The Effect of Intact Protein from Foods and Phenylalanine Free Medical Foods on Large Neutral Amino Acids in Patients with Phenylketonuria.

Objective: The primary aim of this retrospective cohort study was to determine the association between the source of dietary protein intake and the sum of plasma concentration of large neutral amino acids (LNAA) in patients with Phenylketonuria (PKU). A secondary aim of the study was to examine the effect of dietary compliance on plasma concentration of LNAA. Methods: The analysis included combined participant data from two previous studies conducted at the Emory University School of Medicine. Subjects are males (n=34) and females (n=43) with PKU ages 4-50 years. A Student t-test was used to compare total combined plasma LNAA (excluding tryptophan and phenylalanine) by dietary compliance status (alpha=0.05). Correlation statistics were used to determine the association between the ratio of reported intact food protein to medical food protein on plasma levels of LNAA. Multiple regression analysis was used to examine the contribution of intact protein to medical food protein ratio and other variables to plasma LNAA. Results: The median ratio of intact protein to medical food protein reported was 0.354 (IQR: 0.188, 0.914). Median percent of PHE intake over the PHE intake recommendation was 31.64 (Interquartile range [IQR]; 7.44, 104.98). Plasma concentration of LNAA did not differ significantly between those with plasma PHE levels within the therapeutic range μmol/L (compliant; 611.7 μmol/L [n=19]) vs levels above the therapeutic range (non-compliant; 595.3 μmol/L [n=47]); p=0.613). There was an inverse marginal correlation between the ratio of intact protein to medical food protein and plasma concentration of LNAA for those who were compliant (r = -0.436, r = 0.1) although the association was not statistically significant (p=0.08). No correlation was found for patients who were non-compliant. Regression analysis revealed that plasma concentration of LNAA was not significantly affected by the ratio of intact protein to medical food protein ratio, age, or gender. Conclusions: Although not statistically significant, a negative trend was observed between plasma LNAA concentration and the intact protein to medical food protein ratio in patients compliant with the PHE prescription. This suggests that the ratio of intact dietary protein to protein coming from medical food, as reported by patient diet records, may promote increased plasma LNAA levels in the effective treatment of PKU. The majority of the sample (74%) were non-compliant with diet based on plasma PHE levels. Future studies are needed to determine the consequences of non-compliance by decreased intake of medical food protein or increased intake of intact protein on plasma LNAA concentration and downstream health effects

Di-μ-pivalato-κ3 O,O′:O′;κ3 O:O,O′-bis­[(methanol-κO)bis­(2,2,6,6-tetra­methylhepta­ne-3,5-dionato)praseo­dymium(III)]

In the centrosymmetric dimeric title compound, [Pr2(C5H9O2)2(C11H19O2)4(CH3OH)2], the two praseodymium(III) atoms are eight-coordinate and are bridged by O atoms from the two pivalate anions. Each PrIII ion is further coordinated by two chelating 2,2,6,6-tetra­methyl-3,5-hepta­nedionate (thd−) ligands and one methanol mol­ecule. The distance between the two PrIII ions is 4.273 (5) Å. Intra­molecular hydrogen bonds exists between the methanol hy­droxy group on one PrIII atom and a chelating O atom of a thd− ligand coordinated to the symmetry-related PrIII atom

Personality predictors of levels of forgiveness two and a half years after the transgression

The aim of the present study was to explore whether the domains and facets of the five-factor model of personality predicted motivational states for avoidance and revenge following a transgression at a second temporal point distant from the original transgression. A sample of 438 university students, who reported experiencing a serious transgression against them, completed measures of avoidance and revenge motivations around the transgression and five-factor personality domains and facets at time 1, and measures of avoidance and revenge motivations two and a half years later. The findings suggest that neuroticism, and specifically anger hostility, predicts revenge and avoidance motivation

Prediction of individual milk proteins including free amino acids in bovine milk using mid-infrared spectroscopy and their correlations with milk processing characteristics

The aim of this study was to evaluate the effectiveness of mid-infrared spectroscopy in predicting milk protein and free amino acid (FAA) composition in bovine milk. Milk samples were collected from 7 Irish research herds and represented cows from a range of breeds, parities, and stages of lactation. Mid-infrared spectral data in the range of 900 to 5,000 cm(-1) were available for 730 milk samples; gold standard methods were used to quantify individual protein fractions and FAA of these samples with a view to predicting these gold standard protein fractions and FAA levels with available mid-infrared spectroscopy data. Separate prediction equations were developed for each trait using partial least squares regression; accuracy of prediction was assessed using both cross validation on a calibration data set (n = 400 to 591 samples) and external validation on an independent data set (n = 143 to 294 samples). The accuracy of prediction in external validation was the same irrespective of whether undertaken on the entire external validation data set or just within the Holstein-Friesian breed. The strongest coefficient of correlation obtained for protein fractions in external validation was 0.74, 0.69, and 0.67 for total casein, total beta-lactoglobulin, and beta-casein, respectively. Total proteins (i.e., total casein, total whey, and total lactoglobulin) were predicted with greater accuracy then their respective component traits; prediction accuracy using the infrared spectrum was superior to prediction using just milk protein concentration. Weak to moderate prediction accuracies were observed for FAA. The greatest coefficient of correlation in both cross validation and external validation was for Gly (0.75), indicating a moderate accuracy of prediction. Overall, the FAA prediction models overpredicted the gold standard values. Near-unity correlations existed between total casein and beta-casein irrespective of whether the traits were based on the gold standard (0.92) or mid-infrared spectroscopy predictions (0.95). Weaker correlations among FAA were observed than the correlations among the protein fractions. Pearson correlations between gold standard protein fractions and the milk processing characteristics of rennet coagulation time, curd firming time, curd firmness, heat coagulating time, pH, and casein micelle size were weak to moderate and ranged from -0.48 (protein and pH) to 0.50 (total casein and a(30)). Pearson correlations between gold standard FAA and these milk processing characteristics were also weak to moderate and ranged from -0.60 (Val and pH) to 0.49 (Val and K-20). Results from this study indicate that mid-infrared spectroscopy has the potential to predict protein fractions and some FAA in milk at a population level

Prediction of bovine milk technological traits from mid-infrared spectroscopy analysis in dairy cows

Rapid, cost-effective monitoring of milk technological traits is a significant challenge for dairy industries specialized in cheese manufacturing. The objective of the present study was to investigate the ability of mid-infrared spectroscopy to predict rennet coagulation time, curd-firming time, curd firmness at 30 and 60\u2005min after rennet addition, heat coagulation time, casein micelle size, and pH in cow milk samples, and to quantify associations between these milk technological traits and conventional milk quality traits. Samples (n\u2005=\u2005713) were collected from 605 cows from multiple herds; the samples represented multiple breeds, stages of lactation, parities, and milking times. Reference analyses were undertaken in accordance with standardized methods, and mid-infrared spectra in the range of 900 to 5,000\u2005cm 121 were available for all samples. Prediction models were developed using partial least squares regression, and prediction accuracy was based on both cross and external validation. The proportion of variance explained by the prediction models in external validation was greatest for pH (71%), followed by rennet coagulation time (55%) and milk heat coagulation time (46%). Models to predict curd firmness 60\u2005min from rennet addition and casein micelle size, however, were poor, explaining only 25 and 13%, respectively, of the total variance in each trait within external validation. On average, all prediction models tended to be unbiased. The linear regression coefficient of the reference value on the predicted value varied from 0.17 (casein micelle size regression model) to 0.83 (pH regression model) but all differed from 1. The ratio performance deviation of 1.07 (casein micelle size prediction model) to 1.79 (pH prediction model) for all prediction models in the external validation was <2, suggesting that none of the prediction models could be used for analytical purposes. With the exception of casein micelle size and curd firmness at 60\u2005min after rennet addition, the developed prediction models may be useful as a screening method, because the concordance correlation coefficient ranged from 0.63 (heat coagulation time prediction model) to 0.84 (pH prediction model) in the external validation

Omega-3 Long-Chain Polyunsaturated Fatty Acids Intake by Ethnicity, Income, and Education Level in the United States: NHANES 2003-201414.

Although there are many recognized health benefits for the consumption of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA), intake in the United States remains below recommended amounts. This analysis was designed to provide an updated assessment of fish and n-3 LCPUFA intake (eicosapentaenoic (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States adult population, based on education, income, and race/ethnicity, using data from the 2003-2014 National Health and Nutrition Examination Survey (NHANES) (n = 44,585). Over this survey period, participants with less education and lower income had significantly lower n-3 LCPUFA intakes and fish intakes (p \u3c 0.001 for all between group comparisons). N-3 LCPUFA intake differed significantly according to ethnicity (p \u3c 0.001), with the highest intake of n-3 LCPUFA and fish in individuals in the Other category (including Asian Americans). Supplement use increased EPA + DHA intake, but only 7.4% of individuals consistently took supplements. Overall, n-3 LCPUFA intake in this study population was low, but our findings indicate that individuals with lower educational attainment and income are at even higher risk of lower n-3 LCPUFA and fish intake

Self-reported adherence to oral cancer therapy: relationships with symptom distress, depression, and personal characteristics

Background: Therapeutic cancer chemotherapy is most successful when complete dosing is achieved. Because many newer therapeutic agents are oral and self-administered by the patient, adherence is a concern. The purpose of our analysis was to explore relationships between adherence, patient characteristics, and barriers to adherence. Methods: This secondary analysis utilized self-reported data from a randomized trial of self-care management conducted at two cancer centers in the US. Symptom distress was measured using the 15-item Symptom Distress Scale (SDS-15) and depression with the Patient Health Questionnaire-9 (PHQ-9). Adherence to oral medication was self-reported using the 8-item Morisky Medication Adherence Scale (MMAS-8). Measures were collected via Web-based, study-specific software ~8 weeks after treatment start date. Odds of low/medium adherence (score <8) were explored using univariate logistic regression. Given the number of factors and possible relationships among factors, a classification tree was built in lieu of a multivariable logistic regression model. Results: Of the eligible participants enrolled, 77 were on oral therapy and 70 had an MMAS score. Forty-nine (70%) reported a high adherence score (=8). Higher odds of low/medium adherence were associated with greater symptom distress (P=0.09), more depression (P=0.05), chemotherapy vs hormonal oral medication (P=0.03), being female (P=0.02), and being randomized to the control group in the parent trial (P=0.09). Conversely, high adherence was associated with working (P=0.08), being married/partnered (P=0.004), and being older (P=0.02). Factors identified as significantly related to low/medium adherence from the univariate logistic regression analyses were supported by the classification tree results. Conclusion: Nonadherence to therapeutic oral medications in patients with cancer was associated with being unmarried/unpartnered, symptom distress, younger age, not working, and female sex. These findings may help to identify patients at risk for nonadherence and for whom supportive interventions to enhance adherence may be needed

Urinary Bisphenol A Concentrations and Implantation Failure among Women Undergoing in Vitro Fertilization

Background: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size. Objective: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). Methods: We used online solid phase extraction–high performance liquid chromatography–isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-hCG < 6 IU/L) 17 days after egg retrieval. Results: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) µg/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06). Conclusion: There was a positive linear dose–response association between BPA urinary concentrations and implantation failure

Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy

Many prostate cancer (PCa) recurrences are thought to be due to reactivation of disseminated tumor cells (DTCs). We previously found a role of the TAM family of receptor tyrosine kinases TYRO3, AXL, and MERTK in PCa dormancy regulation. However, the mechanism and contributions of the individual TAM receptors is largely unknown. Knockdown of MERTK, but not AXL or TYRO3 by shRNA in PCa cells induced a decreased ratio of Pâ Erk1/2 to Pâ p38, increased expression of p27, NR2F1, SOX2, and NANOG, induced higher levels of histone H3K9me3 and H3K27me3, and induced a G1/G0 arrest, all of which are associated with dormancy. Similar effects were also observed with siRNA. Most importantly, knockdown of MERTK in PCa cells increased metastasis free survival in an intraâ cardiac injection mouse xenograft model. MERTK knockdown also failed to inhibit PCa growth in vitro and subcutaneous growth in vivo, which suggests that MERTK has specificity for dormancy regulation or requires a signal from the PCa microenvironment. The effects of MERTK on the cell cycle and histone methylation were reversed by p38 inhibitor SB203580, which indicates the importance of MAP kinases for MERTK dormancy regulation. Overall, this study shows that MERTK stimulates PCa dormancy escape through a MAP kinase dependent mechanism, also involving p27, pluripotency transcription factors, and histone methylation. J. Cell. Biochem. 118: 891â 902, 2017. © 2016 Wiley Periodicals, Inc.Escape from cellular dormancy is the process where previously dormant single disseminated tumor cells reactivate to form cancer microâ metastases, which continue to grow and ultimately make the disease incurable. Here, were show that Mer tyrosine kinase is important for prostate cancer dormancy escape through a mechanism involving MAP kinases, cell cycle inhibitors, epigenetics, and transcription factors associated with pluripotent cells.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136285/1/jcb25768_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136285/2/jcb25768.pd