Promoting positive physical activity behaviours in children undergoing acute cancer treatment: feasibility of the CanMOVE intervention.

BACKGROUND: Supporting children and adolescents with cancer to be physically active can improve medium- and long-term health outcomes. OBJECTIVE: To assess the feasibility of CanMOVE, a 10-week complex, theoretically-informed, behaviour change intervention to promote physical activity for children and adolescents undergoing acute cancer treatment. METHODS: A feasibility study using a single-group, repeated measures, mixed methods design. Participants completed CanMOVE, which included provision of a Fitbit (child/adolescent and carer) and structured support from a physical therapist. Feasibility domains of demand, acceptability, implementation, practicality, limited efficacy, and integration were evaluated. Data sources included service level data, objective assessment of physical activity, physical function, and health-related quality of life; and qualitative data collected via semi-structured interviews with participants and focus groups with staff. RESULTS: Twenty children/adolescents (median age 13yrs, interquartile-range 9-14) with a mix of cancer diagnoses, 20 parents, and 16 clinicians participated. There was high demand with 95% enrolment rate. CanMOVE was acceptable for participants. All feasibility thresholds set for implementation were met. Under practicality, there were no serious adverse events related to the intervention. Limited efficacy data indicated CanMOVE showed positive estimates of effect in influencing child/adolescent physical activity behaviour, physical function, and health-related quality of life. Positive impacts were also seen in parent and staff attitudes towards physical activity promotion. To improve integration into the clinical setting, it was suggested the duration and scope of CanMOVE could be expanded. CONCLUSION: CanMOVE was feasible to implement in a paediatric cancer setting. CanMOVE is appropriate to be tested in a large-scale trial.

Promoting positive physical activity behaviors for children and adolescents undergoing acute cancer treatment: Development of the CanMOVE intervention using the Behavior Change Wheel.

Background: Increasing participation in physical activity has the potential to improve outcomes for children and adolescents with cancer during treatment and into survivorship. The aim of this study is to outline the theoretical process behind development of CanMOVE, a behavior change intervention designed to increase physical activity for children and adolescents with cancer. Study design: This study followed a theoretical design process consistent with the Behavior Change Wheel to inform the design of a complex intervention. Materials and methods: The three stages of the Behavior Change Wheel intervention design process include: (1) understanding physical activity behavior within the pediatric cancer setting, (2) identifying potential intervention functions, and (3) identifying appropriate behavior change and implementation strategies. Qualitative and behavior change literature relevant to the pediatric cancer treatment setting were used to inform each stage. Results: An individualized and flexible approach to physical activity promotion that considers intrinsic factors specific to the child/adolescent and their environment is required. Fifteen behavioral change strategies were identified to form the intervention components of CanMOVE. Implementation strategies were identified to build motivation, opportunity and capacity toward increasing physical activity behaviors. Key intervention components of CanMOVE include standardized assessment and monitoring (physical activity, physical function, and health-related quality of life), provision of an activity monitor to both child/adolescent and parent, and one-on-one capacity building sessions with a healthcare professional. Capacity building sessions include education, goal setting, an active supervised physical activity session, barrier identification and problem solving, and action planning. Conclusion: CanMOVE is a novel approach to physical activity promotion in the pediatric cancer treatment setting. The use of a theoretical intervention design process will aid evaluation and replication of CanMOVE when it is assessed for feasibility in a clinical setting. The design process utilized here can be used as a guide for future intervention development.

The international Pediatric Oncology Exercise Guidelines (iPOEG).

Physical activity (PA) and exercise are safe and beneficial for children and adolescents affected by cancer. Yet, this population is not active enough to receive benefits. PA guideline and recommendation statements can support individual behavior and practice change. The purpose of this project was to develop the international Pediatric Oncology Exercise Guidelines (iPOEG), comprised of guideline and recommendation statements, to promote PA among children and adolescents affected by cancer. Guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to the iPOEG network (n = 9 core team members, n = 122 expert consensus committee members). Surveys included closed- and open-ended items informed by a literature synthesis and an in-person meeting. Responses were analyzed using descriptive statistics and content analysis. Consensus was defined as ≥ 80% agreement. Response rates to online surveys ranged from 82% to 91%. The iPOEG network agreed on four guideline and five recommendation statements, which highlight that movement is important for all children and adolescents affected by cancer. These statements are generic in nature as more research is still required to provide specific guidance on the frequency, intensity, time, and type of PA for this population. Nevertheless, the iPOEG statements represent available evidence and expert opinion, collectively suggesting that it is time for children and adolescents affected by cancer to move more.

Physical activity is safe and beneficial for children and adolescents affected by cancer. Yet, most are not active enough to receive benefits. Guideline and recommendation statements can help change individual behavior and practice. To develop such statements, guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to an international network (n = 131 experts). Surveys asked closed- and open-ended questions informed by a literature synthesis and an in-person meeting. Findings from the online surveys resulted in the international Pediatric Oncology Exercise Guidelines statements, which highlight that it is time for children and adolescents affected by cancer to move more.

Advancing the Field of Pediatric Exercise Oncology: Research and Innovation Needs.

The field of pediatric exercise oncology explores the relationships between physical activity (PA), including exercise, and a range of outcomes among children and adolescents affected by cancer. Although PA is safe and beneficial for this population, several important gaps in knowledge and practice remain. In this article, we describe research and innovation needs that were developed with a team of international experts and relevant literature, a series of online surveys, and an in-person meeting. Addressing these needs will contribute valuable knowledge and practice outputs to advance this field, ultimately enabling a greater number of children and adolescents affected by cancer to realize the benefits of moving more.

Physical activity for children undergoing acute cancer treatment: A qualitative study of parental perspectives.

BACKGROUND: Little is known about how to facilitate participation in physical activity among children receiving acute cancer treatment. OBJECTIVE: To understand the parental perspectives on physical activity for children during acute cancer treatment and explore strategies to overcome physical inactivity. METHODS: A qualitative study was completed. Data were collected via semistructured interviews with parents of children (aged 4-18 years) who were in their first nine months of cancer treatment. Data were analyzed thematically. RESULTS: Twenty parents were interviewed. A childhood cancer diagnosis and subsequent treatment were described as setting in motion a spiral of physical inactivity. Parents identified movement restrictions as a result of commencing treatment and the hospital environment as factors initiating this decline. Parents described the subsequent impact of movement restrictions on their child over time including loss of independence, isolation, and low motivation. These three consequences further contributed to an inability and unwillingness to be physically active. Parents responded in a variety of ways to their child's inactivity, and many were motivated to overcome the barriers to physical activity yet exhibited a reduced capacity to do so. Suggested intervention strategies highlighted the need for comprehensive support from the organization providing treatment. CONCLUSIONS: Reasons for reduced physical activity in children receiving acute treatment for cancer are complex and multifactorial. Inactivity cannot be addressed by children and parents alone but requires support from the oncology team through changes to the environment, services, and policies to promote physical activity. These findings may be used to inform targeted, effective, and feasible physical activity interventions.

Assessment of physical function in children with cancer: A systematic review.

BACKGROUND: Appropriate selection of robust assessment tools is essential to monitor physical function in children with cancer during and after treatment. This systematic review aims to identify and critically appraise the measurement properties of physical function measures currently used for children with cancer. PROCEDURE: Two systematic searches of seven electronic databases [Cumulative Index to Nursing and Allied Health Literature (CINHAL), Medline, PubMed, PsychINFO, Sportsdiscus, EMBASE, and Allied and Complementary Medicine Database (AMED)] were completed to identify physical function measures used in children with cancer and to evaluate their measurement properties. Methodological quality and the adequacy of measurement properties specific to populations of children with cancer were critically appraised using the COSMIN framework to ascertain which measures have evidence to support their use in children with cancer. RESULTS: One hundred and one physical function measures were identified across 154 studies. Measurement property data were available for 12 measures. The measurement properties of only two outcome measures were assessed in more than one study. Despite some positive measurement property data, there was no assessment tool that had consistent and adequate evidence overall to recommend its use in childhood cancer populations. Poor methodological quality of the included studies was the main limiting factor. CONCLUSIONS: There is very limited population specific evidence to guide the selection of physical function measures in children with cancer. Further research into the reliability, validity and responsiveness of physical function measures in children with cancer is needed to provide a basis for more effective clinical assessment and management.

New ligation independent cloning vectors for expression of recombinant proteins with a self-cleaving CPD/6xHis-tag.

BACKGROUND: Recombinant protein purification is a crucial step for biochemistry and structural biology fields. Rapid robust purification methods utilize various peptide or protein tags fused to the target protein for affinity purification using corresponding matrices and to enhance solubility. However, affinity/solubility-tags often need to be removed in order to conduct functional and structural studies, adding complexities to purification protocols. RESULTS: In this work, the Vibrio cholerae MARTX toxin Cysteine Protease Domain (CPD) was inserted in a ligation-independent cloning (LIC) vector to create a C-terminal 6xHis-tagged inducible autoprocessing enzyme tag, called "the CPD-tag". The pCPD and alternative pCPD/ccdB cloning vectors allow for easy insertion of DNA and expression of the target protein fused to the CPD-tag, which is removed at the end of the purification step by addition of the inexpensive small molecule inositol hexakisphosphate to induce CPD autoprocessing. This process is demonstrated using a small bacterial membrane localization domain and for high yield purification of the eukaryotic small GTPase KRas. Subsequently, pCPD was tested with 40 proteins or sub-domains selected from a high throughput crystallization pipeline. CONCLUSION: pCPD vectors are easily used LIC compatible vectors for expression of recombinant proteins with a C-terminal CPD/6xHis-tag. Although intended only as a strategy for rapid tag removal, this pilot study revealed the CPD-tag may also increase expression and solubility of some recombinant proteins.

The Feasibility of Physical Activity Interventions During the Intense Treatment Phase for Children and Adolescents with Cancer: A Systematic Review.

BACKGROUND: Physical activity may have benefits for children undergoing intense treatment for cancer, but such programmes are challenging to implement. This systematic review aimed to investigate the feasibly of physical activity interventions during intense cancer treatment for children and adolescents. PROCEDURE: A systematic search of seven electronic databases (Cumulative Index to Nursing and Allied Health Literature, Medical Literature Analysis and Retrieval System Online, Public/Publisher MEDLINE, Psychological Information Database, Sportsdiscuss, Excerpta Medica Database, Allied and Complementary Medicine Database) from 2005 to August 2015 was completed. The risk of bias was assessed using the Downs and Black Checklist and The Critical Review Form-Qualitative Studies. Results were summarised descriptively across eight domains of feasibility: acceptability, demand, implementation, adaptation, practicality, integration, expansion and limited efficiency testing (including effectiveness). RESULTS: Eleven quantitative studies and one qualitative study were identified for inclusion. Physical activity interventions were typically supervised, individualised programmes that prescribed a variety of activity types for hospital inpatients. There was evidence that physical activity interventions during the intense phase of cancer treatment were acceptable to parents and children, safe and successfully implemented. A trend of positive effects across all aspects of functioning was noted. Data were unavailable documenting feasibility for the domains of integration, adaptation and expansion. CONCLUSION: There is preliminary evidence that physical activity interventions are feasible, in that they are acceptable, safe and potentially beneficial for children with cancer but more work needs to be done to understand the most effective ways to implement these types of programmes.

Dissecting the Structural Elements for the Activation of ß-Ketoacyl-(Acyl Carrier Protein) Reductase from Vibrio cholerae.

UNLABELLED: ß-Ketoacyl-(acyl carrier protein) reductase (FabG) catalyzes the key reductive reaction in the elongation cycle of fatty acid synthesis (FAS), which is a vital metabolic pathway in bacteria and a promising target for new antibiotic development. The activation of the enzyme is usually linked to the formation of a catalytic triad and cofactor binding, and crystal structures of FabG from different organisms have been captured in either the active or inactive conformation. However, the structural elements which enable activation of FabG require further exploration. Here we report the findings of structural, enzymatic, and binding studies of the FabG protein found in the causative agent of cholera, Vibrio cholerae (vcFabG). vcFabG exists predominantly as a dimer in solution and is able to self-associate to form tetramers, which is the state seen in the crystal structure. The formation of the tetramer may be promoted by the presence of the cofactor NADP(H). The transition between the dimeric and tetrameric states of vcFabG is related to changes in the conformations of the α4/α5 helices on the dimer-dimer interface. Two glycine residues adjacent to the dimer interface (G92 and G141) are identified to be the hinge for the conformational changes, while the catalytic tyrosine (Y155) and a glutamine residue that forms hydrogen bonds to both loop ß4-α4 and loop ß5-α5 (Q152) stabilize the active conformation. The functions of the aforementioned residues were confirmed by binding and enzymatic assays for the corresponding mutants. IMPORTANCE: This paper describes the results of structural, enzymatic, and binding studies of FabG from Vibrio cholerae (vcFabG). In this work, we dissected the structural elements responsible for the activation of vcFabG. The structural information provided here is essential for the development of antibiotics specifically targeting bacterial FabG, especially for the multidrug-resistant strains of V. cholerae.

Crystal structures of putative phosphoglycerate kinases from B. anthracis and C. jejuni.

Phosphoglycerate kinase (PGK) is indispensable during glycolysis for anaerobic glucose degradation and energy generation. Here we present comprehensive structure analysis of two putative PGKs from Bacillus anthracis str. Sterne and Campylobacter jejuni in the context of their structural homologs. They are the first PGKs from pathogenic bacteria reported in the Protein Data Bank. The crystal structure of PGK from Bacillus anthracis str. Sterne (BaPGK) has been determined at 1.68 Å while the structure of PGK from Campylobacter jejuni (CjPGK) has been determined at 2.14 Å resolution. The proteins' monomers are composed of two domains, each containing a Rossmann fold, hinged together by a helix which can be used to adjust the relative position between two domains. It is also shown that apo-forms of both BaPGK and CjPGK adopt open conformations as compared to the substrate and ATP bound forms of PGK from other species.