Perceived and objectively-assessed aspects of the neighbourhood physical environment have been postulated to be key contributors to regular engagement in active travel (AT) in older adults. We ...systematically reviewed the literature on neighbourhood physical environmental correlates of AT in older adults and applied a novel meta-analytic approach to statistically quantify the strength of evidence for environment-AT associations.
Forty two quantitative studies that estimated associations of aspects of the neighbourhood built environment with AT in older adults (aged ≥ 65 years) and met selection criteria were reviewed and meta-analysed. Findings were analysed according to five AT outcomes (total walking for transport, within-neighbourhood walking for transport, combined walking and cycling for transport, cycling for transport, and all AT outcomes combined) and seven categories of the neighbourhood physical environment (residential density/urbanisation, walkability, street connectivity, access to/availability of services/destinations, pedestrian and cycling infrastructure, aesthetics and cleanliness/order, and safety and traffic).
Most studies examined correlates of total walking for transport. A sufficient amount of evidence of positive associations with total walking for transport was found for residential density/urbanisation, walkability, street connectivity, overall access to destinations/services, land use mix, pedestrian-friendly features and access to several types of destinations. Littering/vandalism/decay was negatively related to total walking for transport. Limited evidence was available on correlates of cycling and combined walking and cycling for transport, while sufficient evidence emerged for a positive association of within-neighbourhood walking with pedestrian-friendly features and availability of benches/sitting facilities. Correlates of all AT combined mirrored those of walking for transport. Positive associations were also observed with food outlets, business/institutional/industrial destinations, availability of street lights, easy access to building entrance and human and motorised traffic volume. Several but inconsistent individual- and environmental-level moderators of associations were identified.
Results support strong links between the neighbourhood physical environment and older adults' AT. Future research should focus on the identification of types and mixes of destinations that support AT in older adults and how these interact with individual characteristics and other environmental factors. Future research should also aim to clarify dose-response relationships through multi-country investigations and data-pooling from diverse geographical regions.
Activity-friendly neighbourhood physical environments with access to recreational facilities are hypothesised to facilitate leisure-time physical activity (LTPA) among older adults (≥ 65 years old). ...The aim of the current study was to systematically review and quantitatively summarise study findings on the relationships between physical environmental attributes and LTPA among older adults.
An extensive search of literature, including grey literature, yielded 72 articles eligible for inclusion. The reported associations between seven categories of environmental attributes and six LTPA outcomes were extracted, weighted by sample size and study quality, and quantitatively summarised. Reported moderating effects of individual and environmental characteristics and neighbourhood definition were also examined.
We observed positive associations for walkability (p = 0.01), land-use mix-access (p = 0.02) and aesthetically pleasing scenery (p < 0.001) with leisure-time walking. For leisure-time walking within the neighbourhood, evidence was found for positive associations with land-use mix-access (p = 0.03) and access to public transit (p = 0.05), and a negative association with barriers to walking/cycling (p = 0.03). Evidence for positive relationships between overall LTPA and access to recreational facilities (p = 0.01) and parks/open space (p = 0.04) was found. Several environmental attribute-LTPA outcome combinations were insufficiently studied to draw conclusions. No consistent moderating effects were observed for individual and environmental characteristics and neighbourhood definition.
The observed significant relationships can be used to inform policy makers and planners on how to (re-)design neighbourhoods that promote LTPA among older adults. Many environmental attribute-LTPA outcome relationships have been studied insufficiently and several methodological issues remain to be addressed.
PROSPERO 2016:CRD42016051180.
Identifying attributes of the built environment associated with health-enhancing levels of physical activity (PA) in older adults (≥65 years old) has the potential to inform interventions supporting ...healthy and active ageing. The aim of this study was to first systematically review and quantify findings on built environmental correlates of older adults' PA, and second, investigate differences by type of PA and environmental attribute measurement.
One hundred articles from peer-reviewed and grey literature examining built environmental attributes related to total PA met inclusion criteria and relevant information was extracted. Findings were meta-analysed and weighted by article quality and sample size and then stratified by PA and environmental measurement method. Associations (p < .05) were found in relation to 26 individual built environmental attributes across six categories (walkability, residential density/urbanisation, street connectivity, access to/availability of destinations and services, infrastructure and streetscape, and safety) and total PA and walking specifically. Reported individual- and environmental-level moderators were also examined.
Positive environmental correlates of PA, ranked by strength of evidence, were: walkability (p < .001), safety from crime (p < .001), overall access to destinations and services (p < .001), recreational facilities (p < .001), parks/public open space (p = .002) and shops/commercial destinations (p = .006), greenery and aesthetically pleasing scenery (p = .004), walk-friendly infrastructure (p = .009), and access to public transport (p = .016). There were 26 individual differences in the number of significant associations when the type of PA and environmental measurement method was considered. No consistent moderating effects on the association between built environmental attributes and PA were found.
Safe, walkable, and aesthetically pleasing neighbourhoods, with access to overall and specific destinations and services positively influenced older adults' PA participation. However, when considering the environmental attributes that were sufficiently studied (i.e., in ≥5 separate findings), the strength of evidence of associations of specific categories of environment attributes with PA differed across PA and environmental measurement types. Future research should be mindful of these differences in findings and identify the underlying mechanisms. Higher quality research is also needed.
Parkinson disease (PD) is the fastest growing neurodegenerative disease. The molecular pathology of PD in the prodromal phase is poorly understood; as such, there are no specific prognostic or ...diagnostic tests. A validated Pink1 genetic knockout rat was used to model early-onset and progressive PD. Male Pink1
rats exhibit progressive declines in ultrasonic vocalizations as well as hindlimb and forelimb motor deficits by mid-to-late adulthood. Previous RNA-sequencing work identified upregulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. The purpose of this study was to identify gene pathways within the whole blood of young Pink1
rats (3 months of age) and to link gene expression to early acoustical changes. To accomplish this, limb motor testing (open field and cylinder tests) and ultrasonic vocalization data were collected, immediately followed by the collection of whole blood and RNA extraction. Illumina
Total RNA-Seq TruSeq platform was used to profile differential expression of genes. Statistically significant genes were identified and Weighted Gene Co-expression Network Analysis was used to construct co-expression networks and modules from the whole blood gene expression dataset as well as the open field, cylinder, and USV acoustical dataset. ENRICHR was used to identify the top up-regulated biological pathways.
The data suggest that inflammation and interferon signaling upregulation in the whole blood is present during early PD. We also identified genes involved in the dysregulation of ribosomal protein and RNA processing gene expression as well as prion protein gene expression.
These data identified several potential blood biomarkers and pathways that may be linked to anxiety and vocalization acoustic parameters and are key candidates for future drug-repurposing work and comparison to human datasets.
Methanogenic archaea are a key part of the gut microbiota alongside bacteria. However there is comparatively little research on the role of archaea in health.
As in-vitro and animal experiments have ...demonstrated immunological effects of archaea, we hypothesised that intestinal exposure to archaeal species would influence the risk of asthma and other allergic diseases. We present the first human study connecting gut archaea with childhood asthma.
We performed a cross-sectional analysis nested within the Dutch KOALA Birth Cohort Study. DNA from two common intestinal archaeal species, Methanosphaera stadtmanae and Methanobrevibacter smithii, was quantified in faecal samples from 472 children at school age, using qPCR. Our primary outcome was parent-reported asthma at 6-10 years. Secondary outcomes were questionnaire-reported eczema, total serum IgE levels, sensitisation to aero- and food-allergens and lung function (FEV1/FVC). Associations between the presence/absence of each archaeal species and outcome were assessed with logistic or linear regression models, adjusted for potential confounders.
Presence of M. stadtmanae was significantly associated with a lower risk of asthma, adjusted OR 0.32 (0.08 - 0.98). In addition, asthma risk decreased monotonically across three categories of increasing M. stadtmanae abundance (adjusted p-for-trend = 0.035). We also observed a non-significant tendency for less eczema and IgE sensitisation amongst children with M. stadtmanae. M. smithii was not associated with any outcome.
Further longitudinal and experimental research is needed to explore whether archaea could be directly linked to asthma risk, or if archaeal abundance is indicative of other health-relevant variation in microbiota composition.
Comprehensive global climate models are the only tools that account for the complex set of processes which will determine future climate change at both a global and regional level. Planners are ...typically faced with a wide range of predicted changes from different models of unknown relative quality, owing to large but unquantified uncertainties in the modelling process. Here we report a systematic attempt to determine the range of climate changes consistent with these uncertainties, based on a 53-member ensemble of model versions constructed by varying model parameters. We estimate a probability density function for the sensitivity of climate to a doubling of atmospheric carbon dioxide levels, and obtain a 5-95 per cent probability range of 2.4-5.4 °C. Our probability density function is constrained by objective estimates of the relative reliability of different model versions, the choice of model parameters that are varied and their uncertainty ranges, specified on the basis of expert advice. Our ensemble produces a range of regional changes much wider than indicated by traditional methods based on scaling the response patterns of an individual simulation.
Abstract Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that is ubiquitous in the nervous system and interacts with a myriad of substrates. Its modulation of synaptic ...plasticity and associated mechanisms of learning and memory as well as neurodegeneration and cognitive disease highlights its importance in the human brain. Cdk5 is active throughout the neuron via its kinase activity, protein–protein interactions, and nuclear associations. It regulates functions thought vital to memory and plasticity, including synaptic vesicle recycling, dendritic spine formation, neurotransmitter receptor density, and neuronal excitability. Although conditional knockout of Cdk5 improves learning and plasticity, the associated deleterious effects of increased excitability cast doubts on the therapeutic efficacy of systemic inhibitors. However, through further work on the regulation of Cdk5 and its effectors, this important molecule promises to aid in elucidating key pathways involved in learning and memory and uncover innovative therapeutic targets to treat neurodegenerative and neuropsychiatric diseases.
Vocal dysfunction, including hypophonia, in Parkinson disease (PD) manifests in the prodromal period and significantly impacts an individual's quality of life. Data from human studies suggest that ...pathology leading to vocal deficits may be structurally related to the larynx and its function. The Pink1-/- rat is a translational model used to study pathogenesis in the context of early-stage mitochondrial dysfunction. The primary objective of this work was to identify differentially expressed genes in the thyroarytenoid muscle and examine the dysregulated biological pathways in the female rat.
RNA sequencing was used to determine thyroarytenoid (TA) muscle gene expression in adult female Pink1-/- rats compared with controls. A bioinformatic approach and the ENRICHR gene analysis tool were used to compare the sequencing dataset with biological pathways and processes, disease relationships, and drug-repurposing compounds. Weighted Gene Co-expression Network Analysis was used to construct biological network modules. The data were compared with a previously published dataset in male rats.
Significant upregulated pathways in female Pink1-/- rats included fatty acid oxidation and muscle contraction, synaptic transmission, and neuromuscular processes. Downregulated pathways included anterograde transsynaptic signaling, chemical synaptic transmission, and ion release. Several drug treatment options including cetuximab, fluoxetine, and resveratrol are hypothesized to reverse observed genetic dysregulation.
Data presented here are useful for identifying biological pathways that may underlie the mechanisms of peripheral dysfunction including neuromuscular synaptic transmission to the TA muscle. These experimental biomarkers have the potential to be targeted as sites for improving the treatment for hypophonia in early-stage PD.
NA Laryngoscope, 133:3412-3421, 2023.
Giving it a boost: A mechanistic study of the enantioselective asymmetric titled reaction with allyldiisopropoxyborane catalyzed by chiral biphenols revealed a key ligand exchange process which ...liberates isopropyl alcohol. The addition of iPrOH to the reaction increases the overall rate and enantioselectivity. As a result an improved reaction, employing allyldioxaborinane with 1 and tBuOH, resulted in high product yields and enantioselectivities.
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