Brain-Derived Neurotrophic Factor (BDNF) as a Predictor of Treatment Response in Major Depressive Disorder (MDD): A Systematic Review.

Brain-derived neurotrophic factor (BDNF) has been studied as a biomarker of major depressive disorder (MDD). Besides diagnostic biomarkers, clinically useful biomarkers can inform response to treatment. We aimed to review all studies that sought to relate BDNF baseline levels, or BDNF polymorphisms, with response to treatment in MDD. In order to achieve this, we performed a systematic review of studies that explored the relation of BDNF with both pharmacological and non-pharmacological treatment. Finally, we reviewed the evidence that relates peripheral levels of BDNF and BDNF polymorphisms with the development and management of treatment-resistant depression.

Functional alterations of two novel MC4R mutations found in Argentinian pediatric patients with early onset obesity.

Loss-of-function mutations in melanocortin-4 receptor (MC4R) are the most common cause of monogenic obesity, a severe type of early-onset obesity. Our aim was to determine the prevalence of MC4R mutations in a cohort of 97 Argentinian children with early-onset obesity. We found two novel mutations (p.V52E and p.G233S) and estimated a prevalence of 2.1%. We investigated the pathogenicity of mutations in HEK293T cells expressing wild-type or mutant MC4R and found that both mutants exhibited reduced plasma membrane expression and altered agonist-induced cAMP responses, with no changes in basal activity. Besides, MC4R G233S mutant demonstrated an altered agonist-dependent inhibition of voltage-gated calcium channels type 2.2. Results using a Gαs protein inhibitor suggest that the G233S mutation could be recruiting a different G-protein signaling pathway. The identification of new mutations in MC4R and characterization of their functional impact provide tools for the diagnosis and treatment of monogenic obesity.

Care of patients on home parenteral nutrition during the first year of the COVID-19 pandemic: Management of central line-associated bloodstream infections.

BACKGROUND AND AIM: The aim of this study was to analyze central line-associated bloodstream infections (CLABSI) in home parenteral nutrition (HPN) patients assisted by an interdisciplinary team during the first year of the COVID-19 pandemic in Argentina. METHODS: Longitudinal, retrospective and analytical study of patients on HPN for ≥90 days during 2020. Data collection included age (adults >18 years, pediatric ≤18 years), gender, diagnosis, type of catheter, number of lumens, venous access, days on HPN, infusion modality and number of CLABSI-associated events. In COVID-19 cases, number of patients, disease progression, mortality rate and microorganisms involved were analyzed. RESULTS: A total of 380 patients were included, 120 (31.6%) pediatric and 260 (68.4%) adult patients. Median age was 44.50 years (10; 62.25). Twelve patients (3.15% of the total) had COVID-19; of these, two pediatric and seven adult patients had no complications, and three adults died of COVID-19 pneumonia. The diagnoses observed were benign chronic intestinal failure (CIF, n = 311), grouped into short bowel (n = 214, 56.3%), intestinal dysmotility (n = 56, 14.7%), intestinal fistula (n = 20, 5.3%), and extensive small bowel mucosal disease (n = 21, 5.5%); malignant tumors (n = 52, 13.7%); other (n = 17, 4.4%). Total catheter days were 103,702. Median days of PN duration per patient were 366 (176.2, 366). The types of catheters used were tunneled (317 patients, 83.4%); peripherally inserted central (PICC) line (55 patients, 14.5%) and ports (8 patients; 2.1%). A total of 111 CLABSI was registered, with a prevalence of 1.09/1000 catheter days (adult, 0.86/1000 days; pediatric, 1.51/1000 days). The microorganisms identified in infectious events were Gram + bacteria (38, 34.5%); Gram-bacteria (36, 32%); mycotic (10, 9%); polymicrobial (4, 3.6%); negative culture and signs/symptoms of CLABSI (23, 20.3%). The odds ratio between pediatric and adult patients was 2.29 (1.35, 3.90). CONCLUSION: The rate of CLABSI during the COVID-19 pandemic was within the ranges reported by international scientific societies. The risk of CLABSI was higher in pediatric patients, and mortality rate in COVID-19 infected patients was higher than in the general population.

Riesgo de deficiencia de vitamina D en pacientes pediátricos con parálisis cerebral que reciben nutrición enteral domiciliaria / Risk of vitamin D deficiency in pediatric patientes with cerebral palsy receiving home enteral nutrition

Introducción: La malnutrición y la deficiencia de micronutrientes son complicaciones frecuentes en los pacientes con parálisis cerebral (PC). Objetivo: Analizar los niveles de vitamina D (VitD) en pacientes PC en Nutrición Enteral Domiciliaria (NED). Material y Métodos: Estudio retrospectivo analítico de corte transversal. Se incluyeron pacientes PC, e/ 2-18 años, con dosaje de VitD al final del invierno 2021. Se analizó: sexo, edad, discapacidad por Gross Motor Scale (GMS), estado nutricional, drogas antiepilépticas, fórmula, aporte de VitD, volumen, vía de acceso, gasto energético basal (GEB). Se agruparon: Grupo I (GI VitD ≥ 30 ng/ml) GII (VitD ≤ 29 ng/ml). Resultados: se incluyeron 34 pacientes PC, 15 femeninos (44,11 %), edad media 10,87 años (DS 4,78), todos fueron grado V (GMS). La media de Z score de IMC (OMS) fue -1,33 (DS 3,14). Todos recibieron NE diaria. El aporte medio fue de 1270 Kcal (DE:243), 1,16 (Kcal sobre lo estimado según Schofield). Las fórmulas aportaron el 80% del requerimiento de VitD. Los niveles sanguíneos de VitD mostraron: 16 pacientes ≥ de 30 ng/ml y 18 ≤ 29 ng/ml. 14 fueron deficientes y 4 insuficientes. El 59% (20) de los pacientes recibían medicación anticonvulsivante. No se encontraron diferencias significativas entre G1 y G2 para sexo, edad, Z score de IMC, aporte de VitD, calorías recibidas/ GMB y medicación anticonvulsivante. Conclusión: El alto porcentaje de pacientes PC pediátricos con niveles subóptimos de VitD muestra que se trata de una población de riesgo y sugiere la necesidad del chequeo sistemático para una adecuada prevención y tratamiento

Introduction: Malnutrition and micronutrient deficiencies are frequent complications in patients with cerebral palsy (CP). Objective: to analyze the levels of vitamin D (VitD) in CP patients receiving Home Enteral Nutrition (HEN). Material and Methods: Retrospective analytical cross-sectional study. CP patients, from 2 to 18 years old, with measured VitD at the end of winter 2021, were included. The following study variables were analyzed: sex, age, disability by Gross Motor Scale (GMS), nutritional status, antiepileptic drugs, formula, VitD intake, volume, access route, basal energy expenditure (BEE), according to Schofield P/T. They were grouped: Group I (GI VitD ≥ 30 ng/ml) GII (VitD ≤ 29 ng/ml). Results: 34 CP patients were included, 15 female (44.11 %), mean age 10.87 years (SD 4.78), all grade V (GMS). The mean BMI Z score (WHO) was -1.33 (SD 3.14). EN was daily in all, 33 due to gastrostomy and 1 due to SNG. The average contribution 1270 Kcal (DS243), 1.16 (Kcal received according to Schofield). The formulas provided 80 % of the VitD requirement. VitD blood levels showed: 16 patients (47 %) ≥ 30 ng/ml and 18 (52 %) ≤ 29 ng/ml. 14 (41.17 %) were deficient and 4 insufficient (11.76 %). 59 % (20) of the patients received anticonvulsant medication. No significant differences were found between G1 and G2 for sex, age, BMI Z score, VitD intake, calories received/GMB and anticonvulsant medication. Conclusion: The high percentage of pediatric CP patients with suboptimal levels of Vit D shows that it is a population at risk and suggests the need for systematic check-up for adequate prevention and treatment

Acetilación N-terminal, acetiltransferasas y mutaciones en subunidad auxiliar NAA15 de N-terminal acetiltransferasa A, asociadas a discapacidad intelectual y trastorno del espectro autista: una revisión bibliográfica / N-terminal acetylation, acetyltransferases and variants in NAA15 auxiliary subunit of the N-terminal acetyltransferase A associated with intellectual disability and autism spectrum disorder: a literature review

Las N-terminal acetiltransferasas (NaT) son fundamentales en el desarrollo, funcionamiento y vida media celular, acetilando gran parte del proteoma humano. Entre las ocho NaT identificadas, N-terminal acetiltransferasa A (NaTA) acetila a un mayor número de sustratos, teniendo además un rol fundamental en el neurodesarrollo. Previamente, estudios han demostrado que mutaciones en la subunidad catalítica de NaTA, NAA10, se asocian con trastornos del neurodesarrollo. Sin embargo, nuevas líneas investigativas sugieren que mutaciones de la subunidad auxiliar, NAA15, también tendrían un rol importante en el desarrollo de estos trastornos. Esta revisión se realiza con el objetivo de recopilar evidencia sobre variantes de NAA15 relacionadas con Discapacidad Intelectual (DI) y Trastorno de Espectro Autista (TEA). Se consultaron fuentes actualizadas sobre acetilación N-terminal, NaT, DI y TEA y mutaciones reportadas de NAA15 y sus expresiones fenotípicas, publicadas entre 2011 y 2022. Se concluye que, aun cuando existe relación entre mutaciones de NAA15, DI y TEA, todavía es necesario esclarecer los mecanismos fisiopatológicos de estos trastornos, el rol de NaTA y el impacto de variantes de sus subunidades en las vías moleculares y el fenotipo, lo que se dificulta por razones que van desde la complejidad de estas vías hasta el elevado costo de análisis genéticos. Se sugiere continuar la investigación en esta área, para comprender las bases moleculares subyacentes a estos trastornos y el rol de las mutaciones en subunidades de NaTA, con el fin último de estudiar potenciales tratamientos que mejoren la calidad de vida de las personas con estos trastornos y sus familias.

Nt-acetyltransferases (NaT) are essential in cell development, function and half-life, catalyzing most of the human proteome. Among the eight NaTs identified, N-terminal acetyltransferase A (NaTA) acetylates a greater number of substrates, also having a fundamental role in neurodevelopment. Previously, studies have shown that mutations in the catalytic subunit of NaTA, NAA10, are associated with neurodevelopmental disorders. However, new research lines suggest that mutations of the NAA15 helper subunit also plays an important role in the development of these disorders. This review is carried out with the objective of gathering evidence on NAA15 variants related to Intellectual Disability (ID) and Autism Spectrum Disorder (ASD). Updated sources on N-terminal acetylation, N-acetyltransferases, DI and TEA and reported mutations of NAA15 and their phenotypic expressions, published between 2011 and 2022 were consulted. It is concluded that even though there is a relationship between mutations of NAA15, ID and ASD exists, it is still necessary to clarify the pathophysiological mechanisms of these disorders, the role of NaTA and the impact of variants of its subunits in the molecular pathways and in the phenotype, for reasons ranging from the complexity of these pathways to the high cost of genetic testing. It is suggested to continue research in this area, to understand the molecular bases underlying these disorders and the role of mutations in NatA subunits, with the ultimate aim of studying potential treatments that improve the quality of life of people with these disorders and their families.

Evolución de los parámetros antropométricos de niños con parálisis cerebral asistidos por un equipo especializado en soporte nutricional domiciliario / Evolution of the anthropometric parameters of children with cerebral palsy assisted by a team specialized in home nutritional support

Introducción: los niños con parálisis cerebral (PC) presentan habitualmente compromiso nutricional. Objetivos: evaluar el estado nutricional antropométrico de niños con PC con nutrición enteral (NE) asistidos por un equipo especializado en domicilio. Materiales y métodos: cohorte retrospectiva sobre datos de historia clínica, evaluados durante un año (2018-2019). Se evaluó: z score de .peso (Pz), z score de talla (Tz), z score de índice de masa corporal (IMC) (IMCz). En los que no pudo usarse pediómetro, se utilizó medición de la longitud de la tibia (LT). Se los dividió en: 10 años (Grupo 2). Se excluyeron: síndromes genéticos y/o epilepsia refractaria, y quienes no adhirieron al tratamiento nutricional. Se registraron complicaciones asociadas al tratamiento nutricional. Resultados: se analizaron 72 pacientes, Grupo 1: 38 pacientes; inicio: Tz x -2,85(-4,50;-1,41), Pz x -2,83 (-3,72;-1,59), promedio de IMCz -1,10 (DE 2,25). Final, Tz fue x -2,55 (-3,92; -1,42), el Pz x -2,15 (-3,05;-1,03), promedio IMCz: 0,93 (DE 2,21). Se observó diferencia significativa entre el inicio y el final del período en el Z score peso (p=0,030). En el Grupo 2 se incorporaron 34 pacientes (47%), 22 (64%) de sexo masculino con una mediana de 13,62 de edad (r 11,6-14,83 años). La mediana del Tz fue -3,00 (-3,81; -1,53), el score Pz -2,63 (-3,68; -2,23), la media del IMCz fue -1,75 (DE:1,73). En el final del período observado, la mediana del Tz e -2,84 (-4,13;-1,25), Pz -2,84 (-3,42; -1,83), la media del IMCz fue -1,53 (DE:2,19). Se observaron diferencias significativas entre el inicio y final del período observado en el Pz (p=0,049). No se identificaron complicaciones graves en el período observado (hospitalizaciones, broncoaspiración, fallecimientos). Conclusiones: se observó mejoría del estado nutricional y bajo índice de complicaciones en el período estudiado

Introduction: children with cerebral palsy (CP) usually present nutritional compromise. Objectives: to evaluate the anthropometric nutritional status of children with CP with enteral nutrition (EN) assisted by a specialized team at home. Materials and methods: a retrospective cohort study on clinical report data, evaluated during one year (2018-2019). The following were evaluated: weight z score (Pz), height z score (Tz), BMI z score (BMIz). In those that could not be used a pediometer, measurement of the tibia length (TL) was used. They were divided into: <10 years (Group1) and >10 years (Group2). The following were excluded: genetic syndromes and/or refractory epilepsy, and those who did not adhere to nutritional treatment. Complications associated with nutritional treatment were recorded. Results: 72 patients were analyzed, Group 1: 38 patients: baseline: Tz x -2.85 (-4.50, -1.41), Pz x -2.83 (-3.72, -1.59), BMIz 0,93 (SD 2,21). Final, Tz was x -2.55 (-3.92, -1.42), Pz x -2.15 (-3.05, -1.03), BMI x: 15.95. Significant differences were observed between the start-end in P p<0.001, T p0.001, and Pz p0.030. Group 2: 34 patients, 2018: Tz x -3.00 (-3.81, -1.53), Pz x -2.63 (-3.68, -2.23), BMIz x -1,75 (DE:1,73). Final Tz x -2.84 (-4.13, -1.25), Pz x -2.84 (-3.42,-1.83) BMI -1,53 (DE: 2,19).Significant differences were observed between the beginning and end of the period observed in the Pz (p=0.049). No severe complications were recorded (hospitalizations, bronchial aspiration, death). Conclusions: an improvement in nutritional status and no severe complications were observed in the period studied

Plasma levels of ghrelin, des-acyl ghrelin and LEAP2 in children with obesity: correlation with age and insulin resistance.

OBJECTIVE: The octanoylated peptide hormone ghrelin regulates appetite and glycaemic control. Des-acyl ghrelin abolishes some effects of ghrelin, but does not bind to ghrelin receptor. LEAP2 is a novel ligand for ghrelin receptor that blocks the effects of ghrelin. Some evidences show that plasma levels of these peptides are altered in adults with obesity, but their levels in childhood obesity remain poorly studied. Therefore, the objective of this study was to assess fasting plasma levels of ghrelin, des-acyl ghrelin and LEAP2 in children with normoweight, overweight/obesity and their association with different anthropometric and metabolic variables. DESIGN: A total of 42 females and 40 males, ages 3-12 years old were enrolled as a cross-sectional cohort. RESULTS: Plasma levels of des-acyl ghrelin and LEAP2 (but not ghrelin) were lower and ghrelin/des-acyl ghrelin ratio was higher in children with overweight/obesity. Des-acyl ghrelin negatively correlated with age, BMI z-score, insulin and HOMA index, and the correlations were stronger in children with overweight/obesity. LEAP2 levels negatively correlated with BMI z-score. No gender differences were found. CONCLUSIONS: Our findings suggest that ghrelin tone is increased in childhood obesity, due to a decrease on plasma levels of des-acyl ghrelin and LEAP2, and that des-acyl ghrelin is associated to insulin resistance, particularly in children with overweight/obesity.

Artropatía gotosa evolucionada / Evolved gouty arthropathy

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