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Abstract Purpose Acute respiratory distress syndrome (ARDS) is a prevalent respiratory condition associated with significant mortality. Current literature on ARDS epidemiology reports a wide range of incidence (7.2–78.9/100,000 population/year), hospital mortality (32–51%), and associated costs ($8476–$547,974). We have analyzed epidemiological trends of mechanically ventilated ARDS (MV-ARDS) in Spain from 2000 to 2022 using the Minimum Basic Data Set (MBDS), focusing on MV-ARDS incidence, associated mortality, and economic impact. Methods We conducted a nationwide, population-based retrospective study of all hospitalizations for MV-ARDS in Spanish hospitals—from January 1, 2000 to December 31, 2022—using MBDS records, with an estimated coverage of 99.5%. The study reports MV-ARDS incidence per 100,000 population/year, hospital mortality rate, and mean cost per patient. We also considered the effect of COVID-19 on MV-ARDS epidemiology. Results We analyzed 93,192 records of patients with a new diagnosis of MV-ARDS during the study period. MV-ARDS incidence ranged from 2.96 to 20.14/100,000 population-years, peaking in 2021. Mortality ranged between 38.0 and 55.0%, showing a declining trend, while the cost per patient increased, stabilizing ~€30,000–€40,000 after reaching a peak of €42,812 in 2011. During the COVID-19 pandemic, hospital stay lengthened (p

The present study explored pronunciation views, learning actions and anxiety in two differentiated English learner groups: one group which was studying English in an engineering degree and another group enrolled in an English major degree. The results from a questionnaire and focus group sessions revealed that the groups share some views such as a wish to improve their English pronunciation and adherence to native pronunciation references as well as pronunciation learning actions such as watching series or talking to native speakers. However, we also observed significant differences between the groups as the English major students tended to view pronunciation learning as a discipline, while the engineering students saw it as a communicative skill. The English majors also exhibited more pronunciation anxiety, specifically fear of ridicule and worry of making mistakes. They also revealed more anxiety-related themes in the focus group discussions such as worry about their pronunciation, pronunciation shame or unease because they do not know how to pronounce a word or cannot understand. Finally, the English major group was also more demanding of lecturers’ accurate pronunciation. These results suggest that differences regarding English pronunciation anxiety between different learner profiles may need to be considered during their English language learning progress.

Abstract There are many surgical techniques (packing, Pringle maneuver, etc.) and hemostatic agents to manage hepatic bleeding in trauma surgery. This study compares the effectiveness of two different types of hemostatic agents, one is an active flowable hemostat and the other is a passive hemostat made of modified absorbable polymers [MAP]. Both surgical technique and hemostatic agents can be used together as a means of controlling bleeding. We have hypothesized that a single hemostatic agent might be as effective as a unique hemostatic surgical technique. Twenty swine were prospectively randomized to receive either active Flowable (Floseal) or passive MAP powder (PerClot) hemostatic agents. We used a novel severe liver injury model that caused exsanguinating hemorrhage. The main outcome measure was total blood loss volume. The total volume of blood loss, from hepatic injury to minute 120, was significantly lower in the Flowable group (407.5 cm3; IqR: 195.0–805.0 cm3) compared to MAP group (1107.5 cm3; IqR: 822.5 to 1544.5 cm3) (Hodges–Lehmann median difference: − 645.0 cm3; 95% CI: − 1144.0 to − 280.0 cm3; p = 0.0087). The rate of blood loss was significantly lower in the flowable group compared with the MAP group as measured from time of injury to minutes 3, 9, 12, and 120 (except for 6 min). The mean arterial pressure gradually recovered in the flowable group by 24 h, whereas in the MAP group, the mean arterial pressure was consistently stayed below baseline values. Kaplan–Meier survival analysis indicated similar rates of death between study groups (Logrank test p = 0.3395). Both the flowable and the MAP hemostatic agents were able to effectively control surgical bleeding in a novel severe liver injury model, however, the flowable gelatin–thrombin agent provided quicker and better bleed control.

IntroductionGender incongruence (GI) is characterized by a marked incongruence between an individual’s experienced/expressed gender and the assigned sex at birth. It includes strong displeasure about his or her sexual anatomy and secondary sex characteristics. In some people, this condition produces a strong distress with anxiety and depression named gender dysphoria (GD). This condition appears to be associated with genetic, epigenetics, hormonal as well as social factors. Given that L-glutamate is the major excitatory neurotransmitter in the central nervous system, also associated with male sexual behavior as well as depression, we aimed to determine whether metabotropic glutamate receptors are involved in GD.MethodsWe analyzed 74 single nucleotide polymorphisms located at the metabotropic glutamate receptors (mGluR1, mGluR3, mGluR4, mGluR5, mGluR7 and mGluR8) in 94 transgender versus 94 cisgender people. The allele and genotype frequencies were analyzed by c2 test contrasting male and female cisgender and transgender populations. The strength of the associations was measured by binary logistic regression, estimating the odds ratio (OR) for each genotype. Measurement of linkage disequilibrium, and subsequent measurement of haplotype frequencies were also performed considering three levels of significance: P ≤ 0.05, P ≤ 0.005 and P ≤ 0.0005. Furthermore, false positives were controlled with the Bonferroni correction (P ≤ 0.05/74 = 0.00067).ResultsAfter analysis of allele and genotypic frequencies, we found twenty-five polymorphisms with significant differences at level P ≤ 0.05, five at P ≤ 0.005 and two at P ≤ 0.0005. Furthermore, the only two polymorphisms (rs9838094 and rs1818033) that passed the Bonferroni correction were both related to the metabotropic glutamate receptor 7 (mGluR7) and showed significant differences for multiple patterns of inheritance. Moreover, the haplotype T/G [OR=0.34 (0.19–0.62); P

Second language speech perception and production remain an enduring concern in second language acquisition, as research evidence seems to suggest that there is not a straightforward correspondence between these two speech domains and that their interrelationship seems to be of a complex nature. The present proposal intends to contribute to the inspection of such a relationship by observing the development of perception and production skills of English codas longitudinally in a group of secondary school learners in Spain involved in a content and language integrated learning (CLIL) program, which increases exposure and production opportunities. Results point to a slight overall improvement of both sound perception and production skills during a two-year period, the coda sounds exhibiting variable realizations. Many coda sounds were found to be identified and produced at near/ceiling levels while other codas remained at less successful identification and production levels even after two years of CLIL exposure. The correlation analyses performed indicated that the two dimensions tended to correlate when the development for each coda sound was inspected. No correlations were found when students’ individual overall performance in each dimension were examined, attesting individual differences.

IntroductionPrevalence and mortality of the acute respiratory distress syndrome (ARDS) in intensive care units (ICU) are unacceptably high. There is scarce literature on post-operative sepsis-induced ARDS despite that sepsis and major surgery are conditions associated with ARDS. We aimed to examine the impact of post-operative sepsis-induced ARDS on 60-day mortality.MethodsWe performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups depending on whether they met criteria for ARDS. Primary outcome was 60-day mortality of post-operative sepsis-induced ARDS. Secondary outcome measures were potential risk factors for post-operative sepsis-induced ARDS, and for 60-day mortality.ResultsHigher SOFA score (OR 1.1, 95% CI 1.0–1.3, p = 0.020) and higher lactate (OR 1.9, 95% CI 1.2–2.7, p = 0.004) at study inclusion were independently associated with ARDS. ARDS patients (n = 45) had higher ICU stay [14 (18) vs. 5 (11) days, p < 0.001] and longer need for mechanical ventilation [6 (14) vs. 1 (5) days, p < 0.001] than non-ARDS patients (n = 409). Sixty-day mortality was higher in ARDS patients (OR 2.7, 95% CI 1.1–6.3, p = 0.024). Chronic renal failure (OR 4.0, 95% CI 1.2–13.7, p = 0.026), elevated lactate dehydrogenase (OR 1.7, 95% CI 1.1–2.7, p = 0.015) and higher APACHE II score (OR 2.7, 95% CI 1.3–5.4, p = 0.006) were independently associated with 60-day mortality.ConclusionPost-operative sepsis-induced ARDS is associated with higher 60-day mortality compared to non-ARDS post-operative septic patients. Post-operative septic patients with higher severity of illness have a greater risk of ARDS and worse outcomes. Further investigation is needed in post-operative sepsis-induced ARDS to prevent ARDS.

Background. A prospective, descriptive, and multicenter research that included 1104 women with three or more uncomplicated UTIs following immunoprophylaxis with Uromune® vaccine between 2011 and 2022 is presented. Methods. Objective: to analyze the efficacy of Uromune® and perform a follow-up protocol. Variables: age; bacteria; number of UTIs at baseline and at 3, 6, and 12 months of follow-up; distribution according to age and months of the year; therapy with polybacterial vaccine or autovaccine. Efficacy was defined as 0–2 UTIs during follow-up. Patients were divided into Group 1, with 3–4 UTIs at baseline, and Group 2, with 5 or more. Results. Average age was 72. Escherichia coli represented 64.3% of infections. Overall efficacy was 91.7%, 82.3%, and 57.6% at 3, 6, and 12 months. Efficacy in patients treated with vaccines was 95.8%, 88.4%, and 56.1%, and with autovaccines it was 85.7%, 73.6%, and 60.2%. Results were statistically significant in relation to vaccines (p < 0.05). Group 1 represented 65.2% and Group 2 represented 34.8%. Group 1 had an efficacy of 97.7%, 91.1%, and 64.7% and Group 2 had an efficacy of 80.2%, 64.3%, and 40%. Results were statistically significant in Group 1 (p < 0.05). Conclusions. Patients at baseline with less than five UTIs will have better result and would benefit from a prophylaxis protocol with Uromune®.

We carried out a retrospective exploratory study on 173 patients who underwent major surgery and developed septic shock after surgery. Our findings suggest that CEACAM7 rs1001578, rs10409040, and rs889365 polymorphisms could influence septic shock-related death in individuals who underwent major surgery.

Background: Our goal was to evaluate whether TAP block offers the same analgesic pain control compared to epidural technique in laparoscopic radical prostatectomy surgery through the morphine consumption in the first 48 hours. Methods: In this study, 45 patients were recruited and assigned to either TAP or epidural. The main study outcome was morphine consumption during the first 48 hours after surgery. Other data recorded were pain at rest and upon movement, technique-related complications and adverse effects, surgical and postoperative complications, length of surgery, need for rescue analgesia, postoperative nausea and vomiting, start of intake, sitting and perambulation, first flatus, and length of in-hospital stay. Results: From a total of 45 patients, two were excluded due to reconversion to open surgery (TAP group = 20; epidural group = 23). There were no differences in morphine consumption (0.96 vs. 0.8 mg; p = 0.78); mean postoperative VAS pain scores at rest (0.7 vs. 0.5; p = 0.72); or upon movement (1.6 vs. 1.6; p = 0.32); in the TAP vs. epidural group, respectively. Sitting and perambulation began sooner in TAP group (19 vs. 22 hours, p = 0.03; 23 vs. 32 hours, p = 0.01; respectively). The epidural group had more technique-related adverse effects. Conclusion: TAP blocks provide the same analgesic quality with optimal pain control than epidural technique, with less adverse effects.

Abstract Background Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery. Methods We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation. Results In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded. Conclusions Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.

The integrated valorization of food chain waste is one of the most promising alternatives in the transition to a sustainable bioeconomy. Thus, an efficient solid-phase matrix dispersion extraction method, using experimental factorial design and response surface methodology, has been developed and optimized for the recovery of polyphenols from defatted cherry seeds obtained after cherry liquor manufacture and subsequent fatty acid extraction, evaluating the effect of each processing step on the composition and phenolic content of sweet cherry residues. The phenolic extracts before fermentation showed the highest content of total polyphenols (TPC) and flavonoids (TFC) (3 ± 1 mg QE·g−1 and 1.37 ± 0.08 mg GAE·g−1, respectively), while the highest antioxidant capacity was obtained in the defatted seed extracts after both fermentation and distillation. In addition, high-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer (HPLC-ESI-QTOF-MS) was used to determine the phenolic profile. Dihydroxybenzoic acid, neochlorogenic acid, caffeic acid, and quercetin were the main phenolics found, showing differences in concentration between the stages of liquor production. The results underline the prospective of cherry by-products for obtaining phenol-rich bioactive extracts for possible use in different industrial sectors, offering a feasible solution for the cascade valorization of cherry agri-food waste.

Prunus fruit seeds are one of the main types of agri-food waste generated worldwide during the processing of fruits to produce jams, juices and preserves. To valorize this by-product, the aim of this work was the nutritional analysis of peach, apricot, plum and cherry seeds using the official AOAC methods, together with the extraction and characterization of the lipid profile of seed oils using GC-FID, as well as the measurement of the antioxidant activity and oxidative stability using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging method. Chemometric tools were required for data evaluation and the obtained results indicated that the main component of seeds were oils (30–38%, w). All seed oils were rich in oleic (C18:1n9c) and linoleic (C18:2n6c) acids and presented heart-healthy lipid indexes. Oil antioxidant activity was estimated in the range IC50 = 20–35 mg·mL−1, and high oxidative stability was observed for all evaluated oils during 1–22 storage days, with the plum seed oil being the most antioxidant and stable over time. Oxidative stability was also positively correlated with oleic acid content and negatively correlated with linoleic acid content. Therefore, this research showed that the four Prunus seed oils present interesting healthy characteristics for their use and potential application in the cosmetic and nutraceutical industries.

Abstract Large-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We offer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self.

The fortification of foods with bioactive polyphenols aims to improve their functional properties and to provide health benefits. Yet, to exert their benefits, phenolic compounds must be released from the food matrix and absorbed by the small intestine after digestion, so assessing their bioaccessibility is crucial to determine their potential role. This work aims to incorporate Citrus reticulata Blanco peel extracts into wheat bread as a promising opportunity to increase their bioactive potential, along with supporting the sustainable management of citrus-industry waste. A control and a wheat bread enriched at 2% and 4% (w/v) with a phenolic extract from mandarin peels were prepared and analyzed for antioxidant activity and phenolic composition using LC-MS and UV-Vis spectrophotometry. In addition, in vitro digestion was performed, and the digested extracts were analyzed with HPLC-MS/MS. The results showed a significant increase in total flavonoid content (TFC, 2.2 ± 0.1 mg·g−1), antioxidant activity (IC50 = 37 ± 4 mg·g−1), and contents of quercetin, caffeic acid, and hesperidin in the 4% (w/v) enriched bread. Yet, most polyphenols were completely degraded after the in vitro digestion process, barring hesperidin (159 ± 36 μg·g−1), highlighting the contribution of citrus enrichment in the development of an enriched bread with antioxidant potential.

BackgroundHigh cytokine levels have been associated with severe COVID-19 disease. Although many cytokine studies have been performed, not many of them include combinatorial analysis of cytokine profiles through time. In this study we investigate the association of certain cytokine profiles and its evolution, and mortality in SARS-CoV2 infection in hospitalized patients.MethodsSerum concentration of 45 cytokines was determined in 28 controls at day of admission and in 108 patients with COVID-19 disease at first, third and sixth day of admission. A principal component analysis (PCA) was performed to characterize cytokine profiles through time associated with mortality and survival in hospitalized patients.ResultsAt day of admission non-survivors present significantly higher levels of IL-1α and VEGFA (PC3) but not through follow up. However, the combination of HGF, MCP-1, IL-18, eotaxine, and SCF (PC2) are significantly higher in non-survivors at all three time-points presenting an increased trend in this group through time. On the other hand, BDNF, IL-12 and IL-15 (PC1) are significantly reduced in non-survivors at all time points with a decreasing trend through time, though a protective factor. The combined mortality prediction accuracy of PC3 at day 1 and PC1 and PC2 at day 6 is 89.00% (p

Few studies have gauged the effects of Computer Assisted Language Learning –CALL– on the verbal accuracy of students. The current study explores the use of Hot Potatoes JCloze-type exercises as supplementary classroom work to enhance the English tense accuracy of university students enrolled in three EFL proficiency level courses -high-intermediate (B2) and advanced (C1 and C2). Tense marking was measured before and after a period of autonomous, self-paced CALL work in which students could access theoretical information and practiced with Hot Potatoes exercises. The comparisons revealed that the experience was mainly beneficial for the C1 level course group, the other two experimenting non-significant gains. Results only partially support a boosting effect of CALL additional practice. They also suggest that proficiency should be taken into consideration as it can affect the effect of treatment as not all the proficiency level courses experienced advantages. Alternatives to improve effectiveness are then suggested.

Introduction: Gender incongruence defines a state in which individuals feel discrepancy between the sex assigned at birth and their gender. Some of these people make a social transition from male to female (trans women) or from female to male (trans men). By contrast, the word cisgender describes a person whose gender identity is consistent with their sex assigned at birth. Aim: To analyze the implication of the estrogen receptor α gene (ESR1) in the genetic basis of gender incongruence. Main Outcome Measures: Polymorphisms rs9478245, rs3138774, rs2234693, rs9340799. Method: We carried out the analysis of 4 polymorphisms located at the promoter of the ESR1 gene (C1 = rs9478245, C2 = rs3138774, C3 = rs2234693, and C4 = rs9340799) in a population of 273 trans women, 226 trans men, and 537 cis gender controls. For SNP polymorphisms, the allele and genotype frequencies were analyzed by χ2 test. The strength of the SNP associations with gender incongruence was measured by binary logistic regression. For the STR polymorphism, the mean number of repeats were analyzed by the Mann–Whitney U test. Measurement of linkage disequilibrium and haplotype frequencies were also performed. Results: The C2 median repeats were shorter in the trans men population. Genotypes S/S and S/L for the C2 polymorphism were overrepresented in the trans men group (P = .012 and P = .003 respectively). We also found overtransmission of the A/A genotype (C4) in the trans men population (P = .017), while the A/G genotype (C4) was subrepresented (P = .009]. The analyzed polymorphisms were in linkage disequilibrium. In the trans men population, the T(C1)-L(C2)-C(C3)-A(C4) haplotype was overrepresented (P = .019) while the T(C1)-L(C2)-C(C3)-G(C4) was subrepresented (P = .005). Conclusion: The ESR1 is associated with gender incongruence in the trans men population.Fernández R, Delgado-Zayas E, Ramírez K, et al. Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence. Sex Med 2020;8:490–500.

Obtaining polyphenols from horticultural waste is an emerging trend that enables the valorization of resources and the recovery of value-added compounds. However, a pivotal point in the exploitation of these natural extracts is the assessment of their chemical stability. Hence, this study evaluates the effect of temperature storage (20 and −20 °C) and drying methods on the phenolic composition and antioxidant activity of clementine and lemon peel extracts, applying HPLC-DAD-MS, spectrophotometric methods, and chemometric tools. Vacuum-drying treatment at 60 °C proved to be rather suitable for retaining the highest antioxidant activity and the hesperidin, ferulic, and coumaric contents in clementine peel extracts. Lemon extracts showed an increase in phenolic acids after oven-drying at 40 °C, while hesperidin and rutin were sustained better at 60 °C. Hydroethanolic extracts stored for 90 days preserved antioxidant activity and showed an increase in the total phenolic and flavonoid contents in lemon peels, unlike in clementine peels. Additionally, more than 50% of the initial concentration was maintained up to 51 days, highlighting a half-life time of 71 days for hesperidin in lemon peels. Temperature was not significant in the preservation of the polyphenols evaluated, except for in rutin and gallic acid, thus, the extracts could be kept at 20 °C.

Background: Oxidative stress may be a key player in COVID-19 pathogenesis due to its significant role in response to infections. A defective redox balance has been related to viral pathogenesis developing a massive induction of cell death provoked by oxidative stress. The aim of this study is to perform a complete oxidative stress profile evaluation regarding antioxidant enzymes, total antioxidant capacity and oxidative cell damage in order to characterize its role in diagnosis and severity of this disease. Methods: Blood samples were obtained from 108 COVID-19 patients and 28 controls and metabolites representative of oxidative stress were assessed. The association between lipid peroxidation and 28-day intubation/death risk was evaluated by multivariable regression analysis. Probability of intubation/death to day-28 was analyzed by using Kaplan-Meier curves and tested with the log-rank test. Results: Antioxidant enzymes (Superoxide dismutase (SOD) and Catalase) and oxidative cell damage (Carbonyl and Lipid peroxidation (LPO)) levels were significantly higher in COVID-19 patients while total antioxidant capacity (ABTS and FRAP) levels were lower in these patients. The comparison of oxidative stress molecules’ levels across COVID-19 severity revealed that only LPO was statistically different between mild and intubated/death COVID-19 patients. COX multivariate regression analysis identified LPO levels over the OOP (LPO>1948.17 μM) as an independent risk factor for 28-day intubation/death in COVID-19 patients [OR: 2.57; 95% CI: 1.10–5.99; p = 0.029]. Furthermore, Kaplan-Meier curve analysis revealed that COVID-19 patients showing LPO levels above 1948.17 μM were intubated or died 8.4 days earlier on average (mean survival time 15.4 vs 23.8 days) when assessing 28-day intubation/death risk (p

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064–8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540–50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.

Abstract Background To prospectively analyze the efficacy of uromune® in the prevention of uncomplicated recurrent urinary tract infections at 3 and 6 months, and according to gender and menopause. Methods From September 2011 to December 2017 uromune® was administered sublingually every 24 h along 3 months to 784 patients with history of three or more uncomplicated urinary tract infections in the 12 months prior to the first visit. The variables analyzed with statistical package system for science version 15.0 were age, gender, number of urinary tract infections with positive urine culture in the first consultation, and 3 and 6 months after the end of treatment. The results with positive urine culture were registered at 3 and 6 months after the end of the treatment according to gender and also in the menopausal group with respect to pre-menopausal women. Results Mean age was 73.5 years. 82.7% were women and 94.3% menopausal. The number of episodes of urinary tract infections in the 12 months prior to uromune® were 3 in 37.2%, 4 in 28.1%, 5 in 19.5%, 6 in 9.6%, 7 in 4%, 8 in 1.4%, 9 in 0.1% and 10 in 0.1%. Three months after uromune® 44.1% had 0 urinary tract infections and 27.6% had 1. After 6 months the results were 0 urinary tract infections in 32.3% and 1 in 32.4%. Women had 0 urinary tract infections after 3 months in 45.4% and 1 in 28.5%. At 6 months the female had 0 episodes in 32.7% and 1 in 33.2%. Menopausal women had 0 urinary tract infections at 3 months in 46.5% and 1 in 28% and at 6 months scored 0 episodes in 33.6% and 1 in 32.9%. Conclusions Uromune® was highly effective to reduce the number of episodes of urinary tract infections at three and six months of follow-up. Uromune® reduced the number of episodes to zero or one in 71.7 and 64.7% at three and six months with minimal side effects. The best results were observed in women over 50 years old. Sublingual immunoprophylaxis with uromune® could be the treatment of first choice in the prevention of uncomplicated recurrent urinary tract infections according to the sample analyzed.

IntroductionThe main objective was to carry out a global DNA methylation analysis in a population with gender incongruence before gender-affirming hormone treatment (GAHT), in comparison to a cisgender population.MethodsA global CpG (cytosine-phosphate-guanine) methylation analysis was performed on blood from 16 transgender people before GAHT vs. 16 cisgender people using the Illumina© Infinium Human Methylation 850k BeadChip, after bisulfite conversion. Changes in the DNA methylome in cisgender vs. transgender populations were analyzed with the Partek® Genomics Suite program by a 2-way ANOVA test comparing populations by group and their sex assigned at birth.ResultsThe principal components analysis (PCA) showed that both populations (cis and trans) differ in the degree of global CpG methylation prior to GAHT. The 2-way ANOVA test showed 71,515 CpGs that passed the criterion FDR p < 0.05. Subsequently, in male assigned at birth population we found 87 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2) of which 22 were located in islands. The most significant CpGs were related to genes: WDR45B, SLC6A20, NHLH1, PLEKHA5, UBALD1, SLC37A1, ARL6IP1, GRASP, and NCOA6. Regarding the female assigned at birth populations, we found 2 CpGs that passed both criteria (FDR p < 0.05; fold change ≥ ± 2), but none were located in islands. One of these CpGs, related to the MPPED2 gene, is shared by both, trans men and trans women. The enrichment analysis showed that these genes are involved in functions such as negative regulation of gene expression (GO:0010629), central nervous system development (GO:0007417), brain development (GO:0007420), ribonucleotide binding (GO:0032553), and RNA binding (GO:0003723), among others.Strengths and LimitationsIt is the first time that a global CpG methylation analysis has been carried out in a population with gender incongruence before GAHT. A prospective study before/during GAHT would provide a better understanding of the influence of epigenetics in this process.ConclusionThe main finding of this study is that the cis and trans populations have different global CpG methylation profiles prior to GAHT. Therefore, our results suggest that epigenetics may be involved in the etiology of gender incongruence.

Objetivos: El objetivo de este artículo es analizar cronológicamente los inicios y evolución de la atención sanitaria en España a la transexualidad y variantes de género. Metodología: Se realiza un estudio descriptivo basado en la literatura publicada sobre atención sanitaria a la transexualidad en España, y en la información personal aportada directamente por los profesionales de las Unidades de Género y equipos emergentes de las diferentes comunidades autónomas. Resultados: La primeras reseñas históricas datan de los siglos XV y XVI. En fechas recientes, en el ámbito privado, las primeras vaginoplastias se realizan en el año 1983 y la primera faloplastia en 1989. En hospitales públicos, desde 1986 hay referencias aisladas en historias clínicas de atención psicológica, psiquiátrica o endocrinológica a estas personas, a pesar de la ausencia de respaldo legal. La creación de unidades de identidad de género se inicia en Andalucía (1999), y progresivamente se crean las unidades de Cataluña, Madrid, Aragón (2006), Asturias (2007), País Vasco, Comunidad Valenciana y Canarias (2008), Navarra (2010) y Castilla-León (2014). En los últimos 5 años el resto de comunidades comienzan a diseñar nuevos equipos y protocolos de atención, y se producen cambios en los modelos asistenciales en el contexto de las demandas de colectivos por la autodeterminación del género y descentralización. Conclusiones: En España en los últimos 20 años se han creado de forma secuencial varias unidades multidisciplinares de identidad de género en diversas comunidades, que han alcanzado niveles de calidad, a pesar de los limitados recursos y de las inequidades entre comunidades. En los precedentes 5 años se han producido cambios en estos modelos de atención que, en algunos aspectos metodológicos, difieren de las guías clínicas existentes en los países europeos de nuestro entorno.

ABSTRACT: Introduction: Brain sexual differentiation results from the effects of sex steroids on the developing brain. The presumptive route for brain masculinization is the direct induction of gene expression via activation of the estrogen receptors α and β and the androgen receptor through their binding to ligands and to coactivators, regulating the transcription of multiple genes in a cascade effect. Aim: To analyze the implication of the estrogen receptor coactivators SRC-1, SRC-2, and SRC-3 in the genetic basis of gender incongruence. Main Outcome Measures: Analysis of 157 polymorphisms located at the estrogen receptor coactivators SRC-1, SRC-2, and SRC-3, in 94 transgender versus 94 cisgender individuals. Method: Using SNPStats software, the allele and genotype frequencies were analyzed by χ2, the strength of the association was measured by binary logistic regression, estimating the odds ratio for each genotype. Measurements of linkage disequilibrium and haplotype frequencies were also performed. Results: We found significant differences at level P < .05 in 8 polymorphisms that correspond to 5.09% of the total. Three were located in SRC-1 and 5 in SRC-2. The odds ratio analysis showed significant differences at level P < .05 for multiple patterns of inheritance. The polymorphisms analyzed were in linkage disequilibrium. The SRC-1 haplotypes CGA and CGG (global haplotype association P < .009) and the SRC-2 haplotypes GGTAA and GGTAG (global haplotype association P < .005) were overrepresented in the transgender population. Conclusion: The coactivators SRC-1 and SRC-2 could be considered as candidates for increasing the list of potential genes for gender incongruence. Ramírez KDV, Fernández R, Delgado-Zayas E, et al. Implications of the Estrogen Receptor Coactivators SRC1 and SRC2 in the Biological Basis of Gender Incongruence. Sex Med 2021;9:100368.

We provide T2*-weighted and T1-weighted images acquired on a 3T MRI scanner obtained from 17 transwomen and 29 transmen with gender incongruence; and 22 ciswomen and 19 cismen that identified themselves to the sex assigned at birth. Data from three different techniques that describe global and regional connectivity differences within functional resting-state networks in transwomen and transmen with early-in-life onset gender incongruence are provided: (1) we obtained spatial maps from data-driven independent component analysis using the melodic tool from FSL software; (2) we provide the functional networks interactions of two functional atlases’ seeds from a seed-to-seed approach; (3) and global graph-theoretical metrics such as the smallworld organization, and the segregation and integration properties of the networks. Interpretations of the present dataset can be found in the original article, doi:10.1016/j.neuroimage.2020.116613 [1]. The original and processed nifti images are available in Mendeley datasets. In addition, correlation matrices for the seed-to-seed and graph-theory analyses as well as the graph-theoretical measures were made available in Matlab files. Finally, we present supplementary information for the original article.

Objectives To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency.Design Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain).Participants 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm.Interventions The IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52.Main outcomes Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction.Results The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route.Conclusions Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Trial registration numbers NCT 01476007; EUDRACT (2010-024129-20).

Interferon lambda 3 (IFNL3, previously called IL-28B) is a cytokine with effects against viral and bacterial pathogens. We aimed to analyze the IFNL3 rs12980275 SNP in patients who underwent major surgery, in order to establish its relationship with susceptibility to septic shock and septic shock-related death in these patients. We performed a case-control study on 376 patients to establish the association between IFNL3 rs12980275 SNP and the susceptibility to develop septic shock. Besides, we performed a longitudinal study among 172 septic shock patients using survival analysis with one censoring point of 28-days mortality. The IFNL3 rs12980275 polymorphism was genotyped by Agena Bioscience's MassARRAY platform. IFNL3 rs12980275 polymorphism was not associated with higher susceptibility to infection and septic shock development. Regarding survival analysis, the Kaplan–Meier analysis showed that patients with IFNL3 rs12980275 AA genotype had higher survival than patients with GG genotype (p = 0.003). The Cox regression analysis adjusted by the most relevant clinical and epidemiological characteristics showed that the GG genotype (recessive model) and the presence of the G allele (additive model) were associated with higher risk of death [adjusted hazard ratio (aHR) = 2.15, p = 0.034; aHR = 1.50, p = 0.030, respectively]. In conclusion, IFNL3 rs12980275 polymorphism was associated with septic shock-related death in patients who underwent major surgery. The A allele was linked to protection, and the G allele was associated with an increased risk of death. This is a first preliminary study that suggests for the first time a role of IFNL3 polymorphisms in the prognosis of septic shock.

Functional brain organization in transgender persons remains unclear. Our aims were to investigate global and regional connectivity differences within functional networks in transwomen and transmen with early-in-life onset gender incongruence; and to test the consistency of two available hypotheses that attempted to explain gender variants: (i) a neurodevelopmental cortical hypothesis that suggests the existence of different brain phenotypes based on structural MRI data and genes polymorphisms of sex hormone receptors; (ii) a functional-based hypothesis in relation to regions involved in the own body perception. T2*-weighted images in a 3-T MRI were obtained from 29 transmen and 17 transwomen as well as 22 cisgender women and 19 cisgender men. Resting-state independent component analysis, seed-to-seed functional network and graph theory analyses were performed. Transmen, transwomen, and cisgender women had decreased connectivity compared with cisgender men in superior parietal regions, as part of the salience (SN) and the executive control (ECN) networks. Transmen also had weaker connectivity compared with cisgender men between intra-SN regions and weaker inter-network connectivity between regions of the SN, the default mode network (DMN), the ECN and the sensorimotor network. Transwomen had lower small-worldness, modularity and clustering coefficient than cisgender men. There were no differences among transmen, transwomen, and ciswomen. Together these results underline the importance of the SN interacting with DMN, ECN, and sensorimotor networks in transmen, involving regions of the entire brain with a frontal predominance. Reduced global connectivity graph-theoretical measures were a characteristic of transwomen. It is proposed that the interaction between networks is a keystone in building a gendered self. Finally, our findings suggest that both proposed hypotheses are complementary in explaining brain differences between gender variants.

Abstract Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73–0.88],

The vaccines designed against the SARS-CoV-2 coronavirus are based on the spike (S) protein. Processing of the S protein by antigen-presenting cells (APC) and its subsequent presentation to T cells is an essential part of the development of a humoral response. HLA-class II alleles are considered immune response genes because their codified molecules, expressed on the surface of APCs (macrophages, dendritic, and B cells) present antigenic peptides to T cell via their T cell receptor (TCR). The HLA-class II genes are highly polymorphic, regulating what specific peptides induce follicular helper T cells (TFH) and promote B lymphocyte differentiation into plasma or memory B cells. This work hypothesizes that the presence of certain HLA-class II alleles could be associated with the intensity of the humoral response (amount, length) to the SARS-CoV2 mRNA 1273 vaccine. We have studied the relationship between the HLA-class II typing of 87 health workers and the level of antibodies produced 30 days after vaccination. We show a possible association between the HLA-DRB1* 07:01 allele and the HLA-DRB1*07:01~DQA1*02:01~DQB1*02:02 haplotype to a higher production of antibodies 30 days after the administration of the second dose of mRNA-1273.

Objetivo: Determinar la prevalencia de síntomas sugestivos de vejiga hiperactiva (VH) en una población española y evaluar su impacto en el bienestar y la productividad laboral de esta población. Diseño: Estudio transversal. Emplazamiento: Atención primaria, Madrid, España. Participantes: Varones y mujeres > 30 años. Intervenciones: Clasificación con el instrumento abreviado Overactive Bladder Awareness Tool (OAB-V3). Sujetos con puntuación ≥ 3 y una población control similar con puntuación

Estamos en una época, y esto se acrecentará en un futuro próximo, en que si no apareces en las redes de Internet, es como si no existieras. Antes, el medio de comunicación por excelencia era la televisión, un canal por el que podías estar informado y a la vez entretenerte. Con la aparición y la evolución de Internet y las autopistas de la información, esta función se ha diluido o se ha dividido entre Internet y los medios de comunicación llamados convencionales.

The objectives of this study were to report on the antimicrobial susceptibility of 141 clinically significant anaerobic bacteria isolated from bloodstream infections between January 2016 and April 2020 in a tertiary-care hospital in Granada (Spain) and to describe the main clinical features of the patients. Species identification was performed by MALDI-TOF MS (Bruker Daltonics, Billerica, MA, USA). Antimicrobial susceptibility tests were performed against penicillin, amoxicillin-clavulanic acid, imipenem, moxifloxacin, clindamycin, metronidazole, and piperacillin-tazobactam using the gradient diffusion technique and EUCAST breakpoints, except for moxifloxacin (CLSI breakpoints). The most frequent anaerobes were Bacteroides (43.9%, n = 62), Clostridium (24.1%, n = 34) and Gram-positive anaerobic cocci (GPACs) (15.6%, n = 22). Almost all tested anaerobes were susceptible to imipenem and amoxicillin-clavulanic acid, except for Bacteroides. High overall resistance rates to clindamycin were observed, especially for Gram-positive anaerobic cocci (GPACs) (54.5%) and for Bacteroides spp. (45.1%). Overall, low resistance rates to almost all antibiotics were observed for Clostridium. High resistance rates to penicillin were also observed for Gram-positive anaerobic bacilli (GPABs) (44.4%), as well as to metronidazole (22.2%), although only nine isolates were included. Antimicrobial susceptibility testing for anaerobes should always be performed in severe infections, such as those localized in the bloodstream. The information obtained contributes to selecting empirical treatments according with local data on resistance.

A fascinating characteristic of most members of the genus Flavobacterium is their ability to move over surfaces by gliding motility. Flavobacterium psychrophilum, an important pathogen of farmed salmonids worldwide, contains in its genome the 19 gld and spr genes shown to be required for gliding or spreading in Flavobacterium johnsoniae; however, their relative role in its lifestyle remains unknown. In order to address this issue, two spreading deficient mutants were produced as part of a Tn4351 mutant library in F. psychrophilum strain THCO2-90. The transposons were inserted in gldD and gldG genes. While the wild-type strain is proficient in adhesion, biofilm formation and displays strong proteolytic activity, both mutants lost these characteristics. Extracellular proteome comparisons revealed important modifications for both mutants, with a significant reduction of the amounts of proteins likely transported through the outer membrane by the Type IX secretion system, indicating that GldD and GldG proteins are required for an effective activity of this system. In addition, a significant decrease in virulence was observed using rainbow trout bath and injection infection models. Our results reveal additional roles of gldD and gldG genes that are likely of importance for the F. psychrophilum lifestyle, including virulence.

This study aims at testing the effectiveness of additional CLIL (Content and Language Integrated Learning) exposure on the oral production of secondary school learners of English as a Foreign Language. CLIL learners, who had received a 30% increase in exposure by means of using English as a vehicular language, were compared to mainstream English students in a story-telling task. Analyses indicated that CLIL learners’ productions were holistically perceived to exhibit better fluency, lexis and grammar while no differences were found as regards content and pronunciation. Besides, although Non-CLIL learners’ productions were larger in quantity and longer in time, CLIL learners produced denser and more fluent narrations, as attested by their higher number of different words over total number of words, of words over turn, and of utterances over turn. Additionally, CLIL learners resorted to their first language to a lesser extent and demanded fewer vocabulary clarifications. Our findings thus go along with previous research which has revealed advantages of additional CLIL exposure on oral English production.

For solving nonlinear systems of big size, such as those obtained by applying finite differences for approximating the solution of diffusion problem and heat conduction equations, three-step iterative methods with eighth-order local convergence are presented. The computational efficiency of the new methods is compared with those of some known ones, obtaining good conclusions, due to the particular structure of the iterative expression of the proposed methods. Numerical comparisons are made with the same existing methods, on standard nonlinear systems and a nonlinear one-dimensional heat conduction equation by transforming it in a nonlinear system by using finite differences. From these numerical examples, we confirm the theoretical results and show the performance of the presented schemes.

Objetivo: El reconocimiento del transexualismo como una condición clínica que debe ser atendida de forma disciplinaria es hoy una realidad bien establecida, pero la implementación de la atención sanitaria institucional dista mucho de haberse generalizado en España. El objetivo es conocer la situación actual de la organización asistencial a la transexualidad en el sistema sanitario público español. Método: Estudio descriptivo con los datos aportados por Grupo de la Sociedad Española de Endocrinología sobre Identidad y Diferenciación Sexual (GIDSEEN). Se describe la dotación en las comunidades autónomas cuyas consejerías de salud han creado unidades específicas de atención a estos trastornos. Resultados: Nueve comunidades (55%) diseñan actuaciones, aunque sólo cuatro contemplan cirugías genitoplásticas. La primera en incluir todas las cirugías de reasignación sexual es Andalucía (año 1999). Madrid y Cataluña inician también en esta fecha atención especializada en salud mental y endocrinología, y no incluyen intervenciones y reconocimiento oficial hasta 2007 y 2008, respectivamente. A partir de 2007 se van incorporando otras autonomías. En este trabajo se registran 3303 pacientes (proporción: 1,9/1 transexuales hombre-mujer/transexuales mujer-hombre) y 864 actos quirúrgicos. La composición y dedicación de los especialistas, y la cartera de servicios, son muy diferentes en cada comunidad. Conclusiones: La distribución geográfica y la oferta terapéutica son dispares, con escasa incorporación de procedimientos genitoplásticos en la mayoría de comunidades. El número de solicitudes supera los cálculos estimados por el Sistema Nacional de Salud.Objective: Recognition of transexuality as a clinical entity for which medical attention should be available is currently a well-established reality, but institutional care has not been uniformly instituted throughout Spain. The aim of the present study was to determine the current situation of healthcare for transexualism in the publicly-funded health service in Spain. Materials and methods: A descriptive study based on data provided by the Spanish Society of Endocrinology Group on Identity and Sexual Differentiation was performed. The resources in the regions that have created specific gender units for these disorders are described. Results: Nine autonomous regions (55%) have started to provide various procedures, although only four provide genitoplastic procedures. The first region to include all sex reassignment surgeries was Andalusia (year 1999). At the same time, Madrid and Catalonia also began to provide specialized mental health care and endocrinology but did not include surgical procedures until 2007 and institutional recognition until 2008. Since 2007 other regions have incorporated healthcare for transsexual patients. Overall, 3,303 patients (a male-to female/female-to-male transsexual ratio of 1.9/1) and 864 surgical procedures have been registered in this study. The composition and proportion of working hours of specialists, as well as the kinds of treatments provided, differ widely in each region. Conclusions: The geographical distribution of healthcare to transsexual persons and the services provided vary. Few regions offer genitoplastic procedures. The number of applicants exceeds the number estimated by the national health system.

El objetivo del presente trabajo es presentar l caso de un varón de 88 años que ha presentado en los últimos tres años tres episodios de hiponatremia por SIADH en relación con el uso fármacos inhibidores de la recaptación de serotonina (ISRS) que han requerido de ingreso hospitalario. En dos de estos episodios el paciente estaba en tratamiento concomitante con diuréticos tiazídicos, siendo la sertralina el fármaco antidepresivo implicado, y en uno de los tres episodios el paciente estaba en tratamiento con citalopram sin que existiera tratamiento diurético concomitante alguno. Se revisan los factores de riesgo para esta complicación, se revisa la literatura al respecto y se establecen recomendaciones de control

This study examines the ability to identify the English phonological contrast full vowel-schwa by Spanish learners of English after two different types of training: auditory and articulatory. Perceptual performance was measured in isolated words in order to investigate the effect of training and in sentences to study the robustness of acquisition in generalizing to a context which was not used during training. Subjects were divided into three groups: two experimental groups, one undergoing perceptual training and one undergoing production based training, and a control group. Both experimental groups' perception of the reduced vowel improved significantly after training. Results indicated that students were able to generalize their reduced vowel identification abilities to the new context. The control group did not show any significant improvement. Our findings agree with studies that have demonstrated positive effects of phonetic training (Derwing. Munro & Wiebe, 1998; Rochet, 1995; Cenoz & García Lecumberri, 1995, 1999). Interestingly, the results also support the facilitating view between perception and production since production training proved beneficial in the development of perceptual abilities (Catford & Pisoni, 1970; Mathews, 1997). Finally, our data showed that training resulted in robust learning, since students were able generalize their improved perceptual abilities to a new context.

El presente trabajo versa sobre la enseñanza de las vocales inglesas a estudiantes españoles. En la introducción se analiza la importancia que tiene abordar la pronunciación en el aula de lengua extranjera en la persecución del logro de un acento nativo o de una pronunciación inteligible, se enfatiza el papel tan importante que juega el sistema de sonidos de la primera lengua a la hora de adquirir la pronunciación de un segundo idioma y se revisa el papel del profesor en la enseñanza de la pronunciación. La segunda parte presenta un estudio comparativo de los sistemas vocálicos del inglés y del castellano que ayuda en la comprensión de las diferencias y similitudes existentes entre ambos sistemas a fin de poder entender muchos de los fenómenos presentes en la pronunciación de las vocales inglesas por parte de los hablantes de español. La última sección incluye una serie de recursos didáctico-pedagógicos para la instrucción formal de la pronunciación del inglés, con especial referencia al componente vocálico.

This study examines the ability to identify the English phonological contrast full vowel-schwa by Spanish learners of English after two different types of training: auditory and articulatory. Perceptual performance was measured in isolated words in order to investigate the effect of training and in sentences to study the robustness of acquisition in generalizing to a context which was not used during training. Subjects were divided into three groups: two experimental groups, one undergoing perceptual training and one undergoing production based training, and a control group. Both experimental groups' perception of the reduced vowel improved significantly after training. Results indicated that students were able to generalize their reduced vowel identification abilities to the new context. The control group did not show any significant improvement. Our findings agree with studies that have demonstrated positive effects of phonetic training (Derwing. Munro & Wiebe, 1998; Rochet, 1995; Cenoz & García Lecumberri, 1995, 1999). Interestingly, the results also support the facilitating view between perception and production since production training proved beneficial in the development of perceptual abilities (Catford & Pisoni, 1970; Mathews, 1997). Finally, our data showed that training resulted in robust learning, since students were able generalize their improved perceptual abilities to a new context.

Flavobacterium psychrophilum is a Gram-negative fish pathogen that causes important economic losses in aquaculture worldwide. Although the genome of this bacterium has been determined, the function and relative importance of genes in relation to virulence remain to be established. To investigate their respective contribution to the bacterial pathogenesis, effective tools for gene inactivation are required. In the present study, a markerless gene deletion system has been successfully developed for the first time in this bacterium. Using this method, the F. psychrophilum fcpB gene, encoding a predicted cysteine protease homologous to Streptococcus pyogenes streptopain, was deleted. The developed system involved the construction of a conjugative plasmid that harbors the flanking sequences of the fcpB gene and an I-SceI meganuclease restriction site. Once this plasmid was integrated in the genome by homologous recombination, the merodiploid was resolved by the introduction of a plasmid expressing I-SceI under the control of the fpp2 F. psychrophilum inducible promoter. The resulting deleted fcpB mutant presented a decrease in extracellular proteolytic activity compared to the parental strain. However, there were not significant differences between their LD50 in an intramuscularly challenged rainbow trout infection model. The mutagenesis approach developed in this work represents an improvement over the gene inactivation tools existing hitherto for this "fastidious" bacterium. Unlike transposon mutagenesis and gene disruption, gene markerless deletion has less potential for polar effects and allows the mutation of virtually any non-essential gene or gene clusters.

The asymmetric ligand (E)-4-bromo-2-(((2-((5-bromo-2-hydroxybenzyl)(methyl)amino)ethyl)imino)methyl)phenol has been prepared by a novel seven-step route. All organic compounds isolated in each step have been characterised by elemental analysis, infrared and 1H NMR spectroscopy, and mass spectrometry. Interaction of this ligand with manganese has been investigated employing an electrochemical method. This method leads to the formation of a neutral manganese(II) complex 7 in high yield and purity. The complex has been thoroughly characterised by elemental analysis, infrared spectroscopy, mass spectrometry, magnetic susceptibility measurements, and cyclic voltammetry. Complex 7 behaves as peroxidase mimic in the presence of the water-soluble trap ABTS, probably due to its ease to coordinate the substrate molecule.

Sin resumen

Hemos estudiado 109 pacientes esquizofrénicos atendidos durante un año en el CSM de Getafe. De sus historias clínicas hemos CSM recogido la dosis de mantenimiento con neurolépticos, datos sociodemográficos y las recaídas en el último año. La dosis de mantenimiento con neurolépticos mayoritariamente empleada se cuentra dentro del rango considerado como dosis baja por diferentes autores. El uso de estas bajas dosis no determina un mayor número de recaídas.

En los talleres de arte “Mi ciudad inventada” niños y niñas desarrollaron el diseño de una ciudad propia en escala a partir de materiales de reciclaje. Partiendo como detonante del derecho humano a una vivienda digna, los niños participantes en el taller diseñaron y crearon su propio espacio urbano. La propuesta de diseño se realizó en paralelo con niños hospitalizados durante el período de vacaciones escolares, adaptando los materiales para el uso específico en el hospital.

The Law 54/2007 of 28 December, on International Adoption, which entered in force on 30th December 2007, has amended the rules of procedure relating to international adoption. The objective of this law is to provide the necessary legal instruments so that the adoptive process takes place with maximum guarantees and the respect for the interests of the children to be adopted. The new Act wants to cover all the involved issues of Private International Law: applicable law, jurisdiction, recognition and enforcement of foreign decisions in matters of adoption. The Spanish legislator has intended to eliminate - although sometimes fails - the legal deficiencies which have motivated in the past unfortunate judicial judgments. The interest of this new Act is evident for many reasons and not all of a legal character