Metabolic effects of fructose and the worldwide increase in obesity.

While virtually absent in our diet a few hundred years ago, fructose has now become a major constituent of our modern diet. Our main sources of fructose are sucrose from beet or cane, high fructose corn syrup, fruits, and honey. Fructose has the same chemical formula as glucose (C(6)H(12)O(6)), but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. However, chronically high consumption of fructose in rodents leads to hepatic and extrahepatic insulin resistance, obesity, type 2 diabetes mellitus, and high blood pressure. The evidence is less compelling in humans, but high fructose intake has indeed been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Hepatic de novo lipogenesis and lipotoxicity, oxidative stress, and hyperuricemia have all been proposed as mechanisms responsible for these adverse metabolic effects of fructose. Although there is compelling evidence that very high fructose intake can have deleterious metabolic effects in humans as in rodents, the role of fructose in the development of the current epidemic of metabolic disorders remains controversial. Epidemiological studies show growing evidence that consumption of sweetened beverages (containing either sucrose or a mixture of glucose and fructose) is associated with a high energy intake, increased body weight, and the occurrence of metabolic and cardiovascular disorders. There is, however, no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects. There has also been much concern that consumption of free fructose, as provided in high fructose corn syrup, may cause more adverse effects than consumption of fructose consumed with sucrose. There is, however, no direct evidence for more serious metabolic consequences of high fructose corn syrup versus sucrose consumption.

Hochkalorische Ernährung bei chronischer obstruktiver Lungenkrankheit [High-caloric nutrition in chronic obstructive lung disease]

A body weight lower than 90% of the optional value has an unfavorable influence on the prognosis of chronic obstructive pulmonary disease (COPD). Short term studies of up to three months duration have shown improved function of respiratory muscle exercise tolerance and immunologic parameters by an increased caloric intake of 45 kcal/kg body weight. In a randomized trial of twelve months 14 of 30 patients with an average FEV1 of 0.8 l were instructed to take a high calorie diet. For simplicity a part of the calories were administered as Fresubin, a fluid nutrient formula. Although a weight gain of 7 kg (p = 0.003) was obtained the difference to the control group was statistically not significant (p = 0.08). The same was true for skin fold thickness (12.4 vs 5.7 mm), change of ventilatory parameters and the 6 minute walking distance (-33 vs -86 m). Subjective improvement was, however, impressive in all patients with dietary intervention, explainable probably by increased attention. Dietary counselling for increased intake of calories, vitamins and also calcium is thus very important in the treatment of patients with COPD.

Long-term data from the swiss pulmonary hypertension registry.

BACKGROUND: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE: To provide long-term data of the Swiss PH registry of 1998-2012. METHODS: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.

Effects of aerobic fitness on oxygen uptake kinetics in heavy intensity swimming.

This study aimed to characterise both the [Formula: see text] kinetics within constant heavy-intensity swimming exercise, and to assess the relationships between [Formula: see text] kinetics and other parameters of aerobic fitness, in well-trained swimmers. On separate days, 21 male swimmers completed: (1) an incremental swimming test to determine their maximal oxygen uptake [Formula: see text], first ventilatory threshold (VT), and the velocity associated with [Formula: see text] [Formula: see text] and (2) two square-wave transitions from rest to heavy-intensity exercise, to determine their [Formula: see text] kinetics. All the tests involved breath-by-breath analysis of freestyle swimming using a swimming snorkel. [Formula: see text] kinetics was modelled with two exponential functions. The mean values for the incremental test were 56.0 ± 6.0 ml min(-1) kg(-1), 1.45 ± 0.08 m s(-1); and 42.1 ± 5.7 ml min(-1) kg(-1) for [Formula: see text], [Formula: see text] and VT, respectively. For the square-wave transition, the time constant of the primary phase (τ(p)) averaged 17.3 ± 5.4 s and the relevant slow component (A'(sc)) averaged 4.8 ± 2.9 ml min(-1) kg(-1) [representing 8.9% of the end-exercise [Formula: see text] (%A'(sc))]. τ(p) was correlated with [Formula: see text] (r = -0.55, P = 0.01), but not with either [Formula: see text] (r = 0.05, ns) or VT (r = 0.14, ns). The %A'(sc) did not correlate with either [Formula: see text] (r = -0.14, ns) or [Formula: see text] (r = 0.06, ns), but was inversely related with VT (r = -0.61, P < 0.01). This study was the first to describe the [Formula: see text] kinetics in heavy-intensity swimming using specific swimming exercise and appropriate methods. As has been demonstrated in cycling, faster [Formula: see text] kinetics allow higher aerobic power outputs to be attained. The slow component seems to be reduced in swimmers with higher ventilatory thresholds.

Influence of nutrition on urinary oxalate and calcium in preterm and term infants.

Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1-60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P&lt;0.05) or HM fed (206 vs. 169 mmol/ mol and 283* vs. 232 mmol/mol; *P&lt;0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P &lt; 0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants.

Marqueurs de la filtration glomérulaire en pédiatrie [Glomerular filtration markers in pediatrics]

The assessment of glomerular filtration rate (GFR) is critical for the diagnosis and management of renal diseases in pediatric nephrology. Ideally, it requires the measurement of the renal clearance of a filtration marker. Inulin, an exogenous marker, is the only compound the excretion of which occurs exclusively by glomerular filtration, with no tubular handling. Therefore, inulin clearance provides the most accurate method to measure GFR and is considered as the "gold standard", at all ages including very premature neonates. However, inulin dearance is cumbersome and alternative methods are used in clinical practice. If urine is available, endogenous creatinine clearance is the most reliable method. When urine collection is difficult to obtain, GFR can be estimated by the plasma concentration of endogenous markers mainly eliminated by glomerular filtration, such as creatinine, or the more recently described cystatin C and beta 2-microglobulin. When the endogenous production of these markers is constant, their plasma concentration reflects glomerular filtration; it increases with decreasing renal function. However, in pediatric patients creatinine production depends on muscle mass, which significantly increases with linear growth, as well as age and gender. Mathematical formulas taking these parameters into account have thus been developed. Among these, the so-called "Schwartz formula" is often used and is a reliable estimate of GFR in children. Finally, radionuclide renal scans can be used to evaluate the separate glomerular function of each kidney.

Glomerular filtration rate: measure creatinine and height rather than cystatin C!

AIM: Inulin clearance (Cin) is the gold standard for assessing glomerular filtration rate (GFR). Other methods are based on the plasma creatinine concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic protein produced at a constant rate by all nucleated cells. The present prospective study was thus designed to evaluate the reliability of PcysC as a marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz formula, using Cin as the gold standard. METHODS: Ninety-nine children (51 m/48 f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with normal GFR were comparable for age, height, weight and body mass index. RESULTS: Logistic regression, ROC analysis and linear regression all showed that Ccreat was the best parameter to discriminate between impaired and normal GFR, followed by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being significantly more predictive than the next. CONCLUSION: GFR is better assessed by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore concluded that when urine collection is not possible, simply measuring the child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

Not all inflammatory markers are linked to kidney function: results from a population-based study.

BACKGROUND: Several studies have reported increased levels of inflammatory biomarkers in chronic kidney disease (CKD), but data from the general population are sparse. In this study, we assessed levels of the inflammatory markers C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 across all ranges of renal function. METHODS: We conducted a cross-sectional study in a random sample of 6,184 Caucasian subjects aged 35-75 years in Lausanne, Switzerland. Serum levels of hsCRP, TNF-α, IL-6, and IL-1β were measured in 6,067 participants (98.1%); serum creatinine-based estimated glomerular filtration rate (eGFR(creat), CKD-EPI formula) was used to assess renal function, and albumin/creatinine ratio on spot morning urine to assess microalbuminuria (MAU). RESULTS: Higher serum levels of IL-6, TNF-α and hsCRP and lower levels of IL-1β were associated with a lower renal function, CKD (eGFR(creat) <60 ml/min/1.73 m(2); n = 283), and MAU (n = 583). In multivariate linear regression analysis adjusted for age, sex, hypertension, smoking, diabetes, body mass index, lipids, antihypertensive and hypolipemic therapy, only log-transformed TNF-α remained independently associated with lower renal function (β -0.54 ±0.19). In multivariate logistic regression analysis, higher TNF-α levels were associated with CKD (OR 1.17; 95% CI 1.01-1.35), whereas higher levels of IL-6 (OR 1.09; 95% CI 1.02-1.16) and hsCRP (OR 1.21; 95% CI 1.10-1.32) were associated with MAU. CONCLUSION: We did not confirm a significant association between renal function and IL-6, IL-1β and hsCRP in the general population. However, our results demonstrate a significant association between TNF-α and renal function, suggesting a potential link between inflammation and the development of CKD. These data also confirm the association between MAU and inflammation.

Acute supra-therapeutic oral terbutaline administration has no ergogenic effect in non-asthmatic athletes.

This study aimed to investigate the effects on a possible improvement in aerobic and anaerobic performance of oral terbutaline (TER) at a supra-therapeutic dose in 7 healthy competitive male athletes. On day 1, ventilatory threshold, maximum oxygen uptake [Formula: see text] and corresponding power output were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3, 8 mg of TER or placebo were orally administered in a double-blind process to athletes who rested for 3 h, and then performed a battery of tests including a force-velocity exercise test, running sprint and a maximal endurance cycling test at Δ50 % (50 % between VT and [Formula: see text]). Lactatemia, anaerobic parameters and endurance performance ([Formula: see text] and time until exhaustion) were raised during the corresponding tests. We found that TER administration did not improve any of the parameters of aerobic performance (p > 0.05). In addition, no change in [Formula: see text] kinetic parameters was found with TER compared to placebo (p > 0.05). Moreover, no enhancement of the force-velocity relationship was observed during sprint exercises after TER intake (p > 0.05) and, on the contrary, maximal strength decreased significantly after TER intake (p < 0.05) but maximal power remained unchanged (p > 0.05). In conclusion, oral acute administration of TER at a supra-therapeutic dose seems to be without any relevant ergogenic effect on anaerobic and aerobic performances in healthy athletes. However, all participants experienced adverse side effects such as tremors.

ESPEN Guidelines on Parenteral Nutrition: intensive care.

Nutritional support in the intensive care setting represents a challenge but it is fortunate that its delivery and monitoring can be followed closely. Enteral feeding guidelines have shown the evidence in favor of early delivery and the efficacy of use of the gastrointestinal tract. Parenteral nutrition (PN) represents an alternative or additional approach when other routes are not succeeding (not necessarily having failed completely) or when it is not possible or would be unsafe to use other routes. The main goal of PN is to deliver a nutrient mixture closely related to requirements safely and to avoid complications. This nutritional approach has been a subject of debate over the past decades. PN carries the considerable risk of overfeeding which can be as deleterious as underfeeding. Therefore the authors will present not only the evidence available regarding the indications for PN, its implementation, the energy required, its possible complementary use with enteral nutrition, but also the relative importance of the macro- and micronutrients in the formula proposed for the critically ill patient. Data on long-term survival (expressed as 6 month survival) will also be considered a relevant outcome measure. Since there is a wide range of interpretations regarding the content of PN and great diversity in its practice, our guidance will necessarily reflect these different views. The papers available are very heterogeneous in quality and methodology (amount of calories, nutrients, proportion of nutrients, patients, etc.) and the different meta-analyses have not always taken this into account. Use of exclusive PN or complementary PN can lead to confusion, calorie targets are rarely achieved, and different nutrients continue to be used in different proportions. The present guidelines are the result of the analysis of the available literature, and acknowledging these limitations, our recommendations are intentionally largely expressed as expert opinions.

Long maximal incremental tests accurately assess aerobic fitness in class II and III obese men.

This study aimed to compare two different maximal incremental tests with different time durations [a maximal incremental ramp test with a short time duration (8-12 min) (STest) and a maximal incremental test with a longer time duration (20-25 min) (LTest)] to investigate whether an LTest accurately assesses aerobic fitness in class II and III obese men. Twenty obese men (BMI≥35 kg.m-2) without secondary pathologies (mean±SE; 36.7±1.9 yr; 41.8±0.7 kg*m-2) completed an STest (warm-up: 40 W; increment: 20 W*min-1) and an LTest [warm-up: 20% of the peak power output (PPO) reached during the STest; increment: 10% PPO every 5 min until 70% PPO was reached or until the respiratory exchange ratio reached 1.0, followed by 15 W.min-1 until exhaustion] on a cycle-ergometer to assess the peak oxygen uptake [Formula: see text] and peak heart rate (HRpeak) of each test. There were no significant differences in [Formula: see text] (STest: 3.1±0.1 L*min-1; LTest: 3.0±0.1 L*min-1) and HRpeak (STest: 174±4 bpm; LTest: 173±4 bpm) between the two tests. Bland-Altman plot analyses showed good agreement and Pearson product-moment and intra-class correlation coefficients showed a strong correlation between [Formula: see text] (r=0.81 for both; p≤0.001) and HRpeak (r=0.95 for both; p≤0.001) during both tests. [Formula: see text] and HRpeak assessments were not compromised by test duration in class II and III obese men. Therefore, we suggest that the LTest is a feasible test that accurately assesses aerobic fitness and may allow for the exercise intensity prescription and individualization that will lead to improved therapeutic approaches in treating obesity and severe obesity.

Self-selection and risk selection on the Swiss health insurance market

Abstract This thesis presents three empirical studies in the field of health insurance in Switzerland. First we investigate the link between health insurance coverage and health care expenditures. We use claims data for over 60 000 adult individuals covered by a major Swiss Health Insurance Fund, followed for four years; the data show a strong positive correlation between coverage and expenditures. Two methods are developed and estimated in order to separate selection effects (due to individual choice of coverage) and incentive effects ("ex post moral hazard"). The first method uses the comparison between inpatient and outpatient expenditures to identify both effects and we conclude that both selection and incentive effects are significantly present in our data. The second method is based on a structural model of joint demand of health care and health insurance and makes the most of the change in the marginal cost of health care to identify selection and incentive effects. We conclude that the correlation between insurance coverage and health care expenditures may be decomposed into the two effects: 75% may be attributed to selection, and 25 % to incentive effects. Moreover, we estimate that a decrease in the coinsurance rate from 100% to 10% increases the marginal demand for health care by about 90% and from 100% to 0% by about 150%. Secondly, having shown that selection and incentive effects exist in the Swiss health insurance market, we present the consequence of this result in the context of risk adjustment. We show that if individuals choose their insurance coverage in function of their health status (selection effect), the optimal compensations should be function of the se- lection and incentive effects. Therefore, a risk adjustment mechanism which ignores these effects, as it is the case presently in Switzerland, will miss his main goal to eliminate incentives for sickness funds to select risks. Using a simplified model, we show that the optimal compensations have to take into account the distribution of risks through the insurance plans in case of self-selection in order to avoid incentives to select risks.Then, we apply our propositions to Swiss data and propose a simple econometric procedure to control for self-selection in the estimation of the risk adjustment formula in order to compute the optimal compensations.

Neutron structure of type-III antifreeze protein allows the reconstruction of AFP-ice interface.

Antifreeze proteins (AFPs) inhibit ice growth at sub-zero temperatures. The prototypical type-III AFPs have been extensively studied, notably by X-ray crystallography, solid-state and solution NMR, and mutagenesis, leading to the identification of a compound ice-binding surface (IBS) composed of two adjacent ice-binding sections, each which binds to particular lattice planes of ice crystals, poisoning their growth. This surface, including many hydrophobic and some hydrophilic residues, has been extensively used to model the interaction of AFP with ice. Experimentally observed water molecules facing the IBS have been used in an attempt to validate these models. However, these trials have been hindered by the limited capability of X-ray crystallography to reliably identify all water molecules of the hydration layer. Due to the strong diffraction signal from both the oxygen and deuterium atoms, neutron diffraction provides a more effective way to determine the water molecule positions (as D(2) O). Here we report the successful structure determination at 293 K of fully perdeuterated type-III AFP by joint X-ray and neutron diffraction providing a very detailed description of the protein and its solvent structure. X-ray data were collected to a resolution of 1.05 Å, and neutron Laue data to a resolution of 1.85 Å with a "radically small" crystal volume of 0.13 mm(3). The identification of a tetrahedral water cluster in nuclear scattering density maps has allowed the reconstruction of the IBS-bound ice crystal primary prismatic face. Analysis of the interactions between the IBS and the bound ice crystal primary prismatic face indicates the role of the hydrophobic residues, which are found to bind inside the holes of the ice surface, thus explaining the specificity of AFPs for ice versus water.

Energy balance, physical activity, and thermogenic effect of feeding in premature infants.

In order to assess the contribution of the thermogenic effect of feeding and muscular activity to total energy expenditure, nine premature infants were studied for 2 consecutive days during which time repeated measurements of energy expenditure by indirect calorimetry were performed throughout the day, combined with a visual activity score based on body movement. The infants were growing at 16.6 +/- 4.0 g/kg/day (mean +/- SD) and received 110 +/- 8 kcal/kg/day metabolizable energy (milk formula) and 522 +/- 40 mgN/kg/day. Their total energy expenditure was 68 +/- 4 kcal/kg/day indicating that 41 +/- 7 kcal/kg/day was retained for growth. Based on the combination of energy + N balances it was estimated that 80% of the weight gain was fat-free tissue and 20% was fat tissue. The rate of energy expenditure measured minute-by-minute was significantly and linearly correlated with the activity score in both the premeal (r = 0.75;p less than 0.001) and the postmeal periods (r = 0.74; p less than 0.001) with no difference in the regression slope, but with a significant difference in intercept. In preset feeding schedules the latter allowed an estimation of the thermogenic effect without the confounding effect of activity. This was found to be 3.1 +/- 1.8% when expressed as a percentage of metabolizable energy intake. However when the "classical" approach was used as a comparison (integration of extra energy expenditure induced by the meal), the thermogenic effect was found to be greater, i.e. 9.5 +/- 3.8% of the meal's metabolizable energy, due to the superimposed effect of physical activity in the postprandial state.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effectiveness analysis of immune-modulating nutritional support for gastrointestinal cancer patients.

BACKGROUND & AIM: Immune-modulating nutritional formula containing arginine, omega-3 fatty acids and nucleotides has been demonstrated to decrease complications and length of stay in surgical patients. This study aims at assessing the impact of immune-modulating formula on hospital costs in gastrointestinal cancer surgical patients in Switzerland. METHOD: Based on a previously published meta-analysis, the relative risks of overall and infectious complications with immune-modulating versus standard nutrition formula were computed. Swiss hospital costs of patients undergoing gastrointestinal cancer surgery were retrieved. A method was developed to compute the patients' severity level, not taking into account the complications from the surgery. Incremental costs of complications were computed for both treatment groups, and sensitivity analyses were carried out. RESULTS: Relative risk of complications with pre-, peri- and post-operative use of immune-modulating formula was 0.69 (95%CI 0.58-0.83), 0.62 (95%CI 0.53-0.73) and 0.73 (95%CI 0.35-0.96) respectively. The estimated average contribution of complications to the cost of stay was CHF 14,949 (euro10,901) per patient (95%CI 10,712-19,186), independently of case's severity. Based on this cost, immune-modulating nutritional support decreased costs of hospital stay by CHF 1638 to CHF 2488 per patient (euro1195-euro1814). Net hospital savings were present for baseline complications rates as low as 5%. CONCLUSION: Immune-modulating nutritional solution is a cost-saving intervention in gastrointestinal cancer patients. The additional cost of immune-modulating formula are more than offset by savings associated with decreased treatment of complications.