Convenient synthesis of C75, an inhibitor of FAS and CPT1

C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier.

Prevalencia de la discapacidad en España por comunidades autónomas: el papel de los factores individuales y del entorno geográfico en su variabilidad

Fundamento: La prevalencia de discapacidad en la población general presenta una gran variabilidad geográfica, de manera que identificar aquellos factores que pudieran explicarla será importante para la planificación de políticas sociales. En este trabajo se analiza la variabilidad de la discapacidad por comunidades autónomas desde una doble vertiente, los factores individuales y del entorno. Métodos: Los datos proceden principalmente de la Encuesta de Discapacidad, Deficiencias y Estado de Salud de 1999 y del Inebase, ambas del Instituto Nacional de Estadística (INE). Se calculó la prevalencia de discapacidad simple y ajustada por edad de las CCAA. Se analizan los factores individuales asociados a la discapacidad mediante una regresión logística y los factores individuales y de la comunidad autónoma conjuntamente con una regresión logística de dos niveles. Resultados: La prevalencia de discapacidad muestra una diferencia máxima de 5,75 puntos entre las comunidades autónomas. En la regresión logística la comunidad de residencia fue estadísticamente significativa (OR: 3,35 en la de mayor prevalencia respecto a la de menor) junto con otras variables individuales: edad (OR de 40-64= 1,78 OR de 65-79= 1,87 y OR de >79= 3,34), sexo (OR mujer= 0,66), situación laboral (OR sin trabajo=2,25 OR amas casa/estudiante=1,39 y OR otros=2,03), estado de salud (OR regular= 1,69 OR malo/muy malo= 2,05) y enfermedades crónicas (OR 1-3=1,56 OR4-6=1,82 OR>6=2,59). En la regresión de dos niveles las variables individuales explican poca varianza (s=0,261) y ninguna de las variables relativas a las CCAA mejora el modelo. Conclusiones: Las características individuales no explican suficientemente la variabilidad de la discapacidad entre CCAA y no se han identificado variables del entorno que sean significativas.

Effects of nitrogen supply on wheat and on soil nitrate

Field experiments were conducted at two locations during two growing seasons in the Ebro Valley (Spain), to evaluate the effects of N fertilization on yield and quality of Mediterranean-type wheat in irrigated conditions. Seven N treatments and a control were investigated. The average grain yields ranged from 2117 to 5551 kg ha-1 depending on the year and location. Grain protein ranged from 14.25 to 16.9%, and other quality parameters such as the dough strength (W) also varied with year and location, confirming the suitability of Mediterranean-type wheat and the climate for the production of good bread-making quality wheat. However, grain yields are normally low and both yields and quality can be greatly affected by the variability of this type of climate, even under irrigation. Under these conditions, grain yield increases were mainly due to an increase in the number of grains per m2 without a reduction in the N content per spike, suggesting that N in the grain was not source-limited, possibly due to the lower grain yields and relatively high soil nitrate concentrations. In soils with lower initial soil NO-3N contents, better grain yields could be achieved by applying a N fertilizer rate of about 100 kg N ha-1, whereas in soils with high initial NO-3N contents, no N or a maximum rate of 50 kg N ha-1 is needed to obtain a good grain quality, showing the possibility of producing high-quality wheat with a low amount of N fertilizer and thus increasing the sustainability of the cropping system.

Estudi de la producció i de la qualitat farratgera de les pastures de la finca dels Cingles de l'Avenc (Tavertet). 2011

A Catalunya, la protecció i gestió de zones d’especial interès natural ha estat majoritàriament realitzada pel conjunt de les administracions públiques. Tot i així, en els últims anys han sorgit un conjunt d’iniciatives privades que a través d’acords de custòdia han passat a tenir un paper actiu en la protecció i gestió d’algunes finques amb un alt valor natural. És el cas de la finca els Cingles de l’Avenc, on s’ha dut a terme aquest treball, en la qual es pretén desenvolupar una activitat ramadera compatible amb la conservació dels valors naturals de la finca. L’objectiu principal d’aquest treball és conèixer la producció i qualitat farratgera dels diferents tipus de pastures que hi ha a la finca, i establir la càrrega ramadera que poden admetre. Aquest estudi ha tingut una durada de 3 anys i en aquest treball es presenten els resultats del 2011 i es fa l’anàlisi dels resultats dels 3 anys (2009, 2010, i 2011). L’estudi s’ha portat a terme en els 4 tipus principals de pastures que hi ha a la finca: joncedes, pastures mesòfiles, prats de dall i pastures sembrades. S’han utilitzat 11 parcel·les permanents excloses de la pastura, establertes l’any 2009, que inclouen la diversitat de tipus i zones de pastura. S’ha realitzat un mostreig de la biomassa mensual, d’abril a novembre, que ha consistit en dallar 4 quadrats de 50 x 50 cm, i s’ha calculat la producció anual. S’ha determinat la qualitat farratgera de l’herba de 4 moments de l’any: maig, juny, juliol i octubre. Després dels tres anys d’estudi hem obtingut que les pastures sembrades i els prats de dall són els més productius (1.067 g/m2.any i 1.005 g/m2.any, respectivament). La producció de les pastures mesòfiles i de les joncedes són més baixes (554 g/m2.any i 291 g/m2.any, respectivament). La qualitat farratgera de les pastures és bona a totes les comunitats, amb valors mitjans de proteïna digerible de 6,63%, de fibra bruta de 29,13%, de lignina de 7,29% i de 0,69 (ENL/1,700) unitats farratgeres. La producció anual global obtinguda a la finca durant aquests tres anys permet suportar una càrrega ramadera admissible d’unes 208 UBG (Unitats de Bestiar Gros. 1 U.B.G equival a 1 vaca a partir de 2 anys).

Fast and economic immobilization methods described for non-commercial Pseudomonas lipases

There is an increasing interest to seek new enzyme preparations for the development of new products derived from bioprocesses to obtain alternative bio-based materials. In this context, four non-commercial lipases from Pseudomonas species were prepared, immobilized on different low-cost supports, and examined for potential biotechnological applications. Results: To reduce costs of eventual scaling-up, the new lipases were obtained directly from crude cell extracts or from growth culture supernatants, and immobilized by simple adsorption on Accurel EP100, Accurel MP1000 and Celite (R) 545. The enzymes evaluated were LipA and LipC from Pseudomonas sp. 42A2, a thermostable mutant of LipC, and LipI. 3 from Pseudomonas CR611, which were produced in either homologous or heterologous hosts. Best immobilization results were obtained on Accurel EP100 for LipA and on Accurel MP1000 for LipC and its thermostable variant. Lip I. 3, requiring a refolding step, was poorly immobilized on all supports tested ( best results for Accurel MP1000). To test the behavior of immobilized lipases, they were assayed in triolein transesterification, where the best results were observed for lipases immobilized on Accurel MP1000. Conclusions: The suggested protocol does not require protein purification and uses crude enzymes immobilized by a fast adsorption technique on low-cost supports, which makes the method suitable for an eventual scaling up aimed at biotechnological applications. Therefore, a fast, simple and economic method for lipase preparation and immobilization has been set up. The low price of the supports tested and the simplicity of the procedure, skipping the tedious and expensive purification steps, will contribute to cost reduction in biotechnological lipase-catalyzed processes.

Population-based incidence of myeloid malignancies: fifteen years of epidemiological data in the province of Girona, Spain

Myeloid malignancies (MMs) are a heterogeneous group of hematologic malignancies presenting different incidence, prognosis and survival.1–3 Changing classifications (FAB 1994, WHO 2001 and WHO 2008) and few available epidemiological data complicate incidence comparisons.4,5 Taking this into account, the aims of the present study were: a) to calculate the incidence rates and trends of MMs in the Province of Girona, northeastern Spain, between 1994 and 2008 according to the WHO 2001 classification; and b) to predict the number of MMs cases in Spain during 2013. Data were extracted from the population-based Girona Cancer Registry (GCR) located in the north-east of Catalonia, Spain, and covering a population of 731,864 inhabitants (2008 census). Cases were registered according to the rules of the European Network for Cancer Registries and the Manual for Coding and Reporting Haematological Malignancies (HAEMACARE project). To ensure the complete coverage of MMs in the GCR, and especially myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS), a retrospective search was performed. The ICD-O-2 (1990) codes were converted into their corresponding ICD-O-3 (2000) codes, including MDS, polycythemia vera (PV) and essential thrombocythemia (ET) as malignant diseases. Results of crude rate (CR) and European standardized incidence rate (ASRE) were expressed per 100,000 inhabitants/year

Incidence and survival of chronic myelomonocytic leukemia in Girona (Spain): a populationbased study, 1993-2007

Chronic myelomonocytic leukemia is a very rare blood cancer observed mostly in the elderly. Here we report the incidence trends and survival of patients with chronic myelomonocytic leukemia over a 15-year period (1993-2007). Cases were provided by the population-based Girona Cancer Registry. The crude incidence rate was 0.72/100,000 inhabitants/year. No statistically significant increase in trends was detected over the 15 years. Median overall survival was 28 months although survival markedly decreased with advancing age. The 5-years observed and relative survival were 20% and 29%, respectively. This is the first population-based study that reports the incidence and survival of chronic myelomonocytic leukemia in Spain

Most of the Abundant Protein Fractions of Embryonic Cerebrospinal Fluid are Produced Out of the Brain Anlagen

The microenvironment of the central nervous system is important for neuronal function and development. During the early stages of embryo development the cephalic vesicles are filled by embryonic cerebrospinal fluid, a complex fluid containing different protein fractions, which contributes to the regulation of the survival, proliferation and neurogenesis of neuroectodermal stem cells. The protein content of embryonic cerebrospinal fluid from chick and rat embryos at the start of neurogenesis has already been determined. Most of the identified gene products are thought to be involved in the regulation of developmental processes during embryogenesis. However, due to the crucial roles played by embryonic cerebrospinal fluid during brain development, the embryological origin of the gene products it contains remains an intriguing question. According to the literature most of these products are synthesised in embryonic tissues other than the neuroepithelium. In this study we examined the embryological origin of the most abundant embryonic cerebrospinal fluid protein fractions by means of slot-blot analysis and by using several different embryonic and extraembryonic protein extracts, immunodetected with polyclonal antibodies. This first attempt to elucidate their origin is not based on the proteins identified by proteomic methods, but rather on crude protein fractions detected by SDS-PAGE analysis and to which polyclonal antibodies were specifically generated. Despite some of the limitations of this study, i.e. that one protein fraction may contain more than one gene product, and that a specific gene product may be contained in different protein fractions depending on post-translational modifications, our results show that most of the analysed protein fractions are not produced by the cephalic neuroectoderm but are rather stored in the egg reservoir; furthermore, few are produced by embryo tissues, thus indicating that they must be transported from their production or storage sites to the cephalic cavities, most probably via embryonic serum. These results raise the question as to whether the transfer of proteins from these two embryo compartments is regulated at this early developmental stage.

Visual impairment and multimorbidity in a representative sample of the Spanish population

BACKGROUND: In the context of population aging, visual impairment has emerged as a growing concern in public health. However, there is a need for further research into the relationship between visual impairment and chronic medical conditions in the elderly. The aim of our study was to examine the relationship between visual impairment and three main types of co-morbidity: chronic physical conditions (both at an independent and additive level), mental health and cognitive functioning. METHODS: Data were collected from the COURAGE in Europe project, a cross-sectional study. A total of 4,583 participants from Spain were included. Diagnosis of chronic medical conditions included self-reported medical diagnosis and symptomatic algorithms. Depression and anxiety were assessed using CIDI algorithms. Visual assessment included objective distance/near visual acuity and subjective visual performance. Descriptive analyses included the whole sample (n = 4,583). Statistical analyses included participants aged over 50 years (n = 3,625; mean age = 66.45 years) since they have a significant prevalence of chronic conditions and visual impairment. Crude and adjusted binary logistic regressions were performed to identify independent associations between visual impairment and chronic medical conditions, physical multimorbidity and mental conditions. Covariates included age, gender, marital status, education level, employment status and urbanicity. RESULTS: The number of chronic physical conditions was found to be associated with poorer results in both distance and near visual acuity [OR 1.75 (CI 1.38-2.23); OR 1.69 (CI 1.27-2.24)]. At an independent level, arthritis, stroke and diabetes were associated with poorer distance visual acuity results after adjusting for covariates [OR 1.79 (CI 1.46-2.21); OR 1.59 (CI 1.05-2.42); OR 1.27 (1.01-1.60)]. Only stroke was associated with near visual impairment [OR 3.01 (CI 1.86-4.87)]. With regard to mental health, poor subjective visual acuity was associated with depression [OR 1.61 (CI 1.14-2.27); OR 1.48 (CI 1.03-2.13)]. Both objective and subjective poor distance and near visual acuity were associated with worse cognitive functioning. CONCLUSIONS: Arthritis, stroke and the co-occurrence of various chronic physical diseases are associated with higher prevalence of visual impairment. Visual impairment is associated with higher prevalence of depression and poorer cognitive function results. There is a need to implement patient-centered care involving special visual assessment in these cases.

Multimorbidity patterns in a national representative sample of the Spanish adult population.

BACKGROUND: In the context of population aging, multimorbidity has emerged as a growing concern in public health. However, little is known about multimorbidity patterns and other issues surrounding chronic diseases. The aim of our study was to examine multimorbidity patterns, the relationship between physical and mental conditions and the distribution of multimorbidity in the Spanish adult population. METHODS: Data from this cross-sectional study was collected from the COURAGE study. A total of 4,583 participants from Spain were included, 3,625 aged over 50. An exploratory factor analysis was conducted to detect multimorbidity patterns in the population over 50 years of age. Crude and adjusted binary logistic regressions were performed to identify individual associations between physical and mental conditions. RESULTS: THREE MULTIMORBIDITY PATTERNS ROSE: 'cardio-respiratory' (angina, asthma, chronic lung disease), 'mental-arthritis' (arthritis, depression, anxiety) and the 'aggregated pattern' (angina, hypertension, stroke, diabetes, cataracts, edentulism, arthritis). After adjusting for covariates, asthma, chronic lung disease, arthritis and the number of physical conditions were associated with depression. Angina and the number of physical conditions were associated with a higher risk of anxiety. With regard to multimorbidity distribution, women over 65 years suffered from the highest rate of multimorbidity (67.3%). CONCLUSION: Multimorbidity prevalence occurs in a high percentage of the Spanish population, especially in the elderly. There are specific multimorbidity patterns and individual associations between physical and mental conditions, which bring new insights into the complexity of chronic patients. There is need to implement patient-centered care which involves these interactions rather than merely paying attention to individual diseases.

Impact of multimorbidity on disability and quality of life in the spanish older population

BACKGROUND: Population aging is closely related to high prevalence of chronic conditions in developed countries. In this context, health care policies aim to increase life span cost-effectively while maintaining quality of life and functional ability. There is still, however, a need for further understanding of how chronic conditions affect these health aspects. The aim of this paper is to assess the individual and combined impact of chronic physical and mental conditions on quality of life and disability in Spain, and secondly to show gender trends. METHODS: Cross-sectional data were collected from the COURAGE study. A total of 3,625 participants over 50 years old from Spain were included. Crude and adjusted multiple linear regressions were conducted to detect associations between individual chronic conditions and disability, and between chronic conditions and quality of life. Separate models were used to assess the influence of the number of diseases on the same variables. Additional analogous regressions were performed for males and females. RESULTS: All chronic conditions except hypertension were statistically associated with poor results in quality of life and disability. Depression, anxiety and stroke were found to have the greatest impact on outcomes. The number of chronic conditions was associated with substantially lower quality of life [β for 4+ diseases: -18.10 (-20.95,-15.25)] and greater disability [β for 4+ diseases: 27.64 (24.99,30.29]. In general, women suffered from higher rates of multimorbidity and poorer results in quality of life and disability. CONCLUSIONS: Chronic conditions impact greatly on quality of life and disability in the older Spanish population, especially when co-occurring diseases are added. Multimorbidity considerations should be a priority in the development of future health policies focused on quality of life and disability. Further studies would benefit from an expanded selection of diseases. Policies should also deal with gender idiosyncrasy in certain cases.