Added Value of Deep Sequencing Relative to Population Sequencing in Heavily Pre-Treated HIV-1-Infected Subjects.

OBJECTIVE: To explore the potential of deep HIV-1 sequencing for adding clinically relevant information relative to viral population sequencing in heavily pre-treated HIV-1-infected subjects. METHODS: In a proof-of-concept study, deep sequencing was compared to population sequencing in HIV-1-infected individuals with previous triple-class virological failure who also developed virologic failure to deep salvage therapy including, at least, darunavir, tipranavir, etravirine or raltegravir. Viral susceptibility was inferred before salvage therapy initiation and at virological failure using deep and population sequencing genotypes interpreted with the HIVdb, Rega and ANRS algorithms. The threshold level for mutant detection with deep sequencing was 1%. RESULTS: 7 subjects with previous exposure to a median of 15 antiretrovirals during a median of 13 years were included. Deep salvage therapy included darunavir, tipranavir, etravirine or raltegravir in 4, 2, 2 and 5 subjects, respectively. Self-reported treatment adherence was adequate in 4 and partial in 2; one individual underwent treatment interruption during follow-up. Deep sequencing detected all mutations found by population sequencing and identified additional resistance mutations in all but one individual, predominantly after virological failure to deep salvage therapy. Additional genotypic information led to consistent decreases in predicted susceptibility to etravirine, efavirenz, nucleoside reverse transcriptase inhibitors and indinavir in 2, 1, 2 and 1 subject, respectively. Deep sequencing data did not consistently modify the susceptibility predictions achieved with population sequencing for darunavir, tipranavir or raltegravir. CONCLUSIONS: In this subset of heavily pre-treated individuals, deep sequencing improved the assessment of genotypic resistance to etravirine, but did not consistently provide additional information on darunavir, tipranavir or raltegravir susceptibility. These data may inform the design of future studies addressing the clinical value of minority drug-resistant variants in treatment-experienced subjects.

The influence of individual, social and physical environment factors on physical activity in the adult population in Andalusia, Spain

A person’s physical and social environment is considered as an influencing factor in terms of rates of engagement in physical activity. This study analyses the influence of socio-demographic, physical and social environmental factors on physical activity reported in the adult population in Andalusia. This is a cross-sectional study using data collected in the Andalusia Health Survey in 1999 and 2003. In addition to the influence of the individual’s characteristics, if there are no green spaces in the neighbourhood it is less likely that men and women will take exercise (OR = 1.26; 95% CI = 1.13, 1.41). Likewise, a higher local illiteracy rate also has a negative influence on exercise habits in men (OR = 1.39; 95% CI = 1.21, 1.59) and in women (OR = 1.22; 95% CI = 1.07, 1.40). Physical activity is influenced by individuals’ characteristics as well as by their social and physical environment, the most disadvantaged groups are less likely to engage in physical activity

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35–64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 μg/d respectively. Approximately, 32 % of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.

Central corneal thickness, intraocular pressure, and degree of myopia in an adult myopic population aged 20 to 40 years in southeast Spain: determination and relationships

Objective: To determine the values of, and study the relationships among, central corneal thickness (CCT), intraocular pressure (IOP), and degree of myopia (DM) in an adult myopic population aged 20 to 40 years in Almeria (southeast Spain). To our knowledge this is first study of this kind in this region. Methods: An observational, descriptive, cross-sectional study was done in which a sample of 310 myopic patients (620 eyes) aged 20 to 40 years was selected by gender- and age-stratified sampling, which was proportionally fixed to the size of the population strata for which a 20% prevalence of myopia, 5% epsilon, and a 95% confidence interval were hypothesized. We studied IOP, CCT, and DM and their relationships by calculating the mean, standard deviation, 95% confidence interval for the mean, median, Fisher’s asymmetry coefficient, range (maximum, minimum), and the Brown-Forsythe’s robust test for each variable (IOP, CCT, and DM). Results: In the adult myopic population of Almeria aged 20 to 40 years (mean of 29.8), the mean overall CCT was 550.12 μm. The corneas of men were thicker than those of women (P = 0.014). CCT was stable as no significant differences were seen in the 20- to 40-year-old subjects’ CCT values. The mean overall IOP was 13.60 mmHg. Men had a higher IOP than women (P = 0.002). Subjects over 30 years (13.83) had a higher IOP than those under 30 (13.38) (P = 0.04). The mean overall DM was −4.18 diopters. Men had less myopia than women (P < 0.001). Myopia was stable in the 20- to 40-year-old study population (P = 0.089). A linear relationship was found between CCT and IOP (R2 = 0.152, P ≤ 0.001). CCT influenced the IOP value by 15.2%. However no linear relationship between DM and IOP, or between CCT and DM, was found. Conclusions: CCT was found to be similar to that reported in other studies in different populations. IOP tends to increase after the age of 30 and is not accounted for by alterations in CCT values.

Functional Variants in NOS1 and NOS2A Are Not Associated with Progressive Hearing Loss in Ménière's Disease in a European Caucasian Population

Hearing loss in Meniere's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, wed genotyped three functional variants of NOS1 (rs41279104,rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets(273 patients in total) and 550 controls. A third cohort of American patients was genotyped as replication cohort for the CCTTT repeat. Neither allele nor genotype frequencies of rs41279104 and rs2682826 were associated with MD, although longer alleles of the cytosine-adenosine microsatellite repeat were marginally significant (corrected p = 0.05) in the Mediterranean cohort but not in a second Galicia cohort. Shorter numbers of the CCTTT repeat in NOS2A were significantly more frequent in Galicia controls (OR = 0.37 [CI, 0.18-0.76], corrected p =0.04), but this finding could not be replicated in Mediterranean or American case-control populations. Meta-analysis did not support an association between CCTTT repeats and risk for MD. Severe hearing loss (>75 dB) was also not associated with any functional variants studied. Functional variants of NOS1 and and NOS2A do not confer susceptibility for MD.

CD209 in inflammatory bowel disease: a case-control study in the Spanish population

BACKGROUND The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The CD209 gene is located in a region linked previously to IBD and a CD209 functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this CD209 variant in IBD susceptibility. METHODS We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using chi2 tests. RESULTS No association between CD209 and UC or CD was observed initially. However, stratification of UC patients by HLA-DR3 status, a strong protective allele, showed that carriage of the CD209_G allele could increase susceptibility in the subgroup of HLA-DR3-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04-3.02, vs. controls). CONCLUSION A functional variant in the CD209 gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in HLA-DR3-positive individuals but further studies are necessary.

Serum phospholipid fatty acid profile and dietary intake in an adult Mediterranean population with cystic fibrosis.

The relative importance of the usual diet in serum phospholipids in subjects with cystic fibrosis (CF) has been poorly studied. To compare the fatty acid profile in serum phospholipids from adult CF subjects with that of healthy subjects, and determine the role of the normal diet in this profile, we studied thirty-seven adult CF subjects with stable pulmonary disease and thirty-seven healthy controls matched for age, sex and nutritional status. A dietary questionnaire was obtained, anthropometric data were recorded, and the fatty acid profile measured by GLC. Compared with the controls, the percentages of myristic, palmitoleic and stearic acids and total MUFA were significantly higher in the CF group, and DHA, linoleic acid, total PUFA and n-6 fatty acids were significantly lower in the CF group. The CF subjects with worse pulmonary function and with pancreatic insufficiency had significantly lower levels of linoleic and n-6 fatty acids. The total energy intake was significantly higher in the CF subjects, although the energy distribution in the CF subjects and the controls was not different for the carbohydrates, lipids and proteins. No differences were detected in fat intake for MUFA (51 (SD 4) v. 52 (SD 4) %) or saturated fatty acids (33.5 (SD 5) v. 31.2 (SD 3.8) %), but the PUFA were slightly lower in the CF subjects (15.4 (SD 4.5) v. 17.4 (SD 4.2) %; P=0.02). The usual dietary intake of fatty acids by adult CF subjects does not appear to explain the difference in the fatty acid profile compared with controls. This suggests an abnormal fatty acid metabolism in CF subjects.

Intake and home use of olive oil or mixed oils in relation to healthy lifestyles in a Mediterranean population. Findings from the prospective Pizarra study.

Discordances exist in epidemiological studies regarding the association between the intake of nutrients and death and disease. We evaluated the social and health profile of persons who consumed olive oil in a prospective population cohort investigation (Pizarra study) with a 6-year follow-up. A food frequency questionnaire and a 7 d quantitative questionnaire were administered to 538 persons. The type of oil used in food preparation was determined by direct measurement of the fatty acids in samples obtained from the kitchens of the participants at baseline and after follow-up for 6 years. The fatty acid composition of the serum phospholipids was used as an endogenous marker of the type of oil consumed. Total fat intake accounted for a mean 40 % of the energy (at baseline and after follow-up). The concordance in intake of MUFA over the study period was high. The fatty acid composition of the serum phospholipids was significantly associated with the type of oil consumed and with fish intake. The concentration of polar compounds and polymers, indicative of degradation, was greater in oils from the kitchens where sunflower oil or refined olive oil was used, in oils used for deep frying and in oils that had been reused for frying five times or more. Consumption of olive oil was directly associated with educational level. Part of the discordance found in epidemiological studies between diet and health may be due to the handling of oils during food preparation. The intake of olive oil is associated with other healthy habits.

Early estimates of the effectiveness of the 2011/12 influenza vaccine in the population targeted for vaccination in Spain, 25 December 2011 to 19 February 2012.

We present early estimates of influenza vaccine effectiveness (VE) in the population targeted for vaccination, during 25 December 2011 to 19 February 2012. The adjusted VE was 55% (95% CI: 3 to 79) against any type of influenza virus and 54% (95% CI: 1 to 79) against influenza A(H3N2) virus. This suggests a moderate protective effect of the vaccine in the targeted population in a late influenza epidemic with limited match between vaccine and circulating strains.

Mitochondrial haplogroups and polymorphisms reveal no association with sporadic prostate cancer in a southern European population.

BACKGROUND It is known that mitochondria play an important role in certain cancers (prostate, renal, breast, or colorectal) and coronary disease. These organelles play an essential role in apoptosis and the production of reactive oxygen species; in addition, mtDNA also reveals the history of populations and ancient human migration. All these events and variations in the mitochondrial genome are thought to cause some cancers, including prostate cancer, and also help us to group individuals into common origin groups. The aim of the present study is to analyze the different haplogroups and variations in the sequence in the mitochondrial genome of a southern European population consisting of subjects affected (n = 239) and non-affected (n = 150) by sporadic prostate cancer. METHODOLOGY AND PRINCIPAL FINDINGS Using primer extension analysis and DNA sequencing, we identified the nine major European haplogroups and CR polymorphisms. The frequencies of the haplogroups did not differ between patients and control cohorts, whereas the CR polymorphism T16356C was significantly higher in patients with PC compared to the controls (p = 0.029). PSA, staging, and Gleason score were associated with none of the nine major European haplogroups. The CR polymorphisms G16129A (p = 0.007) and T16224C (p = 0.022) were significantly associated with Gleason score, whereas T16311C (p = 0.046) was linked with T-stage. CONCLUSIONS AND SIGNIFICANCE Our results do not suggest that mtDNA haplogroups could be involved in sporadic prostate cancer etiology and pathogenesis as previous studies performed in middle Europe population. Although some significant associations have been obtained in studying CR polymorphisms, further studies should be performed to validate these results.

Evaluation of Health-Related Quality of Life according to Carbohydrate Metabolism Status: A Spanish Population-Based Study (Di@bet.es Study)

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12 questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2–2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26–2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

Prevalence of diabetes in a cancer population in a Malaga hospital.

BACKGROUND There are multiple risk factors for cancer, including obesity, sedentary lifestyle, diabetes (DM). Hormon Insulin is a growth factor that promotes cellular differentiation. AIMS The aim of our study is to observe impaired glycaemia in cancer population compared with control. METHODS We studied the prevalence of diabetes (DM) and impaired fasting glycaemia (IFG) in 374 patients with different types of cancer before treatment, by medical records in a Malaga hospital (Spain). We compared the prevalence of basal hyperglycaemia in these patients with general population, within an age range and by gender. RESULTS AND DISCUSSION The prevalence of diabetes was 32.35% in our cancer patients. The comparison depends of age range, and by gender prevalence was: 45-54 years, DM: 40.91% in men cases, versus (vs.) 14.5% in men control (p = 0.005). 55-64 years, IFG: 23.08% in women cases, vs. 5.9% in women control (p = 0.001). 65-74 years, DM: 47.13% in men cases, vs. 25.4% in men control (p = 0.000), and IFG: 23.81% in women cases, vs. 9.5% in women control (p = 0.019). We found a higher prevalence of diabetes in specific types of cancer such as prostate (p < 0.005). Moreover, men had a higher prevalence of diabetes or less diabetes control than women in our cancer sample. CONCLUSIONS We recommend an OGTT (oral glucose tolerance test) for better diagnosis of possible DM in patients with cancer, and an appropriate treatment. It may be an independent risk factor for cancer to have decreased insulin activity, or DM.

Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in Spanish population

SUMMARY The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated. METHODS 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model. RESULTS One polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population. CONCLUSIONS The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians.

Vertebral fractures in patients with inflammatory bowel disease compared with a healthy population: a prospective case-control study.

BACKGROUND A prospective study was performed to compare the prevalence of morphometric vertebral fractures (MVF) between patients with inflammatory bowel disease (IBD) and healthy subjects and to identify predictive factors of fracture. METHODS A total of 107 patients with IBD (53 with Crohn's disease and 54 with ulcerative colitis) and 51 healthy subjects participated in the study. Information about anthropometric parameters, toxins, previous fractures, and parameters related to this disease were evaluated. The index of vertebral deformity, bone mass density (BMD), and biochemical parameters were calculated. RESULTS A total of 72 fractures were detected in 38.32% of patients with IBD, and 10 fractures were detected in 13.73% of healthy subjects; the risk of fracture in patients with IBD was higher than that in control subjects (OR, 4.03; 95% CI, 1.652-9.847; p < 0.002). We found no correlation between fracture and BMD in patients with IBD (lumbar spine, r = -0.103, p = 0.17 and femoral neck, r = -0.138, p = 0.07). Corticosteroid treatment was not associated with prevalent vertebral fractures nor with taking corticosteroids (r = 0.135, p = 0.14) or the duration for which they were taken (r = 0.08, p = 0.38), whereas this relationship was present in the controls (r = -0.365, p = 0.01). In the multivariate analysis, none of the measured parameters were significantly predictive of fracture, only to manifested IBD. Hypovitaminosis D was observed in 55.14% of patients with IBD. CONCLUSIONS The prevalence of morphometric vertebral fractures is higher in patients with IBD than in the healthy population, without association with BMD or corticoid treatment. Simply having IBD was proven to be a predictive factor of fracture. We observed a high incidence of hypovitaminosis D in patients with IBD.

Sensitization to Anisakis simplex species in the population of northern Morocco.

OBJECTIVE To investigate sensitization to third-stage Anisakis simplex larvae in a randomly selected population in northern Morocco. METHODS We studied sera obtained from clinical analysis laboratories in Tangier and Tetuouan and from fishermen at Tangier port. The age of the study population ranged from 6 to 83 years. ImmunoCAP and immunoblotting techniques were used to determine total and specific immunoglobulin (Ig) E values and the chi2 and Fisher exact tests were applied to analyze relationships between study variables. RESULTS A seroprevalence of 5.1% was found, with a higher percentage of positive sera in the 31-to-43-year age group. Sensitization was not significantly associated with the origin, sex, occupation, or age of the individuals studied. In sera positive by InmunoCAP, immunoblotting studies detected numerous bands of between 7 kDa and >209 kDa, with a predominance of bands in the approximately 20-kDa to 24-kDa range. CONCLUSIONS Although no cases of human anisakiasis have been reported in Morocco to date, part of a randomly selected population in Northern Morocco shows sensitization to A simplex proteins.