Nutrient and Fiber Intake and Risk of Renal Cell Carcinoma

This study examines the association between nutrient and fiber intake and the risk of renal cell carcinoma (RCC). Between 1994 and 1997 in 8 Canadian provinces, mailed questionnaires were completed by 1,138 incident, histologically confirmed cases of RCC and 5,039 population controls. Measurement included information on socioeconomic status, lifestyle habits, and diet. A 69-item food frequency questionnaire provided data on eating habits 2 yr before data collection. Odds ratios (ORs) and 95% confidence intervals were derived through unconditional logistic regression. Intakes of total fat, saturated fat, monounsaturated fat, trans-fat, and cholesterol were associated with the risk of RCC; the ORs for the highest vs. the lowest quartile were 1.67, 1.53 and 1.46, 1.31, and 1.48, respectively. The positive association was apparently stronger in women, overweight or obese, and never smokers. Sucrose was related to the risk of RCC. High fiber intake was inversely associated with RCC risk. No association was found with intake of total protein and polyunsaturated fat, n-3 and n-6 polyunsaturated fatty acids, and total carbohydrates. The results were consistent across strata of sex, tobacco, and BMI. The findings suggest that a diet low in fats and cholesterol and rich in fiber could favorably affect the risk of RCC.     

High immunogenic potential of p53 mRNA-transfected dendritic cells in patients with primary breast cancer

As pre-existent immunity might be a reflection of an emerging anticancer response, the demonstration of spontaneous T-cell responses against tumor associated antigens (TAAs) in cancer patients may be beneficial before clinical development of dendritic cell (DC)-based cancer vaccines, because it will help to identify likely responders to TAAs among patients who qualify and may benefit from this form of immune therapy. This study aimed to determine pre-existent T-cell reactivity against the tumor suppressor protein p53 in breast cancer patients (BCP) at the time point of primary diagnosis. After a short-term stimulation with autologous wt p53 mRNA-transfected DCs, IFN-γ enzyme-linked immunosorbent spot (ELISPOT) analysis revealed p53-reactive T cells in the peripheral blood of more than 40% (15 of 36) of the tested patients. Both CD4⁺ and CD8⁺ p53-specific T cells secreted IFN-γ after stimulation with p53-transfected DCs. Interestingly, more than 72% (13 of 18) of patients with high p53 (p53^high) expression in tumors were able to mount a p53-specific IFN-γ T-cell response, in contrast to only 10% (1 of 10) of healthy donors and 11% (2 of 18) of patients with low or absent p53 (p53^low) expression in tumors. Furthermore, significantly higher secretion of IL-2 was detected in peripheral blood mononuclear cells after stimulation with p53-transfected DCs from patients with p53^high tumor expression compared to patients with p53^low tumor expression, whereas secretion of IL-10 was predominant in the latter group. The high frequency of spontaneous wt p53-reactive T cells detected in the peripheral blood of primary BCP with accumulation of p53 in tumor provides a rationale to consider DCs transfected with mRNA encoding wt p53 for clinical investigation in these patients.     

Coste económico del paciente asmático en Espa?a (estudio AsmaCost)

ObjectiveThis analysis of the cost of asthma in Spain includes both direct health care costs and indirect costs arising from illness.Patients and MethodsProspective, 12-month observational cohort study of adult patients with asthma diagnosed according to the guidelines of the Global Initiative for Asthma (GINA) and the adapted Spanish criteria (GEMA). We recorded information on health care resources utilized (medications, medical visits, emergency care, hospital admissions, and tests) and indirect costs (patient travel or transfer costs and workdays lost).ResultsA total of 627 patients throughout Spain were studied. Of these, 21.2% had intermittent asthma, 24.6% mild asthma, 27.6% moderate asthma, and 26.6% severe asthma. The total societal cost of asthma (including indirect costs) was €1726 (95% confidence interval [CI], €1314–€2154) per patient annually. Indirect costs accounted for 11.2% of the total. The cost to the National Health Service was €1533 (95% CI, €1133–€1946) per patient annually. The cost of asthma was higher for patients older than 65 years (€2079) and for those with more severe disease (€959 for intermittent asthma; €1598, mild asthma; €1553, moderate asthma; and €2635 severe asthma). Based on these findings, the total annual cost of asthma in Spain is estimated to be €1480 million (95% CI, €382–€2565 million) for patients with demonstrated bronchial hyperreactivity and €3022 million (95% CI, €2472–€3535 million) for patients diagnosed based on symptoms alone.ConclusionsThe average annual cost of asthma in adults in Spain comes to €1726 per patient, considering both direct and indirect costs. The average annual cost per patient to the National Health Service is €1533.     

IL13 variants are associated with total serum IgE and early sensitization to food allergens in children with atopic dermatitis

Increased total and specific serum immunoglobulin E (IgE) levels are common characteristics of atopic diseases and their basal production is proposed to be under strong genetic control. Interleukin 13 (IL13) variants have been consistently associated with total serum IgE levels in white populations with a strongest association in non‐atopics. The aim of this study was to test the IL13 p.R130Q and c.1‐1111C>T variants in children with atopic dermatitis (AD) for associations with total serum IgE and early sensitization to common food and inhalant allergens and with asthma. We included 453 children with AD [participants of the Early Treatment of the Atopic Child (ETAC) study] that were followed from the age of 12–24 months for 3 yr. Total and specific IgE were determined at four time points. We genotyped the IL13 p.R130Q and c.1‐1111C>T variants by melting curve analysis. In children up to 4 yr of age, the 130Q allele was related to slightly higher total IgE levels compared to heterozygotes and 130R homozygotes. More importantly, both IL13 variants were significantly associated with sensitization to food allergens, with most significant results for sensitization to egg (p = 0.0001). Although early sensitization to hen’s egg represents a strong risk factor for subsequent sensitization to inhalant allergens and asthma, the investigated IL13 variants were not associated with these phenotypes at the age of 48–60 months. In summary IL13 variants contribute to elevated levels of total serum IgE in young atopic children and are strongly associated with sensitization to food allergens, particularly to hen’s egg. These findings suggest that IL13 variants play a major role not only in non‐cognate but also in allergen specific IgE synthesis.     

Maternal country of birth and previous pregnancies are associated with breast milk characteristics

Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-β1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.     

Intestinal flora in very low-birth weight infants

Aim:  To study the early faecal microbiota in very low-birth weight infants (VLBW, <1500 g), possible associations between faecal microbiota and faecal calprotectin (f-calprotectin) and to describe the faecal microbiota in cases with necrotizing enterocolitis (NEC) before diagnosis.
Methods:  Stool samples from the first weeks of life were analysed in 48 VLBW infants. Bacterial cultures were performed and f-calprotectin concentrations were measured. In three NEC cases, cultures were performed on stool samples obtained before diagnosis.
Results:  Bifidobacteria and lactobacilli were often identified in the first stool sample, 55% and 71% of cases, respectively within the first week of life. A positive correlation between lactic acid bacteria (LAB) and volume of enteral feed was found. Other bacteria often identified were Escherichia coli , Enterococcus and Staphyloccus sp. F-calprotectin was not associated with any bacterial species. All NEC cases had an early colonization of LAB. Prior to onset of disease, all cases had a high colonization of non- E. coli Gram-negative species.
Conclusion:  In contrast to the previous studies in VLBW infants, we found an early colonization with LAB. We speculate that this may be due to early feeding of non-pasteurized breast milk.     

Anger Mediates the Relation Between Violence Exposure and Violence Perpetration in Incarcerated Boys

Youth who are exposed to violence are more likely to perpetrate violence. Incarcerated youth are a special population that is at a significantly greater risk for violent offending because of their relatively greater rates of violence exposure. Two important outcomes of violence exposure that may help explain its link with violence perpetration are posttraumatic stress disorder and problematic anger. The primary aim of the current study is to examine whether these important risk factors mediate the relation between two types of violence exposure (i.e., witnessing and victimization) and various types of violence perpetration in a sample of 373 incarcerated male adolescent offenders. A second aim is to test whether another well-established correlate of violence in youth, callous-unemotional (CU) traits (lack of empathy, guilt), adds unique variance beyond violence exposure, anger, and PTSD symptomatology. Findings suggest that anger is a robust predictor of violence and appears to at least partially act as the mechanism through which violence exposure is linked with violence perpetration. CU traits also contribute unique variance, beyond the significant effect of anger, to the statistical prediction of community, but not institutional, violence.     

Clinically detectable copy number variations in a Canadian catchment population of schizophrenia

Copy number variation (CNV) is a highly topical area of research in schizophrenia, but the clinical relevance is uncertain and the translation to clinical practice is under-studied. There is a paucity of research involving truly community-based samples of schizophrenia and widely available laboratory techniques. Our objective was to determine the prevalence of clinically detectable CNVs in a community sample of schizophrenia, while mimicking typical clinical practice conditions. We used a brief clinical screening protocol for developmental features in adults with schizophrenia for identifying individuals with 22q11.2 deletions and karyotypically detectable chromosomal anomalies in 204 consecutive patients with schizophrenia from a single Canadian catchment area. Twenty-seven (13.2%) subjects met clinical criteria for a possible syndrome, and 26 of these individuals received clinical genetic testing. Five of these, representing 2.5% of the total sample (95% CI: 0.3%-4.6%), including two of ten patients with mental retardation, had clinically detectable anomalies: two 22q11.2 deletions (1.0%), one 47, XYY, and two other novel CNVs - an 8p23.3-p23.1 deletion and a de novo 19p13.3-p13.2 duplication. The results support the utility of screening and genetic testing to identify genetic syndromes in adults with schizophrenia in clinical practice. Identifying large, rare CNVs (particularly 22q11.2 deletions) can lead to significant changes in management, follow-up, and genetic counselling that are helpful to the patient, family, and clinicians.     

Defining Laterality of the Descending Thoracic Aorta in a 4‐Chamber View of the Heart

Objective. Right descending aortas have been correlated with an increased risk of congenital heart disease. Nevertheless, the aortic position remains a largely overlooked diagnostic tool in second‐trimester sonography because no formal system for assessing the position exists. By developing a method of assigning the position of the aorta relative to the thoracic midline, diagnostic use of the descending aorta's position might be implemented more easily. Methods. The method of assessing the position relative to the midline was tested by comparing the analysis of 2 independent observers, who showed a 94.4% concordance rate. Results. Comparison of the percentages of aortic positions between the gestational ages (GAs) of 18 and 21 weeks showed no significant correlation between the aortic position and GA. Conclusions. We suggest simply paying attention to the aortic position in an already standard view. The extra effort is minimal, and it has the potential to improve the diagnostic accuracy of the 4‐chamber view.     

Mortality in Autism: A Prospective Longitudinal Community-Based Study

The purposes of the present study were to establish the mortality rate in a representative group of individuals (n = 120) born in the years 1962–1984, diagnosed with autism/atypical autism in childhood and followed up at young adult age (≥18 years of age), and examine the risk factors and causes of death. The study group, which constituted a total population sample of children with these diagnoses, were followed up in Swedish registers. Nine (7.5%) of the 120 individuals with autism had died at the time of follow-up, a rate 5.6 times higher than expected. The mortality rate was significantly higher among the females. Associated medical disorders (including epilepsy with cognitive impairment) and accidents accounted for most of the deaths, and it was not possible to determine whether autism “per se” actually carries an increased mortality risk.