Prevention of Falls in Adults Older than 60 Years through Therapeutic Riding: A Critically Appraised Topic

This critically appraised topic paper will address the focus question relating to the intervention of therapeutic riding. A critically appraised topic (CAT) is an overview of scientific literature about an intervention or practical issue and how it relates to practice (Barends et al., 2017). The use of the Ecological Human Performance (EHP) model is to guide this CAT research with a theoretical basis. EHP was chosen for its emphasis on the person, environment, and tasks. The person is described in EHP as including their experiences, sensorimotor, cognition, and psychosocial abilities (Dunn et al., 1994). The use of EHP provides a holistic and comprehensive approach to understand the context and person relating the intervention of therapeutic riding

The Challenges of Detecting Circulating Tumor Cells in Sarcoma

Sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin, many of which have a propensity to develop distant metastases. Cancer cells that have escaped from the primary tumor are able to invade into surrounding tissues, to intravasate into the bloodstream to become circulating tumor cells (CTCs), and are responsible for the generation of distant metastases. Due to the rarity of these tumors and the absence of specific markers expressed by sarcoma tumor cells, the characterization of sarcoma CTCs has to date been relatively limited. Current techniques for isolating sarcoma CTCs are based on size criteria, the identification of circulating cells that express either common mesenchymal markers, sarcoma-specific markers, such as CD99, CD81, or PAX3, and chromosomal translocations found in certain sarcoma subtypes, such as EWS-FLI1 in Ewing’s sarcoma, detection of osteoblast-related genes, or measurement of the activity of specific metabolic enzymes. Further studies are needed to improve the isolation and characterization of sarcoma CTCs, to demonstrate their clinical significance as predictive and/or prognostic biomarkers, and to utilize CTCs as a tool for investigating the metastatic process in sarcoma and to identify novel therapeutic targets. The present review provides a short overview of the most recent literature on CTCs in sarcoma

Ethical ecosurveillance: Mitigating the potential impacts on humans of widespread environmental monitoring

Ecosurveillance has proliferated in recent years, generating vast amounts of data on the natural environment. Ecosurveillance also has significant potential impacts on humans; therefore, researchers and policymakers need new conceptual tools to anticipate and mitigate any negative effects. Surveillance studies is an interdisciplinary field in the social sciences, providing a number of insights and practical lessons for predicting and managing the complex impacts (positive and negative, intended and unintended) of surveillance tools and practices. We draw on surveillance studies literature to propose two tools to guide designers and practitioners of ecosurveillance—a ‘red flag checklist’ to anticipate potential problems, and a ‘considerations guide’ to inform design decisions across a wide range of ecosurveillance systems. These tools will help ensure that the coming era of ecosurveillance is guided by responsible and ethical practices towards wildlife and humans alike, while also realizing the potential of these technologies for improving environmental outcomes.publishedVersio

Literacy in Scotland. Country Report. Children and adolescents

European Literacy Policy Network (ELINET

Inositol 1,4,5-trisphosphate receptor 1, a widespread Ca2+ channel, is a novel substrate of polo-like kinase 1 in eggs

AbstractTo initiate embryo development, the sperm induces in the egg release of intracellular calcium ([Ca2+]i). During oocyte maturation, the inositol 1,4,5-trisphosphate receptor (IP3R1), the channel implicated, undergoes modifications that enhance its function. We found that IP3R1 becomes phosphorylated during maturation at an MPM-2 epitope and that this persists until the fertilization-associated [Ca2+]i responses cease. We also reported that maturation without ERK activity diminishes IP3R1 MPM-2 reactivity and [Ca2+]i responses. Here, we show that IP3R1 is a novel target for Polo-like kinase1 (Plk1), a conserved M-phase kinase, which phosphorylates it at an MPM-2 epitope. Plk1 and IP3R1 interact in an M-phase preferential manner, and they exhibit close co-localization in the spindle/spindle poles area. This co-localization is reduced in the absence of ERK activity, as the ERK pathway regulates spindle organization and IP3R1 cortical re-distribution. We propose that IP3R1 phosphorylation by Plk1, and possibly by other M-phase kinases, underlies the delivery of spatially and temporally regulated [Ca2+]i signals during meiosis/mitosis and cytokinesis

Mitochondria are physiologically maintained at close to 50 degrees C

In endothermic species, heat released as a product of metabolism ensures stable internal temperature throughout the organism, despite varying environmental conditions. Mitochondria are major actors in this thermogenic process. Part of the energy released by the oxidation of respiratory substrates drives ATP synthesis and metabolite transport, but a substantial proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 degrees C, mitochondria were more than 10 degrees C warmer when the respiratory chain (RC) was fully functional, both in human embryonic kidney (HEK) 293 cells and primary skin fibroblasts. This differential was abolished in cells depleted of mitochondrial DNA or treated with respiratory inhibitors but preserved or enhanced by expressing thermogenic enzymes, such as the alternative oxidase or the uncoupling protein 1. The activity of various RC enzymes was maximal at or slightly above 50 degrees C. In view of their potential consequences, these observations need to be further validated and explored by independent methods. Our study prompts a critical re-examination of the literature on mitochondria.Peer reviewe

Pendrin abundance, subcellular distribution, and function are unaffected by either αENaC gene ablation or by increasing ENaC channel activity

The intercalated cell Cl$^{-}$/HCO$_{3}$$^{-}$ exchanger, pendrin, modulates ENaC subunit abundance and function. Whether ENaC modulates pendrin abundance and function is however unknown. Because αENaC mRNA has been detected in pendrin-positive intercalated cells, we hypothesized that ENaC, or more specifically the αENaC subunit, modulates intercalated cell function. The purpose of this study was therefore to determine if αENaC is expressed at the protein level in pendrin-positive intercalated cells and to determine if αENaC gene ablation or constitutively upregulating ENaC activity changes pendrin abundance, subcellular distribution, and/or function. We observed diffuse, cytoplasmic αENaC label in pendrin-positive intercalated cells from both mice and rats, with much lower label intensity in pendrin-negative, type A intercalated cells. However, while αENaC gene ablation within principal and intercalated cells of the CCD reduced Cl$^{-}$ absorption, it did not change pendrin abundance or subcellular distribution in aldosterone-treated mice. Further experiments used a mouse model of Liddle's syndrome to explore the effect of increasing ENaC channel activity on pendrin abundance and function. The Liddle's variant did not increase either total or apical plasma membrane pendrin abundance in aldosterone-treated or in NaCl-restricted mice. Similarly, while the Liddle's mutation increased total Cl$^{-}$ absorption in CCDs from aldosterone-treated mice, it did not significantly affect the change in Cl$^{-}$ absorption seen with pendrin gene ablation. We conclude that in rats and mice, αENaC localizes to pendrin-positive ICs where its physiological role remains to be determined. While pendrin modulates ENaC abundance, subcellular distribution, and function, ENaC does not have a similar effect on pendrin

Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients

Fabry disease (FD) results from mutations in the gene ( GLA ) that encodes the lysosomal enzyme α-galactosidase A (α-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb 3 ). Migalastat hydrochloride (GR181413A) is a pharmacological chaperone that selectively binds, stabilizes, and increases cellular levels of α-Gal A. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. A liquid chromatography-tandem mass spectrometry method was developed to measure lyso-Gb 3 in mouse tissues and human plasma. Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb 3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb 3 levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb 3 in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb 3 is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD

Limited heat tolerance in an Arctic passerine: Thermoregulatory implications for cold-specialized birds in a rapidly warming world

Arctic animals inhabit some of the coldest environments on the planet and have evolved physiological mechanisms for minimizing heat loss under extreme cold. However, the Arctic is warming faster than the global average and how well Arctic animals tolerate even moderately high air temperatures (Ta) is unknown. Using flow-through respirometry, we investigated the heat tolerance and evaporative cooling capacity of snow buntings (Plectrophenax nivalis; ≈31 g, N = 42), a cold specialist, Arctic songbird. We exposed buntings to increasing Ta and measured body temperature (Tb), resting metabolic rate (RMR), rates of evaporative water loss (EWL), and evaporative cooling efficiency (the ratio of evaporative heat loss to metabolic heat production). Buntings had an average (±SD) Tb of 41.3 ± 0.2°C at thermoneutral Ta and increased Tb to a maximum of 43.5 ± 0.3°C. Buntings started panting at Ta of 33.2 ± 1.7°C, with rapid increases in EWL starting at Ta = 34.6°C, meaning they experienced heat stress when air temperatures were well below their body temperature. Maximum rates of EWL were only 2.9× baseline rates at thermoneutral Ta, a markedly lower increase than seen in more heat-tolerant arid-zone species (e.g., ≥4.7× baseline rates). Heat-stressed buntings also had low evaporative cooling efficiencies, with 95% of individuals unable to evaporatively dissipate an amount of heat equivalent to their own metabolic heat production. Our results suggest that buntings’ well-developed cold tolerance may come at the cost of reduced heat tolerance. As the Arctic warms, and this and other species experience increased periods of heat stress, a limited capacity for evaporative cooling may force birds to increasingly rely on behavioral thermoregulation, such as minimizing activity, at the expense of diminished performance or reproductive investment