Predicting longitudinal changes in patterns of tobacco and nicotine product use among adolescents: A Latent Transition Analysis based on the X:IT study.

INTRODUCTION: Understanding factors influencing the transition from non-use to tobacco and nicotine product initiation among adolescents is crucial for designing and implementing effective preventive strategies. This study explores transition patterns among 13-15-year-old adolescents in lower secondary school, focusing on the transition from non-use to tobacco and nicotine product initiation and the influence of individual, social, risk behavioral, and mental health factors on this transition. METHODS: Based on data from a Danish smoking prevention trial between 2017 and 2019, this study employed questionnaire surveys at three time points: baseline (start of seventh grade, n = 1,990, response rate = 86.3%), eight-month follow-up (end of seventh grade, n = 1,666, response rate = 74,8%), and 20-month follow-up (end of eighth grade, n = 1,149, response rate = 70,6%). Tobacco and nicotine use indicators included current and lifetime use of cigarettes and lifetime use of e-cigarettes, smokeless tobacco, and hookah. A latent transition analysis was applied to identify longitudinal transition patterns across waves and to explore predictors of these patterns. RESULTS: Three user classes emerged across all waves: none-use, lifetime e-cigarette and cigarette use, and poly-tobacco use. While the most prevalent class was the non-user class (71%-86%), the proportion of the lifetime e-cigarette and cigarette class increased over time (from 12% to 17%). Similarly, the poly-tobacco user class increased from 2% to 12%. The probability of transitioning from non-use to lifetime e-cigarette and cigarette use increased from 0.5% at baseline to 12% by the second follow-up, while the probability of transitioning from lifetime e-cigarette and cigarette use remained stable over time (12%-15%). Across all waves, elevated risk behavior predicted this transition. For instance, binge-drinking (OR = 3.76, 95% CI: 1.51-9.34), susceptibility to smoking (OR = 7.63, 95% CI: 3.68-16.83), and truancy (OR = 7.00, 95% CI: 1.98-24.59) influenced the transition from non-use at baseline to lifetime e-cigarette and cigarette use at first follow-up. Additionally, boys, adolescents with low socioeconomic status, low life satisfaction, and those with smoking friends or parents were more likely to transition from non-use to lifetime e-cigarette and cigarette use. CONCLUSION: This study demonstrates that sociodemographic, social risk, behavioral, and mental health factors impact the transition from non-use to lifetime e-cigarette and cigarette use. The findings provide valuable insights for developing targeted preventive strategies focusing on these influencing factors.

Decline in HbA1c during the first year of elexacaftor/tezacaftor/ivacaftor treatment in the Danish cystic fibrosis cohort: Short title: Decline in HbA1c after elexacaftor/tezacaftor/ivacaftor treatment.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI. METHODS: We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment. RESULTS: Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters. CONCLUSION: In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels.

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Aims: The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment. Methods: Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT). Participants were classified according to glucose tolerance status and hypoglycaemia was defined as 3-hour glucose <3.9 mmol/L in those with normal glucose tolerance (NGT) and early glucose intolerance (EGI). Results: Among 93 participants, 67 underwent an extended OGTT. In addition to worsening in insulin secretion, the progression to CFRD was associated with signs of beta cell stress, as the fasting proinsulin-to-insulin ratio incrementally increased (p-value for trend=0.013). The maximum proinsulin level (pmol/L) was positively associated with the nadir glucagon, as nadir glucagon increased 6.2% (95% confidence interval: 1.4-11.3%) for each unit increase in proinsulin. Those with hypoglycaemia had higher 60-min glucose, 120-min C-peptide, and 180-min glucagon levels (27.8% [11.3-46.7%], 42.9% [5.9-92.85%], and 80.3% [14.9-182.9%], respectively) and unaltered proinsulin-to-insulin ratio compared to those without hypoglycaemia. Conclusions: The maximum proinsulin concentration was positively associated with nadir glucagon during the OGTT, suggesting that beta cell stress is associated with abnormal alpha cell function in adults with CF. In addition, hypoglycaemia seemed to be explained by a temporal mismatch between glucose and insulin levels rather than by an impaired glucagon response.

Correlates of Iron, Cobalamin, Folate, and Vitamin A Status among Stunted Children: A Cross-Sectional Study in Uganda.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial.

BACKGROUND & AIMS: Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120). METHODS: This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety. RESULTS: A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups. CONCLUSIONS: BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov: NCT03085277.

Effect of aerobic exercise training on the fat fraction of the liver in persons with chronic hepatitis B and hepatic steatosis: Trial protocol for a randomized controlled intervention trial- The FitLiver study.

BACKGROUND: The global prevalence of chronic hepatitis B is more than 300 million people, and in Denmark, 17,000 people are estimated to have chronic hepatitis B. Untreated, chronic hepatitis B can lead to the development of liver cirrhosis and liver cancer. There is no curable therapy. In persons with obesity and chronic hepatitis B infection, the development of hepatic steatosis imposes a double burden on the liver, leading to an increased risk of cirrhosis and liver cancer. In patients without chronic hepatitis B, exercise interventions have shown beneficial effects on hepatic steatosis through improvements in fat fraction of the liver, insulin resistance, fatty acid metabolism, and glucose metabolism, as well as activation of liver-induced regulatory protein secretion (hepatokines) after the exercise intervention. OBJECTIVE: To investigate in persons with chronic hepatitis B and hepatic steatosis: Primary: Whether exercise will decrease the fat fraction of the liver. Secondary: If exercise will affect hepatokine secretion and if it will improve lipid- and glucose metabolism, liver status, markers of inflammation, body composition, and blood pressure. METHODS: A randomized, controlled, clinical intervention trial consisting of 12 weeks of aerobic exercise training or no intervention. Thirty persons with chronic hepatitis B and hepatic steatosis will be randomized 1:1. Before and after the intervention, participants will undergo an MRI scan of the liver, blood sampling, oral glucose tolerance test, fibroscan, VO2max test, DXA scan, blood pressure measurements, and optional liver biopsy. Lastly, a hormone infusion test with somatostatin and glucagon to increase the glucagon/insulin ratio for stimulating secretion of circulating hepatokines will be performed. The training program includes three weekly training sessions of 40 min/session over 12 weeks. DISCUSSION: This trial, investigating high-intensity interval training in persons with chronic hepatitis B and hepatic steatosis, is the first exercise intervention trial performed on this group of patients. If exercise reduces hepatic steatosis and induces other beneficial effects of clinical markers in this group of patients, there might be an indication to recommend exercise as part of treatment. Furthermore, the investigation of the effect of exercise on hepatokine secretion will provide more knowledge on the effects of exercise on the liver. TRIAL REGISTRATION: Danish Capital Regions committee on health research ethics reference: H-21034236 (version 1.4 date: 19-07-2022) and ClinicalTrials.gov: NCT05265026.

Associations between Stunting, Wasting and Body Composition: A Longitudinal Study in 6- to 15-Month-Old Kenyan Children.

BACKGROUND: Early growth and body composition may influence the risk of obesity and health in adulthood. Few studies have examined how undernutrition is associated with body composition in early life. OBJECTIVES: We assessed stunting and wasting as correlates of body composition in young Kenyan children. METHODS: Nested in a randomized controlled nutrition trial, this longitudinal study assessed fat and fat-free mass (FM, FFM) using deuterium dilution technique among children at age 6 and 15 months. This trial was registered at http://controlled-trials.com/ (ISRCTN30012997). Cross-sectional and longitudinal associations between z-score categories of length-for-age (LAZ) or weight-for-length (WLZ) and FM, FFM, fat mass index (FMI), fat-free mass index (FFMI), triceps, and subscapular skinfolds were analyzed by linear mixed models. RESULTS: Among the 499 children enrolled, breastfeeding declined from 99% to 87%, stunting increased from 13% to 32%, and wasting remained at 2% to 3% between 6 and 15 mo. Compared with LAZ >0, stunted children had a 1.12 kg (95% CI: 0.88, 1.36; P < 0.001) lower FFM at 6 mo and increased to 1.59 kg (95% CI: 1.25, 1.94; P < 0.001) at 15 mo, corresponding to differences of 18% and 17%, respectively. When analyzing FFMI, the deficit in FFM tended to be less than proportional to children's height at 6 mo (P ≤ 0.060) but not at 15 mo (P > 0.40). Stunting was associated with 0.28 kg (95% CI: 0.09, 0.47; P = 0.004) lower FM at 6 mo. However, this association was not significant at 15 mo, and stunting was not associated with FMI at any time point. A lower WLZ was generally associated with lower FM, FFM, FMI, and FFMI at 6 and 15 mo. Differences in FFM, but not FM, increased with time, whereas FFMI differences did not change, and FMI differences generally decreased with time. CONCLUSIONS: Overall, low LAZ and WLZ among young Kenyan children were associated with reduced lean tissue, which may have long-term health consequences.

Biomarkers for iron metabolism among patients hospitalized with community-acquired pneumonia caused by infection with SARS-CoV-2, bacteria, and influenza.

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID-19. Few studies have investigated regulators of iron metabolism in the context of COVID-19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community-acquired pneumonia (CAP) caused by SARS-CoV-2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross-sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C-reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS-CoV-2 with 143.8 (100.7-180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1-125.4) and 53.5 (25.2-125.8) ng/mL, respectively. The median ferritin level was more than 2-fold higher in patients with SARS-CoV-2 compared with the other etiologies (p < 0.001). Patients with SARS-CoV-2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS-CoV-2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS-CoV-2 infection.

Fish oil supplementation may improve attention, working memory and attention-deficit/hyperactivity disorder symptoms in adults with autism spectrum disorder: a randomised crossover trial.

Marine n-3 fatty acids (n-3LCPUFA) have shown neurocognitive benefits in children with attention-deficit/hyperactivity disorder (ADHD), but few trials have examined effects in adults with autism spectrum disorder (ASD). We explored, if n-3LCPUFA affect cognitive functions in adults with ASD, and if effects are modified by comorbid ADHD. In a 2 × 4 week crossover study, twenty-six participants were randomised to sequence of supplementation with fish oil (FO, 5·2 g/d n-3PUFA) and safflower oil (SO). At baseline and after each period, we measured primary outcomes: attention (d2-test) and spatial working memory (Corsi test) and secondary outcomes: flexibility (Stroop word-colour test), ADHD symptoms (Conners scales), executive functions (Behavioural Inventory of Executive Function) and social behaviour (Social Responsiveness Scale). The dropout rate was 15 %. Compliance was 94 % and correlated with whole-blood n-3LCPUFA. Corsi scores improved by ∼0·3 × sd (P = 0·032) after FO v. SO, and the odds for d2 errors were 30 % lower (P = 0·016), which was supported by improved Conners scores of attention (P = 0·023). Improvement in Conners ADHD symptom score was limited to participants with ADHD (-3·5(-6·0; -1·0), n 10 v. -0·2(-2·5;2·2), n 11 without ADHD, Pinteraction = 0·096), who also improved their behavioural regulation index by 0·3 × sd after FO (Pinteraction = 0·016). Participants without ADHD gained most in d2 test performance (OR = 0·4(0·2;0·7) v. 0·9(0·6;1·3) in those with ADHD, Pinteraction = 0·002), but their executive function score was exacerbated after FO (5·9(0·0,11·8), Pinteraction = 0·039). Our results did not show any effects on ASD symptoms, but suggest that FO may improve attention and working memory in adults with ASD and ameliorate ADHD symptoms in those with comorbid ADHD.

Does FGF21 Mediate the Potential Decrease in Sweet Food Intake and Preference Following Bariatric Surgery?

The liver-derived hormone fibroblast growth factor 21 (FGF21) has recently been linked to preference for sweet-tasting food. We hypothesized, that surgery-induced changes in FGF21 could mediate the reduction in sweet food intake and preference following bariatric surgery. Forty participants (35 females) with severe obesity (BMI ≥ 35 kg/m2) scheduled for roux-en-y gastric bypass (n = 30) or sleeve gastrectomy (n = 10) were included. Pre- and postprandial responses of intact plasma FGF21 as well as intake of sweet-tasting food assessed at a buffet meal test, the hedonic evaluation of sweet taste assessed using an apple juice with added sucrose and visual analog scales, and sweet taste sensitivity were assessed before and 6 months after bariatric surgery. In a cross-sectional analysis pre-surgery, pre- and postprandial intact FGF21 levels were negatively associated with the hedonic evaluation of a high-sucrose juice sample (p = 0.03 and p = 0.02). However, no changes in pre- (p = 0.24) or postprandial intact FGF21 levels were found 6 months after surgery (p = 0.11), and individual pre- to postoperative changes in pre- and postprandial intact FGF21 levels were not found to be associated with changes in intake of sweet foods, the hedonic evaluation of sweet taste or sweet taste sensitivity (all p ≥ 0.10). In conclusion, we were not able to show an effect of bariatric surgery on circulating FGF21, and individual postoperative changes in FGF21 were not found to mediate an effect of surgery on sweet food intake and preference.

Associations Between Glucose Tolerance, Insulin Secretion, Muscle and Fat Mass in Cystic Fibrosis.

BACKGROUND: A frequent comorbidity in cystic fibrosis (CF) is CF related diabetes (CFRD) caused by a gradual decline in insulin secretion. The reduction in the anabolic hormone, insulin, might explain the weight loss that precedes onset of CFRD. We investigated the association between muscle and fat mass in relation to glucose tolerance and insulin function. METHODS: In a cross-sectional study with CF patients (⩾18 years), we conducted an oral glucose tolerance test and dual energy X-ray absorptiometry scan (DXA). Based on plasma glucose, glucose tolerance was defined as normal (NGT): 1-hour <11.1 mmol/L and 2-hour <7.8 mmol/L, impaired (IGT): 2-hour ⩾7.8 and <11.1 mmol/L or CFRD: 2-hour ⩾11.1 mmol/L. Insulin resistance (HOMA-IR) was derived from fasting levels of plasma glucose and plasma insulin, and fat-free and fat mass index (kg/m2) from DXA. Associations were evaluated using linear regression models adjusted for age, sex, and pancreas insufficiency. RESULTS: Among 79 CF patients with exocrine pancreas insufficiency, impairment of glucose tolerance corresponded to reduced insulin secretion. In the IGT group the fat-free mass index (FFMI) was 1.2 kg/m2 (95% CI: [-2.3, -0.03] kg/m2, P = .044) lower compared to the NGT group. FFMI increased insignificantly by 0.4 kg/m2 (95% CI: [-0.6, 1.5] kg/m2, P = .422) among the insulin-treated CFRD group compared to IGT. Fat mass index (FMI) was not different between groups but tended to decrease with glucose tolerance impairment. For each 100 pmol/L increase in fasting insulin FFMI increased by 1.77 kg/m2 (95% CI: [0.21, 3.33] kg/m2/pmol/L/100) and FMI increased by 6.15 kg/m2 (95% CI: [3.87, 8.44] kg/m2/pmol/L/100). In multivariate analyses, HOMA-IR was positively associated with FFMI (ß = 0.5 kg/m2/HOMA-IR, 95% CI: [0.08, 0.92] kg/m2/HOMA-IR, P = .021) and FMI (ß = 1.5 kg/m2/HOMA-IR, 95% CI: [0.87, 2.15] kg/m2/HOMA-IR, P < .001). CONCLUSIONS: Muscle mass was significantly lower among participants with impaired glucose tolerance (IGT), while muscle mass was normalized among those treated with insulin.

Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes.

We previously observed beneficial effects of a carbohydrate-reduced, high-protein (CRHP) diet on cardiovascular risk markers in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, when all food was provided to subjects as ready-to-eat meals. Here, we report the results from a 6-month open label extension: 28 patients with T2DM were instructed to self-prepare the CRHP diet with dietetic guidance. At weeks 0, 6, 12, and 36, fasting and postprandial (4-h meal test) blood samples were collected for measurements of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triacylglycerol (TG), apolipoproteins A1 and B, non-esterified fatty acids (NEFA), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6. Diurnal blood pressure and heart rate were also assessed. At the end of the study (week 36), concentrations of fasting total and LDL-cholesterol, fasting and postprandial NEFA and TG, and fasting apolipoprotein-B, CRP and TNF-α concentrations were significantly lower compared with week 0 (p < 0.05). A significant decrease in diurnal heart rate was also observed. From week 12 to 36, an increase in HDL-cholesterol and apolipoprotein-A1 concentrations and a further reduction in fasting and postprandial NEFA (p < 0.05) were found. These changes were independent of minor fluctuations in body weight. We conclude that the substitution of dietary carbohydrate for protein and fat has beneficial effects on several cardiovascular risk markers in patients with T2DM, which are maintained or augmented over the next 6 months when patients select and prepare the CRHP diet on their own in a dietitian-supported setting.

Diagnosis of primary hyperfibrinolysis and in vitro investigation of the inhibitory effects of tranexamic acid in a group of dogs with sarcomas - A pilot study.

Primary hyperfibrinolysis is not well characterised in canine cancer. This prospective case-control pilot study aimed to evaluate tissue plasminogen activator-modified thromboelastography (tPA-TEG) for diagnosis of primary hyperfibrinolysis in dogs with cancer and establish the in vitro therapeutic concentration of tranexamic acid (TXA). Nine dogs with sarcomas and normocoagulable thromboelastograms and 11 healthy dogs were included. For each a whole blood tPA-TEG, and four tPA-TEGs with added TXA in different concentrations were analysed. Lysis percentage at 30/60 min following maximal amplitude (LY30/60), clot lysis index (CL30/60), maximum rate of lysis (MRL), and total lysis (L) were investigated as diagnostic parameters of primary hyperfibrinolysis. In vitro TXA concentrations needed to inhibit 50% (IC50) and 90% (IC90) of the fibrinolytic potential were compared between groups. Significant primary hyperfibrinolysis (LY30 (P = 0.0001), LY60 (P = 0.003), CL30 (P = 0.01), and L (P = 0.02)) was observed in dogs with sarcomas. IC50 and IC90 of in vitro TXA for normalizing LY30 were 13.34 (SE 1.52) and 31.10 (SE 3.01) mg/L for dogs with sarcomas and 4.41 (SE 5.84) and 20.00 (SE 6.18) mg/L for healthy dogs. IC50 and IC90 for normalizing LY60 were 22.18 (SE 1.27) and 58.94 (SE 5.47) mg/L for dogs with sarcomas and 11.25 (SE 2.82) and 56.20 (SE 11.61) mg/L for healthy dogs. The IC50 for LY60 was significantly increased for dogs with sarcomas (P = 0.0003). Primary hyperfibrinolysis was documented by tPA-TEG in dogs with sarcomas. In vitro IC50 and IC90 for TXA were established. Clinical studies are required to establish therapeutic dosages in vivo.

Factors Associated with Favorable Changes in Food Preferences After Bariatric Surgery.

PURPOSE: Bariatric surgery may shift food preferences towards less energy-dense foods. Eating behavior is multifactorial, and the mechanisms driving changes in food preferences could be a combination of a physiological response to surgery and social and psychological factors. This exploratory study aimed to identify potential factors explaining the variation in changes in food preferences after bariatric surgery. MATERIALS AND METHODS: Physiological, social, and psychological data were collected before, 6 weeks or 6 months after surgery. All variables were analyzed in combination using LASSO regression to explain the variation in changes in energy density at an ad libitum buffet meal 6 months after bariatric surgery (n=39). RESULTS: The following factors explained 69% of the variation in changes in food preferences after surgery and were associated with more favorable changes in food preferences (i.e., a larger decrease in energy density): female gender, increased secretion of glicentin, a larger decrease in the hedonic rating of sweet and fat and a fatty cocoa drink, a lower number of recent life crises, a low degree of social eating pressure, fulfilling the diagnostic criteria for binge eating disorder, less effort needed to obtain preoperative weight loss, a smaller household composition, a lower degree of self-efficacy and a higher degree of depression, nutritional regime competence, and psychosocial risk level. CONCLUSION: Factors explaining the variation in altered food preferences after bariatric surgery not only include a physiological response to surgery but also social and psychological factors.

The PREVIEW intervention study: Results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes.

AIM: To compare the impact of two long-term weight-maintenance diets, a high protein (HP) and low glycaemic index (GI) diet versus a moderate protein (MP) and moderate GI diet, combined with either high intensity (HI) or moderate intensity physical activity (PA), on the incidence of type 2 diabetes (T2D) after rapid weight loss. MATERIALS AND METHODS: A 3-year multicentre randomized trial in eight countries using a 2 x 2 diet-by-PA factorial design was conducted. Eight-week weight reduction was followed by a 3-year randomized weight-maintenance phase. In total, 2326 adults (age 25-70 years, body mass index ≥ 25 kg/m2 ) with prediabetes were enrolled. The primary endpoint was 3-year incidence of T2D analysed by diet treatment. Secondary outcomes included glucose, insulin, HbA1c and body weight. RESULTS: The total number of T2D cases was 62 and the cumulative incidence rate was 3.1%, with no significant differences between the two diets, PA or their combination. T2D incidence was similar across intervention centres, irrespective of attrition. Significantly fewer participants achieved normoglycaemia in the HP compared with the MP group (P < .0001). At 3 years, normoglycaemia was lowest in HP-HI (11.9%) compared with the other three groups (20.0%-21.0%, P < .05). There were no group differences in body weight change (-11% after 8-week weight reduction; -5% after 3-year weight maintenance) or in other secondary outcomes. CONCLUSIONS: Three-year incidence of T2D was much lower than predicted and did not differ between diets, PA or their combination. Maintaining the target intakes of protein and GI over 3 years was difficult, but the overall protocol combining weight loss, healthy eating and PA was successful in markedly reducing the risk of T2D. This is an important clinically relevant outcome.

Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

BACKGROUND: Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated. METHODS: We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose. RESULTS: No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02). CONCLUSIONS: In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum.

Combining host-derived biomarkers with patient characteristics improves signature performance in predicting tuberculosis treatment outcomes.

Tuberculosis (TB) is a global health concern. Treatment is prolonged, and patients on anti-TB therapy (ATT) often experience treatment failure for various reasons. There is an urgent need to identify signatures for early detection of failure and initiation of a treatment switch.We investigated how gene biomarkers and/or basic patient characteristics could be used to define signatures for treatment outcomes in Indian adult pulmonary-TB patients treated with standard ATT. Using blood samples at baseline, a 12-gene signature combined with information on gender, previously-diagnosed TB, severe thinness, smoking and alcohol consumption was highly predictive of treatment failure at 6 months. Likewise a 4-protein biomarker signature combined with the same patient characteristics was almost as highly predictive of treatment failure. Combining biomarkers and basic patient characteristics may be useful for predicting and hence identification of treatment failure at an early stage of TB therapy.

Predictors of weight loss after bariatric surgery-a cross-disciplinary approach combining physiological, social, and psychological measures.

BACKGROUND: Bariatric surgery leads to a substantial weight loss (WL), however, a subset of patients undergoing surgery fails to achieve adequate WL. The reason for the individual variation in WL remains unexplained. Using an exploratory cross-disciplinary approach, we aimed to identify preoperative and early postoperative factors explaining the variation in WL after bariatric surgery. METHODS: Sixty-one subjects were recruited. Eighteen subjects did not receive surgery and three subjects dropped out, leaving a total sample of 40 subjects. Physiological, social, and psychological data were collected before and 6 months after surgery. All variables were analyzed in combination using a least absolute shrinkage and selection operator (LASSO) regression to explain the variation in WL 18 months after Roux-en-Y gastric bypass (n = 30) and sleeve gastrectomy (n = 10). RESULTS: Mean WL was 31% (range: 10-52%). The following preoperative factors predicted 59% of the variation in WL: type of surgery (14%), diabetes status (12%), economic resources (9%), sex (7%), binge eating disorder (7%), degree of depression (5%), household type (3%), and physical activity (1%). Including information on early responses after surgery increased the ability to predict WL to 78% and was explained by early WL (47%), changes in energy density of food consumed from a buffet meal (9%), changes in glicentin (5%), degree of depression (5%), sex (5%), type of surgery (2%), economic resources (2%), and changes in drive for thinness (1%). CONCLUSIONS: Using a cross-disciplinary approach, a substantial part of the individual variation in WL was explained by a combination of basic patient characteristics, psychological profile, and social conditions as well as physiological, psychological and behavioral responses to surgery. These results suggest that patient characteristics collected in a cross-disciplinary approach may help determine predictors for less successful WL after bariatric surgery. If verified in larger cohorts this may form the basis for individualized postoperative support to optimize WL outcome.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

Oxyntomodulin and Glicentin May Predict the Effect of Bariatric Surgery on Food Preferences and Weight Loss.

BACKGROUND: Alterations in several gastrointestinal hormones are implicated in the postoperative suppression of food intake leading to weight loss after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). The aim was to evaluate changes in responses of gastrointestinal hormones after RYGB and SG and the associations of these changes with weight loss, energy intake, and food preferences. METHODS: Forty-two subjects with severe obesity were included (32 RYGB; 10 SG). Postprandial responses of glicentin, oxyntomodulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin were measured before and 6 months after surgery. Energy intake and energy density were assessed before and 6 months after surgery using a buffet meal test and weight loss was assessed 18 months after surgery. RESULTS: Postprandial concentrations of glicentin, oxyntomodulin, GLP-1, and ghrelin differed between RYGB and SG (all P ≤ .02). Enhanced responses of glicentin and oxyntomodulin predicted a greater weight loss (both P < .01) and were associated with a larger decrease in energy density (P ≤ .04). No associations were found for GLP-1, PYY, and ghrelin, and changes were not associated with changes in energy intake. When combing all hormones, 60%, 19%, and 33% of the variations in weight loss, energy intake, and energy density, respectively, could be explained. CONCLUSION: Postprandial responses of gastrointestinal hormones differed between RYGB and SG. Enhanced responses of glicentin and oxyntomodulin predicted a better weight loss and were associated with a decreased preference for energy-dense foods. Replication of these results could imply an opportunity to identify patients in need of additional support after surgical treatments of obesity.