Sedentary behavior and lifespan brain health.

Higher levels of physical activity are known to benefit aspects of brain health across the lifespan. However, the role of sedentary behavior (SB) is less well understood. In this review we summarize and discuss evidence on the role of SB on brain health (including cognitive performance, structural or functional brain measures, and dementia risk) for different age groups, critically compare assessment approaches to capture SB, and offer insights into emerging opportunities to assess SB via digital technologies. Across the lifespan, specific characteristics of SB (particularly whether they are cognitively active or cognitively passive) potentially act as moderators influencing the associations between SB and specific brain health outcomes. We outline challenges and opportunities for future research aiming to provide more robust empirical evidence on these observations.

In silico analyses of the involvement of GPR55, CB1R and TRPV1: response to THC, contribution to temporal lobe epilepsy, structural modeling and updated evolution.

Introduction: The endocannabinoid (eCB) system is named after the discovery that endogenous cannabinoids bind to the same receptors as the phytochemical compounds found in Cannabis. While endogenous cannabinoids include anandamide (AEA) and 2-arachidonoylglycerol (2-AG), exogenous phytocannabinoids include Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). These compounds finely tune neurotransmission following synapse activation, via retrograde signaling that activates cannabinoid receptor 1 (CB1R) and/or transient receptor potential cation channel subfamily V member 1 (TRPV1). Recently, the eCB system has been linked to several neurological diseases, such as neuro-ocular abnormalities, pain insensitivity, migraine, epilepsy, addiction and neurodevelopmental disorders. In the current study, we aim to: (i) highlight a potential link between the eCB system and neurological disorders, (ii) assess if THC exposure alters the expression of eCB-related genes, and (iii) identify evolutionary-conserved residues in CB1R or TRPV1 in light of their function. Methods: To address this, we used several bioinformatic approaches, such as transcriptomic (Gene Expression Omnibus), protein-protein (STRING), phylogenic (BLASTP, MEGA) and structural (Phyre2, AutoDock, Vina, PyMol) analyzes. Results: Using RNA sequencing datasets, we did not observe any dysregulation of eCB-related transcripts in major depressive disorders, bipolar disorder or schizophrenia in the anterior cingulate cortex, nucleus accumbens or dorsolateral striatum. Following in vivo THC exposure in adolescent mice, GPR55 was significantly upregulated in neurons from the ventral tegmental area, while other transcripts involved in the eCB system were not affected by THC exposure. Our results also suggest that THC likely induces neuroinflammation following in vitro application on mice microglia. Significant downregulation of TPRV1 occurred in the hippocampi of mice in which a model of temporal lobe epilepsy was induced, confirming previous observations. In addition, several transcriptomic dysregulations were observed in neurons of both epileptic mice and humans, which included transcripts involved in neuronal death. When scanning known interactions for transcripts involved in the eCB system (n = 12), we observed branching between the eCB system and neurophysiology, including proteins involved in the dopaminergic system. Our protein phylogenic analyzes revealed that CB1R forms a clade with CB2R, which is distinct from related paralogues such as sphingosine-1-phosphate, receptors, lysophosphatidic acid receptors and melanocortin receptors. As expected, several conserved residues were identified, which are crucial for CB1R receptor function. The anandamide-binding pocket seems to have appeared later in evolution. Similar results were observed for TRPV1, with conserved residues involved in receptor activation. Conclusion: The current study found that GPR55 is upregulated in neurons following THC exposure, while TRPV1 is downregulated in temporal lobe epilepsy. Caution is advised when interpreting the present results, as we have employed secondary analyzes. Common ancestors for CB1R and TRPV1 diverged from jawless vertebrates during the late Ordovician, 450 million years ago. Conserved residues are identified, which mediate crucial receptor functions.

Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies.

Type 2 diabetes mellitus (T2DM) and sarcopenia (low skeletal muscle mass and function) share a bidirectional relationship. The prevalence of these diseases increases with age and they share common risk factors. Skeletal muscle fat infiltration, commonly referred to as myosteatosis, may be a major contributor to both T2DM and sarcopenia in older adults via independent effects on insulin resistance and muscle health. Many strategies to manage T2DM result in energy restriction and subsequent weight loss, and this can lead to significant declines in muscle mass in the absence of resistance exercise, which is also a first-line treatment for sarcopenia. In this review, we highlight recent evidence on established treatments and emerging therapies targeting weight loss and muscle mass and function improvements in older adults with, or at risk of, T2DM and/or sarcopenia. This includes dietary, physical activity and exercise interventions, new generation incretin-based agonists and myostatin-based antagonists, and endoscopic bariatric therapies. We also highlight how digital health technologies and health literacy interventions can increase uptake of, and adherence to, established and emerging treatments and therapies in older adults with T2DM and/or sarcopenia.

Aircraft and satellite observations reveal historical gap between top-down and bottom-up CO2 emissions from Canadian oil sands.

Measurement-based estimates of greenhouse gas (GHG) emissions from complex industrial operations are challenging to obtain, but serve as an important, independent check on inventory-reported emissions. Such top-down estimates, while important for oil and gas (O&G) emissions globally, are particularly relevant for Canadian oil sands (OS) operations, which represent the largest O&G contributor to national GHG emissions. We present a multifaceted top-down approach for estimating CO2 emissions that combines aircraft-measured CO2/NOx emission ratios (ERs) with inventory and satellite-derived NOx emissions from Ozone Monitoring Instrument (OMI) and TROPOspheric Ozone Monitoring Instrument (TROPOMI) and apply it to the Athabasca Oil Sands Region (AOSR) in Alberta, Canada. Historical CO2 emissions were reconstructed for the surface mining region, and average top-down estimates were found to be >65% higher than facility-reported, bottom-up estimates from 2005 to 2020. Higher top-down vs. bottom-up emissions estimates were also consistently obtained for individual surface mining and in situ extraction facilities, which represent a growing category of energy-intensive OS operations. Although the magnitudes of the measured discrepancies vary between facilities, they combine such that the observed reporting gap for total AOSR emissions is ≥(31 ± 8) Mt for each of the last 3 years (2018-2020). This potential underestimation is large and broadly highlights the importance of continued review and refinement of bottom-up estimation methodologies and inventories. The ER method herein offers a powerful approach for upscaling measured facility-level or regional fossil fuel CO2 emissions by taking advantage of satellite remote sensing observations.

Eight-hour time-restricted eating does not lower daily myofibrillar protein synthesis rates: A randomized control trial.

OBJECTIVE: This study aimed to assess the impact of time-restricted eating (TRE) on integrated skeletal muscle myofibrillar protein synthesis (MyoPS) rates in males with overweight/obesity. METHODS: A total of 18 healthy males (age 46 ± 5 years; BMI: 30 ± 2 kg/m2 ) completed this exploratory, parallel, randomized dietary intervention after a 3-day lead-in diet. Participants then consumed an isoenergetic diet (protein: ~1.0 g/kg body mass per day) following either TRE (10:00 a.m. to 6:00 p.m.) or an extended eating control (CON; 8:00 a.m. to 8:00 p.m.) protocol for 10 days. Integrated MyoPS rates were measured using deuterated water administration with repeated saliva, blood, and muscle sampling. Secondary measures included continuous glucose monitoring and body composition (dual-energy x-ray absorptiometry). RESULTS: There were no differences in daily integrated MyoPS rates (TRE: 1.28% ± 0.18% per day, CON: 1.26% ± 0.22% per day; p = 0.82) between groups. From continuous glucose monitoring, 24-hour total area under the curve was reduced following TRE (-578 ± 271 vs. CON: 12 ± 272 mmol/L × 24 hours; p = 0.001). Total body mass declined (TRE: -1.6 ± 0.9 and CON: -1.1 ± 0.7 kg; p < 0.001) with no differences between groups (p = 0.22). Lean mass loss was greater following TRE compared with CON (-1.0 ± 0.7 vs. -0.2 ± 0.5 kg, respectively; p = 0.01). CONCLUSION: Consuming food within an 8-hour time-restricted period does not lower daily MyoPS rates when compared with an isoenergetic diet consumed over 12 hours. Future research should investigate whether these results translate to free-living TRE.

Physical and Chemical Properties of Cloud Droplet Residuals and Aerosol Particles During the Arctic Ocean 2018 Expedition.

Detailed knowledge of the physical and chemical properties and sources of particles that form clouds is especially important in pristine areas like the Arctic, where particle concentrations are often low and observations are sparse. Here, we present in situ cloud and aerosol measurements from the central Arctic Ocean in August-September 2018 combined with air parcel source analysis. We provide direct experimental evidence that Aitken mode particles (particles with diameters ≲70 nm) significantly contribute to cloud condensation nuclei (CCN) or cloud droplet residuals, especially after the freeze-up of the sea ice in the transition toward fall. These Aitken mode particles were associated with air that spent more time over the pack ice, while size distributions dominated by accumulation mode particles (particles with diameters ≳70 nm) showed a stronger contribution of oceanic air and slightly different source regions. This was accompanied by changes in the average chemical composition of the accumulation mode aerosol with an increased relative contribution of organic material toward fall. Addition of aerosol mass due to aqueous-phase chemistry during in-cloud processing was probably small over the pack ice given the fact that we observed very similar particle size distributions in both the whole-air and cloud droplet residual data. These aerosol-cloud interaction observations provide valuable insight into the origin and physical and chemical properties of CCN over the pristine central Arctic Ocean.

Evolution of Atmospheric Total Organic Carbon from Petrochemical Mixtures.

Reactive organic compounds play a central role in the formation of ozone and secondary organic aerosols. The ability to accurately predict their fate, in part, relies upon quantitative knowledge of the chemical and physical parameters associated with the total organic carbon (TOC), which includes both precursors and oxidation products that evolve in the atmosphere over short to long time scales. However, such knowledge, obtained via limited carbon closure experiments, has not been attained for complex anthropogenic emissions. Here we present the first comprehensive characterization of TOC in the atmospheric oxidation of organic vapors from light and heavy oil mixtures associated with oil sand operations. Despite the complexity of the investigated oil mixtures, we are able to achieve carbon closure (83-116%) within the uncertainties (±20%), with the degree of the closure being dependent upon the vapor composition and NOx levels. In contrast to biogenic precursors (e.g., α-pinene), the photochemical time scale required for a largely complete oxidation and evolution of chemical parameters is very long for the petrochemical vapors (i.e., ∼7-10 days vs ∼1 day), likely due to the lower initial precursor reactivity. This suggests that petrochemical emissions and their impacts are likely to extend further spatially than biogenic emissions, and retain more of their complex composition and reactivity for many days. The results of this work provide key parameters to regional models for further improving the representation of the chemical evolution of petrochemical emissions.

Different frequencies of active interruptions to sitting have distinct effects on 22 h glycemic control in type 2 diabetes.

BACKGROUND & AIMS: Whether the frequency of interruptions to sitting time involving simple resistance activities (SRAs), compared to uninterrupted sitting, differentially affected 22 h glycemic control in adults with medication-controlled type 2 diabetes (T2D). METHODS & RESULTS: Twenty-four participants (13 men; mean ± SD age 62 ± 8 years) completed three 8 h laboratory conditions: SIT: uninterrupted sitting; SRA3: sitting interrupted with 3 min of SRAs every 30 min; and, SRA6: sitting interrupted with 6 min of SRAs every 60 min. Flash glucose monitors assessed glycemic control over a 22 h period. No differences were observed between conditions for overall 22 h glycemic control as measured by AUCtotal, mean glucose and time in hyperglycemia. During the 3.5 h post-lunch period, mean glucose was significantly lower during SRA6 (10.1 mmol·L-1, 95%CI 9.2, 11.0) compared to SIT (11.1 mmol·L-1, 95%CI 10.2, 12.0; P = 0.006). Post-lunch iAUCnet was significantly lower during SRA6 (6.2 mmol·h·L-1, 95%CI 3.3, 9.1) compared to SIT (9.9 mmol·h·L-1, 95%CI 7.0, 12.9; P = 0.003). During the post-lunch period, compared to SIT (2.2 h, 95%CI 1.7, 2.6), time in hyperglycemia was significantly lower during SRA6 (1.5 h, 95%CI 1.0, 1.9, P = 0.001). Nocturnal mean glucose was significantly lower following the SRA3 condition (7.6 mmol·L-1, 95%CI 7.1, 8.1) compared to SIT (8.1 mmol·L-1, 95%CI 7.6, 8.7, P = 0.024). CONCLUSIONS: With standardized total activity time, less-frequent active interruptions to sitting may acutely improve glycemic control; while more-frequent interruptions may be beneficial for nocturnal glucose in those with medication-controlled T2D.

Frequency of Interruptions to Sitting Time: Benefits for Postprandial Metabolism in Type 2 Diabetes.

OBJECTIVE: To determine whether interrupting sitting with brief bouts of simple resistance activities (SRAs) at different frequencies improves postprandial glucose, insulin, and triglycerides in adults with medication-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Participants (n = 23, 10 of whom were female, with mean ± SD age 62 ± 8 years and BMI 32.7 ± 3.5 kg · m-2) completed a three-armed randomized crossover trial (6- to 14-day washout): sitting uninterrupted for 7 h (SIT), sitting with 3-min SRAs (half squats, calf raises, gluteal contractions, and knee raises) every 30 min (SRA3), and sitting with 6-min SRAs every 60 min (SRA6). Net incremental areas under the curve (iAUCnet) for glucose, insulin, and triglycerides were compared between conditions. RESULTS: Glucose and insulin 7-h iAUCnet were attenuated significantly during SRA6 (glucose 17.0 mmol · h · L-1, 95% CI 12.5, 21.4; insulin 1,229 pmol · h · L-1, 95% CI 982, 1,538) in comparison with SIT (glucose 21.4 mmol · h · L-1, 95% CI 16.9, 25.8; insulin 1,411 pmol · h · L-1, 95% CI 1,128, 1,767; P < 0.05) and in comparison with SRA3 (for glucose only) (22.1 mmol · h · L-1, 95% CI 17.7, 26.6; P = 0.01) No significant differences in glucose or insulin iAUCnet were observed in comparison of SRA3 and SIT. There was no statistically significant effect of condition on triglyceride iAUCnet. CONCLUSIONS: In adults with medication-controlled T2D, interrupting prolonged sitting with 6-min SRAs every 60 min reduced postprandial glucose and insulin responses. Other frequencies of interruptions and potential longer-term benefits require examination to clarify clinical relevance.

Acute effects of interrupting prolonged sitting on vascular function in type 2 diabetes.

In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D), nor whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 yr) completed three 7-h conditions: 1) uninterrupted sitting (SIT), 2) sitting with 3-min bouts of SRA every 30 min (SRA3), and 3) sitting with 6 min bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow, and endothelin-1 were measured at 0, 1, 3.5, 4.5, and 6.5-7 h. Mean femoral artery FMD over 7 h was significantly higher in SRA3 (4.1 ± 0.3%) compared with SIT (3.7 ± 0.3%, P = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased significantly for SRA3 (45.3 ± 4.1/s, P < 0.001) and SRA6 (46.2 ± 4.1/s, P < 0.001) relative to SIT (33.1 ± 4.1/s). Endothelin-1 concentrations were not statistically different between conditions. Interrupting sitting with activity breaks every 30 min, but not 60 min, significantly increased mean femoral artery FMD over 7 h, relative to SIT. Our findings suggest that more frequent and shorter breaks may be more beneficial than longer, less frequent breaks for vascular health in those with T2D.NEW & NOTEWORTHY This is the first trial to examine both the effects of interrupting prolonged sitting on vascular function in type 2 diabetes and the effects of the frequency and duration of interruptions. Brief, simple resistance activity bouts every 30 min, but not every 60 min, increased mean femoral artery flow-mediated dilation over 7 h, relative to uninterrupted sitting. With further supporting evidence, these initial findings can have important implications for cardiovascular health in type 2 diabetes.

Combined effects of continuous exercise and intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides in adults with obesity: a randomized crossover trial.

BACKGROUND: Postprandial glucose, insulin, and triglyceride metabolism is impaired by prolonged sitting, but enhanced by exercise. The aim of this study was to assess the effects of a continuous exercise bout with and without intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides. METHODS: Sedentary adults who were overweight to obese (n = 67; mean age 67 yr SD ± 7; BMI 31.2 kg∙m- 2 SD ± 4.1), completed three conditions: SIT: uninterrupted sitting (8-h, control); EX+SIT: sitting (1-h), moderate-intensity walking (30-min), uninterrupted sitting (6.5-h); EX+BR: sitting (1-h), moderate-intensity walking (30- min), sitting interrupted every 30-min with 3-min of light-intensity walking (6.5 h). Participants consumed standardized breakfast and lunch meals and blood was sampled at 13 time-points. RESULTS: When compared to SIT, EX+SIT increased total area under the curve (tAUC) for glucose by 2% [0.1-4.1%] and EX+BR by 3% [0.6-4.7%] (all p < 0.05). Compared to SIT, EX+SIT reduced insulin and insulin:glucose ratio tAUC by 18% [11-22%] and 21% [8-33%], respectively; and EX+BR reduced values by 25% [19-31%] and 28% [15-38%], respectively (all p < 0.001 vs SIT, all p < 0.05 EX+SIT-vs-EX+BR). Compared to SIT, EX+BR reduced triglyceride tAUC by 6% [1-10%] (p = 0.01 vs SIT), and compared to EX+SIT, EX+BR reduced this value by 5% [0.1-8.8%] (p = 0.047 vs EX+SIT). The magnitude of reduction in insulin tAUC from SIT-to-EX+BR was greater in those with increased basal insulin resistance. No reduction in triglyceride tAUC from SIT-to-EX+BR was apparent in those with high fasting triglycerides. CONCLUSIONS: Additional reductions in postprandial insulin-glucose dynamics and triglycerides may be achieved by combining exercise with breaks in sitting. Relative to uninterrupted sitting, this strategy may reduce postprandial insulin more in those with high basal insulin resistance, but those with high fasting triglycerides may be resistant to such intervention-induced reductions in triglycerides. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ( ACTRN12614000737639 ).

Distinct effects of acute exercise and breaks in sitting on working memory and executive function in older adults: a three-arm, randomised cross-over trial to evaluate the effects of exercise with and without breaks in sitting on cognition.

BACKGROUND: Sedentary behaviour is associated with impaired cognition, whereas exercise can acutely improve cognition. OBJECTIVE: We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cognition in older adults. METHODS: Sedentary overweight/obese older adults with normal cognitive function (n=67, 67±7 years, 31.2±4.1 kg/m2) completed three conditions (6-day washout): SIT (sitting): uninterrupted sitting (8 hours, control); EX+SIT (exercise + sitting): sitting (1 hour), moderate-intensity walking (30 min), uninterrupted sitting (6.5 hours); and EX+BR (exercise + breaks): sitting (1 hour), moderate-intensity walking (30 min), sitting interrupted every 30 min with 3 min of light-intensity walking (6.5 hours). Cognitive testing (Cogstate) was completed at four time points assessing psychomotor function, attention, executive function, visual learning and working memory. Serum brain-derived neurotrophic growth factor (BDNF) was assessed at six time points. The 8-hour net area under the curve (AUC) was calculated for each outcome. RESULTS: Working memory net AUC z-score·hour (95% CI) was improved in EX+BR with a z-score of +28 (-26 to +81), relative to SIT, -25 (-79 to +29, p=0.04 vs EX+BR). Executive function net AUC was improved in EX+SIT, -8 (- 71 to +55), relative to SIT, -80 (-142 to -17, p=0.03 vs EX+SIT). Serum BDNF net AUC ng/mL·hour (95% CI) was increased in both EX+SIT, +171 (-449 to +791, p=0.03 vs SIT), and EX+BR, +139 (-481 to +759, p=0.045 vs SIT), relative to SIT, -227 (-851 to +396). CONCLUSION: A morning bout of moderate-intensity exercise improves serum BDNF and working memory or executive function in older adults, depending on whether or not subsequent sitting is also interrupted with intermittent light-intensity walking. TRIAL REGISTRATION NUMBER: ACTRN12614000737639.

Morning exercise mitigates the impact of prolonged sitting on cerebral blood flow in older adults.

Preventing declines in cerebral blood flow is important for maintaining optimal brain health with aging. We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cerebral blood velocity over 8 h in older adults. In a randomized crossover trial, overweight/obese older adults ( n = 12, 70 ± 7 yr; 30.4 ± 4.3 kg/m2), completed three acute conditions (6-day washout); SIT: prolonged sitting (8 h, control); EX+SIT: sitting (1 h), moderate-intensity walking (30 min), followed by uninterrupted sitting (6.5 h); and EX + BR: sitting (1 h), moderate-intensity walking (30 min), followed by sitting (6.5 h) interrupted with 3 min of light-intensity walking every 30 min. Bilateral middle cerebral artery velocities (MCAv) were determined using transcranial Doppler at 13 time points across the day. The temporal pattern and average MCAv over 8 h was determined. The pattern of MCAv over 8 h was a negative linear trend in SIT ( P < 0.001), but a positive quadratic trend in EX + SIT ( P < 0.001) and EX + BR ( P < 0.01). Afternoon time points in SIT were lower than baseline within condition ( P ≤ 0.001 for all). A morning dip in MCAv was observed in EX + SIT and EX + BR ( P < 0.05 relative to baseline), but afternoon time points were not significantly lower than baseline. The average MCAv over 8 h was higher in EX + SIT than SIT ( P = 0.007) or EX + BR ( P = 0.024). Uninterrupted sitting should be avoided, and moderate-intensity exercise should be encouraged for the daily maintenance of cerebral blood flow in older adults. The clinical implications of maintaining adequate cerebral blood flow include the delivery of vital oxygen and nutrients to the brain. NEW & NOTEWORTHY This is the first study to measure the combined effects of an exercise bout with breaks in sitting on cerebral blood velocity in older adults. Using frequent recordings over an 8-h period, we have performed a novel analysis of the pattern of cerebral blood velocity, adjusting for concurrent measures of mean arterial pressure and other potential confounders in a linear mixed effects regression.

Structure of SPH (self-incompatibility protein homologue) proteins: a widespread family of small, highly stable, secreted proteins.

SPH (self-incompatibility protein homologue) proteins are a large family of small, disulfide-bonded, secreted proteins, initially found in the self-incompatibility response in the field poppy (Papaver rhoeas), but now known to be widely distributed in plants, many containing multiple members of this protein family. Using the Origami strain of Escherichia coli, we expressed one member of this family, SPH15 from Arabidopsis thaliana, as a folded thioredoxin fusion protein and purified it from the cytosol. The fusion protein was cleaved and characterised by analytical ultracentrifugation, circular dichroism and nuclear magnetic resonance (NMR) spectroscopy. This showed that SPH15 is monomeric and temperature stable, with a ß-sandwich structure. The four strands in each sheet have the same topology as the unrelated proteins: human transthyretin, bacterial TssJ and pneumolysin, with no discernible sequence similarity. The NMR-derived structure was compared with a de novo model, made using a new deep learning algorithm based on co-evolution/correlated mutations, DeepCDPred, validating the method. The DeepCDPred de novo method and homology modelling to SPH15 were then both used to derive models of the 3D structure of the three known PrsS proteins from P. rhoeas, which have only 15-18% sequence homology to SPH15. The DeepCDPred method gave models with lower discreet optimised protein energy scores than the homology models. Three loops at one end of the poppy structures are postulated to interact with their respective pollen receptors to instigate programmed cell death in pollen tubes.

Effect of Morning Exercise With or Without Breaks in Prolonged Sitting on Blood Pressure in Older Overweight/Obese Adults.

Both exercise and breaks in prolonged sitting can reduce blood pressure (BP) in older overweight/obese adults. We investigated whether there is an additive hypotensive effect when exercise is combined with subsequent breaks in sitting. Sex differences and changes in plasma catecholamines as a potential candidate mechanism underlying BP responses were also examined. Sedentary older adults (n=67; 67±7 years; 31.2±4.1 kg/m2) completed 3 conditions in random order-sitting (SIT): uninterrupted sitting (8 hours, control); exercise+sitting (EX+SIT): sitting (1 hour), moderate-intensity walking (30 minutes), uninterrupted sitting (6.5 hours); exercise+breaks (EX+BR): sitting (1 hour), moderate-intensity walking (30 minutes), sitting interrupted every 30 minutes with 3 minutes of light-intensity walking (6.5 hours). Serial BP and plasma epinephrine/norepinephrine measurements occurred during 8 hours. The 8-hour average systolic and diastolic BP (mm Hg 95% CI) was lower in EX+SIT -3.4 (-4.5 to -2.3), -0.8 (-1.6 to -0.04), and EX+BR -5.1 (-6.2 to -4.0), -1.1 (-1.8 to -0.3), respectively, relative to SIT (all P <0.05). There was an additional reduction in average systolic BP of -1.7 (-2.8 to -0.6) in EX+BR relative to EX+SIT ( P=0.003). This additional reduction in systolic BP was driven by women -3.2 (-4.7 to -1.7; P<0.001 EX+BR versus EX+SIT). Average epinephrine decreased in EX+SIT and EX+BR in women (-13% to -12%) but increased in men (+12% to +23%), respectively, relative to SIT ( P<0.05). No differences in average norepinephrine were observed. Morning exercise reduces BP during a period of 8 hours in older overweight/obese adults compared with prolonged sitting. Combining exercise with regular breaks in sitting may be of more benefit for lowering BP in women than in men. Clinical Trial Registration- URL: https://www.anzctr.org.au . Unique identifier: ACTRN12614000737639.

Simple intermittent resistance activity mitigates the detrimental effect of prolonged unbroken sitting on arterial function in overweight and obese adults.

Prolonged sitting contributes to cardiovascular disease (CVD) risk. The underlying mechanisms are unknown but may include changes in arterial function and vasoactive mediators. We examined the effects of prolonged unbroken sitting, relative to regular active interruptions to sitting time, on arterial function in adults at increased CVD risk. In a randomized crossover trial, 19 sedentary overweight/obese adults (mean ± SD age 57 ± 12 yr) completed 2 laboratory-based conditions: 5 h uninterrupted sitting (SIT) and 5 h sitting interrupted every 30 min by 3 min of simple resistance activities (SRA). Femoral artery function [flow-mediated dilation (FMD)], blood flow, and shear rate were measured at 0 h, 30 min, 1 h, 2 h, and 5 h. Brachial FMD was assessed at 0 and 5 h. Plasma was collected hourly for measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). There was a significant decline in femoral artery FMD, averaged over 5 h in the SIT condition, relative to SRA (P < 0.001). Plasma ET-1 total area under the curve over 5 h increased in the SIT condition compared with SRA (P = 0.006). There was no significant difference between conditions in femoral or brachial shear rate, brachial FMD, nitrates/nitrites, VCAM-1, or ICAM-1 (P > 0.05 for all). Five hours of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating ET-1 in overweight/obese adults. There is the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.NEW & NOTEWORTHY This is the first study to examine the effect of prolonged sitting on arterial function in adults at increased cardiovascular disease risk. We have shown that 5 h of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating endothelin-1 in overweight/obese adults. There is now the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.

Study design and methods for the ACTIVity And TEchnology (ACTIVATE) trial.

BACKGROUND: Physical activity is positively associated with survival and quality of life among breast cancer survivors. Despite these benefits, the majority of breast cancer survivors are insufficiently active. The potential health benefits of reducing sedentary behaviour (sitting time) in this population have not been extensively investigated. The ACTIVATE Trial will evaluate the efficacy of an intervention that combines wearable technology (the Garmin Vivofit2®) with traditional behavioural change approaches to increase physical activity and reduce sedentary behaviour performed by breast cancer survivors. METHODS/DESIGN: This randomised controlled trial includes inactive, postmenopausal women diagnosed with stage I-III breast cancer who have completed their primary treatment. Participants are randomly assigned to the primary intervention group (Garmin Vivofit2®; behavioural feedback and goal setting session; and, five telephone-delivered health coaching sessions) or to the wait-list control group. The primary intervention is delivered over a 12-week period. The second 12-week period comprises a maintenance phase for the primary intervention group, and an abridged intervention (Garmin Vivofit2® only) for the wait-list control group. Moderate- to vigorous-intensity physical activity (MVPA) and sedentary behaviour are assessed by accelerometry at baseline (T1), end of intervention (T2), and end of maintenance phase (T3). DISCUSSION: The ACTIVATE Trial is one of the first studies to incorporate wearable technology into an intervention for cancer survivors. If the use of wearable technology (in combination with behaviour change strategies, or alone) proves efficacious, it may become an inexpensive and sustainable addition to the health promotion strategies available to health care providers in the cancer survivorship context. TRIAL REGISTRATION: ACTRN12616000175471.

Sedentary behavior as a risk factor for cognitive decline? A focus on the influence of glycemic control in brain health.

Cognitive decline leading to dementia represents a global health burden. In the absence of targeted pharmacotherapy, lifestyle approaches remain the best option for slowing the onset of dementia. However, older adults spend very little time doing moderate to vigorous exercise and spend a majority of time in sedentary behavior. Sedentary behavior has been linked to poor glycemic control and increased risk of all-cause mortality. Here, we explore a potential link between sedentary behavior and brain health. We highlight the role of glycemic control in maintaining brain function and suggest that reducing and replacing sedentary behavior with intermittent light-intensity physical activity may protect against cognitive decline by reducing glycemic variability. Given that older adults find it difficult to achieve current exercise recommendations, this may be an additional practical strategy. However, more research is needed to understand the impact of poor glycemic control on brain function and whether practical interventions aimed at reducing and replacing sedentary behavior with intermittent light intensity physical activity can help slow cognitive decline.

A short history of hormone measurement.

Huge changes have occurred in the measurement of hormones over the last 50 years or so. Methods have become simplified, sensitivity has increased manyfold, and automation has allowed the analysis of large number of specimens in a single day. The most significant steps in the history of hormone measurement were the development of radioimmunoassay and later the production of monoclonal antibodies. There has also been increased commercialization, the technique has been applied to an ever-increasing range of substances, and radioactive measurement has been replaced with colorimetric, fluorescent, and chemiluminescent end-points. However, all these changes have not been without their problems. Collaboration between laboratories has seen standardization of reagents and methods, the development of reference methods, and the setting up of external quality assurance schemes. All these have led to improved sensitivity, precision, and reliability. More recently tandem mass spectrometry has brought further improvements in the measurement of certain hormones. Although many hormones are now measured by automated systems there is still a place for manual assays whether developed in-house or by using a commercial kit.