Vitamin D and Human Skeletal Muscle Hamilton, B.
Scandinavian journal of medicine & science in sports,
April 2010, Volume:
20, Issue:
2
Journal Article
Peer reviewed
Open access
Vitamin D deficiency is an increasingly described phenomenon worldwide, with well‐known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems ...such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross‐sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non‐genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both underperformance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue.
In the past 20 years, an extra layer of information processing, in addition to that provided by neurons, has been proposed for the CNS. Neuronally evoked increases of the intracellular calcium ...concentration in astrocytes have been suggested to trigger exocytotic release of the 'gliotransmitters' glutamate, ATP and D-serine. These are proposed to modulate neuronal excitability and transmitter release, and to have a role in diseases as diverse as stroke, epilepsy, schizophrenia, Alzheimer's disease and HIV infection. However, there is intense controversy about whether astrocytes can exocytose transmitters in vivo. Resolving this issue would considerably advance our understanding of brain function.
Innovations in Mixed Methods Evaluations Palinkas, Lawrence A; Mendon, Sapna J; Hamilton, Alison B
Annual review of public health,
04/2019, Volume:
40, Issue:
1
Journal Article
Peer reviewed
Open access
Mixed methods research-i.e., research that draws on both qualitative and quantitative methods in varying configurations-is well suited to address the increasing complexity of public health problems ...and their solutions. This review focuses specifically on innovations in mixed methods evaluations of intervention, program or policy (i.e., practice) effectiveness, and implementation. The article begins with an overview of the structure, function, and process of different mixed methods designs and then provides illustrations of their use in effectiveness studies, implementation studies, and combined effectiveness-implementation hybrid studies. The article then examines four specific innovations: procedures for transforming (or "quantitizing") qualitative data, application of rapid assessment and analysis procedures in the context of mixed methods studies, development of measures to assess implementation outcomes, and strategies for conducting both random and purposive sampling, particularly in implementation-focused evaluation research. The article concludes with an assessment of challenges to integrating qualitative and quantitative data in evaluation research.
Although designed as a consumer product to help motivate individuals to be physically active, Fitbit activity trackers are becoming increasingly popular as measurement tools in physical activity and ...health promotion research and are also commonly used to inform health care decisions.
The objective of this review was to systematically evaluate and report measurement accuracy for Fitbit activity trackers in controlled and free-living settings.
We conducted electronic searches using PubMed, EMBASE, CINAHL, and SPORTDiscus databases with a supplementary Google Scholar search. We considered original research published in English comparing Fitbit versus a reference- or research-standard criterion in healthy adults and those living with any health condition or disability. We assessed risk of bias using a modification of the Consensus-Based Standards for the Selection of Health Status Measurement Instruments. We explored measurement accuracy for steps, energy expenditure, sleep, time in activity, and distance using group percentage differences as the common rubric for error comparisons. We conducted descriptive analyses for frequency of accuracy comparisons within a ±3% error in controlled and ±10% error in free-living settings and assessed for potential bias of over- or underestimation. We secondarily explored how variations in body placement, ambulation speed, or type of activity influenced accuracy.
We included 67 studies. Consistent evidence indicated that Fitbit devices were likely to meet acceptable accuracy for step count approximately half the time, with a tendency to underestimate steps in controlled testing and overestimate steps in free-living settings. Findings also suggested a greater tendency to provide accurate measures for steps during normal or self-paced walking with torso placement, during jogging with wrist placement, and during slow or very slow walking with ankle placement in adults with no mobility limitations. Consistent evidence indicated that Fitbit devices were unlikely to provide accurate measures for energy expenditure in any testing condition. Evidence from a few studies also suggested that, compared with research-grade accelerometers, Fitbit devices may provide similar measures for time in bed and time sleeping, while likely markedly overestimating time spent in higher-intensity activities and underestimating distance during faster-paced ambulation. However, further accuracy studies are warranted. Our point estimations for mean or median percentage error gave equal weighting to all accuracy comparisons, possibly misrepresenting the true point estimate for measurement bias for some of the testing conditions we examined.
Other than for measures of steps in adults with no limitations in mobility, discretion should be used when considering the use of Fitbit devices as an outcome measurement tool in research or to inform health care decisions, as there are seemingly a limited number of situations where the device is likely to provide accurate measurement.
•Qualitative methods are critical to implementation research.•Qualitative methods address the hows and whys of implementation.•Interviews and observation are key methods in implementation ...research.•Data collection and analysis are typically driven by an implementation framework.•Rapid turn-around of qualitative findings supports implementation and evaluation.
Qualitative methods are a valuable tool in implementation research because they help to answer complex questions such as how and why efforts to implement best practices may succeed or fail, and how patients and providers experience and make decisions in care. This article orients the novice implementation scientist to fundamentals of qualitative methods and their application in implementation research, describing: 1) implementation-related questions that can be addressed by qualitative methods; 2) qualitative methods commonly used in implementation research; 3) basic sampling and data collection procedures; and 4) recommended practices for data analysis and ensuring rigor. To illustrate qualitative methods decision-making, a case example is provided of a study examining implementation of a primary care-based collaborative care management model for women Veterans with anxiety, depression, and PTSD.
The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of ...p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a “recruit-and-release” mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.
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•p300/CBP and deacetylase activities regulate dynamic (de)activation of enhancers•p300/CBP-catalyzed acetylation promotes PIC assembly and RNAPII recruitment•BRD4 acts as a p300/CBP downstream effector to promote RNAPII pause release•Coupling of RNAPII recruitment and pause release enables rapid enhancer activation
A systems-wide analysis reveals that enhancers are activated by p300/CBP-catalyzed acetylation and deactivated by deacetylation. p300/CBP activity promotes pre-initiation complex assembly and RNAPII recruitment independently of its previously known function in BRD4-dependent pause release. By simultaneously promoting transcription initiation and elongation, p300/CBP activity drives the rapid activation of enhancers and super-enhancers.
Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To ...dissect the role of Erk in both ESC self-renewal and lineage specification, we explored the requirements for this pathway in various in vitro differentiation settings. A combination of pharmacological inhibition of Erk signaling and genetic loss of function reveal a role for Erk signaling in endodermal, but not neural differentiation. Neural differentiation occurs normally despite a complete block to Erk phosphorylation. In support of this, Erk activation in ESCs derepresses primitive endoderm (PrE) gene expression as a consequence of inhibiting the pluripotent/epiblast network. The early response to Erk activation correlates with functional PrE priming, whereas sustained Erk activity results in PrE differentiation. Taken together, our results suggest that Erk signaling suppresses pluripotent gene expression to enable endodermal differentiation.
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•Erk activity is dispensable for exit from pluripotency and neural differentiation•Erk activity suppresses pluripotency gene expression to induce endoderm specification•Erk signaling duration determines the difference between priming and differentiation•Nanog blocks Gata6 induction but not the inhibition of pluripotency by Erk
Hamilton and Brickman show that Erk activity is not required for epiblast nor neural differentiation but promotes primitive endoderm priming and differentiation through suppression of a subset of the ESC gene regulatory network. The duration of Erk signaling determines the difference between reversible priming and differentiation.
Severe primary graft dysfunction affects 15-20% of lung transplant recipients and carries a high mortality risk. In addition to known donor, recipient, and perioperative clinical risk factors, ...numerous biologic factors are thought to contribute to primary graft dysfunction. Our current understanding of the pathogenesis of lung injury and primary graft dysfunction emphasizes multiple pathways leading to lung endothelial and epithelial injury. Protein biomarkers specific to these pathways can be measured in the plasma, bronchoalveolar lavage fluid, and lung tissue. Clarification of the pathophysiology and timing of primary graft dysfunction could illuminate predictors of dysfunction, allowing for better risk stratification, earlier identification of susceptible recipients, and development of targeted therapies. Here, we review much of what has been learned about the association of protein biomarkers with primary graft dysfunction and evaluate this association at different measurement time points.
Archean, Paleoproterozoic, and Mesoproterozoic rocks, assemblages, and structures differ greatly both from each other and from modern ones, and lack evidence for subduction and seafloor spreading ...such as is widespread in Phanerozoic terrains. Most specialists nevertheless apply non-actualistic plate-tectonic explanations to the ancient terrains and do not consider alternatives. This report evaluates popular concepts with multidisciplinary information, and proposes options. The key is fractionation by ca. 4.45
Ga of the hot young Earth into core, severely depleted mantle, and thick mafic protocrust, followed by still-continuing re-enrichment of upper mantle from the top. This is opposite to the popular assumption that silicate Earth is still slowly and unidirectionally fractionating. The protocrust contained most material from which all subsequent crust was derived, either directly, or indirectly after downward recycling. Tonalite, trondhjemite, and granodiorite (TTG), dominant components of Archean crust, were derived mostly by partial melting of protocrust. Dense restitic protocrust delaminated and sank into hot, weak dunite mantle, which, displaced upward, enabled further partial melting of protocrust. Sinkers enriched the upper mantle, in part maintaining coherence as distinct dense rocks, and in part yielding melts that metasomatized depleted-mantle dunite to more pyroxenic and garnetiferous rocks. Not until ca. 3.6
Ga was TTG crust cool enough to allow mafic and ultramafic lavas, from both protocrust and re-enriched mantle, to erupt to the surface, and then to sag as synclinal keels between rising diapiric batholiths; simultaneously upper crust deformed ductily, then brittly, above slowly flowing hot lower TTG crust. Paleoproterozoic and Mesoproterozoic orogens appear to be largely ensialic, developed from very thick basin-filling sedimentary and volcanic rocks on thinned Archean or Paleoproterozoic crust and remaining mafic protocrust, above moderately re-enriched mantle. Subduction, and perhaps the continent/ocean lithospheric dichotomy, began ca. 850
Ma – although fully modern plate-tectonic processes began only in Ordovician time – and continued to enrich the cooling mantle in excess of partial melts that contributed to new crust. “Plumes” from deep mantle do not operate in the modern Earth and did not operate in Precambrian time.
► Pre-Neoproterozoic crust lacks all indicators of plate tectonics. ► Thick mafic protocrust and depleted mantle fractionated before 4.4 Ga. ► “Juvenile” Archean TTG came from protocrust, not mantle. ► Paleoproterozoic and Mesoproterozoic orogens are mostly ensialic. ► Delaminates enriched upper mantle, and plate tectonics began after 850 Ma.
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