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The aims of this study were to 1. define the responses of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and peptide YY (PYY) to an oral meal and to intravenous L-arginine; and 2. examine correlation of enteroendocrine hormones with insulin secretion. We hypothesized a relationship between circulating incretin concentrations and insulin secretion.Subjects with normal glucose tolerance (NGT, n = 23), prediabetes (PDM, n = 17), or with type 2 diabetes (T2DM, n = 22) were studied twice, following a mixed test meal (470 kCal) (mixed meal tolerance test [MMTT]) or intravenous L-arginine (arginine maximal stimulation test [AST], 5 g). GLP-1 (total and active), PYY, GIP, glucagon, and β cell function were measured before and following each stimulus.Baseline enteroendocrine hormones differed across the glucose tolerance (GT) spectrum, T2DM generallyNGT and PDM. In response to MMTT, total and active GLP-1, GIP, glucagon, and PYY increased in all populations. The incremental area-under-the-curve (0-120 min) of analytes like total GLP-1 were often higher in T2DM compared with NGT and PDM (35-51%; P 0.05). At baseline glucose, L-arginine increased total and active GLP-1 and glucagon concentrations in all GT populations (all P 0.05). As expected, the MMTT and AST provoked differential glucose, insulin, and C-peptide responses across GT populations. Baseline or stimulated enteroendocrine hormone concentrations did not consistently correlate with either measure of β cell function.Both MMTT and AST resulted in insulin and enteroendocrine hormone responses across GT populations without consistent correlation between release of incretins and insulin, which is in line with other published research. If a defect is in the enteroendocrine/β cell axis, it is probably reduced response to rather than diminished secretion of enteroendocrine hormones.

Purpose: Suitable ratio of essential fatty acids has an important role in maintaining good health. There is no pure oil with an ideal fatty acid composition and oxidative stability. The main goal of the present study was to evaluate the physical, chemical and nutritional properties of oil obtained by blending flaxseed oil as a rich source of ω3 fatty acids with sesame and olive oils. Methods: Three different ratios (65:30:5, 60:30:10 and 55:30:15) were prepared using olive, sesame and flaxseed oils. These mixtures were stored at 4°C and 24°C and their quality and physicochemical properties were determined by measuring the fatty acid composition, phenolic compound, peroxide, anisidine values and schaal tests. Results: Fatty acid composition indicated that adding 10% and 15% flaxseed oil into blends have suitable ratio of essential fatty acids. The sample which contained 5% flaxseed oil had the highest phenolic content among treatments and these compounds showed a significant decrease during storage. A significant increase (p

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

The aim of this study was to evaluate whether low insulin sensitivity (Si) measured using a modified frequently sampled intravenous glucose tolerance test with minimal model analysis is associated with coronary artery disease (CAD) independent of other cardiovascular risk factors.We studied 1,482 women and men, age 40-69 years old, African American (28%), Hispanic (34%), or non-Hispanic white (38%), with normal (45%), impaired (23%), or diabetic (32%) glucose tolerance. CAD defined as confirmed past myocardial infarction, coronary artery bypass graft, coronary angioplasty, or presence of a major Q-wave was found in 91 participants.The odds ratio (OR) for CAD was greatest among individuals in the two lowest quintiles of Si (2.4, 95% CI 1.0-5.6 and 4.7, 2.1-10.7) compared with the highest Si quintile. After adjusting for demographic and cardiovascular risk factors, a decrement from the 75th to 25th percentile in Si was associated with a 56% increase in CAD (P=0.028). Similar increments in fasting or 2-h insulin levels were associated with, respectively, only 15 (NS) and 3% (NS) increases in CAD. The association between Si and CAD was partially mediated by insulin, HDL cholesterol and triglyceride levels, hypertension, diabetes, and obesity, but not LDL cholesterol or cigarette smoking.Low Si is associated with CAD independently of and stronger than plasma insulin levels. Part of the association is accounted for by dyslipidemia, hypertension, diabetes, and obesity.

Factor analysis, a multivariate correlation technique, has been used to provide insight into the underlying structure of metabolic syndrome, which is characterized by physiological complexity and strong statistical intercorrelation among its key variables. The majority of previous factor analyses, however, have used only surrogate measures of insulin sensitivity. In addition, few have included members of multiple ethnic groups, and only one has presented results separately for subjects with impaired glucose tolerance. The objective of this study was to investigate, using factor analysis, the clustering of physiologic variables using data from 1,087 nondiabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). This study includes information on the directly measured insulin sensitivity index (S(I)) from intravenous glucose tolerance testing among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years at various stages of glucose tolerance. Principal factor analysis identified two factors that explained 28 and 9% of the variance in the dataset, respectively. These factors were interpreted as 1) a " metabolic" factor, with positive loadings of BMI, waist, fasting and 2-h glucose, and triglyceride and inverse loadings of log(S(I)+1) and HDL; and 2) a "blood pressure" factor, with positive loadings of systolic and diastolic blood pressure. The results were unchanged when surrogate measures of insulin resistance were used in place of log(S(I)+1). In addition, the results were similar within strata of sex, glucose tolerance status, and ethnicity. In conclusion, factor analysis identified two underlying factors among a group of metabolic syndrome variables in this dataset. Analyses using surrogate measures of insulin resistance suggested that these variables provide adequate information to explore the underlying intercorrelational structure of metabolic syndrome. Additional clarification of the physiologic characteristics of metabolic syndrome is required as individuals with this condition are increasingly being considered candidates for behavioral and pharmacologic intervention.

Philosophical counselling is an approach that aims to assist people to deal with life events in an effective manner. As such, it is of interest to nurses who are concerned with helping clients who require assistance effectively to manage life events. The approach utilizes both ancient and contemporary philosophical promises and theories. On the promise side, it offers the belief that philosophy can be concerned with providing answers to the question of how people ought to live a good or healthy life. On the theory side, it offers the belief that philosophical inquiry and theory can help people towards such answers. Thus the theory and practice of philosophical counselling is relevant to nurses whose practice aims to promote in their clients a good or healthy lifestyle. The practice of philosophical counselling, in a substance abuse centre, will be explored to demonstrate the theory and methods of the approach.

The enrichment of Foxp3+ regulatory T cells (Tregs) constitutes a central mechanism of immune regulation, but has also been associated with poor patient prognosis in a variety of human cancers. Previous studies have suggested that Treg development, specificity, and mechanism of action are dependent upon antigen recognition; however, little is known about the identity of the antigen presenting cells (APCs) that are directly recognized by Tregs in vivo. Previously, we have identified an endogenously occurring monospecific Treg population, termed “MJ23 Tregs,” that is highly enriched in the prostate tumors of TRAMP mice. Using MJ23 T cells as a probe, we have determined that despite the presence of multiple MHC class II-expressing cell types within tumor lesions, the antigen recognized by MJ23 Tregs is exclusively presented by a distinct subset of dendritic cells (DCs). In order to determine the functional significance of this interaction, ongoing work aims to determine the impact of DC ablation on Treg localization and function, and on prostate cancer development. In all, our work will determine the extent to which the activity of Tregs within tumor lesions is coordinated in trans by the APC.

For some human cancers, elevated densities of Foxp3+ regulatory T cells (Tregs) in the tumor tissue correlate with poor prognosis, suggesting that Tregs may play a functional role in cancer progression. Despite considerable interest in the modulation of tumor-associated Tregs for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. By a TCR sequencing approach of T cells isolated from tumors of mice with oncogene-driven prostate cancer (TRAMP), we identified an endogenous population of antigen-specific Tregs found recurrently enriched in the tumors. These Tregs were not reactive to a tumor-specific antigen, but instead recognized a prostate-associated antigen that is present in tumor-free mice. Transgenic T cells expressing this Treg-derived TCR underwent Treg development in the thymus, but inefficient development in the periphery, indicating a thymic origin of these cells. Taken together, our data support a model in which organ-specific Tregs reactive to peripheral tissue antigens develop as Tregs in the thymus and are co-opted by tumors arising within the associated organ.

While the transcription factor Autoimmune Regulator (AIRE) has been shown to play a critical role in establishing immune tolerance through the negative selection of T cells reactive to peripheral antigens, the role of AIRE in the thymic development of Foxp3+ regulatory T cells (Tregs) remains controversial. Previously in our lab, the naturally occurring Treg T-cell receptor (TCR) “MJ23”, isolated from the prostates of tumor-bearing TRAMP mice, was used to create a monospecific TCR transgenic (tg) mouse model. By generating MJ23 tg low frequency bone marrow chimeras (BMCs), we determined that the MJ23 TCR facilitates thymic Treg development in both male and female hosts, even though MJ23 T cells are reactive to a prostate-specific antigen. By generating MJ23 BMCs into Aire+/+ and Aire-/- hosts, we determined that the thymic development of MJ23 Tregs was Aire-dependent, regardless of host gender. These results were also observed for a second naturally occurring Treg specificity. In BMCs, we found no evidence of Aire-dependent MJ23 negative selection, suggesting that for this specificity, Aire plays an exclusive role in the thymic selection of Tregs. Finally, while autoimmune prostatitis was observed in male Aire-/- mice, we found no indications of Foxp3neg MJ23 T cell expansion in Aire-/- BMC hosts. In sum, our data provide mechanistic evidence that a subset of peripheral organ-specific Tregs are dependent on Aire for their selection into the Foxp3+ Treg lineage in the thymus.

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). Previous studies suggest that the magnitude of the pre-BMT conditioning influences the severity of GVHD. To test this, we developed minor mismatch (129→B6) and major mismatch (Balb/c→B6) models of GVHD. In lethally irradiated WT recipients, major mismatch caused severe GVHD that was fatal in all recipients by 24 days after BMT. Minor mismatch led to a milder GVHD, where 50% of recipients survived to 35 days after BMT. We examined the role of irradiation in these models by minor or major mismatch adoptive transfer (AT) into unconditioned immunodeficient recipients. Major mismatch AT alone resulted in prominent GVHD. In contrast, minor mismatch AT required irradiation conditioning to cause GVHD. Conditioning and minor mismatch AT lead to elevated IFNγ, TNF, and IL-6, and an increased ability of donor cells to kill allogeneic targets in vivo (63±7% vs. 26±6%) compared to AT alone. As the intestine is very sensitive to irradiation, it was possible intestinal damage from the irradiation conditioning was facilitating minor mismatch GVHD. When we induced transient colonic damage with dextran sodium sulfate prior to minor mismatch AT, we observed systemic target organ histopathology characteristic of GVHD. Thus, we conclude that pretransplant conditioning, particularly intestinal damage, is required for minor mismatch GVHD.

This paper examines the literature on patient assessment in nursing, with particular reference to assessment in psychiatric nursing. It finds that most nursing assessment is concerned with gathering physiological information about patients while effectively ignoring psychosocial indices. This phenomenon, it is argued, is due to historical factors in the socialization of nurses, the particular version of nursing process imported into the UK, and an oversimplification of the concept of 'need' which has encouraged nurses to focus on patient disabilities but has ignored their capabilities. It is proposed that nursing assessment should be a relatively lengthy process, increasing in specificity, involving gathering and analysing information from a holistic perspective about individuals'/families' health concerns. Then, by applying concepts from appropriate conceptual models, a nursing diagnosis to those health concerns is proposed. This proposal is supported by a discussion of the process, functions and methods of nursing assessment. Finally, while recognizing the importance of social causation theories in psychiatric care, it is argued that community health assessments are beyond the scope of individual nurses.

THE PURPOSE OF this article is twofold. The first is to present a simple summary of the major events in West Irian's history from the Second World War to the first half of 1977, so that the reader may be in a better position to appreciate the often confusing contemporary events in West Irian. The second is to unfold the story of a particular social class in West Irian, the indigenous educated petty bourgeoisie. The history of nationalism in West Irian is either dominated by its absence or is in large part an account of its successive attempts to seek alliances with a variety of metropolitan classes and fractions, and even institutions. The successive and gradual disillusionment of the educated petty bourgeoisie with the metropolitan bourgeoisie and their representatives has lead to an increased radicalism until, at the present time, the educated petty bourgeoisie seek alliance with the broad masses and espouse armed struggle as the means for attaining national liberation and melanesian socialism as its final goal. This present alliance is a final alliance. In it, the educated petty bourgeoisie will either succeed in liberating West Irian and in establishing socialism, and consequently will decline as a class, or it will be physically exterminated along with its proto-peasant guerillas by the Indonesian para-commandos. Much of the information contained in this paper is based on "oral histories" collected in the field. Where possible, I have attempted to verify the information collected by reference to other sources, especially the work of Paul van der Veurl and the report of Fernando Ortiz-Sans

The auguries for Comparative Administration are not good. The Journal of Comparative Administration has gone. The Comparative Administration Group has spent its half a million dollars and has, to all intents and purposes, disbanded, even though some of its leadership and membership has joined the ASPA Section for International and Comparative Administration, and though fragments of its original network remain. The Duke University Press series in Comparative Administration has come to an end and the only part of the once vigorous publication program of the CAG remaining is the Newsletter. Gone too are the fecund "summer seminars," the easy assurance of panels devoted to the field at professional meetings, and the receptivity of scholarly journals to articles in Comparative Administration. My own experience of dwindling classes and the lessening appeal of coursework to American, as opposed to overseas, students is perhaps a small token of a larger movement mirrored in the small proportion of current dissertations attributable to concerns with Comparative Administration.