Muscle and Bone Health in Young Chilean Adults with Phenylketonuria and Different Degrees of Compliance with the Phenylalanine Restricted Diet.

There are concerns about muscle and bone health in patients with Phenylketonuria (PKU). Our aim was to compare muscle mass, function, and bone health among young adults with PKU who maintained or suspended dietary treatment. METHODS: Three groups were considered-PKU-1: 10 patients who used a protein substitute (PS) without phenylalanine (Phe); PKU-2: 14 patients who used the PS without Phe until eighteen years old and then practiced mostly a vegan diet; and 24 matched healthy controls. A 24 h recall survey, blood parameters, body composition and bone mineral density through DEXA, rectus femoris thickness by ultrasound, hand grip strength, submaximal exercise test, and walking speed were assessed. RESULTS: PKU-1 patients had lower hand grip strength than their matched controls, but no other differences. Compared to controls, the PKU-2 group had lower fat-free mass (p = 0.01), less spine and femoral bone mineral density (p = 0.04 and p < 0.01, respectively), and peak workload on the incremental test (p = 0.03). When comparing PKU groups, blood Phe levels were significantly lower in the PKU-1 group (p = 0.02). CONCLUSIONS: Among PKU patients, abandoning the dietary treatment and maintaining high blood Phe concentrations could be deleterious for muscles and bones. However, we cannot discard other causes of bone and muscle damage in these patients.

Risk of Developing Insulin Resistance in Adult Subjects with Phenylketonuria: Machine Learning Model Reveals an Association with Phenylalanine Concentrations in Dried Blood Spots.

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism where high phenylalanine (Phe) concentrations cause irreversible intellectual disability that can be prevented by newborn screening and early treatment. Evidence suggests that PKU subjects not adherent to treatment could be at risk of insulin resistance (IR). We studied how Phe concentrations (PheCs) relate to IR using machine learning (ML) and derived potential biomarkers. In our cross-sectional study, we analyzed subjects with neonatal diagnoses of PKU, grouped as follows: 10 subjects who adhered to treatment (G1); 14 subjects who suspended treatment (G2); and 24 control subjects (G3). We analyzed plasma biochemical variables, as well as profiles of amino acids and acylcarnitines in dried blood spots (DBSs). Higher PheCs and plasma insulin levels were observed in the G2 group compared to the other groups. Additionally, a positive correlation between the PheCs and homeostatic measurement assessments (HOMA-IRs) was found, as well as a negative correlation between the HOMA-Sensitivity (%) and quantitative insulin sensitivity check index (QUICKI) scores. An ML model was then trained to predict abnormal HOMA-IRs using the panel of metabolites measured from DBSs. Notably, ranking the features' importance placed PheCs as the second most important feature after BMI for predicting abnormal HOMA-IRs. Our results indicate that low adherence to PKU treatment could affect insulin signaling, decrease glucose utilization, and lead to IR.

Calidad microbiológica: detección de Aeromonas sp y Pseudomonas sp en garrafones provenientes de pequeñas plantas purificadoras de agua / Microbiological quality: detection of Aeromonas sp and Pseudomonas sp in jugs from small water purification establishments

RESUMEN Las plantas purificadoras de agua que carecen de un adecuado sistema de control de calidad pueden generar problemas de salud pública. El objetivo de este estudio fue examinar la calidad microbiológica del agua proveniente de pequeñas plantas purificadoras de la ciudad de Puebla, así como, determinar la existencia de bacterias Aeromonas sp y Pseudomonas sp, y caracterizar si presentan un fenotipo patógeno oportunista. Se recolectaron 70 muestras de garrafones de agua de 25 establecimientos. La cuantificación bacteriana se realizó mediante el método de goteo en placa. Se comprobaron los géneros microbianos mediante análisis bioquímico. En las cepas que mostraron discrepancia se utilizó la identificación molecular con base a secuencias parciales del gen 16S rRNA para confirmar su especie y se les evaluaron sus características de patogenicidad: multirresistencia a antibióticos, producción de biopelícula y actividad hemolítica. El 40 % de las plantas purificadoras no cumplieron con la calidad microbiológica del agua para consumo humano. El 41.4 % de los garrafones de agua muestreados incumplió la normativa, presentando coliformes totales 35.7 %, Pseudomonas 30 %, Enterococcus faecalis 8.6 % y bacterias coliformes fecales el 5.7 %. Se obtuvieron 56 aislados, provenientes de los 29 garrafones contaminados; 10 de ellos se caracterizaron molecularmente, resultando 7 aislados relacionados con especies diferentes de P. aeruginosa y 3 con especies de Aeromonas. De los aislados de Pseudomonas, 5 presentaron resistencia a 2 familias de antibióticos y 2 mostraron multirresistencia. El 36 % de los 10 aislados produjeron hemólisis y biopelícula. Dos cepas de Aeromonas mostraron resistencia a Cefalosporina 3a generación pero no produjeron hemólisis. Los 10 aislados analizados fueron clasificados como no patógenos. Es necesario un seguimiento sanitario más estricto para lograr el cumplimiento de las normas nacionales e internacionales relacionadas con el consumo de agua purificada, para evitar dañar la salud de los consumidores.

ABSTRACT Water purification establishments that lack an adequate quality control system can cause public health problems. The objective of this study was to examine the microbiological quality of water from small purification establishments in the city of Puebla, as well as to determine the existence of Aeromonas sp and Pseudomonas sp bacteria, and to characterize whether they present an opportunistic pathogenic phenotype. 70 water jug samples were collected from 25 establishments. Bacterial quantification was performed using the drop plate method. Microbial genera were determined by biochemical analysis using the standard methodology. In the strains that showed discrepancy, molecular identification based on partial sequences of the 16S rRNA gene was used to confirm their species, and their pathogenic characteristics were evaluated: multiresistance to antibiotics, biofilm production, and hemolytic activity. The results showed that 40 % of the purification establishments did not comply with the microbiological quality of water for human consumption. Similarly, 41.4 % of the jugs of water sampled failed to comply with the regulations, presenting total coliforms 35.7 %, Pseudomonas 30 %, Enterococcus faecalis 8.6 % and fecal coliform bacteria 5.7 %. Likewise, 56 isolates were obtained from the 29 contaminated jugs, of which 10 were molecularly characterized, resulting in 4 different species for P. aeruginosa and 3 for Aeromonas. Of the 7 Pseudomonas isolates, 5 presented resistance to 2 families of antibiotics and 2 showed multiresistance. In total, 36 % of the 10 isolates produced hemolysis and biofilm. Two Aeromonas strains showed resistance to 3rd generation Cephalosporin but did not produce hemolysis. The 10 isolates analyzed were classified as non-pathogenic. A stricter sanitary monitoring is necessary to achieve compliance with national and international standards related to the consumption of purified water, to avoid harming the health of consumers.

Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway.

Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients. We included 33 TT1 patients (mean age 11.24 years; 16 male), 31 PKU patients (mean age 10.84; 14 male), and 58 age- and gender-matched healthy controls (mean age 10.82 years; 29 male). IQ (Wechsler-subtests), executive functioning (the Behavioral Rating Inventory of Executive Functioning), mental health (the Achenbach-scales), and social functioning (the Social Skills Rating System) were assessed. Results of TT1 patients, PKU patients, and healthy controls were compared using Kruskal-Wallis tests with post-hoc Mann-Whitney U tests. TT1 patients showed a lower IQ and poorer executive functioning, mental health, and social functioning compared to healthy controls and PKU patients. PKU patients did not differ from healthy controls regarding these outcome measures. Relatively poor outcomes for TT1 patients were particularly evident for verbal IQ, BRIEF dimensions "working memory", "plan and organize" and "monitor", ASEBA dimensions "social problems" and "attention problems", and for the SSRS "assertiveness" scale (all p values <0.001). To conclude, TT1 patients showed cognitive impairments on all domains studied, and appeared to be significantly more affected than PKU patients. More attention should be paid to investigating and monitoring neurocognitive outcome in TT1 and research should focus on explaining the underlying pathophysiological mechanism.

Crononutrición y su relación con la obesidad: Una revisión sistemática

RESUMEN Introducción: A través del reloj central y de los relojes periféricos que se encuentran en un organismo, se regula el ritmo circadiano (RC), el cual interviene en las funciones metabólicas y endocrinas. La "crononutrición" explica la importancia del tiempo y los tipos de alimentación sobre nuestro RC. La obesidad es uno de los mayores problemas de salud pública. Objetivo: Describir la relación que existe entre la crononutrición y la obesidad. Métodos: Revisión sistemática; búsqueda en PubMed, Cochrane Library, Scielo y Medline, entre los años 2014 a 2019, sólo en humanos. Se obtuvieron 19 artículos y de ellos sólo 4 artículos cumplieron con los criterios de inclusión. Resultados: Se observó que valores de Índice de Masa Corporal (IMC) y circunferencia de cintura (CC) eran mayores en personas que no desayunaban y que cenaban con menos de 3 hrs antes de dormir. Se obtuvo que en niños de 4 años con ingestas energética mayores en almuerzo y cena, presentaban mayor probabilidad de sobrepeso u obesidad a los 7 años y además, no desayunar y cenar tardíamente se asoció negativamente con el peso corporal. En otro estudio, se observó que los adolescentes que realizaban sus comidas principales en horarios tardíos, hubo una asociación con el aumento en el IMC y CC. En sujetos con peso normal, independiente de si comían con tendencia hacia la mañana o la noche, pero presentaban una sincronía en su RC, no sufrían mayores alteraciones en su peso, lo cual no sucedió en sujetos con exceso de peso. Conclusiones: Una alimentación no sincronizada con el RC, puede aumentar la probabilidad de desarrollar obesidad en el mediano y largo plazo. Sin embargo, aún se necesita mayor evidencia.

Abstract Introduction: The circadian rhythm is responsible for regulating important metabolic and endocrine functions. "Chrononutrition" explains the importance of time and types of food based on circadian rhythm. Obesity is one of the biggest public health problems. Objective: To describe the relation between chrono-nutrition and obesity. Methods: A systematic review was performed using PubMed, Scielo and Medline databases of articles published between 2014 to 2019 in humans. Nineteen articles were obtained and four articles met inclusion criteria. Results: Higher Body Mass Index (BMI) and weight circumference (WC) values were observed in people who skipped breakfast and ate less than 3 hours before bed. Children 4 years of age with higher energy intakes at lunch and dinner were more likely to be overweight or obese at 7 years. Skipping breakfast and eating dinner later was negatively associated with body weight. Among adolescents, eating main meals late was associated with an increase in BMI and WC. In normal weight subjects, regardless of whether they ate early or late, if eating was aligned with their circadian rhythm, they did not suffer major changes in weight. This was not the case for subjects with excess weight. Conclusions: A diet not aligned with the circadian rhythm, may increase the probability of generating obesity in the medium and long term. However, evidence is still needed.

Advances and Challenges in Classical Galactosemia. Pathophysiology and Treatment

Abstract Classical galactosemia is caused by the genetic deficiency of galactose-1-phosphate-urydyl-transferase resulting in clinical symptoms development during the first weeks of life including jaundice, hypotonia, lethargy, emesis, hepatomegaly, among others. Currently, dietary restriction of galactose is considered the standard for classical galactosemia management. For several years, severe dietary galactose restriction was considered necessary, implying restriction not only of dairy products, but also fruits, vegetables, legumes, and viscera. Such management failed to improve or prevent the appearance of long-term complications, by contrast, such restrictive approach may lead to nutritional deficiencies development. Thus, the last consensus suggests guidelines that are more flexible. In addition, the lack of knowledge regarding the physiopathology of the disease, and the toxicity threshold of the metabolites accumulated, make even more difficult to propose novel and more effective therapeutic approaches. This review summarizes the current state of knowledge regarding classical galactosemia in terms of physiopathology, long-term complications, newborn screening and genetic variants and their implications on galactosemia treatment, summed to the challenges that researchers working on this disease must address in future studies including the analysis of galactose content in foods, galactose tolerance threshold and search for novel therapeutic targets.

NTBC Treatment Monitoring in Chilean Patients with Tyrosinemia Type 1 and Its Association with Biochemical Parameters and Liver Biomarkers.

Treatment and follow-up in Hereditary Tyrosinemia type 1 (HT-1) patients require comprehensive clinical and dietary management, which involves drug therapy with NTBC and the laboratory monitoring of parameters, including NTBC levels, succinylacetone (SA), amino acids, and various biomarkers of liver and kidney function. Good adherence to treatment and optimal adjustment of the NTBC dose, according to clinical manifestations and laboratory parameters, can prevent severe liver complications such as hepatocarcinogenesis (HCC). We analyzed several laboratory parameters for 15 HT-1 patients over one year of follow-up in a cohort that included long-term NTBC-treated patients (more than 20 years), as well as short-term patients (one year). Based on this analysis, we described the overall adherence by our cohort of 70% adherence to drug and dietary treatment. A positive correlation was found between blood and plasma NTBC concentration with a conversion factor of 2.57. Nonetheless, there was no correlation of the NTBC level with SA levels, αFP, liver biomarkers, and amino acids in paired samples analysis. By separating according to the range of the NTBC concentration, we therefore determined the mean concentration of each biochemical marker, for NTBC ranges above 15-25 µmol/L. SA in urine and αFP showed mean levels within controlled parameters in our group of patients. Future studies analyzing a longer follow-up period, as well as SA determination in the blood, are encouraged to confirm the present findings.

Chromosome Number, Ploidy Level, and Nuclear DNA Content in 23 Species of Echeveria (Crassulaceae).

Echeveria is a polyploid genus with a wide diversity of species and morphologies. The number of species registered for Echeveria is approximately 170; many of them are native to Mexico. This genus is of special interest in cytogenetic research because it has a variety of chromosome numbers and ploidy levels. Additionally, there are no studies concerning nuclear DNA content and the extent of endopolyploidy. This work aims to investigate the cytogenetic characteristics of 23 species of Echeveria collected in 9 states of Mexico, analyzing 2n chromosome numbers, ploidy level, nuclear DNA content, and endopolyploidy levels. Chromosome numbers were obtained from root tips. DNA content was obtained from the leaf parenchyma, which was processed according to the two-step protocol with Otto solutions and propidium iodide as fluorochrome, and then analyzed by flow cytometry. From the 23 species of Echeveria analyzed, 16 species lacked previous reports of 2n chromosome numbers. The 2n chromosome numbers found and analyzed in this research for Echeveria species ranged from 24 to 270. The range of 2C nuclear DNA amounts ranged from 1.26 pg in E. catorce to 7.70 pg in E. roseiflora, while the 1C values were 616 Mbp and 753 Mbp, respectively, for the same species. However, differences in the level of endopolyploidy nuclei were found, corresponding to 4 endocycles (8C, 16C, 32C and 64C) in E. olivacea, E. catorce, E. juarezensis and E. perezcalixii. In contrast, E. longiflora presented 3 endocycles (8C, 16C and 32C) and E. roseiflora presented 2 endocycles (8C and 16C). It has been suggested that polyploidization and diploidization processes, together with the presence of endopolyploidy, allowed Echeveria species to adapt and colonize new adverse environments.

Alimentos ultraprocesados y su relación con la obesidad y otras enfermedades crónicas no transmisibles: una revisión sistemática / Ultra-processed foods and their relationship to obesity and other chronic non-communicable diseases: a systematic review

Fundamentos: Revisar estudios con respecto a los alimentos ultraprocesados y sus resultados frente a la obesidad y otras enfermedades crónicas no transmisibles, específicamente: Diabetes Mellitus tipo 2 (DM2), hipertensión, enfermedades cardiovasculares y cáncer. Métodos: Revisión sistemática en la que se utilizaron las bases de datos de PubMed y Scielo. Se seleccionaron nueveartículos. Resultados: Un alto consumo de alimentos ultraprocesadosestá relacionado con el incremento en el riesgo de obesidad, DM2, hipertensión, enfermedad cardiovascular y cáncer.Conclusiones: Es necesario realizar estudios clínicos controlados aleatorizados que evalúen el tipo de alimento, frecuencia y dosis que permitan respaldar los resultados obtenidos en estudios observacionales. (AU)

Background: To review the available literature on the association between consumption of ultra-processed foodsand obesity and other non-communicable diseases,specifically: Diabetes Mellitus type 2 (DM2), hypertension, cardiovascular disease, and cancer. Methods: A systematic review was conducted in thePubMed and Scielo databases. Were selected nine articles. Results: High consumption of ultra-processed foods isrelated increased risk of obesity, DM2, hypertension, cardiovascular disease, and cancer. Conclusions: There is a need for randomized controlledclinical studies that evaluate the type of food, frequency and dose to support the results obtained in observational studies. (AU)

Current Practices and Challenges in the Diagnosis and Management of PKU in Latin America: A Multicenter Survey.

This study aimed to describe the current practices in the diagnosis and dietary management of phenylketonuria (PKU) in Latin America, as well as the main barriers to treatment. We developed a 44-item online survey aimed at health professionals. After a pilot test, the final version was sent to 25 practitioners working with inborn errors of metabolism (IEM) in 14 countries. Our results include 22 centers in 13 countries. Most countries (12/13) screened newborns for PKU. Phenylalanine (Phe) targets at different ages were very heterogeneous among centers, with greater consistency at the 0-1 year age group (14/22 sought 120-240 µmol/L) and the lowest at >12 years (10 targets reported). Most countries had only unflavored powdered amino acid substitutes (10/13) and did not have low-protein foods (8/13). Only 3/13 countries had regional databases of the Phe content of foods, and only 4/22 centers had nutrient analysis software. The perceived obstacles to treatment were: low purchasing power (62%), limited/insufficient availability of low-protein foods (60%), poor adherence, and lack of technical resources to manage the diet (50% each). We observed a heterogeneous scenario in the dietary management of PKU, and most countries experienced a lack of dietary resources for both patients and health professionals.

Efecto de la dieta nórdica en el control de los factores de riesgo de enfermedad cardiovascular: Revisión sistemática

RESUMEN Introducción: El patrón de dieta nórdica (DN) se ha propuesto e implementado como otra alternativa saludable a la clásica dieta mediterránea, tanto para el diario vivir de la población como también para el control y tratamiento de las enfermedades cardiovasculares. Objetivo: Revisar la evidencia científica actualmente publicada sobre la asociación entre el consumo del patrón de la DN y su efecto protector en los factores de riesgo cardiovascular. Material y Métodos: Se realizó una búsqueda electrónica de la literatura científica, usando palabras clave, basada en estudios clínicos controlados (ECA), aleatorizados, estudios de caso y control, publicados en PubMed y Cochrane desde el 2010 hasta la fecha. Se incluyeron: sujetos adultos de ambos sexos, con factores de riesgo cardiovascular como sobrepeso, dislipidemia, hipertensión arterial y/o resistencia a la insulina. Resultados: De los 5 ECA incluidos en esta revisión, se demostró que la DN reduce significativamente los niveles de LDL-C, el radio LDL/HDL y apoB/apoA, además de reducir significativamente el peso corporal y la circunferencia de cintura. En cuanto a los niveles de triglicéridos, VLDL, la sensibilidad a la insulina y la presión arterial, sólo un estudio demostró los efectos favorablemente significativos de estas variables y el estudio Sysdiet, logró demostrar el efecto antiinflamatorio de este patrón de dieta. Conclusión: La DN tiene efectos considerablemente beneficiosos sobre diferentes factores de riesgo cardiovascular como la obesidad, la dislipidemia y la inflamación por lo que resulta una alternativa saludable adicional a la dieta la Mediterránea o la dieta DASH en el control y prevención de las enfermedades cardiovasculares.

ABSTRACT Introduction: The Nordic Diet has been proposed and implemented as another healthy alternative to the classic Mediterranean diet, both for daily living and also for the control and treatment of cardiovascular diseases. Objective: To review the scientific evidence currently published on the association between the uptake of the Nordic Diet (ND) and its protective effect for cardiovascular risk. Methods: An electronic search of the scientific literature was performed, using keywords, based on randomized controlled clinical trials and case-control studies, published in PubMed and Cochrane from 2010 to date. We included: adult subjects of both sexes, with cardiovascular risk factors such as overweight, dyslipidemia, high blood pressure and/or insulin resistance. Results: Of the five randomized controlled clinical trials included in this review, the ND significantly reduces levels of LDL-C, LDL/HDL ratio, and apoB/apoA ratio, in addition to significantly reducing body weight and waist circumference. Regarding triglyceride levels, VLDL, insulin sensitivity and blood pressure, only one study demonstrated significantly favorable effects of these variables and the Sysdiet study was able to demonstrate an anti-inflammatory effect of the ND. Conclusion: The ND has considerably beneficial effects on different cardiovascular risk factors such as obesity, dyslipidemia and inflammation, making it an additional healthy alternative to the Mediterranean diet or the DASH diet in the control and prevention of cardiovascular diseases.

Maple syrup urine disease: Characteristics of diagnosis and treatment in 45 patients in Chile.

Maple urine syrup disease (MSUD) is an autosomal recessive disorder characterized by deficient activity of the branched-chain alpha ketoacid dehydrogenase (BCKAD) enzymatic complex due to biallelic variants in the alpha (BCKDHA) or beta (BCKDHB) subunits or the acyltransferase component (DBT). Treatment consists in leucine (LEU), isoleucine (ILE), and valine (VAL) (branched-chain amino acids) dietary restriction and strict metabolic control. to determine the characteristics of the Chilean cohort with MSUD currently in follow-up at Instituto de Nutrición y Tecnología de los Alimentos, during the 1990-2017 period Retrospective analytical study in 45 MSUD cases. Measured: biochemical parameters (LEU, ILE, and VAL), anthropometric evaluation, and neurocognitive development. In 18 cases undergoing genetic study were analyzed according to the gene and protein location, number of affected alleles, and type of posttranslational modification affected. Then, 45 patients with MSUD diagnosis were identified during the period: 37 were alive at the time of the study. Average diagnosis age was 71 ± 231 days. Average serum diagnosis LEU concentrations: 1.463 ± 854.1 µmol/L, VAL 550 ± 598 µmol/L and ILE 454 ± 458 µmol/L. BCKDHB variants explain 89% cases, while BCKDHA and DBT variants explain 5.5% of cases each. Variants p.Thr338Ile in BCKDHA, p.Pro240Thr and p.Ser342Asn in BCKDHB have not been previously reported in literature. Average serum follow-up LEU concentrations were 252.7 ± 16.9 µmol/L in the <5 years group and 299 ± 123.2 µmol/L in ≥5 years. Most cases presented some degree of developmental delay. Early diagnosis and treatment is essential to improve the long-term prognosis. Frequent blood LEU measurements are required to optimize metabolic control and to establish relationships between different aspects analyzed.

Consumo de lácteos y riesgo de cáncer colorrectal: Una revisión de la literatura científica

RESUMEN El cáncer colorrectal (CCR) es una de las neoplasias más frecuentes y representa una de las principales causas de muerte por cáncer en todo el mundo. Existen fuertes evidencias que factores dietarios influyen en su incidencia. Los lácteos han sido incorporados en numerosas guías nutricionales como parte de una dieta saludable; numerosos estudios han reportado un efecto protector entre el consumo de lácteos y el riesgo de cáncer colorrectal, presuntamente por su contenido de calcio (Ca); sin embargo, la evidencia es inconsistente. Objetivo: Evaluar la evidencia científica actual sobre la relación entre el consumo de lácteos y el riesgo de cáncer colorrectal. Metodología: Se realizó una búsqueda sensible en las bases de datos de PudMed, limitándose a artículos en inglés desde el 2014 hasta el 2019, priorizando estudios de cohorte y caso-control con exposición a productos lácteos como leche, yogurt, mantequilla y/o queso. Se encontró una asociación inversa significativa entre el consumo de productos lácteos totales y el riesgo de cáncer colorrectal. Con relación al calcio proveniente de los lácteos los resultados son inconsistentes. Solo la leche, como lácteo específico, mostró un efecto protector pero no discrimina según el contenido de grasa. La mayor ingesta de productos lácteos totales, la leche y el calcio están asociados con una disminución del riesgo de cáncer colorrectal.

ABSTRACT Colorectal cancer (CRC) is one of the most common malignancies and represents one of the leading causes of cancer death worldwide. There is strong evidence that dietary factors influence CRC incidence. Dairy products have been incorporated into nutritional guidelines as part of a healthy diet; many studies have reported a protective effect between dairy consumption and the risk of colorectal cancer, presumably because of its calcium (Ca) content; however, the evidence is inconsistent. Objective: To evaluate the current scientific evidence on the relationship between dairy consumption and the risk of colorectal cancer. Methodology: A literature search was conducted in the PudMed databases, limited to articles written in English and published between 2014 and November 2019, prioritizing cohort and case-control studies with exposure to dairy products such as milk, yogurt, butter and/or cheese. Results: A significant inverse association was found between the consumption of total dairy products and risk of colorectal cancer. In relation to calcium from dairy products, results are inconsistent. Only milk, as a specific dairy product, showed a protective effect, with no difference by fat content. Conclusions: Increased intake of total dairy products, milk and calcium are associated with a decreased risk of colorectal cancer.

Case report: Maternal tyrosinemia type 1a under NTBC treatment with tyrosine- and phenylalanine restricted diet in Chile.

We report the case of a 17-year-old girl with Tyrosinemia type 1a who carried a planned pregnancy to term while being under 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC, nitisinone) treatment and a tyrosine- and phenylalanine-restricted diet. She was on treatment since 2 months of age with poor metabolic control prior to her pregnancy (tyrosine 838 ± 106 umol/L). NTBC and a low tyrosine and phenylalanine diet were continued during her pregnancy. She unfortunately suffered from urinary tract infection and anemia during her pregnancy, with median plasma tyrosine and phenylalanine levels of 613 ± 106 umol/L (200-400 umol/L) and 40.2 ± 8 umol/L (35-90 umol/L), respectively. After 40 weeks of gestation, the patient gave birth to a healthy boy, with no adverse effects related to the use of NTBC. The newborn presented with a transitory elevation of plasma tyrosine levels and normal phenylalanine, methionine, and succinylacetone levels. By 12 months of age, the child was determined to have normal psychomotor development. At 20 months old, he was diagnosed with a mild developmental delay; however, global cognitive evaluation with the Wechsler Intelligence Scale for Children (WISC) test at 5 years old showed normal performance. Here, we discuss one of the few reported cases of nitisinone treatment during pregnancy and demonstrate a lack of teratogenicity and long-term cognitive disabilities.

Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia.

Biallelic variants of the gene DNAJC12, which encodes a cochaperone, were recently described in patients with hyperphenylalaninemia (HPA). This paper reports the retrospective genetic analysis of a cohort of unsolved cases of HPA. Biallelic variants of DNAJC12 were identified in 20 patients (generally neurologically asymptomatic) previously diagnosed with phenylalanine hydroxylase (PAH) deficiency (phenylketonuria [PKU]). Further, mutations of DNAJC12 were identified in four carriers of a pathogenic variant of PAH. The genetic spectrum of DNAJC12 in the present patients included four new variants, two intronic changes c.298-2A>C and c.502+1G>C, presumably affecting the splicing process, and two exonic changes c.309G>T (p.Trp103Cys) and c.524G>A (p.Trp175Ter), classified as variants of unknown clinical significance (VUS). The variant p.Trp175Ter was detected in 83% of the mutant alleles, with 14 cases homozygous, and was present in 0.3% of a Spanish control population. Functional analysis indicated a significant reduction in PAH and its activity, reduced tyrosine hydroxylase stability, but no effect on tryptophan hydroxylase 2 stability, classifying the two VUS as pathogenic variants. Additionally, the effect of the overexpression of DNAJC12 on some destabilizing PAH mutations was examined and a mutation-specific effect on stabilization was detected suggesting that the proteostasis network could be a genetic modifier of PAH deficiency and a potential target for developing mutation-specific treatments for PKU.

Normal Kinematics of the Syndesmosis and Ankle Mortise During Dynamic Movements.

BACKGROUND: Documenting the healthy articulation of the syndesmosis and talocrural joints, and measurement of 3D medial and lateral clear spaces may improve diagnostic and treatment guidelines for patients suffering from severe syndesmotic injury or chronic instability. This study aimed to define the range of motion (ROM) and displacement of the fibula and talus during static and dynamic activities, and measure the 3D movement in the tibiofibular (syndesmosis) and medial clear space. METHODS: Six healthy volunteers performed dynamic weightbearing motions on a single-leg: heel-rise, squat, torso twist, and box jump. Participants posed in a nonweightbearing neutral stance as well as weightbearing neutral standing, plantarflexion, and dorsiflexion. High-speed stereoradiography measured 3D rotation and translation of the fibula and talus throughout each task. Medial clear space and tibiofibular gap distances were measured under each condition. RESULTS: Total ROM for the fibula was greatest in internal-external rotation (9.3 ± 3.5 degrees), and anteroposterior (3.3 ± 2.2 mm) and superior-inferior (2.5 ± 0.9 mm) translation, rather than lateral widening (1.7 ± 1.0 mm). The total rotational ROM of the talus was greatest in dorsiflexion-plantarflexion (34.7 ± 12.9 degrees) and internal-external rotation (15.0 ± 3.4 degrees). Single-leg squatting increased the lateral clear space (P = .045) and widened the medial tibiofibular joint, whereas single-leg heel-rises decreased the lateral clear space (P = .001) and widened the tibiotalar space. Gap spaces in the tibiofibular and medial clear spaces did not exceed 2.3 ± 0.9 mm and 2.7 ± 1.2 mm, respectively. CONCLUSION: These data support a potential shift in the clinical understanding of fibula displacements during dynamic activities and how implant device constructs might be developed to restore physiologic mechanics. CLINICAL RELEVANCE: Syndesmosis stabilization and rehabilitation should consider restoration of normal physiologic rotation and translation of the fibula and ankle mortise rather than focusing solely on the restriction of lateral translation.

First-year metabolic control guidelines and their impact on future metabolic control and neurocognitive functioning in children with PKU.

There is a consensus on the importance of early and life-long treatment for PKU patients. Still, differences exist on target blood phenylalanine (Phe) concentrations for children with PKU in different countries and treatment centers. For the first time, long-term metabolic control and child development and cognitive functioning is compared between children with mean phenylalanine concentrations under 240 µmol/L (group A), between 240 and 360 µmol/L (group B) or over 360 µmol/L (group C) during their first year of life. METHODS: 70 patients diagnosed with PKU through neonatal screening with Phe > 900 µmol/L, were divided into 3 groups: A, B and C, according to mean Phe concentrations and standard deviation (SD). Metabolic control during childhood, psychomotor development and IQ were compared. RESULTS: In group A, Phe was maintained within the recommended range until 6 years of age, in Group B, until 3 years of age, and in group C, Phe was always over the recommended range. No significant differences were found between the three groups in mental development index (MDI) and motor development index (PDI) scores at 12, 24, and 30 months of age, but group C had the lowest scores on MDI at all age periods. At preschool and school age, IQ was higher in group A compared to group C. CONCLUSION: Results show that mean blood Phe concentrations between 120 and 240 µmol/L during first year of life have a positive impact in metabolic control and cognitive functioning during childhood.

Chilean Nutrition Management Protocol for Patients With Phenylketonuria

Abstract Since neonatal screening and early nutritional treatment began, it has been possible to reverse the neurological damage that phenylketonuria (PKU) causes. Scientific evidence gathered over more than 50 years on the monitoring of individuals with PKU indicates that a phenylalanine level of about 6 mg/dL (360 µmol/L) is ideal and points to the necessity of starting a long-term phenylalanine-restricted diet in which blood phenylalanine level should stay between 2 and 6 mg/dL (120-360 µmol/L). This article aims to establish the general basis for proper monitoring of people with PKU and provide a useful tool for clinicians overseeing treatment. We hope to establish similar criteria throughout Latin America and create a uniform protocol in order to have comparative monitoring results for the region.