Undergraduate medical textbooks do not provide adequate information on intravenous fluid therapy: a systematic survey and suggestions for improvement

<b>Background</b><p></p> Inappropriate prescribing of intravenous (IV) fluid, particularly 0.9% sodium chloride, causes post-operative complications. Fluid prescription is often left to junior medical staff and is frequently poorly managed. One reason for poor intravenous fluid prescribing practices could be inadequate coverage of this topic in the textbooks that are used.<p></p> <b>Methods</b><p></p> We formulated a comprehensive set of topics, related to important common clinical situations involving IV fluid therapy, (routine fluid replacement, fluid loss, fluids overload) to assess the adequacy of textbooks in common use. We assessed 29 medical textbooks widely available to students in the UK, scoring the presence of information provided by each book on each of the topics. The scores indicated how fully the topics were considered: not at all, partly, and adequately. No attempt was made to judge the quality of the information, because there is no consensus on these topics.<p></p> <b>Results</b><p></p> The maximum score that a book could achieve was 52. Three of the topics we chose were not considered by any of the books. Discounting these topics as “too esoteric”, the maximum possible score became 46. One textbook gained a score of 45, but the general score was poor (median 11, quartiles 4, 21). In particular, coverage of routine postoperative management was inadequate.<p></p> <b>Conclusions</b><p></p> Textbooks for undergraduates cover the topic of intravenous therapy badly, which may partly explain the poor knowledge and performance of junior doctors in this important field. Systematic revision of current textbooks might improve knowledge and practice by junior doctors. Careful definition of the remit and content of textbooks should be applied more widely to ensure quality and “fitness for purpose”, and avoid omission of vital knowledge

Cooperation between Wnt and Notch signalling in human breast cancer

The Wnt and Notch signalling pathways play major roles in mammary gland development and tumourigenesis. During development, these pathways have opposing effects. However, in a recent paper Ayyanan and coworkers show that expression of Wnt1 is sufficient to transform primary human mammary epithelial cells, and that this is in part due to activation of the Notch pathway. This indicates that during tumourigenesis the two pathways cooperate. Here we ask why activation of Wnt signalling alone is sufficient to cause transformation; whether there is evidence for inhibitory crosstalk between the pathways during tumourigenesis; and whether cooperation between these pathways occurs in other forms of cancer

Metformin mitigates the impaired development of skeletal muscle in the offspring of obese mice

Background: Maternal obesity is linked with offspring obesity and type 2 diabetes. Skeletal muscle (SM) insulin resistance is central to the development of diabetes. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is inhibited in SM of fetuses born to obese mothers

Acute-Phase-HDL Remodeling by Heparan Sulfate Generates a Novel Lipoprotein with Exceptional Cholesterol Efflux Activity from Macrophages

During episodes of acute-inflammation high-density lipoproteins (HDL), the carrier of so-called good cholesterol, experiences a major change in apolipoprotein composition and becomes acute-phase HDL (AP-HDL). This altered, but physiologically important, HDL has an increased binding affinity for macrophages that is dependent on cell surface heparan sulfate (HS). While exploring the properties of AP-HDL∶HS interactions we discovered that HS caused significant remodeling of AP-HDL. The physical nature of this change in structure and its potential importance for cholesterol efflux from cholesterol-loaded macrophages was therefore investigated. In the presence of heparin, or HS, AP-HDL solutions at pH 5.2 became turbid within minutes. Analysis by centrifugation and gel electrophoresis indicated that AP-HDL was remodeled generating novel lipid poor particles composed only of apolipoprotein AI, which we designate β2. This remodeling is dependent on pH, glycosaminoglycan type, is promoted by Ca2+ and is independent of protease or lipase activity. Compared to HDL and AP-HDL, remodeled AP-HDL (S-HDL-SAA), containing β2 particles, demonstrated a 3-fold greater cholesterol efflux activity from cholesterol-loaded macrophage. Because the identified conditions causing this change in AP-HDL structure and function can exist physiologically at the surface of the macrophage, or in its endosomes, we postulate that AP-HDL contains latent functionalities that become apparent and active when it associates with macrophage cell surface/endosomal HS. In this way initial steps in the reverse cholesterol transport pathway are focused at sites of injury to mobilize cholesterol from macrophages that are actively participating in the phagocytosis of damaged membranes rich in cholesterol. The mechanism may also be of relevance to aspects of atherogenesis

Agri-Environmental Policy Measures in Israel: The Potential of Using Market-Oriented Instruments

This paper examines the possibilities of developing agri-environmental policy measures in Israel, focusing on market-oriented instruments. A conceptual framework for developing agri-environmental policy measures is presented, first in very broad lines (mandatory regulations, economic instruments and advisory measures) and subsequently focusing on economic instruments, and specifically, on market-oriented ones. Two criteria of choice between the measures are suggested: their contribution to improving the effectiveness of the policy; and the feasibility of their implementation. This is the framework used for analyzing agri-environmental measures in Israel. Israel currently implements a mix of mandatory regulations, economic instruments and advisory measures to promote the agri-environment. The use of additional economic instruments may improve the effectiveness of the policy. When comparing the effectiveness of various economic measures, we found that the feasibility of implementation of market-oriented instruments is greater, due to the Israeli public’s preference for strengthening market orientation in the agricultural sector. Four market-oriented instruments were practiced in a pilot project conducted in an Israeli rural area. We found that in this case study, the institutional feasibility and acceptance by stakeholders were the major parameters influencing the implementation of the market-oriented instruments, whereas the instruments’ contribution to enhancing the ecological or economic effectiveness were hardly considered by the stakeholders as arguments in favor of their use

Optimizing the two-step floating catchment area method for measuring spatial accessibility to medical clinics in Montreal

<p>Abstract</p> <p>Background</p> <p>Reducing spatial access disparities to healthcare services is a growing priority for healthcare planners especially among developed countries with aging populations. There is thus a pressing need to determine which populations do not enjoy access to healthcare, yet efforts to quantify such disparities in spatial accessibility have been hampered by a lack of satisfactory measurements and methods. This study compares an optimised and the conventional version of the two-step floating catchment area (2SFCA) method to assess spatial accessibility to medical clinics in Montreal.</p> <p>Methods</p> <p>We first computed catchments around existing medical clinics of Montreal Island based on the shortest network distance. Population nested in dissemination areas were used to determine potential users of a given medical clinic. To optimize the method, medical clinics (supply) were weighted by the number of physicians working in each clinic, while the previous year's medical clinic users were computed by ten years age group was used as weighting coefficient for potential users of each medical clinic (demand).</p> <p>Results</p> <p>The spatial accessibility score (SA) increased considerably with the optimisation method. Within a distance of 1 Km, for instance, the maximum clinic accessible for 1,000 persons is 2.4 when the conventional method is used, compared with 27.7 for the optimized method. The t-test indicates a significant difference between the conventional and the optimized 2SFCA methods. Also, results of the differences between the two methods reveal a clustering of residuals when distance increases. In other words, a low threshold would be associated with a lack of precision.</p> <p>Conclusion</p> <p>Results of this study suggest that a greater effort must be made ameliorate spatial accessibility to medical clinics in Montreal. To ensure that health resources are allocated in the interest of the population, health planners and the government should consider a strategy in the sitting of future clinics which would provide spatial access to the greatest number of people.</p

Mild Electrical Stimulation with Heat Shock Ameliorates Insulin Resistance via Enhanced Insulin Signaling

Low-intensity electrical current (or mild electrical stimulation; MES) influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72) alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS) to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration) together with HS at 42°C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS) and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V)+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor β subunit (IRβ) and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12–15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway

Ablations of Ghrelin and Ghrelin Receptor Exhibit Differential Metabolic Phenotypes and Thermogenic Capacity during Aging

mice are adaptive. mice.Our data therefore suggest that GHS-R ablation activates adaptive thermogenic function(s) in BAT and increases EE, thereby enabling the retention of a lean phenotype. This is the first direct evidence that the ghrelin signaling pathway regulates fat-burning BAT to affect energy balance during aging. This regulation is likely mediated through an as-yet-unidentified new ligand of GHS-R

Sensory Input Pathways and Mechanisms in Swallowing: A Review

Over the past 20 years, research on the physiology of swallowing has confirmed that the oropharyngeal swallowing process can be modulated, both volitionally and in response to different sensory stimuli. In this review we identify what is known regarding the sensory pathways and mechanisms that are now thought to influence swallowing motor control and evoke its response. By synthesizing the current state of research evidence and knowledge, we identify continuing gaps in our knowledge of these mechanisms and pose questions for future research

The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle

Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the “furnace” that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430–435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels