Physical Activity Among Adolescent Cancer Survivors: The PACCS Study

OBJECTIVES Physical activity (PA) may modify risks of late effects after cancer. We aimed to examine levels of PA and sedentary time (ST) in a large, international sample of adolescent childhood cancer survivors in relation to sociodemographic and cancer-related factors and compare levels of PA and ST to reference cohorts. METHODS Survivors from any cancer diagnosis who had completed cancer treatment ≥1 year ago, aged 9 to 16 years, were eligible for the multicenter Physical Activity in Childhood Cancer Survivors study. PA and ST were measured by ActiGraph GT3X+ accelerometers. We performed linear regression analyses to assess factors associated with moderate-to-vigorous PA (MVPA) and ST, and compared marginal means of total PA, MVPA, and ST in 432 survivors to sex- and age-stratified references (2-year intervals) using immediate t-tests for aggregated data. RESULTS Among survivors, 34% fulfilled the World Health Organization's PA recommendation of ≥60 min of daily MVPA on average and their ST was 8.7 hours per day. Being female, older, overweight, a survivor of central nervous system tumor, or having experienced relapse were associated with lower MVPA and/or higher ST. Generally, male survivors spent less time in MVPA compared with references, whereas female survivors had similar levels. Both male and female survivors had higher ST than references in nearly all age groups. CONCLUSIONS The low PA and high ST in this large sample of adolescent childhood cancer survivors is worrisome. Combined, our results call for targeted interventions addressing both PA and ST in follow-up care after childhood cancer

The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) Study: Protocol for an International Mixed Methods Study

BACKGROUND Survivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse. OBJECTIVE The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4). METHODS The PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with ≥1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures. RESULTS Ethical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published. CONCLUSIONS The PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/35838

Validating the Johns Hopkins ACG Case-Mix System of the elderly in Swedish primary health care

BACKGROUND: Individualbased measures for comorbidity are of increasing importance for planning and funding health care services. No measurement for individualbased healthcare costs exist in Sweden. The aim of this study was to validate the Johns Hopkins ACG Case-Mix System's predictive value of polypharmacy (regular use of 4 or more prescription medicines) used as a proxy for health care costs in an elderly population and to study if the prediction could be improved by adding variables from a population based study i.e. level of education, functional status indicators and health perception. METHODS: The Johns Hopkins ACG Case-Mix System was applied to primary health care diagnoses of 1402 participants (60–96 years) in a cross-sectional community based study in Karlskrona, Sweden (the Swedish National study on Ageing and Care) during a period of two years before they took part in the study. The predictive value of the Johns Hopkins ACG Case-Mix System was modeled against the regular use of 4 or more prescription medicines, also using age, sex, level of education, instrumental activity of daily living- and measures of health perception as covariates. RESULTS: In an exploratory biplot analysis the Johns Hopkins ACG Case-Mix System, was shown to explain a large part of the variance for regular use of 4 or more prescription medicines. The sensitivity of the prediction was 31.9%, whereas the specificity was 88.5%, when the Johns Hopkins ACG Case-Mix System was adjusted for age. By adding covariates to the model the sensitivity was increased to 46.3%, with a specificity of 90.1%. This increased the number of correctly classified by 5.6% and the area under the curve by 11.1%. CONCLUSION: The Johns Hopkins ACG Case-Mix System is an important factor in measuring comorbidity, however it does not reflect an individual's capability to function despite a disease burden, which has importance for prediction of comorbidity. In this study we have shown that information on such factors, which can be obtained from short questionnaires increases the probability to correctly predict an individual's use of resources, such as medications

The Tandem CARDs of NOD2: Intramolecular Interactions and Recognition of RIP2

Caspase recruitment domains (CARDs) are homotypic protein interaction modules that link the stimulus-dependent assembly of large signaling platforms such as inflammasomes to the activation of downstream effectors that often include caspases and kinases and thereby play an important role in the regulation of inflammatory and apoptotic signaling pathways. NOD2 belongs to the NOD-like (NLR) family of intracellular pattern recognition receptors (PRR) and induces activation of the NF-κB pathway in response to the recognition of bacterial components. This process requires the specific recognition of the CARD of the protein kinase RIP2 by the tandem CARDs of NOD2. Here we demonstrate that the tandem CARDs of NOD2 are engaged in an intramolecular interaction that is important for the structural stability of this region. Using a combination of ITC and pull-down experiments we identify distinct surface areas that are involved in the intramolecular tandem CARD interaction and the interaction with the downstream effector RIP2. Our findings indicate that while CARDa of NOD2 might be the primary binding partner of RIP2 the two CARDs of NOD2 do not act independently of one another but may cooperate to from a binding surface that is distinct from that of single CARDs

Predominant decay channel for superexcited organic molecules

Photoabsorption and photoionization cross sections of organic molecules are systematically compared for elucidating relation between superexcitation and ionization. The cross sections examined are of alkenes, alkanes, alcohols, and ethers in the energy range of about 2 eV above the first ionization potential. Although the photoabsorption cross sections are much different from one another, the photoionization cross sections are similar in each molecular group. This result indicates that ions are formed only through direct photoionization and most of superexcited molecules dissociate to neutral fragments. Ionization efficiency curves are calculated under the assumption of no autoionization, and they well reproduce the observed ionization curves, which mainly depend on energy difference between the first and second ionization potentials