Glycogen and its metabolism: some new developments and old themes

Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been the subject of extensive investigation and much is known about its regulation by hormones such as insulin, glucagon and adrenaline (epinephrine). There has been debate over the relative importance of allosteric compared with covalent control of the key biosynthetic enzyme, glycogen synthase, as well as the relative importance of glucose entry into cells compared with glycogen synthase regulation in determining glycogen accumulation. Significant new developments in eukaryotic glycogen metabolism over the last decade or so include: (i) three-dimensional structures of the biosynthetic enzymes glycogenin and glycogen synthase, with associated implications for mechanism and control; (ii) analyses of several genetically engineered mice with altered glycogen metabolism that shed light on the mechanism of control; (iii) greater appreciation of the spatial aspects of glycogen metabolism, including more focus on the lysosomal degradation of glycogen; and (iv) glycogen phosphorylation and advances in the study of Lafora disease, which is emerging as a glycogen storage disease

Variable Magnitude and Frequency Financial Reinforcement is Effective at Increasing Adults’ Free-Living Physical Activity

Financial rewards can increase health behaviors, but little research has quantified the effects of different reinforcement schedules on this process. This analysis compares the average moderate-to-vigorous physical activity (MVPA) associated with six distinct positive reinforcement schedules implemented within a physical activity promotion clinical trial. In this trial, participants (N = 512) wore an accelerometer for 1 year and were prescribed one of two types of MVPA goals: a static 30-min goal or an adaptive goal based on the MVPA produced over the previous 9 days. As participants met goals, they transitioned through a sequence of reinforcement stages, beginning with a continuous-fixed magnitude (CRF-FM), then CRF-variable magnitude (CRF-VM), followed by a series of variable ratio-VM (VR-VM) schedules. The average accumulation of MVPA bouts over the last 24 days of each stage was compared to each other. Average MVPA during stage transitions was also examined. The results indicated that immediate reinforcement resulted in more MVPA relative to a comparison group and that the relative effectiveness of adaptive versus static goals was dependent on the magnitude of daily MVPA goals. Schedule effects were qualitatively different for individuals who frequently met their daily goals (Large Intervention Effect subgroup) versus those who did not (Small Intervention Effect subgroup). For the Large Intervention Effect group, the CRF-VM schedule produced the most MVPA, in particular within the adaptive goal condition, with increases observed immediately upon encountering this schedule. In contrast, the CRF-FM schedule produced small amounts of MVPA. This pattern was reversed for the Small Intervention Effect subgroup, where the most MVPA was associated with the CRF-FM stage. Future interventions should focus on discriminating small versus large intervention effects as quickly as possible so that the optimal reinforcement schedule can be used

Correction to: Variable Magnitude and Frequency Financial Reinforcement is Effective at Increasing Adults’ Free-Living Physical Activity

The original article has been corrected to update figures 1, 4, and 5 captions. Original article available on Springer\u27s website or in Chapman University Digital Commons

Rationale, Design, and Baseline Characteristics of WalkIT Arizona: A Factorial Randomized Trial Testing Adaptive Goals and Financial Reinforcement to Increase Walking Across Higher and Lower Walkable Neighborhoods

Little change over the decades has been seen in adults meeting moderate-to-vigorous physical activity (MVPA) guidelines. Numerous individual-level interventions to increase MVPA have been designed, mostly static interventions without consideration for neighborhood context. Recent technologies make adaptive interventions for MVPA feasible. Unlike static interventions, adaptive intervention components (e.g., goal setting) adjust frequently to an individual\u27s performance. Such technologies also allow for more precise delivery of “smaller, sooner incentives” that may result in greater MVPA than “larger, later incentives”. Combined, these factors could enhance MVPA adoption. Additionally, a central tenet of ecological models is that MVPA is sensitive to neighborhood environment design; lower-walkable neighborhoods constrain MVPA adoption and maintenance, limiting the effects of individual-level interventions. Higher-walkable neighborhoods are hypothesized to enhance MVPA interventions. Few prospective studies have addressed this premise. This report describes the rationale, design, intervention components, and baseline sample of a study testing individual-level adaptive goal-setting and incentive interventions for MVPA adoption and maintenance over 2 years among adults from neighborhoods known to vary in neighborhood walkability. We scaled these evidenced-based interventions and tested them against static-goal-setting and delayed-incentive comparisons in a 2 × 2 factorial randomized trial to increase MVPA among 512 healthy insufficiently-active adults. Participants (64.3% female, M age = 45.5 ± 9.1 years, M BMI = 33.9 ± 7.3 kg/m2, 18.8% Hispanic, 84.0% White) were recruited from May 2016 to May 2018 from block groups ranked on GIS-measured neighborhood walkability and socioeconomic status (SES) and classified into four neighborhood types: “high walkable/high SES,” “high walkable/low SES,” “low walkable/high SES,” and “low walkable/low SES.” Results from this ongoing study will provide evidence for some of the central research questions of ecological models

Effects of Goal Type and Reinforcement Type on Self-Reported Domain-Specific Walking Among Inactive Adults: 2×2 Factorial Randomized Controlled Trial

Background: WalkIT Arizona was a 2×2 factorial trial examining the effects of goal type (adaptive versus static) and reinforcement type (immediate versus delayed) to increase moderate to vigorous physical activity (MVPA) among insufficiently active adults. The 12-month intervention combined mobile health (mHealth) technology with behavioral strategies to test scalable population-health approaches to increasing MVPA. Self-reported physical activity provided domain-specific information to help contextualize the intervention effects. Objective: The aim of this study was to report on the secondary outcomes of self-reported walking for transportation and leisure over the course of the 12-month WalkIT intervention. Methods: A total of 512 participants aged 19 to 60 years (n=330 [64.5%] women; n=425 [83%] Caucasian/white, n=96 [18.8%] Hispanic/Latinx) were randomized into interventions based on type of goals and reinforcements. The International Physical Activity Questionnaire-long form assessed walking for transportation and leisure at baseline, and at 6 months and 12 months of the intervention. Negative binomial hurdle models were used to examine the effects of goal and reinforcement type on (1) odds of reporting any (versus no) walking/week and (2) total reported minutes of walking/week, adjusted for neighborhood walkability and socioeconomic status. Separate analyses were conducted for transportation and leisure walking, using complete cases and multiple imputation. Results: All intervention groups reported increased walking at 12 months relative to baseline. Effects of the intervention differed by domain: a significant three-way goal by reinforcement by time interaction was observed for total minutes of leisure walking/week, whereas time was the only significant factor that contributed to transportation walking. A sensitivity analysis indicated minimal differences between complete case analysis and multiple imputation. Conclusions: This study is the first to report differential effects of adaptive versus static goals for self-reported walking by domain. Results support the premise that individual-level PA interventions are domain- and context-specific and may be helpful in guiding further intervention refinement

Reframing pain: the power of individual and societal factors to enhance pain treatment.

The effectiveness of analgesics can be increased if synergistic behavioural, psychological, and pharmacological interventions are provided within a supportive environment

Meditation-based interventions for family caregivers of people with dementia: a review of the empirical literature

Objectives: Providing care for a family member with dementia is associated with increased risk of adverse mental health sequelae. Recently, interventions utilising meditation-based techniques have been developed with the aim of reducing psychological distress among dementia caregivers. The present review aimed to critically evaluate the extant empirical literature in order to determine: (1) whether meditation-based interventions can reduce depression among dementia caregivers and (2) whether meditation-based interventions can reduce subjective burden among dementia caregivers. Method: After adhering to inclusion and exclusion criteria, a total of eight studies were included in the present review. Methodological quality was assessed using one of two scales dependent on study design. Results: The results provide tentative evidence that meditation-based interventions do indeed improve levels of depression and burden in family dementia caregivers. Conclusions: The review highlighted the strengths and weakness of the studies’ methodological designs. Whilst this novel review offers evidence in support of meditation-based interventions to improve the psychological distress of family dementia caregivers, future research should direct efforts to conduct larger scale, more rigorous studies. Clinical implications of the findings are also discussed

Rescue of Aspergillus nidulans severely debilitating null mutations in ESCRT-0, I, II and III genes by inactivation of a salt-tolerance pathway allows examination of ESCRT gene roles in pH signalling.

The Aspergillus pal pathway hijacks ESCRT proteins into ambient pH signalling complexes. We show that components of ESCRT-0, ESCRT-I, ESCRT-II and ESCRT-III are nearly essential for growth, precluding assessment of null mutants for pH signalling or trafficking. This severely debilitating effect is rescued by loss-of-function mutations in two cation tolerance genes, one of which, sltA, encodes a transcription factor whose inactivation promotes hypervacuolation. Exploiting a conditional expression sltA allele, we demonstrate that deletion of vps27 (ESCRT-0), vps23 (ESCRT-I), vps36 (ESCRT-II), or vps20 or vps32 (both ESCRT-III) leads to numerous small vacuoles, a phenotype also suppressed by SltA downregulation. This situation contrasts with normal vacuoles and vacuole-associated class E compartments seen in Saccharomyces cerevisiae ESCRT null mutants. Exploiting the suppressor phenotype of sltA− mutations, we establish that Vps23, Vps36, Vps20 and Vps32 are essential for pH signalling. Phosphatidylinositol 3-phosphate-recognising protein Vps27 (ESCRT-0) is not, consistent with normal pH signalling in rabB null mutants unable to recruit Vps34 kinase to early endosomes. In contrast to the lack of pH signalling in the absence of Vps20 or Vps32, detectable signalling occurs in the absence of ESCRT-III subunit Vps24. Our data support a model in which certain ESCRT proteins are recruited to the plasma membrane to mediate pH signalling