Plant-based diets benefit aerobic performance and do not compromise strength/power performance: a systematic review and meta-analysis.

Plant-based diets have emerged as athletic performance enhancers for various types of exercise. Therefore, the present study evaluated the effectiveness of plant-based diets on aerobic and strength/power performances, as well as on BMI of physically active individuals. This systematic review and meta-analysis was conducted and reported according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A systematic search of electronic databases, including PubMed, Web of Science and SPORTDiscus, was performed. On the basis of the search and inclusion criteria, four and six studies evaluating the effects of plant-based diets on aerobic and strength/power performances in humans were, respectively, included in the systematic review and meta-analysis. Plant-based diets had a moderate but positive effect on aerobic performance (0·55; 95 % CI 0·29, 0·81) and no effect on strength/power performance (-0·30; 95 % CI -0·67, 0·07). The altogether analyses of both aerobic and strength/power exercises revealed that athletic performance was unchanged (0·01; 95 % CI -0·21, 0·22) in athletes who adopted plant-based diets. However, a small negative effect on BMI (-0·27; 95 % CI -0·40, -0·15) was induced by these diets. The results indicate that plant-based diets have the potential to exclusively assist aerobic performance. On the other hand, these diets do not jeopardise strength/power performance. Overall, the predicted effects of plant-based diets on physical performance are impactless, even though the BMI of their adherents is reduced.

Erythrocyte Membrane Nanomechanical Rigidity Is Decreased in Obese Patients.

This work intends to describe the physical properties of red blood cell (RBC) membranes in obese adults. The hypothesis driving this research is that obesity, in addition to increasing the amount of body fat, will also modify the lipid composition of membranes in cells other than adipocytes. Forty-nine control volunteers (16 male, 33 female, BMI 21.8 ± 5.6 and 21.5 ± 4.2 kg/m2, respectively) and 52 obese subjects (16 male and 36 female, BMI 38.2± 11.0 and 40.7 ± 8.7 kg/m2, respectively) were examined. The two physical techniques applied were atomic force microscopy (AFM) in the force spectroscopy mode, which allows the micromechanical measurement of penetration forces, and fluorescence anisotropy of trimethylammonium diphenylhexatriene (TMA-DPH), which provides information on lipid order at the membrane polar-nonpolar interface. These techniques, in combination with lipidomic studies, revealed a decreased rigidity in the interfacial region of the RBC membranes of obese as compared to control patients, related to parallel changes in lipid composition. Lipidomic data show an increase in the cholesterol/phospholipid mole ratio and a decrease in sphingomyelin contents in obese membranes. ω-3 fatty acids (e.g., docosahexaenoic acid) appear to be less prevalent in obese patient RBCs, and this is the case for both the global fatty acid distribution and for the individual major lipids in the membrane phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Moreover, some ω-6 fatty acids (e.g., arachidonic acid) are increased in obese patient RBCs. The switch from ω-3 to ω-6 lipids in obese subjects could be a major factor explaining the higher interfacial fluidity in obese patient RBC membranes.

Environment affects starch composition and kernel hardness in temperate maize.

BACKGROUND: Protein percentage and kernel weight affect the endosperm hardness of maize grains. However, changes in starch composition could also modify kernel hardness, which is often predicted through milling ratio. The objective of this work was to evaluate the relationship between changes in starch composition and endosperm hardness, and to assess the effects of protein content and kernel weight on that relationship. For this, we used information obtained from three temperate hybrids in multi-environmental experiments, as well as experiments conducted under controlled conditions designed to modify starch composition. Milling ratio was determined as maize kernel hardness predictor in both experiments and it was correlated with grain weight and grain composition. RESULTS: In both experiments, milling ratio presented a significant Spearman correlation coefficient with amylose/starch ratio. Milling ratio was significantly related to the amylose/starch ratio using a simple fit with datasets from different experiments and hybrids. Increases in amylose/starch ratio were associated with increases in milling ratio. CONCLUSION: Starch composition was related to milling ratio variations among hybrids of different aptitude for dry milling through different environments, regardless of protein content. Thus, increases in the amylose/starch ratio were related to increases in the milling ratio. © 2022 Society of Chemical Industry.

Partial and total defoliation during the filling period affected grain industrial and nutraceutical quality in soybean.

BACKGROUND: Little is known about soybean grain chemical composition response to defoliation. The objectives of our study were: (i) to quantify the impact of different levels and timing of defoliation during the filling period on soybean grain yield and grain chemical content and composition, including protein, oil, fatty acids, and isoflavones; and (ii) to establish associations between them and the level and timing of defoliation. RESULTS: Yield and grain chemical components were reduced by defoliation treatments, these effects being more pronounced as defoliation increased. Mild defoliation (33%) caused small or non-significant changes in yield, its components, protein, oil, and isoflavone contents and concentrations. However, it affected oil composition, increasing the degree of unsaturation, which became more accentuated as defoliation increased. Moderate defoliation (66%) produced similar relative reductions in protein and oil contents, with small effects in isoflavone content, resulting in a generally greater isoflavone concentration in defatted flour and a greater isoflavone/protein ratio in grain. Total defoliation (100%) produced greater relative reductions in oil and isoflavone contents than in protein content. These resulted in higher protein/oil ratio and protein concentration and lower isoflavone/protein ratio and isoflavone concentration. Analyzed variables were associated with cumulative solar radiation during grain filling; indeed, this parameter successfully captured the effects of defoliation intensity and timing. CONCLUSION: By exploring different levels and timings of defoliation during the filling period, our study provides novel and important information regarding the impact of light interception decreases on grain chemical components, with special emphasis on nutraceuticals. © 2022 Society of Chemical Industry.

Skin field cancerisation: A systematic review of the literature regarding its treatment.

INTRODUCTION: Skin neoplasms are the most frequent malignant lesions, increasing patient's morbidity when associated with skin field cancerisation. There is a need to understand the current therapies, both clinical and surgical. METHODS: A systematic review was performed according to the PRISMA guideline, registered in PROSPERO: CRD42018114826, including studies from 2012 to 2019. RESULTS: Seven hundred and eighty-two studies were found, of which 21 were included. Of these, 8 primary studies were randomised controlled trials: fractional CO2 laser-assisted photodynamic therapy (PDT) vs. PDT (no significance), daylight PDT vs. PDT (no significance, daylight PDT had less adverse effects), trichloroacetic acid peel vs. 5-aminolaevulinic acid PDT (clinical improvement of aminolaevulinic acid PDT), 5-Fluorouracil 0.5%/Salicylic Acid 10% vs. vehicle (clinical improvement of 5-Fluorouracil 0.5%/Salicylic Acid 10%), photolyase vs. sun filters (no significance), sunscreens vs. sunscreens plus DNA repair enzymes (DNA Repair Enzymes was more effective in reducing field cancerisation). Only one systematic review was included in which there was effectiveness of daylight PDT in the treatment of actinic keratoses. The other 12 included studies had a lower level of evidence including surgical studies. CONCLUSION: Clinical studies are more relevant in the treatment of the field cancerisation. There is a lack of surgical studies.

Leaf structure and ultrastructure changes induced by heat stress and drought during seed filling in field-grown soybean and their relationship with grain yield.

Studies focusing on terminal drought combined with heat impacts on plants of agronomic value remain scarce, and even less under field conditions. The objective of this study was to investigate leaf structural and ultrastructural changes induced by heat stress (HS) and drought stress (DS) during seed filling and their relationship with physiological variables and yield determination. Two soybean cultivars were grown in field conditions. During seed filling four treatments were applied, including a control (without manipulation, at ambient temperature and field capacity), HS (episodes exceeding 32°C for 6 h d-1) during 21-d, DS (20% of field capacity soil water content) during 35-d, and HS×DS. Drought principally reduced leaf area, whereas heat decreased leaf thickness, possible as acclimation strategies, but also irreversible reducing CO2 assimilation sites. Both stresses damaged the outer and inner membranes of chloroplasts, causing swollen chloroplasts and accumulation of plastoglobules, loss of chlorophyll content, and negatively affecting chlorophyll fluorescence. Thus, the performance and integrity of the photosynthetic machinery were reduced. Through a morpho-functional perspective and a holistic multiscale approach, our results provide evidence of photosynthesis impairment and yield drops under stressful conditions which were associated with structural and ultrastructural (particularly at the level of chloroplasts) modifications of leaves.

Implementation of an Affordable Method for MPS Diagnosis from Urine Screening to Enzymatic Confirmation: Results of a Pilot Study in Morocco.

BACKGROUND: Rapid and accurate diagnosis of mucopolysaccharidoses (MPS) is still a challenge due to poor access to screening and diagnostic methods and to their extensive clinical heterogeneity. The aim of this work is to perform laboratory biochemical testing for confirming the diagnosis of mucopolysaccharidosis (MPS) for the first time in Morocco. METHODS: Over a period of twelve months, 88 patients suspected of having Mucopolysaccharidosis (MPS) were referred to our laboratory. Quantitative and qualitative urine glycosaminoglycan (GAG) analyses were performed, and enzyme activity was assayed on dried blood spots (DBS) using fluorogenic substrates. Enzyme activity was measured as normal, low, or undetectable. RESULTS: Of the 88 patients studied, 26 were confirmed to have MPS; 19 MPS I (Hurler syndrome; OMIM #607014/Hurler-Scheie syndrome; OMIM #607015), 2 MPS II (Hunter syndrome; OMIM #309900), 2 MPS IIIA (Sanfilippo syndrome; OMIM #252900), 1 MPS IIIB (Sanfilippo syndrome; OMIM #252920) and 2 MPS VI (Maroteaux-Lamy syndrome; OMIM #253200). Parental consanguinity was present in 80.76% of cases. Qualitative urinary glycosaminoglycan (uGAGs) assays showed abnormal profiles in 31 cases, and further quantitative urinary GAG evaluation and Thin Layer Chromatography (TLC) provided important additional information about the likely MPS diagnosis. The final diagnosis was confirmed by specific enzyme activity analysis in the DBS samples. CONCLUSIONS: The present study shows that the adoption of combined urinary substrate analysis and enzyme assays using dried blood spots can facilitate such diagnosis, offer an important tool for an appropriate supporting care, and a specific therapy, when available.

Usefulness of urinary glycosaminoglycans assay for a mucopolysaccharidosis-specific screening.

BACKGROUND: Mucopolysaccharidoses (MPS), a group of inherited metabolic disorders characterized by the accumulation of glycosaminoglycans, can be diagnosed early through newborn screening programs. Establishing newborn screening in Morocco is a challenging task for multiple economic and social reasons. Screening in a Moroccan population using 1,9-dimethylmethylene blue urinary glycosaminoglycan (GAG) assays may allow for an earlier diagnosis of MPS. We studied the feasibility of implementing screening in Moroccan children as an alternative to national newborn screening. We determined the reference ranges for GAGs in the Moroccan population, their stability during transport, the effectiveness of this test as a screening procedure for MPS in patients, and its use as a screening test for MPS in the Imssouane region, where the rate of consanguineous marriage is 38%. METHODS: Using dimethylmethylene blue assays, urine samples of 47 MPS patients were analyzed, together with urine samples from healthy controls (n = 368, age ranging from 1 month to 25 years), and from Imssouane region children (n = 350, age ranging from 6 months to 24 month). Precision, linearity, recovery, limits, and stability were tested. RESULTS: Urinary GAGs reference values are age and ethnicity dependent. The validation parameters established displayed great precision and accuracy leading to recoveries according to internationally accepted values for bioanalytical methods. Urinary GAGs were stable for a maximum of 7 weeks at 40 °C. Screening of Imssouane children resulted in the detection of a 6-month-old child, diagnosed with MPS I. CONCLUSIONS: Our results demonstrate the usefulness of quantifying glycosaminoglycans for early screening of MPS.

Large miRNA survival analysis reveals a prognostic four-biomarker signature for triple negative breast cancer.

Triple negative breast cancer (TNBC) is currently the only major breast tumor subtype without effective targeted therapy and, as a consequence, usually presents a poor outcome. Due to its more aggressive phenotype, there is an urgent clinical need to identify novel biomarkers that discriminate individuals with poor prognosis. We hypothesize that miRNAs can be used to this end because they are involved in the initiation and progression of tumors by altering the expression of their target genes. To identify a prognostic biomarker in TNBC, we analyzed the miRNA expression of a cohort composed of 185 patients diagnosed with TNBC using penalized Cox regression models. We identified a four-biomarker signature based on miR-221, miR-1305, miR-4708, and RMDN2 expression levels that allowed for the subdivision of TNBC into high- or low-risk groups (Hazard Ratio - HR = 0.32; 95% Confidence Interval - CI = 0.11-0.91; p = 0.03) and are also statistically associated with survival outcome in subgroups of postmenopausal status (HR = 0.19; 95% CI = 0.04-0.90; p= 0.016), node negative status (HR = 0.12; 95% CI = 0.01-1.04; p = 0.026), and tumors larger than 2cm (HR = 0.21; 95% CI = 0.05-0.81; p = 0.021). This four-biomarker signature was significantly associated with TNBC as an independent prognostic factor for survival.

A new metabolic disorder in human cationic amino acid transporter-2 that mimics arginase 1 deficiency in newborn screening.

PURPOSE: We report a patient with a human cationic amino acid transporter 2 (CAT-2) defect discovered due to a suspected arginase 1 deficiency observed in newborn screening (NBS). METHODS: A NBS sample was analyzed using tandem mass spectrometry. Screen results were confirmed by plasma and urine amino acid quantification. Molecular diagnosis was done using clinical exome sequencing. Dimethylated arginines were determined by HPLC and nitrate/nitrite levels by a colorimetric assay. The metabolomic profile was analyzed using 1D nuclear magnetic resonance spectroscopy. RESULTS: A Spanish boy of nonconsanguineous parents had high arginine levels in a NBS blood sample. Plasma and urinary cationic amino acids were high. Arginase enzyme activity in erythrocytes was normal and no pathogenic mutations were identified in the ARG1 gene. Massive parallel sequencing detected two loss-of-function mutations in the SLC7A2 gene. Currently, the child receives a protein-controlled diet of 1.2 g/kg/day with protein-and amino-acid free infant formula, 30 g/day, and is asymptomatic. CONCLUSION: We identified a novel defect in human CAT-2 due to biallelic pathogenic variants in the SLC7A2 gene. The characteristic biochemical profile includes high plasma and urine arginine, ornithine, and lysine levels. NBS centers should know of this disorder since it can be detected in arginase 1 deficiency screening.

Asymmetric dimethylarginine as a potential biomarker for management and follow-up of phenylketonuria.

Phenylketonuria's (PKU) treatment based on low-protein diet may affect other metabolic pathways, such as that of asymmetric dimethylarginine (ADMA). The aim of this study was to evaluate the reliability of ADMA as a biomarker of adequate metabolic control and possible nutritional risk in a long-term PKU patient population. One hundred and six dietary-treated PKU patients from four hospitals in Spain were enrolled in this cross-sectional study. Their lipid profile, total homocysteine, ADMA, and symmetric dimethylarginine (SDMA) concentrations were analyzed and compared with a control group. Sensitivity, specificity, and likelihood ratios of the proposed biomarker were calculated. PKU patients had statistically significant lower plasmatic ADMA, SDMA, and arginine concentrations as compared with the control group (p < 0.001). Significant correlations were found between ADMA, phenylalanine, and total homocysteine levels. The ADMA/creatinine ratio correlated with phenylalanine levels as metabolic control and nutritional risk in PKU patients. Its reliability as a management biomarker was studied with positive results. The ADMA/creatinine ratio might serve as an independent biomarker in the management of PKU patients, different from blood phenylalanine levels. It could be of particular usefulness to detect those who are following an unbalanced diet that could have long-term negative effects.Conclusion: In this study, we have evaluated the reliability of ADMA as a potential biomarker of adequate metabolic control and possible nutritional risk in a long-term PKU patient population. What is Known: • Although PKU individuals have lower values of ADMA even with blood Phe levels in the recommended range, little attention is payed to other metabolic pathways. What is New: • ADMA could be used as new biomarker for PKU management and follow-up of the diet, after evaluating their reliability in a long-term PKU patient population.

Physical-mechanical characterization of two amazon woods coming from the second cutting cycle.

Due to changes in the Amazon forest dynamics after the first cutting cycle, non exploited species become dominant in the forest. The lack of technological knowledge makes it hard to commercialize these woods, making the understanding of their physical-mechanical properties a fundamental step to properly define their applications. This study aimed to characterize physically and mechanically the wood of Pseudopiptadenia psilostachya and Eschweilera ovata from the second cutting cycle of the Tapajós National Forest, intending to commercially promote and to identify usages for them, as well as to evaluate the viability of replacement of highly commercialized species. The tests were performed accordingly to the Brazilian standard NBR 7190. P. psilostachya, presented bulk density of 0.683 g.cm-3, medium levels of shrinkage and anisotropy, as well as medium hardness (7366 N) and high strength on compression parallel to grain (71.63 MPa) and on static bending (103.9 MPa). It was generally superior to Euxylophora paraensis, but inferior when compared to Bagasssa guianensis and Apuleia leiocarpa, with possibilities to replace these three species. E. ovata, on the other hand, presented bulk density of 0.798 g.cm-3, high shrinkage and anisotropy values, but high values for hardness (12089 N) and strength on compression parallel to grain (68.67 MPa) and on static bending (127.1 MPa). This species exhibited, in general, similarities with Mezilaurus itauba, although it is a little inferior in relation to Hymenaea sp. and Astronium lecointei. Both species, P. psilostachya and E. ovata fit in the highest strength class described on the Brazilian Standard NBR7190, C60. By means of the results found, it was concluded that although the species studied were unknown, they presented timber with enough quality to replace some Amazon timber species widely commercialized on both national and international market.

The Dietary Antioxidant Piceatannol Inhibits Adipogenesis of Human Adipose Mesenchymal Stem Cells and Limits Glucose Transport and Lipogenic Activities in Adipocytes.

Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty µM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.

Enterococcus faecalis†pCF10-encoded surface proteins PrgA, PrgB (aggregation substance) and PrgC contribute to plasmid transfer, biofilm formation and virulence.

Enterococcus faecalis pCF10 transfers at high frequencies upon pheromone induction of the prgQ transfer operon. This operon codes for three cell wall-anchored proteins - PrgA, PrgB (aggregation substance) and PrgC - and a type IV secretion system through which the plasmid is delivered to recipient cells. Here, we defined the contributions of the Prg surface proteins to plasmid transfer, biofilm formation and virulence using the Caenorhabditis elegans infection model. We report that a combination of PrgB and extracellular DNA (eDNA), but not PrgA or PrgC, was required for extensive cellular aggregation and pCF10 transfer at wild-type frequencies. In addition to PrgB and eDNA, production of PrgA was necessary for extensive binding of enterococci to abiotic surfaces and development of robust biofilms. However, although PrgB is a known virulence factor in mammalian infection models, we determined that PrgA and PrgC, but not PrgB, were required for efficient killing in the worm infection model. We propose that the pheromone-responsive, conjugative plasmids of E. faecalis have retained Prg-like surface functions over evolutionary time for attachment, colonization and robust biofilm development. In natural settings, these biofilms are polymicrobial in composition and constitute optimal environments for signal exchange, mating pair formation and widespread lateral gene transfer.

Methionine and S-adenosylmethionine levels are critical regulators of PP2A activity modulating lipophagy during steatosis.

BACKGROUND & AIMS: Glycine N-methyltransferase (GNMT) expression is decreased in some patients with severe non-alcoholic fatty liver disease. Gnmt deficiency in mice (Gnmt-KO) results in abnormally elevated serum levels of methionine and its metabolite S-adenosylmethionine (SAMe), and this leads to rapid liver steatosis development. Autophagy plays a critical role in lipid catabolism (lipophagy), and defects in autophagy have been related to liver steatosis development. Since methionine and its metabolite SAMe are well known inactivators of autophagy, we aimed to examine whether high levels of both metabolites could block autophagy-mediated lipid catabolism. METHODS: We examined methionine levels in a cohort of 358 serum samples from steatotic patients. We used hepatocytes cultured with methionine and SAMe, and hepatocytes and livers from Gnmt-KO mice. RESULTS: We detected a significant increase in serum methionine levels in steatotic patients. We observed that autophagy and lipophagy were impaired in hepatocytes cultured with high methionine and SAMe, and that Gnmt-KO livers were characterized by an impairment in autophagy functionality, likely caused by defects at the lysosomal level. Elevated levels of methionine and SAMe activated PP2A by methylation, while blocking PP2A activity restored autophagy flux in Gnmt-KO hepatocytes, and in hepatocytes treated with SAMe and methionine. Finally, normalization of methionine and SAMe levels in Gnmt-KO mice using a methionine deficient diet normalized the methylation capacity, PP2A methylation, autophagy, and ameliorated liver steatosis. CONCLUSIONS: These data suggest that elevated levels of methionine and SAMe can inhibit autophagic catabolism of lipids contributing to liver steatosis.

Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

LC-QTOF-MS-based targeted metabolomics of arginine-creatine metabolic pathway-related compounds in plasma: application to identify potential biomarkers in pediatric chronic kidney disease.

Chronic kidney disease (CKD) is a major epidemiologic problem which causes several disturbances in adults and in pediatrics. Despite being a worldwide public health problem, information available for CKD in the pediatric population is scarce. For that reason, an ion-pair reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method has been developed and validated in order to analyze 16 amino acids, amino acid derivatives, and analogous compounds related to the arginine-creatine metabolic pathway that are suspicious of being increased or decreased in plasma from patients with CKD. The analytical method involved the addition of dithiothreitol, a reducing agent which reduces disulfide and thus giving total aminothiol concentration, as well as a simple precipitation of plasma proteins. Moreover, despite amino acids being usually derivatized to improve their retention time and to enhance their signal, for this method, an ion-pairing reagent was used, thus avoiding the need for derivatization. Subsequently, analysis of plasma from pediatric patients suffering from CKD and control pediatrics was carried out. As a result, glycine, citrulline, creatinine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were significantly increased in patients with CKD, regardless of their creatinine level, whereas in addition to these compounds dimethylglycine was also increased when CKD patients had plasma creatinine concentrations above 12 µg mL(-1), thus all are suggested as potential biomarkers for renal impairment.

Vitamin and mineral status in patients with hyperphenylalaninemia.

Natural sources of protein and some vitamins and minerals are limited in phenylketonuria (PKU) treated patients, who should receive optimal supplementation although this is not yet fully established. We conducted a cross-sectional observational multicenter study including 156 patients with hyperphenylalaninemia. Patients were stratified by age, phenotype, disease detection and type of treatment. Annual median blood phenylalanine (Phe) levels, Phe tolerance, anthropometric measurements, and biochemical parameters (total protein, prealbumin, electrolytes, selenium, zinc, B12, folic acid, ferritin, 25-OH vitamin D) were collected in all patients. 81.4% of patients had biochemical markers out of recommended range but no clinical symptoms. Total protein, calcium, phosphorus, B12, ferritin, and zinc levels were normal in most patients. Prealbumin was reduced in 34.6% of patients (74% with PKU phenotype and 94% below 18 years old), showing almost all (96.3%) an adequate adherence to diet. Selenium was diminished in 25% of patients (95% with PKU phenotype) and also 25-OHD in 14%. Surprisingly, folic acid levels were increased in 39% of patients, 66% with classic PKU. Phosphorus and B12 levels were found diminished in patients with low adherence to diet. Patients under BH4 therapy only showed significant lower levels of B12. This study shows a high percentage of prealbumin and selenium deficiencies as well as an increased level of folic acid in PKU treated patients, which should lead us to assess an adjustment for standards supplements formulated milks.

6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype.

BACKGROUND AND AIMS: Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life. METHODS: We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome. RESULTS: No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration. CONCLUSIONS: Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes.

Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial.

BACKGROUND & AIMS: Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk. METHODS: This was a randomized trial, in which newborns <1500 g and/or <32 weeks gestational age were assigned to one of two groups, based on the milk formula they would receive during the first year of life. Initially, 60 newborns entered the study, but ultimately, group A was composed of 24 newborns, who were given formula milk with an ω-6/ω-3 ratio of 2/1, and Group B was composed of 21 newborns, given formula milk with an ω-6/ω-3 ratio of 1/1. The infants were followed up for two years: growth, visual-evoked potentials, brainstem auditory-evoked potentials, and plasma fatty acids were periodically measured, and psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk. RESULTS: At 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55% vs. 4.55 ± 0.78%), as were polyunsaturated fatty acids (41.02 ± 2.09% vs. 38.08 ± 2.32%) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9 vs. 90.8 ± 11, p =0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9 vs. 100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups. CONCLUSIONS: Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02503020.