DR5 disulfide bonding as a sensor and effector of protein folding stress.

New agents are needed that selectively kill cancer cells without harming normal tissues. The TRAIL ligand and its receptors, DR5 and DR4, exhibit cancer-selective toxicity, but TRAIL analogs or agonistic antibodies targeting these receptors have not received FDA approval for cancer therapy. Small molecules for activating DR5 or DR4 independently of protein ligands may bypass some of the pharmacological limitations of these protein drugs.

A Clinically Significant Difference on the COPM: A Review.

The Canadian Occupational Performance Measure (COPM) assists occupational therapists to identify occupational performance problems using a client-centred approach. Since its first publication in 1991, there has been abundant evidence of the ability of the COPM to detect a significant difference as an outcome measure. There has also been a tacit understanding that a difference of 2 points from pre-test to post-test on either Performance or Satisfaction COPM score represents a clinically significant difference.

Anticancer Agents Derived from Cyclic Thiosulfonates: Structure-Reactivity and Structure-Activity Relationships.

Reported are structure-property-function relationships associated with a class of cyclic thiosulfonate molecules-disulfide-bond disrupting agents (DDAs)-with the ability to downregulate the Epidermal Growth Factor Receptor (HER) family in parallel and selectively induce apoptosis of EGFR+ or HER2+ breast cancer cells. Recent findings have revealed that the DDA mechanism of action involves covalent binding to the thiol(ate) from the active site cysteine residue of members of the protein disulfide isomerase (PDI) family. Reported is how structural modifications to the pharmacophore can alter the anticancer activity of cyclic thiosulfonates by tuning the dynamics of thiol-thiosulfonate exchange reactions, and the studies reveal a correlation between the biological potency and thiol-reactivity.

Inhibitors of ERp44, PDIA1, and AGR2 induce disulfide-mediated oligomerization of Death Receptors 4 and 5 and cancer cell death.

Breast cancer mortality remains unacceptably high, indicating a need for safer and more effective therapeutic agents. Disulfide bond Disrupting Agents (DDAs) were previously identified as a novel class of anticancer compounds that selectively kill cancers that overexpress the Epidermal Growth Factor Receptor (EGFR) or its family member HER2. DDAs kill EGFR+ and HER2+ cancer cells via the parallel downregulation of EGFR, HER2, and HER3 and activation/oligomerization of Death Receptors 4 and 5 (DR4/5).

Repurposing Tranexamic Acid as an Anticancer Agent.

Tranexamic Acid (TA) is a clinically used antifibrinolytic agent that acts as a Lys mimetic to block binding of Plasminogen with Plasminogen activators, preventing conversion of Plasminogen to its proteolytically activated form, Plasmin. Previous studies suggested that TA may exhibit anticancer activity by blockade of extracellular Plasmin formation. Plasmin-mediated cleavage of the CDCP1 protein may increase its oncogenic functions through several downstream pathways.

Disulfide bond-disrupting agents activate the tumor necrosis family-related apoptosis-inducing ligand/death receptor 5 pathway.

Disulfide bond-disrupting agents (DDAs) are a new chemical class of agents recently shown to have activity against breast tumors in animal models. Blockade of tumor growth is associated with downregulation of EGFR, HER2, and HER3 and reduced Akt phosphorylation, as well as the induction of endoplasmic reticulum stress. However, it is not known how DDAs trigger cancer cell death without affecting nontransformed cells.

Personal, environmental, and family factors of participation among young children.

Objective: The purpose of this study is to assess the influences of environment, population characteristics, and service utilization on participation frequency and involvement in the home setting among children 0 to 5 years.

Method: Data were collected from parents of 236 children (mean age 3 years and 5 months, SD = 1.30, girls = 152 and boys = 84) using a children's treatment centre in Ontario through an online survey.

A novel proteotoxic combination therapy for EGFR+ and HER2+ cancers.

While HER2 and EGFR are overexpressed in breast cancers and multiple other types of tumors, the use of EGFR and/or HER2 inhibitors have failed to cure many cancer patients, largely because cancers acquire resistance to HER2/EGFR-specific drugs. Cancers that overexpress the HER-family proteins EGFR, HER2, and HER3 are uniquely sensitive to agents that disrupt HER2 and EGFR protein folding. We previously showed that disruption of disulfide bond formation by Disulfide Disrupting Agents (DDAs) kills HER2/EGFR overexpressing cells through multiple mechanisms.

The unfolded protein response as a target for anticancer therapeutics.

The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells, responsible for protein synthesis, folding, sorting, and transportation. ER stress is initiated when the unfolded or misfolded protein load exceeds the capacity of the ER to properly fold protein. Tumor microenvironmental conditions, such as nutrient deprivation, hypoxia, and oxidative stress perturb protein folding and trigger chronic ER stress.

Loss of sirtuin 1 and mitofusin 2 contributes to enhanced ischemia/reperfusion injury in aged livers.

Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood.

The effectiveness of the Pathways and Resources for Engagement and Participation (PREP) intervention: improving participation of adolescents with physical disabilities.

Aim: This study examined the effectiveness of the Pathways and Resources for Engagement and Participation (PREP) intervention in improving the participation of adolescents in community-based activities.

Method: Twenty-eight adolescents (14 males, 14 females), aged 12 to 18 years (mean 14y 6mo, SD 21.6mo) with moderate physical disabilities participated in a 12-week PREP intervention.

Relationships between Adaptive Behaviours, Personal Factors, and Participation of Young Children.

Aim: To examine the extent to which personal factors (age, socioeconomic grouping, and preterm birth) and adaptive behaviour explain the participation patterns of young children.

Methods: 65 Children 2-5 years old with and without a history of preterm birth and no physical or intellectual disability were selected by convenience sampling from Galway University Hospital, Ireland. Interviews with parents were conducted using the Adaptive Behaviour Assessment System, Second Edition (ABAS-II) and the Assessment of Preschool Children's Participation (APCP).

Psychometric Evaluation of the Young Children's Participation and Environment Measure (YC-PEM) for use in Singapore.

Aims: To estimate the psychometric properties of a culturally adapted version of the Young Children's Participation and Environment Measure (YC-PEM) for use among Singaporean families.

Methods: This is a prospective cohort study. Caregivers of 151 Singaporean children with (n = 83) and without (n = 68) developmental disabilities, between 0 and 7 years, completed the YC-PEM (Singapore) questionnaire with 3 participation scales (frequency, involvement, and change desired) and 1 environment scale for three settings: home, childcare/preschool, and community.

Disulfide bond disrupting agents activate the unfolded protein response in EGFR- and HER2-positive breast tumor cells.

Many breast cancer deaths result from tumors acquiring resistance to available therapies. Thus, new therapeutic agents are needed for targeting drug-resistant breast cancers. Drug-refractory breast cancers include HER2+ tumors that have acquired resistance to HER2-targeted antibodies and kinase inhibitors, and "Triple-Negative" Breast Cancers (TNBCs) that lack the therapeutic targets Estrogen Receptor, Progesterone Receptor, and HER2.

Measuring Participation of Children and Environmental Factors at Home, School, and in Community: Construct Validation of the Korean PEM-CY.

Aims: To determine construct validity of the Korean Participation and Environment Measure for Children and Youth (KPEM-CY) in South Korea.

Methods: A total of 184 parents of children with (n = 80) and without disabilities (n = 104) aged 5 to 13 years completed the KPEM-CY. Construct validity was analyzed by assessing differences in the participation and environment scores for children with and without disabilities across age and gender.

Leisure participation-preference congruence of children with cerebral palsy: a Children's Assessment of Participation and Enjoyment International Network descriptive study.

Aim: To examine participation-preference congruence, regional differences in participation-preference congruence, and predictors of whether children with cerebral palsy participate in preferred activities.

Method: The sample (n=236) included 148 males and 88 females aged 10 to 13 years, living in Victoria, Australia (n=110), Ontario (n=80), or Quebec (n=46), Canada. Ninety-nine (41.

Knowledge Translation from Research to Clinical Practice: Measuring Participation of Children with Disabilities.

This knowledge translation project was conducted to increase occupational therapy practitioners' awareness of the importance of measuring participation of children with disabilities. The Knowledge to Action process framework (KTA framework) guided knowledge translation via a web-based seminar (webinar) to practitioners working with children and educators teaching in occupational therapy programs in South Korea. Two hundred and seventy six views of the webinar were recorded within a month and 15 practitioners and 13 educators completed the online evaluation survey.

Participation in Out-of-Home Environments for Young Children With and Without Developmental Disabilities.

This study examines caregivers' perceptions of participation patterns and environmental supports and barriers for young children with and without developmental disabilities within their child care/preschool and community settings. The Young Children's Participation and Environment Measure (YC-PEM) was completed by 151 parents of Singaporean children (0-7 years old) with and without developmental disabilities. Setting-specific summary and item-level scores of these children were compared using ANCOVA, Mann-Whitney U, and Pearson chi-square tests.

CUB domain-containing protein 1 and the epidermal growth factor receptor cooperate to induce cell detachment.

Background: While localized malignancies often respond to available therapies, most disseminated cancers are refractory. Novel approaches, therefore, are needed for the treatment of metastatic disease. CUB domain-containing protein1 (CDCP1) plays an important role in metastasis and drug resistance; the mechanism however, is poorly understood.

Developing a classification system of social communication functioning of preschool children with autism spectrum disorder.

Aim: Impairments in social communication are the hallmark of autism spectrum disorder (ASD). Operationalizing 'severity' in ASD has been challenging; thus, stratifying by functioning has not been possible. The purpose of this study is to describe the development of the Autism Classification System of Functioning: Social Communication (ACSF:SC) and to evaluate its consistency within and between parent and professional ratings.

Comparative Effectiveness Research and Children With Cerebral Palsy: Identifying a Conceptual Framework and Specifying Measures.

Purpose: A step toward advancing research about rehabilitation service associated with positive outcomes for children with cerebral palsy is consensus about a conceptual framework and measures.

Methods: A Delphi process was used to establish consensus among clinicians and researchers in North America.

Results: Directors of large pediatric rehabilitation centers, clinicians from large hospitals, and researchers with expertise in outcomes participated (N = 18).

Current Rehabilitation Practices for Children with Cerebral Palsy: Focus and Gaps.

Aims: To describe the focus of therapy practices in occupational and physical therapy for school-aged children with cerebral palsy, and better understand whether it is congruent with recommended practices.

Methods: A Canada-wide Web-based survey was completed by 62 occupational and 61 physical therapists to identify problems, assessments, and treatment interventions for two case-based scenarios. Data were coded using the International Classification of Functioning, Disability and Health (ICF) definitions for "body functions and structure," "activity and participation," and "environment.

Cross-cultural validation and psychometric evaluation of the Participation and Environment Measure for Children and Youth in Korea.

Purpose: To develop the Korean version of the Participation and Environment Measure for Children and Youth (KPEM-CY) and examine its psychometric properties.

Method: The PEM-CY was cross-culturally translated into Korean using a specific guideline: pre-review of participation items, forward/backward translation, expert committee review, pre-test of the KPEM-CY and final review. To establish internal consistency, test-retest reliability and construct validity of the KPEM-CY, 80 parents of children with disabilities aged 5-13 years were recruited in South Korea.

The role of occupational therapists in the contexts of a natural disaster: a scoping review.

Purpose: To identify and inform the experience and roles of occupational therapists (OTs) in the contexts of a natural disaster.

Method: This scoping review was conducted via five steps: (1) identify the research question, (2) identify relevant academic articles published between 2000 and 2014 in English, (3) select articles based on the inclusion criteria, (4) chart the data and (5) collate, summarise, and report the results of the selected articles. The results were presented using descriptive numerical and thematic analyses.