Characterizing Dysgeusia in Hemodialysis Patients

Dysgeusia (abnormal taste) is common in those with chronic kidney disease and contributes to poor nutritional intake. Previous sensory work has shown that taste improves after dialysis sessions. The goal of this pilot study was to characterize altered taste perceptions in patients on dialysis compared with healthy adults, and to evaluate relationships between serum parameters with taste perceptions. We hypothesized that patients undergoing dialysis would experience blunted taste intensities compared with controls, and that serum levels of potential tastants would be inversely related to taste perception of compounds. Using a cross-sectional design, we carried out suprathreshold sensory assessments (flavor intensity and liking) of tastants/flavors potentially influenced by kidney disease and/or the dialysis procedure. These included sodium chloride, potassium chloride, calcium chloride, sodium phosphate, phosphoric acid, urea, ferrous sulfate, and monosodium glutamate. Individuals on maintenance hemodialysis (n= 17, 10 males, range 23–87 years) were compared with controls with normal gustatory function (n=29, 13 males, range 21–61 years). Unadjusted values for intensity and liking for the solutions showed minimal differences. However, when values were adjusted for participants’ perceptions of water (as a control for taste abnormalities), intensity of monosodium glutamate, sodium chloride, and sodium phosphate solutions were more intense for patients on dialysis compared with controls. Some significant correlations were also observed between serum parameters, particularly potassium, for dialysis patients and sensory ratings. These results suggest altered taste perception in patients during dialysis warrants further study

Effect of dietary cholesterol on erythrocyte peroxidant stress in vitro and in vivo

The effect of dietary variation of plasma cholesterol concentrations on the susceptibility of erythrocytes to in vitro and in vivo peroxidant stress was studied in rats. Malonyldialdehyde, produced in vivo (endogenous malonyldialdehyde) or following in vitro exposure of cells to 10 mM H2O2 (H2O2 malonyldialdehyde, was used as a measure of peroxidant stress. After 5 weeks, the plasma cholesterol concentrations in rats receiving 1.2% cholesterol + 0.6% cholic acid in their diet rose to 6-times that of control rats receiving a diet without added cholesterol; at the same time, erythrocyte H2O2 malonyldialdehyde in the cholesterol-fed rats decreased significantly relative to the control rats. During subsequent exposure of both groups to in vivo peroxidant stress with phenylhydrazine in two separate dose trials, erythrocyte peroxidant stress remained significantly lower in the cholesterol-fed rats: at a dose of 100 [mu]mol/100 g body weight, H2O2 malonyldialdehyde was lower; at a dose of 25 [mu]mol/100 g body weight, both endogenous and H2O2 malonyldialdehyde were lower. Erythrocyte membrane cholesterol concentrations were 12% higher in the cholesterol-fed rats than in controls. The effects of in vivo peroxidant stress on plasma cholesterol were also studied. In vivo peroxidant stress at the higher dose of phenylhydrazine produced a decrease in plasma cholesterol concentrations of control rats. The lower dose had no effect on this group and the plasma cholesterol concentrations were unchanged in the cholesterol-fed rats during both treatments. The data suggest that elevated plasma cholesterol concentrations are protective against erythrocyte peroxidant stress. The mechanism of cholesterol's protective effect is probably mediated through elevated membrane cholesterol concentrations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25615/1/0000163.pd

Gene expression profiling in hepatic tissue of newly weaned pigs fed pharmacological zinc and phytase supplemented diets

<p>Abstract</p> <p>Background</p> <p>Zinc (Zn) is an essential trace element. However, Zn bioavailability from commonly consumed plants may be reduced due to phytic acid. Zn supplementation has been used to treat diarrheal disease in children, and in the U.S. swine industry at pharmacological levels to promote growth and fecal consistency, but underlying mechanisms explaining these beneficial effects remain unknown. Moreover, adding supplemental phytase improves Zn bioavailability. Thus, we hypothesized that benefits of pharmacological Zn supplementation result from changes in gene expression that could be further affected by supplemental phytase. The goal of this study was to investigate the effects of feeding newly weaned pigs dietary Zn (150, 1,000, or 2,000 mg Zn/kg) as Zn oxide with or without phytase [500 phytase units (FTU)/kg] for 14 d on hepatic gene expression. Liver RNA from pigs fed 150, 1,000, or 2,000 mg Zn/kg, or 1,000 mg Zn/kg with phytase (n = 4 per treatment) was reverse transcribed and examined using the differential display reverse transcription polymerase chain reaction technique. Liver RNA from pigs fed 150 or 2,000 mg Zn/kg (n = 4 per treatment) was also evaluated using a 70-mer oligonucleotide microarray.</p> <p>Results</p> <p>Expressed sequence tags for 61 putatively differentially expressed transcripts were cloned and sequenced. In addition, interrogation of a 13,297 element oligonucleotide microarray revealed 650 annotated transcripts (FDR ≤ 0.05) affected by pharmacological Zn supplementation. Seven transcripts exhibiting differential expression in pigs fed pharmacological Zn with sequence similarities to genes encoding <it>GLO1</it>, <it>PRDX4</it>, <it>ACY1</it>, <it>ORM1</it>, <it>CPB2</it>, <it>GSTM4</it>, and <it>HSP70.2 </it>were selected for confirmation. Relative hepatic <it>GLO1 </it>(<it>P </it>< 0.0007), <it>PRDX4 </it>(<it>P </it>< 0.009) and <it>ACY1 </it>(<it>P </it>< 0.01) mRNA abundances were confirmed to be greater in pigs fed 1,000 (n = 8) and 2,000 (n = 8) mg Zn/kg than in pigs fed 150 (n = 7) mg Zn/kg. Relative hepatic <it>HSP70.2 </it>(P < 0.002) mRNA abundance was confirmed to be lower in pigs fed 2,000 mg Zn/kg than in pigs fed 150 or 1,000 mg Zn/kg.</p> <p>Conclusion</p> <p>Results suggest that feeding pharmacological Zn (1,000 or 2,000 mg Zn/kg) affects genes involved in reducing oxidative stress and in amino acid metabolism, which are essential for cell detoxification and proper cell function.</p

Obesity Accelerates Acute Promyelocytic Leukemia in Mice and Reduces Sex Differences in Latency and Penetrance

Objective: Obesity has emerged as a prominent risk factor for multiple serious disease states, including a variety of cancers, and is increasingly recognized as a primary contributor to preventable cancer risk. However, few studies of leukemia have been conducted in animal models of obesity. This study sought to characterize the impact of obesity, diet, and sex in a murine model of acute promyelocytic leukemia (APL). Methods: Male and female C57BL/6J.mCG+/PR mice, genetically predisposed to sporadic APL development, and C57BL/6J (wild type) mice were placed on either a high-fat diet (HFD) or a low-fat diet (LFD) for up to 500 days. Results: Relative to LFD-fed mice, HFD-fed animals displayed increased disease penetrance and shortened disease latency as indicated by accelerated disease onset. In addition, a diet-responsive sex difference in APL penetrance and incidence was identified, with LFD-fed male animals displaying increased penetrance and shortened latency relative to female counterparts. In contrast, both HFD-fed male and female mice displayed 100% disease penetrance and insignificant differences in disease latency, indicating that the sexual dimorphism was reduced through HFD feeding. Conclusions: Obesity and obesogenic diet promote the development of APL in vivo, reducing sexual dimorphisms in disease latency and penetrance

Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens

The standard therapy for preventing copper accumulation in Wilson's disease, D-penicillamine, has been a life-saving drug, but it has many side effects and some patients are completely intolerant. We have been using oral zinc as another approach to the therapy for Wilson's disease, with copper balance studies as the key initial assessment of the adequacy of a given dose or regimen of zinc therapy. We earlier reported that an intensive regimen of zinc (zinc taken every 4 hr) was effective in controlling copper balance. We have now shown with balance studies that a simplified zinc therapy regimen of 50 mg zinc taken 3 times per day is effective in controlling copper balance. Preliminary work presented here with other simplified regimens also indicate their effectiveness. These studies increase the data base, in terms of copper balance, for zinc therapy of Wilson's disease, and expand the dose range and regimens of zinc which have been shown to control copper balance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38334/1/1840070318_ftp.pd

Phosphate Binders and Non-Phosphate Effects in the Gastrointestinal Tract

Phosphate binders are commonly prescribed in patients with end-stage kidney disease to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for nonphosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end products. Other binders (calcium- and noncalcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota, as some of the iron or organic ligands may be used by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the nonphosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome

Ocean acidification research in the \u27post-genomic\u27 era: Roadmaps from the purple sea urchin Strongylocentrotus purpuratus

© 2015 Elsevier Inc. Advances in nucleic acid sequencing technology are removing obstacles that historically prevented use of genomics within ocean change biology. As one of the first marine calcifiers to have its genome sequenced, purple sea urchins (Strongylocentrotus purpuratus) have been the subject of early research exploring genomic responses to ocean acidification, work that points to future experiments and illustrates the value of expanding genomic resources to other marine organisms in this new \u27post-genomic\u27 era. This review presents case studies of S. purpuratus demonstrating the ability of genomic experiments to address major knowledge gaps within ocean acidification. Ocean acidification research has focused largely on species vulnerability, and studies exploring mechanistic bases of tolerance toward low pH seawater are comparatively few. Transcriptomic responses to high pCO2 seawater in a population of urchins already encountering low pH conditions have cast light on traits required for success in future oceans. Secondly, there is relatively little information on whether marine organisms possess the capacity to adapt to oceans progressively decreasing in pH. Genomics offers powerful methods to investigate evolutionary responses to ocean acidification and recent work in S. purpuratus has identified genes under selection in acidified seawater. Finally, relatively few ocean acidification experiments investigate how shifts in seawater pH combine with other environmental factors to influence organism performance. In S. purpuratus, transcriptomics has provided insight into physiological responses of urchins exposed simultaneously to warmer and more acidic seawater. Collectively, these data support that similar breakthroughs will occur as genomic resources are developed for other marine species

Obesity Prevalence and Dietary Factors Among Preschool-Aged Head Start Children in Remote Alaska Native Communities: Baseline Data from the ‘‘Got Neqpiaq?’’ Study

Background: American Indian and Alaska Native preschool-aged children experience a high prevalence of obesity, yet are underrepresented in obesity prevention research. This study examined obesity prevalence and dietary risk factors among Alaska Native preschool-aged children in southwest Alaska. Methods: The study used baseline data from ‘‘Got Neqpiaq?’’ a culturally centered multilevel intervention focused on Yup’ik Alaska Native children, aged 3–5 years, enrolled in Head Start in 12 communities in southwest Alaska (n = 155). The primary outcomes were BMI percentile, overweight, and obesity. Dietary factors of interest were measured using biomarkers: traditional food intake (nitrogen stable isotope ratio biomarker), ultraprocessed food intake (carbon stable isotope ratio biomarker), and vegetable and fruit intake (skin carotenoid status biomarker measured by the Veggie Meter). Cardiometabolic markers (glycated hemoglobin [HbA1c] and blood cholesterol) were also measured. Results: Among the Yup’ik preschool-aged children in the study, the median BMI percentile was 91, and the prevalence of overweight or obesity was 70%. The traditional food intake biomarker was negatively associated with BMI, whereas the ultraprocessed foods and vegetable and fruit biomarkers were not associated with BMI. HbA1c and blood cholesterol were within healthy levels. Conclusions: The burden of overweight and obesity is high among Yup’ik preschool-aged children. Traditional food intake is inversely associated with BMI, which underscores the need for culturally grounded interventions that emphasize traditional values and knowledge to support the traditional food systems in Alaska Native communities in southwest Alaska. Registered with ClinicalTrials.gov #NCT03601299.Ye

DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma

The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and ‘hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma

Fuel Cycle Scenario Definition, Evaluation, and Trade-offs

This report aims to clarify many of the issues being discussed within the AFCI program, including Inert Matrix Fuel (IMF) versus Mixed Oxide (MOX) fuel, single-pass versus multi-pass recycling, thermal versus fast reactors, potential need for transmutation of technetium and iodine, and the value of separating cesium and strontium. It documents most of the work produced by INL, ANL, and SNL personnel under their Simulation, Evaluation, and Trade Study (SETS) work packages during FY2005 and the first half of FY2006. This report represents the first attempt to calculate a full range of metrics, covering all four AFCI program objectives - waste management, proliferation resistance, energy recovery, and systematic management/economics/safety - using a combination of "static" calculations and a system dynamic model, DYMOND. In many cases, we examine the same issue both dynamically and statically to determine the robustness of the observations. All analyses are for the U.S. reactor fleet. This is a technical report, not aimed at a policy-level audience. A wide range of options are studied to provide the technical basis for identifying the most attractive options and potential improvements. Option improvement could be vital to accomplish before the AFCI program publishes definitive cost estimates. Information from this report will be extracted and summarized in future policy-level reports. Many dynamic simulations of deploying those options are included. There are few "control knobs" for flying or piloting the fuel cycle system into the future, even though it is dark (uncertain) and controls are sluggish with slow time response: what types of reactors are built, what types of fuels are used, and the capacity of separation and fabrication plants. Piloting responsibilities are distributed among utilities, government, and regulators, compounding the challenge of making the entire system work and respond to changing circumstances. We identify four approaches that would increase our ability to pilot the fuel cycle system: (1) have a recycle strategy that could be implemented before the 2030-2050 approximate period when current reactors retire so that replacement reactors fit into the strategy, (2) establish an option such as multi-pass blended-core IMF as a downward plutonium control knob and accumulate waste management benefits early, (3) establish fast reactors with flexible conversion ratio as a future control knob that slowly becomes available if/when fast reactors are added to the fleet, and (4) expand exploration of blended assemblies and cores, which appear to have advantages and agility. Initial results suggest multi-pass full-core MOX appears to be a less effective way than multi-pass blended core IMF to manage the fuel cycle system because it requires higher TRU throughput while more slowly accruing waste management benefits. Single-pass recycle approaches for LWRs (we did not study the VHTR) do not meet AFCI program objectives and could be considered a "dead end". Fast reactors appear to be effective options but a significant number of fast reactors must be deployed before the benefit of such strategies can be observed