Detection of blaCTX-M-15 in an integrative and conjugative element in four extensively drug-resistant Haemophilus parainfluenzae strains causing urethritis.

Haemophilus parainfluenzae is a commensal organism with rising numbers of multidrug-resistant (MDR) strains. This pathogen is of increasing clinical relevance in urogenital infection. The aim of this work was to identify and characterise the molecular mechanisms of resistance associated with four cephalosporin-resistant H. parainfluenzae strains collected from patients with urethritis. Antimicrobial resistance was determined by microdilution following European Committee on Antimicrobial Susceptibility Testing criteria. Strains were then analysed by whole-genome sequencing to determine clonal relationship and the molecular basis of antimicrobial resistance. Finally, a phylogenetic analysis was performed on all urogenital MDR strains of H. parainfluenzae previously isolated in our hospital. All strains were resistant to ß-lactams, macrolides, tetracycline, fluoroquinolones, chloramphenicol, cotrimoxazole, and aminoglycosides. The resistance profile was compatible with the presence of an extended-spectrum ß-lactamase (ESBL). Whole-genome sequencing detected blaCTX-M-15 that conferred high minimum inhibitory concentrations to cephalosporins in two novel integrative and conjugative elements (ICEHpaHUB6 and ICEHpaHUB7) that also harboured a blaTEM-1 ß-lactamase. This study shows a novel blaCTX-M-15 ESBL carried in an integrative conjugative element in four extensively drug-resistant H. parainfluenzae strains. This resistance determinant could be transmitted to other sexually transmitted pathogens and this is a cause for concern.

Conflicts and contradictions in current skin cancer screening guidelines.

PURPOSE OF REVIEW: To review skin cancer screening guidelines from major public health/medical organizations. RECENT FINDINGS: No consensus exists on whether or not screening to prevent skin cancer is warranted. SUMMARY: The best evidence of screening efficacy should come from population-based randomized trials, but is unlikely to exist due to feasibility constraints. Consequently, consensus should be built from observational/non-randomized designs, such as the SCREEN study in Germany. Current guidelines often focus on melanoma alone, while potential benefits of screening for non-melanoma skin cancers (NMSC) are largely overlooked. There may be less room for doubt regarding the value of screening, if both diseases were considered. Further, targeted approaches, i.e. screening only in high-risk populations, remain poorly defined and untested. Continuing to state that there is insufficient evidence to recommend screening leads to confusion about whether or not to screen, and is unlikely to result in substantial changes to the morbidity of NMSC and significant mortality from melanoma.

[Predictive factors of eosinophilic esophagitis in esophageal food bolus impaction]. / Factores predictores de esofagitis eosinofílica en impactación esofágica por bolo alimenticio.

BACKGROUND: Food bolus esophageal impaction is often the first symptom in patients diagnosed with eosinophilic esophagitis, representing a change in the epidemiology and management of this urgency. AIM: To detect eosinophilic esophagitis predictive factors in patients with esophageal impaction due to food bolus. METHODS: Patients seen for foreign body impaction were retrospectively analyzed. Epidemiologic characteristics, endoscopic findings, and impaction history were studied. The statistical analysis was carried out using the Student's t test and the chi square test and a logistic regression model. RESULTS: Of the 131 patients, 65% were men and the mean age was 56 years. The endoscopic suspicion of eosinophilic esophagitis was the most frequent finding in patients with food bolus impaction (n=89); those patients that did not have histologic confirmation were excluded (n=7). The remaining patients (n=82) were divided into two groups: confirmed eosinophilic esophagitis (Group A) (n=18) and other endoscopic findings (Group B) (n=64). Group A presented with a lower mean age (36.47 vs. 64.45, P=.001) and a more frequent past history of impaction (38% vs. 6%, OR=15.70, 95% CI (3.60-62.50), P=.001) than Group B. Age and impaction history acted as predictors for eosinophilic esophagitis with 82% sensitivity, 80% specificity, and 84% diagnostic accuracy (P<.001). CONCLUSIONS: Age and a history of impaction predict the presence of eosinophilic esophagitis in patients with food bolus impaction.

Determination of absolute threshold and just noticeable difference in the sensory perception of pungency.

Absolute threshold and just noticeable difference (JND) were determined for the perception of pungency using chili pepper in aqueous solutions. Absolute threshold and JND were determined using 2 alternative forced-choice sensory tests tests. High-performance liquid chromatography technique was used to determine capsaicinoids concentration in samples used for sensory analysis. Sensory absolute threshold was 0.050 mg capsaicinoids/kg sample. Five JND values were determined using 5 reference solutions with different capsaicinoids concentration. JND values changed proportionally as capsaicinoids concentration of the reference sample solutions changed. Weber fraction remained stable for the first 4 reference capsaicinoid solutions (0.05, 0.11, 0.13, and 0.17 mg/kg) but changed when the most concentrated reference capsaicinoids solution was used (0.23 mg/kg). Quantification limit for instrumental analysis was 1.512 mg/kg capsaicinoids. Sensory methods employed in this study proved to be more sensitive than instrumental methods. Practical Application: A better understanding of the process involved in the sensory perception of pungency is currently required because "hot" foods are becoming more popular in western cuisine. Absolute thresholds and differential thresholds are useful tools in the formulation and development of new food products. These parameters may help in defining how much chili pepper is required in a formulated product to ensure a perceptible level of pungency, as well as in deciding how much more chili pepper is required in a product to produce a perceptible increase in its pungency.

Potential target antigens for immunotherapy in human pancreatic cancer.

BACKGROUND: To be effective and selective, immunotherapy ideally targets specifically tumor cells and spares normal tissues. Identification of tumor specific antigens is a prerequisite to establish an effective immunotherapy. Still very little is known about the expression of tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens (CT) are antigens shared by a variety of malignant tumors, but not by normal tissues with the exception of germ cells in testis. Restricted expression in neoplastic tissues and inherent immunogenic features make CT antigens ideal for use in immunotherapy. We analyzed the expression of a selected panel of nine CT antigens that have been proven to elicit an efficient immunogenic response in other malignancies. In addition we analyzed the expression of HERV-K-MEL, an immunogenic antigen of viral origin. METHODS: Pancreatic adenocarcinoma tumor samples (n=130) were obtained intraoperatively, control tissues (n=23) were collected from cadaveric donor and from patients with chronic pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL was assessed by PCR. Sequencing of PCR products were performed to assess the expression of SSX-4 in neoplastic and normal pancreatic tissues. RESULTS: Three of 10 tested antigens were expressed in over 10% of malignant pancreatic tissue samples. SSX-4 was found positive in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No expression of CT antigens was found in non-malignant pancreatic tissue with the exception of SSX-4 and and SSX-2. CONCLUSIONS: Fifty two percentage of the analyzed tissues expressed at least one CT antigen. The concomitant expression of SSX-4 in both malignant and non-malignant pancreatic tissue is a new finding which may raise concerns for immunotherapy. However, HERV-K-MEL is expressed with a relatively high prevalence and may be a candidate for specific immunotherapy in a large subgroup of pancreatic cancer patients. This study advocates the analysis of patients with regard to their immunogenic profile before the onset of antigen-specific immunotherapy.

Specific immune recognition of pancreatic carcinoma by patient-derived CD4 and CD8 T cells and its improvement by interferon-gamma.

Pancreatic carcinoma is a very aggressive disease and little is known about its immunobiology. We here describe the presence in pancreatic cancer patients of spontaneously induced functional CD4 and CD8 memory/effector T cells reactive to autologous tumor cells or to the pancreatic cancer associated antigen, MUC-1. Such specific cells were present in the bone marrow or peripheral blood of most of the 23 tested patients. Low dose stimulation of primary cultures of pancreatic cancer cells with 500 IU/ml IFN-gamma for 72 h enhanced HLA-I expression and induced the de novo expression of HLA-II molecules. This led to a much better immune recognition by autologous HLA-I restricted and purified CD8 T cells and allowed tumor cell recognition by HLA-II restricted purified CD4 T-helper cells. Thus, interferon-gamma appears to be a useful adjuvant cytokine to enhance the immunogenicity of a patients' tumor cells and their recognition by tumor reactive immune cells.

Methodological issues in estimating smoking-attributable mortality in the United States.

The authors explored two methodological issues in the estimation of smoking-attributable mortality for the United States. First, age-specific and age-adjusted relative risk, attributable fraction, and smoking-attributable mortality estimates obtained using data from the American Cancer Society's second Cancer Prevention Study (CPS II), a cohort study of 1.2 million participants (1982-1988), were compared with those obtained using a combination of data from the National Mortality Follow-back Survey (NMFS), a representative sample of US decedents in which information was collected from informants (1986), and the National Health Interview Survey (NHIS), a nationally representative household survey (1987). Second, the potential for residual confounding of the disease-specific age-adjusted smoking-attributable mortality estimates was addressed with a model-based approach. The estimated smoking-attributable mortality based on the CPS II for the four most common smoking-related diseases-lung cancer, chronic obstructive pulmonary disease, coronary heart disease, and cerebrovascular disease-was 19% larger than the estimated smoking-attributable mortality based on the NMFS/NHIS, yet the two data sources yielded essentially the same smoking-attributable mortality estimate for lung cancer alone. Further adjustment of smoking-attributable mortality for disease-appropriate confounding factors (education, alcohol intake, hypertension status, and diabetes status) indicated little residual confounding once age was taken into account.

The relationship between depressive symptoms and cigarette smoking in US adolescents.

AIMS: Data from the Teenage Attitudes and Practices Survey were analyzed to assess the relationship between depressive symptoms and cigarette smoking. DESIGNS, SETTING, PARTICIPANTS: Nationally representative sample of adolescents interviewed in 1989 and again in 1993. MEASUREMENTS: Prevalence rate and adjusted odds ratio for smoking at follow-up by depressive symptoms status at baseline. FINDINGS: Adolescents with depressive symptoms were more likely than other adolescents to start smoking. CONCLUSIONS: The associations between depressive symptoms and regular smoking appears to be established by adolescence.

Long-term trends in cigarette smoking among young U.S. adults.

Retrospective examination of a national probability sample revealed that young women, particularly those who dropped out of high school, have reached smoking rates as high or higher than subgroups of young men. These results suggest that surveillance, research, and public health programs are needed to address the rapid increase in smoking among young women.

Socioeconomic status, race, and death from coronary heart disease.

INTRODUCTION: Data to assess factors associated with differences in coronary heart disease mortality between Caucasians and African Americans are limited. We assessed risks for sudden, nonsudden, and other coronary death between Caucasians and African Americans in relation to known risk factors for coronary disease and socioeconomic status. METHODS: We analyzed data from the 1986 National Mortality Followback Survey, the 1985 National Health Interview Survey, and the U.S. Bureau of the Census. Logistic regression methods were used to create multivariate models to assess the relationship of socioeconomic status and other known modifiable risk factors to death from each of the three coronary diseases for Caucasians and African Americans separately. RESULTS: In an age- and gender-adjusted analysis of data on men 25-44 years old and women 25-54 years old, African Americans had about twice the risk for sudden, nonsudden, or other coronary death as did Caucasians. Adjusted risks for coronary death for Caucasians associated with modifiable risk factors (cigarette smoking, body weight, diabetes, and hypertension) either resembled or were slightly greater than those for African Americans. Half or more of all excess risks for African Americans in multivariate models could be explained by socioeconomic status. About 18% of excess sudden coronary death risk could be further explained by known modifiable coronary heart disease risk factors. CONCLUSIONS: Broad public health efforts are needed to address these causes of excess mortality.

Risk factors for sudden coronary death in the United States.

We assessed risk factors for sudden coronary death among persons without a history of coronary heart disease (unexpected sudden coronary death) and persons with a history of coronary heart disease (sudden coronary heart disease death). We analyzed national data to calculate death rates and odds ratios for both types of sudden coronary death. Among modifiable factors that we examined, only cigarette smoking increased risk for unexpected sudden coronary death [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.2-2.7]. Diabetes mellitus (OR = 3.8; 95% CI = 2.5-5.8 for women), cigarette smoking (OR = 1.5; 95% CI = 1.0-2.1), and hypertension (OR = 1.4; 95% CI = 1.1-1.9) increased the risk for sudden coronary heart disease death. Etiologic factors for sudden death appear to differ depending on the presence or absence of coronary disease. With preexisting coronary disease, factors associated with chronic coronary disease may elevate sudden death risk; without coronary disease, factors that provoke ventricular arrhythmias may trigger sudden death.

Relationship between cigarette smoking and health risk and problem behaviors among US adolescents.

OBJECTIVE: To examine whether sociodemographic factors and health risk and problem behaviors explain the prevalence of cigarette smoking among US adolescents. DESIGN: Probability survey. PARTICIPANTS: A nationally representative sample of US adolescents. MAIN OUTCOME MEASURES: Weighted prevalence, adjusted odds ratio (OR), and 95% confidence intervals (CIs) for current smoking status by health risk and problem behaviors. RESULTS: The prevalence of smoking was highest among adolescents who were white, older, and who had a high school education or lived in the Northeast. When we adjusted for sociodemographic factors and health risk and problem behaviors, smoking was associated with marijuana use (OR, 3.7; 95% CI, 2.7-5.1), binge drinking (OR, 2.1; 95% CI, 1.6-2.8), and fighting (OR, 1.4; 95% CI, 1.1-1.7) among white adolescent males. Similar associations between each of these 3 behaviors and cigarette smoking were found among white adolescent females and African American and Hispanic adolescent males and females. Cigarette smoking was also associated with using smokeless tobacco, having multiple sexual partners, and not using bicycle helmets among white adolescent males and females, having multiple sexual partners among Hispanic adolescent females, and carrying weapons among Hispanic adolescent males. CONCLUSIONS: Marijuana use, binge drinking, and fighting are correlates of cigarette smoking among US adolescents. These associations, which vary by sex and race or ethnicity, suggest clustering to form a risk behavior syndrome.

Comparison of sudden and nonsudden coronary deaths in the United States.

BACKGROUND: The present study was designed to compare risk factor prevalences in coronary heart disease deaths in persons dying within 1 hour of onset of cardiovascular symptoms (sudden coronary death), those dying without such sudden symptoms (nonsudden coronary death), and those with unknown duration of symptoms before death (other coronary death). METHODS AND RESULTS: Data from the 1986 National Mortality Followback Survey and the US Bureau of the Census were examined to assess death rates for sudden, nonsudden, and other coronary deaths. Multivariate logistic regression methods were used to calculate the odds ratio (OR), compared with nonsudden and other coronary deaths, for sudden coronary death associated with socioeconomic status variables, the person's location at death, and coronary heart disease risk factors. Mortality rates for all coronary deaths increased with age, were higher for men than women, and increased with decreasing years of schooling. The rate of sudden coronary death was highest for Hispanics. In 1986, an estimated 251,000 sudden coronary deaths (95% CI = 238,000 to 263,000) occurred in the United States. Sudden coronary deaths were less likely than nonsudden coronary deaths to occur at home (OR = 0.5, 95% CI = 0.4 to 0.6), but individuals who died of sudden coronary death were more likely to have been current cigarette smokers (OR = 1.3, 95% CI = 1.0 to 1.8). No other modifiable risk factors for coronary heart disease distinguished sudden coronary deaths from nonsudden coronary deaths. CONCLUSIONS: Contrary to the commonly held view, coronary deaths in the home are more likely to be nonsudden than sudden. Cigarette smoking more likely results in sudden than nonsudden coronary death, perhaps because of nicotine-induced ventricular arrhythmias.

Evaluation of smoking on the physical activity and depressive symptoms relationship.

Physical activity is inversely associated with depressive symptoms, and cigarette smoking is positively associated with depressive symptoms. Data from the first National Health and Nutrition Examination Survey (NHANES I) and the NHANES I Epidemiologic Follow-up study were analyzed to determine whether the relationship between physical activity and self-reported distress (depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale) was different for cigarette smokers and nonsmokers. Logistic regression was used to calculate odds ratios (adjusted for age, race, sex, education, alcohol use, and perceived health status) for depressive symptoms (> or = 16) associated with physical activity and smoking status among 2,054 respondents. At baseline, the odds ratio for depressive symptoms was about 2 times higher for moderately active smokers and nonsmokers, and 3 times higher for low active smokers and nonsmokers, compared with highly active nonsmokers. For 1,132 persons with a low number of depressive symptoms (< 16) at baseline, the incidence of depressive symptoms after 7-9 yr of follow-up was about 2 times higher for low/moderately active smokers and nonsmokers than for highly active nonsmokers. The association between physical activity and the prevalence and incidence of depressive symptoms is not significantly modified by smoking status.

Smoking prevalence in US birth cohorts: the influence of gender and education.

OBJECTIVES: To assess long-term trends in cigarette smoking according to the combined influence of sex and education, this study examined smoking prevalence in successive US birth cohorts. METHODS: Data from nationally representative surveys were examined to assess smoking prevalence for six successive 10-year birth cohorts stratified by race or ethnicity, sex, and educational attainment. RESULTS: Substantial declines in smoking prevalence were found among men who had a high school education or more, regardless of race or ethnicity, and slight declines among women of the same educational background were revealed. However, little change was found in smoking prevalence among men of all race/ethnic groups with less than a high school education, and large increases were found among women with the same years of schooling, especially if they were White or African American. CONCLUSIONS: These data suggest that persons of low educational attainment have yet to benefit from policies and education about the health consequences of cigarette smoking.

Depression and smoking initiation among US Latinos.

We assessed the relationship between depression and smoking initiation among people of Mexican, Puerto Rican and Cuban ancestry residing in specific geographic areas of the United States. Survey data were examined to calculate incidence of smoking initiation and prevalences and odds ratios for ever smoking by presence of depressed mood, a history of major depression or both conditions. Depressed mood, a history of major depression or both conditions were associated with smoking initiation risks during childhood, adolescence and young adulthood. These findings suggest that the relationship between depressive states and smoking initiation is established early in life. More definitive studies are needed to confirm these findings.

Anabolic-steroid use, strength training, and multiple drug use among adolescents in the United States.

OBJECTIVE: This study examined the relationships between anabolic-steroid use and the use of other drugs, sports participation, strength training, and school performance among a nationally representative sample of US high school students. DESIGN: Randomized survey data from the 1991 Centers for Disease Control and Prevention Youth Risk Behavior Survey. SETTING: Public and private schools in the 50 United States and District of Columbia. PATIENTS: A total of 12,272 9th through 12th grade students. MAIN OUTCOME MEASURED: Prevalence of anabolic-steroid use. RESULTS: The frequency of anabolic-steroid use was significantly associated with the frequency of use of cocaine, the use of other drugs such as amphetamines and heroin, tobacco smoking, and alcohol use. The weighted prevalences of anabolic-steroid use were higher among male (4.08%) than female students (1.2%). Students living in the South (3.46%) reported higher prevalences than students in the Midwest (3.0%), West (2.02%), or Northeast (1.71%). Students with self-perceived below-average academic performances (5.10%) and students reporting injected drug use also reported higher anabolic-steroid use (51.57%). Based on a multiple logistic regression, the following variables were found to be significant predictors of anabolic-steroid use: injectable drug use (odds ratio [OR], 17.86), use of other drugs (OR, 4.19), male gender (OR, 2.79), alcohol use (OR, 1.38), and strength training (OR, 1.73). The variables that were significantly associated with anabolic-steroid use varied by gender and by region of the country. CONCLUSION: These data suggest that adolescent anabolic-steroid users in this country are more likely to engage in strength training, injected drug use, and the use of multiple drugs, even after controlling for sports participation and poorer academic performance. These data confirm previous findings of an association between multiple drug use and anabolic-steroid use. Also, engaging in strength-training exercises continued to be associated with anabolic-steroid use after controlling for drug use and other predictors.

Patterns of alcohol use and the risk of drinking and driving among US high school students.

Approximately one third of deaths among persons aged 15 to 24 years are the result of motor vehicle-related crashes. Data from a national sample of US high school students were used to assess patterns of alcohol use among adolescents in relation to the risk of drinking and driving. Prevalence and odds ratios were calculated for drinking and driving associated with patterns of alcohol use. Drinking and driving increased with increasing frequency of alcohol use and binge drinking and when alcohol was used in addition to other drugs. Efforts to reduce drinking and driving among adolescents should address underage drinking that is frequent or heavy.