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.

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.

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.

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.

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".

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.

Novel pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors: Exploring the benzenesulfonohydrazide SAR.

Structure-activity relationship studies of the pyrazolo[1,5-a]pyridine class of PI3 kinase inhibitors show that substitution off the hydrazone nitrogen and replacement of the sulfonyl both gave a loss of p110α selectivity, with the exception of an N-hydroxyethyl analogue. Limited substitutions were tolerated around the phenyl ring; in particular the 2,5-substitution pattern was important for PI3 kinase activity. The N-hydroxyethyl compound also showed good inhibition of cell proliferation and inhibition of phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity. It had suitable pharmacokinetics for evaluation in vivo, and showed tumour growth inhibition in two human tumour cell lines in xenograft studies. This work has provided suggestions for the design of more soluble analogues.

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.

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).

In vivo and in vitro assessment of the action of SN 28049, a benzonaphthyridine derivative targeting topoisomerase II, on the murine Colon 38 carcinoma.

AIM: SN 28049 (N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide) is a new DNA binding drug that targets topoisomerase II. SN 28049 is curative against the murine Colon 38 adenocarcinoma (CT38) while etoposide, another topoisomerase II-directed drug, shows minimal activity; we investigated the basis for this difference in vivo and in vitro. METHODS: Colon 38 tumours were grown in C57Bl mice and in immunodeficient mice. Tumour sections were examined by staining and TUNEL assays. A new cell line (Co-38P) derived from the in vivo tumour was developed and responses were analysed using flow cytometry. RESULTS: Both SN 28049 and etoposide induced similar tumour histological changes, reducing mitotic index and increasing apoptotic index 8 h after administration. At later times however, SN 28049-treated tumours showed further progressive morphological changes while etoposide-treated tumours reverted to their original growth characteristics. The effects of SN 28049 on tumour growth were delayed and attenuated when Colon 38 tumours were grown in immunodeficient mice. SN 28049 and etoposide both induced dose-dependent increases of γ-phosphorylation of histone H2AX and cell cycle perturbation of the Co-38P cell line, indicative of DNA damage, although SN 28049 had 30-fold higher activity. Following 1-hour drug exposure of Co-38P cells, SN 28049 was more effective that etoposide in inducing persistent cycle arrest for the same degree of DNA damage. CONCLUSION: The superior antitumour activity of SN 28049 may result from its ability to induce long term cycle arrest. Host immune responses contribute to the curative activity of SN 28049 and this could result from the induction of cycle arrest.

Action of SN 28049, a new DNA binding topoisomerase II-directed antitumour drug: comparison with doxorubicin and etoposide.

AIM: We have examined the cellular action of SN 28049 (N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide), a DNA binding drug with curative activity against the Colon 38 transplantable murine carcinoma, on human tumour cells. Its action has been compared with that of two topoisomerase II-targetted drugs, etoposide and doxorubicin. METHODS: The NZM3 melanoma and HCT116 colon carcinoma cell lines, each expressing wild-type p53, were cultured and responses were compared by flow cytometry, electrophoresis, microscopy, and growth of tumour xenografts. RESULTS: Responses of NZM3 cells to all three drugs, as measured by histone H2AX γ-phosphorylation, induction of the p53 pathway and cell cycle arrest, were comparable and typical of those of topoisomerase II poisons. Xenografts of NZM3 cells responded to SN 28049 with a tumour growth delay of 16 days. In contrast, HCT116 cells had an attenuated DNA damage response to the drugs and SN 28049 had no in vivo activity, consistent with low topoisomerase II activity. However, SN 28049 inhibited HCT116 cell growth in vitro and activated the p53 pathway to induce a state with G(2)/M-phase DNA content, low mitotic index and a high proportion of binucleate cells. Treated cells expressed cyclin E and the senescence marker ß-galactosidase but showed low expression of cyclin B and survivin. In comparison, etoposide caused little p53 expression or cycle arrest, and doxorubicin had an intermediate effect. CONCLUSION: The action of SN 28049 in NZM3 cells is typical of a topoisomerase II poison, but the low topoisomerase IIα activity of HCT116 cells allowed the detection of a second antiproliferative action of SN 28049 in which cells undergo post-mitotic cycle arrest and induction of p53.

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.

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.

Type 1 diabetes: children and adolescents' knowledge and questions.

AIM: This paper is a report of a study conducted to describe what children and adolescents who have type 1 diabetes know and want to know about the disease. BACKGROUND: Research indicates that young people's knowledge of diabetes may minimize their health complications, because with greater knowledge they may engage in more effective management practices and adherence. METHODS: In this qualitative study, a purposive sample of 58 children and adolescents with type 1 diabetes were interviewed in 2005 about what they knew and wanted to know about their disease. Through a process of induction, major themes were identified from the data. FINDINGS: The six major themes were: (a) Care, including both physical and emotional care, (b) Physiology, (c) Consequences, including both short- and long-term, as well as positive and negative consequences, (d) Cure, (e) Effects on the Family and (f) Experience at Diagnosis. Themes related to the unique challenges associated with type 1 diabetes were also identified. CONCLUSION: Nurses, diabetes educators and parents should provide developmentally appropriate information about diabetes care and management, scaffolding on existing knowledge. They should provide child-centred contexts in which children and adolescents can freely ask questions about their condition and problem-solve. Programmes that allow young people to develop coping skills and share experiences could also prove beneficial.

Peroxisome-proliferator-activated receptors and the control of levels of prostaglandin-endoperoxide synthase 2 by arachidonic acid in the bovine uterus.

Arachidonic acid is a potential paracrine agent released by the uterine endometrial epithelium to induce PTGS2 [PG (prostaglandin)-endoperoxide synthase 2] in the stroma. In the present study, bovine endometrial stromal cells were used to determine whether PTGS2 is induced by arachidonic acid in stromal cells, and to investigate the potential role of PPARs (peroxisome-proliferator-activated receptors) in this effect. Arachidonic acid increased PTGS2 levels up to 7.5-fold within 6 h. The cells expressed PPARalpha and PPARdelta (also known as PPARbeta) (but not PPARgamma). PTGS2 protein level was increased by PPAR agonists, including polyunsaturated fatty acids, synthetic PPAR ligands, PGA1 and NSAIDs (non-steroidal anti-inflammatory drugs) with a time course resembling that of arachidonic acid. Use of agonists and antagonists indicated PPARalpha (but not PPARdelta or PPARgamma) was responsible for PTGS2 induction. PTGS2 induction by arachidonic acid did not require PG synthesis. PTGS2 levels were increased by the PKC (protein kinase C) activators 4beta-PMA and PGF(2alpha), and the effects of arachidonic acid, NSAIDs, synthetic PPAR ligands and 4beta-PMA were blocked by PKC inhibitors. This is consistent with PPAR phosphorylation by PKC. Induction of PTGS2 protein by 4beta-PMA in the absence of a PPAR ligand was decreased by the NF-kappaB (nuclear factor kappaB) inhibitors MG132 and parthenolide, suggesting that PKC acted through NF-kappaB in addition to PPAR phosphorylation. Use of NF-kappaB inhibitors allowed the action of arachidonic acid as a PPAR agonist to be dissociated from an effect through PKC. The results are consistent with the hypothesis that arachidonic acid acts via PPARalpha to increase PTGS2 levels in bovine endometrial stromal cells.