Social costs associated with fibromyalgia in Spain.

BACKGROUND: Fibromyalgia is a chronic rheumatic disease of unknown aetiology, highly disabling and mainly affecting women. The aim of our work is to estimate, on a national scale, the economic impact of this disease on the employment of patients and non-professional (informal) care dimension. METHODS: Survey on Disabilities, Autonomy and Dependency carried out in Spain in 2020/21 was used to obtain information on disabled individuals with AD and their informal caregivers. Six estimation scenarios were defined as base case, depending on whether the maximum daily informal caregiving time was censored or not, and on the approach chosen for the valuation of informal caregiving time (contingent valuation and replacement time). Another six conservative scenarios were developed using the minimum wage for the estimation of labour losses. RESULTS: Our estimates range from 2,443.6 (willingness to pay, censored informal care time) to 7,164.8 million euros (replacement cost, uncensored informal care time) (base year 2021). Multivariate analyses identified that the degree of dependency of the person suffering from fibromyalgia is the main explanatory variable for both the probability of being employed and the time spent in informal care. Conservative scenarios estimates range from 1,807 to 6,528 million euros. CONCLUSIONS: The high economic impact revealed should help to position a health problem that is relatively unknown in society and for which there are significant research and care gaps to be filled.

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

Walking in pregnancy and prevention of insomnia in third trimester using pedometers: study protocol of Walking_Preg project (WPP). A randomized controlled trial.

BACKGROUND: Previous studies in pregnancy have not focused in evaluating the effect of walking during pregnancy and prevention of insomnia. Our general objective is to determine the effect of a walking program in preventing the appearance of insomnia in the third trimester of pregnancy, increasing sleep quality and improving quality of life throughout pregnancy. METHODS: Randomized Controlled trial in parallel in healthy sedentary pregnant women (n = 265), Walking_Preg Project (WPP), from university hospital in Granada, Spain. At 12th gestational week (GW), they will be invited to participate and randomly assigned to one of the three arms of study: the intervention group I1 (pedometer, goal of 11,000 steps/day), intervention group I2 (pedometer, no goal) and control (no pedometer). Duration of intervention: 13-32 GW. At 12th, 19th and 31st GW the average steps/day will be measured in groups I1 and I2. At 13th, 20th and 32nd GW, Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Adherence to Mediterranean Diet (AMD), physical activity (short IPAQ), quality of life (PSI), and consumption of toxic substances (caffeine, illegal drugs, alcohol and tobacco) will be collected. Student t test or Mann-Whitney U will be used to compare 19th and 31st GW mean of daily steps between I1 and I2 groups. To compare differences between groups in terms of frequency of insomnia/quality of life for each trimester of pregnancy, Pearson's Chi-square test or Fisher's exact test will be used. To determine differences in hours of sleep and quality of sleep throughout each trimester of pregnancy, analysis of variance or Friedman test will be used. McNemar-Bowker test will be used to assess differences in life quality in pre-post analyses in the 3 arms. We will use Stata 15 statistical software. DISCUSSION: promoting walking in second half of pregnancy through use of pedometer and health pre-registration of a goal to be achieved -'10,000-11,000 steps a day'- should prevent appearance of insomnia in third trimester, will increase sleep quality and quality of life in pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03735381 . Registered 8th November, 2018.

Análisis morfométrico e índices corporales del capitán de la sabana / Morphometric analysis and body indexes of the catfish (Eremophilus mutisii)

RESUMEN Con el objetivo de caracterizar la morfometría e índices corporales de Eremophilus mutisii, se usaron treinta y tres peces (27 hembras y 6 machos) provenientes del río Bogotá, específicamente de la región de Suesca. La relación de aspecto de la aleta caudal se determinó mediante el software de análisis de imágenes ImageJ®. Se calculó el índice gonadosomático, hepatosomático y rendimiento en canal para cada pez. Para el análisis de los datos se usaron correlaciones, regresiones y técnicas de análisis multivariado (análisis discriminante canónico). Como resultado del estudio se encontró que el sexo no afecta la forma del cuerpo de los peces. La relación entre la longitud y el peso se ajustó para cada sexo. La relación de aspecto de la aleta caudal presentó un promedio de 1,57 lo que sugiere que la especie presenta hábito sedentario o de natación lenta. El índice gonadosomático de las hembras en maduración (media: 14,43%, rango: 8,84% a 23,22%) aumentó en función del peso corporal y fue mayor que el de los machos (media: 5,32%, rango: 2,31% a 8,29%). Por lo tanto, el rendimiento de la carcasa fue menor en las hembras en maduración. La media del índice hepatosomático para hembras fue 0,86% (rango: 0,43% a 1,88%) y para machos fue 0,63% (rango: 0,39% a 1,09%). En conclusión, Eremophilus mutisii es una especie sedentaria y las hembras se caracterizarán por presentar mayor índice gonadosomático y menor rendimiento en carcasa que los machos.

ABSTRACT With the aim of characterizing the morphometry and body indexes of Eremophilus mutisii, thirty-three fishes (27 females and 6 males) coming from the Bogotá river, specifically of the Suesca region, were used. The aspect ratio of the caudal fin was determined with the aid of the image analysis software ImageJ®. Gonadosomatic and hepatosomatic indexes and carcass yield were determined for each fish. Correlation, regression and multivariate (canonical discriminant analysis) techniques were used for data analysis. Results indicated that sex does not affect the body shape of the fishes. The relationship between length and weight was fitted for each sex. The average aspect ratio of the caudal fin was 1.57, which suggests that the species has sedentary habits or slow swimming. The gonadosomatic index of the maturing females (mean: 14.43 %; range: 8.84 % to 23.22 %) increased as a function of body weight and was greater than in males (mean: 5.32 %; range: 2.31 % to 8.29 %). Therefore, the carcass yield was lower in maturing females than in males. The mean of the hepatosomatic index for females was 0.86 % (range: 0.43 % to 1.88 %) and for males was 0.63 % (range: 0.39 % to 1.09 %). As a conclusion, Eremophilus mutisii is a sedentary fish species, and females exhibit greater gonadosomatic index and lower carcass yield than males.

Correction: NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL.

The original version of this Article contained an error in the spelling of the author Juan Carlos Rodriguez-Manzaneque, which was incorrectly given as J Carlos Rodríguez-Manzaneque. This has now been corrected in both the PDF and HTML versions of the Article.

NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL.

Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive. Here we evaluated whether NG2 distinguishes leukemia-initiating/propagating cells (L-ICs) and/or CNS-infiltrating cells (CNS-ICs) in iMLLr-B-ALL. Clinical data from the Interfant cohort of iMLLr-B-ALL demonstrated that high NG2 expression associates with lower event-free survival, higher number of circulating blasts and more frequent CNS disease/relapse. Serial xenotransplantation of primary MLL-AF4+ leukemias indicated that NG2 is a malleable marker that does not enrich for L-IC or CNS-IC in iMLLr-B-All. However, NG2 expression was highly upregulated in blasts infiltrating extramedullar hematopoietic sites and CNS, and specific blockage of NG2 resulted in almost complete loss of engraftment. Indeed, gene expression profiling of primary blasts and primografts revealed a migratory signature of NG2+ blasts. This study provides new insights on the biology of NG2 in iMLLr-B-ALL and suggests NG2 as a potential therapeutic target to reduce the risk of CNS disease/relapse and to provide safer CNS-directed therapies for iMLLr-B-ALL.

Partner smoking influences whether mothers quit smoking during pregnancy: a prospective cohort study.

OBJECTIVE: To analyse the prevalence and intensity of smoking among pregnant women and their partners, and factors associated with quitting smoking among pregnant women. DESIGN: A prospective cohort study, starting in 2013. SETTING: Andalusia, the south of Spain. SAMPLE: A cohort of 486 healthy pregnant women followed-up on three occasions during pregnancy. METHODS: Estimation of the proportions of women and partners who quit smoking at each trimester. MAIN OUTCOME MEASURES: To determine factors associated in a multivariable model, considering sociodemographic, obstetric, anthropometric, lifestyle variables, and the smoking habits of their partners. RESULTS: A high proportion of women quit smoking during pregnancy (61.08%; 95% confidence interval, 95% CI 53.61-68.55%). The smoking rate amongst mothers decreased from 36.06% (n = 167) before pregnancy to 14.08% (n = 65), 12.39% (n = 54), and 11.92% (n = 51) during the three pregnancy trimesters (P < 0.001), and consumption decreased from 8.71 cigarettes/day in the first trimester to 5.51 cigarettes/day in the second trimester (P < 0.001) and 5.96 cigarettes/day in third trimester (P = 0.0002 first versus third trimester). There was only a minimal decrease in the frequency of smoking among the partners, however: 38.44% (n = 178) before pregnancy, and 36.07% (n = 167), 32.72% (n = 143), and 31.85% (n = 136) during the three trimesters of pregnancy. The consumption of cigarettes did not decrease among partners: 11.75, 11.67, and 12.09 cigarettes/day (P = 0.4299 first versus second trimester; P = 0.654 first versus third trimester). Women whose partner smoked were less likely to quit (adjusted odds ratio, aOR 0.26; 95% CI 0.12-0.55). CONCLUSIONS: About one in ten pregnant women smoked and one in four was a passive smoker. Strategies to reduce tobacco exposure in pregnancy should include a focus on partner smoking. TWEETABLE ABSTRACT: Pregnant women quit smoking cigarettes in pregnancy. What about their partners?

Evaluación de protocolo de bajas dosis en radioscopía para nefrolitotomía percutánea. Comparación de resultados y seguridad en un estudio prospectivo y randomizado / Evaluation of low dose protocol in fluoroscopy for percutaneous nephrolithotomy. Comparison of results and safety in a prospective randomized study

INTRODUCCIÓN: Tradicionalmente, durante la Nefrolitotomía Percutánea (NPL), la radioscopía se efectúa en modo Continuo a 10 FPS (imágenes por segundo). Existe escasa experiencia en la literatura urológica sobre disminución de dosis de radiación durante la radioscopía y su efecto en el éxito de la NPL (eficacia y seguridad). Series de casos, demuestran resultados similares usando radioscopía en modo Pulsado (1-4 FPS), determinando un Tiempo de Radioscopía inferior al modo Contínuo. Dichas experiencias no son basadas en diseños randomizados, ni reportan Dosimetría Directa. Hipótesis: usando radioscopía pulsada, se logran iguales resultados y con igual seguridad, que con radioscopía Contínua, y con exposición a radiación significativamente más baja. MATERIAL Y MÉTODO: Estudio prospectivo, randomizado, ciego simple y experimental (aprobado por Comité de Ética). Muestra de 19 pacientes, entre Abril y Agosto de 2017. De forma aleatoria, aproximadamente la mitad de los pacientes fueron sometidos a NPL con radioscopía Contínua (10 FPS) y la otra mitad con modalidad Pulsada (2 FPS). Intervenidos en el mismo establecimiento, con 1 trayecto, utilizando el mismo equipo de Radioscopía. Se registró Dosimetría Directa, Tiempo de Radioscopía, resultado (Stone Free) y complicaciones, en cada procedimiento. El análisis estadístico se realizó con medidas de tendencia central, se verificó distribución normal de la muestra y comparación de variables mediante t-Test, con intervalo de confianza del 95 por ciento. RESULTADOS: En 8 pacientes se utilizó radioscopía Contínua, y en 11, radioscopía Pulsada. La Dosimetría del grupo radioscopía Contínua promedió 2,7 mSv, para radioscopía Pulsada el promedio fue 3,1 mSv. El Tiempo de Radioscopía del grupo radioscopía Contínua fue de 286,4 s, del grupo radioscopía Pulsada fue de 365,7 s. Ambas diferencias no son estadísticamente significativas (p 0,6 y p 0,3 respectivamente). En relación al Resultado y Complicaciones, no hubo diferencias entre ambos grupos. CONCLUSIONES: Para los pacientes estudiados a la fecha, no se demuestra beneficioso realizar radioscopía Pulsada: la Dosimetría Directa y el Tiempo de Radioscopía fueron mayores en el grupo de modalidad Pulsada. Nuestros resultados son diferentes a lo reportado en la literatura, lo cual hace necesario evaluar el impacto de esta intervención, y considerar otros factores que pudieran influir (AU)

INTRODUCTION: Traditionally, during Percutaneous Nephrolithotomy (PCNL), fluoroscopy is performed in Continuous mode at 10 FPS (images per second). There is little experience in the urological literature on the reduction of radiation dose during fluoroscopy and its effect on the success of the PCNL (efficacy and safety). Several case show similar results, using Pulsed radioscopy (1-4 FPS), determining a Radioscopy Time inferior to the one in Continuous mode. These experiences are not based on randomized designs, nor do they report Direct Dosimetry. Hypothesis: using pulsed fluoroscopy, the same results are obtained and equally safe than with Continuous radioscopy and with exposure to significantly lower radiation. MATERIAL AND METHOD: Prospective, randomized, simple and experimental blind study (approved by the Ethics Committee). Sample of 19 patients, between April and August 2017. Randomly, approximately half of the patients underwent PCNL with continuous radioscopy (10 FPS) and the other half with Pulsed modality (2 FPS). They were intervened in the same establishment, in one journey, using the same Radioscopy equipment. Direct Dosimetry, Radioscopy Time, and complications results (Stone Free) were registered in each procedure. The statistical analysis was performed with central trend measures, normal distribution of the sample was verified and comparison of variables by t-Test, with 95 % confidence interval. RESULTS: Continuous fluoroscopy was used on eight patients, and Pulsed radioscopy on eleven. The Dosimetry of the Continuous fluoroscopy group averaged 2.7 mSv. Pulsed fluoroscopy average was 3.1 mSv. The Radioscopy Time of the Continuous fluoroscopy group was 286.4 s. Pulsed radioscopy group time it was 365.7 s. Both differences are not statistically significant (p 0.6 and p 0.3 respectively). In relation to the Result and Complications, there were no differences between the two groups. CONCLUSIONS: Performance of Pulsed Radioscopy benefits are not shown in the patients studied to date: Direct Dosimetry and Radioscopy Time were greater in the Pulsed modality group. Our results are different from those reported in the literature, which makes it necessary to evaluate the impact of this intervention, and consider other factors that could influence.(AU)

Una revisión de la literatura acerca de las características neuropsicológicas de niños con craneosinostosis simple en diferentes edades / A review of the literature on the neuropsychological characteristics of children with single suture craniosynostosis at different ages

Introduction: Single suture craniosynostosis is the premature closure of one or more cranial sutures. It leads to abnormal skull growth and in some cases to structural and/or functional brain abnormalities. If these anomalies cause a psychomotor development lag and/or cognitive impairment is a controversial topic. This study aims to review the main findings related to psychomotor development and cognitive functioning in children with craniosynostosis, from birth to school age, dividing them into three stages: birth to 3 years, preschool and school. Method: An electronic search was made in PubMed from 2000 to 2015, using the following keywords: "craniosynostosis and neurodevelopment", "craniosynostosis and neuropsychological", "craniosynostosis and cognition". Results: In the early stage of life some children with craniosynostosis can have motor, language and cognition deficits; these impairments are also present in a variable percentage of preschool children, in some cases accompanied with behavior disorders; deficits in attention, executive functions and learning disorders, are reported in school years. Conclusion: Some neuropsychological alterations are found in a variable proportion of patients with craniosynostosis in all stages of development whichare revealed depending on the demands of each age. It is difficult to draw a cognitive profile for this population because of the heterogeneity related to characteristics of the sample, time of assessment, functions assessed and instrument used. It is important to make longitudinal neuropsychological assessments to know how children with craniosynostosis are developing in late stages and to develop consensus about cognitive functions and assessment instruments appropriate for each age.

Introducción: La craneosinostosis simple es el cierre prematuro de una o más suturas craneales que provoca crecimiento anormal del cráneo y en algunos casos anormalidades cerebrales estructurales y/o funcionales. Es un tema controversial si estas anormalidades causan el retraso psicomotor y/o cognitivo reportado en estos pacientes. Esta revisión tiene como objetivo abordar los hallazgos encontrados en el desarrollo psicomotor y cognitivo en niños con craneosinostosis, desde el nacimiento hasta la edad escolar, dividiéndolos en tres etapas: nacimiento a 3 años, etapa preescolar y escolar. Método: Se realizó una búsqueda en PubMed del 2000 al 2015, utilizando estas palabras claves: "craniosynostosis and neurodevelopment", "craniosynostosis and neuropsychological", "Craniosynostosis and cognition". Resultados: En las etapas tempranas de la infancia, los niños con craneosinostosis pueden tener deficiencias motoras, de lenguaje y cognitivas; estos déficits están presentes en un porcentaje variable en la etapa preescolar y pueden acompañarse de alteraciones conductuales; deficiencias atencionales, ejecutivas y de aprendizaje, se reportan en la edad escolar. Conclusión: Se reportan alteraciones neuropsicológicas en un porcentaje variable en estos pacientes en todas las etapas del desarrollo, que se van manifestando conforme las demandas del ambiente. Es difícil establecer un perfil neuropsicológico debido a la heterogeneidad de las características de las muestras en los estudios, el tiempo de la evaluación, las funciones estudiadas y los instrumentos utilizados. Es importante realizar un seguimiento longitudinal para conocer el desarrollo de estos niños, así como el hacer un consenso sobre las funciones cognitivas a evaluar e instrumentos a utilizar para cada edad.

Vascular AMPK as an attractive target in the treatment of vascular complications of obesity.

The key for the survival of all organisms is the regulation and control of energy metabolism. Thus, several strategies have evolved in each tissue in order to balance nutrient supply with energy demand. Adenosine monophosphate-activated protein kinase (AMPK) is now recognized as a key participant in energy metabolism. It ensures an appropriate energetic supply by promoting energy conserving pathways in detriment of anabolic processes not essential for cell survival. Vascular AMPK plays a critical role in the regulation of blood flow and vascular tone through several mechanisms, including vasodilation by stimulating nitric oxide release in endothelial cells. Since obesity leads to endothelial damage and AMPK dysregulation, AMPK activation might be an important strategy to restore vascular function in cardiometabolic alterations. In the present review we focus on the role of vascular AMPK in both endothelial and smooth muscle cells, paying special attention to its dysregulation in obesity- and high-fat diet-related complications, as well as to the mechanisms and benefits of vascular AMPK activation.

The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and regulates their hematopoietic fate.

Notch signaling is essential for definitive hematopoiesis, but its role in human embryonic hematopoiesis is largely unknown. We show that in hESCs the expression of the Notch ligand DLL4 is induced during hematopoietic differentiation. We found that DLL4 is only expressed in a sub-population of bipotent hematoendothelial progenitors (HEPs) and segregates their hematopoietic versus endothelial potential. We demonstrate at the clonal level and through transcriptome analyses that DLL4(high) HEPs are enriched in endothelial potential, whereas DLL4(low/-) HEPs are committed to the hematopoietic lineage, albeit both populations still contain bipotent cells. Moreover, DLL4 stimulation enhances hematopoietic differentiation of HEPs and increases the amount of clonogenic hematopoietic progenitors. Confocal microscopy analysis of whole differentiating embryoid bodies revealed that DLL4(high) HEPs are located close to DLL4(low/-) HEPs, and at the base of clusters of CD45+ cells, resembling intra-aortic hematopoietic clusters found in mouse embryos. We propose a model for human embryonic hematopoiesis in which DLL4(low/-) cells within hemogenic endothelium receive Notch-activating signals from DLL4(high) cells, resulting in an endothelial-to-hematopoietic transition and their differentiation into CD45+ hematopoietic cells.

Experience in retake analysis for digital mammography at a university hospital.

Data from one digital mammograph (flat detector active area of 19.2 × 23 cm(2)) were collected over a 1-year period using locally developed software in order to evaluate retakes, their rates, their causes and the possible measures to reduce their occurrence. Among them, 7.1 % of the images were marked as repetitions, and in 16 % of the studies, at least one image was repeated. When evaluating causes of retakes, the primary cause was incorrect positioning (49 %), closely followed by additional retakes in cases of large breasts (44 %). When dealing with large breasts and using a small flat panel, additional images were necessary to fully visualise the breast, and as a consequence, some breast regions received repeated radiation exposure. Moreover, a small detector increases retakes in breasts slightly wrongly positioned. To try and reduce the retake rate, it is important to plan training sessions based on images selected from the retake analysis.

Mild caloric restriction reduces blood pressure and activates endothelial AMPK-PI3K-Akt-eNOS pathway in obese Zucker rats.

Genetic obesity models exhibit endothelial dysfunction associated to adenosine monophosphate-activated protein kinase (AMPK) dysregulation. This study aims to assess if mild short-term caloric restriction (CR) restores endothelial AMPK activity leading to an improvement in endothelial function. Twelve-week old Zucker lean and obese (fa/fa) male rats had access to standard chow either ad libitum (AL, n=8) or 80% of AL (CR, n=8) for two weeks. Systolic blood pressure was significantly higher in fa/fa AL rats versus lean AL animals, but was normalized by CR. Endothelium-dependent relaxation to acetylcholine (ACh, 10(-9) to 10(-4) M) was reduced in fa/fa AL compared to control lean AL rats (p<0.001), and restored by CR. The AMPK activator AICAR (10(-5) to 8·10(-3) M) elicited a lower relaxation in fa/fa AL rings that was normalized by CR (p<0.001). Inhibition of PI3K (wortmannin, 10(-7) M), Akt (triciribine, 10(-5) M), or eNOS (L-NAME, 10(-4) M) markedly reduced AICAR-induced relaxation in lean AL, but not in fa/fa AL rats. These inhibitions were restored by CR in Zucker fa/fa rings. These data show that mild short-term CR improves endothelial function and lowers blood pressure in obesity due to the activation of the AMPK-PI3K-Akt-eNOS pathway.

Ligand-independent FLT3 activation does not cooperate with MLL-AF4 to immortalize/transform cord blood CD34+ cells.

MLL-AF4 fusion is hallmark in high-risk infant pro-B-acute lymphoblastic leukemia (pro-B-ALL). Our limited understanding of MLL-AF4-mediated transformation reflects the absence of human models reproducing this leukemia. Hematopoietic stem/progenitor cells (HSPCs) constitute likely targets for transformation. We previously reported that MLL-AF4 enhanced hematopoietic engraftment and clonogenic potential in cord blood (CB)-derived CD34+ HSPCs but was not sufficient for leukemogenesis, suggesting that additional oncogenic lesions are required for MLL-AF4-mediated transformation. MLL-AF4+ pro-B-ALL display enormous levels of FLT3, and occasionally FLT3-activating mutations, thus representing a candidate cooperating event in MLL-AF4+ pro-B-ALL. We have explored whether FLT3.TKD (tyrosine kinase domain) mutation or increased expression of FLT3.WT (wild type) cooperates with MLL-AF4 to immortalize/transform CB-CD34+ HSPCs. In vivo, FLT3.TKD/FLT3.WT alone, or in combination with MLL-AF4, enhances hematopoietic repopulating function of CB-CD34+ HSPCs without impairing migration or hematopoietic differentiation. None of the animals transplanted with MLL-AF4+FLT3.TKD/WT-CD34+ HSPCs showed any sign of disease after 16 weeks. In vitro, enforced expression of FLT3.TKD/FLT3.WT conveys a transient overexpansion of MLL-AF4-expressing CD34+ HSPCs associated to higher proportion of cycling cells coupled to lower apoptotic levels, but does not augment clonogenic potential nor confer stable replating. Together, FLT3 activation does not suffice to immortalize/transform MLL-AF4-expressing CB-CD34+ HSPCs, suggesting the need of alternative (epi)-genetic cooperating oncogenic lesions.

Efectividad de consejería de cesación tabáquica en dos tipos de intervenciones en centros de salud de APS en Chile / Effectiveness of two types of smoking cessation counseling

Este estudio explora la efectividad de dos tipos de consejería de cesación tabáquica, para ello se reclutaron 34 mujeres entre 18 y 48 años pertenecientes a dos CESFAM de la Región Metropolitana en Chile, de las cuales 30 cumplían con los criterios de inclusión. Fueron aleatorizadas en 2 grupos homogéneos de 15 personas cada uno y se sometieron a dos modalidades de consejería de cesación tabáquica según estrategia de las 5A.Posteriormente se realizó un seguimiento de 2 meses para observar el cambio de conducta. No hubo diferencias significativas en el porcentaje de cesación de ambos grupos: 23.08 por ciento de las mujeres dejó de fumar en el grupo 1 y 21,43 por ciento en el grupo 2. Se puede evidenciar que a pesar de realizar dos tipos diferentes de intervenciones, no se obtuvieron diferencias significativas en el porcentaje de cesación de ambos grupos.

This study explores the effectiveness of two types of smoking cessation counseling and for this we recruited 34women between 18 and 48 years from two CESFAM Metropolitan Region in Chile, of which 30 met the inclusion criteria. They were randomized into two homogeneous groups of 15 people each and were subjected to two forms of smoking cessation counseling by the 5A strategy. Subsequently followed up for two months to observe the change in behavior. No significant differences in the percentage of cessation of both groups: 23.08 percent of women quit smoking in group I and 21.43 percent in group II. It may show that despite making two different types of interventions, no significant differences in the percentage of cessation of both groups.

Role of arginase-2 and eNOS in the differential vascular reactivity and hypoxia-induced endothelial response in umbilical arteries and veins.

The main vasodilator in the placenta is nitric oxide (NO), which is synthesized by endothelial NO synthase (eNOS). Arginase-2 competes with eNOS for l-arginine, and its activity has been related with vascular dysfunction. Recently, we showed that hypoxia induces arginase-2, and decreases eNOS activity in human umbilical vein endothelial cells (HUVEC). However there is evidence that vascular responses to hypoxia are not similar throughout the placental vascular tree. We studied whether arginase-2 plays a role controlling vascular tone in human umbilical vessels, and the changes in the expression of arginase-2 and eNOS proteins by hypoxia in endothelial cells from umbilical arteries (HUAEC) and veins (HUVEC). In isolated umbilical vessels the presence of eNOS and arginase-2 was determined in the endothelium, and the NO-dependent vasoactive responses in the presence and absence of S-(2-boronoethyl)-L-cysteine (BEC, arginase inhibitor) were studied. Additionally, HUAEC and HUVEC were exposed (0-24 h) to hypoxia (2% O2) or normoxia (5% O2), and protein levels of eNOS (total and phosphorylated at serine-1177) and arginase-2 were determined. In umbilical arteries and veins arginase-2 and eNOS were detected mainly at the endothelium. BEC induced a higher concentration-dependent relaxation in umbilical arteries than veins, and these responses were NOS-dependent. In HUAEC exposed to hypoxia there were no changes in eNOS and arginase-2 levels, however there was a significant increase of p-eNOS. In contrast, HUVEC showed an increase in arginase-2 and a reduction of p-eNOS in response to hypoxia. These results show that arginases have a vascular role in placental vessels counteracting the NOS-dependent relaxation, which is differentially regulated in placental artery and vein endothelial cells.

X-ray absorption and Mössbauer spectroscopies characterization of iron nanoclusters prepared by the gas aggregation technique.

Partially oxidized iron nanoclusters have been prepared by the gas-phase aggregation technique with typical sizes of 2-3 nm. This preparation technique has been reported to obtain clusters with interesting magnetic properties such as very large exchange bias. In this paper, a sample composition study carried out by Mössbauer and X-ray absorption spectroscopies is reported. The information reached by these techniques, which is based on the iron short range order, results to be an ideal way to have a characterization of the whole sample since the obtained data are an average over a very large amount of the clusters. In addition, our results indicate the presence of ferrihydrite, which is a compound typically ignored when studying this type of systems.

Hypoxia-reduced nitric oxide synthase activity is partially explained by higher arginase-2 activity and cellular redistribution in human umbilical vein endothelium.

Hypoxia relates with altered placental vasodilation, and in isolated endothelial cells, it reduces activity of the endothelial nitric oxide synthase (eNOS) and l-arginine transport. It has been reported that arginase-2 expression, an alternative pathway for l-arginine metabolism, is increased in adult endothelial cells exposed to hypoxia as well as in pre-eclamptic placentae. We studied in human umbilical vein endothelial cells (HUVEC) whether hypoxia-reduced NO synthesis results from increased arginase-mediated l-arginine metabolism and changes in subcellular localization of eNOS and arginase-2. In HUVEC exposed (24 h) to 5% (normoxia) or 2% (hypoxia) oxygen, l-arginine transport kinetics, arginase activity (urea assay), and NO synthase (NOS) activity (l-citrulline assay) were determined. Arginase-1, arginase-2 and eNOS expression were determined by RT-PCR and Western blot. Subcellular localization of arginase-2 and eNOS were studied using confocal microscopy and indirect immunofluorescence. Experiments were done in absence or presence of S-(2-boronoethyl)-l-cysteine-HCl (BEC, arginase inhibitor) or N(G)-nitro-l-arginine methyl ester (l-NAME). Hypoxia-induced reduction in eNOS activity was associated with a reduction in eNOS phosphorylation at Serine-1177 and increased phosphorylation at Threonine-495. This was paralleled with an induction in arginase-2 expression and activity, and decreased l-arginine transport. In hypoxia the arginase inhibition, restored NO synthesis and l-arginine transport, without changes in the eNOS post-translational modification status. Hypoxia increased arginase-2/eNOS colocalization, and eNOS redistribution to the cell periphery. Altogether these data reinforce the thought that eNOS cell location, post-translational modification and substrate availability are important mechanisms regulating eNOS activity. If these mechanisms occur in pregnancy diseases where feto-placental oxygen levels are reduced remains to be clarified.

Molecules, wing pattern and distribution: an approach to species delimitation in the "loxurina group" (Lepidoptera: Lycaenidae: Penaincisalia)

The wide range of morphological variations in the "loxurina group" makes taxa identification difficult, and despite several reviews, serious taxonomical confusion remains. We make use of DNA data in conjunction with morphological appearance and available information on species distribution to delimit the boundaries of the "loxurina" group species previously established based on morphology. A fragment of 635 base pairs within the mtDNA gene cytochrome oxidase I (COI) was analysed for seven species of the "loxurina group". Phylogenetic relationships among the included taxa were inferred using maximum parsimony and maximum likelihood methods. Penaincisalia sigsiga (Bálint et al), P. cillutincarae (Draudt), P. atymna (Hewitson) and P. loxurina (C. Felder & R. Felder) were easily delimited as the morphological, geographic and molecular data were congruent. Penaincisalia ludovica (Bálint & Wojtusiak) and P. loxurina astillero (Johnson) represent the same entity and constitute a sub-species of P. loxurina. However, incongruence among morphological, genetic, and geographic data is shown in P. chachapoya (Bálint & Wojtusiak) and P. tegulina (Bálint et al). Our results highlight that an integrative approach is needed to clarify the taxonomy of these neotropical taxa, but more genetic and geographical studies are still required.