Associations between surrogate measures of insulin resistance and waist circumference,cardiovascular risk and the metabolic syndrome across Hispanic and non‐Hispanic white populations

Aims We evaluated the relations between surrogate indices of insulin resistance and waist circumference, metabolic syndrome and coronary heart disease risk across Hispanic and non‐Hispanic white populations. Methods The study was a cross‐sectional analysis of participants without diabetes in the San Antonio Heart Study, Mexico City Diabetes Study and Spanish Insulin Resistance Study. We evaluated commonly used indices of insulin resistance, including homeostasis model assessment, McAuley’s index, Gutt’s insulin sensitivity index, Avignon’s insulin sensitivity index and the Stumvoll index with and without demographics, the modified Matsuda index and the product of the triglycerides and glucose index. The metabolic syndrome was defined by American Heart Association/National Heart, Lung, and Blood Institute criteria and coronary heart disease risk by Framingham risk scores. Results The Stumvoll index with demographics and the Avignon’s insulin sensitivity index had the strongest correlations with waist circumference across populations. The triglycerides and glucose and McAuley’s indices had the most robust correlations with Framingham risk score. The triglycerides and glucose index had the greatest ability to detect individuals with the metabolic syndrome and ≥ 10% coronary heart disease risk. Some indices display significant variability in the strength of the relationship with adiposity and coronary heart disease risk across populations. Conclusions There are significant differences between insulin resistance indices regarding the ability to detect the metabolic syndrome and coronary heart disease risk across populations. Studies may need to consider the index of insulin resistance that best suits the objectives.     

Deletion of the Uracil Permease Gene Confers Cross-Resistance to 5-Fluorouracil and Azoles in Candida lusitaniae and Highlights Antagonistic Interaction between Fluorinated Nucleotides and Fluconazole

We characterized two additional membrane transporters (Fur4p and Dal4p) of the nucleobase cation symporter 1 (NCS1) family involved in the uptake transport of pyrimidines and related molecules in the opportunistic pathogenic yeast Candida lusitaniae. Simple and multiple null mutants were constructed by gene deletion and genetic crosses. The function of each transporter was characterized by supplementation experiments, and the kinetic parameters of the uptake transport of uracil were measured using radiolabeled substrate. Fur4p specifically transports uracil and 5-fluorouracil. Dal4p is very close to Fur4p and transports allantoin (glyoxyldiureide). Deletion of the FUR4 gene confers resistance to 5-fluorouracil as well as cross-resistance to triazoles and imidazole antifungals when they are used simultaneously with 5-fluorouracil. However, the nucleobase transporters are not involved in azole uptake. Only fluorinated pyrimidines, not pyrimidines themselves, are able to promote cross-resistance to azoles by both the salvage and the de novo pathway of pyrimidine synthesis. A reinterpretation of the data previously obtained led us to show that subinhibitory doses of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine also were able to trigger resistance to fluconazole in susceptible wild-type strains of C. lusitaniae and of different Candida species. Our results suggest that intracellular fluorinated nucleotides play a key role in azole resistance, either by preventing azoles from targeting the lanosterol 14-alpha-demethylase or its catalytic site or by acting as a molecular switch for the triggering of efflux transport.     

Impulsive or Depressive Personality Traits Do Not Impede Behavioral Change After Brief Alcohol Interventions

ABSTRACT

The authors investigated whether impulsivity and depression affect the success of interventions to reduce alcohol use. Unadjusted and adjusted regression models were constructed to analyze the effect of impulsivity and depression on 12-month outcomes of participants of a trauma center based randomized trial of brief personalized motivational interventions versus information and advice. Of 497 problem drinkers enrolled in the program, 248 completed the 12-month follow-up. Impulsivity, male gender, being older than 35, and intentional mechanism of injury had a direct association with drinking. After interventions, a decrease in drinking was found that was unaffected by the presence of impulsivity or depression indicators.     

Transition in the Cause of Fever from Malaria to Dengue,Northwestern Ecuador, 1990–2011

In tropical areas, the predominant cause of fever has historically been malaria. However by 2011, among febrile patients in northwestern Ecuador, dengue was identified in 42% and malaria in none. This finding suggests a transition in the cause of fever from malaria to other illnesses, such as dengue.     

Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model

Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.