Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study.

OBJECTIVE Vitamin D (D₃) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA(₁c)) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM. MATERIALS AND METHODS We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D₃ or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA(₁c) levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values. RESULTS After 6 months of D₃ supply, there was a significant intergroup difference in the change in HbA(₁c) levels (relative change [mean ± standard deviation] +2.9% ± 1.5% in the D₃ group vs +6.9% ± 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% ± 5.6% in the D₃ group and increased by 10% ± 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D₃ group from 200 ± 41 to 126 ± 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints. CONCLUSIONS D₃ improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA(₁c) positively compared with placebo in patients with T2DM.

Controversies in the use of hydroxyethyl starch solutions in small animal emergency and critical care

OBJECTIVES: To (1) review the development and medical applications of hydroxyethyl starch (HES) solutions with particular emphasis on its physiochemical properties; (2) critically appraise the available evidence in human and veterinary medicine, and (3) evaluate the potential risks and benefits associated with their use in critically ill small animals. DATA SOURCES: Human and veterinary original research articles, scientific reviews, and textbook sources from 1950 to the present. HUMAN DATA SYNTHESIS: HES solutions have been used extensively in people for over 30 years and ever since its introduction there has been a great deal of debate over its safety and efficacy. Recently, results of seminal trials and meta-analyses showing increased risks related to kidney dysfunction and mortality in septic and critically ill patients, have led to the restriction of HES use in these patient populations by European regulatory authorities. Although the initial ban on the use of HES in Europe has been eased, proof regarding the benefits and safety profile of HES in trauma and surgical patient populations has been requested by these same European regulatory authorities. VETERINARY DATA SYNTHESIS: The veterinary literature is limited mostly to experimental studies and clinical investigations with small populations of patients with short-term end points and there is insufficient evidence to generate recommendations. CONCLUSIONS: Currently, there are no consensus recommendations regarding the use of HES in veterinary medicine. Veterinarians and institutions affected by the HES restrictions have had to critically reassess the risks and benefits related to HES usage based on the available information and sometimes adapt their procedures and policies based on their reassessment. Meanwhile, large, prospective, randomized veterinary studies evaluating HES use are needed to achieve relevant levels of evidence to enable formulation of specific veterinary guidelines.

Iodine-129: Sample preparation, quality control and analyses of pre-nuclear materials and of natural waters from Lower Saxony, Germany

Sample preparation procedures for AMS measurements of 129I and 127I in environmental materials and some methodological aspects of quality assurance are discussed. Measurements from analyses of some pre-nuclear soil and thyroid gland samples and of a systematic investigation of natural waters in Lower Saxony, Germany, are described. Although the up-to-now lowest 129I/127I ratios in soils and thyroid glands were observed, they are still suspect to contamination since they are significantly higher than the pre-nuclear equilibrium ratio in the marine hydrosphere. A survey on all available 129I/127I isotopic ratios in precipitation shows a dramatic increase until the middle of the 1980s and a stabilization since 1987 at high isotopic ratios of about (3.6–8.3)×10−7. In surface waters, ratios of (57–380)×10−10 are measured while shallow ground waters show with ratios of (1.3–200)×10−10 significantly lower values with a much larger spread. The data for 129I in soils and in precipitation are used to estimate pre-nuclear and modern 129I deposition densities.

Balancing Control and Coaching in CSO Governance : A Paradox Perspective on Board Behavior

How can governance of civil society organizations be conceptualized more adequately by accounting for the dual and simultaneous requirements of controlling and coaching in board behavior? Empirically, we seem to agree that effective governance of a civil society organization is crucial to its sustained viability. Conceptually, however, we observe a lack of consensus on how to best conceptualize CSO governance. By critically juxtaposing two major theoretical lenses to conceptualize governance, namely agency and stewardship theory, we identify a number of challenges conceptualizing board-management relations that deserve our attention. While agency theory privileges controlling behavior, stewardship theory emphasizes the coaching behavior of boards. The purpose of this paper is to offer a concept of governance that is informed by a paradox perspective advancing a subtler, more adequate conceptualization of board governance that accounts for the often conflicting demands on CSO governance. Drawing on a longitudinal interpretive case study, we exemplify our propositions empirically. The paper concludes with discussing the implications of our argument for CSO governance research and practice.

Timely Reporting and Interactive Visualization of Animal Health and Slaughterhouse Surveillance Data in Switzerland

The reporting of outputs from health surveillance systems should be done in a near real-time and interactive manner in order to provide decision makers with powerful means to identify, assess, and manage health hazards as early and efficiently as possible. While this is currently rarely the case in veterinary public health surveillance, reporting tools do exist for the visual exploration and interactive interrogation of health data. In this work, we used tools freely available from the Google Maps and Charts library to develop a web application reporting health-related data derived from slaughterhouse surveillance and from a newly established web-based equine surveillance system in Switzerland. Both sets of tools allowed entry-level usage without or with minimal programing skills while being flexible enough to cater for more complex scenarios for users with greater programing skills. In particular, interfaces linking statistical softwares and Google tools provide additional analytical functionality (such as algorithms for the detection of unusually high case occurrences) for inclusion in the reporting process. We show that such powerful approaches could improve timely dissemination and communication of technical information to decision makers and other stakeholders and could foster the early-warning capacity of animal health surveillance systems.

Hypertension control and related variables among urban and rural adults in Taiwan

Literature on hypertension treatment has demonstrated that a healthy life style is one of the best strategies for hypertension control. In exploring the mechanisms of behavioral change for hypertension control, a comprehensive study based on the Transtheoretical Model was carried out in Taiwan during the summer of 2000 with a sample of 350 hypertensive adults living in Taipei urban and rural areas. ^ The relationships among stages of change, processes of change and demographic factors were analyzed for six health behaviors—low fat food consumption, alcohol use, smoking, physical activity, weight control, and routine blood pressure checkups. In addition, differences were assessed between urban and rural populations in changing their behavior for hypertension control. ^ The results showed that rural populations had more difficulties than urban populations in avoiding smoking and engaging in physical activity, and the processes of change being used by urban populations were significantly greater than rural populations. The study findings support a strong association between processes and stages of change. ^ Individuals who use more processes of change will be more inclined to move from precontemplation stage to maintenance stage. Counterconditioning, which is the substitution of alternatives for the problem behaviors, in this study, significantly helped people to change diet, engage in physical activity, and check blood pressure regularly. For example, counterconditioning is eating more vegetables instead of meat, or engaging in physical activity as a time to relax rather than another task to accomplish. ^ In addition, self-reevaluation was the most important process for helping people to engage in physical activity; and social liberation was the most important process for changing diet behavior. The findings in this study may be applied to improve health behaviors among rural populations with low income and low education; however, at the same time, the obesity problems among urban populations should be prevented to control hypertension in Taiwan. ^

Emissions Control and the Regulation of Product Markets: The Case of Automobiles

The paper investigates alternative policies to regulate emissions from polluting product markets, specifically considering the case of the automobiles market. The two policies we consider are: a quota that limits the quantity produced of the polluting model and a more flexible average efficiency standard that requires a minimum energy efficiency across all models produced by a firm, similar to the US Corporate Average Fuel Economy (CAFE) standards. We use a duopoly model of vertical differentiation where firms produce both an economy (i.e., low polluting) version and a luxury (i.e., high polluting) version of a given product. We show that while a quota can raise firm profit over a certain range, CAFE always reduces firm profit relative to the pre-regulation. We also show that while the quota reduces emissions, it is possible that emissions increase under CAFE. The optimal policy choice will depend on the magnitude of unit damages. We show that when unit damages are sufficiently high, the quota policy is more efficient than the average efficiency standard. This suggests that instead of tightening CAFE to limit damages from emissions, policy makers can shift to a quota policy which is both welfare enhancing and more profitable for firms.

Investigations of stress responses in Saccharomyces cerevisiae: Transcriptional control and heat shock protein function

The baker's yeast, Saccharomyces cerevisiae responds to the cytotoxic effects of elevated temperature (37-42°C) by activating transcription of ∼150 genes, termed heat shock genes, collectively required to compensate for the abundance of misfolded and aggregated proteins and various physiological modifications necessary for the cell to survive and grow at heat shock temperatures. An intriguing facet of the yeast heat shock response is the remarkable similarity it shares with the global remodeling that occurs in mammalian cells in response to numerous pathophysiological conditions including cancer and cardiovascular disease and thus provides an ideal model system. I have therefore investigated several novel features of stress signaling, transcriptional regulation, and physiology. Initial work focused on the characterization of SYM1, a novel heat shock gene in yeast which was demonstrated to be required for growth on the nonfermentable carbon source ethanol at elevated temperature, and to be the functional ortholog of the mammalian kidney disease gene, Mpv17. Additional work addressed the role of two proteins, the Akt-related kinase, Sch9, and Sse1, the yeast Hsp110 protein chaperone homolog, in signaling by protein kinase A, establishing Sse1 as a critical negative regulator of this pathway. Furthermore, I have demonstrated a role for Sse1 in biogenesis and stability of the stress-response transcription factor, Msn2; a finding that has been extended to include a select subset of additional high molecular weight proteins, suggesting a more global role for this chaperone in stabilizing the cellular proteome. The final emphasis of my doctoral work has included the finding that celastrol, a compound isolated from the plant family Celasfraceae, a component of traditional Chinese herbal medicine, can activate heat shock transcription factor (Hsf1) in yeast and mammalian cells through an oxidative stress mechanism. Celastrol treatment simultaneously activates both heat shock and oxidative stress response pathways, resulting in increased cytoprotection. ^

XIPHOPHORUS ENZYME GENE EXPRESSION: TISSUE SPECIFICITY, GENETIC CONTROL, AND STABILITY IN CULTURED CELLS

Five permanent cell lines were developed from Xiphophorus maculatus, X. helleri, and their hybrids using three tissue sources, including adults and embryos of different stages. To evaluate cell line gene expression for retention of either tissue-of-origin-specific or ontogenetic stage-specific characters, the activity distribution of 44 enzyme loci was determined in 11 X. maculatus tissues, and the developmental genetics of 17 enzyme loci was charted in X. helleri and in helleri x maculatus hybrids using starch gel electrophoresis. In the process, eight new loci were discovered and characterized for Xiphophorus.^ No Xiphophorus cell line showed retention of tissue-of-origin-specific or ontogenetic stage-specific enzyme gene expressional traits. Instead, gene expression was similar among the cell lines. One enzyme, adenosine deaminase (ADA) was an exception. Two adult-origin cell lines expressed ADA, whereas, three cell lines derived independently from embryos did not. ADA('-) expression of Xiphophorus embryo-derived cell lines may represent retention of an embryonic gene expressional trait. In one cell line (T(,3)) derived from 13 pooled interspecific hybrid (F(,2)) embryos, shifts with time were observed at enzyme loci polymorphic between the two species. This suggested shifts in ratios of cells of different genotypes in the population rather than unstable gene expression in one dominant cell type.^ Verification of this hypothesis was attempted by cloning the culture--seeking clones having different genetic signatures. The large number of loci electrophoretically polymorphic between the two species and whose alleles segregated independently into the 13 progeny from which this culture originated almost guaranteed the presence of different genetic signatures (lineages) in T(,3).^ Seven lineages of cells were found within T(,3), each expressing genotypes at some loci not characteristic of the expression of the culture-as-a-whole, supporting the hypothesis tested. Quantitative studies of ADA expression in the whole culture (ADA('-)) and in clones of these seven lineages suggested the predominance in T(,3) of ADA deficient cell lineages, although moderate to high ADA output clones also occurred. Thus, T(,3) has the potential to shift phenotypes from ADA('-) to ADA('+) by simply changing proportions of its constituent cell types, demonstrating that such shifts can occur in any cell culture containing cells of mixed expressional characteristics.^