| 1. |
- Benedict, Christian, et al.
(författare)
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Association between physical activity and brain health in older adults
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.
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| 2. |
- Benedict, Christian, et al.
(författare)
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Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly
- 2012
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:3, s. 488-494
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEImpaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.RESEARCH DESIGN AND METHODSInsulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).RESULTSThe HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.CONCLUSIONSThese cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.
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| 3. |
- Burgos, Jonathan R
(författare)
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Central and Peripheral Neuroendocrine Factors in Cancer-Associated Anorexia and Cachexia
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer anorexia-cachexia syndrome (CACS) develops in response to tumor-host biochemical interactions. A loss of appetite (anorexia) and increased metabolism results in a progressive wasting of adipose and skeletal muscle tissues (cachexia). This syndrome is linked to a reduced tolerance to anti-cancer treatments, lower quality of life, and poor prognosis. The specific mechanisms that cause CACS are still unknown, and there exists no curative treatment for this syndrome. In this thesis, rodent models for induced anorexia, MCG101 tumor-induced CACS, and acute inflammation paradigms were used. The first stages of this thesis project were aimed at identifying central mechanisms by which cancer-associated anorexia could be overriding homeostatic feeding controls. Our initial investigations involved cocaine- and amphetamine-regulated transcript peptides (CARTp) and the thyrotropin receptor (TSHr). Centrally acting CARTp are known to potently inhibit feeding. Similarly, infusions of TSH into the lateral ventricles have been shown to reduce food intake in rats. The precise mechanisms through which CARTp elicits its effects, and the distribution of functional TSHr have been unknown. A previous in vitro study showed CARTp activity was antagonized by PACAP6-38. We built upon previous findings by showing that PACAP6-38 could block CARTp-induced anorexia in vivo in rats; thus, we provided further support that PACAP6-38 is a useful tool for elucidating endogenous CARTp effects. In addition, we report that TSHr proteins are present in nuclei of the hypothalamus and brainstem with relevance for feeding. Indeed, putative stimulation of TSHr in the nucleus of the solitary tract reduced solid food intake in healthy rats. Using mouse models for acute inflammation and CACS, we investigated gene expression changes in areas of the brain with relevance for feeding, namely the hypothalamic paraventricular nucleus (PVN), arcuate nucleus (ARC), and the dorsal vagal complex of the brainstem. We investigated mRNA for compounds expressed in brain regions involved in feeding behavior under healthy conditions: CART, TSHr, TSH, thyrostimulin, nesfatin-1, and corticotropin-releasing hormone (CRH). Acute inflammation was associated with reduced gene expression for TSHr and CART in the ARC and increased expression of CART mRNA in the pituitary. CACS also resulted in a decrease in CART gene expression in the PVN, which was a response secondary to reduced food intake as shown by pair-fed controls. Interestingly, we saw a tumor-specific effect on nesfatin-1 gene expression in the PVN. Therefore, it appears that CARTp is not inducing anorexia in CACS, but seems to participate in an adaptive response. In addition, hypothalamic nesfatin-1 may be a likely candidate for mediating a CACS response. Acute inflammation induced a prostanoid-independent increase of plasma CARTp, which correlated positively with degree of inflammation. Tumor-bearing mice similarly had elevated plasma CARTp concentrations. Putative antagonism of circulating CARTp by PACAP6-38 in tumor-bearing animals protected against loss of fat mass, but did not improve food intake or any other metrics. These findings highlight plasma CARTp as a potential mediator of lipolysis in CACS.
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| 4. |
- Burgos, Jonathan R, et al.
(författare)
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LPS immune challenge reduces arcuate nucleus TSHR and CART mRNA and elevates plasma CART peptides.
- 2019
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Ingår i: BMC neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to examine the impact of lipopolysaccharide-induced systemic inflammation on expression of mRNA for cocaine- and amphetamine-regulated transcript (CART) and the thyrotropin receptor (TSHR) and its ligands in CNS areas of relevance for feeding controls and metabolism. Lipopolysaccharide effects on plasma levels of TSH and CART peptides were also examined.Lipopolysaccharide (150-200μg/mouse) was injected in C57BL/6J mice and tissue and plasma samples taken after 24h. To establish if plasma increase in CART peptide levels were prostanoid dependent, indomethacin was given via the drinking water beginning 48h prior to LPS. We evaluated mRNA expression for CART, TSHR, TSHβ, and thyrostimulin in brain and pituitary extracts. Plasma levels of TSH, CARTp, and serum amyloid P component were analyzed by ELISA.Lipopolysaccharide suppressed TSHR mRNA expression in the arcuate nucleus and the pituitary. CART mRNA expression was reduced in the arcuate nucleus but elevated in the pituitary of mice treated with Lipopolysaccharide, whereas plasma TSH remained unchanged. Plasma CART peptide concentration increased after LPS treatment in a prostanoid-independent manner, and CART peptide levels correlated positively to degree of inflammation.Our findings suggest that central and peripheral CART is affected by acute inflammation. Considering the role of the arcuate nucleus in feeding controls, our data highlight TSHR and CART as putative neuroendocrine signaling components that respond to inflammation, perhaps to maintain weight and metabolic homeostasis during states of disease.
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| 5. |
- Burgos, Jonathan R, et al.
(författare)
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MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.
- 2016
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Ingår i: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 35:4, s. 2425-2430
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor perse. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid Pcomponent (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.
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| 6. |
- Burgos, Jonathan R, et al.
(författare)
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Pituitary adenylate cyclase-activating polypeptide 6-38 blocks cocaine- and amphetamine-regulated transcript Peptide-induced hypophagia in rats.
- 2013
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Cocaine- and amphetamine-regulated transcript peptides (CARTp) suppress nutritional intake after administration into the fourth intracerebral ventricle. Recent in vitro studies have shown that PACAP 6-38, a pituitary adenylate cyclase-activating polypeptide (PACAP) fragment, could act as a competitive antagonist against CARTp 55-102 on a common CARTp-sensitive receptor structure. Here, we show for the first time in vivo that the reduction in solid food intake induced by exogenous CARTp 55-102 (0.3 nmol: 1.5 µg) administered fourth i.c.v. is blocked by pretreatment with PACAP 6-38 (3 nmol). The PACAP 6-38 fragment had no effect by itself either when given into the fourth ventricle or subcutaneously. Although effective to block the CARTp-effect on feeding and short-term body weight, PACAP 6-38 failed to attenuate CARTp-associated gross motor behavioral changes suggesting at least two CARTp-sensitive receptor subtypes. In conclusion, PACAP 6-38 acts as a functional CARTp antagonist in vivo and blocks its effects on feeding and short term weight gain.
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| 7. |
- Burgos, Jonathan R, et al.
(författare)
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Presence of TSH receptors in discrete areas of the hypothalamus and caudal brainstem with relevance for feeding controls—Support for functional significance
- 2016
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Ingår i: Brain research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1642, s. 278-286
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that brain-derived thyroid-stimulating hormone (TSH) and its receptor (TSHr) are present in hypothalamic extracts. No studies investigating both the anatomical location and functional significance of putative TSHr proteins in specific central nervous system (CNS) nuclei involved in feeding controls have yet been conducted. The aim was thus to determine whether TSHr are present in nuclei associated with feeding behavior, and if such receptors may be functional.
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| 8. |
- Gkouskos, Dimitrios, et al.
(författare)
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I'm in! Towards participatory healthcare of elderly through IOT
- 2017
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Ingår i: Procedia Computer Science. - : Elsevier. - 1877-0509. ; 113:Special issue : The 8th International Conference on Emerging Ubiquitous Systems and Pervasive Networks (EUSPN 2017) / The 7th International Conference on Current and Future Trends of Information and Communication Technologies in Healthcare (ICTH-2017) / Affiliated Workshops, s. 647-652
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Tidskriftsartikel (refereegranskat)abstract
- People today are a capable of living longer, healthier lives than ever before, which results in a growing elderly population. The elderly face issues of reduced physical ability, having to manage multiple health issues over long periods of time, and being digital immigrants. These issues pose unique challenges that often lead to elderly feeling loss of agency due to not being actively involved in managing their own well-being. In this paper, we propose participatory design of IOT technologies to enact universal design in order to better include elderly in managing their health, and thus improving their quality of life. (c) 2017 The Authors. Published by Elsevier B.V.
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| 9. |
- Gkouskos, Dimitrios, Assistant Professor, 1983-, et al.
(författare)
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Teaching Design Ethics Through Tabletop Game Prototyping
- 2023
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Ingår i: The 7th International Conference for Design Education Researchers. - London, UK : Design Research Society.
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Konferensbidrag (refereegranskat)abstract
- Design Ethics is a challenging yet vital topic to address and teach, especially in an age where designers may think they are not ethically responsible for their creations. This paper describes the design of an ethics course where instructors used Research Through Design as a vehicle to teach design ethics to a class of master’s students. We describe how we introduced tabletop game prototyping using the Design Games Framework, a lecture-workshop-supervision format supported by a design diary, and student-led sessions to create a pedagogical structure for students to unpack and explore ethical issues. We discuss the design diaries and present reflections on developing reflexivity through game making, framing design as exploration rather than solution-making, and moving beyond dramatic elements when game-making. The course design and reflections provide guidance for design educators in integrating game-making activities in design ethics courses.
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| 10. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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