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Background: Limited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain. Methods: Urine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay. Results: In our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways. Conclusions: Exposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.

Introduction: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. Objectives: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8‑oxo‑7,8‑dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study). Methods: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants. Results: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03–1.27) for Mo, 1.17 (1.05–1.31) for Ba, 1.23 (1.04–1.46) for Cr and 1.18 (1.00–1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03–1.24) for Zn and 1.12 (1.02–1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01–1.23) for Zn and 1.09 (0.99–1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA. Conclusions: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation. Keywords: Urine metals, Oxidative stress, Metal mixtures, Population-based

Cary Wolfe señala que el poshumanismo se suele concentrar en “el descentramiento de lo humano en relación a las coordenadas tanto evolutivas, ecológicas o tecnológicas” (xvi). En este sentido, Lágrimas en la lluvia, novela de ciencia ficción de la autora madrileña Rosa Montero, construye con bastante acierto una versión poshumana de una sociedad futura, partiendo del fenómeno neuro-cognitivo complejo que representa la memoria biológica y su duplicación artificial a través de avances tecnológicos. Este artículo se enfoca principalmente en delinear cómo en la novela de Montero la memoria se convierte en una sugerente metáfora para profundizar de manera crítica en la convergencia entre biología y tecnología, y para mostrar una retórica en torno a la fragilidad de la memoria artificial y la propia memoria biológica a la hora de construir la identidad del sujeto, la historia y la ficción. La novela de Rosa Montero es además una provocativa plataforma textual para indagar en el concepto de singularidad tecnológica que da origen a una nueva especie: “la civilización humana-máquina” (Kurzweil 5); al converger bio y tecno dentro de un mismo sistema cognitivo.

This is a brief presentation/introduction to the following articles related to Rosa Montero´s novel "Lágrimas en la lluvia".

Antecedentes: La diabetes tipo 2 tiene implicaciones económicas en el ingreso familiar y el gasto de bolsillo. Objetivo: Determinar el gasto de bolsillo familiar en la atención de la diabetes mellitus tipo 2 y el porcentaje que representa en el ingreso familiar. Material y métodos: Estudio de gasto de bolsillo de las familias con pacientes con diabetes tipo 2 atendidos en el primer nivel de atención. El gasto de bolsillo familiar incluyó gasto en traslado, alimentos-bebidas y medicamentos externos. El ingreso familiar correspondió al total de ingresos económicos aportados por los miembros de la familia. El porcentaje del gasto de bolsillo con relación al ingreso familiar se identificó con la relación entre estas dos variables. El análisis estadístico incluyó promedios y porcentajes. Resultados: El gasto de bolsillo familiar anual en transporte fue de $2621.24, en alimentos y bebidas fue de $1075.67 y en medicamentos externos fue de $722.08. El gasto familiar de bolsillo total anual fue de $4418.89 y correspondió a 4.73 % del ingreso familiar. Conclusión: El gasto de bolsillo en las familias con un paciente con diabetes mellitus tipo 2 fue de $4418.89 y representó 4.73 % del ingreso familiar.

Abstract Background and objective Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non‐motor, cognition, and dependency) and five stages, correlated with disease severity and patients’ quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. Patients and methods Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross‐sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory‐II (BDI‐II), PQ‐10, and EUROHIS‐QOL 8‐item index (EUROHIS‐QOL8). Results Two hundred and twenty‐four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4–5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p

Abstract Background Excellent revisions about antibiotic-loaded bone cement (ALBC) have been recently published. In the present article, we review the principles and limitations of local antibiotic delivery in the context of recent advances in the pathogenesis of prosthetic joint infections (PJI), with particular attention paid to the potential association between ALBC and antimicrobial resistance. Main body Recalcitrance of PJI is related to the ability of pathogens to adapt to particular environments present in bone tissue and protect themselves from host immunity in different ways. Accordingly, delivery of high local antimicrobial concentrations using ALBC is needed. Most relevant clinical data showing the efficacy of ALBC for PJI prophylaxis and treatment are reviewed, and we dissected the limitations on the basis of the recent findings from animal models and suggested that aminoglycosides, in particular, could not be the best option. One of the major concerns associated with ALBC is the emergence of resistance because of theoretical prolonged exposure to low antibiotic concentrations. We summarize the mechanisms for the selection of resistant microorganisms, and we critically reviewed the evidence from animal models and clinical data from observational and registry studies and concluded that there is no evidence to support this association. Conclusion While waiting for better evidence from well-designed clinical trials, ALBC shows a beneficial effect as a prophylaxis in arthroplasty, and to avoid the colonization of spacers used for two-stage revision in patients with PJI. Experimental models and clinical evidence suggest the need to achieve high local antimicrobial concentrations to obtain the highest prophylactic and therapeutic effect. The current evidence does not support the risk of increasing resistance with use of ALBC. In the future, it is necessary to evaluate new carriers and different antimicrobials to improve clinical outcomes.

Implementation research addresses how well a programme is conducted when applied in real-world conditions. However, research based on quality standards is still scarce as it requires monitoring context, process, and participant response. This study applies implementation quality standards to 57 Spanish parenting and family support programmes identified in the COST European Family Support Network project, using an ten-component evaluation sheet sheet. Descriptive analyses showed a good implementation level. The latent profile analysis identified four patterns defined by programme setting: profile 1, Social Services/NGO setting (21.1%), profile 2, Health setting (31.6%), profile 3, Multi-setting (14%), and profile 4, Educational setting (33.3%), differing in professional discipline, training, participant response, and professional perception of implementation. Profile memberships were related to programme outcomes, scaling up, and sustainability. Findings illustrate conceptual and practical challenges that researchers and professionals usually encounter during implementation, and the efforts required to deliver programmes effectively in real-world settings in Spain.

Abstract Quality of life (QOL) plays an important role in independent living in Parkinson’s disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson’s disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p

Introduction. Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results. The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p

The design and fabrication of a integrated symmetric directional coupler dependent o the pumping power and operating at a 1534 nm wavelength is reported. The twin-core waveguide was inscribed into Er3+/Yb3+ co-doped phosphate glass by a femtosecond laser direct writing technique. By optical pumping, the coupling ratio can be modulated due to the changes induced in the refractive index of the material. The experimental results demonstrated that the coupling ratio can be tuned continuously from 100/0 to 50/50 by increasing the pump’s power from 0 to 350 mW. The developed twin-core coupler has promising applications for on-chip all-optical signal processing and communication systems.

ABSTRACT The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student’s epistemic beliefs to achieving positive learning outcomes.

Background: Clinical prediction rules have been designed to reduce variability and improve the diagnostic process. However, there are no unanimous criteria regarding which of them is the most efficient for the diagnosis of acute appendicitis. Aim: The primary aim of this study was to assess the diagnostic efficacy of the most commonly used clinical prediction rules. The second aim was to identify the combination of the smallest number of clinical and analytical variables that would allow a costeffective diagnostic approach. Methods: A retrospective observational study was conducted of 458 patients who were evaluated for right iliac fossa pain between January 2010 and December 2016. The scores tested were Alvarado, AIR, RIPASA, and AAS. Univariate and multiple regressions were used for validation. Results: Alvarado one was the most efficient to establish a positive diagnosis of acute appendicitis. However, the most simplified and predictive combination variables included anorexia, white blood cell count > 8275 leukocytes/μL, neutrophilia (> 75%), abdominal pain < 48 h, migrating pain, and temperature out the range of 37-39ºC. Conclusions: A new and effective CPR (HMC score) for predicting appendicitis in patients presenting with the right iliac fossa pain has been established.

A method based on the photographic recording of the power distribution laterally diffused by cationic-network (CN) hydrogel waveguides is first checked against the well-established cut-back method and then used to determine the different contributions to optical power attenuation along the hydrogel-based waveguide. Absorption and scattering loss coefficients are determined for 450 nm, 532 nm and 633 nm excitation. The excellent optical loss values obtained (0.32–1.95 dB/cm), similar to others previously described, indicate their potential application as waveguides in different fields, including soft robotic and light-based therapies.

Modal decomposition of light is essential to study its propagation properties in waveguides and photonic devices. Modal analysis can be carried out by implementing a computer-generated hologram acting as a match filter in a spatial light modulator. In this work, a series of aspects to be taken into account in order to get the most out of this method are presented, aiming to provide useful operational procedures. First of all, a method for filter size adjustment based on the standard fiber LP-mode symmetry is presented. The influence of the mode normalization in the complex amplitude encoding-inherent noise is then investigated. Finally, a robust method to measure the phase difference between modes is proposed. These procedures are tested by wavefront reconstruction in a conventional few-mode fiber.

The acid–base reaction of 1,4-benzodioxane 2-carboxylic acid with calcium carbonate furnished the centrosymmetric title compound, [Ca(C9H7O4)2(H2O)4], in which the metal ion is octahedrally coordinated by two monodentate 1,4-benzodioxane 2-carboxylate ligands and four water molecules. In the crystal, O—H...O and C—H...O hydrogen bonds link the molecules into a three-dimensional network.

Objective: The aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson’s disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score ≥ 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 ± 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 ± 36.48 vs. 34.3 ± 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 ± 37.37) compared to those who did not develop MF (+6.2 ± 25.8) (p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (β = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up.

Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

Background and objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD). Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%. Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.

Summary: Molecular factors that define stem cell identity have recently emerged as oncogenic drivers. For instance, brachyury, a key developmental transcriptional factor, is also implicated in carcinogenesis, most notably of chordoma, through mechanisms that remain elusive. Here, we show that brachyury is a crucial regulator of stemness in chordoma and in more common aggressive cancers. Furthermore, this effect of brachyury is mediated by control of synthesis and stability of Yes-associated protein (YAP), a key regulator of tissue growth and homeostasis, providing an unexpected mechanism of control of YAP expression. We further demonstrate that the brachyury-YAP regulatory pathway is associated with tumor aggressiveness. These results elucidate a mechanism of controlling both tumor stemness and aggressiveness through regulatory coupling of two developmental factors. : Malignant neoplasms exhibit uninhibited and dysregulated growth coupled with acquisition of stem-like properties that are integral to the development and progression of disease. Shah et al. demonstrate a critical role of brachyury in regulating stemness and growth by activating YAP through direct transcriptional and post-transcriptional mechanisms in various cancers. Keywords: brachyury, YAP, chordoma, stremness, growth, glioblastoma, lung carcinoma

Climatic conditions throughout the year and age of plants affect both yield and quality of forage grasses. In this research, we evaluated the effects of age of regrowth and seasonal conditions on dry matter accumulation and crude protein concentration in 5 cultivars of Brachiaria spp.: Señal, Xaraés, Marandú, Piatá and Mulato II, harvested at 2, 4, 6, 8 and 10 weeks after a uniformity cut, during the rainy and dry seasons. The variables were: total dry matter (TDM), leaf dry matter (LDM) and stem dry matter (SDM) yields, leaf area index (LAI), specific leaf area (SLA) and crude protein (CP) concentration. For TDM yield, in the rainy season there was no significant difference (P>0.05) among cultivars, with mean DM yield over 10 weeks of 6.34 t/ha; however, during the dry season Xaraés presented a higher (P Keywords: Brachiaria decumbens, Brachiaria brizantha, Brachiaria hybrid cv. Mulato II, leaf area index, specific leaf area.

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students’ learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our “formative frustration” hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of “formative frustration” is an important aspect for a successful CURE.

Introducción y objetivos: La fibrilación auricular es la arritmia cardiaca más frecuente y una de las complicaciones más temidas es la embolia sistémica y/o el accidente cerebrovascular (ACV). En la actualidad se cuenta con diversas terapias antitrombóticas para prevención del primero, sin embargo, hay temor por complicaciones relacionadas con la anticoagulación, y aunque existen recomendaciones de diferentes guías de prácticas clínicas, continúa el uso subóptimo de la misma. El objetivo del estudio es describir datos clínicos, diagnósticos y terapéuticos de pacientes con fibrilación auricular que ingresan al servicio de urgencias, además, se realizó una correlación entre el riesgo de embolia sistémica y de sangrado con el tipo de terapia recibida. Métodos: Estudio descriptivo retrospectivo tipo serie de casos de pacientes con diagnóstico de la fibrilación auricular no valvular durante un año. Se reportan las frecuencias de comorbilidades, diagnósticos de ingreso y tipo de terapia específica. Resultados: Se incluyeron 98 pacientes, la media de edad fue 72 años, la falla cardiaca y la hipertensión arterial fueron las principales comorbilidades; el 92% tenían indicación de anticoagulación por la escala CHA2DS2VASc, 54% de estos pacientes no la venían recibiendo a pesar de que se calculó en la mayoría bajo riesgo de sangrado. El 5% de los pacientes ingresaron con diagnóstico de ACV isquémico y el 5% presentaban sobreanticogulación. Conclusión: Las características de nuestra población con la fibrilación auricular es similar a la descrita en la literatura, pero existe baja adherencia a las recomendaciones terapéuticas en anticoagulación.

Background: The Zebu cattle are represented by a diverse group of breeds in México. Traditionally these breeds have been associated with the tough beef characteristic. Validated genetic markers have the potential to be included in marker-assisted selection and management programs in order to improve traits such as beef tenderness. The incidence and distribution of Calpain and Calpastatin polymorphisms strongly associated with beef tenderness were estimated in registered cattle of five Zebu breeds in Mexico. Results: A low and in some cases null frequency of favorable C allele of CAPN316 was determined in all breeds. Conversely, a more equilibrated frequency in CAPN4751 and CAST loci was observed. Conclusions: Although the relatively low occurrence of favorable alleles in assessed loci may limit their use in selection programs, genotyping availability might be a practical and comprehensive tool for introgression programs by marker assisted selection and management as to improve meat tenderness of Zebu breeds.

Group A Streptococcus (GAS) is a human-adapted pathogen that causes a variety of diseases, including pharyngitis and invasive infections. GAS strains are categorized by variation in the nucleotide sequence of the gene (emm) that encodes the M protein. To identify the emm types of GAS strains causing pharyngitis in Ontario, Canada, we sequenced the hypervariable region of the emm gene in 4,635 pharyngeal GAS isolates collected during 2002–2010. The most prevalent emm types varied little from year to year. In contrast, fine-scale geographic analysis identified inter-site variability in the most common emm types. Additionally, we observed fluctuations in yearly frequency of emm3 strains from pharyngitis patients that coincided with peaks of emm3 invasive infections. We also discovered a striking increase in frequency of emm89 strains among isolates from patients with pharyngitis and invasive disease. These findings about the epidemiology of GAS are potentially useful for vaccine research.

El virus de papiloma humano tipo 16 (HPV-16) es la principal causa de cáncer entre las mujeres en Colombia. Es importante desarrollar pruebas de bajo costo y confiables para detectar la presencia de este virus en las primeras etapas de la enfermedad. Los péptidos pueden ser usados para detectar anticuerpos en sueros, pero a menudo no son activos. Sin embargo, péptidos restringidos que imiten epitopes conformacionales pueden ser más efectivos.

De los extractos etanólicos de hojas, corteza y madera de Zanthoxylum monophyllum (Rutaceae) se aislaron e identificaron cinco lignanos: sesamina, eudesmina, asarinina, hinokinina y cubebina (mezcla de epímeros); dos alcaloides: y-fagarina y skimmianina; dos terpenos: sltosterol y lupeol; un ácido graso y un éster: ácido oleico y linoleato de etilo; dos acetofenonas: xanthoxylina y 2,4-dihidroxi-6-metoxiacetofenona; tres coumarinas: osthenol, arnottinina y columbianetina. Sus estructuras fueron determinadas por análisis espectroscópico, comparación con muestras auténticas y datos reportados en la literatura.

En los espectros de RMN 13C, tomados con la secuencia de pulsos DEPT, el grupo metilenodioxi tiene un comportamiento diferente al de otros grupos CH2 , por lo cual se estudio la variación de las intensidades de su señal en función del ángulo de irradiación 0.

Del extracto bencénico de la corteza de Iryanthera laevis (Myristicaceae), se aislaron e identificaron cuatro dihidrochalconas que corresponden a: 2', 4'-dihidroxl-4,6'-dimetoxidihidrochalcona,2',4'-dihidroxi-3.4-metilenodioxi-6'-metoxidihidrochalcona, 2',4'-dihidroxi-3,4,6'-trimetoxidihidrochalcona y 3'-(1",4"-di-phidroxifenil-2",3"-dimetilbutil)-2',4'-dihidroxi-4,6'-dimetoxidihidrochalcona. Las estructuras fueron establecidas por métodos espectroscópicos.

Del extracto toluénico de las hojas de Osteophloeum sulcatum (Myrísticaceae) se aislaron e identificaron cinco lignanos que corresponden a: Hidroxiotobaina, otobafenol, ácido (-) dihidroguaiarético, verrucosin y el reí. (7S,8S,8'R)-7-hidroxi-3,4-3',4'-dimetilenodioxi-8,8'-lignano (saururinol). Este último se reporta por primera vez como producto natural. Las estructuras fueron establecidas por métodos espectroscópicos.

Se ilustra la metodología para la deducción total de la estructura de una molécula orgánica desconocida, del tipo piranocoumarina (5-metoxiseselin), utilizando espectros de RMN bidimensionales de diferentes clases: COSY H-H, NOESY y HETCOR C-H a un enlace y a larga distancia.

La atribución sin ambigüedad de cada una de las señales de los espectros de RMN 1H y 13C del 2,3-dimetil-7-hidroxi-6-metoxi-1-(3', 4' - metilenodioxifenil) naftaleno, fue realizada por medio de sus espectros bidimensionales de correlación homonuclear 1H-1H y de correlación heteronuclear 1C y 3H obtenido utilizando en la respectiva secuencia de pulsos tiempos de espera correspondientes

De la madera de Virola sebifera fueron aislados tres díarilpropanos: 1-(4'-hidroxi-2'-metoxifenil-3-(3"-hidrox¡-4"-metoxifenil)-propano, Virolanol B y Virolanol C. De la madera de Virola calophylloidea fue aislado el 3-¡ndolcarboxaldehido.

Objetivo: Este trabajo integra información de la secuencia del ADNmt del norte de Suramérica con Puerto Rico, con el fin de comprender el poblamiento del Caribe, especialmente de los taínos. De paso, arroja información sobre hechos demográficos en la Colombia precolombina. Metodología: Se obtuvieron 59 muestras de Colombia y Venezuela, las cuales fueron analizadas junto a otras dos pertenecientes a los indios warao y disponibles en el Genbank. Se alinearon secuencias HVR-I y II (Hypervariable Region) y se compararon con el rCRS. El 93,4% de las muestras resultaron ser de origen amerindio. Resultados: Un venezolano exhibió mutaciones relacionadas con el linaje antiguo C-II de Puerto Rico, el cual se estima que arribó a Puerto Rico en la era prearahuaca. Mediante secuenciación completa del ADNmt se demostró que esta muestra, VE6, pertenece al clado americano nativo C1b. Dos personas de Colombia y Venezuela presentaban la transición 16129 que define el linaje A-VIII de Puerto Rico. Dicha transición dentro del haplogrupo A también se ha encontrado en los ciboneyes de Cuba y en otras tribus americanas. La deleción de un par de bases -498d- define el linaje B-I de Colombia (Bogotá y Villa de Leyva, Boyacá), un polimorfismo encontrado en los departamentos correspondientes a la cordillera Oriental y que se extiende al Valle del Cauca y a Panamá. Conclusión: Este linaje experimentó una expansión demográfica en la cordillera Oriental que lo llevó a expandirse geográficamente hasta Panamá. Sería recomendable ampliar el muestreo de la costa norte de Colombia y Venezuela, para encontrar más conexiones precolombinas con Puerto Rico. Además, sería conveniente verificar la distribución geográfica de 498d con un muestreo más numeroso y que cubra una zona más amplia de Colombia.

En la hidrogenación catalítica de (3R, 48, 2E)-2—(hexadec—15-inilideno)— 3—hidroxl—4—metllbutanolido (una dihidro—mahuba—lactona), utilizando H2/Pd— C en metanol, se obtuvo un producto con un rendimiento del 86% , ocurriendo una hidrogenación estereoselectiva. Haciendo uso del espectro de RMN H del acetato del producto de hidrogenación y de la ecuación de Karplus, se muestra que el hidroxilo alílico actúa como un "ancla" en el catalizador.

De las hojas de Virola Calophylla (Mynsticaceae) se aislaron e identificaron dos neolignanos nuevos, calophyn y calophyllin, y dos neolignanos conocidos, ácido meso-dihidroguaiarético y austrobailignano-6. Las estructuras fueron establecidas por métodos espectroscópicos.

Del extracto bencénico de la madre del tronco de Iryanthera triclomis fueron aislados tres diarilpropanos: 1-(4'-hidroxi- 2'-metoxifenil)-3-(4'-hkiroxi-3'-metoxifenil)-propano (la), 1-(2', 4'-dihidroxifenil)-3-(3", 4"- metilenodioxifenil)-propano (1a) y 1-(2'4'- dihidroxifenil)-3-(4 ,5- metllenodioxi-2"-metoxifenil)-propano (1c). Estas sustancias ya son conocidas en la literatura. pero algunos datos físicos y espectroscópicos de ellas y de sus acetatos se describen aquí por primera vez.

Del extracto clorofórmico de la corteza del tronco de Pera nítida (Benth.) Jablonski se aisló una sustancia amarilla que fue identificada como 5—hidro.x¡-2— metil —1,4—naftoquinona. Esta sustancia es conocida como plumbagina y ha mostrado una destacada acción biológica. La estructura fue deducida con base en los datos espectroscópicos y su presencia en esta especie tiene importancia quimiotaxonómica.

Del extracto bencénico de la madera de Virola calophylloldea (Myristicaceae) se separaron seis sustancias tipo esteroidal, valiéndose de las técnicas de Cromatografía de gases (CG) y Cromatografía líquida de alta eficiencia (HPLC). Utilizando los tiempos de retención con relación al colesterol (t^j.) en CG y HPLC, junto con los pesos moleculares obtenidos por CG—MS se infiere la presencia de algunos esteroides.- " • ' ;

De las hojas de Virola sebifera fueron aislados tres lignanos furofuránicos: (+ )-sesamina, (+ )-kobusina y (-t- )-eudesmina. Se describe una adaptación de la técnica de cromatografía liquida al vacío.

Se desarrolló un ensayo inmunoenzimático de fase sólida (ELISA) indirecto para cuantificar anticuerpos IgG específicos antipolisacárido C en ratón, utilizando un prerrecubrimiento con Poli-L-lisina y luego el polisacárido capsular de Neisseria meningitidis serogrupo C (Instituto Finlay, La Habana, Cuba), para evaluar la respuesta inmune contra este componente en candidatos vacunales en estudios preclínicos. Como conjugado se utilizó anti-IgG ratón conjugado a fosfatasa alcalina, el cual se une a los anticuerpos antipolisacárido C producidos en ratones. La reacción es evidenciada por la degradación del sustrato p-nitrofenilfosfato. La detectibilidad del ensayo fue de 123,74 U/mL y la especificidad fue alta. La precisión interensayo, intraensayo y total, así como las desviaciones de la recuperación, linealidad y paralelismo no sobrepasaron el 10%. El ELISA permitió cuantificar los anticuerpos antipolisacárido C inducidos en ratones tanto por candidatos vacunales conjugados, como por la vacuna VA-MENGOC-BC y el polisacárido C sin conjugar.

Las infecciones meningocócicas son una causa importante de morbilidad y mortalidad en el mundo. Los serogrupos B y C son los responsables de la mayoría de los casos reportados en muchos países e incluso en países desarrollados. Las vacunas meningocócicas que contienen al polisacárido capsular purificado del meningococo C inducen en adultos protección por la presencia de anticuerpos bactericidas en sueros, pero son pobremente inmunogénicos en niños pequeños y pueden inducir tolerancia. La inmunogenicidad de los polisacáridos o sus fragmentos puede ser mejorada por la conjugación a proteínas transportadoras. El objetivo de este estudio fue obtener oligosacáridos C (Os-C) a partir de la depolimerización del polisacárido de Neisseria meningitidis serogrupo C (Ps-C) por hidrólisis ácida, calor y peryodato de sodio y evaluar la conservación de sus propiedades antigénicas mediante un ELISA de inhibición. Se determinó la pérdida de grupos O-acetilos, así como, la talla molecular relativa por filtración en gel y se observaron diferencias significativas entre los OS-C obtenidos en cada método. Las propiedades antigénicas fueron dependientes del tamaño molecular de los Os-C, así como de la presencia de los grupos O-acetilos en los oligosacáridos. Los Os-C obtenidos por la hidrólisis ácida mostraron similares propiedades antigénicas a las del polisacárido.

La alta incidencia mundial de meningitis meningocócica por Neisseria meningitidis serogrupo B (N. meningitidis) movilizó los recursos de la ciencia hacia su enfrentamiento en un período corto de tiempo. Para el estudio de esta enfermedad fue imprescindible desarrollar modelos experimentales que posibilitaran caracterizar no sólo la capacidad inmunogénica y protectora de los candidatos vacunales, sino también la toxigenicidad del producto. El estudio basado en el modelo ratón Balb/c con la utilización de factores estimulantes de la virulencia, posibilitó el desarrollo experimental de la enfermedad. Consistió en la aplicación de diferentes esquemas de dosis y diluciones de la vacuna (1/2, 1/4, 1/8, 1/16) en solución salina fisiológica 0,85%. Se conformaron 15 grupos de ocho animales cada uno que previamente recibieron Dextrana Férrica (IMEFA) y mucina gástrica de cerdo 8% en un volumen total de 0,4 mL, y un grupo control al que le fue administrada la vacuna pura. Se empleó para el reto la cepa 385 de N. meningitidis con una concentración del inóculo de 107 UFC/mL. El esquema de vacunación contempló grupos vacunados con 1, 2, y 3 dosis a los 0,15 y 30 días. Se administraron 0,2 mL del inóculo de N. meningitidis por vía intraperitoneal. Se determinó la dosis letal media (DL50), anticuerpos bactericidas, respuesta serológica por el método de ELISA y se calculó la protección conferida. Se aplicó el método de Log rank para la comparación de los tiempos de sobrevivencia y para el ensayo de ELISA se aplicó el método de superficie ajustada por SPLINE. Hemos demostrado la utilidad del biomodelo ratón Balb/c para comprobar la eficacia de la vacuna VA-MENGOC-BC®. Quedó demostrada la correlación entre los niveles de anticuerpos y la protección conferida por la vacuna, comprobándose además por los ensayos de reto. Se logró obtener una aproximación con respecto a los límites de eficacia de VA-MENGOC-BC® mediante diluciones consecutivas del producto en la línea de ratones Balb/c.

Se realizó una revisión sobre la estandarización de técnicas inmunoenzimáticas para ensayos preclínicos y clínicos de vacunas, elaborándose una guía práctica. Se analizan los principios a usar y los pasos a seguir para la optimización de un ensayo, incluyendo la preparación de estándares y controles. Se exponen nuestras experiencias.

Se realizó una revisión y actualización sobre la importancia de la validación de los inmunoensayos cualitativos usados para evaluar la inmunogenicidad de vacunas, sus principios y procedimientos. Se discutieron los principales parámetros empleados para evaluar estas técnicas. Se analizaron detalladamente los procedimientos para estudiar la sensibilidad, especificidad, valores predictivos positivos y negativos, valor de discriminación y zona gris. Se exponen nuestras experiencias.

Abstract Background A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern. Methods This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure