Revealing novel biomarkers for diagnosing chronic kidney disease in pediatric patients.

Pediatric chronic kidney disease (CKD) is a clinical condition characterized by progressive renal function deterioration. CKD diagnosis is based on glomerular filtration rate, but its reliability is limited, especially at the early stages. New potential biomarkers (citrulline (CIT), symmetric dimethylarginine (SDMA), S-adenosylmethionine (SAM), n-butyrylcarnitine (nC4), cis-4-decenoylcarnitine, sphingosine-1-phosphate and bilirubin) in addition to creatinine (CNN) have been proposed for early diagnosis. To verify the clinical value of these biomarkers we performed a comprehensive targeted metabolomics study on a representative cohort of CKD and healthy pediatric patients. Sixty-seven children with CKD and forty-five healthy children have been enrolled in the study. Targeted metabolomics based on liquid chromatography-triple quadrupole mass spectrometry has been used for serum and plasma samples analysis. Univariate data analysis showed statistically significant differences (p < 0.05) in the concentration of CNN, CIT, SDMA, and nC4 among healthy and CKD pediatric patients. The predictive ability of the proposed biomarkers was also confirmed through specificity and sensitivity expressed in Receiver Operating Characteristic curves (AUC = 0.909). In the group of early CKD pediatric patients, AUC of 0.831 was obtained, improving the diagnostic reliability of CNN alone. Moreover, the models built on combined CIT, nC4, SDMA, and CNN allowed to distinguish CKD patients from healthy control regardless of blood matrix type (serum or plasma). Our data demonstrate potential biomarkers in the diagnosis of early CKD stages.

Genetic architecture of trait variance in craniofacial morphology.

The genetic architecture of trait variance has long been of interest in genetics and evolution. One of the earliest attempts to understand this architecture was presented in Lerner's Genetic Homeostasis (1954). Lerner proposed that heterozygotes should be better able to tolerate environmental perturbations because of functional differences between the alleles at a given locus, with each allele optimal for slightly different environments. This greater robustness to environmental variance, he argued, would result in smaller trait variance for heterozygotes. The evidence for Lerner's hypothesis has been inconclusive. To address this question using modern genomic methods, we mapped loci associated with differences in trait variance (vQTL) on 1,101 individuals from the F34 of an advanced intercross between LG/J and SM/J mice. We also mapped epistatic interactions for these vQTL in order to understand the influence of epistasis for the architecture of trait variance. We did not find evidence supporting Lerner's hypothesis, that heterozygotes tend to have smaller trait variances than homozygotes. We further show that the effects of most mapped loci on trait variance are produced by epistasis affecting trait means and that those epistatic effects account for about a half of the differences in genotypic-specific trait variances. Finally, we propose a model where the different interactions between the additive and dominance effects of the vQTL and their epistatic partners can explain Lerner's original observations but can also be extended to include other conditions where heterozygotes are not the least variable genotype.

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.

Função reprodutiva em portadoras de hiperplasia adrenal congênita: revisão narrativa da literatura / Reproductive health of patients with congenital adrenal hyperplasia: a narrative review

A hiperplasia adrenal congênita (HAC) pode cursar com redução da fertilidade na mulher. Entretanto, nos casos em que ocorre gestação, os recém-nascidos das por- tadoras de hiperplasia adrenal congênita exibem risco de hiperandrogenismo, com todas as suas consequências. A presente revisão atualiza o tema, considerando também as necessidades da assistência a essas pacientes. A busca identificou 294 artigos na base de dados MEDLINE/PubMed de 1961 a março/2023, e os resultados mostraram que as portadoras de hiperplasia adrenal congênita exibem significativa redução da fertilidade. Nos casos de interesse de gestação, as portadoras de hiper- plasia adrenal congênita devem fazer um planejamento reprodutivo, envolvendo a fase antenatal, o acompanhamento pré-natal especializado, o parto e o aleitamento.

Congenital adrenal hyperplasia may lead to reduced male and female fertility. Mo- reover, when the pregnancy occurs, the newborns of patients with congenital adrenal hyperplasia are at risk of hyperandrogenism with all its consequences. This review updates the theme and emphasizes assistance needs. The search identified 294 ar- ticles in the MEDLINE/PubMed database from 1961 to March/2023, and the results showed that patients with congenital adrenal hyperplasia truly exhibit a significant reduction in fertility. In cases of interest in pregnancy, patients with congenital adre- nal hyperplasia should carry out reproductive planning, involving the antenatal pha- se, specialized prenatal care, till delivery and breastfeeding.

Is physical performance affected by non-steroidal anti-inflammatory drugs use? A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aim to analyze the effects of ingesting non-steroidal anti-inflammatory drugs (NSAIDs) on physical performance, muscle strength, and muscle damage in three different moments: immediately, 24 and 48 h after resistance exercise practice. METHODS: Relevant studies were researched in three databases (PubMed, Web of Science and SPORTDiscus) in April 2023. After excluding duplicates, the decision to include or exclude studies was made by two independent investigators in the following steps: (I) the study title; (II) the study abstract; and (III) the complete study manuscript. The following characteristics were recorded: (I) first author, (II) year of publication, (III) sample size, (IV) method of NSAIDs administration, (V) exercise protocol, and (VI) analyzed variable results. The studies selected were divided into trials that evaluated the effects of NSAIDs ingestion on performance indices of resistance exercise, endurance exercise and resistance training. RESULTS: The meta-analysis, based only on resistance exercises, revealed that both performance and muscle strength were similar between placebo or NSAID treatment immediately and 24 h after resistance exercise practice. An ergolytic effect was found 48 hours after resistance exercise (mean effect size (ES) = -0.42; 95% CI: -0.71, -0.12; p = 0.132), as well as reduced muscle strength (ES = -0.50; 95% CI: -0.83, -0.16; p = 0.072). Additionally, NSAID use did not prevent muscle waste as seen by the unchanged CK plasma concentration at all timetables. CONCLUSION: The data of the present meta-analysis indicate that NSAID use is ineffective in improving resistance performance and muscle strength, as well as exercise recovery. When considering the practical application of using NSAIDs to improve exercise capacity and strength gains, the present data supports that consumption of analgesic drugs as an endurance performance enhancer or as a muscle anabolic must not be recommended.

Overview of SARS-COV-2 infection at the Butantan Penitentiary Progression Center.

OBJECTIVE: To estimate the prevalence of exposure to the SARS-CoV-2 virus among individuals living in restricted freedom. METHODS: A seroprevalence survey was carried out with the population of the female penitentiary of the Centro de Progressão Penitenciária (CPP) in Butantan (municipality of São Paulo), between June 24 and August 20, 2020. During this period, according to the Secretariat of Penitentiary Administration (SAP), the positivity of rapid tests among inmates ranged from 65% to 78%. The evaluation method used in the study was the "One Step COVID-19" rapid test (chromatography), from the company Wondfo, also using the RT-PCR method in symptomatic participants to confirm the viral condition. The study population consisted of 879 female inmates and 170 employees of the institution. RESULTS: The prevalence of total antibodies (IgG/IgM) against the SARS-CoV-2 virus in the total population of 1049 study participants was 6.1%; among the population of 879 inmates,a prevalence of 5.8% was observed, and among the institution's employees, 7.5%. CONCLUSIONS: The prevalence of covid-19 at the Butantan CPP was low, which is due to the implementation of simple prevention measures at the institution, such as the use of masks (with appropriate changes), emphasis on hygiene, hand washing and social distancing, in addition to other strategies, such as suspending inmates' visits from relatives and friends and cutting back on elective medical appointments and outside work.

Overview of SARS-COV-2 infection at the butantan penitentiary progression center

OBJECTIVE: To estimate the prevalence of exposure to the SARS-CoV-2 virus among individuals living in restricted freedom. METHODS: A seroprevalence survey was carried out with the population of the female penitentiary of the Centro de Progressão Penitenciária (CPP) in Butantan (municipality of São Paulo), between June 24 and August 20, 2020. During this period, according to the Secretariat of Penitentiary Administration (SAP), the positivity of rapid tests among inmates ranged from 65% to 78%. The evaluation method used in the study was the “One Step COVID-19” rapid test (chromatography), from the company Wondfo, also using the RT-PCR method in symptomatic participants to confirm the viral condition. The study population consisted of 879 female inmates and 170 employees of the institution. RESULTS: The prevalence of total antibodies (IgG/IgM) against the SARS-CoV-2 virus in the total population of 1049 study participants was 6.1%; among the population of 879 inmates, a prevalence of 5.8% was observed, and among the institution’s employees, 7.5%. CONCLUSIONS: The prevalence of covid-19 at the Butantan CPP was low, which is due to the implementation of simple prevention measures at the institution, such as the use of masks (with appropriate changes), emphasis on hygiene, hand washing and social distancing, in addition to other strategies, such as suspending inmates’ visits from relatives and friends and cutting back on elective medical appointments and outside work.

Overview of SARS-COV-2 infection at the Butantan Penitentiary Progression Center / Panorama da infecção pelo SARS-COV-2 no Centro de Progressão Penitenciária do Butantan

ABSTRACT OBJECTIVE To estimate the prevalence of exposure to the SARS-CoV-2 virus among individuals living in restricted freedom. METHODS A seroprevalence survey was carried out with the population of the female penitentiary of the Centro de Progressão Penitenciária (CPP) in Butantan (municipality of São Paulo), between June 24 and August 20, 2020. During this period, according to the Secretariat of Penitentiary Administration (SAP), the positivity of rapid tests among inmates ranged from 65% to 78%. The evaluation method used in the study was the "One Step COVID-19" rapid test (chromatography), from the company Wondfo, also using the RT-PCR method in symptomatic participants to confirm the viral condition. The study population consisted of 879 female inmates and 170 employees of the institution. RESULTS The prevalence of total antibodies (IgG/IgM) against the SARS-CoV-2 virus in the total population of 1049 study participants was 6.1%; among the population of 879 inmates,a prevalence of 5.8% was observed, and among the institution's employees, 7.5%. CONCLUSIONS The prevalence of covid-19 at the Butantan CPP was low, which is due to the implementation of simple prevention measures at the institution, such as the use of masks (with appropriate changes), emphasis on hygiene, hand washing and social distancing, in addition to other strategies, such as suspending inmates' visits from relatives and friends and cutting back on elective medical appointments and outside work.

RESUMO OBJETIVO Estimar a prevalência da exposição ao vírus SARS-CoV-2 entre indivíduos vivendo em restrição de liberdade. MÉTODOS Foi realizado inquérito de soroprevalência com a população da penitenciária feminina do Centro de Progressão Penitenciária (CPP) do Butantan (município de São Paulo), entre 24 de junho e 20 de agosto de 2020. Nesse período, segundo a Secretaria de Administração Penitenciária (SAP), a positividade dos testes rápidos entre detentos variou de 65 a 78%. O método de avaliação utilizado no estudo foi o teste rápido "One Step COVID-19" (cromatografia), da empresa Wondfo, empregando-se também o método RT-PCR em participantes sintomáticos para confirmação do quadro viral. A população do estudo foi constituída por 879 reeducandas e 170 funcionários da instituição. RESULTADOS A prevalência de anticorpos totais (IgG/IgM) contra o vírus SARS-CoV-2 na população total de 1.049 participantes do estudo foi de 6,1%; entre a população de 879 reeducandas foi observada prevalência de 5,8% e entre os servidores da instituição, 7,5%. CONCLUSÃO Houve baixa prevalência de covid-19 no CPP do Butantan, o que se deve à implementação de medidas de prevenção simples na instituição, como o uso de máscaras (com trocas adequadas), ênfase na higiene, lavagem das mãos e distanciamento social, além de outras estratégias, como suspensão de visitas de familiares e amigos das reeducandas, cortes de consultas médicas eletivas e do trabalho externo.

Randomized Clinical Trial: Effects of ß-Hydroxy-ß-Methylbutyrate (HMB)-Enriched vs. HMB-Free Oral Nutritional Supplementation in Malnourished Cirrhotic Patients.

ß-Hydroxy-ß-methylbutyrate (HMB) supplementation increases muscle and strength mass in some muscle-wasting disorders. Malnutrition and sarcopenia are often present in liver cirrhosis. We aimed to investigate the effects of oral HMB supplementation on changes in body composition and liver status in patients with cirrhosis and malnutrition. In a randomized, controlled, double-blind trial, 43 individuals were randomized to receive twice a day and for 12 weeks an oral nutritional supplement (ONS) enriched with 1.5 g of calcium HMB per bottle or another supplement with similar composition devoid of HMB. Inclusion criteria were liver cirrhosis with at least one previous decompensation and clinical malnutrition. Liver function, plasma biochemistry analyses, and physical condition assessment were carried out at baseline, then after six and 12 weeks of supplementation. A total of 34 patients completed the clinical trial. An improvement in liver function and an increase in fat mass index were observed in both groups. None of the two ONS changed the fat-free mass. However, we observed an upward trend in handgrip strength and a downward trend in minimal hepatic encephalopathy in the HMB group. At the end of the trial and regardless of the supplement administered, fat mass content increased with no change in fat-free mass, while liver function scores and nutritional analytic markers also improved.

Genome-wide promoter methylation profiling in a cellular model of melanoma progression reveals markers of malignancy and metastasis that predict melanoma survival.

The epigenetic changes associated with melanoma progression to advanced and metastatic stages are still poorly understood. To shed light on the CpG methylation dynamics during melanoma development, we analyzed the methylome profiles of a four-stage cell line model of melanoma progression: non-tumorigenic melanocytes (melan-a), premalignant melanocytes (4C), non-metastatic melanoma cells (4C11-), and metastatic melanoma cells (4C11+). We identified 540 hypo- and 37 hypermethylated gene promoters that together characterized a malignancy signature, and 646 hypo- and 520 hypermethylated promoters that distinguished a metastasis signature. Differentially methylated genes from these signatures were correlated with overall survival using TCGA-SKCM methylation data. Moreover, multivariate Cox analyses with LASSO regularization identified panels of 33 and 31 CpGs, respectively, from the malignancy and metastasis signatures that predicted poor survival. We found a concordant relationship between DNA methylation and transcriptional levels for genes from the malignancy (Pyroxd2 and Ptgfrn) and metastasis (Arnt2, Igfbp4 and Ptprf) signatures, which were both also correlated with melanoma prognosis. Altogether, this study reveals novel CpGs methylation markers associated with malignancy and metastasis that collectively could improve the survival prediction of melanoma patients.

Climate change linked to functional homogenization of a subtropical estuarine system.

Climate change causes marine species to shift and expand their distributions, often leading to changes in species diversity. While increased biodiversity is often assumed to confer positive benefits on ecosystem functioning, many examples have shown that the relationship is specific to the ecosystem and function studied and is often driven by functional composition and diversity. In the northwestern Gulf of Mexico, tropical species expansion was shown to have increased estuarine fish and invertebrate diversity; however, it is not yet known how those increases have affected functional diversity. To address this knowledge gap, two metrics of functional diversity, functional richness (FRic) and functional dispersion (FDis), were estimated in each year for a 38-year study period, for each of the eight major bays along the Texas coast. Then, the community-weighted mean (CWM) trait values for each of the functional traits are calculated to assess how functional composition has changed through time. Finally, principal component analysis (PCA) was used to identify species contributing most to changing functional diversity. We found significant increases in log-functional richness in both spring and fall, and significant decreases in functional dispersion in spring, suggesting that although new functional types are entering the bays, assemblages are becoming more dominated by similar functional types. Community-weighted trait means showed significant increases in the relative abundance of traits associated with large, long-lived, higher trophic level species, suggesting an increase in periodic and equilibrium life-history strategists within the bays. PCA identified mainly native sciaenid species as contributing most to functional diversity trends although several tropical species also show increasing trends through time. We conclude that the climate-driven species expansion in the northwestern Gulf of Mexico led to a decrease in functional dispersion due to increasing relative abundance of species with similar life-history characteristics, and thus the communities have become more functionally homogeneous.

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.

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.

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.

Relating multivariate shapes to genescapes using phenotype-biological process associations for craniofacial shape.

Realistic mappings of genes to morphology are inherently multivariate on both sides of the equation. The importance of coordinated gene effects on morphological phenotypes is clear from the intertwining of gene actions in signaling pathways, gene regulatory networks, and developmental processes underlying the development of shape and size. Yet, current approaches tend to focus on identifying and localizing the effects of individual genes and rarely leverage the information content of high-dimensional phenotypes. Here, we explicitly model the joint effects of biologically coherent collections of genes on a multivariate trait - craniofacial shape - in a sample of n = 1145 mice from the Diversity Outbred (DO) experimental line. We use biological process Gene Ontology (GO) annotations to select skeletal and facial development gene sets and solve for the axis of shape variation that maximally covaries with gene set marker variation. We use our process-centered, multivariate genotype-phenotype (process MGP) approach to determine the overall contributions to craniofacial variation of genes involved in relevant processes and how variation in different processes corresponds to multivariate axes of shape variation. Further, we compare the directions of effect in phenotype space of mutations to the primary axis of shape variation associated with broader pathways within which they are thought to function. Finally, we leverage the relationship between mutational and pathway-level effects to predict phenotypic effects beyond craniofacial shape in specific mutants. We also introduce an online application that provides users the means to customize their own process-centered craniofacial shape analyses in the DO. The process-centered approach is generally applicable to any continuously varying phenotype and thus has wide-reaching implications for complex trait genetics.

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.

Urine Phenylacetylglutamine Determination in Patients with Hyperphenylalaninemia.

Phenylketonuria (PKU), an autosomal-recessive inborn error of phenylalanine (Phe) metabolism is the most prevalent disorder of amino acid metabolism. Currently, clinical follow-up relies on frequent monitoring of Phe levels in blood. We hypothesize that the urine level of phenylacetylglutamine (PAG), a phenyl-group marker, could be used as a non-invasive biomarker. In this cross-sectional study, a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS) method was used for urinary PAG quantification in 35 participants with hyperphenylalaninemia (HPA) and 33 age- and sex-matched healthy controls. We have found that (a) PKU patients present higher urine PAG levels than healthy control subjects, and that (b) there is a significant correlation between urine PAG and circulating Phe levels in patients with HPA. In addition, we show a significant strong correlation between Phe levels from venous blood samples and from capillary finger-prick dried blood spot (DBS) samples collected at the same time in patients with HPA. Further research in order to assess the potential role of urine PAG as a non-invasive biomarker in PKU is warranted.

Treatment adherence in tyrosinemia type 1 patients.

BACKGROUND: While therapeutic advances have significantly improved the prognosis of patients with hereditary tyrosinemia type 1 (HT1), adherence to dietary and pharmacological treatments is essential for an optimal clinical outcome. Poor treatment adherence is well documented among patients with chronic diseases, but data from HT1 patients are scarce. This study evaluated pharmacological and dietary adherence in HT1 patients both directly, by quantifying blood levels nitisinone (NTBC) levels and metabolic biomarkers of HT1 [tyrosine (Tyr), phenylalanine (Phe), and succinylacetone]; and indirectly, by analyzing NTBC prescriptions from hospital pharmacies and via clinical interviews including the Haynes-Sackett (or self-compliance) test and the adapted Battle test of patient knowledge of the disease. RESULTS: This observational study analyzed data collected over 4 years from 69 HT1 patients (7 adults and 62 children; age range, 7 months-35 years) who were treated with NTBC and a low-Tyr, low-Phe diet. Adherence to both pharmacological and, in particular, dietary treatment was poor. Annual data showed that NTBC levels were lower than recommended in more than one third of patients, and that initial Tyr levels were high (> 400 µM) in 54.2-64.4% of patients and exceeded 750 µM in 25.8% of them. Remarkably, annual normalization of NTBC levels was observed in 29.4-57.9% of patients for whom serial NTBC determinations were performed. Poor adherence to dietary treatment was more refractory to positive reinforcement: 36.2% of patients in the group who underwent multiple analyses per year maintained high Tyr levels during the entire study period, and, when considering each of the years individually this percentage ranged from 75 to 100% of them. Indirect methods revealed percentages of non-adherent patients of 7.3 and 15.9% (adapted Battle and Haynes tests, respectively). CONCLUSIONS: Despite initially poor adherence to pharmacological and especially dietary treatment among HT1 patients, positive reinforcement at medical consultations resulted in a marked improvement in NTBC levels, indicating the importance of systematic positive reinforcement at medical visits.

Análise da agressividade docente na cena pedagógica: implicações para a formação de professoras(es) / Teachers' aggressiveness analysis at pedagogical scene: implications for teachers' training / Análisis de la agresividad docente en la escena pedagógica: implicaciones para la formación

A partir da teoria psicanalítica laplancheana e winnicottiana da agressividade, objetivou-se analisar a agressividade de uma docente e seus efeitos na cena pedagógica através do estudo de caso de uma professora da Educação Infantil. Numa pesquisa qualitativa, recorrendo à triangulação entre observação, entrevista e grupo focal, tomou-se como unidade de análise a cena pedagógica (definida como o conjunto de interações entre docentes e discentes e dos significados intersubjetivos dessas interações nos vínculos envolvendo esses sujeitos). Constataram-se condutas docentes agressivas na interação com alunos da turma, o que levou à hipótese de que as dificuldades subjetivas da professora em lidar com a própria agressividade interferiam no manejo da agressividade discente. Considerando a subjetividade da docente, a participação da professora em formação docente continuada promovida durante a pesquisa viabilizou a tomada de consciência de novos arranjos relacionais entre a professora e as crianças de sua turma, favorecendo a qualidade do seu manejo.

From Laplanche's and Winnicott's psychoanalytic theories of aggressiveness, it was aimed to analyse the aggressiveness of a teacher and its effects on the pedagogical scene, through a case study about an Early Childhood Education teacher. In a qualitative research, resorting data triangulation between observation, interview and focus group, it was taken, as an analytical unit, the pedagogical scene (defined as the set of interactions between teachers and students, and the intersubjective meanings os these interactions considering the ties involving these subjects). Teacher's aggressive conducts were found on the interactions with her students, leading to the hypotheses: teacher's subjective difficulty in dealing with her own aggressiveness interfered on her management of students' aggressiveness. Considering the teacher's subjectivity, her participation on a teachers' continued qualification, promoted during the research, enabled the awareness of new relational arrangements between her and the children, favouring the quality of her management.

Basándose en la teoría psicoanalítica laplancheana y winnicottiana de la violencia, el objetivo fue analizar la agresividad de una docente y sus efectos en el escenario pedagógico, a través del estudio de caso de una maestra de Educación Infantil. En una investigación cualitativa, utilizando la triangulación entre observación, entrevista y grupo focal, se consideró como unidad de análisis el escenario pedagógico (definido como el conjunto de interacciones entre docentes y estudiantes, y los significados intersubjetivos de estas interacciones en los vínculos que se relacionan con estos sujetos). Se verificaron las conductas de maestros agresivos en la interacción con los estudiantes en la clase, lo que resultó llegar a la hipótesis de que las dificultades subjetivas de la docente para retener su propia violencia interferían en el manejo de la agresividad de los estudiantes. Respecto a la subjetividad del docente, la participación de la docente en la formación continua del profesorado promovida durante la investigación posibilitó la toma de conciencia de nuevos arreglos relacionales entre el docente y los niños de su clase, que favoreció la calidad de su estrategia de retención de la violencia.

Therapeutics of xeroderma pigmentosum: A PRISMA-compliant systematic review.

Xeroderma pigmentosum is a rare hereditary autosomal recessive genodermatosis. At present, there are many treatment options for xeroderma pigmentosum, covering medical/procedural, surgical and combined modalities. However, the quality of these interventions has not been assessed. Our study aimed to perform a systematic review of the literature regarding the treatment of xeroderma pigmentosum. Multiple medical databases were accessed with the Medical Subject Headings terms; "xeroderma pigmentosum," "therapeutics" and "surgical procedures, operative" from January 2000 to April 2019, including articles published in Portuguese, Spanish and English (PROSPERO-CRD42018114858). Two hundred and ninety-eight studies were found in the databases researched, of which, after applying the inclusion criteria, only 33 studies remained. The 33 complete articles were read by three of the authors, having been found: 16 reported medical/procedural and 17 reported surgical treatments. Only one clinical study presented a good level of evidence (EL: 2): a randomized clinical trial using a T4 endonuclease V (T4N5) liposome lotion which reduced the development of skin lesions in patients with xeroderma pigmentosum. Amongst surgical modalities, all studies presented low evidence level (EL: 4). Three illustrative cases are also presented, to emphasize the multiple number of times that surgical modalities may be required in these patients. The therapeutic modalities, both clinical and surgical, for xeroderma pigmentosum presented a low level of scientific evidence which did not allow meta-analysis. More therapeutic studies, both clinical and surgical, with better scientific evidence are needed.