Combination of phenotype and polygenic risk score in breast cancer risk evaluation in the Spanish population: a case -control study.

BACKGROUND: In recent years, the identification of genetic and phenotypic biomarkers of cancer for prevention, early diagnosis and patient stratification has been a main objective of research in the field. Different multivariable models that use biomarkers have been proposed for the evaluation of individual risk of developing breast cancer. METHODS: This is a case control study based on a population-based cohort. We describe and evaluate a multivariable model that incorporates 92 Single-nucleotide polymorphisms (SNPs) (Supplementary Table S1) and five different phenotypic variables and which was employed in a Spanish population of 642 healthy women and 455 breast cancer patients. RESULTS: Our model allowed us to stratify two groups: high and low risk of developing breast cancer. The 9th decile included 1% of controls vs 9% of cases, with an odds ratio (OR) of 12.9 and a p-value of 3.43E-07. The first decile presented an inverse proportion: 1% of cases and 9% of controls, with an OR of 0.097 and a p-value of 1.86E-08. CONCLUSIONS: These results indicate the capacity of our multivariable model to stratify women according to their risk of developing breast cancer. The major limitation of our analysis is the small cohort size. However, despite the limitations, the results of our analysis provide proof of concept in a poorly studied population, and opens up the possibility of using this method in the routine screening of the Spanish population.

Dark Matter Search Results from the PICO-60 C_{3}F_{8} Bubble Chamber.

New results are reported from the operation of the PICO-60 dark matter detector, a bubble chamber filled with 52 kg of C_{3}F_{8} located in the SNOLAB underground laboratory. As in previous PICO bubble chambers, PICO-60 C_{3}F_{8} exhibits excellent electron recoil and alpha decay rejection, and the observed multiple-scattering neutron rate indicates a single-scatter neutron background of less than one event per month. A blind analysis of an efficiency-corrected 1167-kg day exposure at a 3.3-keV thermodynamic threshold reveals no single-scattering nuclear recoil candidates, consistent with the predicted background. These results set the most stringent direct-detection constraint to date on the weakly interacting massive particle (WIMP)-proton spin-dependent cross section at 3.4×10^{-41} cm^{2} for a 30-GeV c^{-2} WIMP, more than 1 order of magnitude improvement from previous PICO results.

Dark Matter Search Results from the PICO-2L C3F8 Bubble Chamber.

New data are reported from the operation of a 2 liter C3F8 bubble chamber in the SNOLAB underground laboratory, with a total exposure of 211.5 kg days at four different energy thresholds below 10 keV. These data show that C3F8 provides excellent electron-recoil and alpha rejection capabilities at very low thresholds. The chamber exhibits an electron-recoil sensitivity of <3.5×10(-10) and an alpha rejection factor of >98.2%. These data also include the first observation of a dependence of acoustic signal on alpha energy. Twelve single nuclear recoil event candidates were observed during the run. The candidate events exhibit timing characteristics that are not consistent with the hypothesis of a uniform time distribution, and no evidence for a dark matter signal is claimed. These data provide the most sensitive direct detection constraints on WIMP-proton spin-dependent scattering to date, with significant sensitivity at low WIMP masses for spin-independent WIMP-nucleon scattering.

Resistance to benzalkonium chloride, peracetic acid and nisin during formation of mature biofilms by Listeria monocytogenes.

Increase of resistance to the application of benzalkonium chloride (BAC), peracetic acid (PA) and nisin during biofilm formation at 25 °C by three strains of Listeria monocytogenes (CECT 911, CECT 4032, CECT 5873 and BAC-adapted CECT 5873) in different scenarios was compared. For this purpose, resistance after 4 and 11-days of biofilm formation was quantified in terms of lethal dose 90% values (LD(90)), determined according with a dose-response logistic mathematical model. Microscopic analyses after 4 and 11-days of L. monocytogenes biofilm formation were also carried out. Results demonstrated a relation between the microscopic structure and the resistance to the assayed biocides in matured biofilms. The worst cases being biofilms formed by the strain 4032 (in both stainless steel and polypropylene), which showed a complex "cloud-type" structure that correlates with the highest resistance of this strain against the three biocides during biofilm maturation. However, that increase in resistance and complexity appeared not to be dependent on initial bacterial adherence, thus indicating mature biofilms rather than planctonic cells or early-stage biofilms must be considered when disinfection protocols have to be optimized. PA seemed to be the most effective of the three disinfectants used for biofilms. We hypothesized both its high oxidizing capacity and low molecular size could suppose an advantage for its penetration inside the biofilm. We also demonstrated that organic material counteract with the biocides, thus indicating the importance of improving cleaning protocols. Finally, by comparing strains 5873 and 5873 adapted to BAC, several adaptative cross-responses between BAC and nisin or peracetic acid were identified.

Multidisciplinary approach and multimodal therapy in resected pancreatic cancer. Observational study.

OBJECTIVE: Analysis and evaluation of a multidisciplinary approach, postoperative results and survival of a group of patients with resected pancreatic cancer after a multimodal therapy. DESIGN: DESCRIPTIVE, prospective and observational study. PATIENTS: Between January 2004 and December 2004, 124 patients with pancreatic cancer were evaluated. In 30 patients pancreatic resection was performed, and they are the object of this study. Results of preoperative evaluation, postoperative morbidity and mortality, and long term survival were studied. RESULTS: Diagnostic evaluation was completed in ambulatory basis in 20% of the patients. In 63% of cases, admission was done in the same day of surgery. In 3 patients (9%), tumor resection was not achieved, therefore, concordance between radiological and surgical resectability rate was 91%. Resectability rate was 24.1%. Surgical Mortality was 3.3%, with a global morbidity rate of 56.6%. Survival at one, two, three and, four years was 76.2%, 56.3%, 43%, y 27.3% respectively. CONCLUSIONS: Technological development and coordination of efforts in multidisciplinary teams offer an accurate evaluation of tumor involvement, and may reduce the number of laparotomies without tumor resection. The application of a systematic and generalized multimodal treatment in pancreatic cancer is progressively showing a tendency of progressive increase in resectability and survival rates in pancreatic cancer.

Effects of mussel processing soils on the adherence of Listeria monocytogenes to polypropylene and stainless steel.

A comparative study of adhesion kinetics of L. monocytogenes (strains CECT 5873, CECT 936, CECT 911, and CECT 4032, representing serotypes 1/2a, 1/2b, 1/2c, and 4b, respectively) to polypropylene (PP) and stainless steel (SS) under two surface contamination conditions in plants processing cooked mussel was carried out. The conditions were either (i) contamination of clean surfaces with mussel cooking juice carrying L. monocytogenes or (ii) contamination with L. monocytogenes after soiling with mussel cooking juice, i.e., conditioning film (CF). The kinetics of adhesion were successfully described by a modified logistic model. Adhesion to PP was higher than to SS in all strains, except CECT 5873. Adhesion was initially higher in the presence of CF, but numbers of adherent cells decreased sharply in the late phase of study in three of eight cases as a result of cell detachment. Combinations of strain, surface material, and surface conditioning where adhesion was most enhanced were defined as the worst-case scenarios (CECT 911-PP, 4032-PP-CF, 5873-SS, and 4032-SS-CF). Subsequently, adhesion in worst-case scenarios was compared with a similar contamination event taking place in plants processing live mussels, using intervalvar water of mussel as a food residue matrix. Adhesion levels were higher in intervalvar water than in cooking juice, especially in both cases with no CF; this was attributed to more space available for adhesion or to physicochemical conditions enhancing cells to adhere.

Application of nisin and pediocin against resistance and germination of Bacillus spores in sous vide products.

Sous vide and other mild preservation techniques are increasingly demanded by consumers. However, spores often will survive in minimally processed foods, causing both spoilage and safety problems. The main objective of the present work was to solve an industrial spoilage problem associated with two sous vide products: mushrooms and shellfish salad. Bacillus subtilis and Bacillus licheniformis predominated as the most heat-resistant organisms isolated from mushrooms and shellfish salad, respectively. The combined effects of nisin and pediocin against resistance and germination of both Bacillus species were described by empirical equations. Whereas nisin was more effective for decreasing thermal resistance of B. subtilis spores, pediocin was more effective against B. licheniformis. However, a significant positive interaction between both biopeptides for decreasing the proportion of vegetative cells resulting from thermoresistant spores was demonstrated in later experiments, thus indicating the increased efficacy of applying high concentrations of both bacteriocins. This efficacy was further demonstrated in additional challenge studies carried out at 15 degrees C in the two sous vide products: mushrooms and shellfish salad. Whereas no vegetative cells were detected after 90 days in the presence of bacteriocins, almost 100% of the population in nontreated samples of mushrooms and shellfish salad was in the vegetative state after 17 and 43 days of storage at 15 degrees C, respectively.

Vesicular nanostructures composed of oleic acid and phosphatidylcholine: Effect of pH and molar ratio.

Phospholipids and fatty acids are the main building blocks of biological membranes. Oleic acid is a monounsaturated omega-9 fatty acid commonly found in many natural sources. Its characteristic kinked structure grants this molecule with a great number of biological properties. To better understand the role that this kind of fatty acids play into phospholipid membranes, nanostructured systems formed with hydrogenated soy phosphatidylcholine and oleic acid were studied in this work by means of cryo-electron microscopy, dynamic light scattering and differential scanning calorimetry. Differences concerning size, morphology and phase behavior were found when those systems were prepared at different conditions of pH and molar ratio between both compounds. Broadly, it was seen how alkaline mediums and high proportions of oleic acid reduced the size of the structures and increased the fluidity of the membranes. The ease of preparation of these lipid systems, and the response to pH suggests a future use of these systems as model membranes or delivery systems.

[A current overview of the teaching of Tropical Medicine, International Health and Global Health in the Spanish university]. / Panorama actual de la enseñanza de la Medicina Tropical, Salud Internacional y Salud Global en la universidad española.

OBJECTIVE: The teaching of tropical medicine, international health or global health in the Spanish Schools of Medicine and Pharmacy is unknown. The objective of this study is to show a current overview of teaching in degree and post-graduate. METHODS: The curricula are reviewed, identifying those subjects and postgraduate courses with the denomination "Tropical Medicine", "International Health", "Global Health" or "Imported Diseases". RESULTS: In 15 of the 40 (37.5%) schools of Medicine the subject of Tropical Medicine, International Health or Global Health is taught during the degree. In 14 of them (93.3%) with an optional character and in one (6.7%) with obligatory character. In 4 out of 22 (18.1%) Pharmacy schools are taught in the degree of Tropical Medicine, International Health or Global Health. CONCLUSIONS: The teaching in Tropical Medicine, International Health and Global Health in the Schools of Medicine and Pharmacy in Spain has, currently, a limited presence.

Quantitative image analysis to characterize the dynamics of Listeria monocytogenes biofilms.

This work shows that the combination of two-dimensional (2D) and three-dimensional (3D) analyses of images acquired by confocal laser scanning microscopy facilitates the quantitative spatiotemporal characterization of architectures formed by Listeria monocytogenes biofilms. In particular, the analysis of structural features such as maximum thickness, biovolume, areal porosity and maximum diffusion distance allowed elucidating differences in biofilm formation of three L. monocytogenes strains (L1A1, CECT5873 and CECT4032). The analysis showed a common sequence for all strains. In the first phase, independent clusters evolve to interconnected clusters and honeycomb-like structures. Flat biofilms characterized the second phase. The structures disappear in the third phase. Nevertheless, the duration of the phases differed from strain to strain. L1A1 strain exhibited the slowest dynamics and the thickest biofilms while the strain CECT4032 presented the faster dynamics and the thinnest biofilms. Also, the number of dead cells varies significantly from strain to strain. From the results of the analysis, it can be concluded that 2D parameters are critical to differentiating morphological features while 3D parameters ease the interpretation and comparative study of the different phases during the life cycle of biofilms.

Withdrawing and withholding life support in the intensive care unit: a Spanish prospective multi-centre observational study.

OBJECTIVE: To determine how frequently life support is withheld or withdrawn from adult critically ill patients, and how physicians and patients families agree on the decision regarding the limitation of life support. DESIGN: Prospective multi-centre cohort study. SETTING: Six adult medical-surgical Spanish intensive care units (ICUs). PATIENTS AND PARTICIPANTS: Three thousand four hundred ninety-eight consecutive patients admitted to six ICUs were enrolled. MEASUREMENTS AND RESULTS: Data collected included age, sex, SAPS II score on admission and within 24 h of the decision to limit treatment, length of ICU stay, outcome at ICU discharge, cause and mode of death, time to death after the decision to withhold or withdraw life support, consultation and agreement with patient's family regarding withholding or withdrawal, and the modalities of therapies withdrawn or withheld. Two hundred twenty-six (6.6%) of 3,498 patients had therapy withheld or withdrawn and 221 of them died in the ICU. Age, SAPS II and length of ICU stay were significantly higher in patients dying patients who had therapy withheld or withdrawn than in patients dying despite active treatment. The proposal to withhold or withdraw life support was initiated by physicians in 210 (92.9%) of 226 patients and by the family in the remaining cases. The patient's family was not involved in the decision to withhold or withdraw life support therapy in 64 (28.3%) of 226 cases. Only 21 (9%) patients had expressed their wish to decline life-prolonging therapy prior to ICU admission. CONCLUSIONS: The withholding and withdrawing of treatment was frequent in critically ill patients and was initiated primarily by physicians.

Effect of cyclosporin A on inflammatory cytokine production by human alveolar macrophages.

Cyclosporin A (CsA) is an immunomodulator drug that has been used in the treatment of several types of advanced pulmonary interstitial disease. This beneficial effect occurs mainly in circumstances in which alveolitis due to CD4 lymphocytes is absent, suggesting that CsA acts on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by human alveolar macrophages (AMs). Human AMs were collected by bronchoalveolar lavage from four control subjects and 13 patients with interstitial lung disease. Purified human AMs were incubated with different concentrations of CsA (200, 20 and 2 ng ml-1) in the presence or absence of lipopolysaccharide (LPS). Interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 levels were measured in supernatants using specific enzyme-linked immunosorbent assays. It was found that CsA inhibits basal secretion of TNF-alpha and IL-8 at 20 and 200 ng ml-1. However, none of the different concentrations of CsA modified basal secretion of IL-1 beta nor IL-6. By contrast, a lower concentration of CsA (2 ng ml-1) inhibits LPS-stimulated secretion of all inflammatory cytokines. It is concluded that CsA exerts a modest effect on inflammatory cytokine production by human AMs.

Determination by high-performance liquid chromatography of phenylbutazone in samples of plasma from fighting bulls.

The purpose of this study was to investigate the possible presence of phenylbutazone in plasma samples from fighting bulls killed in 2nd and 3rd category bullrings in the province of Salamanca (Spain) in 1998, 1999 and 2000. For quantitative and qualitative determination, a high-performance liquid chromatograph was used, equipped with a photodiode-array detector and setting wavelengths at 240, 254 and 284 nm. The mobile phase optimized for the simultaneous detection of dexamethasone, betamethasone, flunixin and phenylbutazone, was 0.01 M acetic acid pH 3 in methanol (35:65 v/v) at a flow rate of 1 ml/min. Plasma samples were deproteinized with 400 microl of acetonitrile and 20 microl of the supernatant were injected directly into the chromatographic system equipped with a Lichrospher 60 RP select B column and guard column. For the quantitative analysis, standard calibration curves were made in a concentration range between 0.25 and 30 microg/ml, using betamethasone as internal standard. The retention time of phenylbutazone was 8.7 +/- 0.2 min and recovery was 83%. The detection and quantification limits were 0.016 and 0.029, respectively for A=240 nm. The study results show that 17 of the 74 samples analyzed in 1998, 18 of those from 1999 and 10 of those from 2000 were positive for phenylbutazone.

Effect of various cryostabilizers on the production and reactivity of formaldehyde in frozen-stored minced blue whiting muscle.

The production of formaldehyde in frozen-stored minced blue whiting muscle was described by a rectangular hyperbolic model, and the effectiveness of each cryostabilizer is discussed in terms of its parameters. The maltodextrins assayed noticeably inhibited formaldehyde production, this effect being greater at -20 degrees C than at -10 degrees C. Sucrose was only effective at -20 degrees C. It seems that these compounds act by restricting molecular diffusion. The effect of each cryostabilizer on formaldehyde binding was closely regulated by its effect on production. This is discussed in terms of the binding equation parameters. The binding of formaldehyde during frozen storage was dependent on protein rearrangements leading to reactive groups becoming available. The constraints of cryostabilizers on molecular diffusion reduced the exposure of these groups. Consequently, the interpretation of formaldehyde reactivity was biased, leading to conclusions different from those that would be obtained from a study done under standard conditions.

Apparent antifungal activity of several lactic acid bacteria against Penicillium discolor is due to acetic acid in the medium.

Fifty-six dairy bacteria belonging to the genera Lactococcus, Lactobacillus, Pediococcus, Propionibacterium, Streptococcus, Enterococcus, Leuconostoc, and Brevibacterium were screened for antifungal activity against four species of fungi relevant to the cheese industry (Penicillium discolor, Penicillium commune, Penicillium roqueforti, and Aspergillus vesicolor). Most of the active strains belonged to the genus Lactobacillus, whereas Penicillium discolor was found to be the most sensitive of the four fungi investigated. Further studies on P. discolor showed antifungal activity only below pH 5. This effect of pH suggests that organic acids present in the culture could be involved in the detected activity. Determination of acid composition revealed lactic acid production for active dairy strains and the presence of acetic acid in active as well as inactive strains. It was demonstrated that the undissociated acetic acid originates from the bacterial growth medium. The synergistic effect of the acetic acid present and the lactic acid produced was likely the main factor responsible for the antifungal properties of the selected bacteria. These results could explain some discrepancies in reports of the antifungal properties of lactic acid bacteria, since the role of acetic acid has not been considered in previous studies.

Joint effect of nisin, CO2, and EDTA on the survival of Pseudomonas aeruginosa and Enterococcus faecium in a food model system.

A study on the joint effect of either nisin or Nisaplin, headspace CO2 levels, and EDTA on the survival of Pseudomonas aeruginosa and Enterococcus faecium was carried out in a water-soluble fish muscle extract at 3 degrees C using a second-order rotatable factorial design. E. faecium was completely deactivated by all processing after 2 days of storage. In contrast, P. aeruginosa was much less susceptible to treatments, and cell death was satisfactorily described by two models. Nisin increased cell death, whereas Nisaplin (commercial form of nisin) was not suitable, as it caused undesirable interference, presumably due to its co-compounds. Interactions between Nisaplin or nisin and either EDTA or CO2 were found to be nonstatistically significant. Factors that could account for this unexpected lack of synergism are discussed. However, a statistically significant positive interaction was found between CO2 and EDTA. This finding could allow CO2 levels to be decreased and hence to reduce the main disadvantages of CO2 application, namely, exudation and acidification.

Comparative study of different essential oils of Bupleurum gibraltaricum Lamarck.

A comparative study was performed of the essential oil extracted from the fruiting apex of Bupleurum gibraltaricum Lamarck (Umbelliferae) collected in different areas within the province of Granada, including the Cázulas mountains, the Balcón de Canales and the Quéntar Reservoir. All three essential oils were very similar in chemical composition, consisting mainly of monoterpenic hydrocarbons (delta 3-carene and alpha-pinene). When anti-inflammatory activity against both acute (carrageenin-induced plantar edema) and subchronic inflammation (granuloma technique) was assayed, quantitative differences came to light: the essential oil of the Cázulas Mountains population was most active against acute inflammation owing to its high delta 3-carene content, whereas the Quéntar Reservoir essential oil of B. gibraltaricum was most effective against granuloma induced inflammation.

Numerical spatio-temporal characterization of Listeria monocytogenes biofilms.

As the structure of biofilms plays a key role in their resistance and persistence, this work presents for the first time the numerical characterization of the temporal evolution of biofilm structures formed by three Listeria monocytogenes strains on two types of stainless-steel supports, AISI 304 SS No. 2B and AISI 316 SS No. 2R. Counting methods, motility tests, fluorescence microscopy and image analysis were combined to study the dynamic evolution of biofilm formation and structure. Image analysis was performed with several well-known parameters as well as a newly defined parameter to quantify spatio-temporal distribution. The results confirm the interstrain variability of L. monocytogenes species regarding biofilm structure and structure evolution. Two types of biofilm were observed: homogeneous or flat and heterogeneous or clustered. Differences in clusters and in attachment and detachment processes were due mainly to the topography and composition of the two surfaces although an effect due to motility was also found.

Mesenteric vein thrombosis after laparoscopic sleeve gastrectomy.

Mesenteric vein thrombosis is a rare complication of bariatric laparoscopic surgery. We report a case of a 47-year-old man with obesity who had mesenteric vein thrombosis 14 days after laparoscopic sleeve gastrectomy. He was treated with heparin anticoagulation with a good therapeutic response. This case and literature review illustrate that mesenteric vein thrombosis has to be included in the differential diagnosis of abdominal pain after a bariatric procedure and listed formally as a complication of bariatric surgery.

Comparison between the resistance of benzalkonium chloride-adapted and -nonadapted biofilms of Listeria monocyogenes to modified atmosphere packaging and nisin once transferred to mussels.

Benzalkonium chloride-adapted and -nonadapted Listeria monocytogenes biofilm cells were transferred by contact to cooked or live mussels and packed in rich CO(2) and O(2), respectively. The viabilities of transferred cells during storage of these packed samples at 2.5 °C were compared. In addition, in cooked mussels the combined effect of CO(2) and nisin against the survival of L. monocytogenes was also studied by using a first-order factorial design. The results obtained demonstrated that biofilms formed by benzalkonium chloride-adapted L. monocytogenes cells could be more resistant to the application of modified atmospheres rich in CO(2) and nisin once they have been transferred to cooked mussels by contact (simulating cross-contamination). This implies an increase in the risk associated with the presence of these cells in food processing plants. Significant empirical equations obtained after 7, 11, and 20 days showed an inhibitory effect of CO(2) and nisin against L. monocytogenes. However, a significant positive interaction between both variables highlights an incompatibility between CO(2) and nisin at high concentrations. Results also demonstrated that L. monocytogenes could persist after cross-contamination during the processing of live mussels, so L. monocytogenes is of concern as a contaminant in live mussels packaged in high-O(2) atmospheres.