Physical activity (PA) interventions are generally effective in supporting short-term behaviour change, but increases are not always maintained. This review examined the effectiveness of PA ...interventions for behaviour change maintenance in young and middle–aged adults, and investigated which Behaviour Change Techniques (BCTs) and other intervention features were associated with maintenance.
Six databases (Medline, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, CINAHL, Web of Science) were systematically searched. Eligibility criteria were controlled trials investigating the effectiveness of PA interventions with adult (mean age 18–64 years) non-clinical populations using validated measures of PA behaviour at baseline and ≥six months’ post-baseline. Results were pooled in meta-analyses using standardised mean differences (SMD) at five time intervals (6–9, 9–15, 15–21, 21–24, >24 months). Moderator analyses investigated the influence of sample and intervention characteristics on PA maintenance at 6–9 months.
Sixty-two studies were included. PA interventions had a significant effect on behaviour maintenance 6–15 months post-baseline relative to controls. Interventions had a larger effect on maintenance at 6–9 months (SMD = 0.28; 95% CI: 0.20, 0.35; I2 = 73%) compared to 9–15 months (SMD = 0.20; 95% CI: 0.13, 0.26; I2 = 70%). Beyond 15 months, PA measurements were infrequent with little evidence supporting maintenance. Moderator analyses showed some BCTs and intervention settings moderated PA outcomes at 6–9 months. A multivariable meta-regression model showed interventions using the BCTs ‘Prompt self-monitoring of behavioural outcome’ (b = 1.46, p < 0.01) and ‘Use of follow-up prompts’ (b = 0.38, p < 0.01) demonstrated greater effectiveness at promoting PA maintenance at 6–9 months. Interventions implemented in primary care (versus community or workplace/university) settings (b = −0.13, p = 0.10) tended to demonstrate less effectiveness.
This review provides evidence of some effective BCTs for maintaining behaviour to 15 months. Greater consideration must be given to how future interventions encourage and measure maintenance of changes, and investigate broader psychological, social and environmental influences of PA behaviour.
PROSPERO 2015:CRD42015025462.
•Physical activity interventions have maintained effects up to 15 months.•After 15 months measurements are infrequent and show little effectiveness.•Primary care interventions are less effective than community or workplace settings.•Monitoring behavioural outcomes, use of follow-up prompts are effective techniques.•Longer follow-up with consideration of social and physical environments is needed.
Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca(2+) homeostasis through the regulation of parathyroid hormone secretion. It functions as a ...disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation. Our structures reveal multiple binding sites for Ca(2+) and PO4(3-) ions. Both ions are crucial for structural integrity of the receptor. While Ca(2+) ions stabilize the active state, PO4(3-) ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.
AU-rich element-binding proteins (ARE-BP) regulate the stability and/or translational efficiency of mRNAs containing cognate binding sites. Many targeted transcripts encode factors that control ...processes such as cell division, apoptosis, and angiogenesis, suggesting that dysregulated ARE-BP expression could dramatically influence oncogenic phenotypes. Using several approaches, we evaluated the expression of four well-characterized ARE-BPs across a variety of human neoplastic syndromes. AUF1, TIA-1, and HuR mRNAs were not systematically dysregulated in cancers; however, tristetraprolin mRNA levels were significantly decreased across many tumor types, including advanced cancers of the breast and prostate. Restoring tristetraprolin expression in an aggressive tumor cell line suppressed three key tumorgenic phenotypes: cell proliferation, resistance to proapoptotic stimuli, and expression of vascular endothelial growth factor mRNA. However, the cellular consequences of tristetraprolin expression varied across different cell models. Analyses of gene array data sets revealed that suppression of tristetraprolin expression is a negative prognostic indicator in breast cancer, because patients with low tumor tristetraprolin mRNA levels were more likely to present increased pathologic tumor grade, vascular endothelial growth factor expression, and mortality from recurrent disease. Collectively, these data establish that tristetraprolin expression is frequently suppressed in human cancers, which in turn can alter tumorigenic phenotypes that influence patient outcomes.
CO ₂ capture and storage (CCS) has the potential to develop into an important tool to address climate change. Given society’s present reliance on fossil fuels, widespread adoption of CCS appears ...indispensable for meeting stringent climate targets. We argue that for conventional CCS to become a successful climate mitigation technology—which by necessity has to operate on a large scale—it may need to be complemented with air capture, removing CO ₂ directly from the atmosphere. Air capture of CO ₂ could act as insurance against CO ₂ leaking from storage and furthermore may provide an option for dealing with emissions from mobile dispersed sources such as automobiles and airplanes.
Plasma cells constitute the majority of tumor cells in multiple myeloma (MM) but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate ...disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC). These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.
Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1) as revealed by quantitative real-time PCR.
Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms.
Ireland has one of the lowest BF rates in the world. This study investigates the association between breastfeeding and infant health in Ireland.
A cross-sectional, secondary analysis of data ...collected from Growing Up in Ireland (GUI): the National Longitudinal Study of Children was conducted. The average morbidity for 2212. infants exclusively breastfed for at least 90 days (EBF90days) was compared to data for 3987 infants in the non-breastfed (Non-BF) group. Data were weighted using entropy balancing to ensure the comparability of groups. Sensitivity analyses considered alternative definitions of the breastfeeding group.
Infants who were EBF90days were significantly less likely to be admitted to hospital (CI: - 0.06 to - 0.03), spent less nights in hospital (CI: - 0.37 to - 0.11), and were less likely to develop respiratory diseases including asthma (CI: - 0.03 to - 0.01), chest infections (CI: - 0.12 to - 0.08), snuffles/common colds (CI: - 0.07 to - 0.02), ear infections (CI: - 0.08 to - 0.04), eczema (CI: - 0.08 to - 0.04), skin problems (CI: - 0.04 to - 0.00), wheezing or asthma (CI: - 0.06 to - 0.03), vomiting (CI: - 0.03 to - 0.00), and colic (CI: - 0.04 to - 0.01). Further outcomes such as current health of the infant at time of interview (CI: - 0.04 to - 0.00), feeding problems (CI: - 0.04 to - 0.02) and sleeping problems (CI: - 0.02 to - 0.00) indicated a protective effect of EBF90days versus Non-BF. However, these infants were also more likely to fail to gain weight (CI: 0.01 to 0.02) and were at a slightly higher risk of developing nappy rash (CI: 0.00 to 0.02).
Exclusive breastfeeding for 90+ days is associated with protection against childhood morbidity. Given the protective effect of breastfeeding on adverse health effects in infants, policy makers should prioritise policies that support, promote and protect exclusive breastfeeding.
The calcium-sensing receptor (CaSR) is critical for skeletal development, but its mechanism of action in osteoblasts is not well-characterized. In the central nervous system (CNS), Homer scaffolding ...proteins form signaling complexes with two CaSR-related members of the G protein–coupled receptor (GPCR) family C, metabotropic glutamate receptor 1 (mGluR1) and mGluR5. Here, we show that CaSR and Homer1 are co-expressed in mineralized mouse bone and also co-localize in primary human osteoblasts. Co-immunoprecipitation experiments confirmed that Homer1 associates with CaSR in primary human osteoblasts. The CaSR–Homer1 protein complex, whose formation was increased in response to extracellular Ca2+, was bound to mechanistic target of rapamycin (mTOR) complex 2 (mTORC2), a protein kinase that phosphorylates and activates AKT Ser/Thr kinase (AKT) at Ser473. siRNA-based gene-silencing assays with primary osteoblasts revealed that both CaSR and Homer1 are required for extracellular Ca2+-stimulated AKT phosphorylation and thereby inhibit apoptosis and promote AKT-dependent β-catenin stabilization and cellular differentiation. To confirm the role of the CaSR–Homer1 complex in AKT initiation, we show that in HEK-293 cells, co-transfection with both Homer1c and CaSR, but neither with Homer1c nor CaSR alone, establishes sensitivity of AKT–Ser473 phosphorylation to increases in extracellular Ca2+ concentrations. These findings indicate that Homer1 mediates CaSR-dependent AKT activation via mTORC2 and thereby stabilizes β-catenin in osteoblasts.
Evidence suggests that dietary intake of UK children is suboptimal. As schools provide an ideal natural environment for public health interventions, effective and sustainable methods of improving ...food knowledge and dietary habits in this population must be identified. Project Daire aimed to improve children's health-related quality of life, wellbeing, food knowledge and dietary habits via two multi-component interventions.
Daire was a randomised-controlled, factorial design trial evaluating two interventions across four arms. Primary schools in Northern Ireland were randomised to one of four 6-month intervention arms: i) 'Nourish', ii) 'Engage', iii) 'Nourish' and 'Engage' and iv) Control (Delayed). 'Nourish' was an intervention aiming to alter the whole-school food environment, provide food-related experiences and exposure to locally produced foods. 'Engage' was an age-appropriate, cross-curricular educational intervention on food, agriculture, nutrition science and related careers. Primary outcomes were emotional and behavioural wellbeing and health-related quality of life. A number of secondary outcomes, including dietary intake, cooking competence and food-related knowledge, were also measured.
Fifteen schools from areas of varying socio-economic status participated in the randomised trial. A total of 903 (n = 445 aged 6-7 years and n = 458 aged 10-11 years) primary school pupils took part. Total Difficulties Score improved in all pupils (6-7 and 10-11 year old pupils) who received the 'Nourish' intervention compared with those that did not (adjusted difference in mean = - 0.82; 95% CI -1.46, - 0.17; P < 0.02). No statistically significant difference in Health-Related Quality of Life was observed. The 'Nourish' intervention also produced some changes in school-based dietary behaviour, which were most apparent in the 10-11 year old pupils. The 'Nourish' intervention also produced improvements in understanding of food labels (adjusted difference in mean = 0.15; 95% CI 0.05, 0.25; P < 0.01) and knowledge of vegetables in season (adjusted difference in mean = 0.29; 95% CI 0.01,0.56; P = 0.04) whilst an increased willingness to try new foods and improved perceived cooking competence was also observed.
Improvements in childhood emotional and behavioural wellbeing, dietary intake, knowledge about food, cooking skills and willingness to try new foods were associated with the 'Nourish' whole-school food environment intervention. Exploration of the sustainability and long-term effectiveness of such whole-school food interventions should be conducted.
National Institute of Health (NIH) U.S. National Library of Medicine Clinical Trials.gov (ID: NCT04277312 ).
The extracellular Ca-sensing receptor (CaSR) is a sensor for a number of key nutrients within the body, including Ca ions (Ca²⁺) and L-amino acids. The CaSR is expressed in a number of specialised ...cells within the gastrointestinal (GI) tract, and much work has been done to examine CaSR's role as a nutrient sensor in this system. This review article examines two emerging roles for the CaSR within the GI tract--as a mediator of kokumi taste modulation in taste cells and as a regulator of dietary hormone release in response to L-amino acids in the intestine.
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