Catabolic Rate Research Articles

Test-Retest Reliability and Validity of the Nutrition-Specific Quality of Life Questionnaire

The purpose of this study is to test the Nutrition-Specific Quality of Life (NSQOL) questionnaire for test-retest reliability and validity in a sample of patients on maintenance hemodialysis (MHD). Test-retest reliability of the NSQOL questionnaire via two patient interviews and comparison of the NSQOL questionnaire to a comprehensive nutrition assessment performed by a registered dietitian nutritionist for validity testing. This study was conducted in one outpatient MHD center in Chicago, IL. Adults, aged 18years or older, treated with MHD for at least sixmonths prior to start of the study. A Spearman's correlation coefficient was used to determine test-retest reliability and a Cronbach's alpha was used to determine the internal consistency of the 2 NSQOL questionnaires. Validity testing was done by comparing the NSQOL questionnaire to the most recent comprehensive nutrition assessment. The sample consisted of 17 men (63%) and 10 women (37%), with a mean age of 60±13, who were mostly African American (63%) and Caucasian (26%). There was a significant correlation (P=.001) between the initial NSQOL interview and repeat NSQOL interview in all questions except for question 14 (P=.100). The NSQOL questionnaire was found to have excellent internal consistency with an α=0.900. No significant relationship was found among total NSQOL score and age, dialysis vintage, albumin, or normalized protein catabolic rate; however, older participants had lower total NSQOL questionnaire scores. Although not statistically significant, there was variability between NSQOL questionnaire score and nutritional status. The NSQOL questionnaire was found to be reliable and had high internal consistency in this sample of patients receiving MHD. The NSQOL questionnaire may be beneficial for monitoring nutrition quality of life changes in-between nutrition assessment intervals.

SUN-059 Significance of fibroblast growth factor-23 (FGF23) level in hemodialysis patients

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone, and its levels increases as kidney function declines. Increased levels of FGF23 occur primarily as a result of a net positive phosphate balance leading to increased renal phosphate excretion. Although FGF23 helps to prevent hyperphosphatemia, elevated circulating levels are independently associated with vascular dysfunction, left ventricular hypertrophy, and increased risk for death in patients with CKD. Because few studies have investigated parameters associated with FGF23 levels in hemodialysis (HD) patients, we examined the clinical significance of FGF23 cross-sectionally. One hundred and nineteen HD patients were enrolled. Their mean age was 68.3±10.9 years, and the mean duration of HD treatment was 9.4±8.7 years. Forty-seven patients had diabetes mellitus (DM) and twenty-three patients had heart diseases. We identified prospective studies reporting associations between FGF23 concentration and parameters. The level of FGF23 was significantly correlated with the levels of Ca (P=0.02), P (P=0.001), intact-PTH (P=0.017) and Mg (P=0.001). On the other hand, arteriosclerosis, aldosterone, β2-microglobulin, dialysis efficiency, medicine, body mass index (BMI), normalized protein catabolism rate (nPCR), arteriosclerosis score, bone density, heart echo findings, blood pressure (BP), carotid artery echo findings, and survival prognosis were not correlated with FGF23 levels. When the patients were divided in DM group and non-DM group, there were significant differences of age, HD duration, hemoglobin concentration, BMI and nPCR. In non-DM group, the level of FGF23 was correlated with left ventricular muscle mass index (LVMI). However, it was not correlated in DM group. The level of FGF23 was correlated with LVMI in non-DM hemodialysis patients. We suggested that FGF23 directly induced LVMI because there were no changes in the levels of aldosterone and BP.

Targeted Deletion of Hepatocyte Abca1 Increases Plasma HDL (High-Density Lipoprotein) Reverse Cholesterol Transport via the LDL (Low-Density Lipoprotein) Receptor.

The role of hepatocyte Abca1 (ATP binding cassette transporter A1) in trafficking hepatic free cholesterol (FC) into plasma versus bile for reverse cholesterol transport (RCT) is poorly understood. We hypothesized that hepatocyte Abca1 recycles plasma HDL-C (high-density lipoprotein cholesterol) taken up by the liver back into plasma, maintaining the plasma HDL-C pool, and decreasing HDL-mediated RCT into feces. Approach and Results: Chow-fed hepatocyte-specific Abca1 knockout (HSKO) and control mice were injected with human HDL radiolabeled with 125I-tyramine cellobiose (125I-TC; protein) and 3H-cholesteryl oleate (3H-CO). 125I-TC and 3H-CO plasma decay, plasma HDL 3H-CO selective clearance (ie, 3H-125I fractional catabolic rate), liver radiolabel uptake, and fecal 3H-sterol were significantly greater in HSKO versus control mice, supporting increased plasma HDL RCT. Twenty-four hours after 3H-CO-HDL injection, HSKO mice had reduced total hepatic 3H-FC (ie, 3H-CO hydrolyzed to 3H-FC in liver) resecretion into plasma, demonstrating Abca1 recycled HDL-derived hepatic 3H-FC back into plasma. Despite similar liver LDLr (low-density lipoprotein receptor) expression between genotypes, HSKO mice treated with LDLr-targeting versus control antisense oligonucleotide had slower plasma 3H-CO-HDL decay, reduced selective 3H-CO clearance, and decreased fecal 3H-sterol excretion that was indistinguishable from control mice. Increased RCT in HSKO mice was selective for 3H-CO-HDL, since macrophage RCT was similar between genotypes. Hepatocyte Abca1 deletion unmasks a novel and selective FC trafficking pathway that requires LDLr expression, accelerating plasma HDL-selective CE uptake by the liver and promoting HDL RCT into feces, consequently reducing HDL-derived hepatic FC recycling into plasma.

Adaptation to Amino Acid Kinetics and Urea Production in Adult Cats (Felis catus) Fed Below Their Protein Requirement (P09-008-19)

ObjectivesCats are obligate carnivores that evolved eating meat-based diets and have high requirements for amino acids (AA). However, little is known about how they regulate AA metabolism, especially at intakes below their requirement. This study was undertaken to examine the effect of dietary protein level above and below their requirement on urea production and AA metabolism in cats. MethodsCats (n = 18) were allocated to three treatments (7.5, 15, or 40% ME intake as crude protein), fed at maintenance for 3 wk, and then fitted with saphanous and cephalic vein catheters. On the following day, they received primed continuous infusions of [13C]bicarbonate, [1-13C]Leu and [15N2]urea from 0 to 120, 120 to 480 and 0 to 480 min, respectively. Cats were fed hourly during infusion and Leu entry rate from diet was calculated. Breath was sampled at 0, 100, 110, 120, 440, 460, and 480 min to measure 13CO2, with blood sampled at 0, 440, 460, and 480 min to measure 13C enrichments in Leu and ketoisocaproate, and [15N2]urea. ResultsValues for non-oxidative Leu disposal (NOLD, an indicator of protein synthesis), Leu rate of appearance in plasma (Ra, an indicator of protein degradation), Leu oxidation, and urea production rate (an indicator of net protein catabolism) are shown in Table 1. There were no differences in any measurements in cats fed at (15%) or below (7.5%) their requirement for protein. However, those fed with 7.5% of ME intake as crude protein had numerically lowest rates of whole body AA catabolism and oxidation, whereas, Leu Ra was numerically greatest. ConclusionsUsing Leu kinetics to trace AA metabolism, there did not seem to be a difference between cats fed at or below their requirement for protein. This may indicate that cats are able to adapt to dietary protein content more than what was previously believed. Funding SourcesMassey University Research Fund, and the McGeorge Research Fund Supporting Tables, Images and/or Graphs▪

MIS and SGA Indices as Predictors of Mortality and Their Relationship with Nutrition Parameters in Hemodialysis Patients (P18-009-19)

ObjectivesTo compare the value of Subjective Global Assessment (SGA) and Malnutrition-Inflammation Score (MIS) for the prediction of mortality and examine their relationship with other nutritional parameters. MethodsNutrition status was assessed at baseline by SGA and MIS; albumin, protein catabolic rate (nPCR) were obtained from chart; 24-hr dietary recalls were used to estimate daily dietary protein intake (DPI) and dietary energy intake (DEI). Deaths were recorded for 12 months ResultsSeventy-seven participants receiving HD were included, with a mean age of 63.2 ± 14.2 years; 71.2% were male, 58.4% had diabetes and the average time on dialysis was 6.2 ± 4.2 years. The Mean ± SD of nPCR was 0.9 ± 0.2, albumin was 3.8 ± 0.3, DEI was 1867.3 ± 367.9 kcal/kg and DPI was 80.0 ± 15.8 gm/kg. MIS ≥ 6 and SGA > 1 were used as cut-off values to detect malnourished participants; 46% were malnourished by MIS vs. 35% by SGA. Albumin, nPCR, DPI and DEI were all inversely correlated with both indices (P < 0.05). Ten patients (13%) died of cardiovascular disease. Well-nourished participants with MIS < 6 lived longer (11.8 months, CI 95%, 11.6–12.1) than malnourished with MIS ≥ 6 (10.9 months, CI 95%, 10.1–11.7) (Log Rank P = 0.04). MIS was a significant predictor of mortality, while SGA did not reach significance (P = 0.264). ConclusionsMIS was a more sensitive index to detect malnutrition than SGA among HD patients. Only MIS was a significant predictor of mortality. Both indices were strongly correlated to the examined nutrition parameters. Funding SourcesNo funding sources.

The Effect of Protein Supplementation and Nutrition Counselling on Protein Catabolic Rates Among Persons with End-Stage Renal Disease on Maintenance Haemodialysis (P12-035-19)

ObjectivesTo compare the impact of protein supplementation versus nutrition education/counselling on protein intakes (indexed by normalized protein catabolic rates (nPCR)) among persons on maintenance haemodialysis. MethodsAn intervention study design was employed in this investigation. Participating dialysis centers were randomly selected and persons attending those centers were invited to participate in the study. Participants had anthropometry and biochemical variables recorded at baseline and on two occasion 1 month apart during each of the interventions. Persons in the intervention group (IVG) received a supplement containing 36 grams of whey protein daily for 6 weeks in. Following a 2-week washout period, they received personalized weekly nutrition education/counselling for an additional 6 weeks. The control group (NIVG) did not receive any supplementation or nutrition education/counselling. Both groups received received the routine facility care. Participation was voluntary. The study was approved by the Ethics Committee, The University of The West Indies. ResultsSixty-eight persons (IVG = 32; NIVG = 36) participated in the study. There was no significant difference in the mean nPCR between IVG and NIVG at baseline (0.84 ± 0.17 vs. 0.84 ± 0.17 mg/kg; P = 0.76). IVG had significantly higher mean nPCR than NIVG during protein supplementation (0.95 ± 0.21 vs. 0.78 ± 0.15 mg/kg; P < 0.001) and nutritional education/counselling (0.87 ± 0.17 vs. 0.79 ± 0.18 mg/kg; P = 0.02 phases of the study. Among IVG, protein supplementation (+Δ 12.8 ± 3.0 mg/kg (±S.E.) but not nutrition education/counselling (+Δ 2.8 ± 2.7 mg/kg; P = 0.32) resulted in a significant increase in mean nPCR compared to baseline.with no significant changes in biochemical variables. ConclusionsAmong participants nPCR increased significantly with protein supplementation but not nutrition education/counselling without adversely affecting biochemical variables. Funding SourcesGrant and Publication Fund, The University of The West Indies.

Predictive Factors for Achieving the Recommended AUA Daily Urine Production in Patients With Nephrolithiasis.

ObjectiveTo identify factors that predict kidney stone patient's ability to produce 2.5 L urine volume per day on metabolic evaluation.Patients and MethodsIn a retrospective chart review, the first analysis evaluated initial 24-hour urine collections with respect to those who achieved or did not achieve a urine volume of 2.5 L/day. The second analysis evaluated those who achieved or did not achieve a daily urine volume of 2.5 L on their subsequent collection. Several variables were assessed.ResultsPatients’ initial collections (n=1100) that achieved 2.5 L/day (n=274) were of younger age and had a higher body mass index, increased urine sodium, phosphorus, calcium levels, increased protein catabolic rate, and decreased supersaturation of calcium oxalate. In the second analysis (n=273), decreased supersaturation of calcium oxalate, increased urine urea nitrogen level, and increased protein catabolic rate were observed in subsequent collections with a urine volume of 2.5 L/day or more. Patients with a diagnosis of hyponatremia were less likely to achieve 2.5 L/day urine volume. Collection date, other comorbidities, and diuretic use were not associated with achieving 2.5 L/day urine volume. Patients’ mean creatinine per kilogram for all study cohorts were within the range of adequate collection.ConclusionPredictive factors for a urine volume of 2.5 L/day or more include increased fluid intake, higher salt and animal protein diet, elevated body mass index, and male sex. Patients with these factors may require interventions other than hydration recommendations to optimize their prevention of future kidney.

Serum myokine (myostatin and IGF-1) measurement as predictors in hemodialysis patients

BackgroundAlthough individuals undergoing maintenance hemodialysis are a major sarcopenic population, there are few methods to assess their skeletal muscle mass conveniently. Here, we investigated the usefulness of serum myostatin and insulin-like growth factor-1 (IGF-1) measurements for the evaluation of skeletal muscle mass.MethodsWe examined 117 patients undergoing conventional hemodialysis. The serum myostatin level and IGF-1 level were measured once and compared to clinical parameters (especially skeletal muscle mass-related factors) in hemodialysis patients.ResultsThe myostatin levels were positively correlated with body cell mass, arm muscle circumference, basal metabolic rate, creatinine, creatinine phosphokinase, and albumin and negatively correlated with body fat rate, arm circumference–arm muscle circumference, age, and C-reactive protein (CRP). The IGF-1 levels were positively correlated with body cell mass, body mass index, arm muscle circumference, arm circumference–arm muscle circumference, blood urea nitrogen, creatinine, protein catabolism rate, transferrin, cholesterol, and triglyceride, and negatively with age and human atrial natriuretic polypeptide.ConclusionsOur findings indicate that serum myostatin might be a useful biomarker for predicting muscle mass and serum IGF-1 might be a useful predictor of nutritional status in hemodialysis patients.

The association between six month intra-dialytic resistance training and muscle strength or physical performance in patients with maintenance hemodialysis: a multicenter retrospective observational study

BackgroundReduced muscle strength and physical performance are prevalent in patients of maintenance hemodialysis (MHD), and deleterious changes in these parameters are associated with increased mortality.MethodsThis retrospective observational study included 306 patients, who received a 6-month resistance exercise program during hemodialysis, three times per week on an outpatient basis. The training protocol consisted of two sets of 10 repetitions of knee extension, hip abduction, and hip flexion, using an elastic band in a sitting or supine position. Primary outcome measures included muscle strength, measured by percent knee extension muscle power to dry body weight (pKEMP-dBW), and physical performance, measured by short physical performance battery (SPPB). The adjusted mean differences in these variables during the 6 months were estimated using a multivariate linear regression model.ResultsThe mean age with standard deviation was 70 ± 11 years. One hundred and sixty patients (52.3%) were men and the dry weight was 55.6 ± 11.3 kg. Sarcopenia, defined as SPPB ≤8, was present in 21.4% patients. Their hemodialysis adequacy was acceptable, with a Kt/V of 1.65 ± 0.29, and their nutritional status was good, with a normalized protein catabolism rate of 0.89 ± 0.18 g/kg/day. During the 6 months, both pKEMP-dBW and SPPB showed a slight but significant increase with an adjusted mean difference of 2.8 (95% confidence interval 1.3–4.3, p < 0.001) and 0.6 (0.4–0.9, p < 0.001), respectively.ConclusionsSix-month resistance training was associated with improved muscle strength and physical performance in patients with MHD.

A brief comparative trial on Lp(a)

Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein characterized by apolipoprotein(a) [apo(a)] covalently bounded to apoB-100 (apoB). However, the metabolism of apo(a) and apoB within plasma Lp(a) particles in patients on statins remains unclear.The kinetics of Lp(a)-apo(a) and Lp(a)-apoB were determined in 20 patients with elevated Lp(a) (≥0.8 g/L; n = 10) and normal Lp(a) (≤0.3 g/L; n = 10) using stable isotope techniques and compartmental modeling. Plasma apo(a) concentration was measured using liquid chromatography–mass spectrometry. All patients were on statin therapy and were studied in the fasting state.The fractional catabolic rate (FCR) of Lp(a)-apo(a) was not significantly different from that of Lp(a)-apoB in statin-treated patients with elevated or normal Lp(a) (P > 0.05 in both). Lp(a)-apo(a) FCR was significantly correlated with Lp(a)-apoB in patients with elevated and normal Lp(a) concentrations (r = 0.970 and r = 0.979, respectively; all P < 0.001) with Lin's concordance test showing substantial agreement between the FCRs of Lp(a)-apo(a) and Lp(a)-apoB in patients with elevated and normal Lp(a) concentrations (rc = 0.978 and rc = 0.966, respectively).Our data indicate that the apo(a) and apoB proteins within Lp(a) particles have similar FCR and are therefore tightly coupled as an Lp(a) holoparticle in statin-treated patients with elevated and normal Lp(a) concentrations.

Evaluating haemodialysis patient's nutritional status: Body mass index or body cell mass index?

Evaluate which of two combinations of parameters based on International Society of Renal Nutrition and Metabolism recommendations could better identify patients with protein-energy wasting (PEW) and to compare the relationship of these two combinations with other clinical and body composition parameters. This was a multicentre longitudinal study with 24 months of follow-up. The PEW patients were characterized by: Group A (GA ) - normalized protein catabolic rate (nPCR) < 1.0 g/kg per day, albumin <3.8 g/dL and body cell mass index (BCMI) < 6.4 kg/m2 (n = 203); Group B (GB ) - nPCR <1.0 g/kg per day, albumin <3.8 g/dL and body mass index (BMI) <23 kg/m2 (n = 109). All the patients who did not meet these requirements were considered "well-nourished" (GA : n = 1818; GB : n = 3292). When compared to the well-nourished patients, PEW patients in the GA presented higher age, Kt/V, C-reactive protein, relative overhydration, fat tissue index (FTI); lower creatinine, albumin, nPCR, PTH, haemoglobin, phosphorus, calcium X phosphorus product, potassium, dry weight, BMI, BCMI, lean tissue index, %IDWG . In the GB , well-nourished patients FTI was significantly higher. In Cox analysis, the combination with BCMI was a strong independent predictor of mortality in these patients (hazard ratio: 1.48; confidence interval: 1.00-2.19; P = 0.048), even after adjustment. Although GB combination seemed to be also a predictor of death (hazard ratio: 2.67; confidence interval: 1.92-3.71; P < 0.001), when adjusted, the association remained no longer significant. A new combination of parameters including protein intake, albumin and BCMI demonstrated significant associations with other nutrition and inflammation parameters as well as with mortality.

Fractional turnover of apolipoprotein(a) and apolipoprotein B-100 within plasma lipoprotein(a) particles in statin-treated patients with elevated and normal Lp(a) concentration

ContextLipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein characterized by apolipoprotein(a) [apo(a)] covalently bounded to apoB-100 (apoB). However, the metabolism of apo(a) and apoB within plasma Lp(a) particles in patients on statins remains unclear. MethodsThe kinetics of Lp(a)-apo(a) and Lp(a)-apoB were determined in 20 patients with elevated Lp(a) (≥0.8 g/L; n = 10) and normal Lp(a) (≤0.3 g/L; n = 10) using stable isotope techniques and compartmental modeling. Plasma apo(a) concentration was measured using liquid chromatography–mass spectrometry. All patients were on statin therapy and were studied in the fasting state. ResultsThe fractional catabolic rate (FCR) of Lp(a)-apo(a) was not significantly different from that of Lp(a)-apoB in statin-treated patients with elevated or normal Lp(a) (P > 0.05 in both). Lp(a)-apo(a) FCR was significantly correlated with Lp(a)-apoB in patients with elevated and normal Lp(a) concentrations (r = 0.970 and r = 0.979, respectively; all P < 0.001) with Lin's concordance test showing substantial agreement between the FCRs of Lp(a)-apo(a) and Lp(a)-apoB in patients with elevated and normal Lp(a) concentrations (rc = 0.978 and rc = 0.966, respectively). ConclusionOur data indicate that the apo(a) and apoB proteins within Lp(a) particles have similar FCR and are therefore tightly coupled as an Lp(a) holoparticle in statin-treated patients with elevated and normal Lp(a) concentrations.

Parameter Identification for a Model of Neonatal Fc Receptor-Mediated Recycling of Endogenous Immunoglobulin G in Humans.

Salvage of endogenous immunoglobulin G (IgG) by the neonatal Fc receptor (FcRn) is implicated in many clinical areas, including therapeutic monoclonal antibody kinetics, patient monitoring in IgG multiple myeloma, and antibody-mediated transplant rejection. There is a clear clinical need for a fully parameterized model of FcRn-mediated recycling of endogenous IgG to allow for predictive modeling, with the potential for optimizing therapeutic regimens for better patient outcomes. In this paper we study a mechanism-based model incorporating nonlinear FcRn-IgG binding kinetics. The aim of this study is to determine whether parameter values can be estimated using the limited in vivo human data, available in the literature, from studies of the kinetics of radiolabeled IgG in humans. We derive mathematical descriptions of the experimental observations—timecourse data and fractional catabolic rate (FCR) data—based on the underlying physiological model. Structural identifiability analyses are performed to determine which, if any, of the parameters are unique with respect to the observations. Structurally identifiable parameters are then estimated from the data. It is found that parameter values estimated from timecourse data are not robust, suggesting that the model complexity is not supported by the available data. Based upon the structural identifiability analyses, a new expression for the FCR is derived. This expression is fitted to the FCR data to estimate unknown parameter values. Using these parameter estimates, the plasma IgG response is simulated under clinical conditions. Finally a suggestion is made for a reduced-order model based upon the newly derived expression for the FCR. The reduced-order model is used to predict the plasma IgG response, which is compared with the original four-compartment model, showing good agreement. This paper shows how techniques for compartmental model analysis—structural identifiability analysis, linearization, and reparameterization—can be used to ensure robust parameter identification.

Cellular energetics and mitochondrial uncoupling in canine aging.

The first domesticated companion animal, the dog, is currently represented by over 190 unique breeds. Across these numerous breeds, dogs have exceptional variation in lifespan (inversely correlated with body size), presenting an opportunity to discover longevity-determining traits. We performed a genome-wide association study on 4169 canines representing 110 breeds and identified novel candidate regulators of longevity. Interestingly, known functions within the identified genes included control of coat phenotypes such as hair length, as well as mitochondrial properties, suggesting that thermoregulation and mitochondrial bioenergetics play a role in lifespan variation. Using primary dermal fibroblasts, we investigated mitochondrial properties of short-lived (large) and long-lived (small) dog breeds. We found that cells from long-lived breeds have more uncoupled mitochondria, less electron escape, greater respiration, and capacity for respiration. Moreover, our data suggest that long-lived breeds have higher rates of catabolism and β-oxidation, likely to meet elevated respiration and electron demand of their uncoupled mitochondria. Conversely, cells of short-lived (large) breeds may accumulate amino acids and fatty acid derivatives, which are likely used for biosynthesis and growth. We hypothesize that the uncoupled metabolic profile of long-lived breeds likely stems from their smaller size, reduced volume-to-surface area ratio, and therefore a greater need for thermogenesis. The uncoupled energetics of long-lived breeds lowers reactive oxygen species levels, promotes cellular stress tolerance, and may even prevent stiffening of the actin cytoskeleton. We propose that these cellular characteristics delay tissue dysfunction, disease, and death in long-lived dog breeds, contributing to canine aging diversity.

Modeled Daily Ingested, Absorbed and Bound Phosphorus: New Measures of Mineral Balance in Hemodialysis Patients

Background: Control of predialysis serum phosphorus in hemodialysis patients is challenging. We explored the utility of a novel kinetic phosphorus modeling program. Methods: As part of a quality assurance program, urea kinetic modeling results were combined with those from phosphorus kinetic modeling to compute modeled daily ingested phosphorus (DIP) and components making up this metric, including absorbed, bound, and nonabsorbed, nonbound phosphorus. Results: In 182 hemodialysis patients, DIP averaged 1,089 ± 348 mg/day in men and 934 ± 292 in women (p < 0.002) and correlated substantially with body weight. DIP/kg bodyweight (12.8 ± 3.40 mg/kg) was not significantly different between the sexes. Prescribed equivalent binder dose (EBD) was 4.98 ± 3.61 and 4.53 ± 3.02 g/day in men and women, respectively (p NS). Protein catabolic rate (PCR) was significantly higher in men (64.4 ± 18) g/day vs. women (48.2 ± 15.6, p < 0.001), and the DIP/PCR ratio was 17.4 ± 4.81 in men vs. 20.1 ± 5.76 in women (p < 0.001). Presence of residual kidney function was associated with a lower prescribed EBD dose (4.08 ± 2.62 vs. 5.38 ± 3.81 g/day, p < 0.01). Self-reported poor binder compliance was associated with higher DIP or DIP/kg as well as higher prescribed EBD. In anuric patients, DIP/kg was increased in patients consuming diets with high phosphate additive content and those reporting poor compliance with the prescribed dose of phosphate binders. Conclusions: The combination of urea kinetic and phosphorus modeling can be used to estimate measures related to phosphorus intake. High DIP/PCR or DIP/kg body weight values in anuric patients suggest consumption of a diet high in phosphorus additives or noncompliance with the prescribed amount of phosphorus binders.

Role of RpoN from Labrenzia aggregata LZB033 (Rhodobacteraceae) in Formation of Flagella and Biofilms, Motility, and Environmental Adaptation.

Labrenzia aggregata LZB033 (Rhodobacteraceae), which produces dimethylsulfoniopropionate (DMSP) and reduces nitrate to nitrogen, was isolated from seawater of the East China Sea. Its genome encodes a large number of transcriptional regulators which may be important for its adaptation to diverse marine environments. The alternative σ54 factor (RpoN) is a central regulator of many bacteria, regulating the transcription of multiple genes and controlling important cellular functions. However, the exact role of RpoN in Labrenzia spp. is unknown. In this study, an in-frame rpoN deletion mutant was constructed in LZB033, and the function of RpoN was determined. To systematically identify RpoN-controlled genes, we performed a detailed analysis of gene expression differences between the wild-type strain and the ΔrpoN mutant using RNA sequencing. The expression of 175 genes was shown to be controlled by RpoN. Subsequent phenotypic assays showed that the ΔrpoN mutant was attenuated in flagellar biosynthesis and swimming motility, utilized up to 13 carbon substrates differently, lacked the ability to assimilate malic acid, and displayed markedly decreased biofilm formation. In addition, stress response assays showed that the ΔrpoN mutant was impaired in the ability to survive under different challenge conditions, including osmotic stress, oxidative stress, temperature changes, and acid stress. Moreover, both the DMSP synthesis and catabolism rates of LZB033 decreased after rpoN was knocked out. Our work provides essential insight into the regulatory function of RpoN, revealing that RpoN is a key determinant for LZB033 flagellar formation, motility, biofilm formation, and environmental fitness, as well as DMSP production and degradation.IMPORTANCE This study established an in-frame gene deletion method in the alphaproteobacterium Labrenzia aggregata LZB033 and generated an rpoN gene mutant. A comparison of the transcriptomes and phenotypic characteristics between the mutant and wild-type strains confirmed the role of RpoN in L. aggregata LZB033 flagellar formation, motility, biofilm formation, and carbon usage. Most importantly, RpoN is a key factor for survival under different environmental challenge conditions. Furthermore, the ability to synthesize and metabolize dimethylsulfoniopropionate (DMSP) was related to RpoN. These features revealed RpoN to be an important regulator of stress resistance and survival for L. aggregata LZB033 in marine environments.

Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics.

BackgroundTriglyceride‐rich lipoproteins and their remnants have emerged as major risk factors for cardiovascular disease. New experimental approaches are required that permit simultaneous investigation of the dynamics of chylomicrons (CM) and apoB48 metabolism and of apoB100 in very low‐density lipoproteins (VLDL).MethodsMass spectrometric techniques were used to determine the masses and tracer enrichments of apoB48 in the CM, VLDL 1 and VLDL 2 density intervals. An integrated non‐steady‐state multicompartmental model was constructed to describe the metabolism of apoB48‐ and apoB100‐containing lipoproteins following a fat‐rich meal, as well as during prolonged fasting.ResultsThe kinetic model described the metabolism of apoB48 in CM, VLDL 1 and VLDL 2. It predicted a low level of basal apoB48 secretion and, during fat absorption, an increment in apoB48 release into not only CM but also directly into VLDL 1 and VLDL 2. ApoB48 particles with a long residence time were present in VLDL, and in subjects with high plasma triglycerides, these lipoproteins contributed to apoB48 measured during fasting conditions. Basal apoB48 secretion was about 50 mg day−1, and the increment during absorption was about 230 mg day−1. The fractional catabolic rates for apoB48 in VLDL 1 and VLDL 2 were substantially lower than for apoB48 in CM.DiscussionThis novel non‐steady‐state model integrates the metabolic properties of both apoB100 and apoB48 and the kinetics of triglyceride. The model is physiologically relevant and provides insight not only into apoB48 release in the basal and postabsorptive states but also into the contribution of the intestine to VLDL pool size and kinetics.

Prediction of Mortality and Hospitalization Risk Using Nutritional Indicators and Their Changes Over Time in a Large Prevalent Hemodialysis Cohort

Malnutrition and protein-energy wasting are associated with morbidity and mortality in hemodialysis patients. Existing nutritional scores rely primarily on cross-sectional data. Using readily available nutritional indicators, we developed models to predict the risk of mortality and hospitalization in prevalent hemodialysis patients. In this retrospective study, we constructed prediction models of 1-year mortality and hospitalization using generalized linear models, generalized additive models (GAM), classification tree, and random forest models. The models were compared using area under the receiver-operating characteristics curve (AUC) and calibration curves. Model predictors included nutritional and inflammation indicators, demographics, comorbidities, and slopes of all continuous variables over 6months. Patients were randomly split in the ratio 2:1:1 into training, testing, and validation cohorts, respectively. We included patients with hemodialysis vintage ≥1year from Fresenius Medical Care North America clinics from July 2011 to December 2012 (N=21,802 in mortality analysis; N=13,892 in hospitalization analysis).The outcome variables were 1-year mortality and hospitalization. For mortality prediction, GAM was the best model (AUC = 0.85, 95% confidence interval = 0.83-0.86), comprised of neutrophil-to-lymphocyte ratio slope, serum bicarbonate slope, and vintage as nonlinear predictors, and age, serum albumin, and creatinine as linear predictors. For hospitalization prediction, GAM was also the best model (AUC = 0.70, 95% confidence interval= 0.62-0.79) and included neutrophil-to-lymphocyte ratio slope, bicarbonate slope, volume of urea distribution, vintage, and phosphate slope as nonlinear predictors, in addition to albumin, congestive heart failure, age, phosphate, equilibrated normalized protein catabolic rate, and creatinine as linear predictors. Both models demonstrated good calibration, with mild overestimation of hospitalization risk at the highest risk interval. The GAM model can accurately predict the risk of mortality and hospitalization. Application of these prediction models could inform allocation of nutritional interventions to patients at highest nutritional risk.

Aerobic Degradation of Clothianidin to 2-Chloro-methyl Thiazole and Methyl 3-(Thiazole-yl) Methyl Guanidine Produced by Pseudomonas stutzeri smk.

Overuse of pesticides in agriculture may harm environmental and agricultural yields. Sustainable maintenance of soil fertility and management of the environment have become a concern due to the persistence of pesticides in the soil. Microbes have various mechanisms for the bioremediation of persistent organic pollutants from the environment. A bacterium that degrades clothianidin was isolated from the pesticide and applied to agricultural soil by the enrichment technique. The identity of the bacterium was determined by studying morphological, cultural, and biochemical characteristics and 16S rRNA gene sequences. The ability to metabolize clothianidin was confirmed using UV-visible spectrophotometric, chromatographic, and spectroscopic analyses. A Gram-negative bacterium, designated smk, isolated from clothianidin-contaminated soil was confirmed to be a member of Pseudomonas stutzeri. The biodegradation of clothianidin was studied using P. stutzeri smk. Approximately 62% degradation of clothianidin was achieved within two weeks when grown at 30°C and pH 7. The effects of various physicochemical parameters, including pH, temperature, and clothianidin concentrations, on catabolic rates were studied. The biodegradation studies using UV-Vis spectrophotometry, HPLC, FTIR, and LC-MS indicated the production of the following metabolites: 2-chloro-5-methyl thiazole (CMT), methyl nitroguanidine (MNG), methyl 3-[thiazole-yl], and methyl guanidine (TMG). Identification of specific degradation metabolites indicates that bioremediation of toxic neonicotinoid insecticides may be achieved by application of P. stutzeri smk.

Effects of diammonia phosphate addition on the chemical constituents in lychee wine fermented with Saccharomyces cerevisiae

This study evaluated the effects of diammonia phosphate (DAP) on the non-volatile and volatile compounds of lychee wine fermented with Saccharomyces cerevisiae, when added in two different quantities (0.5 mmol/L and 1.5 mmol/L). It was found that DAP supplementation improved the utilization of ammonia and inhibited the consumption of proline and valine, which regulated the production of α-ketoglutaric, succinic and fatty acids. The addition of 0.5 mmol/L DAP improved the rate of sugar catabolism by slightly increasing yeast growth, thus inducing a higher production of glycerol than of ethanol. Additionally, more odor-active terpene derivatives (trans-β-damascenone, o-cymene, δ-guaiene) in lychee juice were retained after the fermentation added with 0.5 mmol/L DAP. However, the addition of 1.5 mmol/L DAP slowed rates of sugar metabolism and glycerol production, and significantly enhanced the production of acetic acid. Furthermore, with the exception of limonene, the higher DAP addition did not retain more terpene derivatives. These findings, therefore, suggest that a moderate addition of DAP could enhance the flavorful character of lychee wine.