Identification and in vitro reactivity of celiac immunoactive peptides in an apparent gluten-free beer.

Gluten content from barley, rye, wheat and in certain oat varieties, must be avoid in individuals with celiac disease. In most of the Western countries, the level of gluten content in food to be considered as gluten-free products is below 20 parts per million measured by ELISA based on specific anti-gluten peptide antibody. However, in beverages or food suffering complex hydrolytic processes as beers, the relative proportion of reactive peptides for celiac patients and the analytical techniques may differ, because of the diversity of the resulting peptide populations after fermentations. A beer below 20 parts per million of gluten but yet detectable levels of gluten peptides by anti-gliadin 33-mer antibodies (G12 and A1) was analyzed. We identified and characterized the relevant peptides for either antibody recognition or immunoactivity in celiac patients. The beer was fractionated by HPLC. The relative reactivity of the different HPLC fractions to the G12/A1 antibodies correlated to the reactivity of peripheral blood mononuclear cells isolated from 14 celiac individuals. Peptides from representative fractions classified according to the relative reactivity to G12/A1 antibodies were identified by mass spectrometry. The beer peptides containing sequences with similarity to those of previously described G12 and A1 epitopes were synthesized and confirmed significant reactivity for the antibodies. The most reactive peptides for G12/A1 also confirmed the highest immunogenicity by peripheral blood mononuclear cell activation and interferon γ production from celiac patients. We concluded that preparative HPLC combined with anti-gliadin 33-mer G12/A1 antibodies were very sensitive and specific methods to analyze the relevant immunogenic peptides in hydrolyzed gluten.

HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.

BACKGROUND Multiple Sclerosis (MS) is an autoimmune demyelinating disease that occurs more frequently in women than in men. Multiple Sclerosis Associated Retrovirus (MSRV) is a member of HERV-W, a multicopy human endogenous retroviral family repeatedly implicated in MS pathogenesis. MSRV envelope protein is elevated in the serum of MS patients and induces inflammation and demyelination but, in spite of this pathogenic potential, its exact genomic origin and mechanism of generation are unknown. A possible link between the HERV-W copy on chromosome Xq22.3, that contains an almost complete open reading frame, and the gender differential prevalence in MS has been suggested. RESULTS MSRV transcription levels were higher in MS patients than in controls (U-Mann-Whitney; p = 0.004). Also, they were associated with the clinical forms (Spearman; p = 0.0003) and with the Multiple Sclerosis Severity Score (MSSS) (Spearman; p = 0.016). By mapping a 3 kb region in Xq22.3, including the HERV-W locus, we identified three polymorphisms: rs6622139 (T/C), rs6622140 (G/A) and rs1290413 (G/A). After genotyping 3127 individuals (1669 patients and 1458 controls) from two different Spanish cohorts, we found that in women rs6622139 T/C was associated with MS susceptibility: [χ2; p = 0.004; OR (95% CI) = 0.50 (0.31-0.81)] and severity, since CC women presented lower MSSS scores than CT (U-Mann-Whitney; p = 0.039) or TT patients (U-Mann-Whitney; p = 0.031). Concordantly with the susceptibility conferred in women, rs6622139*T was associated with higher MSRV expression (U-Mann-Whitney; p = 0.003). CONCLUSIONS Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS.

Sulfur speciation and stable isotope trends of water-soluble sulfates in mine tailings profiles

Sulfur speciation and the sources of water-soluble sulfate in three oxidizing sulfidic mine tailings impoundments were investigated by selective dissolution and stable isotopes. The studied tailings impoundments-Piuquenes, Cauquenes, and Salvador No. 1-formed from the exploitation of the Rio Blanco/La Andina, El Teniente, and El Salvador Chilean porphyry copper deposits, which are located in Alpine, Mediterranean, and hyperarid climates, respectively. The water-soluble sulfate may originate from dissolution of primary ore sulfates (e.g., gypsum, anhydrite, jarosite) or from oxidation of sulfide minerals exposed to aerobic conditions during mining activity. With increasing aridity and decreasing pyrite content of the tailings, the sulfur speciation in the unsaturated oxidation zones showed a trend from dominantly Fe(Ill) oxyhydroxide fixed sulfate (e.g., jarosite and schwertmannite) in Piuquenes toward increasing presence of water-soluble sulfate at Cauquenes and Salvador No. 1. In the saturated primary zones, sulfate is predominantly present in water-soluble form (mainly as anhydrite and/or gypsum). In the unsaturated zone at Piuquenes and Cauquenes,the delta(34)S(S04) values ranged from +0.5 parts per thousand to +2.0 parts per thousand and from -0.4 parts per thousand to +1.4 parts per thousand Vienna Canyon Diablo Troilite (V-CDT), respectively, indicating a major sulfate source from pyrite oxidation (delta(34)S(pyrite) -1.1 parts per thousand and -0.9 parts per thousand). In the saturated zone at Piuquenes and Cauquenes, the values ranged from -0.8%. to +0.3 parts per thousand and from +2.2 parts per thousand to +3.9 parts per thousand, respectively. At Cauquenes the 34 S enrichment in the saturated zone toward depth indicates the increasing contribution of isotopically heavy dissolved sulfate from primary anhydrite (similar to+10.9%o). At El Salvador No. 1, the delta(34)S(SO4) average value is -0.9 parts per thousand, suggesting dissolution of supergene sulfate minerals (jarosite, alunite, gypsum) with a delta(34)S similar to -0.7 parts per thousand as the most probable sulfate source. The gradual decrease Of delta(18)O(S04) values from the surface to the oxidation front in the tailings impoundments at Piuquenes (from -4.5 parts per thousand to -8.6 parts per thousand Vienna Standard Mean Ocean Water, V-SMOW) and at Cauquenes (from -1.3 parts per thousand to -3.5 parts per thousand) indicates the increasing importance of ferric iron as the main electron acceptor in the oxidation of pyrite. The different delta(18)O(SO4) values between the tailings impoundments studied here reflect the local climates.

Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study.

PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

Discriminant validity and test-retest reliability of a self-administered Internet-based questionnaire testing doctors' knowledge in evidence-based medicine.

Aims and objectives  This study aimed to determine the discriminant validity and the test-retest reliability of a questionnaire testing the impact of evidence-based medicine (EBM) training on doctors' knowledge and skills. Methods  Questionnaires were sent electronically to all doctors working as residents and chief residents in two French speaking hospital networks in Switzerland. Participants completed the questionnaire twice, within a 4-week interval. The discriminant validity was examined in comparing doctors' performance according to their reported EBM previous training. Proportion of agreement between both sessions of the questionnaire, Cohen's kappa and 'uniform kappa' determined its test-retest reliability. Results  The participation rate was 9.8%/7.1% to first/second session. Performance increased according to the level of doctors' previous training in EBM. The observed proportion of agreement between both sessions was over 70% for 14/19 questions, and the 'uniform kappa' was superior to 0.60 for 15/19 questions. Conclusion  The discriminant validity and test-retest reliability of the questionnaire were satisfying. The low participation rate did not prevent the study from achieving its aims.

Social and medical vulnerability factors of emergency department frequent users in a universal health insurance system.

OBJECTIVES: The objectives were to identify the social and medical factors associated with emergency department (ED) frequent use and to determine if frequent users were more likely to have a combination of these factors in a universal health insurance system. METHODS: This was a retrospective chart review case-control study comparing randomized samples of frequent users and nonfrequent users at the Lausanne University Hospital, Switzerland. The authors defined frequent users as patients with four or more ED visits within the previous 12 months. Adult patients who visited the ED between April 2008 and March 2009 (study period) were included, and patients leaving the ED without medical discharge were excluded. For each patient, the first ED electronic record within the study period was considered for data extraction. Along with basic demographics, variables of interest included social (employment or housing status) and medical (ED primary diagnosis) characteristics. Significant social and medical factors were used to construct a logistic regression model, to determine factors associated with frequent ED use. In addition, comparison of the combination of social and medical factors was examined. RESULTS: A total of 359 of 1,591 frequent and 360 of 34,263 nonfrequent users were selected. Frequent users accounted for less than a 20th of all ED patients (4.4%), but for 12.1% of all visits (5,813 of 48,117), with a maximum of 73 ED visits. No difference in terms of age or sex occurred, but more frequent users had a nationality other than Swiss or European (n = 117 [32.6%] vs. n = 83 [23.1%], p = 0.003). Adjusted multivariate analysis showed that social and specific medical vulnerability factors most increased the risk of frequent ED use: being under guardianship (adjusted odds ratio [OR] = 15.8; 95% confidence interval [CI] = 1.7 to 147.3), living closer to the ED (adjusted OR = 4.6; 95% CI = 2.8 to 7.6), being uninsured (adjusted OR = 2.5; 95% CI = 1.1 to 5.8), being unemployed or dependent on government welfare (adjusted OR = 2.1; 95% CI = 1.3 to 3.4), the number of psychiatric hospitalizations (adjusted OR = 4.6; 95% CI = 1.5 to 14.1), and the use of five or more clinical departments over 12 months (adjusted OR = 4.5; 95% CI = 2.5 to 8.1). Having two of four social factors increased the odds of frequent ED use (adjusted = OR 5.4; 95% CI = 2.9 to 9.9), and similar results were found for medical factors (adjusted OR = 7.9; 95% CI = 4.6 to 13.4). A combination of social and medical factors was markedly associated with ED frequent use, as frequent users were 10 times more likely to have three of them (on a total of eight factors; 95% CI = 5.1 to 19.6). CONCLUSIONS: Frequent users accounted for a moderate proportion of visits at the Lausanne ED. Social and medical vulnerability factors were associated with frequent ED use. In addition, frequent users were more likely to have both social and medical vulnerabilities than were other patients. Case management strategies might address the vulnerability factors of frequent users to prevent inequities in health care and related costs.

Traducción comentada de “Genetically Modified Organisms (GMOs): Transgenic Crops and Recombinant DNA Technology”

The purpose of this paper is to provide a translation into Spanish of a review articleabout genetically modified organisms (GMOs) entitled “Genetically ModifiedOrganisms (GMOs): Transgenic Crops and Recombinant DNA Technology” publishedby the well-known scientific journal Nature. In a world where English has become thelingua franca when it comes to transferring scientific knowledge and information, itmust be taken into account that not everyone—from scientist to the general public—hasa good enough command of English so that they can feel comfortable enough reading inthis language. Translators are consequently needed resulting from a great demand oftranslation activity into, for example, Spanish. This is the reason why the proposedSpanish translation is followed by a detailed analysis emphasizing the difficulties andproblems that characterize scientific—and also general—translation (i.e. terminology,syntax, semantics, pragmatics, and ideology), for which different approaches as how tosolve them are provided. On the basis of the analysis, it can be concluded thatexperience will be of much help to scientific translators, given that specificterminological knowledge and style requirements must always be born in mind whentranslating in this field. Moreover, this paper is intended to serve as a guide forTranslation students specializing in the field of science and the expectation is to helpthem make the right decisions when it comes to translating. However, it is clear that itcan only be thought of as an introduction that should be completed with further researchand documentation tasks in order to offer a complete reference tool: the ultimatehandbook of scientific translation.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI.

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied. In vitro study. University based hospital. Fifty-four women undergoing intracytoplasmic sperm injection (ICSI). Oocytes were retrieved, fertilized in vitro using ICSI, and the resulting embryos transferred. Serum was collected immediately prior to oocyte retrieval. Adiponectin isoforms (high molecular weight (HMW), medium and low molecular weight) were determined in serum and FF. Total adiponectin and the different isoform levels were compared with leptin and ovarian steroid concentrations. Adiponectin isoforms in serum and FF. Adiponectin isoform distribution differed between serum and FF; the HMW fraction made up half of all adiponectin in the serum but only 23.3% in the FF. Total and HMW adiponectin in both serum and FF correlated negatively with the body mass index and the concentration of leptin. No correlations were observed for total adiponectin or its isoforms with estradiol, progesterone, anti-Mullerian hormone, inhibin B, or the total follicle stimulating hormone (FSH) dose administered during the ovarian stimulation phase. This study shows for the first time that adiponectin isoform distribution varies between the serum and FF compartments in gonadotropin stimulated patients. A trend towards higher HMW adiponectin serum levels in successful ICSI cycles compared to implantation failures was observed; studies with larger patient groups are required to confirm this observation.

Comparative advantage and the cross-section of business cycles

Business cycles are both less volatile and more synchronized with the world cycle in rich countries than in poor ones. We develop two alternative explanations based on the idea that comparative advantage causes rich countries to specialize in industries that use new technologies operated by skilled workers, while poor countries specialize in industries that use traditional technologies operated by unskilled workers. Since new technologies are difficult to imitate, the industries of rich countries enjoy more market power and face more inelastic product demands than those of poor countries. Since skilled workers are less likely to exit employment as a result of changes in economic conditions, industries in rich countries face more inelastic labour supplies than those of poor countries. We show that either asymmetry in industry characteristics can generate cross-country differences in business cycles that resemble those we observe in the data.

Reproduction and fertility life table of three aphid species (Macrosiphini) at different temperatures

Temperature is a key abiotic factor influencing the development and reproduction of aphids. The effect of temperature on the reproduction of three aphid species Aulacorthum solani (Kaltenbach), Macrosiphum euphorbiae (Thomas) and Uroleucon ambrosiae (Thomas) (Aphididae, Macrosiphini) has been investigated and fertility life tables were determined. Nymphs were reared in climatic chambers at temperatures of 16, 19, 22, 25, and 28 ± 1ºC, RH 70 ± 10% and 12 h photophase. Female adult aphids developed at these temperatures were then used in experiments in which pre-reproductive and reproductive periods were evaluated every 24 h. In addition, the number of nymphs produced and longevity were determined at each temperature. The reproduction period of A. solani and M. euphorbiae decreased with increasing temperature, whereas that of U. ambrosiae was maintained between 19 and 25ºC. The total number of nymphs produced by the aphids decreased as the temperature increased. The longevities of A. solani and M. euphorbiae decreased with increasing temperature but remained stable for U. ambrosiae between 19 and 25ºC. The largest survival rate (l x) and specific fertility (m x) values were found at 16 and 22ºC for all three species. The most favourable temperature for reproduction of A. solani, M. euphorbiae and U. ambrosiae was 22ºC, as demonstrated by the l x and m x profiles, the high values of net reproductive rates and intrinsic rates of increase, and the short intervals between generation and doubling times.

Feasibility and electromagnetic compatibility study of the ClearPEM front-end electronics for simultaneous PET-MR imaging

In this work we present a first feasibility study of the ClearPEM technology for simultaneous PET-MR imaging. The mutual electromagnetic interference (EMI) effects between both systems were evaluated on a 7 T magnet by characterizing the response behavior of the ClearPEM detectors and front-end electronics to pulsed RF power and switched magnetic field gradients; and by analyzing the MR system performance degradation from noise pickup into the RF receiver chain, and from magnetic susceptibility artifacts caused by PET front-end materials.

Population growth and within-plant distribution of the striped mealybug Ferrisia virgata (Cockerell) (Hemiptera, Pseudococcidae) on cotton

Population growth and within-plant distribution of the striped mealybug Ferrisia virgata (Cockerell) (Hemiptera, Pseudococcidae) on cotton. The striped mealybug, Ferrisia virgata (Cockerell) (Hemiptera, Pseudococcidae), is a widely distributed and polyphagous pest species, which naturally occurs on cotton plants in Brazil. This study evaluated the establishment and population growth as well as the within-plant distribution of F. virgata on four cotton cultivars: CNPA 7H (white fibers), BRS Verde, BRS Safira, and BRS Rubi (colored fibers). The experiment was conducted in a complete randomized design with four treatments (cultivars) and 18 replications of each. Thus, cotton plants of each cultivar were infested with 100 newly hatched nymphs of F. virgata. The number of adult female mealybugs and the total number of mealybugs per plant were quantified, respectively, at 25 and 50 days after infestation. The developmental and pre-reproductive periods were also determined. Furthermore, we verified the distribution of F. virgata on the plant parts at 25 and 50 days after infestation. Ferrisia virgata showed similar growth of 412-fold in the four cotton cultivars studied. Also, the nymphs were spread on infested leaves; the secondgeneration nymphs were spread and established in all plant parts. Our results characterize F. virgata as having much potential as an important cotton pest in Brazil.

Prognostication in comatose survivors of cardiac arrest: An advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

OBJECTIVES: To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS: GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS: Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron-specific enolase at 48-72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

Short-term and sustained renal effects of angiotensin II receptor blockade in healthy subjects.

We investigated the short-term and sustained hormonal and renal effects of angiotensin II (Ang II) receptor blockade in normotensive healthy volunteers. Twenty-four subjects maintained on a fixed sodium diet were randomized to receive for 8 days a placebo or 10 or 50 mg doses of the Ang II antagonist irbesartan (SR 47436, BMS 186295) according to a double-blind, parallel group design. Plasma renin activity, plasma immunoreactive Ang II and aldosterone levels, blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 8 hours after the first and eighth administration of each dose of irbesartan or placebo. Ang II receptor blockade with irbesartan induced a dose-dependent compensatory increase in plasma renin activity and plasma angiotensin levels and a significant decrease in plasma aldosterone levels. The compensatory rise in plasma renin activity and Ang II levels was more pronounced on day 8, reflecting a long duration of the blocking effect of irbesartan. Irbesartan induced small changes in blood pressure and did not significantly modify renal blood flow and glomerular filtration rate. However, a significant decrease in filtration fraction was observed during receptor blockade on days 1 and 8. The tubular effects of irbesartan were characterized by a dose-dependent increase in sodium and chloride excretions. Interestingly, the cumulative natriuretic response to Ang II receptor blockade was similar on days 1 and 8, suggesting that in these subjects, renal Ang II receptors are not blocked over 24 hours during repeated administration even though this antagonist has a long duration of action (t1/2 of 15 to 17 hours).(ABSTRACT TRUNCATED AT 250 WORDS)