Pilot study to harmonize the reported influenza intensity levels within the Spanish Influenza Sentinel Surveillance System (SISSS) using the Moving Epidemic Method (MEM).

The intensity of annual Spanish influenza activity is currently estimated from historical data of the Spanish Influenza Sentinel Surveillance System (SISSS) using qualitative indicators from the European Influenza Surveillance Network. However, these indicators are subjective, based on qualitative comparison with historical data of influenza-like illness rates. This pilot study assesses the implementation of Moving Epidemic Method (MEM) intensity levels during the 2014-2015 influenza season within the 17 sentinel networks covered by SISSS, comparing them to historically reported indicators. Intensity levels reported and those obtained with MEM at the epidemic peak of the influenza wave, and at national and regional levels did not show statistical difference (P = 0·74, Wilcoxon signed-rank test), suggesting that the implementation of MEM would have limited disrupting effects on the dynamic of notification within the surveillance system. MEM allows objective influenza surveillance monitoring and standardization of criteria for comparing the intensity of influenza epidemics in regions in Spain. Following this pilot study, MEM has been adopted to harmonize the reporting of intensity levels of influenza activity in Spain, starting in the 2015-2016 season.

Estimating influenza vaccine effectiveness in Spain using sentinel surveillance data.

We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case­control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0­14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.

Effects of long chain fatty acid synthesis and associated gene expression in microalga Tetraselmis sp.

With the depletion of global fish stocks, caused by high demand and effective fishing techniques, alternative sources for long chain omega-3 fatty acids are required for human nutrition and aquaculture feeds. Recent research has focused on land-based cultivation of microalgae, the primary producers of omega-3 fatty acids in the marine food web. The effect of salinity on fatty acids and related gene expression was studied in the model marine microalga, Tetraselmis sp. M8. Correlations were found for specific fatty acid biosynthesis and gene expression according to salinity and the growth phase. Low salinity was found to increase the conversion of C18:4 stearidonic acid (SDA) to C20:4 eicosatetraenoic acid (ETA), correlating with increased transcript abundance of the Δ-6-elongase-encoding gene in salinities of 5 and 10 ppt compared to higher salinity levels. The expression of the gene encoding ß-ketoacyl-coenzyme was also found to increase at lower salinities during the nutrient deprivation phase (Day 4), but decreased with further nutrient stress. Nutrient deprivation also triggered fatty acids synthesis at all salinities, and C20:5 eicosapentaenoic acid (EPA) increased relative to total fatty acids, with nutrient starvation achieving a maximum of 7% EPA at Day 6 at a salinity of 40 ppt.

Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study.

Adjusted early estimates of the 2013/14 influenza vaccine effectiveness (VE) in Spain for all age groups was 35% (95% CI: -9 to 62), 33% (95% CI: -33 to 67) and 28% (95% CI: -33 to 61) against any influenza virus type, A(H1N1)pdm09 and A(H3N2) viruses, respectively. For the population targeted for vaccination, the adjusted VE was 44% (95% CI: -11 to 72), 36% (95% CI: -64 to 75) and 42% (95% CI: -29 to 74), respectively. These preliminary results in Spain suggest a suboptimal protective effect of the vaccine against circulating influenza viruses.

Microalgal biofactories: a promising approach towards sustainable omega-3 fatty acid production.

Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide significant health benefits and this has led to an increased consumption as dietary supplements. Omega-3 fatty acids EPA and DHA are found in animals, transgenic plants, fungi and many microorganisms but are typically extracted from fatty fish, putting additional pressures on global fish stocks. As primary producers, many marine microalgae are rich in EPA (C20:5) and DHA (C22:6) and present a promising source of omega-3 fatty acids. Several heterotrophic microalgae have been used as biofactories for omega-3 fatty acids commercially, but a strong interest in autotrophic microalgae has emerged in recent years as microalgae are being developed as biofuel crops. This paper provides an overview of microalgal biotechnology and production platforms for the development of omega-3 fatty acids EPA and DHA. It refers to implications in current biotechnological uses of microalgae as aquaculture feed and future biofuel crops and explores potential applications of metabolic engineering and selective breeding to accumulate large amounts of omega-3 fatty acids in autotrophic microalgae.

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.

Toxicological assessment of Xanthigen® nutraceutical extract combination: Mutagenicity, genotoxicity and oral toxicity.

Xanthigen® is a nutraceutical combination for weight management capable of increasing energy expenditure via uncoupling protein 1 (UCP-1) in white adipose tissue. It consists of brown seaweed Undaria pinnatifida extract, rich in the carotenoid fucoxanthin (FX) and pomegranate seed oil (PSO), rich in punicic acid. Xanthigen was screened to determine its genotoxicity and 90-days repeated oral toxicity. Genotoxicity was assessed with the Ames test (TA89, TA100, TA1535, TA1537, WP2), chromosomal aberration assay (Chinese hamster ovary cells) and mammalian micronucleus test (in mice). Xanthigen did not exhibit genotoxicity in any tested strain. Sub-chronic toxicity was evaluated with daily oral administration of 250, 500 and 1000 mg/kg/day doses of Xanthigen® to Sprague-Dawley rats over 90 days. No deaths and no deleterious effects were observed during the 90-day treatment, indicating an absence of sub-chronic toxicity and a no observed adverse effect level greater than 1000 mg/kg/day. A statistically significant decrease in bodyweight and food intake in Xanthigen® treated groups was attributed to the weight loss property of Xanthigen®. Overall, Xanthigen® shows no significant mutagenic or toxic effects.

miRNAs: una nueva mirada de la enfermedad de Vogt-Koyanagi-Harada / miRNAs: a new look at Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada disease (VKH) is an autoimmune multisystemic syndrome that includes bilateral intraocular inflammation, associated with exudative retinal detachments, and systemic manifestations in the auditory, integumentary, and central nervous systems. The frequency of VKH disease in the world is variable, but in Santiago, Chile, it causes approximately 17% of non-infectious uveitis, an incidence 2 to 3-fold greater than in the USA or European countries. The evidence shows that the pathogenesis of VKH would be caused by cell-mediated autoimmunity directed against melanocytes present in the uveal tissue. CD4+ T lymphocytes (especially hyperactivity of Th17 and Th1 cells), B lymphocytes, cytokines (e.g., TGF-ß, IL-2, IL-6, IL-23 and INF-γ) and chemokines appear to play an important role in the development of VKH. Several lines of evidence support that the pathogenesis of uveitis observed in VKH involves an altered pattern of micro-ribonucleic acids (miRNA) expression, driving the loss of immunological tolerance. In this review, we discuss the evidence related to regulation and altered expression of miRNA associated with Vogt-Koyanagi-Harada and other autoimmune diseases. (AU)

RNA-Seq and metabolic flux analysis of Tetraselmis sp. M8 during nitrogen starvation reveals a two-stage lipid accumulation mechanism.

To map out key lipid-related pathways that lead to rapid triacylglyceride accumulation in oleaginous microalgae, RNA-Seq was performed with Tetraselmis sp. M8 at 24h after exhaustion of exogenous nitrogen to reveal molecular changes during early stationary phase. Further gene expression profiling by quantitative real-time PCR at 16-72h revealed a distinct shift in expression of the fatty acid/triacylglyceride biosynthesis and ß-oxidation pathways, when cells transitioned from log-phase into early-stationary and stationary phase. Metabolic reconstruction modeling combined with real-time PCR and RNA-Seq gene expression data indicates that the increased lipid accumulation is a result of a decrease in lipid catabolism during the early-stationary phase combined with increased metabolic fluxes in lipid biosynthesis during the stationary phase. During these two stages, Tetraselmis shifts from reduced lipid consumption to active lipid production. This process appears to be independent from DGAT expression, a key gene for lipid accumulation in microalgae.

Safety and efficacy of Omniscan (gadodiamide injection) at 0.1 mmol/kg for MRI in infants younger than 6 months of age: phase III open multicenter study.

RATIONALE AND OBJECTIVES: To demonstrate that gadodiamide injection is a safe and efficient contrast agent for MRI in infants younger than 6 months of age. METHODS: The authors designed a phase III multicenter nonrandomized study using a control group. Gadodiamide injection at a dosage of 0.1 mmol/kg body weight was administered to 39 children; 20 received no contrast. The mean age was 10.6 weeks in the contrast group and 9.3 weeks in the control group. MR examinations, blood (serum creatinine, S-ASAT, S-ALAT, S-bilirubin, alkaline phosphatase) and urine (proteins, blood, others) sampling before sedation and after examination, heart rate (electrocardiography) and oxygen saturation (pulse oximetry) during examination, adverse events, and efficacy parameters were analyzed. RESULTS: In the contrast group, 18 (51.4%) children had 31 abnormal changes in one or more of the safety parameters and vital signs. In the control group there were 16 (80.0%) children with 19 abnormal changes. Gadodiamide injection had no negative influence on the safety parameters. No serious adverse events occurred, and only three clinically relevant adverse events (elevation of S-ALAT and S-ASAT, elevation of bilirubin) in two patients in the contrast group and one event (vomiting) in one patient in the control group were documented. The benefit of the contrast medium was clearly shown for all evaluated parameters. CONCLUSIONS: Gadodiamide injection is safe, well tolerated, and effective in infants younger than 6 months of age.

Effects of omega-toxins on noradrenergic neurotransmission in beating guinea pig atria.

The effects of four omega-toxins, known to block various subtypes of neuronal voltage-activated Ca2+ channels, on the beating guinea pig left atrium have been analyzed. Atria were suspended in oxygenated Krebs-bicarbonate solution at 32 degrees C and driven with electrical pulses delivered by a stimulator at 1 Hz, 1 ms, 4 V. A 10-fold increase of voltage caused a potent and rapid enhancement of the size of contractions (about 3- to 4-fold above basal), which reflects the release of endogenous noradrenaline from sympathetic nerve terminals. omega-Conotoxin MVIIC, omega-conotoxin MVIIA and omega-conotoxin GVIA inhibited the inotropic responses to 10 x V stimulation with IC50 values of 191, 44 and 20.4 nM, respectively. omega-Agatoxin IVA did not affect the contractile responses. The inotropic responses to exogenous noradrenaline were unaffected by the toxins. The potent blocking effects of omega-conotoxin GVIA were present even in conditions in which the release of noradrenaline was strongly facilitated by presynaptic alpha 2-adrenoceptor blockade by phenoxybenzamine. These effects were not reversed upon repeated washing of the tissue with toxin-free medium. In contrast, the blockade induced by omega-conotoxin MVIIC and omega-conotoxin MVIIA were fully reversed, with t1/2 of 13.5 and 31.2 min, respectively. omega-Conotoxin MVIIC (1 microM) protected against the irreversibility of the blockade induced by omega-conotoxin GVIA (100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Tuberculosis in Spain: epidemiological pattern and clinical practice.

SETTING: Thirteen Autonomous Regions in Spain. OBJECTIVE: To study the incidence of all forms of tuberculosis (TB) and investigate clinical practice in TB. DESIGN: Cases of all forms of tuberculosis diagnosed in the study setting from May 1986 to April 1997 were identified though active search of different databases. Clinical and epidemiological information on cases was collected from clinical records or by interview with physicians. RESULTS: The overall incidence of all forms of tuberculosis was 38.5/100,000 and the incidence of smear-positive disease was 13.83/100,000. Most cases (97.1%) were Spanish nationals, with rates higher in men than in women (52.7/100,000 vs. 24.87/100,000) and in groups aged 25-34 and 75 years and over (61.35/100,000 and 59.35/100,000, respectively). Disseminated forms were frequent (6.6%), and the most common risk factor was human immunodeficiency virus (HIV) infection (17.7% of cases). Hospitalisation was common (71.6%). Microbiological confirmation of diagnosis was sought for 87.7% of the cases (91.8% of pulmonary vs. 75.5% of extra-pulmonary cases), and 65.2% were culture-positive (73.8% of pulmonary vs. 39.7% of extra-pulmonary cases). HIV-infected patients were treated in almost equal proportions with three or four drugs (49.7% and 48.2%, respectively), while HIV-negative cases or those whose HIV status was unknown were usually treated with three drugs. CONCLUSION: The epidemiological pattern of TB in Spain is different to other industrialised countries in the age distribution of cases and the proportions of foreigners and cases with HIV infection. Microbiological confirmation of diagnosis is more common in pulmonary than in extra-pulmonary disease, and treatment with four drugs more frequent in HIV-positive cases.

Etidronate inhibits the production of IL-6 by osteoblast-like cells.

IL-6 is a resorbing cytokine synthesized by osteoblasts and monocytes that has been implicated in the pathogenesis of osteoporosis. Bisphosphonates are well-known antiresorptive drugs, the antiosteoclastic effect of which has been recently suggested to be brought about at least in part through osteoblasts. Based on these facts, we have studied the effect of etidronate on the production of IL-6 by two tumoral cell lines of human osteoblastic phenotype (MG63 and SaOs cells), and by peripheral blood mononuclear cells (PBMC). For comparison, another antiresorptive drug, estradiol, was included in the study. MG63 cells were stimulated with LPS and IL-1 beta, SaOs cells with LPS, IL-1 beta and PMA, and PBMC with LPS and PMA. Etidronate was tested at 10(-7), 10(-6), 10(-5), and 10(-4) M, and 17beta-estradiol was tested at 10(-10), 10(-9), 10(-8), and 10(-7) M. IL-6 was determined in supernatants by an ELISA. No significant effect of either etidronate or estradiol on IL-6 secretion by LPS or PMA-stimulated PBMC was found. However, in osteoblastic-like cells, an inhibition of IL-6 production by etidronate in LPS-stimulated cultures was found. At the highest concentrations tested, IL-6 production values were 58 +/- 9% and 53 +/- 8% of those at base line for MG63 and SaOs cells, respectively. Estradiol did not modify IL-6 secretion under any condition. In conclusion, our study supports the contention that the antiresorptive effect of bisphosphonates may be due in part to a decrease in IL-6 production by osteoblasts.

[Behavior of brain perfusion with SPECT tomography 99mTc ethylene dicysteine (ECD) in alcohol and cocaine dependents during abstinence]. / Comportamiento de la perfusión cerebral con tomografía SPECT- 99mTc etilencisteína dímero (ECD) en dependientes a alcohol y cocaína durante abstinencia.

Brain perfusion abnormalities after an abstinence period of 28 days in a group of patients with alcohol and / or cocaine dependence was investigated. They were related with gender, consumption period and number of drugs. Fifty men and 10 women were included and SPECT perfusion was performed using 99mTc ethylene cysteine dimer (ECD) with qualitative and semiquantitative section analysis. Perfusion abnormalities were observed in 60% of the patients, principally in frontal, temporal and parietal lobes. The abnormalities were focal in 58.3%, diffuse in 41.7% and bilateral in 95% of all patients. Abnormalities were observed in 68% of the men and in only 20% of the women (p = 0.01). Patients with brain perfusion abnormalities had a longer period of consumption corresponding to a median of 17.5 years in patients with abnormalities versus nine years in those with no abnormalities (p = 0.036), however, their ages as well as the number of drugs consumed were not significantly different. In conclusion, after 28 days of alcohol and / or cocaine abstinence there is significant presence of brain perfusion abnormalities with 99mTc ECD. This could be explained by vasospasm and / or secondary endothelial lesions.

[Assessment of coronary revascularization with 99mTC-sestamibi SPECT. Quantitative analysis of segmentary perfusion]. / Evaluación de la revascularización coronaria con 99m Tc-sestamibi SPECT. Análisis cuantitativo de perfusión segmentaria.

UNLABELLED: We analyzed the change in myocardial perfusion recovery after revascularization using Dipyridamole-99mTc-Sestamibi SPECT in 37 patients (mean age 59 years old; 33 males), all of whom had wall motion abnormalities and 84% who had myocardial infarction. The perfusion defects were evaluated before the revascularization and at 64 days of the angioplasty in 18 cases and of the coronary artery bypass graft (CABG) in 19 and were compared with a normal Dipyridamole database. The bullseye parameters were: decrease in severity, size and ischemia area of the defect and worsening of the defect. It was found that the defects decreased in an average of 31. 4% for extension and 35,8% for severity (with no significant differences between the 2 techniques); the ischemia was reduced in 75.7%. No new defects appeared although some presented a slight worsening. The net change in reduction was 26% for extension and 29% for severity. CONCLUSION: In patients with a high prevalence of myocardial infarction, revascularization obtained a moderate decrease in the perfusion defects and a significant ischemia decrease.

Towards sustainable sources for omega-3 fatty acids production.

Omega-3 fatty acids eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA), provide significant health benefits for brain function/development and cardiovascular conditions. However, most EPA and DHA for human consumption is sourced from small fatty fish caught in coastal waters and, with depleting global fish stocks, recent research has been directed towards more sustainable sources. These include aquaculture with plant-based feeds, krill, marine microalgae, microalgae-like protists and genetically-modified plants. To meet the increasing demand for EPA and DHA, further developments are needed towards land-based sources. In particular large-scale cultivation of microalgae and plants is likely to become a reality with expected reductions in production costs, yield increasese and the adequate addressing of genetically modified food acceptance issues.

Acetohydroxyacid synthase (AHAS) in vivo assay for screening imidazolinone-resistance in sunflower (Helianthus annuus L.).

The objective of this work was to evaluate the in vivo acetohydroxyacid synthase (AHAS) activity response to imidazolinones and its possible use as a selection method for evaluating AHAS inhibitor resistance. In vivo AHAS assay and the comparison of parameters from dose-response curves have been used as a valid tool for comparing sunflower lines and hybrids differing in imidazolinone resistance. The sunflower resistant genotypes evaluated here were 100-fold and 20-fold more resistant compared with the susceptible line for imazethapyr and imazapyr, respectively. This assay also allowed discrimination of homozygous from heterozygous genotypes for I(mr1) locus that codify for the catalytic subunit of AHAS. The in vivo AHAS assay described in this study was useful for the selection of sunflower genotypes differing in herbicide resistance and could be a useful tool when breeding for imidazolinone resistance in sunflower.

Sunflower propagation.

Sunflower (Helianthus annuus L.) has been cultivated both as an oilseed and as an ornamental plant. Several protocols have been described for the micropropagation, direct plant regeneration by organogenesis being acceptable for this plant species. Besides a strong genotype dependency, the type and ontogenic stage of explants, environmental conditions of the culture, and media composition affect sunflower organogenesis. Several problems have hindered the ability to regenerate normal shoots; the most common being hyperhydricity and precocious flowering. This chapter describes a protocol for direct shoot regeneration from cotyledons developed and established in our laboratory, as well as the improvement regenerated shoot quality.