| 211. |
- Middleton, Steven J, et al.
(författare)
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Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.
- 2022
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 145:10, s. 3637-3653
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Tidskriftsartikel (refereegranskat)abstract
- Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.
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| 212. |
- Migale, Roberta, et al.
(författare)
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Specific Lipopolysaccharide Serotypes Induce Differential Maternal and Neonatal Inflammatory Responses in a Murine Model of Preterm Labor.
- 2015
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Ingår i: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 185:9, s. 2390-401
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Tidskriftsartikel (refereegranskat)abstract
- Intrauterine inflammation is recognized as a key mediator of both normal and preterm birth but is also associated with neonatal neurological injury. Lipopolysaccharide (LPS) is often used to stimulate inflammatory pathways in animal models of infection/inflammation-induced preterm labor; however, inconsistencies in maternal and neonatal responses to LPS are frequently reported. We hypothesized that LPS serotype-specific responses may account for a portion of these inconsistencies. Four different Escherichia coli LPS serotypes (O111:B4, O55:B5, O127:B8, and O128:B12) were administered to CD1 mice via intrauterine injection at gestational day 16. Although control animals delivered at term 60±15 hours postinjection (p.i.), those administered with O111:B4 delivered 7 ± 2 hours p.i., O55:B5 delivered 10 ± 3 hours p.i., O127:B8 delivered 16 ± 10 hours p.i., and O128:B12 delivered 17 ± 2 hours p.i. (means ± SD). A correlation between the onset of preterm labor and myometrial activation of the inflammatory transcription factor, activator protein 1, but not NF-κB was observed. Specific LPS serotypes induced differential activation of downstream contractile and inflammatory pathways in myometrium and neonatal pup brain. Our findings demonstrate functional disparity in inflammatory pathway activation in response to differing LPS serotypes. Selective use of LPS serotypes may represent a useful tool for targeting specific inflammatory response mechanisms in these models.
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| 213. |
- Robitaille, Annie, et al.
(författare)
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Transitions across cognitive states and death among older adults in relation to education: A multistate survival model using data from six longitudinal studies
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:4, s. 462-472
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 the Alzheimer's Association. Introduction: This study examines the role of educational attainment, an indicator of cognitive reserve, on transitions in later life between cognitive states (normal Mini-Mental State Examination (MMSE), mild MMSE impairment, and severe MMSE impairment) and death. Methods: Analysis of six international longitudinal studies was performed using a coordinated approach. Multistate survival models were used to estimate the transition patterns via different cognitive states. Life expectancies were estimated. Results: Across most studies, a higher level of education was associated with a lower risk of transitioning from normal MMSE to mild MMSE impairment but was not associated with other transitions. Those with higher levels of education and socioeconomic status had longer nonimpaired life expectancies. Discussion: This study highlights the importance of education in later life and that early life experiences can delay later compromised cognitive health. This study also demonstrates the feasibility and benefit in conducting coordinated analysis across multiple studies to validate findings.
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| 214. |
- Song, Ruixue, et al.
(författare)
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Association of cardiovascular risk burden with risk of dementia and brain pathologies : A population-based cohort study
- 2021
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:12, s. 1914-1922
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies. Methods Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies. Results The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12). Conclusions A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.
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| 215. |
- Song, Ruixue, et al.
(författare)
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Associations Between Cardiovascular Risk, Structural Brain Changes, and Cognitive Decline
- 2020
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 75:20, s. 2525-2534
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear. OBJECTIVES This study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences. METHODS Within the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models. RESULTS In all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 +/- 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (beta = -0.019; 95% confidence interval [CI]: -0.035 to -0.003), episodic memory (beta = -0.023; 95% CI: -0.041 to -0.004), working memory (beta = -0.021; 95% CI: -0.035 to -0.007), and perceptual speed (beta = -0.027; 95% CI: -0.042 to -0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (beta = -0.021; 95% CI: -0.042 to -0.000), gray matter (beta = -1.569; 95% CI: -2.757 to -0.382), and total brain (beta = -1.588; 95% CI: -2.832 to -0.344), and greater volume of white matter hyperintensities (beta = 0.035; 95% CI: 0.001 to 0.069). CONCLUSIONS Higher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.
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| 216. |
- Tigchelaar, Michelle, et al.
(författare)
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The vital roles of blue foods in the global food system
- 2022
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Ingår i: Global Food Security. - : Elsevier BV. - 2211-9124. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Blue foods play a central role in food and nutrition security for billions of people and are a cornerstone of the livelihoods, economies, and cultures of many coastal and riparian communities. Blue foods are extraordinarily diverse, are often rich in essential micronutrients and fatty acids, and can often be produced in ways that are more environmentally sustainable than terrestrial animal-source foods. Capture fisheries constitute the largest wild-food resource for human extraction that would be challenging to replace. Yet, despite their unique value, blue foods have often been left out of food system analyses, policies, and investments. Here, we focus on three imperatives for realizing the potential of blue foods: (1) Bring blue foods into the heart of food system decision-making; (2) Protect and develop the potential of blue foods to help end malnutrition; and (3) Support the central role of small-scale actors in fisheries and aquaculture. Recognition of the importance of blue foods for food and nutrition security constitutes a critical justification to preserve the integrity and diversity of aquatic species and ecosystems.
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| 217. |
- Trendafilova, Teodora, et al.
(författare)
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Sodium-calcium exchanger-3 regulates pain “wind-up” : From human psychophysics to spinal mechanisms
- 2022
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 110:16, s. 2571-2587.e13
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Tidskriftsartikel (refereegranskat)abstract
- Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is “wind-up,” in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was expressed in mouse dorsal horn neurons, and mice lacking NCX3 showed normal, acute pain but hypersensitivity to the second phase of the formalin test and chronic constriction injury. Dorsal horn neurons lacking NCX3 showed increased intracellular calcium following repetitive stimulation, slowed calcium clearance, and increased wind-up. Moreover, virally mediated enhanced spinal expression of NCX3 reduced central sensitization. Our study highlights Ca2+ efflux as a pathway underlying temporal summation and persistent pain, which may be amenable to therapeutic targeting.
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| 218. |
- Wang, Jingya, et al.
(författare)
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Association of Pulmonary Function With Motor Function Trajectories and Disability Progression Among Older Adults : A Long-Term Community-Based Cohort Study
- 2022
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 77:12, s. 2524-2531
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association of pulmonary function (PF) with motor function and disability remains unclear. We investigate the association of PF with motor function trajectories and disability progression, and explore the role of social activity, cognitive function, and cardiovascular diseases (CVDs) in this relationship.Methods: Within the Rush Memory and Aging Project, 1 403 disability-free participants (mean age: 79.28 years) were followed for up to 22 years. PF was measured with a composite score based on peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity at baseline. Global motor function including dexterity, gait, and hand strength was assessed annually using 10 motor tests. Disability was evaluated according to the basic activities of daily living. Social activity was defined as the frequency of common types of social interaction. Global cognitive function was assessed using a battery of 19 cognitive performance tests. CVDs (including stroke, congestive heart failure, and heart diseases) were ascertained at baseline. Linear mixed-effects models were used.Results: Compared to high PF, low PF was related to faster decline in global motor function (β = −0.005, 95% confidence interval [CI]: −0.008 to −0.001) and all 3 specific motor abilities (p < .05), as well as faster progression of disability (β = 0.012, 95% CI: 0.009 to 0.014). There was a statistically significant interaction between PF and social activity/cognitive function on disability progression (β = 0.005, 95% CI: 0.001 to 0.009, p = .010/β = 0.004, 95% CI: 0.001 to 0.009, p = .025).Conclusion: Poor PF accelerates motor function decline and the progression of disability. A high level of social activity and cognitive function appear to decelerate disability progression related to poor PF.
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| 219. |
- Wang, Jiao, et al.
(författare)
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Pulmonary function is associated with cognitive decline and structural brain differences
- 2022
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1335-1344
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Tidskriftsartikel (refereegranskat)abstract
- The association of poor pulmonary function (PF) with cognitive trajectories and structural brain differences remains unclear. Within the Rush Memory and Aging Project, 1377 dementia-free subjects were followed up to 21 years. PF was assessed with a composite score measured at baseline. Global and domain-specific cognitive function was assessed annually constructed from 19 cognitive tests. A subsample of 351 participants underwent brain magnetic resonance imaging to investigate the cross-sectional association between PF and structural brain volumes. We found that low PF was related to faster decline in global cognition, and domain-specific function including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed. In addition, low PF was associated with smaller volumes of total brain, white matter and gray matter, and larger white matter hyperintensities volume. Our results suggest that low PF is associated with faster cognitive decline, and both neurodegeneration and vascular brain lesions may underlie the association.
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| 220. |
- Wang, Zhangyu, et al.
(författare)
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Influence of Cardiovascular Risk Burden on Motor Function Among Older Adults : Mediating Role of Cardiovascular Diseases Accumulation and Cognitive Decline
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to investigate the association of the cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) with the trajectories of motor function over time and to assess the mediating effects of cardiovascular diseases (CVDs) accumulation and cognitive decline in such association.Methods: In Rush Memory and Aging Project, a total of 1,378 physical health participants (mean age: 79.3 ± 7.3 years) were followed up for up to 22 years. FGCRS at baseline was assessed and categorized into tertiles (lowest, middle, and highest). Global motor function (including dexterity, gait, and hand strength) was assessed annually with 10 motor tests. CVDs (including stroke, congestive heart failure, and other heart diseases) were ascertained at baseline and follow-ups, and the number of CVDs accumulation over time was assessed. Global cognitive function was tested annually by 19 tests. Data were analyzed using the linear mixed-effects models and mediation analysis.Results: At baseline, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Over the follow-up (median: 5.3 years; interquartile range: 2.9–9.0 years), in multi-adjusted mixed-effects models, the highest FGCRS was associated with faster decline in global motor function (β = −0.0038; 95% confidence interval [CI]: −0.0069 to −0.0008), dexterity (β = −0.0056; 95% CI: −0.0093 to −0.0020), gait (β = −0.0039; 95% CI: −0.0077 to −0.0001), and hand strength (β = −0.0053; 95% CI: −0.0098 to −0.0008) compared with the lowest tertile. In mediation analysis, CVDs accumulation and cognitive decline mediated 8.4% and 42.9% of the association between FGCRS and global motor function over time, respectively.Conclusion: Higher cardiovascular risk burden is associated with a faster decline in motor function including dexterity, gait, and hand strength. CVDs accumulation and cognitive decline may partially mediate the association between cardiovascular risk burden and global motor function decline.
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