DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik

Development of a self-management program for employees with complaints of the arm, neck, and/or shoulder: an intervention mapping approach

Nathan Hutting,1,2 Sarah I Detaille,2,3 Josephine A Engels,2 Yvonne F Heerkens,2 J Bart Staal,1,4 Maria WG Nijhuis-van der Sanden1 1Radboud University Medical Center, Radboud Institute for Health Sciences, the Scientific Institute for Quality of Healthcare, 2Hogeschool van Arnhem en Nijmegen (HAN) University of Applied Sciences, Faculty of Health and Social Studies, Research Group Occupation and Health, 3HAN University of Applied Sciences, Department HAN Seneca, 4HAN University of Applied Sciences, Faculty of Health and Social Studies, Research Group Musculoskeletal Rehabilitation, Nijmegen, the Netherlands Purpose: To develop a self-management program with an additional eHealth module, using the six steps of the intervention mapping (IM) protocol, to help employees with complaints of the arm, neck, and/or shoulder (CANS) cope with their problems.Methods: In Step 1 of the IM protocol, a needs assessment was performed consisting of a review of the Dutch multidisciplinary guidelines on CANS, and of focus group sessions with employees with CANS (n=15) and with relevant experts (n=17). After the needs assessment, the objectives of the intervention and the determinants of self-management at work were formulated (Step 2). Furthermore, theory-based intervention methods and practical strategies were selected (Step 3), and an intervention program (including the eHealth module) was developed (Step 4). Finally, plans for implementation and evaluation of the program were developed (Steps 5 and 6).Results: Step 1 of the IM protocol revealed that employees with CANS should be stimulated to search for information about the cause of their complaints, about how to deal with their complaints, and in which manner they can influence their complaints themselves. In Step 2, the overall goal of the intervention was defined as “self-management behavior at work” with the aim to alleviate the perceived disability of the participants. Step 3 described how the intervention methods were translated into practical strategies, and goal setting was introduced as an important method for increasing self-efficacy. The product of Step 4 was the final program plan, consisting of 6-weekly group sessions of 2.5 hours each and an eHealth module. In Step 5, a recruitment plan and course materials were developed, a steering committee was set up, trainers were recruited, and the final program was tested. In Step 6, an evaluation plan was developed, which consists of a randomized controlled trial with a 12-month follow-up period and a qualitative evaluation (interviews) with some of the participants.Conclusion: This study resulted in a theory- and practice-based self-management program, based on behavioral change theories, guideline-related evidence, and practice-based knowledge that fits the needs of employees with CANS. Keywords: CANS, work-related upper extremity disorders, WRUED, behavioral change theory, intervention development, perceived disabilit

Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design

Background: In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients' experiences with NET and to identify influencing factors on treatment results. Methods: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n = 25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the understanding of quantitative outcomes. Discussion: The results of this study will provide more insight into influencing factors for clinical changes in this population

Successful use of albuterol in a patient with central core disease and mitochondrial dysfunction

Albuterol, a selective beta-adrenergic agonist, has been used experimentally in combination with exercise therapy in a few inherited neuromuscular disorders to increase muscle strength and muscle volume . We report on a 9-year-old boy with central core disease and mitochondrial dysfunction due to compound heterozygous RYR1 mutations receiving albuterol treatment for 1 year. Throughout the period of albuterol administration, the patient underwent an aerobic exercise regime of training sessions three times a week that lasted 20 min each. No side effects of albuterol use were seen. Significant clinical progress, including self care, sitting up, raising arms above the shoulders, independent feeding, and better speech and writing were observed compared with minimal development of these abilities in the previous years on physiotherapy. Improved forced expiratory volume in 1 s (FEV1) score was detected and increased muscle strength was noted: progress was measured using various functional tests and assessment scales. The only complication observed was a mild progression of the joint contractures, possibly due to an unbalance between the flexor and extensor musculature. In general, in this pilot study in a complex case of metabolic myopathy our patient has shown promising results following albuterol treatment and aerobic exercise therapy.status: publishe