Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study.

BACKGROUND AND OBJECTIVE: Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD: Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS: Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION: RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.

Experimental and thermodynamic studies of phosphate behavior during the hydrothermal carbonization of sewage sludge.

Recovered phosphate from sewage sludge is becoming a key product in the fertilizer market. This study investigates the fate of phosphate during the hydrothermal carbonization of digested sewage sludge to support the development of an economic and sustainable solution for dealing with sewage sludge for phosphate recovery. The solid products from the hydrothermal carbonization of digested sewage sludge in a batch reactor (180, 220, and 260 °C; 1, 2, and 4 h; digested sewage sludge-to-water ratios of 0.2 and 0.1 w/w) were analyzed using a sequential chemical extraction procedure to understand and predict the formation of phosphate species and the related extraction behavior of phosphate. The obtained results were compared with the thermochemical equilibrium composition of hydrothermal carbonization products, calculated using the software FactSage 7.2. The majority of phosphate was retained as Al, Ca, and Fe salts in hydrochar. The decomposition of organic phosphates was observed by processing at lower temperatures. Hydrothermal carbonization at temperatures higher than 180 °C resulted in the transformation of the Al-bound phosphate into Ca-bound phosphate. Hydroxyapatite (Ca5(PO4)3(OH)) and Fe7(PO4)6 were calculated as stable phosphate-containing minerals at equilibrium. This study suggests that kinetic constraints inhibit the formation of these minerals in the batch reactor and presents a mechanism of phosphate transformation using the obtained data. The results allow for targeted optimization of phosphate recovery strategy.

Stretching-Induced Conductance Increase in a Spin-Crossover Molecule.

We investigate transport through mechanically triggered single-molecule switches that are based on the coordination sphere-dependent spin state of Fe(II)-species. In these molecules, in certain junction configurations the relative arrangement of two terpyridine ligands within homoleptic Fe(II)-complexes can be mechanically controlled. Mechanical pulling may thus distort the Fe(II) coordination sphere and eventually modify their spin state. Using the movable nanoelectrodes in a mechanically controlled break-junction at low temperature, current-voltage measurements at cryogenic temperatures support the hypothesized switching mechanism based on the spin-crossover behavior. A large fraction of molecular junctions formed with the spin-crossover-active Fe(II)-complex displays a conductance increase for increasing electrode separation and this increase can reach 1-2 orders of magnitude. Theoretical calculations predict a stretching-induced spin transition in the Fe(II)-complex and a larger transmission for the high-spin configuration.

Single-Molecule Spin Switch Based on Voltage-Triggered Distortion of the Coordination Sphere.

Here, we report on a new single-molecule-switching concept based on the coordination-sphere-dependent spin state of Fe(II) species. The perpendicular arrangement of two terpyridine (tpy) ligands within heteroleptic complexes is distorted by the applied electric field. Whereas one ligand fixes the complex in the junction, the second one exhibits an intrinsic dipole moment which senses the E field and causes the distortion of the Fe(II) coordination sphere triggering the alteration of its spin state. A series of complexes with different dipole moments have been synthesized and their transport features were investigated via mechanically controlled break-junctions. Statistical analyses support the hypothesized switching mechanism with increasing numbers of junctions displaying voltage-dependent bistabilities upon increasing the Fe(II) complexes' intrinsic dipole moments. A constant threshold value of the E field required for switching corroborates the mechanism.

Preferences of patients undergoing hemodialysis - results from a questionnaire-based study with 4,518 patients.

BACKGROUND: Chronic kidney disease is an increasing health problem worldwide and in its final stage (stage V) can only be treated by renal replacement therapy, mostly hemodialysis. Hemodialysis has a major influence on the everyday life of patients and many patients report dissatisfaction with treatment. Little is known about which aspects of treatment are considered important by hemodialysis patients. The objective of this study was to rate the relative importance of different outcomes for hemodialysis patients and to analyze whether the relative importance differed among subgroups of patients. PATIENTS AND METHODS: Within the framework of a yearly questionnaire which is distributed among patients receiving hemodialysis by the largest hemodialysis provider in Germany, we assessed the relative importance of 23 outcomes as rated on a discrete visual analog scale. Descriptive statistics were used to rank the outcomes. Subgroup analyses were performed using Mann-Whitney U or Kruskal-Wallis tests. RESULTS: Questionnaires of 4,518 hemodialysis patients were included in the analysis. The three most important outcomes were safety of treatment, health-related quality of life, and satisfaction with care. Further important outcomes were hospital stays, accompanying symptoms, hemodialysis duration, and the improvement or preservation of a good emotional state. Age, profession, and education had the strongest influence on relevant differences of preferences for outcomes; no relevant influence of sex or comorbidity was observed. CONCLUSION: Outcomes concerning the delivery or provision of care and aspects influencing quality of life are rated by patients to be at least as important as clinical outcomes. Many of the outcomes judged to be important by the patients are not regularly considered in research, evaluation studies, or quality programs.

Interdialytic weight gain, systolic blood pressure, serum albumin, and C-reactive protein levels change in chronic dialysis patients prior to death.

Reports from a United States cohort of chronic hemodialysis patients suggested that weight loss, a decline in pre-dialysis systolic blood pressure, and decreased serum albumin may precede death. However, no comparative studies have been reported in such patients from other countries. Here we analyzed dynamic changes in these parameters in hemodialysis patients and included 3593 individuals from 5 Asian countries; 35,146 from 18 European countries; 8649 from Argentina; and 4742 from the United States. In surviving prevalent patients, these variables appeared to have notably different dynamics than in patients who died. While in all populations the interdialytic weight gain, systolic blood pressure, and serum albumin levels were stable in surviving patients, these indicators declined starting more than a year ahead in those who died with the dynamics similar irrespective of gender and geographic region. In European patients, C-reactive protein levels were available on a routine basis and indicated that levels of this acute-phase protein were low and stable in surviving patients but rose sharply before death. Thus, relevant fundamental biological processes start many months before death in the majority of chronic hemodialysis patients. Longitudinal monitoring of these dynamics may help to identify patients at risk and aid the development of an alert system to initiate timely interventions to improve outcomes.

Monitoring dialysis outcomes across the world--the MONDO Global Database Consortium.

BACKGROUND/AIMS: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. METHODS: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. RESULTS: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. CONCLUSION: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.

Josiphos-catalyzed asymmetric homodimerization of ketoketenes.

In this paper the development of a chiral phosphine-catalyzed homodimerization of ketoketenes that provides access to a variety of highly substituted ketoketene dimer ß-lactones (11 examples) is reported. The Josiphos catalytic system displays good to excellent enantioselectivity (up to 96% ee). Ring-opening reactions of the enantioenriched ketoketene dimers were also carried out to access 1,3-diketones, enol esters, and ß-hydroxyketones with good diastereoselectivity.

Organocatalytic dimerization of ketoketenes.

A general method for the catalytic dimerization of ketoketenes is described. Tri-n-butylphosphine was found to be the optimal organocatalyst for the racemic reaction. When lithium iodide was used as an additive, the reaction was rendered selective for dimer formation (dimer/trimer > or = 16:1). Ring-opening reactions of the ketoketene dimers as well as preliminary studies toward the development of an asymmetric variant are also reported.

Significant role for Fas in the pathogenesis of autoimmune diabetes.

Programmed cell death represents an important pathogenic mechanism in various autoimmune diseases. Type I diabetes mellitus (IDDM) is a T cell-dependent autoimmune disease resulting in selective destruction of the beta cells of the islets of Langerhans. beta cell apoptosis has been associated with IDDM onset in both animal models and newly diagnosed diabetic patients. Several apoptotic pathways have been implicated in beta cell destruction, including Fas, perforin, and TNF-alpha. Evidence for Fas-mediated lysis of beta cells in the pathogenesis of IDDM in nonobese diabetic (NOD) mice includes: 1) Fas-deficient NOD mice bearing the lpr mutation (NOD-lpr/lpr) fail to develop IDDM; 2) transgenic expression of Fas ligand (FasL) on beta cells in NOD mice may result in accelerated IDDM; and 3) irradiated NOD-lpr/lpr mice are resistant to adoptive transfer of diabetes by cells from NOD mice. However, the interpretation of these results is complicated by the abnormal immune phenotype of NOD-lpr/lpr mice. Here we present novel evidence for the role of Fas/FasL interactions in the progression of NOD diabetes using two newly derived mouse strains. We show that NOD mice heterozygous for the FasL mutation gld, which have reduced functional FasL expression on T cells but no lymphadenopathy, fail to develop IDDM. Further, we show that NOD-lpr/lpr mice bearing the scid mutation (NOD-lpr/lpr-scid/scid), which eliminates the enhanced FasL-mediated lytic activity induced by Fas deficiency, still have delayed onset and reduced incidence of IDDM after adoptive transfer of diabetogenic NOD spleen cells. These results provide evidence that Fas/FasL-mediated programmed cell death plays a significant role in the pathogenesis of autoimmune diabetes.