Effectiveness of offloading interventions for people with diabetes-related foot ulcers: A systematic review and meta-analysis.

BACKGROUND: Offloading treatment is crucial to heal diabetes-related foot ulcers (DFU). This systematic review aimed to assess the effectiveness of offloading interventions for people with DFU. METHODS: We searched PubMed, EMBASE, Cochrane databases, and trials registries for all studies relating to offloading interventions in people with DFU to address 14 clinical question comparisons. Outcomes included ulcers healed, plantar pressure, weight-bearing activity, adherence, new lesions, falls, infections, amputations, quality of life, costs, cost-effectiveness, balance, and sustained healing. Included controlled studies were independently assessed for risk of bias and had key data extracted. Meta-analyses were performed when outcome data from studies could be pooled. Evidence statements were developed using the GRADE approach when outcome data existed. RESULTS: From 19,923 studies screened, 194 eligible studies were identified (47 controlled, 147 non-controlled), 35 meta-analyses performed, and 128 evidence statements developed. We found non-removable offloading devices likely increase ulcers healed compared to removable offloading devices (risk ratio [RR] 1.24, 95% CI 1.09-1.41; N = 14, n = 1083), and may increase adherence, cost-effectiveness and decrease infections, but may increase new lesions. Removable knee-high offloading devices may make little difference to ulcers healed compared to removable ankle-high offloading devices (RR 1.00, 0.86-1.16; N = 6, n = 439), but may decrease plantar pressure and adherence. Any offloading device may increase ulcers healed (RR 1.39, 0.89-2.18; N = 5, n = 235) and cost-effectiveness compared to therapeutic footwear and may decrease plantar pressure and infections. Digital flexor tenotomies with offloading devices likely increase ulcers healed (RR 2.43, 1.05-5.59; N = 1, n = 16) and sustained healing compared to devices alone, and may decrease plantar pressure and infections, but may increase new transfer lesions. Achilles tendon lengthening with offloading devices likely increase ulcers healed (RR 1.10, 0.97-1.27; N = 1, n = 64) and sustained healing compared to devices alone, but likely increase new heel ulcers. CONCLUSIONS: Non-removable offloading devices are likely superior to all other offloading interventions to heal most plantar DFU. Digital flexor tenotomies and Achilles tendon lengthening in combination with offloading devices are likely superior for some specific plantar DFU locations. Otherwise, any offloading device is probably superior to therapeutic footwear and other non-surgical offloading interventions to heal most plantar DFU. However, all these interventions have low-to-moderate certainty of evidence supporting their outcomes and more high-quality trials are needed to improve our certainty for the effectiveness of most offloading interventions.

Negligible In Vitro Recovery of Macromolecules from Microdialysis Using 100 kDa Probes and Dextran in Perfusion Fluid.

Microdialysis is applied in neurointensive care to monitor cerebral glucose metabolism. If recoverable, macromolecules may also serve as biomarkers in brain disease and provide clues to their passage across the blood-brain barrier. Our study aimed to investigate the in vitro recovery of human micro- and macromolecules using microdialysis catheters and perfusion fluids approved for clinical use. In vitro microdialysis of a bulk solution containing physiological or supraphysiological concentrations of glucose, lactate, pyruvate, human IgG, serum albumin, and hemoglobin was performed using two different catheters and perfusion fluids. One had a membrane cut-off of 20 kDa and was used with a standard CNS perfusion fluid, and the other had a membrane cut-off of 100 kDa and was perfused with the same solution supplemented with dextran. The flow rate was 0.3 µl/min. We used both push and push-pull methods. Dialysate samples were collected at 2-h intervals for 6 h and analyzed for relative recovery of each substance. The mean relative recovery of glucose, pyruvate, and lactate was > 90% in all but two sets of experiments. In contrast, the relative recovery of human IgG, serum albumin, and hemoglobin from both bulk solutions was below the lower limit of quantification (LLOQ). Using a push-pull method, recovery of human IgG, serum albumin, and hemoglobin from a bulk solution with supraphysiological concentrations were above LLOQ but with low relative recovery (range 0.9%-1.6%). In summary, exchanging the microdialysis setup from a 20 kDa catheter with a standard perfusion fluid for a 100 kDa catheter with a perfusion solution containing dextran did not affect the relative recovery of glucose and its metabolites. However, it did not result in any useful recovery of the investigated macromolecules at physiological levels, either with or without a push-pull pump system.

Trends in childhood body mass index between 1936 and 2011 showed that underweight remained more common than obesity among 398 970 Danish school children.

AIM: To examine trends in all body mass index (BMI) groups in children from 1936 to 2011. METHODS: We included 197 694 girls and 201 276 boys from the Copenhagen School Health Records Register, born between 1930 and 1996, with longitudinal weight and height measurements (6-14 years). Using International Obesity Task Force criteria, BMI was classified as underweight, normal-weight, overweight and obesity. Sex- and age-specific prevalences were calculated. RESULTS: From the 1930s, the prevalence of underweight was stable until a small increase occurred from 1950 to 1970s, and thereafter it declined into the early 2000s. Using 7-year-olds as an example, underweight changed from 10% to 7% in girls and from 9% to 6% in boys during the study period. The prevalence of overweight plateaued from 1950 to 1970s and then steeply increased from 1970s onwards and in 1990-2000s 15% girls and 11% boys at 7 years had overweight. The prevalence of obesity particularly increased from 1980s onwards and in 1990-2000s 5% girls and 4% boys at 7 years had obesity. These trends slightly differed by age. CONCLUSION: Among Danish schoolchildren, the prevalence of underweight was greater than overweight until the 1980s and greater than obesity throughout the period. Thus, monitoring the prevalence of childhood underweight remains an important public health issue.

Eliminating finite-size effects on the calculation of x-ray scattering from molecular dynamics simulations.

Structural studies using x-ray scattering methods for investigating molecules in solution are shifting focus toward describing the role and effects of the surrounding solvent. However, forward models based on molecular dynamics (MD) simulations to simulate structure factors and x-ray scattering from interatomic distributions such as radial distribution functions (RDFs) face limitations imposed by simulations, particularly at low values of the scattering vector q. In this work, we show how the value of the structure factor at q = 0 calculated from RDFs sampled from finite MD simulations is effectively dependent on the size of the simulation cell. To eliminate this error, we derive a new scheme to renormalize the sampled RDFs based on a model of the excluded volume of the particle-pairs they were sampled from, to emulate sampling from an infinite system. We compare this new correction method to two previous RDF-correction methods, developed for Kirkwood-Buff theory applications. We present a quantitative test to assess the reliability of the simulated low-q scattering signal and show that our RDF-correction successfully recovers the correct q = 0 limit for neat water. We investigate the effect of MD-sampling time on the RDF-corrections, before advancing to a molecular example system, comprised of a transition metal complex solvated in a series of water cells with varying densities. We show that our correction recovers the correct q = 0 behavior for all densities. Furthermore, we employ a simple continuum scattering model to dissect the total scattering signal from the solvent-solvent structural correlations in a solute-solvent model system to find two distinct contributions: a non-local density-contribution from the finite, fixed cell size in NVT simulations, and a local contribution from the solvent shell. We show how the second contribution can be approximated without also including the finite-size contribution. Finally, we provide a "best-practices"-checklist for experimentalists planning to incorporate explicit solvation MD simulations in future work, offering guidance for improving the accuracy and reliability of structural studies using x-ray scattering methods in solution.

Incidence and predictors of recurrent and other new diabetic foot ulcers: a retrospective cohort study.

AIMS: To estimate progression rates, evaluate risk factors for progression, and study rate ratios for progression among people with a healed diabetic foot ulcer according to whether the healed ulcer was neuropathic, neuro-ischaemic or critically ischaemic. METHODS: We conducted a retrospective cohort study in all individuals with a healed diabetic foot ulcer treated at the Steno Diabetes Centre Copenhagen foot clinic in the period 2010 to 2016. The outcome of interest was recurrent/other new diabetic foot ulcers. RESULTS: A total of 780 people had a healed diabetic foot ulcer in the study period (2010-2016). The participants were followed for 1249 person-years [median (Q1-Q3) 1.04 (0.38-2.46) person-years] in total. One-third (33.1%) developed a recurrent/other new diabetic foot ulcer per year. Male gender, people with Type 2 diabetes and smokers had a statistically significantly higher risk of progression to a recurrent/other new diabetic foot ulcer compared to participants without these risk factors. Participants with neuro-ischaemic or critically ischaemic diabetic foot ulcers had statistically significantly higher progression rates than participants with neuropathic diabetic foot ulcers. CONCLUSIONS: Focus should be on preventing future recurrent/other new diabetic foot ulcers especially in people with ischaemia.

Nutrient re-routing and altered gut-islet cell crosstalk may explain early relief of severe postprandial hypoglycaemia after reversal of Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass is associated with an increased risk of postprandial hyperinsulinaemic hypoglycaemia, but the underlying pathophysiology remains poorly understood. We therefore examined the effect of re-routing of nutrient delivery on gut-islet cell crosstalk in a person with severe postprandial hypoglycaemia after Roux-en-Y gastric bypass. CASE REPORT: A person with severe postprandial hypoglycaemia, who underwent surgical reversal of Roux-en-Y gastric bypass, was studied before reversal and at 2 weeks and 3 months after reversal surgery using liquid mixed meal tests and hyperinsulinaemic-euglycaemic clamps. The nadir of postprandial plasma glucose rose from 2.8 mmol/l to 4.1 mmol/l at 2 weeks and to 4.4 mmol/l at 3 months after reversal. Concomitant insulin- and glucagon-like peptide-1 secretion (peak concentrations and area under the curve) clearly decreased after reversal, while concentrations of glucose-dependent insulinotropic polypeptide and ghrelin increased. Insulin clearance declined after reversal, whereas clamp-estimated peripheral insulin sensitivity was unchanged. The person remained without symptoms of hypoglycaemia, but had experienced significant weight gain at 15-month follow-up. DISCUSSION: Accelerated nutrient absorption may be a driving force behind postprandial hyperinsulinaemic hypoglycaemia after Roux-en-Y gastric bypass. Re-routing of nutrients by reversal of the Roux-en-Y gastric bypass diminished postprandial plasma glucose excursions, alleviated postprandial insulin and glucagon-like peptide-1 hypersecretion and eliminated postprandial hypoglycaemia, which emphasizes the importance of altered gut-islet cell crosstalk for glucose metabolism after Roux-en-Y gastric bypass.

Spontaneous breathing trials after prolonged mechanical ventilation monitored by electrical impedance tomography: an observational study.

BACKGROUND: The study objective was to examine the correlation between regional ventilation distribution measured with electrical impedance tomography (EIT) and weaning outcomes during spontaneous breathing trial (SBT). METHODS: Fifteen patients received 100% automatic tube compensation (ATC) during the first and 70% during the second hour. Another 15 patients received external continuous positive airway pressure (CPAP) of 5 and 7.5 cmH2 O during the first and second hours, respectively. Regional ventilation distributions were monitored with EIT. RESULTS: Tidal volume and tidal variation of impedance correlated significantly during assist-control ventilation and ATC in all patients (r2 = 0.80 ± 0.18, P < 0.001). Higher support levels resulted in similar ventilation distribution and tidal volume, but higher end-expiratory lung impedance (EELI) (P < 0.05). Analysis of regional intratidal gas distribution revealed a redistribution of ventilation towards dorsal regions with lower support level in 13 of 30 patients. These patients had a higher weaning success rate (only 1 of 13 patients failed). Eight of 17 other patient failed (P < 0.05). The number of SBT days needed for weaning was significantly lower in the former group of 13 patients (13.1 ± 4.0 vs. 20.9 ± 11.2 days, P < 0.05). CONCLUSIONS: Regional ventilation distribution patterns during inspiration were associated with weaning outcomes, and they may be used to predict the success of extubation.

Effects of hydroxyethyl starch 130/0.42 vs. Ringer's acetate on cytokine levels in severe sepsis.

BACKGROUND: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased 90-day mortality with hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate. To explore the underlying pathophysiology, we compared early changes in plasma cytokine concentrations between patients resuscitated with HES vs. Ringer's acetate. METHODS: In a subgroup of 226 patients from the 6S trial, we calculated delta plasma concentrations of tumour necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-10 from randomization to day 2. We used multiple linear and logistic regression analyses to assess differences between the groups and associations between delta cytokine concentrations and 90-day mortality, respectively. RESULTS: Baseline characteristics and day 2 mortality were comparable between the groups. We observed similar delta cytokine concentrations in the HES vs. Ringer's group (mean difference in delta TNF-α: -1.5 pg/ml (95% CI, -4.9 to 1.9), P = 0.39; IL-6: 36.0 pg/ml (-24.1 to 96.1), P = 0.24; IL-10: -3.9 pg/ml (-21.1 to 28.9), P = 0.76). In all included patients, we observed a linear relationship between increases in TNF-α and 90-day mortality (P = 0.005). CONCLUSION: Resuscitation with HES 130/0.42 vs. Ringer's acetate did not appear to affect plasma concentrations of TNF-α, IL-6 or IL-10 differently during the first days after randomization into the 6S trial. In the overall cohort, increases in TNF-α were associated with increased 90-day mortality. Although interpretation should be done with caution, it seems unlikely that the increased mortality observed with the use HES in the 6S trial is signalled by early changes in three biomarkers of systemic inflammation.

Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery.

BACKGROUND/OBJECTIVES: Exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) may explain appetite reduction and weight loss after Roux-en-Y gastric bypass (RYGB), but causality has not been established. We hypothesized that food intake decreases after surgery through combined actions from GLP-1 and PYY. GLP-1 actions can be blocked using the GLP-1 receptor antagonist Exendin 9-39 (Ex-9), whereas PYY actions can be inhibited by the administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor preventing the formation of PYY3-36. SUBJECTS/METHODS: Appetite-regulating gut hormones and appetite ratings during a standard mixed-meal test and effects on subsequent ad libitum food intake were evaluated in two studies: in study 1, nine patients with type 2 diabetes were examined prospectively before and 3 months after RYGB with and without Ex-9. In study 2, 12 RYGB-operated patients were examined in a randomized, placebo-controlled, crossover design on four experimental days with: (1) placebo, (2) Ex-9, (3) the DPP-4 inhibitor, sitagliptin, to reduce formation of PYY3-36 and (4) Ex-9/sitagliptin combined. RESULTS: In study 1, food intake decreased by 35% following RYGB compared with before surgery. Before surgery, GLP-1 receptor blockage increased food intake but no effect was seen postoperatively, whereas PYY secretion was markedly increased. In study 2, combined GLP-1 receptor blockage and DPP-4 inhibitor mediated lowering of PYY3-36 increased food intake by ~20% in RYGB patients, whereas neither GLP-1 receptor blockage nor DPP-4 inhibition alone affected food intake, perhaps because of concomitant marked increases in the unblocked hormone. CONCLUSIONS: Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY3-36, resulted in concomitant increased secretion of the other, probably explaining the absent effect on food intake on these experimental days. Combined blockade of GLP-1 and PYY actions increased food intake after RYGB, supporting that these hormones have a role in decreased food intake postoperatively.

Probing spin-vibronic dynamics using femtosecond X-ray spectroscopy.

Ultrafast pump-probe spectroscopy within the X-ray regime is now possible owing to the development of X-ray Free Electrons Lasers (X-FELs) and is opening new opportunities for the direct probing of femtosecond evolution of the nuclei, the electronic and spin degrees of freedom. In this contribution we use wavepacket dynamics of the photoexcited decay of a new Fe(ii) complex, [Fe(bmip)2]2+ (bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)pyridine), to simulate the experimental observables associated with femtosecond Fe K-edge X-ray Absorption Near-Edge Structure (XANES) and X-ray emission (XES) spectroscopy. We show how the evolution of the nuclear wavepacket is translated into the spectroscopic signal and the sensitivity of these approaches for following excited state dynamics.

[Ultrasound artifacts and their diagnostic significance in internal medicine and gastroenterology - part 2: color and spectral Doppler artifacts]. / Artefakte in der Sonografie und ihre Bedeutung für die internistische und gastroenterologische Diagnostik - Teil 2: Artefakte im Farb- und Spektraldoppler.

Artifacts in ultrasonographic diagnostics are a result of the physical properties of the ultrasound waves and are caused by interaction of the ultrasound waves with biological structures and tissues of the body and with foreign materials. On the one hand, they may be diagnostically helpful. On the other hand, they may be distracting and may lead to misdiagnosis. Profound knowledge of the causes, avoidance, and interpretation of artifacts is a necessary precondition for correct clinical appraisal of ultrasound images. Part 1 of this review commented on the physics of artifacts and described the most important B-mode artifacts. Part 2 focuses on the clinically relevant artifacts in Doppler and color-coded duplex sonography. Problems and pitfalls of interpretation arising from artifacts, as well as the diagnostic use of Doppler and colour-coded duplex sonography, are discussed.

[Ultrasound artifacts and their diagnostic significance in internal medicine and gastroenterology - Part 1: B-mode artifacts]. / Artefakte in der Sonografie und ihre Bedeutung für die internistische und gastroenterologische Diagnostik - Teil 1: B-Mode-Artefakte.

Artifacts in ultrasonographic diagnostics are a result of the physical properties of the ultrasound waves and are caused by interaction of the ultrasound waves with biological structures and tissues and with foreign bodies. On the one hand, they may be distracting and may lead to misdiagnosis. On the other hand, they may be diagnostically helpful. Ultrasound imaging suffers from artifacts, because in reality, parameters assumed to be constant values, such as sound speed, sound rectilinear propagation, attenuation, etc., are often different from the actual parameters. Moreover, inadequate device settings may cause artifacts. Profound knowledge of the causes, avoidance, and interpretation of artifacts is a necessary precondition for correct clinical appraisal of ultrasound images. Part 1 of this review comments on the physics of artifacts and describes the most important B-mode artifacts. Pitfalls, as well as diagnostic chances resulting from B-mode artifacts, are discussed.

[Surgery in Salivary Gland Diseases]. / Operative Therapie bei Erkrankungen der großen Kopfspeicheldrüsen.

Salivary gland surgery is a common procedure in otorhinolaryngology. Parotidectomy and submandibulectomy represent the treatment of choice in benign and malignant tumors of the salivary glands. However, as to this point there are no guidelines are concerning diagnostic and therapeutic approaches of benign and malignant tumors of the salivary gland. Since the introduction of sialendoscopy there are new diagnostic and therapeutic procedures available in treating obstructive sialadenitis. The present article provides an overview of anatomical principles, diagnostic approaches and the most important salivary gland surgeries for future otorhinolaryngologists under specialist training.

An outbreak of enterotoxigenic Escherichia coli (ETEC) infection in Norway, 2012: a reminder to consider uncommon pathogens in outbreaks involving imported products.

We investigated an outbreak of gastroenteritis following a Christmas buffet served on 4-9 December 2012 to ~1300 hotel guests. More than 300 people were reported ill in initial interviews with hotel guests. To identify possible sources of infection we conducted a cohort investigation through which we identified 214 probable cases. Illness was associated with consumption of scrambled eggs (odds ratio 9·07, 95% confidence interval 5·20-15·84). Imported chives added fresh to the scrambled eggs were the suspected source of the outbreak but were unavailable for testing. Enterotoxigenic Escherichia coli (ETEC) infection was eventually confirmed in 40 hotel guests. This outbreak reinforces that ETEC should be considered in non-endemic countries when the clinical picture is consistent and common gastrointestinal pathogens are not found. Following this outbreak, the Norwegian Food Safety Authority recommended that imported fresh herbs should be heat-treated before use in commercial kitchens.

Antimicrobial resistance in faecal samples from buffalo, wildebeest and zebra grazing together with and without cattle in Tanzania.

AIM: The aim of this study was to determine whether the practice of co-grazing with cattle and wild life constitutes a risk of transmission of antibiotic resistant bacteria to wild ungulates. METHODS AND RESULTS: Faecal samples were collected from buffalo (n = 35), wildebeest (n = 40), zebra (n = 40) and cattle (N = 20) from Mikumi National Park, Tanzania (MNP), where cattle is prohibited and from Ngorongoro Conservation Area (NCA) where co-grazing is practiced. The number of coliforms and enterococci resistant to selected antibiotics was determined. Wild life generally harboured higher number of resistant Escherichia coli and Enterococci than cattle, but with no general influence in wild life of co-grazing with cattle. Vancomycin-resistant Enterococci were detected in wild life samples, and E. coli resistant to cefotaxime and enrofloxacin were observed among isolates from all wild life, but not from cattle. Culture independent estimates of the number of sulII gene copies obtained by qPCR did not differ between wild life from the two sample sites, while tetW was significantly higher in samples from MPN than from NCA. CONCLUSIONS: Antibiotic resistant bacteria were not more frequently found in ungulates grazing together with cattle than ungulates without this interaction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study did not indicate that transmission of antibiotic resistant bacteria is a frequent event following co-grazing of wild life and cattle.

Determination of 'recruited volume' following a PEEP step is not a measure of lung recruitability.

BACKGROUND: It has been proposed that the analysis of positive end-expiratory pressure (PEEP)-induced volume changes can quantify alveolar recruitment. The potential of a lung to be recruited is expected to be high in acute respiratory distress syndrome (ARDS), where collapsed lung tissue is very common. The volume change that is beyond the delta volume because of the patient's compliance has been termed 'recruited volume' (RecV). However, data of patients with low and high RecV showed less severe lung disease in high 'recruiters', indicating that RecV may not equal the 'potentially recruitable lung tissue' seen in computed tomography scans. We hypothesized that RecV is higher in lung-healthy (LH) patients with little collapsed lung compared with ARDS patients. METHODS: RecV and inspiratory capacity (IC) were determined in 12 LH and in 25 ARDS patients during incremental PEEP (steps of 2 cmH2 O). RecV was determined as the time-dependent increase in end-expiratory volume following the first expiration to the new PEEP level (ΔTDV). Gas distribution in LH patients was analyzed by electric impedance tomography. RESULTS: Cumulative RecV(ΔTDV) and IC were higher (P < 0.01) in LH compared with ARDS patients, 1739 ml vs. 832 ml and 4432 ml vs. 2020 ml, respectively. In both groups, RecV correlated excellently with IC (R(2) = 0.86). In LH, RecV emanated mainly from nondependent lung regions at PEEP below 15 cmH2O. Maximum plateau pressure was reached with fewer PEEP steps in ARDS compared with LH patients (11 vs. 14, P < 0.01). CONCLUSION: Our findings suggest that RecV predominately measures a slow fraction of inflation of already aerated lung tissue and not recruitment of collapsed alveoli.

Hexamethylcyclopentadiene: time-resolved photoelectron spectroscopy and ab initio multiple spawning simulations.

Progress in our understanding of ultrafast light-induced processes in molecules is best achieved through a close combination of experimental and theoretical approaches. Direct comparison is obtained if theory is able to directly reproduce experimental observables. Here, we present a joint approach comparing time-resolved photoelectron spectroscopy (TRPES) with ab initio multiple spawning (AIMS) simulations on the MS-MR-CASPT2 level of theory. We disentangle the relationship between two phenomena that dominate the immediate molecular response upon light absorption: a spectrally dependent delay of the photoelectron signal and an induction time prior to excited state depopulation in dynamics simulations. As a benchmark molecule, we have chosen hexamethylcyclopentadiene, which shows an unprecedentedly large spectral delay of (310 ± 20) fs in TRPES experiments. For the dynamics simulations, methyl groups were replaced by "hydrogen atoms" having mass 15 and TRPES spectra were calculated. These showed an induction time of (108 ± 10) fs which could directly be assigned to progress along a torsional mode leading to the intersection seam with the molecular ground state. In a stepladder-type approach, the close connection between the two phenomena could be elucidated, allowing for a comparison with other polyenes and supporting the general validity of this finding for their excited state dynamics. Thus, the combination of TRPES and AIMS proves to be a powerful tool for a thorough understanding of ultrafast excited state dynamics in polyenes.

Do contaminants compromise the use of recycled nutrients in organic agriculture? A review and synthesis of current knowledge on contaminant concentrations, fate in the environment and risk assessment.

Use of nutrients recycled from societal waste streams in agriculture is part of the circular economy, and in line with organic farming principles. Nevertheless, diverse contaminants in waste streams create doubts among organic farmers about potential risks for soil health. Here, we gather the current knowledge on contaminant levels in waste streams and recycled nutrient sources, and discuss associated risks. For potentially toxic elements (PTEs), the input of zinc (Zn) and copper (Cu) from mineral feed supplements remains of concern, while concentrations of PTEs in many waste streams have decreased substantially in Europe. The same applies to organic contaminants, although new chemical groups such as flame retardants are of emerging concern and globally contamination levels differ strongly. Compared to inorganic fertilizers, application of organic fertilizers derived from human or animal feces is associated with an increased risk for environmental dissemination of antibiotic resistance. The risk depends on the quality of the organic fertilizers, which varies between geographical regions, but farmland application of sewage sludge appears to be a safe practice as shown by some studies (e.g. from Sweden). Microplastic concentrations in agricultural soils show a wide spread and our understanding of its toxicity is limited, hampering a sound risk assessment. Methods for assessing public health risks for organic contaminants must include emerging contaminants and potential interactions of multiple compounds. Evidence from long-term field experiments suggests that soils may be more resilient and capable to degrade or stabilize pollutants than often assumed. In view of the need to source nutrients for expanding areas under organic farming, we discuss inputs originating from conventional farms vs. non-agricultural (i.e. societal) inputs. Closing nutrient cycles between agriculture and society is feasible in many cases, without being compromised by contaminants, and should be enhanced, aided by improved source control, waste treatment and sound risk assessments.

Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass.

OBJECTIVE: To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB). DESIGN: Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender. MATERIALS AND METHODS: Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3-36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite. RESULTS: Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition. CONCLUSION: Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Plasma follistatin is elevated in patients with type 2 diabetes: relationship to hyperglycemia, hyperinsulinemia, and systemic low-grade inflammation.

BACKGROUND: Plasma follistatin is elevated in patients with low-grade inflammation and insulin resistance as observed with polycystic ovary syndrome. In the present study, we evaluated plasma follistatin in patients with type 2 diabetes characterised by low-grade inflammation and assessed the acute effects of hyperglycemia, hyperinsulinemia and LPS on plasma follistatin. METHODS: Baseline plasma follistatin and inflammatory biomarkers were measured in a cross-sectional study that involved 95 patients with type 2 diabetes and 103 matched controls. To determine the acute effect of hyperglycemia and hyperinsulinemia on follistatin, hyperglycemic and hyperinsulinemic-euglycemic clamps were performed in five healthy males. Furthermore, 15 patients with type 2 diabetes and 22 healthy controls were challenged with low-dose LPS to determine the effect on follistatin. RESULTS: Patients with type 2 diabetes have higher HOMA2-IR values mean [95% CI] 1.64 [1.40-1.93] versus mean 0.86 [0.75-0.99], p < 0.001 and inflammatory markers compared with controls. Baseline plasma follistatin is elevated in patients with type 2 diabetes compared with controls mean 1564 [1456-1680] versus mean 1328 [1225-1440] ng/L, p = 0.003 and correlates with fasting glucose levels (r = 0.44, p < 0.0001), 2 h glucose (r = 0.48, p < 0.0001), HbA1c (r = 0.41, p < 0.0001), triacylglycerol (r = 0.28, p = 0.008) and total cholesterol (r = 0.33, p = 0.004) in patients but not in controls. No correlation exists between plasma follistatin and inflammatory biomarkers in either of the groups. Neither hyperglycemia, hyperinsulinemia nor LPS increase plasma follistatin. CONCLUSIONS: Plasma follistatin is moderately elevated in patients with type 2 diabetes. Our findings suggest that this is not likely caused by hyperglycemia, hyperinsulinemia or systemic low-grade inflammation.