Aging and urinary control: Alterations in the brain-bladder axis.

Age-associated alterations in bladder control affect millions of older adults, with a heavy burden added to families both economically and in quality of life. Therapeutic options are limited with poor efficacy in older adults, lending to a growing need to address the gaps in our current understanding of urinary tract aging. This review summarizes the current knowledge of age-associated alterations in the structure and function of the brain-bladder axis and identifies important gaps in the field that have yet to be addressed. Urinary aging is associated with decreased tissue responsiveness, decreased control over the voiding reflex, signaling dysfunction along the brain-bladder axis, and structural changes within the bladder wall. Studies are needed to improve our understanding of how age affects the brain-bladder axis and identify genetic targets that correlate with functional outcomes

Madrid: Literary Fiction and the Imaginary Urban Destination

This study selects novels from French and Spanish language traditions, which may not be available to English-speakers, in order to determine if specific aspects throw light on our understanding of Madrid as a destination. Marc Lambron's L'Impromptu de Madrid and Antonio Munoz Molina’s Mysteries of Madrid are taken as proof of the influence the narrative can exert on social daily life and consumption. Narrative foregrounds the fictions which are at stake in imagining the city as destination and also provides a vehicle for presenting the much broader social forces that converge in the author at the time of imagining and writing

Challenging the negative images of Haiti at a pre-visit stage using visual online learning materials

Post-conflict destinations can struggle to attract visitors because of their negative image. Research addressing this remains limited. The same can be said about the education of tourists. This research paper contributes to the literature in both areas as it examines the proposition that the education of tourists at a pre-visit stage using online, game-based material could be effective in challenging the negative perception of these destinations. From a destination management point of view, this paper offers an alternative to existing promotional material as there is little evidence at the moment that existing strategies are effective. From a conceptual point of view, this paper contributes to the very limited academic research in Gamification by adding the fact that Gamification can be a very efficient tryvertising tool if using subtle and implicit marketing elements

β3-Adrenoceptor-mediated relaxation of rat and human urinary bladder:roles of BKCa channels and Rho kinase

Previous studies suggest that the large-conductance Ca2+-activated K+ (BKCa) channel and Rho-kinase play major roles in the control of urinary bladder tone. Here, we investigated their involvement in beta-adrenoceptor (AR)-mediated relaxation of rat and human bladder. Concentration-response curves of isoprenaline and mirabegron-induced bladder relaxation were generated against passive tension and KCl- and carbachol-induced tone, in the absence or presence of the BKCa channel inhibitor iberiotoxin (100 nM) or the Rho-kinase inhibitor Y27,632 (1 mu M). Myosin light chain (MLC) phosphorylation was studied by Western blot. In rat, iberiotoxin only slightly altered isoprenaline- and mirabegron-induced relaxation against KCl-induced tone but attenuated relaxation by both agonists against carbachol-induced tone. Y27,632 enhanced isoprenaline- or mirabegron-induced relaxation only against carbachol-induced tone. In humans, iberiotoxin slightly enhanced relaxation by both agonists against carbachol-induced pre-contraction. Y27,632 did not change isoprenaline-induced relaxation but enhanced that by mirabegron. Under passive tension, MLC phosphorylation was markedly reduced by both beta-AR agonists, an effect insensitive to Y27,632. In the presence of carbachol, both beta-AR agonists increased MLC phosphorylation, an effect reduced by Y27,632 only in the presence of 1 mu M carbachol. These results indicate that the extent of BKCa channel and Rho-kinase involvement in relaxation induced by beta-AR agonists depends on pre contractile stimulus and species

Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart.

Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, whereas processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process

A multi-tissue full lifespan epigenetic clock for mice.

Human DNA-methylation data have been used to develop highly accurate biomarkers of aging ( epigenetic clocks ). Recent studies demonstrate that similar epigenetic clocks for mice (Mus Musculus) can be slowed by gold standard anti-aging interventions such as calorie restriction and growth hormone receptor knock-outs. Using DNA methylation data from previous publications with data collected in house for a total 1189 samples spanning 193,651 CpG sites, we developed 4 novel epigenetic clocks by choosing different regression models (elastic net- versus ridge regression) and by considering different sets of CpGs (all CpGs vs highly conserved CpGs). We demonstrate that accurate age estimators can be built on the basis of highly conserved CpGs. However, the most accurate clock results from applying elastic net regression to all CpGs. While the anti-aging effect of calorie restriction could be detected with all types of epigenetic clocks, only ridge regression based clocks replicated the finding of slow epigenetic aging effects in dwarf mice. Overall, this study demonstrates that there are trade-offs when it comes to epigenetic clocks in mice. Highly accurate clocks might not be optimal for detecting the beneficial effects of anti-aging interventions

Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals

The aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient days of care during the nine-year study period. The rate of candidemia doubled in the study period, reaching an incidence of 0.71 episodes per 10,000 patient days in 1995. The general increase in candidemia was paralleled by an increase in non-Candida albicans bloodstream infections, mainly due to Candida glabrata. However, more than 60% of the infections were caused by Candida albicans. Fluconazole-resistant species such as Candida krusei did not emerge during the study period. The increasing rate of candidemia found in Dutch university hospitals is similar to the trend observed in the USA, but the rate is lower acid the increase is less pronounced.</p

Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals

The aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient days of care during the nine-year study period. The rate of candidemia doubled in the study period, reaching an incidence of 0.71 episodes per 10,000 patient days in 1995. The general increase in candidemia was paralleled by an increase in non-Candida albicans bloodstream infections, mainly due to Candida glabrata. However, more than 60% of the infections were caused by Candida albicans. Fluconazole-resistant species such as Candida krusei did not emerge during the study period. The increasing rate of candidemia found in Dutch university hospitals is similar to the trend observed in the USA, but the rate is lower acid the increase is less pronounced.</p

Cambios en el paisaje en un valle del oeste catamarqueño durante el Holoceno tardío. Integrando arqueología, palinología y geomorfología

The El Bolsón Valley (Belén, Catamarca Province) is located between two geographical and cultural areas of great interest for the region’s (Northwest Argentina - NOA) archaeology. Given its location – helmed by the Puna and the lower valleys – it constitutes an ideal place in which to study environmental changes at a local scale, elucidating its relationship with known paleoenvironmental sequences of the wider NOA region. Studies on fossilized pollen extracted from a Laguna Cotagua sedimentary sequence, identified changes in local vegetation dating to 5581 ± 40 years BP. Sedimentology studies of these sequences, as well as others from fluvial terraces containing archaeological material, show abrupt geomorphological changes in the valley from ca. 3,000 years BP, onwards. Geoarchaeological studies on these records, contributed data that allowed us to chronologically arrange sediment erosion and deposition events that impacted on the local Prehispanic population’s life-ways and settlement of the valley. The aim of this article is to integrate this data, with the available archaeological information, thereby contributing to the corpus of paleoenvironmental data for the NOA region.El Valle de El Bolsón (Belén, Catamarca) se ubica entre dos áreas geográficas y culturales de gran interés en la arqueología del NOA. Por su ubicación, entre la Puna y los valles bajos, se presenta como un lugar desde donde estudiar los cambios ambientales a nivel local y su relación a las secuencias paleoambientales conocidas en la región. Estudios de polen fósil contenido en la secuencia sedimentaria de Laguna Cotagua informan sobre los cambios en la vegetación a partir de los 5581 años cal AP. El estudio sedimentológico del mismo y de terrazas fluviales con materiales arqueológicos en estratigrafía evidencian abruptos cambios en la geomorfología del valle desde ca. 3000 años AP. El estudio geoarqueológico de los mismos aportó información para ordenar cronológicamente eventos de erosión y deposición de sedimentos que en alguna medida tuvieron impacto en las formas en que las poblaciones prehispánicas habitaron el valle. La finalidad de este trabajo es presentar la integración de estos datos a la información arqueológica disponible y aportar al corpus de datos paleoambientales del NOA

Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity

We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in C. elegans and similar to screens that preselected candidates based on longevity-correlated metrics (e.g., stress resistance). Of the 50 genes that affected lifespan, 46 were previously unreported. The five genes with the greatest impact on lifespan (>20% extension) encode the enzyme kynureninase (kynu-1), a neuronal leucine-rich repeat protein (iglr-1), a tetraspanin (tsp-3), a regulator of calcineurin (rcan-1), and a voltage-gated calcium channel subunit (unc-36). Knockdown of each gene extended healthspan without impairing reproduction. kynu-1(RNAi) alone delayed pathology in C. elegans models of Alzheimer's disease and Huntington's disease. Each gene displayed a distinct pattern of interaction with known aging pathways. In the context of published work, kynu-1, tsp-3, and rcan-1 are of particular interest for immediate follow-up. kynu-1 is an understudied member of the kynurenine metabolic pathway with a mechanistically distinct impact on lifespan. Our data suggest that tsp-3 is a novel modulator of hypoxic signaling and rcan-1 is a context-specific calcineurin regulator. Our results validate C. elegans as a comparative tool for prioritizing human candidate aging genes, confirm age-associated gene expression data as valuable source of novel longevity determinants, and prioritize select genes for mechanistic follow-up