Amino acids, glucose metabolism and clinical relevance for phenylketonuria management

It is general knowledge that glycaemia is affected by digested nutrients.Amino acids intake appears to be an important regulator in this regard. Many questions need to be answered, such as the real mediators of this responseand the mechanisms underlying this metabolic behavior. Studies have been undertaken in order to investigate the role of amino acids on metabolic parameters. Their main fndings suggest that the ingestion of free aminoacids have a pivotal role in avoiding glycaemia excursions, improving glucosetolerance. In parallel, several important molecules for glucose metabolism have been exploited. Insulin and glucagon-like peptide - 1 (GLP-1) release seemto be the main triggers of this response. This insulinogenic effect is attributed to some amino acids, particularly the branched-chain amino acids (leucine, isoleucine and valine). GLP-1 may exert its effects by activating its receptor inpancreas and enhancing insulin release by β-cells or through its extrapancreaticactions. The mechanisms that may justify the aforementioned effects remainto be answered, being the mTOR pathway activation a possible key. Thesemetabolic effects may have a special interest within the nutritional management of Phenylketonuria (PKU), an inborn metabolic disease of phenylalanine (Phe) catabolism. Since a Phe restricted diet is the mainstay of PKU treatment, a chronic supplementation with a Phe-free amino acid mixture is used. Although scientifc evidence is scarce, it is hypothesized whether this chronic ingestion may modulate glycaemia

Disease prevention versus data privacy : using landcover maps to inform spatial epidemic models

The availability of epidemiological data in the early stages of an outbreak of an infectious disease is vital for modelers to make accurate predictions regarding the likely spread of disease and preferred intervention strategies. However, in some countries, the necessary demographic data are only available at an aggregate scale. We investigated the ability of models of livestock infectious diseases to predict epidemic spread and obtain optimal control policies in the event of imperfect, aggregated data. Taking a geographic information approach, we used land cover data to predict UK farm locations and investigated the influence of using these synthetic location data sets upon epidemiological predictions in the event of an outbreak of foot-and-mouth disease. When broadly classified land cover data were used to create synthetic farm locations, model predictions deviated significantly from those simulated on true data. However, when more resolved subclass land use data were used, moderate to highly accurate predictions of epidemic size, duration and optimal vaccination and ring culling strategies were obtained. This suggests that a geographic information approach may be useful where individual farm-level data are not available, to allow predictive analyses to be carried out regarding the likely spread of disease. This method can also be used for contingency planning in collaboration with policy makers to determine preferred control strategies in the event of a future outbreak of infectious disease in livestock

Prediction of the effect of dapagliflozin on kidney and heart failure outcomes based on short-term changes in multiple risk markers

BACKGROUND: Besides improving glucose control, sodium-glucose co-transporter 2 inhibition with dapagliflozin reduces blood pressure, body weight and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes (T2DM). The parameter response efficacy (PRE) score was developed to predict how short-term drug effects on cardiovascular risk markers translate into long-term changes in clinical outcomes. We applied the PRE score to clinical trials of dapagliflozin to model the effect of the drug on kidney and heart failure (HF) outcomes in patients with T2DM and impaired kidney function. METHODS: The relationships between multiple risk markers and long-term outcome were determined in a background population of patients with T2DM with a multivariable Cox model. These relationships were then applied to short-term changes in risk markers observed in a pooled database of dapagliflozin trials (n = 7) that recruited patients with albuminuria to predict the drug-induced changes to kidney and HF outcomes. RESULTS: A total of 132 and 350 patients had UACR >200 mg/g and >30 mg/g at baseline, respectively, and were selected for analysis. The PRE score predicted a risk change for kidney events of -40.8% [95% confidence interval (CI) -51.7 to -29.4) and -40.4% (95% CI -48.4 to -31.1) with dapagliflozin 10 mg compared with placebo for the UACR >200 mg/g and >30 mg/g subgroups. The predicted change in risk for HF events was -27.3% (95% CI -47.7 to -5.1) and -21.2% (95% CI -35.0 to -7.8), respectively. Simulation analyses showed that even with a smaller albuminuria-lowering effect of dapagliflozin (10% instead of the observed 35% in both groups), the estimated kidney risk reduction was still 26.5 and 26.8%, respectively. CONCLUSIONS: The PRE score predicted clinically meaningful reductions in kidney and HF events associated with dapagliflozin therapy in patients with diabetic kidney disease. These results support a large long-term outcome trial in this population to confirm the benefits of the drug on these endpoints

Mortality after emergency department intubation

Introduction The purpose of this study is to identify the rate of emergency department (ED) intubation and the mortality associated with ED intubation. Methods We conducted a retrospective chart review of all patients intubated in the ED between 1 January 2004 an

Decolorization of synthetic melanoidins-containing wastewater by a bacterial consortium

The presence of melanoidins in molasses wastewater leads to water pollution both due to its dark brown color and its COD contents. In this study, a bacterial consortium isolated from waterfall sediment was tested for its decolorization. The identification of culturable bacteria by 16S rDNA based approach showed that the consortium composed of Klebsiella oxytoca, Serratia mercescens, Citrobacter sp. and unknown bacterium. In the context of academic study, prevention on the difficulties of providing effluent as well as its variations in compositions, several synthetic media prepared with respect to color and COD contents based on analysis of molasses wastewater, i.e., Viandox sauce (13.5% v/v), caramel (30% w/v), beet molasses wastewater (41.5% v/v) and sugarcane molasses wastewater (20% v/v) were used for decolorization using consortium with color removal 9.5, 1.13, 8.02 and 17.5%, respectively, within 2 days. However, Viandox sauce was retained for further study. The effect of initial pH and Viandox concentration on decolorization and growth of bacterial consortium were further determined. The highest decolorization of 18.3% was achieved at pH 4 after 2 day of incubation. Experiments on fresh or used medium and used or fresh bacterial cells, led to conclusion that the limitation of decolorization was due to nutritional deficiency. The effect of aeration on decolorization was also carried out in 2 L laboratory-scale suspended cell bioreactor. The maximum decolorization was 19.3% with aeration at KLa = 2.5836 h-1 (0.1 vvm)

Five genomic regions have a major impact on fat composition in Iberian pigs

Abstract The adipogenic nature of the Iberian pig defines many quality attributes of its fresh meat and dry-cured products. The distinct varieties of Iberian pig exhibit great variability in the genetic parameters for fat deposition and composition in muscle. The aim of this work is to identify common and distinct genomic regions related to fatty acid composition in Retinto, Torbiscal, and Entrepelado Iberian varieties and their reciprocal crosses through a diallelic experiment. In this study, we performed GWAS using a high density SNP array on 382 pigs with the multimarker regression Bayes B method implemented in GenSel. A number of genomic regions showed strong associations with the percentage of saturated and unsaturated fatty acid in intramuscular fat. In particular, five regions with Bayes Factor >100 (SSC2 and SSC7) or >50 (SSC2 and SSC12) explained an important fraction of the genetic variance for miristic, palmitoleic, monounsaturated (>14%), oleic (>10%) and polyunsaturated (>5%) fatty acids. Six genes (RXRB, PSMB8, CHGA, ACACA, PLIN4, PLIN5) located in these regions have been investigated in relation to intramuscular composition variability in Iberian pigs, with two SNPs at the RXRB gene giving the most consistent results on oleic and monounsaturated fatty acid content