independent of insulin. Based on our previous findings in COPD, we hypothesized that whole body protein anabolism is enhanced to a comparable extent by the separate and combined co-ingestion of CHO and LEU with protein.Methods: To disentangle the protein anabolic effects of CHO and/or free LEU when co-ingested with a high-quality protein, we studied 10 patients with moderate to very severe COPD and dyspnea (GOLD: II-IV, mMRC dyspnea scale >= 2), at risk for muscle loss, and 10 healthy age- and gender-matched controls. On four occasions, in a single-blind randomized crossover design, each subject ingested a drink containing 0.6 g/kg fat-free mass (ffm) hydrolyzed casein protein with, a) no add-ons (protein), b) 0.3 g/kg ffm CHO (protein + CHO), c) 0.095 g/kg ffm leucine (protein + LEU), d) both add-ons (protein + CHO + LEU). Whole body protein breakdown (PB), protein synthesis (PS), and net protein balance (= PS - PB) were measured by IV primed and continuous infusion of L-[ring-H-2(5)]-phenylalanine and L-[C-13(9),N-15]-tyrosine. L-[N-15]-phenylalanine was added to the protein drinks to measure splanchnic extraction.Results: In both groups, whole body PS, PB and net protein balance responses were comparable between the four protein drinks, despite higher postprandial plasma LEU concentrations for the LEU supplemented drinks (P Conclusions: Adding CHO and/or LEU to a serving of high-quality protein does not further augment whole body protein anabolism in dyspneic COPD patients at risk for muscle loss or healthy older adults. Trial registry: ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

MIIND is a software platform for easily and efficiently simulating the behaviour of interacting populations of point neurons governed by any 1D or 2D dynamical system. The simulator is entirely agnostic to the underlying neuron model of each population and provides an intuitive method for controlling the amount of noise which can significantly affect the overall behaviour. A network of populations can be set up quickly and easily using MIIND's XML-style simulation file format describing simulation parameters such as how populations interact, transmission delays, post-synaptic potentials, and what output to record. During simulation, a visual display of each population's state is provided for immediate feedback of the behaviour and population activity can be output to a file or passed to a Python script for further processing. The Python support also means that MIIND can be integrated into other software such as The Virtual Brain. MIIND's population density technique is a geometric and visual method for describing the activity of each neuron population which encourages a deep consideration of the dynamics of the neuron model and provides insight into how the behaviour of each population is affected by the behaviour of its neighbours in the network. For 1D neuron models, MIIND performs far better than direct simulation solutions for large populations. For 2D models, performance comparison is more nuanced but the population density approach still confers certain advantages over direct simulation. MIIND can be used to build neural systems that bridge the scales between an individual neuron model and a population network. This allows researchers to maintain a plausible path back from mesoscopic to microscopic scales while minimising the complexity of managing large numbers of interconnected neurons. In this paper, we introduce the MIIND system, its usage, and provide implementation details where appropriate., Frontiers in Neuroinformatics, 15, ISSN:1662-5196

Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process.Prospective randomized, placebo-controlled double blind trial.ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days.magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15.body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI.Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p 0.001), but not different between the groups (p = 0.86). In the HMB group, net protein breakdown (Δ Estimate HMB-Placebo: -153 [-242, -63]; p = 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p = 0.0247), and SF-12 global health improved more (Δ Estimate HMB-Placebo: 27.39 [1.594, 53.19], p = 0.04).HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. CLINICALTRIALS.NCT03628365.

Nations the world over are increasingly turning to quantitative performance-based metrics to evaluate the quality of research outputs, as these metrics are abundant and provide an easy measure of ranking research. In 2010, the Danish Ministry of Science and Higher Education followed this trend and began portioning out a percentage of the available research funding according to how many research outputs each Danish university produces. Not all research outputs are eligible: only those published in a curated list of academic journals and publishers, the so-called BFI list, are included. The BFI list is ranked, which may create incentives for academic authors to target certain publication outlets or publication types over others. In this study we examine the potential effect these relatively new research evaluation methods have had on the publication patterns of researchers in Denmark. The study finds that publication behaviors in the Natural Sciences & Technology, Social Sciences and Humanities (SSH) have changed, while the Health Sciences appear unaffected. Researchers in Natural Sciences & Technology appear to focus on high impact journals that reap more BFI points. While researchers in SSH have also increased their focus on the impact of the publication outlet, they also appear to have altered their preferred publication types, publishing more journal articles in the Social Sciences and more anthologies in the Humanities.

An important class of black-box optimization problems relies on using simulations to assess the quality of a given candidate solution. Solving such problems can be computationally expensive because each simulation is very time-consuming. We present an approach to mitigate this problem by distinguishing two factors of computational cost: the number of trials and the time needed to execute the trials. Our approach tries to keep down the number of trials by using Bayesian optimization (BO) –known to be sample efficient– and reducing wall-clock times by parallel execution of trials. We compare the performance of four parallelization methods and two model-free alternatives. Each method is evaluated on all 24 objective functions of the Black-Box-Optimization-Benchmarking (BBOB) test suite in their five, ten, and 20-dimensional versions. Additionally, their performance is investigated on six test cases in robot learning. The results show that parallelized BO outperforms the state-of-the-art CMA-ES on the BBOB test functions, especially for higher dimensions. On the robot learning tasks, the differences are less clear, but the data do support parallelized BO as the ‘best guess’, winning on some cases and never losing.

Current climate targets require negative carbon dioxide (CO2) emissions. Direct air capture is a promising negative emission technology, but energy and material demands lead to trade-offs with indirect emissions and other environmental impacts. Here, we show by life-cycle assessment that the commercial direct air capture plants in Hinwil and Hellisheiði operated by Climeworks can already achieve negative emissions today, with carbon capture efficiencies of 85.4% and 93.1%. The climate benefits of direct air capture, however, depend strongly on the energy source. When using low-carbon energy, as in Hellisheiði, adsorbent choice and plant construction become more important, inducing up to 45 and 15 gCO2e per kilogram CO2 captured, respectively. Large-scale deployment of direct air capture for 1% of the global annual CO2 emissions would not be limited by material and energy availability. However, the current small-scale production of amines for the adsorbent would need to be scaled up by more than an order of magnitude. Other environmental impacts would increase by less than 0.057% when using wind power and by up to 0.30% for the global electricity mix forecasted for 2050. Energy source and efficiency are essential for direct air capture to enable both negative emissions and low-carbon fuels. Direct air capture (DAC) of CO2 has garnered interest as a negative emissions technology to help achieve climate targets, but indirect emissions and other environmental impacts must be better understood. Here, Deutz and Bardow perform a life-cycle assessment of DAC plants operated by Climeworks, based on industrial data.

Circular economy (CE) is a concept that is gaining attention as an approach to help accelerate the transition towards sustainability. Research has focused on the adoption of CE practices in the business sector while the adoption within public sector organisations has been relatively overlooked. Examining CE adoption in the public sector through the perceptive of employees is crucial because of their expertise in the organisation where they work. The main aim of this study is to identify what public employees perceive as suitable CE practices for their organisations and their critical role in implementation. As the adoption of CE practices is influenced by social and material configurations, this research has taken a case study approach, focused on the Portuguese Central Public Administration. Semi-structured interviews were conducted with public employees working on CE and sustainability issues, and a complementary analysis was undertaken of governmental reports and legislative documents. The results show that public employees view the existence and potential of CE practices mainly in the area of public procurement but also in resource efficiency and optimisation, dematerialisation and in practices related to the R-hierarchy including reduce and reuse. Both technical-oriented practices aimed to achieve traditional resource efficiency, and human-centred practices targeted at reducing consumption and sharing resources have been identified. This research provides insights into how a specific group of stakeholders envisions CE activities for their sector. Identification of practices for central public sector has the potential to assist decision-makers in the process of defining priorities for CE planning, implementation and monitoring. This study focusing on CE practices in central public sector organisations contributes to the calls for an inclusion of human/socially-based practices centred around consumption reduction, sharing and dematerialisation activities to enhance the transformative and innovative potential of CE.

Introduction Reduced skeletal muscle function and cognitive performance are common extrapulmonary features in Chronic Obstructive Pulmonary Disease (COPD) but their connection remains unclear. Whether presence or absence of skeletal muscle dysfunction in COPD patients is linked to a specific phenotype consisting of reduced cognitive performance, comorbidities and nutritional and metabolic disturbances needs further investigation. Methods Thirty-seven patients with COPD (grade II–IV) were divided into two phenotypic cohorts based on the presence (COPD dysfunctional, n = 25) or absence (COPD functional, n = 12) of muscle dysfunction. These cohorts were compared to 28 healthy, age matched controls. Muscle strength (dynamometry), cognitive performance (Trail Making Test and STROOP Test), body composition (Dual-energy X-Ray Absorptiometry), habitual physical activity, comorbidities and mood status (questionnaires) were measured. Pulse administration of stable amino acid tracers was performed to measure whole body production rates. Results Presence of muscle dysfunction in COPD was independent of muscle mass or severity of airflow obstruction but associated with impaired STROOP Test performance (p = 0.04), reduced resting O2 saturation (p = 0.003) and physical inactivity (p = 0.01), and specific amino acid metabolic disturbances (enhanced leucine (p = 0.02) and arginine (p = 0.06) production). In contrast, COPD patients with normal muscle function presented with anxiety, increased fat mass, plasma glucose concentration, and metabolic syndrome related comorbidities (hypertension and dyslipidemia). Conclusion COPD patients with muscle dysfunction show characteristics of a cognitive – metabolic impairment phenotype, influenced by the presence of hypoxia, whereas those with normal muscle function present a phenotype of metabolic syndrome and mood disturbances.

UID/AMB/04085/2019 Repair is an essential aspect of circular economy (CE) strategies to extend the life of products and materials, and has further been suggested as a key sector to benefit from employment through CE transitions. At the same time, CE narratives around repair have been criticised as highly technocratic, neglecting the body of literature exploring repair as a relational act embedded in daily life. Hull, UK has been characterised as a structurally disadvantaged city, which might benefit from development opportunities offered through an expanded repair economy. However, a better understanding of the demographics of repair users is needed to promote its expansion. Therefore, this research aims to increase understanding of public perceptions, attitudes and behaviours relating to repair as both an option for consumers and as potential employment. The study combines literature in CE, human geography, and consumer behaviour to critically analyse a public survey (n = 740) conducted in partnership with Hull City Council. Results explore demographic associations with repair behaviour, identifying a profile of repair economy participants. Furthermore, an interdisciplinary discussion identifies a tension between repair as an act of necessity, which often carries a negative stigma, and that of choice for those privileged with skills and excess leisure time. Gender discrepancies between public perceptions, attitudes, and behaviours are identified, and policy recommendations for the development of an inclusive repair economy are made. While an opportunity for an expanded repair economy in the city is apparent, further research is needed to assess the quality of work in the sector. publishersversion published

As industrial activities account for a large part of environmental degradation and carbon emissions in China, the geographic location of industries significantly shapes the environmental performance and quality of life of surrounding areas. Since the late-2000s, China has sought to combat environmental degradation through the relocation of polluting industries particularly from industrial areas within inner cities. Using the concept of industrial transfer, which has been used in the Chinese context to capture not only the relocation of, but also structural and procedural changes to, firms, the paper analyses recent changes to China&rsquo, s industrial structure. These occurred during the so-called eco-transformation, which seeks to improve China&rsquo, s environmental performance. The paper expands the concept of industrial transfer by focusing on the intra-regional processes of this wider policy-led eco-transformation process based on the case studies of three traditional industrial areas in Hunan province. Case study results suggest that the ongoing phase of industrial transfer differs from previous regional transfers as it considers environmental impacts, elevates the relevance of the urban and local scale, involves new actor groups and offers benefits to both original and new locations.

OBJECTIVES: Optimal feeding in patients recovering from sepsis is critical to preserve muscle mass. In sepsis, glutamine (Gln) is considered a conditional essential amino acid and low plasma level of its precursor glutamate (Glu), is associated with higher mortality. An essential amino acid (EAA) mixture restores protein anabolism in the early recovery phase of acute septicemia in the pig. However, it is unclear whether interorgan Glu-Gln kinetics is also improved. Therefore, we measured the interorgan kinetics of Glu-Gln during a nutritional intervention with a balanced free amino acid (TAA) or EAA mixture in the early recovery phase of acute septicemia in the pig. METHODS: In catheterized pigs (±25 kg), acute septicemia was present for 6 hours (Pseudomonas aeruginosa: 3e,(8) CFU/ml/h IV). At t = 6 h, recovery was started by a single dose gentamycin (5 mg/kg) and intra-gastric continuous feeding of a balanced free TAA or EAA mixture (pig muscle profile, 31 mg N/kg bw/h, 30% daily intake and dextrose 781 mg/kg bw/h) for 6 hours. We studied 3 groups (Healthy: H-TAA n = 12; Sepsis: S-TAA n = 13, S-EAA n = 12) over the last 3 hours of the intervention by measuring arterial and venous plasma concentrations (expressed as mean[low, high 95%CI]) and organ net balances of the portal drained viscera (PDV), liver, kidneys and hindquarter (HQ, muscle). Statistics: Net balances were tested with Wilcoxon Signed Rank Test. Group comparisons with ANOVA. Significance: P

OBJECTIVES: For several decades, the ketogenic diet has been studied as a replacement for the western diet for weight management and disease treatment. However, there is a lack of understanding regarding the mechanism of change in metabolism induced by the diet. To better understand the diet's physiological effects, we hypothesize that protein turnover in specific organs, like the heart, are modified by the different diets. Therefore, we studied organ protein fractional synthesis rate (FSR) in several organ tissues of mice given ketogenic and a control western diets. METHODS: To assess protein FSR of various organs, we studied 4–6 week-old A/J mice) and randomly provided a ketogenic diet (high fat, no carbohydrate, n = 10) or a western diet (high fat, high carbohydrate, n = 10) for 3 months. One day before tissue collection, a D2O bolus was administered via intraperitoneal injection, and mice were provided D2O enriched drinking water to enrich the total body water to about 5% D2O. Eleven tissues (kidney, heart, lung, muscle, fat, jejunum, ileum, liver, brain, skin, and bone) were collected and analyzed for alanine enrichment in the intracellular and protein-bound pool (LC-MS/MS). FSR was calculated as -ln(1-enrichment) as fraction per day. Data are expressed as mean ± SE (unpaired t-test: GraphPad Prism 8.2). RESULTS: We found a significantly lower heart protein FSR in ketogenic diet compared to the western diet (ketogenic: 0.0795 ± 0.0021, western: 0.0873 ± 0.0015, P = 0.0076). We did not find any difference between protein FSR of the ketogenic and western diet mice in any of the other measured organs. CONCLUSIONS: The ketogenic diet in mice reduces cardiac protein synthesis, which could potentially indicate benefits of a ketogenic diet. We hypothesize that the mechanism of a ketogenic diet to reduce cardiac protein synthesis is via reduced inflammation and normalized heart function (e.g., reduced blood pressure). FUNDING SOURCES: Sydney and J.L. Huffines Institute for Sports Medicine, Human Performance Student Research Grant and CTRAL Grant.

Purpose: Gottingen minipig (G-MP) displays classic gastrointestinal acute radiation syndrome (GI-ARS) following total body irradiation (TBI) at GI doses which are lethal by 10–14 days. In collabora...

Preserving muscle is not only crucial for maintaining proper physical movement, but also for its many metabolic and homeostatic roles. Low muscle mass has been shown to adversely affect health outcomes in a variety of disease states (eg, chronic obstructive pulmonary disease, cancer, cardiovascular disease) and leads to an increased risk for readmission and mortality in hospitalized patients. Low muscle mass is now included in the most recent diagnostic criteria for malnutrition. Current management strategies for malnutrition may not prioritize the maintenance and restoration of muscle mass. This likely reflects the challenge of identifying and measuring this body composition compartment in clinical practice and the lack of awareness by health care professionals of the importance that muscle plays in patient health outcomes. As such, we provide a review of current approaches and make recommendations for managing low muscle mass and preventing muscle loss in clinical practice. Recommendations to assist the clinician in the optimal management of patients at risk of low muscle mass include the following: (1) place muscle mass at the core of nutritional assessment and management strategies; (2) identify and assess low muscle mass; (3) develop a management pathway for patients at risk of low muscle mass; (4) optimize nutrition to focus on muscle mass gain versus weight gain alone; and (5) promote exercise and/or rehabilitation therapy to help maintain and build muscle mass. The need to raise awareness of the importance of screening and managing 'at risk' patients so it becomes routine is imperative for change to occur. Health systems need to drive clinicians to treat patients with this focused approach, and the economic benefits need to be communicated to payers. Lastly, further focused research in the area of managing patients with low muscle mass is warranted.

Background & aims: Gastrointestinal symptoms are prevalent extrapulmonary systemic manifestations of Chronic Obstructive Pulmonary Disease (COPD), but have been rarely studied. We dissected the perturbations in intestinal function in human patients with COPD using comprehensive metabolic and physiological approaches. Methods: In this observational study, small intestinal membrane integrity and active carrier-mediated glucose transport were quantified by sugar permeability test in 21 clinically stable patients with moderate to severe COPD (mean FEV1, 41.2 (3.2) % of predicted) and 16 healthy control subjects. Protein digestion and absorption was analyzed using stable tracer kinetic methods. Plasma acetate, propionate, and butyrate concentrations were measured as markers of intestinal microbial metabolism. Results: Compared with healthy controls, non carrier-mediated permeability was higher (0.062 (95% CI [0.046, 0.078]) vs. 0.037 (95% CI [0.029, 0.045]), P = 0.009) and active glucose transport lower in COPD (31.4 (95% CI [23.4, 39.4])% vs. 48.0 (95% CI [37.8, 58.3])%, P = 0.010). Protein digestion and absorption was lower in COPD (0.647 (95% CI [0.588, 0.705]) vs. 0.823 (95% CI [0.737, 0.909]), P = 0007), and impairment greater in patients with dyspnea (P = 0.038), exacerbations in preceding year (P = 0.052), and reduced transcutaneous oxygen saturation (P = 0.051), and was associated with reduced physical activity score (P = 0.016) and lower quality of life (P = 0.0007). Plasma acetate concentration was reduced in COPD (41.54 (95% CI [35.17, 47.91]) vs. 80.44 (95% CI [54.59, 106.30]) mmol/L, P = 0.001) suggesting perturbed intestinal microbial metabolism. Conclusions: We conclude that intestinal dysfunction is present in COPD, worsens with increasing disease severity, and is associated with reduced quality of life. (c) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background Lean mass (LM) loss during extended bed rest contributes to long term functional decline in older adults. Identifying blood biomarkers that predict a hospitalized individual’s risk of losing LM could allow for timely intervention. Methods LM from 19 healthy subjects (age 60–76 y, 4 males, 15 females), who were confined to 10 days of complete bed rest, was measured pre- and post-bed rest. One hundred eighty-seven biomarkers from pre-bed rest fasted serum samples were obtained from all evaluable subjects (n = 18), analyzed using multiplexed immunoassay array and pooled. Decision tree analysis was used to identify pre-bed rest markers that predict LM loss over bed rest. Results Sixty-three markers were excluded due to being below assay detection limits. One pair of markers, Tissue inhibitor of metalloprotease-1 (TIMP1) and tenascin C (TNC), were found to correlate with percent change in total LM over bed rest: [R2 = 0.71, all subjects; R2 = 0.76, females]. Subjects with pre-bed rest TIMP1 ≥ 141 ng/ml had the highest loss of total LM over bed rest, whereas subjects with pre-bed rest TIMP1 Conclusions Panels of blood biomarkers associated with the muscle extracellular matrix may predict the likelihood for LM loss over extended bed rest.

Wild game consumption has been associated with health benefits, but the influence on protein metabolism remains unknown. We compared the feeding-induced response to 2 oz of free-range reindeer (FR) versus commercial beef (CB) using stable isotope methodology. Seven male and female participants (age: 38±12 years; body mass index: 24±3 kg/m2) completed two studies using a randomized, crossover design in which they ingested 2 oz of FR or CB. L-[ring 2H5]phenylalanine & L-[ring 2H2]tyrosine were delivered via primed, continuous intravenous infusion. Blood samples were collected during the basal period and following consumption of FR or CB. Feeding-induced changes in whole body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) were determined via analysis of plasma samples for phenyalanine and tyrosine enrichment by gas chromatography mass spectrometry; plasma essential amino acid concentrations were determined by liquid chromatography-electrospray ionization-mass spectrometry. Plasma post-prandial essential amino acid (EAA) concentrations were higher with the ingestion of FR compared to CB (P=0.02). The acute feeding-induced response in PS was not different in either trial, but PB was reduced with the ingestion of FR compared to CB (P

Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance in a heterogeneous group of COPD and non-COPD (control) subjects, and to identify risk factors underlying balance impairment using a large panel of methods. In COPD and control subjects, who were mostly overweight and sedentary, postural and functional balance were assessed using center-of-pressure displacement in anterior-posterior (AP) and medio-lateral (ML) directions, and the Berg Balance Scale (BBS), respectively. COPD showed 23% greater AP sway velocity (p = 0.049). The presence of oxygen therapy, fat mass, reduced neurocognitive function, and the presence of (pre)diabetes explained 71% of the variation in postural balance in COPD. Transcutaneous oxygen saturation, a history of exacerbation, and gait speed explained 83% of the variation in functional balance in COPD. Neurocognitive dysfunction was the main risk factor for postural balance impairment in the control group. This suggests that specific phenotypes of COPD patients can be identified based on their type of balance impairment.

Background & aims: Bile acids (BAs) play a key role in lipid uptake and metabolic signalling in different organs including gut, liver, muscle and brown adipose tissue. Portal and peripheral plasma BA concentrations increase after a meal. However, the exact kinetics of postprandial BA metabolism have never been described in great detail. We used a conscious porcine model to investigate postprandial plasma concentrations and transorgan fluxes of BAs, glucose and insulin using the para-aminohippuric acid dilution method.Methods: Eleven pigs with intravascular catheters received a standard mixed-meal while blood was sampled from different veins such as the portal vein, abdominal aorta and hepatic vein. To translate the data to humans, fasted venous and portal blood was sampled from non-diabetic obese patients during gastric by-pass surgery.Results: The majority of the plasma bile acid pool and postprandial response consisted of glycine-conjugated forms of primary bile acids. Conjugated bile acids were more efficiently cleared by the liver than unconjugated forms. The timing and size of the postprandial response showed large interindividual variability for bile acids compared to glucose and insulin.Conclusions: The liver selectively extracts most BAs and BAs with highest affinity for the most important metabolic BA receptor, TGR5, are typically low in both porcine and human peripheral circulation. Our findings raise questions about the magnitude of a peripheral TGR5 signal and its ultimate clinical application. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Purpose of review β-Hydroxy β-methylbutyrate (HMB) has been used for many years in athletes for muscle buildup and strength, and endurance enhancement. In recent years, its interest quickly expanded in older (diseased) populations and during (exercise) rehabilitation and recovery from hospitalization and surgery. We will discuss recent literature about HMB metabolism, its pharmacokinetics compared with the frequently used metabolite leucine, effectiveness of HMB to improve outcome in older diseased adults, and novel approaches for HMB use. Recent findings HMB supplementation resulted in positive outcomes on muscle mass and functionality, related to its anabolic and anticatabolic properties and prolonged half-life time in blood. Furthermore, it was able to increase the benefits of (exercise) rehabilitation programs to enhance recovery from illness or medical procedures. There is promising evidence that HMB might support bone density, improve cognitive function, and reduce abdominal obesity, which is of importance particularly in the older (diseased) population. Summary The older diseased population might benefit from dietary HMB because of its established positive properties as well as its long lasting (pharmacological) effect. In addition to evaluating its efficacy and application in various clinical conditions, more research is needed into the mechanisms of action, the optimal dosage, and its potential additional beneficial effects on outcome.

This study investigated the effect of hippotherapy on gross motor function (Gross Motor Function Measure [GMFM]-66, GMFM dimension E and D) and quality of life (Child Health Questionnaire [CHQ 28], KIDSCREEN-27 parental versions) in children with bilateral spastic cerebral palsy. Seventy-three children (age: 9.1 ± 3.3 years; male = 44; GMFCS levels II = 27; III = 17; IV = 29) were randomized to an early (n = 35) or late (n = 38) treatment group. Data from 66 probands were available for further analysis. Probands received hippotherapy once to twice weekly during a period of 16 to 20 weeks (mean: 17 treatments) in a crossover approach. Whereas no significant changes were found for total GMFM scores and quality of life parameters, a significant increase in GMFM dimension E was found. Children terminating the study early showed lower mean psychosocial quality of life scores than children who completed the whole study (CHQ-28 “psychosocial dimension”; KIDSCREEN-27 “mood and emotional dimension”). Our data are in line with previous reports and suggest that hippotherapy shows distinct therapeutic strengths with regard to promoting upright stand and gait in children with cerebral palsy. Children with higher psychosocial burden of disease may need special support to get access to and benefit from intensified physiotherapy programs.