Gestational Diabetes-Placental Expression of Human Equilibrative Nucleoside Transporter 1 (hENT1): Is Delayed Villous Maturation an Adaptive Pattern?

Gestational diabetes mellitus (GDM) is a metabolic disease that can affect placental villous maturation and villous vascularity. The main effects of GDM on placental growth are a delay of villous maturation (DVM) and decreased formation of vasculo-syncytial membranes (VSM). Human equilibrative nucleoside transporter-1 (hENT1) is an adenosine transporter expressed in the human umbilical vein endothelial cells (HUVEC) and human placental microvascular endothelium cells (hPMEC). Its role is crucial in maintaining physiological fetal adenosine levels during pregnancy, and its reduction has been described in GDM. Twenty-four placentas from pregnancies with a confirmed diagnosis of GDMd and twenty-four matched non-GDM placentas (controls) were retrospectively analyzed to investigate the immunohistochemical expression of hENT1 in HUVEC and hPMEC. The study included the quantitative evaluation of VSM/mm2 in placental tissue and the immunohistochemical quantitative evaluation of Ki-67, PHH3, and p57 in villous trophoblast. hENT1 expression was higher in all the vascular districts of the control cases compared to the GDMd placentas (p < 0.0001). The VSM/mm2 were lower in the GDMd cases, while the Ki-67, PHH3, and p57 were higher when compared to the control cases. To our knowledge, this is the first report of hENT1 expression in the human placentas of GDM patients. The absence/low expression of hENT1 in all the GDMd patients may indicate a potential role in microvascular adaptative mechanisms. The trophoblasts' proliferative/antiapoptotic pattern (high Ki-67, high PHH3, and high p57 count) may explain the statistically significant lower number of VSM/mm2 found in the GDMd cases.

Is psychological treatment efficacious for attention deficit hyperactivity disorder (ADHD)? Review of non-pharmacological treatments in children and adolescents with ADHD.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children and adolescents, and has a great impact on the psychological development of affected patients. Even though its efficacy is proven, the use of medication for ADHD has several limitations, and non-pharmacological interventions are considered a necessary component of treatment. METHODOLOGY: This work is a review of evidence-based non-pharmacological treatments with demonstrated efficacy for ADHD in children and adolescents, analyzed by age groups. RESULTS: Non-pharmacological treatments that have shown scientific evidence of efficacy are psychological and psychoeducational interventions. Psychological interventions include behavioral therapy, parent training (PT) and social skills training. Psychoeducational interventions include a set of practices to improve learning and are carried out in the school setting. Scientific evidence of efficacy in preschool children is limited to PT, while different psychological and psychoeducational interventions have been shown to be beneficial in school-age children. The available evidence for non-pharmacological treatment in adolescence is so far insufficient. CONCLUSIONS: Though more randomized controlled trials are necessary for non-pharmacological interventions to become established practices, there are clear indications of their efficacy. For more severe cases of ADHD, a combination of non-pharmacological and pharmacological treatment is recommended.

¿Es el tratamiento psicológico eficaz para el trastorno por déficit de atención con hiperactividad (TDAH)? Revisión sobre los tratamientos no farmacológicos en niños y adolescentes con TDAH / Is psychological treatment effi cacious for attention deficit hyperactivity disorder (ADHD)? Review of non-pharmacological treatments in children and adolescents with ADHD

Introducción: El trastorno por déficit de atención con hiperactividad (TDAH) es el trastorno psiquiátrico más prevalente en la edad infanto-juvenil, y tiene un gran impacto sobre el desarrollo psicológico de los niños afectados. Aunque su eficacia está comprobada, el uso de la medicación para el TDAH tiene varias limitaciones, y las intervenciones no farmacológicas se consideran un componente necesario del tratamiento. Metodología: El presente trabajo es una revisión de los tratamientos no farmacológicos basados en la evidencia que han demostrado eficacia para el TDAH en niños y adolescentes, analizados por grupos de edad. Resultados: Los tratamientos no farmacológicos que han mostrado evidencia científica de su eficacia son las intervenciones psicológicas y psicopedagógicas. Las intervenciones psicológicas incluyen la terapia de conducta, el entrenamiento para padres (EP) y el entrenamiento en habilidades sociales. Las intervenciones psicopedagógicas incluyen un conjunto de prácticas para mejorar el aprendizaje que se realizan en el contexto escolar. La evidencia científica de eficacia para niños de edad preescolar se circunscribe al EP , mientras que diferentes intervenciones psicológicas y psicopedagógicas han demostrado ser beneficiosas para los niños de edad escolar. La evidencia disponible sobre el tratamiento no farmacológico en la adolescencia es todavía insuficiente. Conclusiones: Aunque son necesarios más ensayos controlados aleatorizados para que las intervenciones no farmacológicas se conviertan en prácticas establecidas, existen indicaciones claras de su eficacia. En los casos más graves de TDAH se recomienda el tratamiento no farmacológico combinado con la medicación(AU)

Introduction: Attention deficit hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children and adolescents, and has a great impact on the psychological development of affected patients. Even though its efficacy is proven, the use of medication for ADHD has several limitations, and non-pharmacological interventions are considered a necessary component of treatment. Methodology: This work is a review of evidence-based non-pharmacological treatments with demonstrated efficacy for ADHD in children and adolescents, analysed by age groups. Results: Non-pharmacological treatments that have shown scientific evidence of efficacy are psychological and psychoeducational interventions. Psychological interventions include behavioural therapy, parent training (PT) and social skills training. Psychoeducational interventions include a set of practices to improve learning that are carried out in the school setting. Scientific evidence of efficacy in preschool children is limited to PT, while different psychological and psychoeducational interventions have been shown to be beneficial in school-age children. The available evidence for non-pharmacological treatment in adolescence is so far insufficient. Conclusions: Though more randomized controlled trials are necessary for non-pharmacological interventions to become established practices, there are clear indications of their efficacy. For more severe cases of ADHD, a combination of non-pharmacological and pharmacological treatment is recommended(AU)

Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways.

BACKGROUND: The involvement of microRNAs (miRNAs) in neuronal differentiation and synaptic plasticity suggests a role for miRNAs in psychiatric disorders; association analyses and functional approaches were used to evaluate the implication of miRNAs in the susceptibility for panic disorder. METHODS: Case-control studies for 712 single-nucleotide polymorphisms (SNPs) tagging 325 human miRNA regions were performed in 203 Spanish patients with panic disorder and 341 control subjects. A sample of 321 anxiety patients and 642 control subjects from Finland and 102 panic disorder patients and 829 control subjects from Estonia was used as a replica. Reporter-gene assays and miRNA overexpression experiments in neuroblastoma cells were used to functionally evaluate the spectrum of genes regulated by the associated miRNAs. RESULTS: Two SNPs associated with panic disorder: rs6502892 tagging miR-22 (p < .0002), and rs11763020 tagging miR-339 (p < .00008). Other SNPs tagging miR-138-2, miR-488, miR-491, and miR-148a regions associated with different panic disorder phenotypes. Replication in the north-European sample supported several of these associations, although they did not pass correction for multiple testing. Functional studies revealed that miR-138-2, miR-148a, and miR-488 repress (30%-60%) several candidate genes for panic disorder--GABRA6, CCKBR and POMC, respectively--and that miR-22 regulates four other candidate genes: BDNF, HTR2C, MAOA, and RGS2. Transcriptome analysis of neuroblastoma cells transfected with miR-22 and miR-488 showed altered expression of a subset of predicted target genes for these miRNAs and of genes that might be affecting physiological pathways related to anxiety. CONCLUSIONS: This work represents the first report of a possible implication of miRNAs in the etiology of panic disorder.

Overexpression of miR-128 specifically inhibits the truncated isoform of NTRK3 and upregulates BCL2 in SH-SY5Y neuroblastoma cells.

BACKGROUND: Neurotrophins and their receptors are key molecules in the regulation of neuronal differentiation and survival. They mediate the survival of neurons during development and adulthood and are implicated in synaptic plasticity. The human neurotrophin-3 receptor gene NTRK3 yields two major isoforms, a full-length kinase-active form and a truncated non-catalytic form, which activates a specific pathway affecting membrane remodeling and cytoskeletal reorganization. The two variants present non-overlapping 3'UTRs, indicating that they might be differentially regulated at the post-transcriptional level. Here, we provide evidence that the two isoforms of NTRK3 are targeted by different sets of microRNAs, small non-coding RNAs that play an important regulatory role in the nervous system. RESULTS: We identify one microRNA (miR-151-3p) that represses the full-length isoform of NTRK3 and four microRNAs (miR-128, miR-485-3p, miR-765 and miR-768-5p) that repress the truncated isoform. In particular, we show that the overexpression of miR-128 - a brain enriched miRNA - causes morphological changes in SH-SY5Y neuroblastoma cells similar to those observed using an siRNA specifically directed against truncated NTRK3, as well as a significant increase in cell number. Accordingly, transcriptome analysis of cells transfected with miR-128 revealed an alteration of the expression of genes implicated in cytoskeletal organization as well as genes involved in apoptosis, cell survival and proliferation, including the anti-apoptotic factor BCL2. CONCLUSIONS: Our results show that the regulation of NTRK3 by microRNAs is isoform-specific and suggest that neurotrophin-mediated processes are strongly linked to microRNA-dependent mechanisms. In addition, these findings open new perspectives for the study of the physiological role of miR-128 and its possible involvement in cell death/survival processes.

Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders.

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins.

Ubiquitination is a post-translation modification in which ubiquitin chains or single ubiquitin molecules are appended to target proteins, giving rise to poly- or monoubiquitination, respectively. Polyubiquitination targets proteins for destruction by the proteasome. The role of monoubiquitination is less understood, although a function in membrane trafficking is emerging, at least in yeast. Here we report that a short amino-acid stretch at the carboxy-termini of the monoubiquitinated endocytic proteins Eps15 and eps15R is indispensable for their monoubiquitination. A similar sequence, also required for this modification, is found in other cytosolic endocytic proteins, such as epsins and Hrs. These sequences comprise a protein motif, UIM (ref. 6), which has been proposed to bind to ubiquitin. We confirm this for the UIMs of eps15, eps15R, epsins and Hrs. Thus, the same motif in several endocytic proteins is responsible for ubiquitin recognition and monoubiquitination. Our results predict the existence of a UIM:ubiquitin-based intracellular network. Eps15/eps15R, epsins and Hrs may function as adaptors between ubiquitinated membrane cargo and either the clathrin coat or other endocytic scaffolds. In addition, through their own ubiquitination, they may further contribute to the amplification of this network in the endocytic pathway.

Assistência de enfermagem em estomaterapia: atividade independente / Nursing assistance in stomatherapy independent activity

As autoras destacaram as funçöes de enfermeiro estomaterapeuta segundo o World Council of Enterostomal Therapy. Ao lado disso propuzeram-se verificar junto a alguns enfermeiros que realizam atividade "independente" de assistência como eles caracterizam este tipo de atividade, a fim de obter dados que contribuíssem para esclarecer a assistência de enfermagem em Estomaterapia como atividade "independente". Os dados foram coletados por meio de um formulário e, após analisados, grupados em quadros. Chegaram à conclusäo que a assistência de enfermagem em Estomaterapia é "independente" somente do ponto de vista da especificidade de atuaçäo do enfermeiro estomaterapeuta.

Particularidades de la asistencia de enfermería en estomaterapia : actividad independiente / Particularities of the nursing care in stomatherapy : independent activity

Las autoras destacan las funciones de la enfermera estomaterapeuta según los patrones de la World Council of Enterostomal Therapist (W.C.E.T.) y se propusieron desenvolver un estudio con el objeto de verificar junto a algunos enfermeros, como ellos caracterizan una actividad "independiente" de asistencia de enfermería en estomaterapia como actividad independiente. La muestra fue constituída por cinco enfemeras, siendo tres estomaterapeutas. Los datos fueron recolectados, por medio de un formulario compuesto por siete preguntas semi-abiertas y abiertas, sus respuestas posteriormente analizadas, fueron agrupadas en cuadros. La actividad independiente de asistencia de enfermería fue analizada en cuanto: al significado, actividad exclusiva de la enfermera y necesidad de conocimiento técnico-científico; la opinión sobre la actividad que realizan, actividad que no está subordinada directamente a una institución; al tipo de actividad relacionada a la función asistencial, de enseñanza y administrativas; la metodología en la realización, visita domiciliaria, seguimiento ambulatorial y asistencia en el pre, trans y post-operatorio; exigencias legales y administrativas, además de otras, el respaldo de las exigencias de la W.C.E.T.; finalmente, opinión de dos enfermeras estomaterapeutas sobre la estomaterapia como actividad "independiente" de asistencia de enfermería. Se llegó a la conclusión que la asistencia en estomaterapia es independiente solamente desde el punto de vista de la especifícidad de actuación de la enfermera estomaterapeuta(AU)

Particularidades de la asistencia de enfermería en estomaterapia : actividad independiente / Particularities of the nursing care in stomatherapy : independent activity

Las autoras destacan las funciones de la enfermera estomaterapeuta según los patrones de la World Council of Enterostomal Therapist (W.C.E.T.) y se propusieron desenvolver un estudio con el objeto de verificar junto a algunos enfermeros, como ellos caracterizan una actividad "independiente" de asistencia de enfermería en estomaterapia como actividad independiente. La muestra fue constituída por cinco enfemeras, siendo tres estomaterapeutas. Los datos fueron recolectados, por medio de un formulario compuesto por siete preguntas semi-abiertas y abiertas, sus respuestas posteriormente analizadas, fueron agrupadas en cuadros. La actividad independiente de asistencia de enfermería fue analizada en cuanto: al significado, actividad exclusiva de la enfermera y necesidad de conocimiento técnico-científico; la opinión sobre la actividad que realizan, actividad que no está subordinada directamente a una institución; al tipo de actividad relacionada a la función asistencial, de enseñanza y administrativas; la metodología en la realización, visita domiciliaria, seguimiento ambulatorial y asistencia en el pre, trans y post-operatorio; exigencias legales y administrativas, además de otras, el respaldo de las exigencias de la W.C.E.T.; finalmente, opinión de dos enfermeras estomaterapeutas sobre la estomaterapia como actividad "independiente" de asistencia de enfermería. Se llegó a la conclusión que la asistencia en estomaterapia es independiente solamente desde el punto de vista de la especifícidad de actuación de la enfermera estomaterapeuta