Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations

Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case–control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11–0.15) and cancer cases (0.14, 95% CI=0.12–0.16) compared with controls (0.11, 95% CI=0.10–0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97–1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05–1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population.     

Sucrose synthase activity in the sus1/sus2/sus3/sus4 Arabidopsis mutant is sufficient to support normal cellulose and starch production

Sucrose synthase (SUS) catalyzes the reversible conversion of sucrose and a nucleoside diphosphate into the corresponding nucleoside diphosphate-glucose and fructose. In Arabidopsis, a multigene family encodes six SUS (SUS1-6) isoforms. The involvement of SUS in the synthesis of UDP-glucose and ADP-glucose linked to Arabidopsis cellulose and starch biosynthesis, respectively, has been questioned by Barratt et al. [(2009) Proc Natl Acad Sci USA 106:13124-13129], who showed that (i) SUS activity in wild type (WT) leaves is too low to account for normal rate of starch accumulation in Arabidopsis, and (ii) different organs of the sus1/sus2/sus3/sus4 SUS mutant impaired in SUS activity accumulate WT levels of ADP-glucose, UDP-glucose, cellulose and starch. However, these authors assayed SUS activity under unfavorable pH conditions for the reaction. By using favorable pH conditions for assaying SUS activity, in this work we show that SUS activity in the cleavage direction is sufficient to support normal rate of starch accumulation in WT leaves. We also demonstrate that sus1/sus2/sus3/sus4 leaves display WT SUS5 and SUS6 expression levels, whereas leaves of the sus5/sus6 mutant display WT SUS1-4 expression levels. Furthermore, we show that SUS activity in leaves and stems of the sus1/sus2/sus3/sus4 and sus5/sus6 plants is ～85% of that of WT leaves, which can support normal cellulose and starch biosynthesis. The overall data disprove Barratt et al. (2009) claims, and are consistent with the possible involvement of SUS in cellulose and starch biosynthesis in Arabidopsis.     

Prognostic factors and survival in a prospective cohort of patients with high-grade glioma treated with carmustine wafers or temozolomide on an intention-to-treat basis

Background  

Patients with high-grade glioma can be treated with carmustine wafers or following the Stupp protocol. As far as we are aware, no scientific evidence has been published comparing the two treatments. The primary objective of this study was to analyse the survival of groups of patients with each of these treatment modalities. The secondary objective was to assess the influence of the usual prognostic factors on the patients in our hospital.     

Evaluation of Phi29-based whole-genome amplification for microarray-based comparative genomic hybridisation

For the optimal performance of high throughput genomic technologies sufficient yields of high-quality DNA are crucial. Following microdissection, most samples fail to produce sufficient quantities of DNA for genome-wide experiments. Various PCR-based amplification methods have been used, but these usually produce nonuniform representations of the genome. Bacteriophage Phi29 DNA polymerase random-primed DNA amplification is based on isothermal multiple displacement amplification. We sought to define the genome representation of this method in a bacterial artificial chromosome microarray comparative genomic hybridisation (aCGH) platform. Test genomic female DNA was amplified using Phi29 amplification at four different starting concentrations (0.5, 5, 10 and 50 ng). These products were combined with unamplified and amplified genomic female DNA as reference. In addition, 50 ng of DNA from five microdissected breast cancer frozen samples, were amplified using the same method. Three combinations were performed: unamplified test with unamplified reference, amplified test with unamplified reference and both amplified tumour and reference DNA. aCGH was performed with an in-house 16 K BAC platform (a resolution of approximately 100 Kb). Pearson's correlation tests and hierarchical clustering were performed to compare the profiles obtained. aCGH profiles obtained with amplified test and unamplified reference female genomic DNA showed copy number biases throughout the genome. These biases were more conspicuous with smaller amounts of starting material and mapped to regions of known copy number polymorphisms. When similar concentrations of test and reference DNA were amplified, the biases were significantly reduced, rendering accurate profiles. For the tumours, representative profiles were obtained when both test and reference DNA were amplified. Phi29 amplification induces copy number biases and unamplified material remains the gold standard for copy number analysis. For accurate results using Phi29 amplification, samples subjected to aCGH analysis should be combined with reference DNA amplified with the same method, using similar amounts of starting template.     

Gender differences in negative mood states in secondary school students: health survey in Catalonia (Spain)

Objective

To determine the prevalence of negative mood states in adolescents according to gender, to analyze variability among schools, and to evaluate the associated factors.

Methods

A cross-sectional study with a cluster design was carried out. We administered the High-school students health survey to a sample of 9,340 students (aged 14-16 years) in the third and fourth year of Compulsory Secondary Education in Catalonia, Spain, during the 2005-6 academic year. The main outcome measure was evidence of a negative mood state. A multilevel logistic regression model stratified by gender was used to identify the factors associated with negative mood states and to determine variability among distinct schools.

Results

Approximately 19% of adolescents reported evidence of a negative mood state, with a higher prevalence in girls (25%). The most significant factors associated with negative mood states were “use of tranquilizers” and “having eating disorders” in girls and “not exercising” and “poor self-perception of health status” in boys. In both genders, variability was found among schools in the prevalence of negative mood states (girls: variance = 0.078; p <0.001; boys: variance = 0.079; p = 0.012).

Conclusions

The prevalence of negative mood states in adolescent boys and girls was high. Differences were observed between genders in the factors related to these health states. The variability observed in the prevalence of negative mood states among distinct schools could not be explained by the study variables. Our results emphasize the association between the use of tranquilizers and negative mood states.     

Review and update of the prognostic factors in lung metastasis surgery

Introduction

Since the International Registry of Lung Metastases established the factors that determine survival after performing lung metastasectomy in 1997, numerous studies have attempted to determine these prognostic factors of survival. Our objective has been to analyse the mortality, survival and disease-free survival lung metastasis surgery by studying the different variables that determine them.

Patients and method

All patients subjected to surgery for lung metastasectomy between 1998 and 2008 were included in this study. The Kaplan-Meier and log-rank tests were performed, as well as a Cox regression using multivariate analysis.

Results

A total of 178 lung metastases were removed in 146 patients during this period. The mean age was 62.22 years (median 63 years) and 64.6% were males. There were 2 cases (1.1%) of mortality and the incidence of complications was 5.02% (9 cases). The overall survival was 67.75 months with a 3 and 5 year survival of 67.4% and 52.4%, respectively. The variables that showed statistical significance in the multivariate analysis were: age disease free interval, number of nodules and size of nodules. The “state of the margins” variable was almost significant (P = .054).

Discussion

To have only one metastasis and it is less than 1 cm, a long disease free interval, and a resection with free margins, are the most favourable prognostic factors after resection of lung metastasis.     

Effectiveness and Safety of Air-Filled Balloon Heliosphere BAG® in 82 Consecutive Obese Patients

Background

Intragastric balloon is a widely used technique to treat obesity that is considered to be more efficient than conservative treatment before bariatric surgery. To describe air-filled balloon (Heliosphere BAG®) effectiveness [absolute weight loss, body mass index (BMI) loss, percentage of body weight loss (BWL), percentage of excess weight loss (EWL)] and complications 6 months after its insertion.

Methods

Eighty-four consecutive intragastric balloons were placed endoscopically. Individualized nutritional counseling was given. The follow-up was carried out in an endocrinology outpatient clinic. Due to the weight or height data missed in two cases, only 82 patients were included in this report, 63 women with a mean age 39 years (SD, 11.1); mean BMI, 39.1 kg/m² (SD, 5.8). The median follow-up was 182 days.

Results

The mean weight loss and BMI loss were 14.5 kg (SD, 8.2); and 5.3 kg/m² (SD, 2.8), respectively (for difference, p?10%. The percentage of EWL reached 33.2% (SD, 19.2). After adjusting by sex and initial BMI, absolute weight loss (p?=?0.033), BMI loss (p?=?0.034), percentage of BWL (p?=?0.034), and percentage of EWL (p?=?0.034) were inversely related to age. Absolute weight loss and BMI loss were greater in higher initial BMI, but the percentage of EWL was lower. Two spontaneous deflations occurred (3%), but only one surgical early removal (1.2%) was required. Nausea and vomiting developed in 7.4% of the patients during the first week.

Conclusions

Air-filled Heliosphere BAG® has been effective in achieving a relevant loss of body weight.