Therapeutic Enhancement of Protective Immunity during Experimental Leishmaniasis

Leishmaniasis is an infectious disease that causes a large burden of morbidity and mortality in the tropics. Caused by protozoan parasites of the genus Leishmania that are transmitted by sandflies, leishmaniasis causes a wide spectrum of human disease. The severe end of the spectrum, visceral leishmaniasis, causes an annual mortality of approximately 50,000, largely in India and Sudan. Available therapies for leishmaniasis are problematic due to emerging drug resistance, toxicity and/or the need for lengthy courses of treatment. There is thus an urgent need for novel therapeutic approaches to this neglected tropical disease. To address this problem, the authors examined whether a commercially available drug developed for cancer therapy (Ontak), reported to have immunological activity of relevance to the immunobiology of Leishmania infection, exhibited efficacy in mouse models of leishmaniasis. The study found therapeutic efficacy for the drug alone in these models, as well as additive therapeutic efficacy in combination with standard antimicrobial therapy. Rational reinvestigation of the efficacy of already approved drugs in experimental models of neglected tropical diseases has promise in providing needed new candidates to the drug discovery pipeline

Fish and Shellfish Intake and Diabetes in a Costal Population of the Adriatic

Objective: To examine the association between fish and shellfish intake and diabetes in an island population. Design: Cross-sectional. Setting: Two independent population-based field surveys conducted in Hvar Island of the eastern Adriatic coast of Croatia in May 2007 and May 2008. Subjects: A total of 1,379 adults participated. Results: In multivariable logistic regression models, total fish intake was positively associated with diabetes prevalence in the total population (OR Q4 vs Q1 = 1.64; 95% CI = 1.01-2.66; p-trend = 0.09). Oily fish intake also exhibited a positive association with diabetes prevalence in the total population (OR Q4 vs Q1 = 2.22; 95% CI = 1.35-3.64; p-trend = 0.01) and in analyses stratified by body mass index, males and those with a high waist circumference. Conclusions: The study suggests an association between oily fish intake and diabetes in the population of the Hvar Island in Croatia. Longitudinal studies incorporating measures of persistent organic pollutants and local cooking practices are warranted to identify factors in fatty fish that may influence the development or persistence of diabetes

Dietary Patterns in Adults from an Adriatic Island of Croatia and Their Associations with Metabolic Syndrome and Its Components

Adriatic islanders have a high prevalence of metabolic syndrome (MetS) although they have traditionally practiced an active lifestyle and adhered to a Mediterranean diet. We performed a cross-sectional study to identify dietary patterns in a sample of 1442 adults from the island of Hvar, and determined whether MetS and its components: waist-circumference, serum triglycerides, fasting plasma glucose, HDL-cholesterol, and blood pressure, were related to an altered pattern of the traditional Mediterranean diet. Dietary intake was assessed by a food frequency questionnaire. MetS was defined using the International Diabetes Federation criteria. Our study showed that dietary patterns in this population have diversified from the traditional diet. Principal component analysis identified three major patterns. The meat, alcohol, and fish pattern (MAFp), sweets, grains, and fats pattern (SGFp), and an olive-oil, vegetables, and fruits pattern (OVFp) explained 30.6% of total dietary variance. The MAFp associated significantly with MetS (p=0.027) and high plasma glucose (p=0.006)

Staging of biliary atresia at diagnosis by molecular profiling of the liver

Abstract Background Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. Methods We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. Results Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival. Conclusions Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes.http://deepblue.lib.umich.edu/bitstream/2027.42/112492/1/13073_2010_Article_154.pd

Fish and Shellfish Intake and Diabetes in a Costal Population of the Adriatic

Objective: To examine the association between fish and shellfish intake and diabetes in an island population. Design: Cross-sectional. Setting: Two independent population-based field surveys conducted in Hvar Island of the eastern Adriatic coast of Croatia in May 2007 and May 2008. Subjects: A total of 1,379 adults participated. Results: In multivariable logistic regression models, total fish intake was positively associated with diabetes prevalence in the total population (OR Q4 vs Q1 = 1.64; 95% CI = 1.01-2.66; p-trend = 0.09). Oily fish intake also exhibited a positive association with diabetes prevalence in the total population (OR Q4 vs Q1 = 2.22; 95% CI = 1.35-3.64; p-trend = 0.01) and in analyses stratified by body mass index, males and those with a high waist circumference. Conclusions: The study suggests an association between oily fish intake and diabetes in the population of the Hvar Island in Croatia. Longitudinal studies incorporating measures of persistent organic pollutants and local cooking practices are warranted to identify factors in fatty fish that may influence the development or persistence of diabetes

Dietary Patterns in Adults from an Adriatic Island of Croatia and Their Associations with Metabolic Syndrome and Its Components

Adriatic islanders have a high prevalence of metabolic syndrome (MetS) although they have traditionally practiced an active lifestyle and adhered to a Mediterranean diet. We performed a cross-sectional study to identify dietary patterns in a sample of 1442 adults from the island of Hvar, and determined whether MetS and its components: waist-circumference, serum triglycerides, fasting plasma glucose, HDL-cholesterol, and blood pressure, were related to an altered pattern of the traditional Mediterranean diet. Dietary intake was assessed by a food frequency questionnaire. MetS was defined using the International Diabetes Federation criteria. Our study showed that dietary patterns in this population have diversified from the traditional diet. Principal component analysis identified three major patterns. The meat, alcohol, and fish pattern (MAFp), sweets, grains, and fats pattern (SGFp), and an olive-oil, vegetables, and fruits pattern (OVFp) explained 30.6% of total dietary variance. The MAFp associated significantly with MetS (p=0.027) and high plasma glucose (p=0.006)

Informative Models for the Joint Distribution of a Vector from Its Marginal Distributions – An Application to the Spina Bifida Condition

<p>We propose a model, which has information on the joint distribution of the vector from its marginal distributions. We outline a method of extracting information on the joint distribution from the marginal distributions. </p&gt

Reliability of Systematic and Targeted Biopsies versus Prostatectomy

Systematic Biopsy (SBx) has been and continues to be the standard staple for detecting prostate cancer. The more expensive MRI guided biopsy (MRITBx) is a better way of detecting cancer. The prostatectomy can provide an accurate condition of the prostate. The goal is to assess how reliable SBx and MRITBx are vis à vis prostatectomy. Graded Gleason scores are used for comparison. Cohen’s Kappa index and logistic regression after binarization of the graded Gleason scores are some of the methods used to achieve our goals. Machine learning methods, such as classification trees, are employed to improve predictability clinically. The Cohen’s Kappa index is 0.31 for SBx versus prostatectomy, which means a fair agreement. The index is 0.34 for MRITBx versus prostatectomy, which again means a fair agreement. A direct comparison of SBx versus prostatectomy via binarized graded scores gives sensitivity 0.83 and specificity 0.50. On the other hand, a direct comparison of MRITBx versus prostatectomy gives sensitivity 0.78 and specificity 0.67, putting MRITBx on a higher level of accuracy. The SBx and MRITBx do not yet match the findings of prostatectomy completely, but they are useful. We have developed new biomarkers, considering other pieces of information from the patients, to improve the accuracy of SBx and MRITBx. From a clinical point of view, we provide a prediction model for prostatectomy Gleason grades using classification tree methodology

Sample Size Calculations in Simple Linear Regression: A New Approach

The problem tackled is the determination of sample size for a given level and power in the context of a simple linear regression model. The standard approach deals with planned experiments in which the predictor X is observed for a number n of times and the corresponding observations on the response variable Y are to be drawn. The statistic that is used is built on the least squares’ estimator of the slope parameter. Its conditional distribution given the data on the predictor X is utilized for sample size calculations. This is problematic. The sample size n is already presaged and the data on X is fixed. In unplanned experiments, in which both X and Y are to be sampled simultaneously, we do not have data on the predictor X yet. This conundrum has been discussed in several papers and books with no solution proposed. We overcome the problem by determining the exact unconditional distribution of the test statistic in the unplanned case. We have provided tables of critical values for given levels of significance following the exact distribution. In addition, we show that the distribution of the test statistic depends only on the effect size, which is defined precisely in the paper