AR Blockers

Access Recirculation (AR) severely decreases the efficiency of dialysis while having the potential to lead to a variety of complications (Fig. 3). If recirculation occurs during treatment, the patient may be at risk of developing stenosis (narrowing of blood vessels), leading to thrombosis (the local coagulation/clotting of blood) [4]. The most influential cause of recirculation results from the misplacement of the arterial and venous needles that will significantly harm the patient, wasting both money and resources. It is clear that the medical community has focused their energy on developing a proactive approach to monitoring AR, instead of preventing it. Creating biomedical devices that closely monitor the occurrence of AR isn’t sufficient enough. In order to prevent further complications and ensure dialysis is as efficient as possible, the goal should be to eliminate AR. There is a clear need for a device that can be implemented during hemodialysis treatments to reduce the percentage of recirculated blood, thus, reducing the occurrence of treatment for an individual and aiding the nurses in proper needle placement

Prevention of Access Recirculation During Hemodialysis Treatment

Approximately 660,000 Americans are being treated for kidney failure or end stage renal disease annually. Access recirculation can happen to any patient, varying from treatment to treatment, as it is a problem with the current technology of two butterfly needles used during a dialysis procedure and not with the patient. Access Recirculation severely decreases the efficiency of dialysis while having the potential to lead to a variety of complications.There is a clear need for a device that can be implemented during hemodialysis treatments to reduce the percentage of recirculated blood, thusly reducing the occurrence of treatment for an individual and aiding the nurses in proper needle placement. Our proposed design is the Cannulation Pilot and it is responsible for reducing recirculation during dialysis by holding the two butterfly needles necessary for treatment at a fixed distance of 5 cm apart from one another and at an angle of insertion between 20 to 35 degrees; as this should drastically reduce or halt recirculation form occurring during treatment

The effect of infrared heating on the functional and nutritional qualities of green lentil and yellow pea flours

The effect of seed tempering moisture (20 vs. 30%) and infrared heating temperature (120 vs 140oC) on the nutritional and functional properties of the resulting flours from green lentil and yellow pea were evaluated. For both pulses, proximate composition remained unchanged relative to the unprocessed pulses, although seeds became a little darker in colour. The damaged/gelatinized starch content of the control flours steadily increased as both tempering moisture and infrared heat applied to the seeds prior to milling increased. For all processing conditions, surface hydrophobicity (SH) increased relative to the control, whereas surface charge (zeta potential (mV)) remained unchanged. The secondary protein structure of both pulse types transitioned from a more ordered state composed of β-sheet and α-helix structures, to state with a higher relative percentage of random coil structures as processing conditions increased. Functional properties of the flours were mildly affected as a result of tempering and infrared heating, and in most cases were correlated with the SH and damaged/gelatinized starch content of the flours. Protein solubility at pH 5 was unchanged in response to processing, however at pH 7 a slight processing effect was seen, which led to lower solubility. The water and oil holding capacities (WHC, OHC) of the processed flours were improved in comparison to the control group flours, although OHC tended to decline as infrared heat temperatures increased from 120 to 140oC. Poor foaming capacities (FC) and relatively stable foaming stabilities (FS) were observed for both pulse types. Intensifying processing of the pulse seeds improved emulsion activity (EA) and emulsion stability (ES) up until a critical point, where it then significantly declined. The oil emulsion capacity (OEC) declined with processing relative to the control for both pulse types. The peak and final viscosities of the flours decreased, and pasting temperature increased, as processing temperature and moisture increased, relative to the control group flours. In-vitro protein digestibility (IVPD) of processed flours increased relative to the control group flour, with the exception of yellow pea flours, where a slight decrease in IVPD was found for flours tempered to 30% moisture and heated to 140oC. Amino acid contents remained unchanged between control and processed flours in both pulse types, and the limiting amino acid (LAA) was found to be tryptophan in both yellow pea and green lentil flours. The in-vitro protein digestibility corrected amino acid scores (IV-PDCAAS) of the flours were not significantly altered by processing. Rapidly (RDS) and slowly (SDS) digestible starches increased with processing, whereas the amount of resistance starch (RS) declined. RDS and SDS values increased with increased temperature, and with increased moisture when processed. In contrast, RS decreased with increasing temperature and increased moisture. The overall conclusions in this study are that the combined effect of tempering moisture and infrared heat as a pre-milling treatment either did not significantly affect, or slightly reduced, the studied functional properties of the treated flours in comparison to the control group (with the exception of WHC). It was also found that flours that were tempered and infrared heated prior to milling had improved levels of protein and starch digestibility, but not protein quality

Analysis of gene expression in operons of Streptomyces coelicolor

BACKGROUND: Recent studies have shown that microarray-derived gene-expression data are useful for operon prediction. However, it is apparent that genes within an operon do not conform to the simple notion that they have equal levels of expression. RESULTS: To investigate the relative transcript levels of intra-operonic genes, we have used a Z-score approach to normalize the expression levels of all genes within an operon to expression of the first gene of that operon. Here we demonstrate that there is a general downward trend in expression from the first to the last gene in Streptomyces coelicolor operons, in contrast to what we observe in Escherichia coli. Combining transcription-factor binding-site prediction with the identification of operonic genes that exhibited higher transcript levels than the first gene of the same operon enabled the discovery of putative internal promoters. The presence of transcription terminators and abundance of putative transcriptional control sequences in S. coelicolor operons are also described. CONCLUSION: Here we have demonstrated a polarity of expression in operons of S. coelicolor not seen in E. coli, bringing caution to those that apply operon prediction strategies based on E. coli 'equal-expression' to divergent species. We speculate that this general difference in transcription behavior could reflect the contrasting lifestyles of the two organisms and, in the case of Streptomyces, might also be influenced by its high G+C content genome. Identification of putative internal promoters, previously thought to cause problems in operon prediction strategies, has also been enabled

New pleiotropic effects of eliminating a rare tRNA from Streptomyces coelicolor, revealed by combined proteomic and transcriptomic analysis of liquid cultures

Background: In Streptomyces coelicolor, bldA encodes the only tRNA for a rare leucine codon, UUA. This tRNA is unnecessary for growth, but is required for some aspects of secondary metabolism and morphological development. We describe a transcriptomic and proteomic analysis of the effects of deleting bldA on cellular processes during submerged culture: conditions relevant to the industrial production of antibiotics. Results: At the end of rapid growth, a co-ordinated transient up-regulation of about 100 genes, including many for ribosomal proteins, was seen in the parent strain but not the ΔbldA mutant. Increased basal levels of the signal molecule ppGpp in the mutant strain may be responsible for this difference. Transcripts or proteins from a further 147 genes classified as bldA-influenced were mostly expressed late in culture in the wild-type, though others were significantly transcribed during exponential growth. Some were involved in the biosynthesis of seven secondary metabolites; and some have probable roles in reorganising metabolism after rapid growth. Many of the 147 genes were "function unknown", and may represent unknown aspects of Streptomyces biology. Only two of the 147 genes contain a TTA codon, but some effects of bldA could be traced to TTA codons in regulatory genes or polycistronic operons. Several proteins were affected posttranslationally by the bldA deletion. There was a statistically significant but weak positive global correlation between transcript and corresponding protein levels. Different technical limitations of the two approaches were a major cause of discrepancies in the results obtained with them. Conclusion: Although deletion of bldA has very conspicuous effects on the gross phenotype, the bldA molecular phenotype revealed by the "dualomic" approach has shown that only about 2% of the genome is affected; but this includes many previously unknown effects at a variety of different levels, including post translational changes in proteins and global cellular physiology

Curing vector for IncI1 plasmids and its use to provide evidence for a metabolic burden of IncI1 CTX-M-1 plasmid pIFM3791 on Klebsiella pneumoniae

Using a sequence based approach we previously identified an IncI1 CTX-M-1 plasmid,pIFM3791, on a single pig farm in the UK that was harboured by K. pneumoniae,Escherichia coli and Salmonella enterica serotype 4,5,12,i:-. To test the hypothesis that the plasmid had spread rapidly into these differing host bacteria we wished to assess whether the plasmid conferred a fitness advantage. To do this an IncI1 curing vector was constructed and used to displace the IncI1 CTX-M-1 plasmids from K. pneumoniae strain B3791 and several other unrelated IncI1 harbouring strains indicating the potential wider application of the curing plasmid. The IncI1 CTX-M-1 plasmid was re-introduced by conjugation into the cured K. pneumoniae strain and also a naturally IncI1 plasmid free S. enterica serotype 4,5,12,i:-, S348/1. Original, cured and complemented strains were tested for metabolic competence using BiologTM technology and in competitive growth, association to mammalian cells and biofilm formation experiments. The plasmid-cured K. pneumoniae strain grew more rapidly than either the original plasmid-carrying strain or plasmid-complemented strains in competition experiments. Additionally, the plasmid-cured strain was significantly better at respiring with L-sorbose as a carbon source and putrescine, γ-amino-n-butyric acid,L-alanine, L-proline as a nitrogen sources. By contrast, no differences in phenotype were found when comparing plasmid harbouring and plasmid free S. enterica S348/11. In conclusion, the IncI1 curing vector successfully displaced multiple IncI plasmids. The IncI1 CTX-M1 plasmid conferred a growth disadvantage upon K. pneumoniae, possibly by imposing a metabolic burden the mechanism of which remains to be determined

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation

Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon

Development of high-density microarrays for global analysis of gene expression and transcription factor binding in Streptomyces coelicolor suggests a novel role for HspR in stress adaptation