Evaluating the feasibility, fidelity, and preliminary effectiveness of a school-based intervention to improve the school participation and feelings of connectedness of elementary school students on the autism spectrum.

In My Shoes is a peer supported, teacher-led, school-based intervention that aims to improve the school participation and connectedness of students on the autism spectrum. The aim of this study was to explore the feasibility, fidelity, and preliminary effectiveness of In My Shoes in mainstream elementary schools. Ten Grade 3 and 4 students on the autism spectrum and 200 of their typically developing peers across eight classrooms and six schools participated. The following aspects of feasibility were explored: recruitment capability and sample characteristics, data collection procedures and outcome measures, appropriateness, implementation, and practicality of the intervention. Fidelity was explored by evaluating the delivery of intervention components against set criteria. Preliminary effectiveness was investigated by evaluating changes in intervention outcomes pre-post intervention using a range of outcome measures. Study findings are encouraging, suggesting In My Shoes is a feasible and appropriate intervention, and shows promise in improving the self-report school engagement of all student participants, as well the classroom participation and subjective school experiences of students on the autism spectrum. Useful insights into ways the intervention and the design of future research can be improved are discussed.

Closing the Gap Between Theory and Practice: Conceptualisation of a School-Based Intervention to Improve the School Participation of Primary School Students on the Autism Spectrum and Their Typically Developing Peers.

Limited interventions exist that support student's school participation. This paper describes a theoretical model of school participation and the iterative process that led to the development of an intervention that aims to improve the school participation of students on the autism spectrum and their typically developing peers. Literature on autism, school participation and intervention research were integrated to develop a theoretical model. Focus groups, a Delphi study, online surveys, and reference group consultation helped to develop and refine the intervention. A novel school-based intervention was developed. The impetus to develop interventions with a strong theoretical rationale is discussed.

School participation: The shared perspectives of parents and educators of primary school students on the autism spectrum.

BACKGROUND: An international focus on the inclusion of students with disabilities in mainstream schools and the increased prevalence of autism spectrum disorder (ASD) has contributed to increasing numbers of students with ASD enrolling in mainstream schools. The school participation restrictions of adolescent students with ASD is widely researched, but less is known about the challenges faced by primary school students with ASD and how early in their schooling these challenges arise. METHODS: Focus groups were used to explore the perspectives of parents and educators on the school participation of primary school students with ASD. Focus group data were analysed thematically. RESULTS: Four themes were derived from the data: (1) more than just being there; (2) meeting in the middle; (3) consistency of supports; and (4) embrace difference. CONCLUSIONS: Findings from this study highlight that students aged between 6 and 11 years experience school participation restrictions due to a range of intrinsic (e.g., sense of self and school belonging) and extrinsic factors (e.g., school culture, educator knowledge and skills). It is imperative school based interventions are developed and implemented in the early primary years, that not only target students' skills, but the range of environmental enablers and barriers impacting student school participation.

Evaluating the psychometric quality of school connectedness measures: A systematic review.

INTRODUCTION: There is a need to comprehensively examine and evaluate the quality of the psychometric properties of school connectedness measures to inform school based assessment and intervention planning. OBJECTIVE: To systematically review the literature on the psychometric properties of self-report measures of school connectedness for students aged six to 14 years. METHODS: A systematic search of five electronic databases and gray literature was conducted. The COnsensus-based Standards for the selection of heath Measurement INstruments (COSMIN) taxonomy of measurement properties was used to evaluate the quality of studies and a pre-set psychometric criterion was used to evaluate the overall quality of psychometric properties. RESULTS: The measures with the strongest psychometric properties was the School Climate Measure and the 35-item version Student Engagement Instrument exploring eight and 12 (of 15) school connectedness components respectively. CONCLUSIONS: The overall quality of psychometric properties was limited suggesting school connectedness measures available require further development and evaluation.

A Kinesin-14 Motor Activates Neocentromeres to Promote Meiotic Drive in Maize.

Maize abnormal chromosome 10 (Ab10) encodes a classic example of true meiotic drive that converts heterochromatic regions called knobs into motile neocentromeres that are preferentially transmitted to egg cells. Here, we identify a cluster of eight genes on Ab10, called the Kinesin driver (Kindr) complex, that are required for both neocentromere motility and preferential transmission. Two meiotic drive mutants that lack neocentromere activity proved to be kindr epimutants with increased DNA methylation across the entire gene cluster. RNAi of Kindr induced a third epimutant and corresponding loss of meiotic drive. Kinesin gliding assays and immunolocalization revealed that KINDR is a functional minus-end-directed kinesin that localizes specifically to knobs containing 180 bp repeats. Sequence comparisons suggest that Kindr diverged from a Kinesin-14A ancestor ∼12 mya and has driven the accumulation of > 500 Mb of knob repeats and affected the segregation of thousands of genes linked to knobs on all 10 chromosomes.

Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins.

Regular usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with reduced incidence of a variety of cancers. The molecular mechanisms underlying these chemopreventive effects remain poorly understood. This current investigation showed that in gastric cancer cells: (1) Indomethacin treatment enhanced the degradation of chromosomal passenger proteins, Survivin and Aurora B kinase; (2) Indomethacin treatment down-regulated Aurora B kinase activity in a cell cycle-independent fashion; (3) siRNA knockdown of Survivin level promoted Aurora B kinase protein degradation, and vice versa; (4) ectopic overexpression of Survivin blocked reduction of Aurora B kinase level and activity by indomethacin treatment, and vice versa; (5) siRNA knockdown of Aurora B kinase level and AZD1152 inhibition of its activity induced apoptosis, and overexpression of Aurora B kinase inhibited indomethacin-induced apoptosis; (6) indomethacin treatment reduced Aurora B kinase level, coinciding with reduction of Survivin level and induction of apoptosis, in KATO III and HT-29 cells, and in mouse gastric mucosa. A role for Aurora B kinase function in NSAID-induced apoptosis was not previously explored. Thus this report provides better understanding of the molecular mechanisms underlying the anti-cancer effect of NSAIDs by elucidating a significant role for Aurora B kinase in indomethacin-induced apoptosis.

Sulindac sulfide induces autophagic death in gastric epithelial cells via survivin down-regulation: a mechanism of NSAIDs-induced gastric injury.

Sulindac sulfide, a nonsteroidal anti-inflammatory drug (NSAID), has anti-tumorigenic and anti-inflammatory activities, but causes gastric mucosal damage. NSAIDs cause gastric injury in part by down-regulation of Survivin, an apoptosis inhibitor, resulting in apoptosis induction. Autophagy is a process that promotes cellular health by destroying unwanted cellular materials. Excessive autophagy induction could lead to a non-apoptotic cell death (autophagic cell death). The present study showed that sulindac sulfide at a physiological concentration also induces autophagic death in human gastric epithelial AGS and rat gastric epithelial RGM-1 cells, and that Survivin down-regulation is a mechanism involved: Sulindac sulfide treatment increased LC3b-II and APG7 levels and cytosolic vacuole formation, indications of autophagy induction, in AGS and RGM-1 cells. Sulindac sulfide treatment induced AGS and RGM-1 cell death, which was significantly reduced by pretreatment with the autophagy inhibitors 3-methyladenine and chloroquine, indicating that sulindac sulfide induced autophagic cell death. Stable overexpression of Survivin in RGM-1 cells did not inhibit the induction of LC3b-II levels or vacuole formation by sulindac sulfide, but significantly reduced the resulting cell death, suggesting that Survivin may inhibit autophagic cell death downstream of LC3b-II induction and vacuole formation. Indeed, siRNA depletion of LC3b in AGS cells inhibited the down-regulation of Survivin levels and the induction of cell death by sulindac sulfide, confirming that down-regulation of Survivin occurs in the autophagy pathway downstream of LC3b-II induction by sulindac sulfide. Induction of Survivin-dependent autophagic cell death is a novel mechanism by which sulindac sulfide induces gastric mucosal injury.

Suppression of growth arrest and DNA damage-inducible 45alpha expression confers resistance to sulindac and indomethacin-induced gastric mucosal injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac and indomethacin are a major cause of gastric erosions and ulcers. Induction of apoptosis by NSAIDs is an important mechanism involved. Understanding how NSAIDs affect genes that regulate apoptosis is useful for designing therapeutic or preventive strategies and for evaluating the efficacy of safer drugs being developed. We investigated whether growth arrest and DNA damage-inducible 45alpha (GADD45alpha), a stress signal response gene involved in regulation of DNA repair and induction of apoptosis, plays a part in NSAID-induced gastric mucosal injury and apoptosis in vivo in mice and in vitro in cultured human AGS and rat RGM-1 gastric epithelial cells. Intraperitoneal administration of sulindac and indomethacin both resulted in up-regulation of GADD45alpha expression and induction of significant injury and apoptosis in gastric mucosa of wild-type mice. GADD45alpha(-/-) mice were markedly more resistant to both sulindac- and indomethacin-induced gastric mucosal injury and apoptosis than wild-type mice. Sulindac sulfide and indomethacin treatments also concentration-dependently increased GADD45alpha expression and apoptosis in AGS and RGM-1 cells. Antisense suppression of GADD45alpha expression significantly reduced sulindac and indomethacin-induced activation of caspase-9 and apoptosis in AGS cells. Pretreatments with exogenous prostaglandins and small interfering RNA suppression of cyclooxygenase (COX)-1 and -2 did not affect up-regulation of GADD45alpha by sulindac sulfide and indomethacin in AGS cells. These findings indicate that GADD45alpha up-regulation is a COX-independent mechanism that is required for induction of severe gastric mucosal apoptosis and injury by NSAIDs, probably via a capase-9-dependent pathway of programmed cell death.

Chronic pain syndrome associated with health anxiety: a qualitative thematic comparison between pain patients with high and low health anxiety.

OBJECTIVES: Based on the high prevalence of health anxiety among patients with chronic pain and the conceptual overlap between the diagnostic criteria for hypochondriasis and pain disorder, it has been suggested that the cognitive-behavioural theory of severe and persistent health anxiety can be applied to understand the problems presented by a subgroup of chronic pain patients. This study aimed to provide qualitative data to complement the progress of the existing experimental research and theory development. DESIGN: A cross-sectional design with two groups was adopted. METHOD: In-depth semi-structured interviews were conducted with 60 chronic pain patients seeking medical treatment from a specialist clinic, and theoretical thematic analysis was performed on a subset of interview transcripts drawn from the five most health anxious and the five least health anxious of this sample. RESULTS: Five themes emerged from the analysis, and they concerned (1) pain appraisal, (2) pain preoccupation, (3) coping strategies, (4) self-identity, and (5) suicidal ideation. Differences were observed between the health anxious and non-health anxious pain patients consistently across all these themes. CONCLUSIONS: The phenomenological information both informs and supports the idea that the cognitive-behavioural model of health anxiety can be adapted for the understanding of and development of treatments for pain patients with health anxiety. The findings also challenge the common practice of 'lumping' pain patients into a single group and underline the importance of matching treatments to the patients' psychological characteristics.

Effects of mood on pain responses and pain tolerance: an experimental study in chronic back pain patients.

Although chronic pain and depression commonly co-occur, causal relationships have yet to be established. A reciprocal relationship, with depression increasing pain and vice versa, is most frequently suggested, but experimental evidence is needed to validate such a view. The most straightforward approach would be a demonstration that increasing or decreasing depressed mood predictably modifies pain responses. The current experiment tested whether experimentally induced depressed and happy mood have differential effects on pain ratings and tolerance in 55 patients suffering from chronic back pain. Participants were randomly assigned to depressed, neutral (control) or elated mood induction conditions. They completed a physically passive baseline task prior to receiving mood induction, then a clinically relevant physically active task (holding a heavy bag) to elicit pain responses and tolerance. Measures were taken immediately after the baseline task and immediately after the mood induction to assess the changes in mood, pain ratings and tolerance before and after the experimental manipulation. Results indicate that the induction of depressed mood resulted in significantly higher pain ratings at rest and lower pain tolerance, whilst induced happy mood resulted in significantly lower pain ratings at rest and greater pain tolerance. Correlations between changes in mood on the one hand and changes in pain response and pain tolerance on the other hand were consistent with these findings. It is concluded that, in chronic back pain patients, experimentally induced negative mood increases self-reported pain and decreases tolerance for a pain-relevant task, with positive mood having the opposite effect.