490 research outputs found

    Urban tourism and population change: Gentrification in the age of mobilities

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    The prepandemic unbridled growth of tourism has triggered a significant debate regarding the future of cities; several authors suggest that neighbourhood change produced by tourism should be conceived as a form of gentrification. Yet research on population shifts—a fundamental dimension of gentrification—in such neighbourhoods is scarce. Our exploration of the Gòtic area in Barcelona, using quantitative and qualitative techniques, reveals a process of population restructuring characterised by a decrease of long-term residents and inhabited dwellings, and the arrival of young and transnational gentrifiers that are increasingly mobile and form a transient population. We then use some insights from the mobilities literature to make sense of these results. In the gentrification of the Gòtic, the attractiveness of the area for visitors and for a wider palette of transnational dwellers feeds one another, resulting in an uneven negotiation whereby more wealthy and ‘footloose’ individuals gain access and control of space and housing over less mobile and more dependent populations.info:eu-repo/semantics/publishedVersio

    Morphological Description of Telaepolella tubasferens n. g., n. sp., Isolate ATCC© 50593™, a Filose Amoeba in the Gracilipodida, Amoebozoa

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    We describe the amoeboid isolate ATCC© 50593™ as a new taxon, Telaepolella tubasferens n. gen. n. sp. This multinucleated amoeba has filose pseudopods and is superficially similar to members of the vampyrellids (Rhizaria) such as Arachnula impatiens Cienkowski, 1876, which was the original identification upon deposition. However, previous multigene analyses place this taxon within the Gracilipodida Lahr and Katz 2011 in the Amoebozoa. Here, we document the morphology of this organism at multiple life history stages and describe data underlying the description as a new taxon. We demonstrate that T. tubaspherens is distinct from Arachnula and other rhizarians (Theratromyxa, Leptophrys) in a suite of morphological characters such as general body shape, relative size of pseudopods, distinction of ecto- and endoplasmic regions, and visibility of nuclei in non-stained cells (an important diagnostic character). Although Amoebozoa taxa generally have lobose pseudopods, genera in Gracilipodida such as Flamella and Filamoeba as well as several organisms previously classified as protosteloid amoebae (e.g. schizoplasmodiis, cavosteliids and Stemonitales) present filose pseudopodia. Thus, classification of amoeboid organisms merely by filose-lobose distinction must be reconsidered

    Targeting Astrocytes Ameliorates Neurologic Changes in a Mouse Model of Alzheimer\u27s Disease

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    Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer\u27s disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically activated phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific Gfa2 promoter to target hippocampal astrocytes in APP/PS1 mice. AAV-Gfa2 vectors drove the expression of VIVIT, a peptide that interferes with the immune/inflammatory calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway, shown by our laboratory and others to orchestrate biochemical cascades leading to astrocyte activation. After several months of treatment with Gfa2-VIVIT, APP/PS1 mice exhibited improved cognitive and synaptic function, reduced glial activation, and lower amyloid levels. The results confirm a deleterious role for activated astrocytes in AD and lay the groundwork for exploration of other novel astrocyte-based therapies

    Long-Term Survival in Octogenarians After Surgical Treatment for Colorectal Cancer:Prevention of Postoperative Complications is Key

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    BackgroundWhether to treat octogenarians with colorectal cancer (CRC) in the same manner as younger patients remains a challenging issue. The purpose of this study was to analyse postoperative complications and long-term survival in a consecutive cohort of octogenarians who were surgically treated for CRC.MethodsOctogenarians with primary CRC suitable for curative surgery between January 2008 and December 2011 were included. Data about comorbidities, tumour stage, and complications were retrospectively collected from patient files. Data about survival were retrieved with use of the Dutch database for persons and addresses. To identify factors associated with severe postoperative complications and postoperative survival, logistic regression analyses, and Cox regression analyses were performed. Odds ratios and hazard ratios (HR) with 95% confidence intervals (CI) were estimated.ResultsIn a series of 108 octogenarians, median age was 83years (range 80-94years). Median follow-up was 47 (range 1-107) months. Major postoperative complications occurred in 25% of the patients. No risk factors for development of severe postoperative complications could be identified. The 30-day mortality was 7%; 1- and 5-year mortality was 19% and 56%, respectively. Overall median survival was 48months: 66months in patients without complications versus 13months in patients with postoperative complications. Postoperative complications were most predictive of decreased survival (HR 3.16; 95% CI 1.79-5.59), even including tumour characteristics, comorbidity, and emergency surgery.ConclusionsLong-term survival in octogenarians deemed fit for surgery is reasonably good. Prevention of major postoperative complications could further improve clinical outcome.</p

    Optical absorption spectra of metal oxides from time-dependent density functional theory and many-body perturbation theory based on optimally-tuned hybrid functiona

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    Using both time-dependent density functional theory (TDDFT) and the “single-shot” GW plus Bethe-Salpeter equation (GW-BSE) approach, we compute optical band gaps and optical absorption spectra from first principles for eight common binary and ternary closed-shell metal oxides (MgO, Al2O3, CaO, TiO2, Cu2O, ZnO, BaSnO3, and BiVO4), based on the nonempirical Wannier-localization-based, optimally tuned, screened range-separated hybrid functional. Overall, we find excellent agreement between our TDDFT and GW-BSE results and experiment, with a mean absolute error smaller than 0.4 eV, including for Cu2O and ZnO that are traditionally considered to be challenging for both methods

    Calcium\u27s Role as Nuanced Modulator of Cellular Physiology in the Brain

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    Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can alter neuronal communication and synaptic strength in positive ways, without necessarily killing neurons. Here, we focus on the evidence that calcium has a subtle and distinctive role in shaping and controlling synaptic events that underpin neuronal communication and that these subtle changes in aging or AD may contribute to cognitive decline. We emphasize that calcium imaging in dendritic components is ultimately necessary to directly test for the presence of age- or disease-associated alterations during periods of synaptic activation

    A simple and robust method for connecting small-molecule drugs using gene-expression signatures

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    Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties. The Connectivity Map was a novel concept and innovative tool first introduced by Lamb et al to connect small molecules, genes, and diseases using genomic signatures [Lamb et al (2006), Science 313, 1929-1935]. However, the Connectivity Map had some limitations, particularly there was no effective safeguard against false connections if the observed connections were considered on an individual-by-individual basis. Further when several connections to the same small-molecule compound were viewed as a set, the implicit null hypothesis tested was not the most relevant one for the discovery of real connections. Here we propose a simple and robust method for constructing the reference gene-expression profiles and a new connection scoring scheme, which importantly allows the valuation of statistical significance of all the connections observed. We tested the new method with the two example gene-signatures (HDAC inhibitors and Estrogens) used by Lamb et al and also a new gene signature of immunosuppressive drugs. Our testing with this new method shows that it achieves a higher level of specificity and sensitivity than the original method. For example, our method successfully identified raloxifene and tamoxifen as having significant anti-estrogen effects, while Lamb et al's Connectivity Map failed to identify these. With these properties our new method has potential use in drug development for the recognition of pharmacological and toxicological properties in new drug candidates.Comment: 8 pages, 2 figures, and 2 tables; supplementary data supplied as a ZIP fil

    Adherence to Statin Therapy and Attainment of LDL Cholesterol Targets in an Outpatient Population of Type 2 Diabetes Patients:Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT)

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    Objective: To assess adherence to statin therapy and its association with sociodemographic data, medical characteristics, LDLc levels, and LDLc target attainment in real-world T2D patients treated in secondary care.Research Design and Methods: Cross-sectional analyses were performed on baseline data of 393 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT). The medication possession ratio (MPR), calculated with pharmacy dispensing data, was used to determine adherence to statins for an intended period of 24 months. Statins were included in the analyses if they were used for at least six consecutive months with at least three dispenses. Adherence was defined as an MPR >= 80%. Associations with adherence were assessed using descriptive statistics and binary logistic regression.Results: Overall, 80% of the patients had a statin prescription and of those, 89% were adherent. The proportion of patients who reached LDLc targets o

    Effects of Long-Term Pioglitazone Treatment on Peripheral and Central Markers of Aging

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    BACKGROUND: Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer\u27s disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD\u27s actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions. METHODS AND FINDINGS: We used the F344 rat model of aging, and monitored behavioral, electrophysiological, and molecular variables to assess the effects of pioglitazone (PIO-Actos® a TZD) on several peripheral (blood and liver) and central (hippocampal) biomarkers of aging. Starting at 3 months or 17 months of age, male rats were treated for 4-5 months with either a control or a PIO-containing diet (final dose approximately 2.3 mg/kg body weight/day). A significant reduction in the Ca2+-dependent afterhyperpolarization was seen in the aged animals, with no significant change in long-term potentiation maintenance or learning and memory performance. Blood insulin levels were unchanged with age, but significantly reduced by PIO. Finally, a combination of microarray analyses on hippocampal tissue and serum-based multiplex cytokine assays revealed that age-dependent inflammatory increases were not reversed by PIO. CONCLUSIONS: While current research efforts continue to identify the underlying processes responsible for the progressive decline in cognitive function seen during normal aging, available medical treatments are still very limited. Because TZDs have been shown to have benefits in age-related conditions such as T2DM and AD, our study was aimed at elucidating PIO\u27s potentially beneficial actions in normal aging. Using a clinically-relevant dose and delivery method, long-term PIO treatment was able to blunt several indices of aging but apparently affected neither age-related cognitive decline nor peripheral/central age-related increases in inflammatory signaling

    Low Physical Activity in Patients with Complicated Type 2 Diabetes Mellitus Is Associated with Low Muscle Mass and Low Protein Intake

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    Objective: In order to promote physical activity (PA) in patients with complicated type 2 diabetes, a better understanding of daily movement is required. We (1) objectively assessed PA in patients with type 2 diabetes, and (2) studied the association between muscle mass, dietary protein intake, and PA. Methods: We performed cross-sectional analyses in all patients included in the Diabetes and Lifestyle Cohort Twente (DIALECT) between November 2016 and November 2018. Patients were divided into four groups: = 10,000 steps/day. We studied the association between muscle mass (24 h urinary creatinine excretion rate, CER) and protein intake (by Maroni formula), and the main outcome variable PA (steps/day, Fitbit Flex device) using multivariate linear regression analyses. Results: In the 217 included patients, the median steps/day were 6118 (4115-8638). Of these patients, 48 patients (22%) took 7000-9999 steps/day, 37 patients (17%) took >= 10,000 steps/day, and 78 patients (36%) took = 10,000 steps/day, a higher body mass index (BMI) (33 +/- 6 vs. 30 +/- 5 kg/m(2), p = 0.009), lower CER (11.7 +/- 4.8 vs. 14.8 +/- 3.8 mmol/24 h, p = 0.001), and lower protein intake (0.84 +/- 0.29 vs. 1.08 +/- 0.22 g/kg/day, p < 0.001). Both creatinine excretion (beta = 0.26, p < 0.001) and dietary protein intake (beta = 0.31, p < 0.001) were strongly associated with PA, which remained unchanged after adjustment for potential confounders. Conclusions: Prevalent insufficient protein intake and low muscle mass co-exist in obese patients with low physical activity. Dedicated intervention studies are needed to study the role of sufficient protein intake and physical activity in increasing or maintaining muscle mass in patients with type 2 diabetes
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