Occupational Therapist Perceptions on How Eye Movement Therapy Supports Working Memory in Children Diagnosed with Attention Deficit/Hyperactivity Disorder

Previous research reports that children with attention-deficit/hyperactivity disorder (ADHD) show a deficit in their working memory. Working memory is the ability to temporarily manipulate, store, and retrieve information during cognitive tasks. Working memory is considered a critical deficiency in individuals diagnosed with ADHD. Working memory has been shown to be a mechanism for symptoms of disorganization and inattention in individuals diagnosed with ADHD. This qualitative research study reviewed occupational therapists’ perceptions on their role working with children, aged six to 10 years old, diagnosed with ADHD and low working memory, who have had eye movement therapy. The occupational therapists’ perceptions of the effects of eye movement therapy on working memory, conduct, and academic ability were investigated. ADHD and low working memory have been reported and characterized in two formats. First, children diagnosed with ADHD with hyperactive-impulsive subtype exhibit advanced levels of impulsive behavior, while those diagnosed with ADHD without hyperactive-impulsive subtype show a significant decrease in working memory to reduced reaction times. This research explored the effects of eye therapy treatment on the cognition of children diagnosed with ADHD from an occupational therapist professional perspective. Previous research has shown that eye therapy has improved working memory in children diagnosed with ADHD. Overall, during this study, occupational therapists discovered that integrating EMT with other interventions, such as cognitive-behavioral and sensory integration therapies, with children diagnosed with ADHD resulted in improvements in their working memories, attention, and academic performances

Les competències dels professors d'Educació Física des de la perspectiva dels alumnes. Validació i prova pilot d'un instrument ad hoc per a la seva anàlisi

L’actual preocupació social per l‘educació i pel fet educatiu passa també per la reflexió sobre la figura i l’actuació del professor com agent directament implicat i responsable, en gran part, de la direcció i gestió del procés d’ensenyament-aprenentatge en el seu sentit més ampli, i alhora particular. En aquest sentit, intentar millorar la comprensió sobre el rol del professor ens podria donar elements que ens ajudessin a millorar alguns aspectes del procés educatiu. Aquesta tesi doctoral té la voluntat d’analitzar el paper del professor d’Educació Física. Per fer-ho, s’ha dissenyat un instrument ad hoc que permeti identificar les competències professionals del professor d’Educació Física des de la perspectiva d’un dels altres protagonistes directes del procés educatiu: els propis alumnes. Per construir l’instrument que hauria de permetre copsar la percepció i l’opinió dels alumnes s’ha decidit, en una fase inicial, triangular amb diferents agents que guarden relació amb l’acció professional del professor d’Educació Física (professors, alumnes, formadors i directors de centres educatius) a través de grups de discussió i entrevistes per identificar les dimensions d’estudi sobre les que fonamentar i estructurar el qüestionari. Aquest qüestionari s’ha passat a una mostra de 1010 alumnes de batxillerat de centres públics i privats de la regió metropolitana de Barcelona, com prova pilota, per valorar, a partir del procés de passació i dels resultats obtinguts, l’adequació del mateix. Els resultats obtinguts mostren, a partir de l’anàlisi descriptiva i estadística, l’adequació i la utilitat de l’instrument com a eina vàlida per estudiar quines són les competències professionals del professor d’Educació Física des de l’òptica dels alumnes de batxillerat.La actual preocupación social por la educación y por el hecho educativo pasa también por la reflexión sobre la figura y la actuación del profesor como agente directamente implicado y responsable, en gran medida, de la dirección y de la gestión del proceso de enseñanza-aprendizaje en su sentido más amplio, y a su vez particular. En este sentido, intentar mejorar la comprensión sobre el rol del profesor nos podría dar elementos que nos ayudasen a mejorar algunos aspectos del proceso educativo. Esta tesis doctoral tiene la voluntad de analizar el papel del profesor de Educación Física. Para ello, se ha diseñado un documento ad hoc que permita identificar las competencias profesionales del profesor de Educación Física desde la perspectiva de uno de los otros protagonistas directos del proceso educativo: los propios alumnos. Para construir el instrumento que deberá permitir captar la percepción y la opinión de los alumnos se ha decidido, en una fase inicial, triangular con diferentes agentes que guardan relación con la acción profesional del profesor de Educación Física (profesores, alumnos, formadores y directores de centros educativos) a través de grupos de discusión y entrevistas para identificar a las dimensiones de estudio sobre las que fundamentar y estructurar el cuestionario. Dicho cuestionario se pasó a una muestra de 1010 alumnos de bachillerato de centros públicos y privados de la región metropolitana de Barcelona, como prueba piloto, para valorar, a partir del proceso de pasación y de los resultados obtenidos, la adecuación del mismo. Los resultados obtenidos muestran, a partir del análisis descriptivo y estadístico, la adecuación y utilidad del instrumento como herramienta válida para estudiar cuales son las competencias profesionales del profesor de Educación Física desde la óptica de los alumnos de bachillerato.The current social concern on education and the educational process also involves a reflection upon the teacher’s figure and its performance as an agent directly involved widely in the management of the teaching-learning process both in general and specific terms. Therefore, a better understanding of the teacher's role will help us to reveal those elements able to contribute on the improvement of certain aspects of the educational process. The aim of this PhD thesis is to analyse the role of the Physical Education teacher. In order to do so, an ad hoc instrument has been designed to identify his/her professional competence from the point of view of another main actor directly involved in the educational process: the student. In order to build this instrument to capture students' perceptions and opinions, it was decided at an initial stage to compare different agents related to the professional activity of the Physical Education teacher (teachers, students, trainers and directors of education centres) though Focus Group methodology and interviews to identify the scope of the research upon which establishing and structuring a questionnaire. The questionnaire was passed to 1010 participants of A level (batxillerat) students from both private and public schools located in urban sorroundings location of Barcelona area as a pilot test to assess its adequacy on the bases of the results obtained. Descriptives and Cronbach’s alpha, Friedman’s, Wilcoxon’s and Kruskal-Wallis’s tests were applied. The results obtained showed the adequacy and usefulness of the instrument as a valid tool to study the different aspects of the professional competence of the Physical Education teacher of A level students

Altered patterns of retinoblastoma gene product expression in adult soft-tissue sarcomas.

Altered expression of the retinoblastoma (RB) tumour-suppressor gene product (pRB) has been detected in sporadic bone and soft-tissue sarcomas. Earlier studies, analysing small cohorts of sarcoma patients, have suggested that these alterations are more commonly associated with high-grade tumours, metastatic lesions and poorer survival. This study was designed to re-examine the prevalence and clinical significance of altered pRB expression in a large and selected group of soft-tissue sarcomas from 174 adult patients. Representative tissue sections from these sarcomas were analysed by immunohistochemistry using a well-characterised anti-pRB monoclonal antibody. Tumours were considered to have a positive pRB phenotype only when pure nuclear staining was demonstrated, and cases were segregated into one of three groups. Group 1 (n = 36) were patients whose tumours have minimal or undetectable pRB nuclear staining (< 20% of tumour cells) and were considered pRB negative. Patients with tumours staining in a heterogeneous pattern (20-79% of tumour cells) were classified as group 2 (n = 99). The staining of group 3 (n = 39) was strongly positive with a homogeneous pRB nuclear immunoreactivity (80-100% of tumour cells). pRB alterations were frequently observed in both low- and high-grade lesions. Altered pRB expression did not correlate with known predictors of survival and was not itself an independent predictor of outcome in the long-term follow-up. These findings support earlier observations that alterations of pRB expression are common events in soft-tissue sarcomas; nevertheless, long-term follow-up results indicate that altered patterns of pRB expression do not influence clinical outcome of patients affected with soft-tissue sarcomas. It is postulated that RB alterations are primary events in human sarcomas and may be involved in tumorigenesis or early phases of tumour progression in these neoplasias

Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor

In the present study the role of Akt/PKB (protein kinase B) in PIF- (proteolysis-inducing factor) induced protein degradation has been investigated in murine myotubes. PIF induced transient phosphorylation of Akt at Ser(473) within 30 min, which was attenuated by the PI3K (phosphoinositide 3-kinase) inhibitor LY294002 and the tyrosine kinase inhibitor genistein. Protein degradation was attenuated in myotubes expressing a dominant-negative mutant of Akt (termed DNAkt), compared with the wild-type variant, whereas it was enhanced in myotubes containing a constitutively active Akt construct (termed MyrAkt). A similar effect was observed on the induction of the ubiquitin-proteasome pathway. Phosphorylation of Akt has been linked to up-regulation of the ubiquitin-proteasome pathway through activation of NF-kappaB (nuclear factor kappaB) in a PI3K-dependent process. Protein degradation was attenuated by rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin), when added before, or up to 30 min after, addition of PIF. PIF induced transient phosphorylation of mTOR and the 70 kDa ribosomal protein S6 kinase. These results suggest that transient activation of Akt results in an increased protein degradation through activation of NF-kappaB and that this also allows for a specific synthesis of proteasome subunits

Interplay between Polo kinase, LKB1-activated NUAK1 kinase, PP1β^MYPT1phosphatase complex and the SCF^βTrCP E3 ubiquitin ligase

NUAK1 (NUAK family SnF1-like kinase-1) and NUAK2 protein kinases are activated by the LKB1 tumour suppressor and have been implicated in regulating multiple processes such as cell survival, senescence, adhesion and polarity. In the present paper we present evidence that expression of NUAK1 is controlled by CDK (cyclin-dependent kinase), PLK (Polo kinase) and the SCF(βTrCP) (Skp, Cullin and F-box(βTrCP)) E3 ubiquitin ligase complex. Our data indicate that CDK phosphorylates NUAK1 at Ser(445), triggering binding to PLK, which subsequently phosphorylates NUAK1 at two conserved non-catalytic serine residues (Ser(476) and Ser(480)). This induces binding of NUAK1 to βTrCP, the substrate-recognition subunit of the SCF(βTrCP) E3 ligase, resulting in NUAK1 becoming ubiquitylated and degraded. We also show that NUAK1 and PLK1 are reciprocally controlled in the cell cycle. In G(2)–M-phase, when PLK1 is most active, NUAK1 levels are low and vice versa in S-phase, when PLK1 expression is low, NUAK1 is more highly expressed. Moreover, NUAK1 inhibitors (WZ4003 or HTH-01-015) suppress proliferation by reducing the population of cells in S-phase and mitosis, an effect that can be rescued by overexpression of a NUAK1 mutant in which Ser(476) and Ser(480) are mutated to alanine. Finally, previous work has suggested that NUAK1 phosphorylates and inhibits PP1β(MYPT1) (where PP1 is protein phosphatase 1) and that a major role for the PP1β(MYPT1) complex is to inhibit PLK1 by dephosphorylating its T-loop (Thr(210)). We demonstrate that activation of NUAK1 leads to a striking increase in phosphorylation of PLK1 at Thr(210), an effect that is suppressed by NUAK1 inhibitors. Our data link NUAK1 to important cell-cycle signalling components (CDK, PLK and SCF(βTrCP)) and suggest that NUAK1 plays a role in stimulating S-phase, as well as PLK1 activity via its ability to regulate the PP1β(MYPT1) phosphatase

Cohort profile:the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands

PURPOSE: The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D). PARTICIPANTS: Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected. FINDINGS TO DATE: Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia. FUTURE PLANS:Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function. TRIAL REGISTRATION NUMBER: NCT04977635.</p

Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection.

BACKGROUND: Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. METHODS: DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. RESULTS: The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. CONCLUSIONS: Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2514-8) contains supplementary material, which is available to authorized users

During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation

Loss of myofibrillar proteins is a hallmark of atrophying muscle. Expression of muscle RING-finger 1 (MuRF1), a ubiquitin ligase, is markedly induced during atrophy, and MuRF1 deletion attenuates muscle wasting. We generated mice expressing a Ring-deletion mutant MuRF1, which binds but cannot ubiquitylate substrates. Mass spectrometry of the bound proteins in denervated muscle identified many myofibrillar components. Upon denervation or fasting, atrophying muscles show a loss of myosin-binding protein C (MyBP-C) and myosin light chains 1 and 2 (MyLC1 and MyLC2) from the myofibril, before any measurable decrease in myosin heavy chain (MyHC). Their selective loss requires MuRF1. MyHC is protected from ubiquitylation in myofibrils by associated proteins, but eventually undergoes MuRF1-dependent degradation. In contrast, MuRF1 ubiquitylates MyBP-C, MyLC1, and MyLC2, even in myofibrils. Because these proteins stabilize the thick filament, their selective ubiquitylation may facilitate thick filament disassembly. However, the thin filament components decreased by a mechanism not requiring MuRF1

The Myostatin gene: an overview of mechanisms of action and its relevance to livestock animals

Myostatin, also known as Growth Differentiation Factor 8, a member of the Transforming Growth Factor-beta (TGF-β) super-family is a negative regulator of muscle development. Myostatin acts at key points during pre- and post-natal life of amniotes which ultimately determine the overall muscle mass of an animal. Mutations have already demonstrated the impact of attenuating Myostatin activity on muscle development. A number of large animals including cattle, sheep, dogs and humans display the ‘double muscled’ phenotype due to mutations in the Myostatin gene. Here we firstly give an overview of the molecular pathways regulated by Myostatin that control muscle development. Then we describe the natural mutations and their associated phenotypes as well as the physiological influence of altering Myostatin expression in livestock animals (cattle, sheep, goat, horse, pig, rabbit and chicken). Knowledge of null alleles and polymorphisms in the Myostatin gene are of great interest in the animal breeding field and it could be utilized to improve meat production in livestock animals

The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

Although the canonical transforming growth factor &beta; signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin&ndash;dependent process, whereas increased BMP&ndash;Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders