Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men

In healthy subjects, we recently demonstrated that during acute administration of GLP‐1, cardiac output increased significantly, whereas renal blood flow remained constant. We therefore hypothesize that GLP‐1 induces vasodilation in other organs, for example, adipose tissue, skeletal muscle, and/or splanchnic tissues. Nine healthy men were examined twice in random order during a 2‐hour infusion of either GLP‐1 (1.5 pmol kg(−1) min(−1)) or saline. Cardiac output was continuously estimated noninvasively concomitantly with measurement of intra‐arterial blood pressure. Subcutaneous, abdominal adipose tissue blood flow (ATBF) was measured by the (133)Xenon clearance technique. Leg and splanchnic blood flow were measured by Fick's Principle, using indocyanine green as indicator. In the GLP‐1 study, cardiac output increased significantly together with a significant increase in arterial pulse pressure and heart rate compared with the saline study. Subcutaneous, abdominal ATBF and leg blood flow increased significantly during the GLP‐1 infusion compared with saline, whereas splanchnic blood flow response did not differ between the studies. We conclude that in healthy subjects, GLP‐1 increases cardiac output acutely due to a GLP‐1‐induced vasodilation in adipose tissue and skeletal muscle together with an increase in cardiac work

Laypersons' understanding of relative risk reductions: Randomised cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Despite increasing recognition of the importance of involving patients in decisions on preventive healthcare interventions, little is known about how well patients understand and utilise information provided on the relative benefits from these interventions. The aim of this study was to explore whether lay people can discriminate between preventive interventions when effectiveness is presented in terms of relative risk reduction (RRR), and whether such discrimination is influenced by presentation of baseline risk.</p> <p>Methods</p> <p>The study was a randomised cross-sectional interview survey of a representative sample (n = 1,519) of lay people with mean age 59 (range 40–98) years in Denmark. In addition to demographic information, respondents were asked to consider a hypothetical drug treatment to prevent heart attack. Its effectiveness was randomly presented as RRR of 10, 20, 30, 40, 50 or 60 percent, and half of the respondents were presented with quantitative information on the baseline risk of heart attack. The respondents had also been asked whether they were diagnosed with hypercholesterolemia or had experienced a heart attack.</p> <p>Results</p> <p>In total, 873 (58%) of the respondents consented to the hypothetical treatment. While 49% accepted the treatment when RRR = 10%, the acceptance rate was 58–60% for RRR>10. There was no significant difference in acceptance rates across respondents irrespective of whether they had been presented with quantitative information on baseline risk or not.</p> <p>Conclusion</p> <p>In this study, lay people's decisions about therapy were only slightly influenced by the magnitude of the effect when it was presented in terms of RRR. The results may indicate that lay people have difficulties in discriminating between levels of effectiveness when they are presented in terms of RRR.</p

Altered Ratio of D1 and D2 Dopamine Receptors in Mouse Striatum Is Associated with Behavioral Sensitization to Cocaine

BACKGROUND: Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R) availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. METHODS AND FINDINGS: ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT) and G protein coupled receptor associated sorting protein-1 (GASP-1) knock out (KO) mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. CONCLUSIONS: Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization

Vitamin D Status and Bone and Connective Tissue Turnover in Brown Bears (Ursus arctos) during Hibernation and the Active State

BACKGROUND: Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. AIM: To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D₂ and D₃), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)₂D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. MATERIAL AND METHODS: We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. RESULTS: Serum 25-hydroxy-cholecalciferol (25OHD₃) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p-2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD₂) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)₂D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. CONCLUSIONS: Dramatic changes were documented in the vitamin D₃/D₂ ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease

Deliverable 1.1 review document on the management of marine areas with particular regard on concepts, objectives, frameworks and tools to implement, monitor, and evaluate spatially managed areas

The main objectives if this document were to review the existing information on spatial management of marine areas, identifying the relevant policy objectives, to identify parameters linked to the success or failure of the various Spatially Managed marine Areas (SMAs) regimes, to report on methods and tools used in monitoring and evaluation of the state of SMAs, and to identify gaps and weaknesses in the existing frameworks in relation to the implementation, monitoring, evaluation and management of SMAs. The document is naturally divided in two sections: Section 1 reviews the concepts, objectives, drivers, policy and management framework, and extraneous factors related to the design, implementation and evaluation of SMAs; Section 2 reviews the tools and methods to monitor and evaluate seabed habitats and marine populations.peer-reviewe

Deliverable 3.6 zoning plan of case studies : evaluation of spatial management options for the case studies

Within MESMA, nine case studies (CS) represent discrete marine European spatial entities, at different spatial scales, where a spatial marine management framework is in place, under development or considered. These CS (described in more details below) are chosen in such a way (MESMA D. 3.1 ) that they encompass the complexity of accommodating the various user functions of the marine landscape in various regions of the European marine waters. While human activities at sea are competing for space, there is also growing awareness of the possible negative effects of these human activities on the marine ecosystem. As such, system specific management options are required, satisfying current and future sectoral needs, while safeguarding the marine ecosystem from further detoriation. This integrated management approach is embedded in the concept of ecosystem based management (EBM). The goal of marine EBM is to maintain marine ecosystems in a healthy, productive and resilient condition, making it possible that they sustain human use and provide the goods and services required by society (McLeod et al. 2005). Therefore EBM is an environmental mangagement approach that recognises the interactions within a marine ecosystem, including humans. Hence, EBM does not consider single issues, species or ecosystems good and services in isolation. Operationalisation of EBM can be done through place-based or spatial management approaches (Lackey 1998), such as marine spatial planning (MSP). MSP is a public process of analysing and allocating the spatial and temporal distribution of human activities aiming at achieving ecological, economic and social objectives. These objectives are usually formulated through political processes (Douvere et al. 2007, Douvere 2008). Within MESMA, a spatially managed area (SMA) is then defined as “a geographical area within which marine spatial planning initiatives exist in the real world”. Marine spatial planning initiatives refer to existing management measures actually in place within a defined area, or in any stage of a process of putting management in place, e.g. plans or recommendations for a particular area. Management can include management for marine protection (e.g. in MPAs), or management for sectoral objectives (e.g. building a wind farm to meet renewable energy objectives). Within MESMA, SMAs can have different spatial scales. A SMA can be a small, specific area that is managed/planned to be managed for one specific purpose, but it can also be a larger area within which lots of plans or ‘usage zones’ exist. This definition is different from the definition mentioned in the DoW (page 60). The original definition was adapted during a CS leader workshop (2-4 May 2012 in Gent, Belgium) and formally accepted by the MESMA ExB during the ExB meeting in Cork (29-30 May 2012). MSP should result in a marine spatial management plan that will produce the desired future trough explicit decisions about the location and timing of human activities. Ehler & Douvere (2009) consider this spatial management as a beginning toward the the implementation of desired goals and objectives. They describe the spatial management plan as a comprehensive, strategic document that provides the framework and direction for marine spatial management decisions. The plan should identify when, where and how goals and objectives will be met. Zoning (the development of zoning plans) is often an important management measure to implement spatial management plans. The purpose of a zoning plan (Ehler & Douvere 2009) is: To provide protection for biologically and ecologically important habitats, ecosystems, and ecological processes. To seperate conflicting human activities, or to combine compatible activities. To protect the natural values of the marine management area (in MESMA terminology: the SMA) while allowing reasonable human uses of the area. To allocate areas for reasonable human uses while minimising the effects of these human uses on each other, and nature. To preserve some areas of the SMA in their natural state undisturbed by humans except for scientific and educational purposes.peer-reviewe

Roadmap for Optical Tweezers 2023

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nanoparticle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration