Development and validation of a Context-sensitive Positive Health Questionnaire (CPHQ): A factor analysis and multivariate regression study.

BACKGROUND: The concept of Positive Health (PH) has gained increasing attention as a way of measuring individuals' ability to adapt in the face of contextual challenges. However, a suitable measurement instrument for PH that encompasses contextual factors has not yet been developed. This paper responds to this need by developing a Context-specific Positive Health (CPH) measurement instrument that aligns with the Capability Approach (CA). METHODS: The measurement instrument was developed and tested among a representative sample of 1002 Dutch internet survey panel members with diverse sociodemographic backgrounds. The instrument was developed in two stages: a preparation phase consisting of focus groups and expert consultations, and a validation among a representative panel of Dutch citizens. The goal of the preparation phase, was to pilot test and refine previously proposed Positive Health questionnaires into an initial version of the CPHQ. The validation phase aimed to examine the initial CPHQ's factorial validity using Factor Analysis, and its concurrent validity using Multivariate Regression Analysis. RESULTS: The developed questionnaire demonstrated adequate factorial and concurrent validity. Furthermore, it explicitly includes an assessment of resilience, this being a key component of PH. CONCLUSIONS: The introduced measurement tool, the CPHQ, comprises 11 dimensions that we have labeled as follows: relaxation, autonomy, fitness, perceived environmental safety, exclusion, social support, financial resources, political representation, health literacy, resilience, and enjoyment. In this article, we present four major contributions. Firstly, we embedded the measurement in a theoretical framework. Secondly, we focused the questionnaire on a key concept of Positive Health - the "ability to adapt." Thirdly, we addressed issues of health inequality by considering contextual factors. Finally, we facilitated the development of more understandable measurement items.

Protein and energy intake in intensive care unit survivors during the first year of recovery: A descriptive cohort study.

BACKGROUND: Many intensive care unit (ICU) survivors suffer long-term health issues that affect their quality of life. Nutrition inadequacy can limit their rehabilitation potential. This study investigates nutrition intake and support during ICU admission and recovery. METHODS: In this prospective cohort study, 81 adult ICU patients with stays ≥48 h were included. Data on dietary intake, feeding strategies, baseline and ICU characteristics, and 1-year outcomes (physical health and readmission rates) were collected. The number of patients achieving 1.2 gram per kilogram per day of protein and 25 kilocalories per kilogram per day at 3 months, 6 months, and 12 months after ICU admission was recorded. The impact of dietary supplementation during the year was assessed. Baseline characteristics, intake barriers, and rehabilitation's influence on nutrition intake at 12 months were evaluated, along with the effect of inadequate intake on outcomes. RESULTS: After 12 months, only 10% of 60 patients achieved 1.2 g/kg/day protein intake, whereas 28% reached the advised 25 kcal/kg/day energy target. Supplementary feeding significantly increased protein intake at 3, 6, and 12 months (P = 0.003, P = 0.012, and P = 0.033, respectively) and energy intake at 3 months (P = 0.003). A positive relation was found between female sex and energy intake at 12 months after ICU admission (ß = 4.145; P = 0.043) and taste issues were independently associated with higher protein intake (ß = 0.363; P = 0.036). However, achieving upper-quartile protein or energy intake did not translate into improved physical health outcomes. CONCLUSION: Continuous and improved nutrition care is urgently needed to support patients in reaching nutrition adequacy.

Effect of dietary interventions on markers of type 2 inflammation in asthma: A systematic review.

INTRODUCTION: Type 2 (T2) inflammation is a key mechanism in the pathophysiology of asthma. Diet may have immunomodulatory effects, and a role for diet in T2 inflammation has been suggested in the literature. Indeed, diet and food allergies play a role in children with atopic asthma, but less is known about diet in relation to adult asthma, which is often non-atopic. OBJECTIVE: To review the effect of dietary interventions on markers of T2 inflammation in adults with asthma. METHODS: The databases PubMed, Embase, Cochrane Library, and CINAHL were searched for eligible studies until December 2022. We included studies of all types of foods, nutrients, diets or supplements, either as an exposure or as an intervention, in adults and adolescents with asthma. Outcomes of interest included the T2 biomarkers FeNO, eosinophils, IL-4, IL-5, IL-13, eosinophil cationic protein and eosinophil peroxidase. The methodological quality of eligible studies was systematically evaluated, and the results were summarised according to dietary clusters. RESULTS: The systematic search identified studies on the dietary clusters antioxidants (n = 14), fatty acids, (n = 14), Mediterranean-style diets (n = 5), phytotherapy (n = 7), prebiotics & probiotics (n = 8), vitamin D (n = 7), and other dietary factors (n = 5). Studies within the phytotherapy and omega-3 poly-unsaturated fatty acids (PUFA) clusters showed possible improvements in T2 inflammation. Furthermore, we found little evidence for an effect of antioxidants, prebiotics & probiotics, and Mediterranean-style diets on T2 inflammation. However, heterogeneity in study protocols, methodological shortcomings and limited power of almost all studies make it difficult to fully determine the impact of different dietary approaches on T2 inflammation in asthma. CONCLUSIONS: Overall, the current evidence does not support a specific dietary intervention to improve T2 inflammation in asthma. Interventions involving phytotherapy and omega-3 PUFA currently have the best evidence and warrant further evaluation in well-designed and adequately powered studies, while taking into account T2-high phenotypes of asthma.

The prevalence of mental frailty in ICU survivors and informal caregiver strain: A 1-year retrospective study of the Frisian aftercare cohort.

Background: Intensive care unit (ICU) survivors often suffer from long-term mental problems and a reduced health-related quality of life (HRQoL). Symptoms of depression, anxiety, and post-traumatic stress disorder may render patients mentally frail post-ICU, resulting in impaired recovery and an increased informal caregiver burden. The aim of this study was to investigate the prevalence of mental frailty up to 12 months after ICU admission and pinpoint markers for early risk-assessment in clinical practice. Methods: A retrospective cohort study (2012-2018) in which clinical and post-ICU data of long-stay (⩾48 h) ICU-patients was used. Mental frailty was identified as clinically relevant symptoms of depression, anxiety, or post-traumatic distress disorder at 12 months after discharge. Results: The prevalence of mental frailty at 12 months post-ICU among the total group of 239 patients was 38%. Mental frailty was defined as clinically relevant symptoms of depression, anxiety, and/or trauma. To achieve this, previously validated cut off values were used for the HADS (HADS-Anxiety ⩾ 8; HADS-Depression ⩾ 8) and TSQ (⩾6), and CSI (⩾7). Conclusion: A significant proportion of ICU-survivors can be identified as mentally frail, which is associated with impaired HRQoL at baseline and post-ICU, and high caregiver strain. These findings emphasize the need for integrative aftercare programs for both the patient and their informal caregivers.

Identification of an alternative triglyceride biosynthesis pathway.

Triacylglycerols (TAGs) are the main source of stored energy in the body, providing an important substrate pool for mitochondrial beta-oxidation. Imbalances in the amount of TAGs are associated with obesity, cardiac disease and various other pathologies1,2. In humans, TAGs are synthesized from excess, coenzyme A-conjugated fatty acids by diacylglycerol O-acyltransferases (DGAT1 and DGAT2)3. In other organisms, this activity is complemented by additional enzymes4, but whether such alternative pathways exist in humans remains unknown. Here we disrupt the DGAT pathway in haploid human cells and use iterative genetics to reveal an unrelated TAG-synthesizing system composed of a protein we called DIESL (also known as TMEM68, an acyltransferase of previously unknown function) and its regulator TMX1. Mechanistically, TMX1 binds to and controls DIESL at the endoplasmic reticulum, and loss of TMX1 leads to the unconstrained formation of DIESL-dependent lipid droplets. DIESL is an autonomous TAG synthase, and expression of human DIESL in Escherichia coli endows this organism with the ability to synthesize TAG. Although both DIESL and the DGATs function as diacylglycerol acyltransferases, they contribute to the cellular TAG pool under specific conditions. Functionally, DIESL synthesizes TAG at the expense of membrane phospholipids and maintains mitochondrial function during periods of extracellular lipid starvation. In mice, DIESL deficiency impedes rapid postnatal growth and affects energy homeostasis during changes in nutrient availability. We have therefore identified an alternative TAG biosynthetic pathway driven by DIESL under potent control by TMX1.

Dietary Inflammatory Index and Clinical Outcome Measures in Adults With Moderate-to-Severe Asthma.

BACKGROUND: Diet is increasingly recognized as a modifiable factor in lung health, predominantly due to the immunomodulatory effects of nutrients. The Dietary Inflammatory Index (DII) is a score developed to express the inflammatory potential of a diet. OBJECTIVE: We aimed to assess the association of the DII and food groups, with clinical, functional, and inflammatory asthma outcomes in adults with asthma. METHODS: Patients with moderate-to-severe asthma were included in this cross-sectional study between June 2019 and October 2021, and completed a 3-day food diary, to calculate the DII and intake of food groups (ie, fruits, whole grains, processed meats, and sugar-sweetened beverages). Functional outcomes included pulmonary function tests and the 6-minute walking distance, whereas clinical outcomes were assessed using questionnaires on asthma control, quality of life, and health care utilization. Inflammatory markers were exhaled nitric oxide and blood leukocytes, eosinophils, and IL-6. Multivariable regression analyses were used to examine the association of DII and food groups with asthma outcomes. RESULTS: A total of 109 patients participated (35% male, mean ± standard deviation age 51.8 ± 14.2 years, body mass index 27.4 ± 5.3 kg/m2). Overall, 62% had a DII score >0, indicating a proinflammatory diet, which was not related to asthma severity. A more proinflammatory diet was consistently associated with lower forced vital capacity (%pred), but inconsistent results were observed with respect to airway obstruction. Neither the DII nor food groups were associated with clinical outcomes. Except for higher levels of exhaled nitric oxide in relation to an anti-inflammatory diet, we found no associations between inflammatory markers and the DII. CONCLUSION: Results from this cross-sectional study among patients with moderate-to-severe asthma do not support the hypothesis that a proinflammatory diet is associated with worse asthma outcomes, although limitations in study design and dietary intake estimation should be considered. Future well-designed experimental studies are needed to assess whether targeting the inflammatory potential of diet could lead to better outcomes in adults with asthma.

Muscular and kinematic features in speed skaters indicate a task-specific dystonia.

OBJECTIVE: Skater's cramp is a movement disorder in speed skaters. We investigated whether affected skaters matched the disease profile of task-specific dystonia, specifically whether there was evidence of maladaptive muscle activity occurring simultaneously with aberrant movements (jerking). We further examined different skating intensities, positing no change would be more indicative of task-specific dystonia. METHODS: We analyzed video, kinematic and muscle activity in 14 affected skaters. We measured the angular velocity and electromyographic activity of normalized speed skating strokes using one dimensional statistical non-parametric mapping. Skaters were matched with comparably skilled controls, and filled out a bespoke clinical questionnaire. RESULTS: Skaters' impacted leg showed over-activation in the peroneus longus, tibialis anterior and gastrocnemius that coincided with higher foot movement compared to their healthy leg and controls. This pattern persisted regardless of skating intensity. Clinical features indicated it was task-specific and painless with common trigger factors including stress, equipment change, and falling. CONCLUSIONS: We showed aberrant muscular and kinematic activity in a movement disorder in speed skaters indicative of task-specific dystonia. SIGNIFICANCE: Understanding skater's cramp as a task-specific dystonia could reduce the damage that misdiagnosis and unsuccessful invasive operations have caused. Our quantitative method has value in testing future treatment efficacy.

Diet quality, food intake and incident adult-onset asthma: a Lifelines Cohort Study.

PURPOSE: Dietary factors have been suggested as drivers of the rising prevalence of adult-onset asthma, but evidence is inconclusive, possibly due to the complex interrelation with obesity. We aim to explore the relation of diet quality and food intake with incident adult-onset asthma in normal weight and overweight adults of the prospective population-based Lifelines Cohort Study. METHODS: Incident adult-onset asthma was defined as self-reported asthma at ± 4-year follow-up, in adults free of airway disease at baseline. Diet quality scores and food group intake were assessed at baseline. Log-binomial regression analyses were used to estimate adjusted relative risks (RR) between dietary intake (per portion) and incident adult-onset asthma, in categories of BMI (cutoff: 25 kg/m2). RESULTS: 477 incident asthma cases (75% female, 62% overweight) and 34,698 controls (60% female, 53% overweight) were identified. Diet quality-assessed by the Lifelines Diet Score and Mediterranean Diet Score-was not associated with incident adult-onset asthma in the two BMI groups. Although the dietary intake of several food groups differed between cases and controls, after adjustment for confounders only few remained associated with adult-onset asthma, including red and processed meat (RR: 0.93 per 15 g intake; 95% CI 0.86-0.99) in the normal weight group and intake of cheese (RR 1.09 per 20 g intake; 95% CI 1.00-1.17) and vegetables (RR 1.10 per 50 g intake; 95% CI 1.00-1.21) in the overweight group. CONCLUSION: The results of this study question the role of food as a 'simple' predictor of adult-onset asthma and call for an integrative approach, including a range of modifiable lifestyle factors and further asthma phenotyping.

Intestinal Farnesoid X Receptor Modulates Duodenal Surface Area but Does Not Control Glucose Absorption in Mice.

Bile acids facilitate the intestinal absorption of dietary lipids and act as signalling molecules in the maintenance of metabolic homeostasis. Farnesoid X receptor (FXR) is a bile acid-responsive nuclear receptor involved in bile acid metabolism, as well as lipid and glucose homeostasis. Several studies have suggested a role of FXR in the control of genes regulating intestinal glucose handling. We applied a novel dual-label glucose kinetic approach in intestine-specific FXR-/- mice (iFXR-KO) to directly assess the role of intestinal FXR in glucose absorption. Although iFXR-KO mice showed decreased duodenal expression of hexokinase 1 (Hk1) under obesogenic conditions, the assessment of glucose fluxes in these mice did not show a role for intestinal FXR in glucose absorption. FXR activation with the specific agonist GS3972 induced Hk1, yet the glucose absorption rate remained unaffected. FXR activation increased the duodenal villus length in mice treated with GS3972, while stem cell proliferation remained unaffected. Accordingly, iFXR-KO mice on either chow, short or long-term HFD feeding displayed a shorter villus length in the duodenum compared to wild-type mice. These findings indicate that delayed glucose absorption reported in whole-body FXR-/- mice is not due to the absence of intestinal FXR. Yet, intestinal FXR does have a role in the small intestinal surface area.

Muscle Function in Moderate to Severe Asthma: Association With Clinical Outcomes and Inflammatory Markers.

BACKGROUND: Patients with severe asthma have been shown to have low muscle mass, but the clinical consequences are unknown. OBJECTIVE: In a clinical cohort of patients with moderate to severe asthma, we aimed to assess muscle mass and strength and their relation with functional and clinical outcomes, as well as with systemic inflammatory markers. METHODS: Muscle mass and strength were assessed by the fat-free mass index (FFMI), creatinine excretion in a 24-hour urine sample, and handgrip strength test. Functional outcomes included pulmonary function tests and the 6-minute walking distance, whereas clinical outcomes were assessed with questionnaires on asthma control, quality of life, and health care use. Associations of muscle mass and strength with asthma outcomes were assessed with multivariable regression analyses. RESULTS: A total of 114 patients participated (36% male; mean age, 51.9 ± 14.4 years; body mass index, 27.7 ± 5.7 kg/m2). According to predefined criteria, 16% had a low FFMI and 8% a low urinary creatinine excretion, which did not differ between categories of asthma severity. Both lower FFMI and urinary creatinine excretion were associated with lower values of FEV1 and 6-minute walking distance, whereas a lower handgrip strength was related to worse asthma control, poorer quality of life, and a higher probability of emergency visits (all P < .05). Except for higher leukocytes in relation to lower FFMI, we did not find associations between systemic inflammatory markers and muscle function. CONCLUSIONS: This study demonstrates that low muscle mass is prevalent in patients with moderate to severe asthma and, along with low muscle strength, is associated with poorer clinical and functional outcomes. Our results encourage longitudinal studies into muscle function as a potential target for treatment to improve asthma outcomes.

The association of low muscle mass with prevalence and incidence of type 2 diabetes in different BMI classes.

OBJECTIVE: The aim of this study is to investigate whether muscle mass is associated with the prevalence and incidence of type 2 diabetes and whether this association differs within men and women of normal weight, overweight or obesity. METHODS: Adult participants were included from the Lifelines cohort study. Low muscle mass was defined as < -1SD of the gender-stratified creatinine excretion rate (CER). Multivariate logistic regression analysis was used to assess the association between muscle mass and the prevalence and incidence of type 2 diabetes. RESULTS: Muscle mass was associated with the prevalence of type 2 diabetes both in men and in women (OR 1.51 [95 %CI 1.32-1.72]; P < 0.001 and OR 1.53 [1.36 - 1.73]; P < 0.001). Incident type 2 diabetes was associated with a decreased muscle mass for both men and women (male; OR 1.22 [1.05 - 1.43]; P = 0.01 and female; OR 1.36 [1.17 - 1.59]; P < 0.001), and remained significant after adjustments in normal weight women (OR 1.77 [1.16-2.70]; P = 0.008). CONCLUSIONS: Both a low muscle mass and loss of muscle mass are associated with the prevalence and incidence of diabetes in the general population. This association is strongest in people with normal weight, and weakens in people within higher BMI subgroups.

Perinatal exposure to UDCA prevents neonatal cholestasis in Cyp2c70-/- mice with human-like bile acids.

BACKGROUND: Cyp2c70-/- mice with a human-like bile acid (BA) composition display features of neonatal cholestasis. We assessed whether perinatal ursodeoxycholic acid (UDCA) exposure prevents neonatal cholestasis in Cyp2c70-/- mice and reduces cholangiopathy development later in life. METHODS: Cyp2c70+/- males were crossed with Cyp2c70+/- females fed either a regular chow diet or a 0.1% UDCA-containing diet during breeding, gestation, and suckling. Cholestasis and liver function parameters were assessed in their Cyp2c70-/- and wild-type offspring at 3 and 8 weeks of age. RESULTS: Three-week-old Cyp2c70-/- pups showed features of neonatal cholestasis, including elevated plasma BAs and transaminases, which were completely prevented in Cyp2c70-/- pups upon perinatal UDCA exposure. In addition, UDCA administration to the dams corrected altered hepatic gene expression patterns in Cyp2c70-/- pups, reduced markers of fibrogenesis and inflammation, and prevented cholangiocyte proliferation. Yet, these beneficial effects of perinatal UDCA exposure were not retained into adulthood upon discontinuation of treatment. CONCLUSION: Perinatal exposure of Cyp2c70-/- mice to UDCA has beneficial effects on liver function parameters, supporting a direct role of BA hydrophobicity in the development of neonatal cholestasis in these mice. However, prevention of neonatal cholestasis in Cyp2c70-/- mice has no long-lasting effects on liver pathophysiology. IMPACT: This is the first study showing that perinatal UDCA exposure prevents features of neonatal cholestasis that are observed in mice with a human-like bile acid composition, i.e., Cyp2c70-/- mice. Perinatal UDCA exposure of Cyp2c70-/- pups leads to UDCA enrichment in their circulating bile acid pool and, consequently, to a reduced hydrophobicity of biliary bile acids. Perinatal UDCA exposure of Cyp2c70-/- pups has no long-lasting effects on the development of cholangiopathy after discontinuation of treatment. The results in this study expand current knowledge regarding acute and long-lasting effects of UDCA treatment in early life.

Long-term health-related quality of life, healthcare utilisation and back-to-work activities in intensive care unit survivors: Prospective confirmatory study from the Frisian aftercare cohort.

PURPOSE: More substantial information on recovery after Intensive Care Unit (ICU) admission is urgently needed. In a previous retrospective study, the proportion of non-recovery patients was 44%. The aim of this prospective follow-up study was to evaluate changes in Health-Related Quality of Life (HRQoL) in the first year after ICU-admission. METHODS: Long-stay adult ICU-patients (≥ 48 hours) were included. HRQoL was evaluated with the Dutch translation of the RAND-36 item Health Survey (RAND-36) at baseline via proxy measurement, and at three, six, and twelve months after ICU admission. Subsequently, the relation between physical functioning, healthcare utilisation, and work activities was explored. RESULTS: A total of 81 patients were included in this study. Fifty-five percent of patients did not meet criteria for full recovery and were allocated to the Non Recovery (NR)-group (Physical Functioning domain-score: 35 [15-55]). Baseline physical HRQoL differed significantly between the Recovery (R) and NR-group. Patients in the NR-group received home care more often and had higher healthcare utilisation (44 versus 17% in the first three months post-ICU, p = 0.013). Only fourteen percent of NR-patients were able to participate in work activities. Moreover, NR-patients persistently showed impaired overall HRQoL throughout the year after critical illness. CONCLUSIONS: Limited recovery in ICU survivors is reflected in overall impaired HRQoL, as well as in far-reaching consequences for patients' healthcare needs and their ability to reintegrate into society. In our study, baseline HRQoL appeared to be an important predictor of long-term outcomes, but not Clinical Frailty Scale (CFS) score. And, (proxy-derived) HRQoL may help to identify patients at risk of long-term non-recovery.

Autocrine FGF1 signaling promotes glucose uptake in adipocytes.

Fibroblast growth factor 1 (FGF1) is an autocrine growth factor released from adipose tissue during over-nutrition or fasting to feeding transition. While local actions underlie the majority of FGF1's anti-diabetic functions, the molecular mechanisms downstream of adipose FGF receptor signaling are unclear. We investigated the effects of FGF1 on glucose uptake and its underlying mechanism in murine 3T3-L1 adipocytes and in ex vivo adipose explants from mice. FGF1 increased glucose uptake in 3T3-L1 adipocytes and epididymal WAT (eWAT) and inguinal WAT (iWAT). Conversely, glucose uptake was reduced in eWAT and iWAT of FGF1 knockout mice. We show that FGF1 acutely increased adipocyte glucose uptake via activation of the insulin-sensitive glucose transporter GLUT4, involving dynamic crosstalk between the MEK1/2 and Akt signaling proteins. Prolonged exposure to FGF1 stimulated adipocyte glucose uptake by MEK1/2-dependent transcription of the basal glucose transporter GLUT1. We have thus identified an alternative pathway to stimulate glucose uptake in adipocytes, independent from insulin, which could open new avenues for treating patients with type 2 diabetes.

Educating health care professionals on the importance of proper diets. An online course on nutrition, health, and sustainability.

The majority of university curricula for health professionals does not incorporate courses on human nutrition and its links with human and planetary health. This primarily applies to medical and pharmacy students, who have important counselling roles and are at the forefront of public health. To address this important issue, EIT Food recently launched an online course on nutrition, health, and sustainability. Learners were able to provide feedback on the course through an end-of-course survey and social interaction on the FutureLearn platform. The course was very well attended worldwide and received positive feedback from learners. A total of 3,858 students enrolled in the program, from >20 countries. Learners reported inadequate training on nutrition in their own curriculum and indicated they would use key insights from the course to inform their own practice. This report provides insights from the course, which could be used as guidance for future initiatives.

FGF1 and insulin control lipolysis by convergent pathways.

Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production (HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral delivery of exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediated by the adipose FGF receptor (FGFR) 1. However, its mechanism of action is not known. Here, we report that FGF1 acutely lowers HGP by suppressing adipose lipolysis. On a molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating phosphodiesterase 4D (PDE4D), which separates it mechanistically from the inhibitory actions of insulin via PDE3B. We identify Ser44 as an FGF1-induced regulatory phosphorylation site in PDE4D that is modulated by the feed-fast cycle. These findings establish the FGF1/PDE4 pathway as an alternate regulator of the adipose-HGP axis and identify FGF1 as an unrecognized regulator of fatty acid homeostasis.

Altered bile acid kinetics contribute to postprandial hypoglycaemia after Roux-en-Y gastric bypass surgery.

BACKGROUND/OBJECTIVES: Bile acids (BA) act as detergents in intestinal fat absorption and as modulators of metabolic processes via activation of receptors such as FXR and TGR5. Elevated plasma BA as well as increased intestinal BA signalling to promote GLP-1 release have been implicated in beneficial health effects of Roux-en-Y gastric bypass surgery (RYGB). Whether BA also contribute to the postprandial hypoglycaemia that is frequently observed post-RYGB is unknown. METHODS: Plasma BA, fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), GLP-1, insulin and glucose levels were determined during 3.5 h mixed-meal tolerance tests (MMTT) in subjects after RYGB, either with (RYGB, n = 11) or without a functioning gallbladder due to cholecystectomy (RYGB-CC, n = 11). Basal values were compared to those of age, BMI and sex-matched obese controls without RYGB (n = 22). RESULTS: Fasting BA as well as FGF19 levels were elevated in RYGB and RYGB-CC subjects compared to non-bariatric controls, without significant differences between RYGB and RYGB-CC. Postprandial hypoglycaemia was observed in 8/11 RYGB-CC and only in 3/11 RYGB. Subjects who developed hypoglycaemia showed higher postprandial BA levels coinciding with augmented GLP-1 and insulin responses during the MMTT. The nadir of plasma glucose concentrations after meals showed a negative relationship with postprandial BA peaks. Plasma C4 was lower during MMTT in subjects experiencing hypoglycaemia, indicating lower hepatic BA synthesis. Computer simulations revealed that altered intestinal transit underlies the occurrence of exaggerated postprandial BA responses in hypoglycaemic subjects. CONCLUSION: Altered BA kinetics upon ingestion of a meal, as frequently observed in RYGB-CC subjects, appear to contribute to postprandial hypoglycaemia by stimulating intestinal GLP-1 release.

Measuring Muscle Mass and Strength in Obesity: a Review of Various Methods.

Lower muscle mass in populations with obesity is associated obesity-related diseases like hypertension and type 2 diabetes mellitus. Bariatric surgery leads to sustained weight loss. During the weight reduction, loss of muscle should be minimized. Thus reliable quantification of muscle mass is much needed and therefore the also the need for validated methods. Imaging methods, magnetic resonance imaging and computed tomography scan, have been the gold standard for many years. However, these methods are costly and have limitations such as the maximum weight. Dual-energy X-ray absorptiometry is currently the most used alternative. Other, less expensive methods are very limited in their validation in populations with morbid obesity. This narrative review summarizes the current knowledge regarding measuring muscle mass and strength in obesity.

Patient-reported physical functioning is limited in almost half of critical illness survivors 1-year after ICU-admission: A retrospective single-centre study.

Post-intensive care unit (ICU) sequelae, including physical and mental health problems, are relatively unexplored. Characteristics commonly used to predict outcome lack prognostic value when it comes to long-term physical recovery. Therefore, the objective of this study was to assess the incidence of non-recovery in long-stay ICU-patients. In this single-centre study, retrospective data of adults with an ICU stay >48 hours who visited the specialized post-ICU clinic, and completed the Dutch RAND 36-item Short Form questionnaire at 3 and 12 months post-ICU, were retrieved from electronic patient records. In cases where physical functioning scores at 12 months were below reference values, patients were allocated to the physical non-recovery (NR) group. Significantly different baseline and (post-)ICU-characteristics were assessed for correlations with physical recovery at 12 months post-ICU. Of 250 patients, 110 (44%) fulfilled the criteria for the NR-group. Neither the severity of illness, type of admission, nor presence of sepsis did not differ between groups. However, NR-patients had a higher age, were more often female, and had a higher incidence of co-morbidities. Shorter LOS ICU, lower incidence of medical comorbidities, and better physical performance at 3 months were significantly correlated with 1-year physical recovery. Comorbidities and reduced physical functioning at 3 months were identified as independent risk-factors for long-term physical non-recovery. In conclusion, a substantial proportion of long-stay ICU-patients who visited the standard care post-ICU clinic did not fulfil the criteria for full physical recovery at 12 months post-ICU. Commonly used ICU-characteristics, such as severity of illness, do not have sufficient prognostic value when it comes to long-term recovery of health-related quality of life.

Potential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease.

Farnesoid X receptor controls bile acid metabolism, both in the liver and intestine. This potent nuclear receptor not only maintains homeostasis of its own ligands, i.e., bile acids, but also regulates glucose and lipid metabolism as well as the immune system. These findings have led to substantial interest for FXR as a therapeutic target and to the recent approval of an FXR agonist for treating primary biliary cholangitis as well as ongoing clinical trials for other liver diseases. Given that FXR biology is complex, including moderate expression in tissues outside of the enterohepatic circulation, temporal expression of isoforms, posttranscriptional modifications, and the existence of several other bile acid-responsive receptors such as TGR5, clinical application of FXR modulators warrants thorough understanding of its actions. Recent findings have demonstrated remarkable physiological effects of targeting FXR specifically in the intestine (iFXR), thereby avoiding systemic release of modulators. These include local effects such as improvement of intestinal barrier function and intestinal cholesterol turnover, as well as systemic effects such as improvements in glucose homeostasis, insulin sensitivity, and nonalcoholic fatty liver disease (NAFLD). Intriguingly, metabolic improvements have been observed with both an iFXR agonist that leads to production of enteric Fgf15 and increased energy expenditure in adipose tissues and antagonists by reducing systemic ceramide levels and hepatic glucose production. Here we review the recent findings on the role of intestinal FXR and its targeting in metabolic disease.