Effects of physical activity interventions for caregivers of adults: A meta-analysis.

OBJECTIVES: Caregivers of adults afflicted with a variety of chronic physical and mental health conditions are at risk for poorer well-being and reduced health related to chronic stress. Physical activity (PA) interventions may alleviate aspects of this burden, as well as provide benefits to physical health. However, notable limitations exist in the previous reviews that have attempted to synthesize the evidence for the benefits of PA interventions. METHOD: A meta-analysis was conducted investigating and quantifying the impact of PA interventions on different domains of mental and physical health for caregivers of adults, including only randomized and nonrandomized control trials. RESULTS: A comprehensive search yielded 25 studies. PA interventions led to small-to-medium effects (Hedges' g = .37, 95% confidence interval [.18, .56]) on mental health, with the most notable impact on quality of life (Hedges' g = .74, 95% CI [48, 1.01]). PA interventions led to trivial effects on physical health (Hedges' g = .15, 95% CI [.01, .31]), with small but significant effects found for mobility outcomes (Hedges' g = .28, 95% CI [.10, .47]). Yoga interventions yielded large effects (g = .85, 95% CI [.52, 1.17], p < .001) compared to other forms of PA (g = .24, 95% CI [.40, .43], p = .018), primarily within the domain of mental health. CONCLUSIONS: PA interventions appear to be effective for improving caregiver health, particularly in relation to psychological health. Further high-quality research using standardized measures for outcome comparison is needed to determine the type, formats, and length of PA interventions that best serve different caregiving populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A collaborative approach to adopting/adapting guidelines. The Australian 24-hour movement guidelines for children (5-12 years) and young people (13-17 years): An integration of physical activity, sedentary behaviour, and sleep.

BACKGROUND: In 2018, the Australian Government updated the Australian Physical Activity and Sedentary Behaviour Guidelines for Children and Young People. A requirement of this update was the incorporation of a 24-hour approach to movement, recognising the importance of adequate sleep. The purpose of this paper was to describe how the updated Australian 24-Hour Movement Guidelines for Children and Young People (5 to 17 years): an integration of physical activity, sedentary behaviour and sleep were developed and the outcomes from this process. METHODS: The GRADE-ADOLOPMENT approach was used to develop the guidelines. A Leadership Group was formed, who identified existing credible guidelines. The Canadian 24-Hour Movement Guidelines for Children and Youth best met the criteria established by the Leadership Group. These guidelines were evaluated based on the evidence in the GRADE tables, summaries of findings tables and recommendations from the Canadian Guidelines. We conducted updates to each of the Canadian systematic reviews. A Guideline Development Group reviewed, separately and in combination, the evidence for each behaviour. A choice was then made to adopt or adapt the Canadian recommendations for each behaviour or create de novo recommendations. We then conducted an online survey (n=237) along with three focus groups (n=11 in total) and 13 key informant interviews. Stakeholders used these to provide feedback on the draft guidelines. RESULTS: Based on the evidence from the Canadian systematic reviews and the updated systematic reviews in Australia, the Guideline Development Group agreed to adopt the Canadian recommendations and, apart from some minor changes to the wording of good practice statements, maintain the wording of the guidelines, preamble, and title of the Canadian Guidelines. The Australian Guidelines provide evidence-informed recommendations for a healthy day (24-hours), integrating physical activity, sedentary behaviour (including limits to screen time), and sleep for children (5-12 years) and young people (13-17 years). CONCLUSIONS: To our knowledge, this is only the second time the GRADE-ADOLOPMENT approach has been used to develop movement behaviour guidelines. The judgments of the Australian Guideline Development Group did not differ sufficiently to change the directions and strength of the recommendations and as such, the Canadian Guidelines were adopted with only very minor alterations. This allowed the Australian Guidelines to be developed in a shorter time frame and at a lower cost. We recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines that was developed using the GRADE approach is available with all supporting materials. Other countries may consider this approach when developing and/or revising national movement guidelines.

Is greater public transport use associated with higher levels of physical activity in a regional setting? Findings from a pilot study.

BACKGROUND: Public transport users often accumulate more physical activity than motor vehicle users, but most studies have been conducted in large metropolitan areas with multiple public transport options with limited knowledge of the relationship in regional and rural areas. In a regional city, this pilot study aimed to (1) test the feasibility of preliminary hypotheses to inform future research, (2) test the utility of survey items, and (3) establish stakeholder engagement. METHODS: Data were collected via a cross-sectional online survey of 743 Tasmanian adults. Physical activity outcomes were walking (min/week), total moderate- to vigorous-intensity physical activity (min/week) and attainment of physical activity guidelines (yes/no). Transport variables were frequency of public and private transport use per week. Truncated and log binomial regression examined associations between public/private transport use and physical activity. RESULTS: Neither frequency of public nor private transport use was associated with minutes of walking (public transport: B - 24.4, 95% CI: - 110.7, 61.9; private transport: B - 1.1, 95% CI: - 72.4, 70.1), minutes of total physical activity (public transport: B - 90.8, 95% CI: - 310.0, 128.5; private transport: B 0.4, 95% CI: - 134.0, 134.9) or not meeting physical activity guidelines (public transport: RR 1.02, 95%CI: 0.95, 1.09; private transport: RR 1.02, 95%CI: 0.96, 1.08). CONCLUSIONS: The hypothesis that public transport users would be more physically active than private transport users was not supported in this pilot study. Stakeholders were engaged and involved in various phases of the research including development of research questions, participant recruitment, and interpretation of findings. Further studies using representative samples and refined measures are warranted to confirm or refute findings.

Change in Perceived Stress and Health Behaviors of Emerging Adults in the Midst of the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented disruptions, restrictions, and concerns about physical and mental health. Emerging adulthood, including the first year of college, is associated with declines in healthy eating and physical activity, as well as possible heightened distress. The impact of COVID-19 may exacerbate these concerns. PURPOSE: The purpose of this study was to examine changes in health behaviors and perceived stress in emerging adults over the first year of college and to determine whether prepandemic health behaviors were protective for mental health and stress during the initial changes after the COVID-19 pandemic. METHODS: First-year college students (N = 234, 58.6% female) completed three surveys during their first year of school, the third being after the onset of COVID-19 and during a stay-at-home order. At Time 3, we also assessed symptoms of anxiety and depression. RESULTS: Using linear mixed modeling, sedentary time increased and physical activity decreased over time, but 20%-35% of students reported improvements in these behaviors. Dietary changes appeared mixed, with some improvements noted early during COVID-19. Perceived stress increased over time. Multiple regression indicated that of the health behaviors examined for protective effects on mental health and stress during the pandemic, only diet quality emerged as a significant predictor. CONCLUSIONS: Although notable declines in some health habits were observed over time, including following COVID-19 disruptions, some students reported improved health behaviors. Efforts should be directed at identifying and intervening with students most at risk for poor functioning.

Genomic and signalling pathway characterization of the NZM panel of melanoma cell lines: A valuable model for studying the impact of genetic diversity in melanoma.

Melanoma is a disease associated with a very high mutation burden and thus the possibility of a diverse range of oncogenic mechanisms that allow it to evade therapeutic interventions and the immune system. Here, we describe the characterization of a panel of 102 cell lines from metastatic melanomas (the NZM lines), including using whole-exome and RNA sequencing to analyse genetic variants and gene expression changes in a subset of this panel. Lines possessing all major melanoma genotypes were identified, and hierarchical clustering of gene expression profiles revealed four broad subgroups of cell lines. Immunogenotyping identified a range of HLA haplotypes as well as expression of neoantigens and cancer-testis antigens in the lines. Together, these characteristics make the NZM panel a valuable resource for cell-based, immunological and xenograft studies to better understand the diversity of melanoma biology and the responses of melanoma to therapeutic interventions.

Socio-demographic, behavioural and health-related characteristics associated with active commuting in a regional Australian state: Evidence from the 2016 Tasmanian Population Health Survey.

ISSUE ADDRESSED: Physical activity is lower and rates of preventable common diseases are higher in regional/rural than urban Australia. Active commuting (walking/bicycling to get from one place to another) may benefit health through increased physical activity, but most evidence of its correlates come from urban studies. This study aimed to investigate associations between active commuting, socio-demographic characteristics, behaviours, total physical activity and health in a regional/rural Australian state. METHODS: This study used data from the 2016 Tasmanian Population Health Survey, a representative cross-sectional self-report survey of 6,300 adults in Tasmania, Australia. Logistic regression modelling investigated associations between socio-demographic, behavioural and health characteristics and past week active commuting frequency. RESULTS: In multivariable models, being younger, having tertiary qualifications, living in a socio-economically advantaged area, being physically active, having a healthy body mass index and good/excellent self-rated health were associated with engaging in more active commuting. Inner regional dwellers were no more likely than outer regional dwellers to actively commute after covariate adjustment. CONCLUSION: Strategies to promote active commuting in regional/rural areas might consider targeting older adults, those less educated, those living in socio-economically disadvantaged areas, those less physically active, those with poorer health and those with higher body mass index. Research could further investigate why these groups appear to be less active for commuting purposes. SO WHAT?: Increasing physical activity and active commuting may help to reduce rates of preventable common diseases in regional/remote areas.

Derivation of Breast Cancer Cell Lines Under Physiological (5%) Oxygen Concentrations.

Background: Most human breast cancer cell lines currently in use were developed and are cultured under ambient (21%) oxygen conditions. While this is convenient in practical terms, higher ambient oxygen could increase oxygen radical production, potentially modulating signaling pathways. We have derived and grown a series of four human breast cancer cell lines under 5% oxygen, and have compared their properties to those of established breast cancer lines growing under ambient oxygen. Methods: Cell lines were characterized in terms of appearance, cellular DNA content, mutation spectrum, hormone receptor status, pathway utilization and drug sensitivity. Results: Three of the four lines (NZBR1, NZBR2, and NZBR4) were triple negative (ER-, PR-, HER2-), with NZBR1 also over-expressing EGFR. NZBR3 was HER2+ and ER+ and also over-expressed EGFR. Cell lines grown in 5% oxygen showed increased expression of the hypoxia-inducible factor 1 (HIF-1) target gene carbonic anhydrase 9 (CA9) and decreased levels of ROS. As determined by protein phosphorylation, NZBR1 showed low AKT pathway utilization while NZBR2 and NZBR4 showed low p70S6K and rpS6 pathway utilization. The lines were characterized for sensitivity to 7-hydroxytamoxifen, doxorubicin, paclitaxel, the PI3K inhibitor BEZ235 and the HER inhibitors lapatinib, afatinib, dacomitinib, and ARRY-380. In some cases they were compared to established breast cancer lines. Of particular note was the high sensitivity of NZBR3 to HER inhibitors. The spectrum of mutations in the NZBR lines was generally similar to that found in commonly used breast cancer cell lines but TP53 mutations were absent and mutations in EVI2B, LRP1B, and PMS2, which have not been reported in other breast cancer lines, were detected. The results suggest that the properties of cell lines developed under low oxygen conditions (5% O2) are similar to those of commonly used breast cancer cell lines. Although reduced ROS production and increased HIF-1 activity under 5% oxygen can potentially influence experimental outcomes, no difference in sensitivity to estrogen or doxorubicin was observed between cell lines cultured in 5 vs. 21% oxygen.

The Effect of Type of Feedback in Multiple-Choice Testing on Long-Term Retention.

We investigated how different types of feedback in multiple-choice testing influence long-term retention. Participants completed an initial multiple-choice test on general-knowledge questions. Then, they were randomly placed into one of the following four conditions: feedback displaying the original question and four alternative options including the correct answer (Feedback 1); feedback displaying the original question and the correct answer (Feedback 2); feedback displaying only the correct answer (Feedback 3); and no feedback (Control). On the final test two days later, participants in the feedback conditions showed improved retention-even participants who received Feedback 3 outperformed the control group, regardless of whether feedback followed correct or incorrect responses. There was no difference between the feedback conditions when feedback followed correct responses, but Feedback 1 was superior to Feedback 3 when feedback followed incorrect responses. The function of feedback in multiple-choice testing is to maintain correct responses and to correct erroneous responses.

Novel pyrazolo[1,5-a]pyridines with improved aqueous solubility as p110α-selective PI3 kinase inhibitors.

As part of our investigation into pyrazolo[1,5-a]pyridines as novel p110α selective PI3 kinase inhibitors, we report a range of analogues with improved aqueous solubility by the addition of a basic amine. The compounds demonstrated comparable p110α potency and selectivity to earlier compounds but with up to 1000× greater aqueous solubility, as the hydrochloride salts. The compounds also displayed good activity in a cellular assay of PI3 kinase activity.

The Effectiveness of a Physical Activity Educational Campaign in a Rural Obstetrics and Gynecology Office.

Objectives The objective of this study was to evaluate the effectiveness of an early intervention health education campaign to positively influence physical activity (PA) knowledge, intention, and performance among prenatal women and women of reproductive age. Methods This study employed a quantitative, quasi-experimental, control-group comparison design with nonprobability sampling methodology. Implemented in rural healthcare settings located in the Southeastern portion of the United States, participants included prenatal patients and patients of reproductive age (n = 325) from two separate obstetrics and gynecology (OB/GYN) offices. While the intervention group was solicited from an OB/GYN office where the information-based health education campaign was implemented, the comparison group was solicited from a comparable OB/GYN office that did not implement the health education campaign. Results The women exposed to the PA health education campaign were significantly more likely to report that PA information was provided at their physician's office, scored higher on PA knowledge, and were more likely to meet the guidelines for vigorous PA and strength training (p < 0.05). Conclusions Physical activity educational campaigns are a cost effective intervention that can be implemented in healthcare settings to promote maternal and child health.

Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: synthesis, biological evaluation and molecular modelling.

A novel series of TGX-221 analogues was prepared and tested for their potency against the p110α, p110ß, and p110δ isoforms of the PI3K enzyme, and in two cellular assays. The biological results were interpreted in terms of a p110ß comparative model, in order to account for their selectivity towards this isoform. A CH2NH type linker is proposed to allow binding into the specificity pocket proposed to accommodate the high p110ß-selectivity of TGX-221, although there was limited steric tolerance for substituents on the pendant ring with the 2-position most favourable for substitution.

Perceived barriers to physical activity among pregnant women living in a rural community.

OBJECTIVE: The purpose of this research was to describe perceived barriers to physical activity among pregnant women living in a rural community. DESIGN AND SAMPLE: The project followed a simple descriptive design. The sample included 88 healthy pregnant women from a rural community in the southeast United States. MEASURES: The women completed the International Physical Activity Questionnaire (IPAQ) and an open-ended item seeking a description of personal barriers to engagement in regular physical activity. RESULTS: Scores on the IPAQ were generally equally distributed across categories of low, moderate, and high activity. A total of 42 barriers was described from 34% of the women. Seven themes emerged among the reported barriers: (1) symptoms of pregnancy, (2) family and childrearing activities, (3) lack of personal motivation, (4) time and employment demands, (5) perceptions of sufficient activity from daily life, (6) fear of injury, and (7) lack of a habit of activity. CONCLUSIONS: Barriers reported by the rural women were similar to those identified in other settings. Some perceptions confirmed myths about the health value of exercise during pregnancy, but did not confirm barriers commonly cited or assumed for reduced physical activity among rural residents.

American rural women's exercise self-efficacy and awareness of exercise benefits and safety during pregnancy.

Though the positive link between physical activity and maternal health is well documented, physical activity declines during pregnancy and, internationally, rural mothers are less likely than urban mothers to engage in physical activity. Some evidence suggests that self-efficacy is related to sustained engagement in physical activity. The purpose of this study was to examine self-efficacy, perceived benefits, and knowledge of safe exercise among 88 rural pregnant women in a southeastern region of the United States. Exercise self-efficacy was significantly related to maternal age and gestation. Women over age 26 years, and those in the second and third trimesters, scored significantly higher than younger women or those in the first trimester. Fifty-two percent (n = 46) of participants perceived that activity would decrease energy levels, 37.5% (n = 33) did not know that exercise can decrease the risk of gestational diabetes, and 47.6% (n = 41) were unaware that a mother who is overweight is more likely to have an overweight child. Results confirm a need for education to improve women's knowledge about health benefits and safety information related to physical activity during pregnancy.

Comparison of responses of human melanoma cell lines to MEK and BRAF inhibitors.

The NRAS and BRAF genes are frequently mutated in melanoma, suggesting that the NRAS-BRAF-MEK-ERK signaling pathway is an important target for therapy. Two classes of drugs, one targeting activated BRAF and one targeting MEK, are currently undergoing clinical evaluation. We have analysed the NRAS and BRAF mutational status of a series of 44 early passage lines developed from New Zealand patients with metastatic melanoma. 41% of the lines analysed had BRAF mutations, 23% had NRAS mutations, and 36% had neither. We then determined IC50 values (drug concentrations for 50% growth inhibition) for CI-1040, a commonly used inhibitor of MEK kinase; trametinib, a clinical agent targeting MEK kinase; and vemurafenib, an inhibitor of mutant BRAF kinase. Cell lines with activating BRAF mutations were significantly more sensitive to vemurafenib than lines with NRAS mutations or lines lacking either mutation (p < 0.001). IC50 values for CI-1040 and trametinib were strongly correlated (r = 0.98) with trametinib showing ~100-fold greater potency. Cell lines sensitive to vemurafenib were also sensitive to CI-1040 and trametinib, but there was no relationship between IC50 values and NRAS mutation status. A small number of lines lacking a BRAF mutation were sensitive to CI-1040 but resistant to vemurafenib. We used western blotting to investigate the effect on ERK phosphorylation of CI-1040 in four lines, of vemurafenib in two lines and of trametinib in two lines. The results support the view that MEK inhibitors might be combined with BRAF inhibitors in the treatment of melanomas with activated BRAF. The high sensitivity to trametinib of some lines with wildtype BRAF status also suggests that MEK inhibitors could have a therapeutic effect against some melanomas as single agents.

Measuring exercise self-efficacy in pregnant women: psychometric properties of the pregnancy-exercise self-efficacy scale (P-ESES).

BACKGROUND AND PURPOSE: This study assessed the psychometric properties of a modified self-efficacy scale-the Pregnancy-Exercise Self-Efficacy Scale (P-ESES). METHODS: Pregnant women completed the P-ESES and physical activity questionnaires (N = 88). RESULTS: Internal consistency was confirmed by Cronbach's alpha (alpha = 0.838) and equal-length Spearman-Brown (alpha = 8.22). Squared multiple correlation coefficients were calculated showing 9 of 10 items with values greater than the desired .5. A nonrotated exploratory principal components analysis confirmed the same 9 of 10 items loaded on a single factor, accounting for 46.1% of the variance. Each item had an acceptable load value of .40 or higher. CONCLUSIONS: Initial testing of the P-ESES confirmed validity and reliability with the exception of 1 item from the original measure: "Exercising without physician approval".

Costs of treating depression with individual versus family therapy.

Depression is one of the most common concerns that bring clients to treatment. Although marriage and family therapy has been shown to be an effective treatment, little research exists regarding the cost-effectiveness of related services. In this study, we examined claims data for 164,667 individuals diagnosed with depression to determine (a) differences in the cost of treating depression according to type of therapy and license type, (b) differences in recidivism rates by age, gender, type of therapy, and type of mental health professional, and (c) differences in cost-effectiveness by therapy modality and type of professional. The results showed that services provided by marriage and family therapists resulted in the lowest recidivism rate, and family therapy services were the least expensive.

Parental perceptions of sibling relationships in families rearing a child with a chronic condition.

This study examined sibling relationships in families raising children with autism, Down syndrome, orthopedic conditions, and diabetes. Parents from 108 families independently completed the 28-item Schaefer Sibling Inventory of Behavior. Parents rated siblings as very empathetic, fairly often kind and involved, and rarely avoidant. Mothers rated sibling empathy higher than fathers did and older siblings more avoidant than younger siblings. Fathers rated male siblings kinder than female siblings; they also rated siblings of children with Down syndrome or autism more kind and involved than siblings of children with orthopedic conditions or diabetes. Sibling intervention efforts should consider these findings and be individualized according to the need of each child and family.

Therapeutic reactivation of mutant p53 protein by quinazoline derivatives.

PURPOSE: The human tumour suppressor protein p53 is mutated in nearly half of human tumours and most mutant proteins have single amino acid changes. Several drugs including the quinazoline derivative 1 (CP-31398) have been reported to restore p53 activity in mutant cells. The side chain of 1 contains a styryl linkage that compromises its stability and we wished to explore the activity of analogues containing more stable side chains. METHODS: Reactivation of p53 function was measured by flow cytometry as the ability to potentiate radiation-induced G(1)-phase cell cycle arrest and by western blotting to determine expression of p21(WAF1). DNA binding was measured by competition with ethidium and preliminary pharmacological and xenograft studies were carried out. RESULTS: Screening of analogues for potentiation of radiation-induced G(1)-phase cell cycle arrest using NZOV11, an ovarian tumour cell line containing a p53(R248Q) mutation, demonstrated that the (2-benzofuranyl)-quinazoline derivative 5 was among the most active of the analogues. Compound 5 showed similar effects in several other p53 mutant human tumour cell lines but not in a p53 null cell line. 5 also potentiated p21(WAF1) expression induced by radiation. DNA binding affinity was measured and found to correlate with p53 reactivation activity. Plasma concentrations of 5 in mice were sufficient to suggest in vivo activity and a small induced tumour growth delay (7 days) of NZM4 melanoma xenografts was observed. CONCLUSION: Compound 5 restores p53-like function to a human tumour cells lines expressing a variety of mutant p53 proteins, thus providing a basis for the design of further new drugs.

Discovery of pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors.

We have made a novel series of pyrazolo[1,5-a]pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110α isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo[1,5-a]pyridine ring system, and found compound 5x to be a particularly potent example (p110α IC(50) 0.9nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, and showed in vivo activity in an HCT-116 human xenograft model.