Nutritional management of chronic renal failure by dietitians - the South African experience

Objective: The objective of this descriptive study was to assess the practices of South African dietitians regarding the dietary treatment of patients with chronic renal failure.Subjects and design: A questionnaire was mailed to 600 randomly selected dietitians registered with the Health Professions Council of South Africa. Practices were compared to international standards for pre-dialysis, haemodialysis (HD) and peritoneal dialysis (PD) patients.Results: A 26% response rate was obtained, with only 28% of these dietitians indicating that they counsel renal patients. The majority of dietitians met the international dietary recommendations, but a substantial number deviated from them. This was especially evident in PD patients, where the deviation ranged from 20% (4 dietitians) in the case of energy and phosphate, to 55% (11 dietitians) in the case of calcium. Parameters used for the assessment of nutritional status included body mass index (45% of dietitians), serum albumin (44%), clinical examinations (43%), bioelectrical impedance (37%) and diet history (36%). Methods used to monitor dietary compliance included biochemistry, dietary history, anthropometric measurements and clinical investigation. The most frequently used approaches in the management of protein-energy malnutrition included supplemental drinks (86%) and dietary enrichment at household level (76%).Conclusion: Although the majority of dietitians met international standards for most nutrients, there was some variation and uncertainty. Ongoing education will enable South African dietitians to treat renal patients competently and with confidence.South African Journal of Clinical Nutrition Vol. 18(2) 2005: 60-6

MALT1 is an intrinsic regulator of regulatory T cells

Regulatory T cells (Tregs) are crucial for the maintenance of immunological self-tolerance and their absence or dysfunction can lead to autoimmunity. However, the molecular pathways that govern Treg biology remain obscure. In this study, we show that the nuclear factor-κB signalling mediator mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an important novel regulator of both Tregs originating in the thymus (‘natural’ or nTregs) and Tregs induced to differentiate from naive thymocyte helper (Th) cells in the periphery (‘induced’ or iTregs). Our examination of mice deficient for MALT1 revealed that these mutants have a reduced number of total Tregs. In young Malt1−/− mice, nTregs are totally absent and iTreg are diminished in the periphery. Interestingly, total Treg numbers increase in older Malt1−/− mice as well as in Malt1−/− mice subjected to experimentally induced inflammation. iTregs isolated from WT and Malt1−/− mice were indistinguishable with respect to their ability to suppress the activities of effector T cells, but Malt1−/− iTregs expressed higher levels of Toll-like receptor (TLR) 2. Treatment of WT and Malt1−/− Th cells in vitro with the TLR2 ligand Pam3Cys strongly enhanced the induction and proliferation of Malt1−/− iTregs. Our data suggest that MALT1 supports nTreg development in the thymus but suppresses iTreg induction in the periphery during inflammation. Our data position MALT1 as a key molecule that contributes to immune tolerance at steady-state while facilitating immune reactivity under stress conditions.This work was supported by grants by the Canadian Institutes of Health Research (to TWM). DB is supported by the ATTRACT Programme of the National Research Fund Luxembourg (FNR).This study was further supported by the Alexander von Humboldt Foundation (SKA2010) and the German Research Council (LA2558/3-1)

Characterisation of gut microbiota of obesity and type 2 diabetes in a rodent model

Various studies have suggested that the gut microbiome interacts with the host and may have a significant role in the aetiology of obesity and Type 2 Diabetes (T2D). It was hypothesised that bacterial communities in obesity and T2D differ from control and compromise normal interactions between host and microbiota. Obesity and T2D were developed in rats by feeding a high-fat diet or a high-fat diet plus a single low-dose streptozotocin administration, respectively. The microbiome profiles and their metabolic potentials were established by metagenomic 16S rRNA sequencing and bioinformatics. Taxonomy and predicted metabolism-related genes in obesity and T2D were markedly different from controls and indeed from each other. Diversity was reduced in T2D but not in Obese rats. Factors likely to compromise host intestinal, barrier integrity were found in Obese and T2D rats including predicted, decreased bacterial butyrate production. Capacity to increase energy extraction via ABC-transporters and carbohydrate metabolism were enhanced in Obese and T2D rats. T2D was characterized by increased proinflammatory molecules. While obesity and T2D show distinct differences, results suggest that in both conditions Bacteroides and Blautia species were increased indicating a possible mechanistic link

Variant supercurrent multiplets

In N = 1 rigid supersymmetric theories, there exist three standard realizations of the supercurrent multiplet corresponding to the (i) old minimal, (ii) new minimal and (iii) non-minimal off-shell formulations for N = 1 supergravity. Recently, Komargodski and Seiberg in arXiv:1002.2228 put forward a new supercurrent and proved its consistency, although in the past it was believed not to exist. In this paper, three new variant supercurrent multiplets are proposed. Implications for supergravity-matter systems are discussed.Comment: 11 pages; V2: minor changes in sect. 3; V3: published version; V4: typos in eq. (2.3) corrected; V5: comments and references adde

Influence of hyperhomocysteinemia on the cellular redox state - Impact on homocysteine-induced endothelial dysfunction

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteines deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteineinduced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide

Accelerated apoptotic death and <i>in vivo</i> turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2

The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk−/−) and corresponding wild-type mice (msk+/+). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk−/− and msk+/+ mice, but reticulocyte count was significantly increased in msk−/− mice. Cell membrane PS exposure was similar in untreated msk−/− and msk+/+ erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk−/− erythrocytes than in msk+/+ erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk−/− erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk−/− mice. The spleens from msk−/− mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk+/+ mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice

Comments on Supercurrent Multiplets, Supersymmetric Field Theories and Supergravity

We analyze various supersymmetry multiplets containing the supercurrent and the energy-momentum tensor. The most widely known such multiplet, the Ferrara-Zumino (FZ) multiplet, is not always well-defined. This can happen once Fayet-Iliopoulos (FI) terms are present or when the Kahler form of the target space is not exact. We present a new multiplet S which always exists. This understanding of the supersymmetry current allows us to obtain new results about the possible IR behavior of supersymmetric theories. Next, we discuss the coupling of rigid supersymmetric theories to supergravity. When the theory has an FZ-multiplet or it has a global R-symmetry the standard formalism can be used. But when this is not the case such simple gauging is impossible. Then, we must gauge the current S. The resulting theory has, in addition to the graviton and the gravitino, another massless chiral superfield Phi which is essential for the consistency of the theory. Some of the moduli of various string models play the role of Phi. Our general considerations, which are based on the consistency of supergravity, show that such moduli cannot be easily lifted thus leading to constraints on gravity/string models.Comment: 27 pages. v2: references added and minor changes. v3: minor changes. v4: minor clarification

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Taurine: a potential marker of apoptosis in gliomas

New cancer therapies are being developed that trigger tumour apoptosis and an in vivo method of apoptotic detection and early treatment response would be of great value. Magnetic resonance spectroscopy (MRS) can determine the tumour biochemical profile in vivo, and we have investigated whether a specific spectroscopic signature exists for apoptosis in human astrocytomas. High-resolution magic angle spinning (HRMAS) 1H MRS provided detailed 1H spectra of brain tumour biopsies for direct correlation with histopathology. Metabolites, mobile lipids and macromolecules were quantified from presaturation HRMAS 1H spectra acquired from 41 biopsies of grades II (n=8), III (n=3) and IV (n=30) astrocytomas. Subsequently, TUNEL and H&E staining provided quantification of apoptosis, cell density and necrosis. Taurine was found to significantly correlate with apoptotic cell density (TUNEL) in both non-necrotic (R=0.727, P=0.003) and necrotic (R=0.626, P=0.0005) biopsies. However, the ca 2.8 p.p.m. polyunsaturated fatty acid peak, observed in other studies as a marker of apoptosis, correlated only in non-necrotic biopsies (R=0.705, P<0.005). We suggest that the taurine 1H MRS signal in astrocytomas may be a robust apoptotic biomarker that is independent of tumour necrotic status