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Background: The administration of colostrum through its absorption at the oropharyngeal level stimulates the mucosa-associated lymphoid tissue, providing a local immunological protection barrier. The study aimed to investigate the association of oropharyngeal colostrum administration with the reduction of inflammatory indices. Materials and methods: This was an observational, ambispective, analytical study of newborns < 32 weeks of gestation at risk of sepsis. Oropharyngeal colostrum was administered at 0.2 mL every 4 h for 5 days. Inflammatory indices were analyzed. Statistical analysis included frequencies, percentages, mean and Standard deviation, contingency coefficient, and Kolmogorov–Smirnov test for the distribution curve of the numerical data. Results: There were 50 patients, 33 (66%) female and 17 (34%) male, with a median gestational age of 30-31 weeks (95% confidence interval [CI]). Nineteen patients had sepsis. A lower positivity rate in C-reactive protein was found, with a median of 0.5-0.6 (95% CI) at 5 days of colostrum administration versus 0.5-1.1 (95% CI) as the initial C-reactive protein. Analysis with χ2 yielded a p = 0.13, and the contingency coefficient showed a p = 0.196, indicating an association. Conclusion: Oropharyngeal colostrum administration was associated with a lower C-reactive protein positivity rate and clinical improvement in premature newborns at risk of sepsis.

Objetivo: Conocer la asociación de hallazgos del ultrasonido abdominal en recién nacidos pretérmino con enterocolitis necrosante (ECN). Método: Estudio transversal, analítico, pacientes con ECN. Se realizó ultrasonido abdominal: líquido libre, pared intestino grueso más de 2.5 mm, pared intestino delgado menos de 1.1 mm, gas en vena porta, neumatosis intestinal, disminución y/o ausencia de peristalsis, aumento y/o ausencia de perfusión sanguínea intestinal. Se utilizó chi cuadrada, U de Mann-Whitney para asociación hallazgos ecográficos y ECN, alfa < 0.05, programa SPSS v.23. Resultados: 37 pacientes. Estadio IA: pared de intestino delgado menor de 1.1 mm fueron 15 (40%) pacientes, líquido libre 13 (35%), peristalsis disminuida 11 (29%), ausencia de peristalsis en algunas zonas 8 (21%). Estadio IB: líquido libre y perfusión sanguínea aumentada 2 (5%). Estadio IIA: peristalsis disminuida 7 (18%), pared de intestino delgado menor de 1.1 mm 4(10%), líquido libre 3(8.%), neumatosis 2 (5%), perfusión sanguínea ausente 1 (2%). Estadio IIIA: 1(2%) líquido libre, adelgazamiento de pared de intestino delgado menor de 1.1 mm, ausencia de peristalsis, perfusión sanguínea ausente. Conclusión: Existe asociación de los hallazgos ultrasonográficos en pacientes con ECN. El más frecuente fue adelgazamiento de la pared intestinal de intestino delgado, líquido libre y peristalsis disminuida, sería útil como método diagnóstico para toma de decisiones médico quirúrgico.

Bacteria have developed fine-tuned responses to cope with potential zinc limitation. The Zur protein is a key player in coordinating this response in most species. Comparative proteomics conducted on the cyanobacterium Anabaena highlighted the more abundant proteins in a zur mutant compared to the wild type. Experimental evidence showed that the exoprotein ZepA mediates zinc uptake. Genomic context of the zepA gene and protein structure prediction provided additional insights on the regulation and putative function of ZepA homologs. Phylogenetic analysis suggests that ZepA represents a primordial system for zinc acquisition that has been conserved for billions of years in a handful of species from distant bacterial lineages. Furthermore, these results show that Zur may have been one of the first regulators of the FUR family to evolve, consistent with the scarcity of zinc in the ecosystems of the Archean eon.

Abstract Background Modelling the course of a disease regarding severe events and identifying prognostic factors is of great clinical relevance. Multistate models (MSM) can be used to describe diseases or processes that change over time using different states and the transitions between them. Specifically, they are useful to analyse a disease with an increasing degree of severity, that may precede death. The complexity of these models changes depending on the number of states and transitions taken into account. Due to that, a web tool has been developed making easier to work with those models. Results MSMpred is a web tool created with the shiny R package that has two main features: 1) to allow to fit a MSM from specific data; 2) to predict the clinical evolution for a given subject. To fit the model, the data to be analysed must be upload in a prespecified format. Then, the user has to define the states and transitions as well as the covariates (e.g., age or gender) involved in each transition. From this information, the app returns histograms or barplots, as appropriate, to represent the distributions of the selected covariates and boxplots to show the patient’ length of stay (for uncensored data) in each state. To make predictions, the values of selected covariates from a new subject at baseline has to be provided. From these inputs, the app provides some indicators of the subject’s evolution such as the probability of 30-day death or the most likely state at a fixed time. Furthermore, visual representations (e.g., the stacked transition probabilities plot) are given to make predictions more understandable. Conclusions MSMpred is an intuitive and visual app that eases the work of biostatisticians and facilitates to the medical personnel the interpretation of MSMs.

Abstract Background The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period. Methods We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The distribution of the incubation period was estimated using the generalized odds-rate class of regression models. Results From 406 surveyed patients, 242 provided adequate information to be included in the analysis. The median incubation period was 2.8 days (95%CI: 2.5–3.1) and no differences between vaccinated and unvaccinated patients were found. Sex and age are neither shown not to be significantly related to the COVID-19 incubation time. Conclusions Knowing the incubation period is crucial for controlling the spread of an infectious disease: decisions on the duration of the quarantine or on the periods of active monitoring of people who have been at high risk of exposure depend on the length of the incubation period. Furthermore, its probability distribution is a key element for predicting the prevalence and the incidence of the disease.

Antecedentes: Las malformaciones del tracto urinario representan el 15-20% de las anomalías por ecografía prenatal; la prevalencia oscila entre 3 y 6 por cada 1,000 nacimientos. Objetivo: Conocer el desenlace clínico de los recién nacidos diagnosticados prenatalmente con malformación del tracto urinario. Material y métodos: Observacional, analítico, ambispectivo. Recién nacidos con diagnóstico prenatal de malformación urinaria. Evaluación posnatal con pruebas diagnósticas, analizamos días de estancia hospitalaria, intervención quirúrgica y seguimiento. Resultados: 45 pacientes, 55% varones, 65% de término, 77% cesárea. El diagnóstico prenatal más frecuente fue hidronefrosis, 100% se realizó ultrasonido renal posnatal, 27% cistograma miccional, 42% gammagrama renal; 60% requirió estancia hospitalaria prolongada, 27% intervención quirúrgica, 60% seguimiento. 89% de los casos diagnosticados prenatalmente se corroboró algún tipo de malformación del tracto urinario, solo en el 75% de los casos fue el mismo diagnóstico. Conclusión: La evaluación posnatal siempre requiere la realización de un ultrasonido renal y no en todos los casos realización de cistograma miccional o gammagrama renal.

La internacionalización es uno de los objetivos de la Educación Superior, aspecto abordado en relación a la iniciativa “El pelo/cabello es epistemología”, actividad de participación binacional, con el (re)conocimiento de temas de estudio tan relevantes como poder, pelo/cabello, feminismo y (anti)racismo. Realizamos la sistematización de un intercambio de experiencias entre la Universidad Técnica “Luis Vargas Torres” de Esmeraldas (Ecuador) y la Universidad de Jaén (España), a través de un proceso iniciado “desde abajo” y que ha propuesto otra forma de cooperar. La metodología ha rodeado el artivismo desde una decidida posición (anti)racista y feminista. El objetivo ha sido crear un espacio activista de cooperación para compartir proyectos de intervención e investigación que innovasen y tuvieran compromiso con el territorio, partiendo del conflicto que produce el pelo/cabello asociado a “raza” y ésta al poder, triangulación extrapolable a otros sures de fuerte evidencia sociocultural en el impacto de la acción (anti)racista.

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [−2.79 mg/dl (95% CI: −4.25, −1.34) and −5.15 mg/dl (95% CI: −7.38, −2.93), p-values = 0.0002 and

ABSTRACT Marine Synechococcus, together with Prochlorococcus, contribute to a significant proportion of the primary production on Earth. The spatial distribution of these two groups of marine picocyanobacteria depends on different factors such as nutrient availability and temperature. Some Synechococcus ecotypes thrive in mesotrophic and moderately oligotrophic waters, where they exploit both oxidized and reduced forms of nitrogen. Here, we present a comprehensive study, which includes transcriptomic and proteomic analyses of the response of Synechococcus sp. strain WH7803 to nanomolar concentrations of nitrate, compared to micromolar ammonium or nitrogen starvation. We found that Synechococcus has a specific response to a nanomolar nitrate concentration that differs from the response shown under nitrogen starvation or the presence of standard concentrations of either ammonium or nitrate. This fact suggests that the particular response to the uptake of nanomolar concentrations of nitrate could be an evolutionary advantage for marine Synechococcus against Prochlorococcus in the natural environment. IMPORTANCE Marine Synechococcus are a very abundant group of photosynthetic organisms on our planet. Previous studies have shown blooms of these organisms when nanomolar concentrations of nitrate become available. We have assessed the effect of nanomolar nitrate concentrations by studying the transcriptome and proteome of Synechococcus sp. WH7803, together with some physiological parameters. We found evidence that Synechococcus sp. strain WH7803 does sense and react to nanomolar concentrations of nitrate, suggesting the occurrence of specific adaptive mechanisms to allow their utilization. Thus, very low concentrations of nitrate in the ocean seem to be a significant nitrogen source for marine picocyanobacteria.

Abstract Background Sample size calculation is a key point in the design of a randomized controlled trial. With time-to-event outcomes, it’s often based on the logrank test. We provide a sample size calculation method for a composite endpoint (CE) based on the geometric average hazard ratio (gAHR) in case the proportional hazards assumption can be assumed to hold for the components, but not for the CE. Methods The required number of events, sample size and power formulae are based on the non-centrality parameter of the logrank test under the alternative hypothesis which is a function of the gAHR. We use the web platform, CompARE, for the sample size computations. A simulation study evaluates the empirical power of the logrank test for the CE based on the sample size in terms of the gAHR. We consider different values of the component hazard ratios, the probabilities of observing the events in the control group and the degrees of association between the components. We illustrate the sample size computations using two published randomized controlled trials. Their primary CEs are, respectively, progression-free survival (time to progression of disease or death) and the composite of bacteriologically confirmed treatment failure or Staphylococcus aureus related death by 12 weeks. Results For a target power of 0.80, the simulation study provided mean (± SE) empirical powers equal to 0.799 (±0.004) and 0.798 (±0.004) in the exponential and non-exponential settings, respectively. The power was attained in more than 95% of the simulated scenarios and was always above 0.78, regardless of compliance with the proportional-hazard assumption. Conclusions The geometric average hazard ratio as an effect measure for a composite endpoint has a meaningful interpretation in the case of non-proportional hazards. Furthermore it is the natural effect measure when using the logrank test to compare the hazard rates of two groups and should be used instead of the standard hazard ratio.

El rabdomioma es el tumor intracardiaco primario más frecuente en niños. Presentamos el caso de un paciente con diagnóstico de múltiples rabdomiomas intracardiacos durante la vida fetal y al nacimiento con cianosis persistente. Se detectan ecocardiográficamente tumoraciones en atrio derecho con protrusión hacia el ventrículo derecho, obstruyendo el flujo de la válvula tricúspide. El flujo sistémico dependía del foramen oval (cortocircuito de derecha a izquierda) y el pulmonar del conducto arterioso (cortocircuito de izquierda a derecha), asemejando una atresia tricuspidea. Se inició tratamiento con sirolimus y prostaglandinas y se intentó colocar un stent en el conducto arterioso, sin éxito. Se realizó resección del rabdiomioma que obstruía la válvula tricúspide. Durante la cirugía, el paciente presentó taquicardia supraventricular y falleció por falla cardiaca poscardiotomía. Aunque la mayoría de los rabdomiomas tienen regresión espontánea o responden al manejo con inhibidores de mTOR, la afectación hemodinámica indica el manejo quirúrgico.

Background: According to the literature, probiotics are an attractive alternative to prevent necrotizing enterocolitis (NEC). However, due to differences in probiotic composition, randomized controlled trials are necessary to compare different probiotic mixtures. The objective of this study was to compare single strain (Lactobacillus acidophilus boucardii) versus multispecies probiotics on NEC incidence and faecal secretory Immunoglobulin A (sIgA) levels in very low preterm newborns. Methods: We performed a double-blind randomized trial in 90 newborns. L. acidophilus boucardii strain or multispecies probiotics were randomly assigned to preterm newborns. As the primary outcome, we evaluated NEC incidence on the total length of neonatal intensive care unit (NICU) stay. As the secondary outcome, we measured the change in faecal sIgA levels from baseline to 3 weeks following the use of probiotics. Results: NEC incidence was similar between groups (0% vs. 2.2% for the single strain and multispecies probiotic, respectively). Faecal sIgA levels increased significantly (p 0.45 mg/dl showed higher gestational age, birth weight, and weight at the second and third weeks of follow up than neonates with a faecal sIgA level increment ≤0.45 mg/dl. No adverse effects were found after probiotics use. Conclusions: No difference between strains of probiotics used was found on NEC incidence or in the increase of faecal sIgA levels. Faecal sIgA levels were positively related to gestational age and body weight in very low preterm infants. ClinicalTrials.gov/NCT02245815. Key Words: birth weight, preterm newborns, probiotics

Abstract Background Allogeneic cardiac-derived progenitor cells (CPC) without immunosuppression could provide an effective ancillary therapy to improve cardiac function in reperfused myocardial infarction. We set out to perform a comprehensive preclinical feasibility and safety evaluation of porcine CPC (pCPC) in the infarcted porcine model, analyzing biodistribution and mid-term efficacy, as well as safety in healthy non-infarcted swine. Methods The expression profile of several pCPC isolates was compared with humans using both FACS and RT-qPCR. ELISA was used to compare the functional secretome. One week after infarction, female swine received an intracoronary (IC) infusion of vehicle (CON), 25 × 106 pCPC (25 M), or 50 × 106 pCPC (50 M). Animals were followed up for 10 weeks using serial cardiac magnetic resonance imaging to assess functional and structural remodeling (left ventricular ejection fraction (LVEF), systolic and diastolic volumes, and myocardial salvage index). Statistical comparisons were performed using Kruskal-Wallis and Mann-Whitney U tests. Biodistribution analysis of 18F-FDG-labeled pCPC was also performed 4 h after infarction in a different subset of animals. Results Phenotypic and functional characterization of pCPC revealed a gene expression profile comparable to their human counterparts as well as preliminary functional equivalence. Left ventricular functional and structural remodeling showed significantly increased LVEF 10 weeks after IC administration of 50 M pCPC, associated to the recovery of left ventricular volumes that returned to pre-infarction values (LVEF at 10 weeks was 42.1 ± 10.0% in CON, 46.5 ± 7.4% in 25 M, and 50.2 ± 4.9% in 50 M, p

Nucleoside hydrolases (NSH; nucleosidases) catalyze the cleavage of nucleosides into ribose and free nucleobases. These enzymes have been postulated as key elements controlling the ratio between nucleotide salvage and degradation. Moreover, they play a pivotal role in ureidic legumes by providing the substrate for the synthesis of ureides. Furthermore, nucleotide metabolism has a crucial role during germination and early seedling development, since the developing seedlings require high amount of nucleotide simultaneously to the mobilization of nutrient in cotyledons. In this study, we have cloned two nucleosidases genes from Phaseolus vulgaris, PvNSH1 and PvNSH2, expressed them as recombinant proteins, and characterized their catalytic activities. Both enzymes showed a broad range of substrate affinity; however, PvNSH1 exhibited the highest activity with uridine, followed by xanthosine, whereas PvNSH2 hydrolyses preferentially xanthosine and shows low activity with uridine. The study of the regulation of nucleosidases during germination and early postgerminative development indicated that nucleosidases are induced in cotyledons and embryonic axes just after the radicle emergence, coincident with the induction of nucleases activity and the synthesis of ureides in the embryonic axes, with no remarkable differences in the level of expression of both nucleosidase genes. In addition, nucleosides and nucleobase levels were determined as well in cotyledons and embryonic axes. Our results suggest that PvNSH1 and PvNSH2 play an important role in the mobilization of nutrients during this crucial stage of plant development.

Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine. Romidepsin treatment resulted in increased histone acetylation, cell-associated HIV-1 RNA, and T-cell activation, which were associated with a marginally significant reduction of the viral reservoir. Vaccinations boosted robust and broad HIVconsv-specific T cells, which were strongly refocused toward conserved regions of the HIV-1 proteome. During a monitored ART interruption phase using plasma viral load over 2,000 copies/ml as a criterium for ART resumption, 23% of individuals showed sustained suppression of viremia up to 32 weeks without evidence for reseeding the viral reservoir. Results from this pilot study show that the combined kick&kill intervention was safe and suggest a role for this strategy in achieving an immune-driven durable viremic control.

Human cardiac progenitor cells (hCPC) are considered a good candidate in cell therapy for ischemic heart disease, demonstrating capacity to improve functional recovery after myocardial infarction (MI), both in small and large preclinical animal models. However, improvements are required in terms of cell engraftment and efficacy. Based on previously published reports, insulin-growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) have demonstrated substantial cardioprotective, repair and regeneration activities, so they are good candidates to be evaluated in large animal model of MI. We have validated porcine cardiac progenitor cells (pCPC) and lentiviral vectors to overexpress IGF-1 (co-expressing eGFP) and HGF (co-expressing mCherry). pCPC were transduced and IGF1-eGFPpos and HGF-mCherrypos populations were purified by cell sorting and further expanded. Overexpression of IGF-1 has a limited impact on pCPC expression profile, whereas results indicated that pCPC-HGF-mCherry cultures could be counter selecting high expresser cells. In addition, pCPC-IGF1-eGFP showed a higher cardiogenic response, evaluated in co-cultures with decellularized extracellular matrix, compared with native pCPC or pCPC-HGF-mCherry. In vivo intracoronary co-administration of pCPC-IGF1-eGFP and pCPC-HFG-mCherry (1:1; 40 × 106/animal), one week after the induction of an MI model in swine, revealed no significant improvement in cardiac function.

Abstract Streptococcus pneumoniae is responsible for diseases causing major global public health problems, including meningitis, pneumonia and septicaemia. Despite recent advances in antimicrobial therapy, pneumococcal meningitis remains a life-threatening disease. Furthermore, long-term sequelae are a major concern for survivors. Hence, a better understanding of the processes occurring in the central nervous system is crucial to the development of more effective management strategies. We used mass spectrometry based quantitative proteomics to identify protein changes in cerebrospinal fluid from children with Streptococcus pneumoniae infection, compared with children admitted to hospital with bacterial meningitis symptoms but negative diagnosis. Samples were analysed, by label free proteomics, in two independent cohorts (cohort 1: cases (n = 8) and hospital controls (n = 4); cohort 2: cases (n = 8), hospital controls (n = 8)). Over 200 human proteins were differentially expressed in each cohort, of which 65% were common to both. Proteins involved in the immune response and exosome signalling were significantly enriched in the infected samples. For a subset of proteins derived from the proteome analysis, we corroborated the proteomics data in a third cohort (hospital controls (n = 15), healthy controls (n = 5), cases (n = 20)) by automated quantitative western blotting, with excellent agreement with our proteomics findings. Proteomics data are available via ProteomeXchange with identifier PXD004219.

Two paths of female writer are here compared, the Colombian Soledad Acosta de Samper and the Spanish Emilia Pardo Bazán, both contemporary and both supporters of intellectual and social self-sufficiency of women with respect to men as well as its potential value to contribute to national regeneration.

Context: Sechium edule (Jacq.) Sw. (Cucurbitaceae) is used in ethnomedicine, but the diversity of the varietal groups of this species has not often been considered. This is important because we previously reported that different variety of species exhibit different activities across different tumor cell lines. Objective: This study investigates the chemical composition and biological activities of extracts obtained from S. edule var. nigrum spinosum. Materials and methods: The leukemia P388 cell line and mononuclear bone marrow cells (MNCBMs) were treated with the extract at a concentration ranging from 40 to 2370 μg/mL for cytotoxicity and viability assays. CD-1 mice were treated with 8–5000 mg/kg extract and monitored every hour for the first 24 h and subsequently for seven days for signs of toxicity (LD50). In addition, the chromatographic profile of the extract was determined by HPLC. Results: The extract inhibits the proliferation of both P388 cells and MNCBMs, with IC50 values of 927 and 1911 μg/mL, respectively, but reduced the viability and induced the apoptosis of only leukemia cells. The LD50 was higher than 5000 mg/kg, and this concentration did not alter the blood chemistry or cell count but doubled the mitotic index in the bone marrow. The HPLC showed the presence of cucurbitacins, phloridzin, naringenin, phloretin, apigenin, and gallic, chlorogenic, vanillic, p-hydroxybenzoic, caffeic, and p-coumaric acids. Discussion and conclusion: Sechium edule var. nigrum spinosum contains bioactive compounds that explain the antiproliferative and nutraceutical activities, and its lack of physiological side effects constitutes an added value to a widely consumed vegetable.

The incubation period of coronavirus disease 2019 (COVID-19) is not always observed exactly due to uncertain onset times of infection and disease symptoms. In this paper, we demonstrate how to estimate the distribution of incubation and its association with patient demographic factors when the exact dates of infection and symptoms’ onset may not be observed. The findings from analysis of the confirmed COVID-19 cases indicate that age could be associated with the incubation period, and an age-specific quarantine policy might be more efficient than a unified one in confining COVID-19.

ABSTRACT Prochlorococcus requires the capability to accommodate to environmental changes in order to proliferate in oligotrophic oceans, in particular regarding nitrogen availability. A precise knowledge of the composition and changes in the proteome can yield fundamental insights into such a response. Here we report a detailed proteome analysis of the important model cyanobacterium Prochlorococcus marinus SS120 after treatment with azaserine, an inhibitor of ferredoxin-dependent glutamate synthase (GOGAT), to simulate extreme nitrogen starvation. In total, 1,072 proteins, corresponding to 57% of the theoretical proteome, were identified—the maximum proteome coverage obtained for any Prochlorococcus strain thus far. Spectral intensity, calibrated quantification by the Hi3 method, was obtained for 1,007 proteins. Statistically significant changes (P value of

Objetivos: Mostrar 2 métodos estadísticos para estimar la evolución de la incidencia de consumo de heroína y cocaína en Barcelona. Métodos: Los inicios de tratamiento por consumo de heroína y cocaína del Sistema de Información de Drogas de Barcelona entre 1991 y 2003. Se seleccionaron 4.367 sujetos con un primer tratamiento por heroína y 2.147 por cocaína. Se ha empleado el método Reporting Delay Adjustment (RDA) y modelos logarítmicos lineales (MLL), considerando para el RDA los inicios de tratamiento cuyo inicio de consumo era entre 1991 y 2003, y para el MLL entre 1967 y 2003 para la heroína y entre 1971 y 2003 para la cocaína. Además, para cada droga y método se estudió la distribución del período de latencia (PL) (años entre el primer consumo y el primer tratamiento). Resultados: Según la distribución del PL, los consumidores de heroína tardan menos tiempo en iniciar su primer tratamiento que los de cocaína, indistintamente del método empleado. En general, la incidencia estimada de consumo de heroína en Barcelona disminuyó progresivamente desde 1982. En cambio, para la cocaína aumentó rápidamente hasta 1998, y fue irregular posteriormente. A principios de los noventa la incidencia de consumo de cocaína empezó a ser importante, años antes de manifestarse como problemática. Conclusión: El RDA subestima la incidencia respecto al MLL, pero la incidencia de heroína con MLL puede estar sesgada antes de 1991 por cambios en la oferta de tratamiento. Aunque la incidencia estimada se refiere a los sujetos que hacen tratamiento alguna vez en la vida, su evolución ayuda a prever acciones futuras.Objectives: To describe 2 statistical methods for estimating trends in the incidence of heroin and cocaine use in Barcelona. Methods: Admissions for treatment of heroin and cocaine consumption recorded by the Barcelona Drug Information System between 1991 and 2003 were used. We selected 4,367 subjects initiating treatment for the first time for heroin use, and 2,147 for cocaine use. Two statistical techniques were employed: Reporting Delay Adjustment (RDA) and the Log-linear Model (LLM). RDA was used in subjects who initiated drug consumption between 1991 and 2003, and LLM for those who began heroin use between 1967 and 2003 and cocaine use between 1971 and 2003. In addition, for each drug and method the latency period (LP) was determined (years between first consumption and first treatment). Results: Comparison of the distributions of the LP for each drug revealed that heroin users initiated treatment for the first time sooner than cocaine users, regardless of the method employed. In general, the estimated incidence of heroin use in Barcelona fell progressively after 1982. In contrast, the incidence of cocaine use rose rapidly until 1998, and has been irregular since. The incidence of cocaine use began to be substantial in the early 1990s, but took several years to manifest itself as problematic. Conclusion: The estimated incidence was underestimated by RDA compared with LLM, but the incidence of heroin use could be biased before 1991 due to changes in treatment provisions. Although the estimated incidence is relative to individuals who are admitted for treatment at some time in their life, trends in incidence can be used to plan future actions.

Glutamine synthetase plays a key role in nitrogen metabolism, thus the fine regulation of this enzyme in Prochlorococcus, which is especially important in the oligotrophic oceans where this marine cyanobacterium thrives. In this work, we studied the metal-catalyzed oxidation of glutamine synthetase in cultures of Prochlorococcus marinus strain PCC 9511 subjected to nutrient limitation. Nitrogen deprivation caused glutamine synthetase to be more sensitive to metal-catalyzed oxidation (a 36% increase compared to control, non starved samples). Nutrient starvation induced also a clear increase (three-fold in the case of nitrogen) in the concentration of carbonyl derivatives in cell extracts, which was also higher (22%) upon addition of the inhibitor of electron transport, DCMU, to cultures. Our results indicate that nutrient limitations, representative of the natural conditions in the Prochlorococcus habitat, affect the response of glutamine synthetase to oxidative inactivating systems. Implications of these results on the regulation of glutamine synthetase by oxidative alteration prior to degradation of the enzyme in Prochlorococcus are discussed.

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El proyecto liberal constituye un eje vertebrador del siglo XIX; sin embargo, apenas afectará, a las mujeres, a las que se les priva de la ciudadanía social, civil y política, no por razones de carácter jurídico, sino por otras de carácter puramente fisiológico: el sexo. Ahora bien, el creciente proceso de modernización que experimenta la sociedad española durante la Restauración, no cuestionará únicamente el sistema político vigente y sus fundamentos ideológicos, sino que se proyectará también en el ámbito femenino. Lentamente, as mujeres irán consiguiendo mayores cotas de igualdad en el ámbito educativo, laboral, e incluso en el político. Y a la postre, este conjunto de de cambios, aunque frenados por múltiples inercias, vendrá a cuestionar lo que hasta entonces había constituido la identidad femenina. Una identidad que se había considerado inamovible pero que se mostraba dinámica y cambiante con los tiempos.

El objeto de estas reflexiones es buscar un acercamiento al horizonte sociocultural de fines del siglo XIX y comienzos del siglo XX a través del discurso de Jacinto Benavente. El dramaturgo vive la crisis finisecular, participa de las inquietudes del 98 y da cabida en su obra a una serie de cuestiones que son tema de preocupación para los intelectuales, tales como darwinismo social, casticismo y europización, oligarquía, caciquismo, estrechez de la vida provinciana, difícil acceso a la ciudadanía, encarnación social del cristianismo, regeneración, familia... El presente artículo hace referencia a ello, si bien se centra muy especialmente en un tema relativo a la vida privada: el matrimonio.

The enzyme isocitrate dehydrogenase (ICDH; EC 1.1.1.42) catalyzes the oxidative decarboxylation of isocitrate, to produce 2-oxoglutarate. The incompleteness of the tricarboxylic acids cycle in marine cyanobacteria confers a special importance to isocitrate dehydrogenase in the C/N balance, since 2-oxoglutarate can only be metabolized through the glutamine synthetase/glutamate synthase pathway. The physiological regulation of isocitrate dehydrogenase was studied in cultures of Prochlorococcus sp. strain PCC 9511, by measuring enzyme activity and concentration using the NADPH production assay and Western blotting, respectively. The enzyme activity showed little changes under nitrogen or phosphorus starvation, or upon addition of the inhibitors DCMU, DBMIB and MSX. Azaserine, an inhibitor of glutamate synthase, induced clear increases in the isocitrate dehydrogenase activity and icd gene expression after 24 h, and also in the 2-oxoglutarate concentration. Iron starvation had the most significant effect, inducing a complete loss of isocitrate dehydrogenase activity, possibly mediated by a process of oxidative inactivation, while its concentration was unaffected. Our results suggest that isocitrate dehydrogenase responds to changes in the intracellular concentration of 2-oxoglutarate and to the redox status of the cells in Prochlorococcus.

INTRODUCTION:The decline in birth rates is a concern in public health. Fertility is partly determined before birth by the intrauterine environment and prenatal exposure to maternal stress could, through hormonal disturbance, play a role. There has been such evidence from animal studies but not from humans. We aimed to examine the association between prenatal stress due to maternal bereavement following the death of a relative and childbirths in the offspring. MATERIALS AND METHODS:This population-based cohort study included all subjects born in Denmark after 1968 and in Sweden after 1973 and follow-up started at the age of 12 years. Subjects were categorized as exposed if their mothers lost a close relative during pregnancy or the year before and unexposed otherwise. The main outcomes were age at first child and age-specific mean numbers of childbirths. Data was analyzed using Cox Proportional Hazards models stratified by gender and adjusted for several covariates. Subanalyses were performed considering the type of relative deceased and timing of bereavement. RESULTS:A total of 4,121,596 subjects were followed-up until up to 41 years of age. Of these subjects, 93,635 (2.3%) were exposed and 981,989 (23.8%) had at least one child during follow-up time. Compared to unexposed, the hazard ratio (HR) [95% confidence interval] of having at least one child for exposed males and females were 0.98 [0.96-1.01] and 1.01 [0.98-1.03], respectively. We found a slightly reduced probability of having children in females born to mothers who lost a parent with HR = 0.97 [0.94-0.99] and increased probability in females born to mothers who lost another child (HR = 1.09 [1.04-1.14]), the spouse (HR = 1.29 [1.12-1.48]) or a sibling (HR = 1.13 [1.01-1.27]). CONCLUSIONS:Our results suggested no overall association between prenatal exposure to maternal stress and having a child in early adulthood but a longer time of follow-up is necessary in order to reach a firmer conclusion.

BACKGROUND: Algorithms for bone mineral density (BMD) management in HIV-infected patients are lacking. Our objective was to assess how often a dual-energy x-ray absorptiometry (DXA) scan should be performed by assessing time of progression to osteopenia/osteoporosis. METHODS: All DXA scans performed between 2000 and 2009 from HIV-infected patients with at least two DXA were included. Time to an event (osteopenia and osteoporosis) was assessed using the Kaplan-Meier method. Strata (tertiles) were defined using baseline minimum T scores. Differences between strata in time to an event were compared with the log-rank test. RESULTS: Of 391 patients (1,639 DXAs), 49.6% had osteopenia and 21.7% osteoporosis at their first DXA scan. Of the 112 (28.6%) with normal BMD, 35.7% progressed to osteopenia; median progression time was 6.7 years. These patients were stratified: "low-risk" (baseline minimum T score >-0.2 SD), "middle-risk" (between -0.2 and -0.6 SD), and "high-risk" (from -0.6 to -1 SD); median progression time to osteopenia was 8.7, >7.2, and 1.7 years, respectively (p8.5 years. Progression time was >8.2 years in "low-risk" tertile (T score between -1.1 and -1.6 SD), >8.5 years in "middle-risk" (between -1.6 and -2), and 3.2 years in "high-risk" (from -2 to -2.4) (p

The marine cyanobacteria Prochlorococcus have been considered photoautotrophic microorganisms, although the utilization of exogenous sugars has never been specifically addressed in them. We studied glucose uptake in different high irradiance- and low irradiance-adapted Prochlorococcus strains, as well as the effect of glucose addition on the expression of several glucose-related genes. Glucose uptake was measured by adding radiolabelled glucose to Prochlorococcus cultures, followed by flow cytometry coupled with cell sorting in order to separate Prochlorococcus cells from bacterial contaminants. Sorted cells were recovered by filtration and their radioactivity measured. The expression, after glucose addition, of several genes (involved in glucose metabolism, and in nitrogen assimilation and its regulation) was determined in the low irradiance-adapted Prochlorococcus SS120 strain by semi-quantitative real time RT-PCR, using the rnpB gene as internal control. Our results demonstrate for the first time that the Prochlorococcus strains studied in this work take up glucose at significant rates even at concentrations close to those found in the oceans, and also exclude the possibility of this uptake being carried out by eventual bacterial contaminants, since only Prochlorococcus cells were used for radioactivity measurements. Besides, we show that the expression of a number of genes involved in glucose utilization (namely zwf, gnd and dld, encoding glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and lactate dehydrogenase, respectively) is strongly increased upon glucose addition to cultures of the SS120 strain. This fact, taken together with the magnitude of the glucose uptake, clearly indicates the physiological importance of the phenomenon. Given the significant contribution of Prochlorococcus to the global primary production, these findings have strong implications for the understanding of the phytoplankton role in the carbon cycle in nature. Besides, the ability of assimilating carbon molecules could provide additional hints to comprehend the ecological success of Prochlorococcus.

Preguntarse por la estética de la existencia supone, para Foucault, focalizar el análisis en el sujeto actual que se forma en lasprácticas del yo y no en el sujeto abstracto. Por esa razón, el siguiente ensayo pretende analizar la estética de la existenciatomando como sujeto de la experiencia a Rodolfo Walsh, un hombre que, fundamentalmente, no se dejó moldear por ladeterminación de las normas y pretendió darse forma a sí mismo.Tal como lo explica Schimid (2002), el sujeto está inserto en la encrucijada de múltiples relaciones de poder que actúan sobre él,pero la formación de su propia existencia no es un simple repliegue a lo privado, sino que supone la conexión entre la ética y elanálisis del poder. Pensando en ello, el propósito de este trabajo es indagar acerca de los caminos escogidos por Walsh comopráctica de libertad, como manera de autoconstituirse que no fueron los únicos posibles pero sí los que él eligió para responder, ymuchas veces resistir, a la máquina de dominación. Sus investigaciones periodísticas, sus diagnósticos de la realidad políticosocialo las noticias difundidas a través de ANCLA y la cadena informativa, son algunos ejemplos.

Sin resumen

El objetivo de este artículo es dar cuenta de la fervorosa acogida y el entusiasmo que tanto el pueblo español como sus autoridades, desplegaron hacia Eva Duarte, la esposa del General Perón durante su estancia en nuestro país, del ocho al veintiséis de junio de 1947. Para entender el alcance internacional del mismo, se ha creído necesario partir de la contextualización internacional de ambos países y de los objetivos que cada uno se proponía al buscar el mutuo acercamiento. Acercamiento que adquiere gran resonancia con el viaje de Eva Duarte a España.The main purpose of this article is to give an account of the warm and enthusiastic welcome Eva Duarte, General Peron's wife, received from both the Spanish authorities and people, during her stay in our country, from the eighth to the twenty-sixth of June, 1947. In order to understand its international extent, it's necessary to start with both countries' international context and each country's main goals for mutual rapprochement. Such rapprochement was achieved with Eva Duarte's journey to Spain.